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Arkansas first state to ban transgender medical treatments for youths
Arkansas has become the first state to pass a law prohibiting doctors from giving gender-affirming medical treatments to transgender youths, CNN reported.
Gov. Asa Hutchinson had vetoed the bill on April 5, calling it a “product of the cultural war in America.” But on April 6, the state House and Senate voted to override the veto, making it state law, CNN reported.
At least 17 other states are considering similar legislation, but the Arkansas bill was the first to reach the governor’s desk, the Washington Post reported.
The bill bans doctors from prescribing puberty blockers, hormone therapies, or genital-altering surgeries for anybody under 18. Ever referring a youth for such treatment from another doctor is prohibited.
“It is of grave concern to the General Assembly that the medical community is allowing individuals who experience distress at identifying with their biological sex to be subjects of irreversible and drastic nongenital gender reassignment surgery and irreversible, permanently sterilizing genital gender reassignment surgery, despite the lack of studies showing that the benefits of such extreme interventions outweigh the risks,” the text of the bill said.
Gov. Hutchinson, a Republican, had called the measure a “vast government overreach” in announcing his veto.
“The bill is overbroad, extreme, and does not grandfather those young people who are currently under hormone treatment,” Gov. Hutchinson said. “The young people who are currently under a doctor’s care will be without treatment when this law goes into effect. That means they will be looking to the black market or go out of state ... to find the treatment that they want and need. This is not the right path to put them on.”
Many medical groups have come out against this kind of legislation. The American Academy of Child and Adolescent Psychiatry says it “strongly opposes any efforts – legal, legislative, and otherwise – to block access to these recognized interventions.”
Chase Strangio, the deputy director for transgender justice with the American Civil Liberty Union’s LGBTQ & HIV Project, complimented Gov. Hutchinson for his veto. On April 6, he said the ACLU is preparing to challenge the bill in court, CNN said.
A version of this article first appeared on Medscape.com.
Arkansas has become the first state to pass a law prohibiting doctors from giving gender-affirming medical treatments to transgender youths, CNN reported.
Gov. Asa Hutchinson had vetoed the bill on April 5, calling it a “product of the cultural war in America.” But on April 6, the state House and Senate voted to override the veto, making it state law, CNN reported.
At least 17 other states are considering similar legislation, but the Arkansas bill was the first to reach the governor’s desk, the Washington Post reported.
The bill bans doctors from prescribing puberty blockers, hormone therapies, or genital-altering surgeries for anybody under 18. Ever referring a youth for such treatment from another doctor is prohibited.
“It is of grave concern to the General Assembly that the medical community is allowing individuals who experience distress at identifying with their biological sex to be subjects of irreversible and drastic nongenital gender reassignment surgery and irreversible, permanently sterilizing genital gender reassignment surgery, despite the lack of studies showing that the benefits of such extreme interventions outweigh the risks,” the text of the bill said.
Gov. Hutchinson, a Republican, had called the measure a “vast government overreach” in announcing his veto.
“The bill is overbroad, extreme, and does not grandfather those young people who are currently under hormone treatment,” Gov. Hutchinson said. “The young people who are currently under a doctor’s care will be without treatment when this law goes into effect. That means they will be looking to the black market or go out of state ... to find the treatment that they want and need. This is not the right path to put them on.”
Many medical groups have come out against this kind of legislation. The American Academy of Child and Adolescent Psychiatry says it “strongly opposes any efforts – legal, legislative, and otherwise – to block access to these recognized interventions.”
Chase Strangio, the deputy director for transgender justice with the American Civil Liberty Union’s LGBTQ & HIV Project, complimented Gov. Hutchinson for his veto. On April 6, he said the ACLU is preparing to challenge the bill in court, CNN said.
A version of this article first appeared on Medscape.com.
Arkansas has become the first state to pass a law prohibiting doctors from giving gender-affirming medical treatments to transgender youths, CNN reported.
Gov. Asa Hutchinson had vetoed the bill on April 5, calling it a “product of the cultural war in America.” But on April 6, the state House and Senate voted to override the veto, making it state law, CNN reported.
At least 17 other states are considering similar legislation, but the Arkansas bill was the first to reach the governor’s desk, the Washington Post reported.
The bill bans doctors from prescribing puberty blockers, hormone therapies, or genital-altering surgeries for anybody under 18. Ever referring a youth for such treatment from another doctor is prohibited.
“It is of grave concern to the General Assembly that the medical community is allowing individuals who experience distress at identifying with their biological sex to be subjects of irreversible and drastic nongenital gender reassignment surgery and irreversible, permanently sterilizing genital gender reassignment surgery, despite the lack of studies showing that the benefits of such extreme interventions outweigh the risks,” the text of the bill said.
Gov. Hutchinson, a Republican, had called the measure a “vast government overreach” in announcing his veto.
“The bill is overbroad, extreme, and does not grandfather those young people who are currently under hormone treatment,” Gov. Hutchinson said. “The young people who are currently under a doctor’s care will be without treatment when this law goes into effect. That means they will be looking to the black market or go out of state ... to find the treatment that they want and need. This is not the right path to put them on.”
Many medical groups have come out against this kind of legislation. The American Academy of Child and Adolescent Psychiatry says it “strongly opposes any efforts – legal, legislative, and otherwise – to block access to these recognized interventions.”
Chase Strangio, the deputy director for transgender justice with the American Civil Liberty Union’s LGBTQ & HIV Project, complimented Gov. Hutchinson for his veto. On April 6, he said the ACLU is preparing to challenge the bill in court, CNN said.
A version of this article first appeared on Medscape.com.
Contradictions abound in ‘The End of Mental Illness’
Daniel G. Amen, MD, is an American psychiatrist well-known for his eponymous clinics, television appearances, and series of books on mental health. One of his latest books, “The End of Mental Illness,” summarizes many of his views on the causes of and treatments for mental illnesses.
Dr. Amen’s approaches – such as his advocacy for the widespread use of single photon emission computed tomography (SPECT) imaging – are somewhat controversial and at times fall outside the mainstream of current psychiatric thought. So does “The End of Mental Illness” contain anything of value to the average practicing psychiatrist? (It should be noted that I listened to this as an audiobook and took notes as I listened. This does limit my ability to directly quote portions of the text, but I believe my notes are reliable.)
He begins the book by pointing out that the term “mental illness” might be better replaced with the term “brain illness.” With this shift in terminology, Dr. Amen introduces a theme that recurs throughout the book: That mental illnesses ultimately stem from various ways in which the brain can be harmed. While the suggested change in terminology might help reduce the stigma associated with psychiatric illnesses, Dr. Amen is surprisingly timid about implementing this term in his own book. He repeatedly refers to “brain health/mental health” issues instead of discarding the “mental” term altogether. Even his BRIGHT MINDS acronym for risk factors for mental illnesses includes the term “mind” instead of “brain.”
Continuing the theme of challenging terminology, Dr. Amen goes on to decry the weaknesses of the DSM system of nosology. This is a valid point, because under the current system, the same patient may receive differing diagnoses depending on which provider is seen and how certain symptoms are interpreted. Yet, here again, Dr. Amen does not seem to adhere to his own advice: He uses DSM terminology throughout the book, speaking of depression, anxiety, bipolar disorder, and ADHD. An oddity (which, admittedly, could have been the audiobook reader’s mistake rather than an error in the original text) is that the DSM is referred to as the “Diagnostic and Structural Manual” rather than the Diagnostic and Statistical Manual. He criticizes the DSM for its imprecision, pointing out the variety of symptom combinations that can produce the same diagnoses and how similar symptoms may overlap between differing diagnoses. Yet, his descriptions of common SPECT patterns (his preferred tool to assist in diagnosis) make it clear that here, too, there is a lot of overlap. As an example, ADHD was associated with at least three of the imaging patterns he described. It is also somewhat ironic how Dr. Amen obliquely criticizes the American Psychiatric Association for profiting from the use of the DSM, when SPECT imaging is expensive and profits his own organization.
Dr. Amen repeatedly asserts that psychiatry is unique among medical specialties for making diagnoses based on symptom clusters rather than direct visualization of the affected organ. Yet, psychiatry is not, in fact, unique in making diagnoses in this way. Some examples of diagnoses based on symptom clusters from other medical specialties are systemic lupus erythematosus, fibromyalgia, and chronic fatigue syndrome. Although he asserts that SPECT imaging better demonstrates the root cause of mental illnesses, it is unclear from his book whether this is actually the case.
The descriptions for the ways in which Dr. Amen uses SPECT (which, admittedly, are vague and presumably simplified for a general audience) suggest that he has made observations correlating specific imaging patterns with certain emotional/behavioral outcomes. However, the imaging patterns he describes in the book can be interpreted to represent multiple different mental conditions, making it clear that SPECT is not a laserlike diagnostic tool that produces a single, indisputable diagnosis. Accuracy with SPECT seems especially questionable in light of two case examples he shares where brain imaging was interpreted as representing illness, but the patients were not demonstrating any signs of mental dysfunction. In one case, Dr. Amen opined that the patient’s vibrant spiritual life “overrode” the sick brain, but if this is true,
Patient testimonials are provided, asserting that SPECT imaging helped them know “exactly” what treatment would help them. One cannot help but wonder whether part of the benefit of SPECT imaging is a placebo effect, boosting the confidence of patients that the treatment they are receiving is personalized and scientifically sound. A similar trend is currently seen more broadly in psychiatry with the widespread promotion of pharmacogenetic testing. Such testing may bolster patient confidence in their medication, but its value in improving patient outcomes has not been established.1
Dr. Amen outlines a brief history of mental health care, including differing approaches and therapies from the time of Sigmund Freud up to the present. His outline is somewhat critical of the perceived shortcomings of his psychiatric forebears, yet this seems entirely unnecessary. All scientific disciplines must start somewhere and build from limited knowledge to greater. Is it necessary to belittle Freud for not being able to do SPECT imaging in the 1800s?
Interestingly, Dr. Amen leaves cognitive-behavioral therapy (CBT), a landmark, evidence-based form of psychotherapy, out of his overview of the history of psychiatry. He does go on to mention CBT as part of the treatment offerings of the Amen Clinics, which could leave the lay reader with the incorrect impression that CBT is a treatment unique to Amen Clinics. Similarly, at one point Dr. Amen writes about “what I call automatic negative thoughts.” This phrasing could confuse readers who might not know that automatic thoughts are a concept endemic to CBT.
Dr. Amen writes repeatedly about the Amen Clinics 4 Circles, four key areas of life that can contribute to mental health. These areas are biological, psychological, social, and spiritual. While Amen Clinics may have come up with the term “4 Circles,” the biopsychosocial model of understanding illness was developed by George Engel, MD, in 1977, and current discussions of this model frequently incorporate a spiritual dimension as well.2
Dr. Amen’s writing at times mischaracterizes psychotropic medications in unhelpful ways. He speaks of psychotropic medications generally as being addictive. While this is certainly true for stimulants and benzodiazepines, most would agree that this does not apply to many other commonly used medications in psychiatry, including selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, antipsychotics, and mood stabilizers. He also paints with a broad brush when he states that anxiety medications can cause dementia. A concerning link has been demonstrated between benzodiazepine use and dementia,3 but SSRIs (which are considered first-line medications for anxiety) are not known to cause dementia and may actually delay progression from mild cognitive impairment to Alzheimer’s dementia.4 His mention of medication use affecting a patient’s insurability could have the unfortunate effect of scaring away suffering individuals from seeking help. The one category of psychiatric medication he does not seem concerned about is psychostimulants, which is odd – given the addictive, cardiovascular, and other risks associated with that medication class.
In contrast to his skepticism regarding many psychotropic medications, Dr. Amen expresses significant enthusiasm regarding nutraceutical use. While there has been research in this area supporting a role for some nutraceutical interventions, there is still a need for more rigorous studies.5 To support his endorsement of natural remedies, Dr. Amen mentions that Hippocrates recommended herbs and spices for many health conditions. But Hippocrates lived more than 2,000 years ago, and the state of medicine has advanced significantly since then.
Dr. Amen also mentions that 80% of the developing world relies upon natural or herbal remedies as the primary source of medicine. While he frames this statement as supporting his endorsement of such remedies, it could conversely be said that this is evidence of the need to make pharmacological interventions more widely available in the developing world.
Much of “The End of Mental Illness” is dedicated to reviewing specific risk factors that could cause harm to a person’s mental well-being. One example is head trauma. Dr. Amen documents at least one instance in which he was convinced that his patient had experienced head trauma, and questioned the patient again and again about possible brain injuries. One must wonder whether the positive results of such focused, repetitive questioning might be evidence of confirmation bias, as a search to confirm the preexisting belief of head trauma could lead to overlooking alternative explanations for a patient’s symptoms.
Another risk factor dwelt upon is exposure to toxins. One toxin Dr. Amen rightly recommends avoiding is tobacco smoke. Yet, his approach to advocate for a tobacco-free lifestyle is somewhat problematic. He lists chemicals contained in tobacco smoke, and then names unpleasant items that share those ingredients, such as paint. This smacks of the same sloppy logic manifested in social media memes decrying the use of vaccines by listing their ingredients alongside scary-sounding products that contain identical ingredients (for example, vaccines contain formaldehyde, which is used to embalm dead bodies!). This is analogous to saying that water is bad for you because it contains hydrogen, which is also an ingredient in atomic bombs.
Dr. Amen makes the blanket recommendation to avoid products containing “chemicals.” This is a difficult recommendation to interpret, since literally all matter is made of chemicals. It seems that Dr. Amen is leaning into the vague idea of a “chemical” as something artificially created in a lab, which must, therefore, be dangerous.
Along these lines, Dr. Amen suggests that if a person doesn’t know what is in a specific food item, it should not be eaten. Although this sounds reasonable on the surface, if people were told the names of the proteins and chemical compounds that make up many naturally occurring plants or meats, they would likely not recognize many of them. Dr. Amen dedicates space to list seemingly benign exposures – such as eating nonorganic produce, using two or more beauty products each day, or touching grocery store receipts – as possible “toxins.” By contrast, there is a certain irony in the absence of any mention of the risks associated with radiation from the SPECT imaging he staunchly advocates for. One potential risk of the book listing so many “toxins” to avoid is that patients could waste valuable time and energy eliminating exposures that pose little or no risk, rather than focusing efforts on well-established treatments.
In light of the observations and critiques offered above, one might come away with the impression that I would not recommend “The End of Mental Illness.” However, although one can nitpick details in the book, some of its bigger ideas make it worth commending to readers. Dr. Amen rightfully emphasizes the need for psychiatrists and patients to think more broadly about mental health issues beyond the use of pills. He justifiably criticizes the “15-minute med check” model of practice and the idea that medications are the end-all, be-all of treatment. He demonstrates an appropriate appreciation for the serious risks of reliance on benzodiazepines.6 Dr. Amen points out important contributions from Viktor Frankl, MD, to the field of psychiatry, which may go overlooked today. He also helpfully points out that bipolar disorder may often be misdiagnosed (although he attributes the misdiagnosis to traumatic brain injury, whereas other psychiatrists might say the misdiagnosis is due to borderline personality disorder).
Much of what Dr. Amen writes is sensible, and psychiatrists would do well to adopt the following steps he advocates for: Taking a comprehensive biopsychosocial-spiritual approach to the assessment and treatment of patients; thinking broadly in their differential diagnoses and not forgetting their medical training; understanding that medication alone is often not sufficient to make lasting, positive change in a person’s life; paying attention to healthy habits such as diet, exercise, sleep, and social activity; and knowing that CBT is a valuable tool that can change lives.
There is much to appreciate in “The End of Mental Illness,” especially the overarching idea that psychiatry isn’t just a symptom checklist and a prescription pad. Rather, achieving mental well-being often requires broader thinking and sustained lifestyle changes.
Although I did not agree with everything in the book, it did cause me to think and reflect on my own practice. I read “The End of Mental Illness” with colleagues in my department, and it stimulated a lively discussion. Isn’t that ultimately what a psychiatrist would want from a book like this – the opportunity to reflect, discuss, and potentially improve one’s own practice?
Dr. Weber is physician lead in the department of psychiatry at Intermountain Healthcare Budge Clinic, Logan (Utah) Psychiatry. He disclosed no relevant financial relationships.
References
1. JAMA Netw Open. 2020;3(12). doi: 10.1001/jamanetworkopen.2020.27909.
2. Curr Opin Psychiatry. 2014;27:358-63.
3. BMJ 2014. doi: 10.1136/bmj.g5205.
4. Am J Psychiatry. 2018 Mar 1;175:232-41.
5. Am J Psychiatry. 2016 Jun 1;173:575-87.
6. Current Psychiatry. 2018 Feb;17(2):22-7.
Daniel G. Amen, MD, is an American psychiatrist well-known for his eponymous clinics, television appearances, and series of books on mental health. One of his latest books, “The End of Mental Illness,” summarizes many of his views on the causes of and treatments for mental illnesses.
Dr. Amen’s approaches – such as his advocacy for the widespread use of single photon emission computed tomography (SPECT) imaging – are somewhat controversial and at times fall outside the mainstream of current psychiatric thought. So does “The End of Mental Illness” contain anything of value to the average practicing psychiatrist? (It should be noted that I listened to this as an audiobook and took notes as I listened. This does limit my ability to directly quote portions of the text, but I believe my notes are reliable.)
He begins the book by pointing out that the term “mental illness” might be better replaced with the term “brain illness.” With this shift in terminology, Dr. Amen introduces a theme that recurs throughout the book: That mental illnesses ultimately stem from various ways in which the brain can be harmed. While the suggested change in terminology might help reduce the stigma associated with psychiatric illnesses, Dr. Amen is surprisingly timid about implementing this term in his own book. He repeatedly refers to “brain health/mental health” issues instead of discarding the “mental” term altogether. Even his BRIGHT MINDS acronym for risk factors for mental illnesses includes the term “mind” instead of “brain.”
Continuing the theme of challenging terminology, Dr. Amen goes on to decry the weaknesses of the DSM system of nosology. This is a valid point, because under the current system, the same patient may receive differing diagnoses depending on which provider is seen and how certain symptoms are interpreted. Yet, here again, Dr. Amen does not seem to adhere to his own advice: He uses DSM terminology throughout the book, speaking of depression, anxiety, bipolar disorder, and ADHD. An oddity (which, admittedly, could have been the audiobook reader’s mistake rather than an error in the original text) is that the DSM is referred to as the “Diagnostic and Structural Manual” rather than the Diagnostic and Statistical Manual. He criticizes the DSM for its imprecision, pointing out the variety of symptom combinations that can produce the same diagnoses and how similar symptoms may overlap between differing diagnoses. Yet, his descriptions of common SPECT patterns (his preferred tool to assist in diagnosis) make it clear that here, too, there is a lot of overlap. As an example, ADHD was associated with at least three of the imaging patterns he described. It is also somewhat ironic how Dr. Amen obliquely criticizes the American Psychiatric Association for profiting from the use of the DSM, when SPECT imaging is expensive and profits his own organization.
Dr. Amen repeatedly asserts that psychiatry is unique among medical specialties for making diagnoses based on symptom clusters rather than direct visualization of the affected organ. Yet, psychiatry is not, in fact, unique in making diagnoses in this way. Some examples of diagnoses based on symptom clusters from other medical specialties are systemic lupus erythematosus, fibromyalgia, and chronic fatigue syndrome. Although he asserts that SPECT imaging better demonstrates the root cause of mental illnesses, it is unclear from his book whether this is actually the case.
The descriptions for the ways in which Dr. Amen uses SPECT (which, admittedly, are vague and presumably simplified for a general audience) suggest that he has made observations correlating specific imaging patterns with certain emotional/behavioral outcomes. However, the imaging patterns he describes in the book can be interpreted to represent multiple different mental conditions, making it clear that SPECT is not a laserlike diagnostic tool that produces a single, indisputable diagnosis. Accuracy with SPECT seems especially questionable in light of two case examples he shares where brain imaging was interpreted as representing illness, but the patients were not demonstrating any signs of mental dysfunction. In one case, Dr. Amen opined that the patient’s vibrant spiritual life “overrode” the sick brain, but if this is true,
Patient testimonials are provided, asserting that SPECT imaging helped them know “exactly” what treatment would help them. One cannot help but wonder whether part of the benefit of SPECT imaging is a placebo effect, boosting the confidence of patients that the treatment they are receiving is personalized and scientifically sound. A similar trend is currently seen more broadly in psychiatry with the widespread promotion of pharmacogenetic testing. Such testing may bolster patient confidence in their medication, but its value in improving patient outcomes has not been established.1
Dr. Amen outlines a brief history of mental health care, including differing approaches and therapies from the time of Sigmund Freud up to the present. His outline is somewhat critical of the perceived shortcomings of his psychiatric forebears, yet this seems entirely unnecessary. All scientific disciplines must start somewhere and build from limited knowledge to greater. Is it necessary to belittle Freud for not being able to do SPECT imaging in the 1800s?
Interestingly, Dr. Amen leaves cognitive-behavioral therapy (CBT), a landmark, evidence-based form of psychotherapy, out of his overview of the history of psychiatry. He does go on to mention CBT as part of the treatment offerings of the Amen Clinics, which could leave the lay reader with the incorrect impression that CBT is a treatment unique to Amen Clinics. Similarly, at one point Dr. Amen writes about “what I call automatic negative thoughts.” This phrasing could confuse readers who might not know that automatic thoughts are a concept endemic to CBT.
Dr. Amen writes repeatedly about the Amen Clinics 4 Circles, four key areas of life that can contribute to mental health. These areas are biological, psychological, social, and spiritual. While Amen Clinics may have come up with the term “4 Circles,” the biopsychosocial model of understanding illness was developed by George Engel, MD, in 1977, and current discussions of this model frequently incorporate a spiritual dimension as well.2
Dr. Amen’s writing at times mischaracterizes psychotropic medications in unhelpful ways. He speaks of psychotropic medications generally as being addictive. While this is certainly true for stimulants and benzodiazepines, most would agree that this does not apply to many other commonly used medications in psychiatry, including selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, antipsychotics, and mood stabilizers. He also paints with a broad brush when he states that anxiety medications can cause dementia. A concerning link has been demonstrated between benzodiazepine use and dementia,3 but SSRIs (which are considered first-line medications for anxiety) are not known to cause dementia and may actually delay progression from mild cognitive impairment to Alzheimer’s dementia.4 His mention of medication use affecting a patient’s insurability could have the unfortunate effect of scaring away suffering individuals from seeking help. The one category of psychiatric medication he does not seem concerned about is psychostimulants, which is odd – given the addictive, cardiovascular, and other risks associated with that medication class.
In contrast to his skepticism regarding many psychotropic medications, Dr. Amen expresses significant enthusiasm regarding nutraceutical use. While there has been research in this area supporting a role for some nutraceutical interventions, there is still a need for more rigorous studies.5 To support his endorsement of natural remedies, Dr. Amen mentions that Hippocrates recommended herbs and spices for many health conditions. But Hippocrates lived more than 2,000 years ago, and the state of medicine has advanced significantly since then.
Dr. Amen also mentions that 80% of the developing world relies upon natural or herbal remedies as the primary source of medicine. While he frames this statement as supporting his endorsement of such remedies, it could conversely be said that this is evidence of the need to make pharmacological interventions more widely available in the developing world.
Much of “The End of Mental Illness” is dedicated to reviewing specific risk factors that could cause harm to a person’s mental well-being. One example is head trauma. Dr. Amen documents at least one instance in which he was convinced that his patient had experienced head trauma, and questioned the patient again and again about possible brain injuries. One must wonder whether the positive results of such focused, repetitive questioning might be evidence of confirmation bias, as a search to confirm the preexisting belief of head trauma could lead to overlooking alternative explanations for a patient’s symptoms.
Another risk factor dwelt upon is exposure to toxins. One toxin Dr. Amen rightly recommends avoiding is tobacco smoke. Yet, his approach to advocate for a tobacco-free lifestyle is somewhat problematic. He lists chemicals contained in tobacco smoke, and then names unpleasant items that share those ingredients, such as paint. This smacks of the same sloppy logic manifested in social media memes decrying the use of vaccines by listing their ingredients alongside scary-sounding products that contain identical ingredients (for example, vaccines contain formaldehyde, which is used to embalm dead bodies!). This is analogous to saying that water is bad for you because it contains hydrogen, which is also an ingredient in atomic bombs.
Dr. Amen makes the blanket recommendation to avoid products containing “chemicals.” This is a difficult recommendation to interpret, since literally all matter is made of chemicals. It seems that Dr. Amen is leaning into the vague idea of a “chemical” as something artificially created in a lab, which must, therefore, be dangerous.
Along these lines, Dr. Amen suggests that if a person doesn’t know what is in a specific food item, it should not be eaten. Although this sounds reasonable on the surface, if people were told the names of the proteins and chemical compounds that make up many naturally occurring plants or meats, they would likely not recognize many of them. Dr. Amen dedicates space to list seemingly benign exposures – such as eating nonorganic produce, using two or more beauty products each day, or touching grocery store receipts – as possible “toxins.” By contrast, there is a certain irony in the absence of any mention of the risks associated with radiation from the SPECT imaging he staunchly advocates for. One potential risk of the book listing so many “toxins” to avoid is that patients could waste valuable time and energy eliminating exposures that pose little or no risk, rather than focusing efforts on well-established treatments.
In light of the observations and critiques offered above, one might come away with the impression that I would not recommend “The End of Mental Illness.” However, although one can nitpick details in the book, some of its bigger ideas make it worth commending to readers. Dr. Amen rightfully emphasizes the need for psychiatrists and patients to think more broadly about mental health issues beyond the use of pills. He justifiably criticizes the “15-minute med check” model of practice and the idea that medications are the end-all, be-all of treatment. He demonstrates an appropriate appreciation for the serious risks of reliance on benzodiazepines.6 Dr. Amen points out important contributions from Viktor Frankl, MD, to the field of psychiatry, which may go overlooked today. He also helpfully points out that bipolar disorder may often be misdiagnosed (although he attributes the misdiagnosis to traumatic brain injury, whereas other psychiatrists might say the misdiagnosis is due to borderline personality disorder).
Much of what Dr. Amen writes is sensible, and psychiatrists would do well to adopt the following steps he advocates for: Taking a comprehensive biopsychosocial-spiritual approach to the assessment and treatment of patients; thinking broadly in their differential diagnoses and not forgetting their medical training; understanding that medication alone is often not sufficient to make lasting, positive change in a person’s life; paying attention to healthy habits such as diet, exercise, sleep, and social activity; and knowing that CBT is a valuable tool that can change lives.
There is much to appreciate in “The End of Mental Illness,” especially the overarching idea that psychiatry isn’t just a symptom checklist and a prescription pad. Rather, achieving mental well-being often requires broader thinking and sustained lifestyle changes.
Although I did not agree with everything in the book, it did cause me to think and reflect on my own practice. I read “The End of Mental Illness” with colleagues in my department, and it stimulated a lively discussion. Isn’t that ultimately what a psychiatrist would want from a book like this – the opportunity to reflect, discuss, and potentially improve one’s own practice?
Dr. Weber is physician lead in the department of psychiatry at Intermountain Healthcare Budge Clinic, Logan (Utah) Psychiatry. He disclosed no relevant financial relationships.
References
1. JAMA Netw Open. 2020;3(12). doi: 10.1001/jamanetworkopen.2020.27909.
2. Curr Opin Psychiatry. 2014;27:358-63.
3. BMJ 2014. doi: 10.1136/bmj.g5205.
4. Am J Psychiatry. 2018 Mar 1;175:232-41.
5. Am J Psychiatry. 2016 Jun 1;173:575-87.
6. Current Psychiatry. 2018 Feb;17(2):22-7.
Daniel G. Amen, MD, is an American psychiatrist well-known for his eponymous clinics, television appearances, and series of books on mental health. One of his latest books, “The End of Mental Illness,” summarizes many of his views on the causes of and treatments for mental illnesses.
Dr. Amen’s approaches – such as his advocacy for the widespread use of single photon emission computed tomography (SPECT) imaging – are somewhat controversial and at times fall outside the mainstream of current psychiatric thought. So does “The End of Mental Illness” contain anything of value to the average practicing psychiatrist? (It should be noted that I listened to this as an audiobook and took notes as I listened. This does limit my ability to directly quote portions of the text, but I believe my notes are reliable.)
He begins the book by pointing out that the term “mental illness” might be better replaced with the term “brain illness.” With this shift in terminology, Dr. Amen introduces a theme that recurs throughout the book: That mental illnesses ultimately stem from various ways in which the brain can be harmed. While the suggested change in terminology might help reduce the stigma associated with psychiatric illnesses, Dr. Amen is surprisingly timid about implementing this term in his own book. He repeatedly refers to “brain health/mental health” issues instead of discarding the “mental” term altogether. Even his BRIGHT MINDS acronym for risk factors for mental illnesses includes the term “mind” instead of “brain.”
Continuing the theme of challenging terminology, Dr. Amen goes on to decry the weaknesses of the DSM system of nosology. This is a valid point, because under the current system, the same patient may receive differing diagnoses depending on which provider is seen and how certain symptoms are interpreted. Yet, here again, Dr. Amen does not seem to adhere to his own advice: He uses DSM terminology throughout the book, speaking of depression, anxiety, bipolar disorder, and ADHD. An oddity (which, admittedly, could have been the audiobook reader’s mistake rather than an error in the original text) is that the DSM is referred to as the “Diagnostic and Structural Manual” rather than the Diagnostic and Statistical Manual. He criticizes the DSM for its imprecision, pointing out the variety of symptom combinations that can produce the same diagnoses and how similar symptoms may overlap between differing diagnoses. Yet, his descriptions of common SPECT patterns (his preferred tool to assist in diagnosis) make it clear that here, too, there is a lot of overlap. As an example, ADHD was associated with at least three of the imaging patterns he described. It is also somewhat ironic how Dr. Amen obliquely criticizes the American Psychiatric Association for profiting from the use of the DSM, when SPECT imaging is expensive and profits his own organization.
Dr. Amen repeatedly asserts that psychiatry is unique among medical specialties for making diagnoses based on symptom clusters rather than direct visualization of the affected organ. Yet, psychiatry is not, in fact, unique in making diagnoses in this way. Some examples of diagnoses based on symptom clusters from other medical specialties are systemic lupus erythematosus, fibromyalgia, and chronic fatigue syndrome. Although he asserts that SPECT imaging better demonstrates the root cause of mental illnesses, it is unclear from his book whether this is actually the case.
The descriptions for the ways in which Dr. Amen uses SPECT (which, admittedly, are vague and presumably simplified for a general audience) suggest that he has made observations correlating specific imaging patterns with certain emotional/behavioral outcomes. However, the imaging patterns he describes in the book can be interpreted to represent multiple different mental conditions, making it clear that SPECT is not a laserlike diagnostic tool that produces a single, indisputable diagnosis. Accuracy with SPECT seems especially questionable in light of two case examples he shares where brain imaging was interpreted as representing illness, but the patients were not demonstrating any signs of mental dysfunction. In one case, Dr. Amen opined that the patient’s vibrant spiritual life “overrode” the sick brain, but if this is true,
Patient testimonials are provided, asserting that SPECT imaging helped them know “exactly” what treatment would help them. One cannot help but wonder whether part of the benefit of SPECT imaging is a placebo effect, boosting the confidence of patients that the treatment they are receiving is personalized and scientifically sound. A similar trend is currently seen more broadly in psychiatry with the widespread promotion of pharmacogenetic testing. Such testing may bolster patient confidence in their medication, but its value in improving patient outcomes has not been established.1
Dr. Amen outlines a brief history of mental health care, including differing approaches and therapies from the time of Sigmund Freud up to the present. His outline is somewhat critical of the perceived shortcomings of his psychiatric forebears, yet this seems entirely unnecessary. All scientific disciplines must start somewhere and build from limited knowledge to greater. Is it necessary to belittle Freud for not being able to do SPECT imaging in the 1800s?
Interestingly, Dr. Amen leaves cognitive-behavioral therapy (CBT), a landmark, evidence-based form of psychotherapy, out of his overview of the history of psychiatry. He does go on to mention CBT as part of the treatment offerings of the Amen Clinics, which could leave the lay reader with the incorrect impression that CBT is a treatment unique to Amen Clinics. Similarly, at one point Dr. Amen writes about “what I call automatic negative thoughts.” This phrasing could confuse readers who might not know that automatic thoughts are a concept endemic to CBT.
Dr. Amen writes repeatedly about the Amen Clinics 4 Circles, four key areas of life that can contribute to mental health. These areas are biological, psychological, social, and spiritual. While Amen Clinics may have come up with the term “4 Circles,” the biopsychosocial model of understanding illness was developed by George Engel, MD, in 1977, and current discussions of this model frequently incorporate a spiritual dimension as well.2
Dr. Amen’s writing at times mischaracterizes psychotropic medications in unhelpful ways. He speaks of psychotropic medications generally as being addictive. While this is certainly true for stimulants and benzodiazepines, most would agree that this does not apply to many other commonly used medications in psychiatry, including selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, antipsychotics, and mood stabilizers. He also paints with a broad brush when he states that anxiety medications can cause dementia. A concerning link has been demonstrated between benzodiazepine use and dementia,3 but SSRIs (which are considered first-line medications for anxiety) are not known to cause dementia and may actually delay progression from mild cognitive impairment to Alzheimer’s dementia.4 His mention of medication use affecting a patient’s insurability could have the unfortunate effect of scaring away suffering individuals from seeking help. The one category of psychiatric medication he does not seem concerned about is psychostimulants, which is odd – given the addictive, cardiovascular, and other risks associated with that medication class.
In contrast to his skepticism regarding many psychotropic medications, Dr. Amen expresses significant enthusiasm regarding nutraceutical use. While there has been research in this area supporting a role for some nutraceutical interventions, there is still a need for more rigorous studies.5 To support his endorsement of natural remedies, Dr. Amen mentions that Hippocrates recommended herbs and spices for many health conditions. But Hippocrates lived more than 2,000 years ago, and the state of medicine has advanced significantly since then.
Dr. Amen also mentions that 80% of the developing world relies upon natural or herbal remedies as the primary source of medicine. While he frames this statement as supporting his endorsement of such remedies, it could conversely be said that this is evidence of the need to make pharmacological interventions more widely available in the developing world.
Much of “The End of Mental Illness” is dedicated to reviewing specific risk factors that could cause harm to a person’s mental well-being. One example is head trauma. Dr. Amen documents at least one instance in which he was convinced that his patient had experienced head trauma, and questioned the patient again and again about possible brain injuries. One must wonder whether the positive results of such focused, repetitive questioning might be evidence of confirmation bias, as a search to confirm the preexisting belief of head trauma could lead to overlooking alternative explanations for a patient’s symptoms.
Another risk factor dwelt upon is exposure to toxins. One toxin Dr. Amen rightly recommends avoiding is tobacco smoke. Yet, his approach to advocate for a tobacco-free lifestyle is somewhat problematic. He lists chemicals contained in tobacco smoke, and then names unpleasant items that share those ingredients, such as paint. This smacks of the same sloppy logic manifested in social media memes decrying the use of vaccines by listing their ingredients alongside scary-sounding products that contain identical ingredients (for example, vaccines contain formaldehyde, which is used to embalm dead bodies!). This is analogous to saying that water is bad for you because it contains hydrogen, which is also an ingredient in atomic bombs.
Dr. Amen makes the blanket recommendation to avoid products containing “chemicals.” This is a difficult recommendation to interpret, since literally all matter is made of chemicals. It seems that Dr. Amen is leaning into the vague idea of a “chemical” as something artificially created in a lab, which must, therefore, be dangerous.
Along these lines, Dr. Amen suggests that if a person doesn’t know what is in a specific food item, it should not be eaten. Although this sounds reasonable on the surface, if people were told the names of the proteins and chemical compounds that make up many naturally occurring plants or meats, they would likely not recognize many of them. Dr. Amen dedicates space to list seemingly benign exposures – such as eating nonorganic produce, using two or more beauty products each day, or touching grocery store receipts – as possible “toxins.” By contrast, there is a certain irony in the absence of any mention of the risks associated with radiation from the SPECT imaging he staunchly advocates for. One potential risk of the book listing so many “toxins” to avoid is that patients could waste valuable time and energy eliminating exposures that pose little or no risk, rather than focusing efforts on well-established treatments.
In light of the observations and critiques offered above, one might come away with the impression that I would not recommend “The End of Mental Illness.” However, although one can nitpick details in the book, some of its bigger ideas make it worth commending to readers. Dr. Amen rightfully emphasizes the need for psychiatrists and patients to think more broadly about mental health issues beyond the use of pills. He justifiably criticizes the “15-minute med check” model of practice and the idea that medications are the end-all, be-all of treatment. He demonstrates an appropriate appreciation for the serious risks of reliance on benzodiazepines.6 Dr. Amen points out important contributions from Viktor Frankl, MD, to the field of psychiatry, which may go overlooked today. He also helpfully points out that bipolar disorder may often be misdiagnosed (although he attributes the misdiagnosis to traumatic brain injury, whereas other psychiatrists might say the misdiagnosis is due to borderline personality disorder).
Much of what Dr. Amen writes is sensible, and psychiatrists would do well to adopt the following steps he advocates for: Taking a comprehensive biopsychosocial-spiritual approach to the assessment and treatment of patients; thinking broadly in their differential diagnoses and not forgetting their medical training; understanding that medication alone is often not sufficient to make lasting, positive change in a person’s life; paying attention to healthy habits such as diet, exercise, sleep, and social activity; and knowing that CBT is a valuable tool that can change lives.
There is much to appreciate in “The End of Mental Illness,” especially the overarching idea that psychiatry isn’t just a symptom checklist and a prescription pad. Rather, achieving mental well-being often requires broader thinking and sustained lifestyle changes.
Although I did not agree with everything in the book, it did cause me to think and reflect on my own practice. I read “The End of Mental Illness” with colleagues in my department, and it stimulated a lively discussion. Isn’t that ultimately what a psychiatrist would want from a book like this – the opportunity to reflect, discuss, and potentially improve one’s own practice?
Dr. Weber is physician lead in the department of psychiatry at Intermountain Healthcare Budge Clinic, Logan (Utah) Psychiatry. He disclosed no relevant financial relationships.
References
1. JAMA Netw Open. 2020;3(12). doi: 10.1001/jamanetworkopen.2020.27909.
2. Curr Opin Psychiatry. 2014;27:358-63.
3. BMJ 2014. doi: 10.1136/bmj.g5205.
4. Am J Psychiatry. 2018 Mar 1;175:232-41.
5. Am J Psychiatry. 2016 Jun 1;173:575-87.
6. Current Psychiatry. 2018 Feb;17(2):22-7.
Everyday chemicals are linked to declines in human fertility
Chemicals that pervade our modern world – plastics, pesticides, stain repellents, components of personal hygiene products – are contributing to a decades-long decline in fertility and could pose health risks even into future generations, according to an explosive new book by Shanna Swan, PhD, an environmental and reproductive epidemiologist at the Icahn School of Medicine at Mount Sinai, New York.
Dr. Swan laid out the case that endocrine-disrupting chemicals (EDCs) such as phthalates and bisphenol A (BPA) threaten human existence, a conclusion that stems in part from her 2017 meta-analysis that showed a 52% drop in sperm counts from 1973 to 2011 in men in North America, Europe, and Australia.
“This alarming rate of decline could mean the human race will be unable to reproduce itself if the trend continues,” Dr. Swan said in her book, “Count Down: How Our Modern World Is Threatening Sperm Counts, Altering Male and Female Reproductive Development, and Imperiling the Future of the Human Race,” (New York: Scribner, 2021) coauthored with health journalist Stacey Colino.
Her premise that EDCs pose a risk to both male and female fertility is underscored by new research. A March 2021 article in Human Reproduction links prenatal chemical exposures to lowered fertility in a study of 1,045 Swiss military conscripts.
The Swiss men, aged 18-22 years, were significantly more likely to have low semen volume and low total sperm count if their mothers reported that they had occupational exposures to four or more endocrine-disrupting chemicals while they were pregnant. These EDCs, which mimic natural hormones, included pesticides, heavy metals, phthalates, alkylphenolic compounds, and solvents that can be found in agricultural work or hair and beauty salons.
These chemicals are not so-called “forever chemicals” that persist in the human body. But the Swiss study still showed an association between exposure during pregnancy and the future fertility of the male children. “Those apparently small exposures that pass quickly can affect development,” said Dr. Swan, who was not affiliated with the research. “It takes very little in terms of time and amount of chemicals to alter fetal development.”
Health risks beyond reproduction
While Count Down is placing a new spotlight on chemical hazards, some major medical organizations have already taken positions on the risks. “Reducing exposure to toxic environmental agents is a critical area of intervention for ob.gyns.,” the American College of Obstetricians and Gynecologists said in an environmental policy priority. “The Endocrine Society is concerned that human health is at risk because the current extensive scientific knowledge on EDCs and their health effects is not effectively translated to regulatory policies that fully protect populations from EDC exposures.”
But for the medical community, addressing the impact of EDCs goes beyond advocacy for regulatory and legislative changes, Dr. Swan said in an interview. Physicians should talk to patients about the importance of reducing their chemical exposure to safeguard their overall health.
“Reproductive health and particularly sperm count, subfertility, and infertility are predictors of lifelong health,” she said. That includes associations between reproductive disorders and “the risk of heart disease, obesity, reproductive cancers and, perhaps most dramatically, with a shortened lifespan.”
Some medical schools are including information on environmental health and exposure risks in the curriculum, said Tracey Woodruff, PhD, MPH, director of the program on reproductive health and the environment at the University of California, San Francisco. She urged physicians to ask patients about potential occupational exposures to hazardous chemicals and provide information about ways to reduce everyday exposures.
For example, safer options include buying organic produce, microwaving food in glass rather than plastic containers and avoiding products that contain phthalate or BPA. “If you’re going to talk to people about what they eat, that’s a perfect venue for talking about the environment,” said Dr. Woodruff, who coedited the textbook, Environmental Impacts on Reproductive Health and Fertility (Cambridge University Press: Cambridge, England, 2010).
The UCSF program provides patient guides in English and Spanish with suggestions of ways to reduce chemical exposures at work and at home.
Limits in the data
Michael Eisenberg, MD, a urologist and director of male reproductive medicine and surgery at Stanford (Calif.) University Medical Center, often gets questions from patients about how lifestyle and environmental exposures affect male fertility. (In her book, Dr. Swan also discusses how factors such as diet, exercise, smoking, and stress can affect male and female fertility.)
He found the evidence convincing that certain chemicals impact fertility – although, of course, it isn’t ethically possible to do randomized, controlled trials in which some people are intentionally exposed to chemicals to measure the effects. Along with adopting other healthy habits, he advised patients to avoid chemical exposures.
“It’s reasonable to try to eat organic and be mindful of where some of these exposures come from and try to minimize them to the extent possible,” he said.
Rebecca Sokol, MD, MPH, an endocrinologist and expert in male reproductive health, demonstrated the toxic effects of lead on sperm production in studies conducted on rats. But she views low-dose chemical exposure from everyday products as just one aspect of modern reproductive risks, some of which have stronger associations. For example, testosterone therapy impairs sperm production, and finasteride (a medication for male pattern baldness) has been linked to a reversible decline in sperm count.
“When it comes to these ubiquitous chemicals like phthalate and BPA, we explain to the patient that maybe they’re harmful, but we can’t say for sure,” because of the lack of causal data, said Dr. Sokol, professor emerita at the University of Southern California, who was on the panel that drafted the American Urological Association and American Society of Reproductive Medicine guideline on the diagnosis and treatment of male infertility.
Nonetheless, she advised patients to try to reduce exposures. “I don’t see us eradicating all the chemicals that might be bad for us unless we go back to another era. But we can do the best we can to avoid what we can.”
A call to action
Dr. Swan likened awareness of the health threat of chemical exposures to the gradual recognition of the climate crisis as a global imperative. Yet in some ways, the scientific work on chemical effects is even more daunting. The Environmental Protection Agency lists more than 86,000 chemicals on its inventory of chemical substances manufactured or imported into the United States.
Little is known about the potential effects of many chemicals that we inhale, ingest or absorb through our skin, Dr. Swan said. In her book, she noted the impact on wildlife – for example, reproductive abnormalities in frogs, alligators, and birds that were exposed to EDCs.
Yet Dr. Swan also takes solace in the lessons from the animal kingdom. Decades after the pesticide DDT, a neurotoxin and endocrine-disruptor, was banned in the United States in 1972, the bald eagle has made a comeback from near-extinction. She also pointed to a 2018 study which found that, while mice exposed to bisphenols passed on reproductive effects to offspring, when the exposures stopped, the effects disappeared after several generations.
“If we stop poisoning ourselves, we can turn this around,” said Dr. Swan. “That’s what I want people to know.”
Count Down frames the issues in language that is much starker than typically found in academic publications. But that is what’s necessary to draw attention to the effects of chemical exposures on human health and reproduction, Dr. Swan said. “I’m saying this in fairly extreme terms to alarm people, to make them realize it is a crisis and they have to act.”
No disclosures were reported.
Chemicals that pervade our modern world – plastics, pesticides, stain repellents, components of personal hygiene products – are contributing to a decades-long decline in fertility and could pose health risks even into future generations, according to an explosive new book by Shanna Swan, PhD, an environmental and reproductive epidemiologist at the Icahn School of Medicine at Mount Sinai, New York.
Dr. Swan laid out the case that endocrine-disrupting chemicals (EDCs) such as phthalates and bisphenol A (BPA) threaten human existence, a conclusion that stems in part from her 2017 meta-analysis that showed a 52% drop in sperm counts from 1973 to 2011 in men in North America, Europe, and Australia.
“This alarming rate of decline could mean the human race will be unable to reproduce itself if the trend continues,” Dr. Swan said in her book, “Count Down: How Our Modern World Is Threatening Sperm Counts, Altering Male and Female Reproductive Development, and Imperiling the Future of the Human Race,” (New York: Scribner, 2021) coauthored with health journalist Stacey Colino.
Her premise that EDCs pose a risk to both male and female fertility is underscored by new research. A March 2021 article in Human Reproduction links prenatal chemical exposures to lowered fertility in a study of 1,045 Swiss military conscripts.
The Swiss men, aged 18-22 years, were significantly more likely to have low semen volume and low total sperm count if their mothers reported that they had occupational exposures to four or more endocrine-disrupting chemicals while they were pregnant. These EDCs, which mimic natural hormones, included pesticides, heavy metals, phthalates, alkylphenolic compounds, and solvents that can be found in agricultural work or hair and beauty salons.
These chemicals are not so-called “forever chemicals” that persist in the human body. But the Swiss study still showed an association between exposure during pregnancy and the future fertility of the male children. “Those apparently small exposures that pass quickly can affect development,” said Dr. Swan, who was not affiliated with the research. “It takes very little in terms of time and amount of chemicals to alter fetal development.”
Health risks beyond reproduction
While Count Down is placing a new spotlight on chemical hazards, some major medical organizations have already taken positions on the risks. “Reducing exposure to toxic environmental agents is a critical area of intervention for ob.gyns.,” the American College of Obstetricians and Gynecologists said in an environmental policy priority. “The Endocrine Society is concerned that human health is at risk because the current extensive scientific knowledge on EDCs and their health effects is not effectively translated to regulatory policies that fully protect populations from EDC exposures.”
But for the medical community, addressing the impact of EDCs goes beyond advocacy for regulatory and legislative changes, Dr. Swan said in an interview. Physicians should talk to patients about the importance of reducing their chemical exposure to safeguard their overall health.
“Reproductive health and particularly sperm count, subfertility, and infertility are predictors of lifelong health,” she said. That includes associations between reproductive disorders and “the risk of heart disease, obesity, reproductive cancers and, perhaps most dramatically, with a shortened lifespan.”
Some medical schools are including information on environmental health and exposure risks in the curriculum, said Tracey Woodruff, PhD, MPH, director of the program on reproductive health and the environment at the University of California, San Francisco. She urged physicians to ask patients about potential occupational exposures to hazardous chemicals and provide information about ways to reduce everyday exposures.
For example, safer options include buying organic produce, microwaving food in glass rather than plastic containers and avoiding products that contain phthalate or BPA. “If you’re going to talk to people about what they eat, that’s a perfect venue for talking about the environment,” said Dr. Woodruff, who coedited the textbook, Environmental Impacts on Reproductive Health and Fertility (Cambridge University Press: Cambridge, England, 2010).
The UCSF program provides patient guides in English and Spanish with suggestions of ways to reduce chemical exposures at work and at home.
Limits in the data
Michael Eisenberg, MD, a urologist and director of male reproductive medicine and surgery at Stanford (Calif.) University Medical Center, often gets questions from patients about how lifestyle and environmental exposures affect male fertility. (In her book, Dr. Swan also discusses how factors such as diet, exercise, smoking, and stress can affect male and female fertility.)
He found the evidence convincing that certain chemicals impact fertility – although, of course, it isn’t ethically possible to do randomized, controlled trials in which some people are intentionally exposed to chemicals to measure the effects. Along with adopting other healthy habits, he advised patients to avoid chemical exposures.
“It’s reasonable to try to eat organic and be mindful of where some of these exposures come from and try to minimize them to the extent possible,” he said.
Rebecca Sokol, MD, MPH, an endocrinologist and expert in male reproductive health, demonstrated the toxic effects of lead on sperm production in studies conducted on rats. But she views low-dose chemical exposure from everyday products as just one aspect of modern reproductive risks, some of which have stronger associations. For example, testosterone therapy impairs sperm production, and finasteride (a medication for male pattern baldness) has been linked to a reversible decline in sperm count.
“When it comes to these ubiquitous chemicals like phthalate and BPA, we explain to the patient that maybe they’re harmful, but we can’t say for sure,” because of the lack of causal data, said Dr. Sokol, professor emerita at the University of Southern California, who was on the panel that drafted the American Urological Association and American Society of Reproductive Medicine guideline on the diagnosis and treatment of male infertility.
Nonetheless, she advised patients to try to reduce exposures. “I don’t see us eradicating all the chemicals that might be bad for us unless we go back to another era. But we can do the best we can to avoid what we can.”
A call to action
Dr. Swan likened awareness of the health threat of chemical exposures to the gradual recognition of the climate crisis as a global imperative. Yet in some ways, the scientific work on chemical effects is even more daunting. The Environmental Protection Agency lists more than 86,000 chemicals on its inventory of chemical substances manufactured or imported into the United States.
Little is known about the potential effects of many chemicals that we inhale, ingest or absorb through our skin, Dr. Swan said. In her book, she noted the impact on wildlife – for example, reproductive abnormalities in frogs, alligators, and birds that were exposed to EDCs.
Yet Dr. Swan also takes solace in the lessons from the animal kingdom. Decades after the pesticide DDT, a neurotoxin and endocrine-disruptor, was banned in the United States in 1972, the bald eagle has made a comeback from near-extinction. She also pointed to a 2018 study which found that, while mice exposed to bisphenols passed on reproductive effects to offspring, when the exposures stopped, the effects disappeared after several generations.
“If we stop poisoning ourselves, we can turn this around,” said Dr. Swan. “That’s what I want people to know.”
Count Down frames the issues in language that is much starker than typically found in academic publications. But that is what’s necessary to draw attention to the effects of chemical exposures on human health and reproduction, Dr. Swan said. “I’m saying this in fairly extreme terms to alarm people, to make them realize it is a crisis and they have to act.”
No disclosures were reported.
Chemicals that pervade our modern world – plastics, pesticides, stain repellents, components of personal hygiene products – are contributing to a decades-long decline in fertility and could pose health risks even into future generations, according to an explosive new book by Shanna Swan, PhD, an environmental and reproductive epidemiologist at the Icahn School of Medicine at Mount Sinai, New York.
Dr. Swan laid out the case that endocrine-disrupting chemicals (EDCs) such as phthalates and bisphenol A (BPA) threaten human existence, a conclusion that stems in part from her 2017 meta-analysis that showed a 52% drop in sperm counts from 1973 to 2011 in men in North America, Europe, and Australia.
“This alarming rate of decline could mean the human race will be unable to reproduce itself if the trend continues,” Dr. Swan said in her book, “Count Down: How Our Modern World Is Threatening Sperm Counts, Altering Male and Female Reproductive Development, and Imperiling the Future of the Human Race,” (New York: Scribner, 2021) coauthored with health journalist Stacey Colino.
Her premise that EDCs pose a risk to both male and female fertility is underscored by new research. A March 2021 article in Human Reproduction links prenatal chemical exposures to lowered fertility in a study of 1,045 Swiss military conscripts.
The Swiss men, aged 18-22 years, were significantly more likely to have low semen volume and low total sperm count if their mothers reported that they had occupational exposures to four or more endocrine-disrupting chemicals while they were pregnant. These EDCs, which mimic natural hormones, included pesticides, heavy metals, phthalates, alkylphenolic compounds, and solvents that can be found in agricultural work or hair and beauty salons.
These chemicals are not so-called “forever chemicals” that persist in the human body. But the Swiss study still showed an association between exposure during pregnancy and the future fertility of the male children. “Those apparently small exposures that pass quickly can affect development,” said Dr. Swan, who was not affiliated with the research. “It takes very little in terms of time and amount of chemicals to alter fetal development.”
Health risks beyond reproduction
While Count Down is placing a new spotlight on chemical hazards, some major medical organizations have already taken positions on the risks. “Reducing exposure to toxic environmental agents is a critical area of intervention for ob.gyns.,” the American College of Obstetricians and Gynecologists said in an environmental policy priority. “The Endocrine Society is concerned that human health is at risk because the current extensive scientific knowledge on EDCs and their health effects is not effectively translated to regulatory policies that fully protect populations from EDC exposures.”
But for the medical community, addressing the impact of EDCs goes beyond advocacy for regulatory and legislative changes, Dr. Swan said in an interview. Physicians should talk to patients about the importance of reducing their chemical exposure to safeguard their overall health.
“Reproductive health and particularly sperm count, subfertility, and infertility are predictors of lifelong health,” she said. That includes associations between reproductive disorders and “the risk of heart disease, obesity, reproductive cancers and, perhaps most dramatically, with a shortened lifespan.”
Some medical schools are including information on environmental health and exposure risks in the curriculum, said Tracey Woodruff, PhD, MPH, director of the program on reproductive health and the environment at the University of California, San Francisco. She urged physicians to ask patients about potential occupational exposures to hazardous chemicals and provide information about ways to reduce everyday exposures.
For example, safer options include buying organic produce, microwaving food in glass rather than plastic containers and avoiding products that contain phthalate or BPA. “If you’re going to talk to people about what they eat, that’s a perfect venue for talking about the environment,” said Dr. Woodruff, who coedited the textbook, Environmental Impacts on Reproductive Health and Fertility (Cambridge University Press: Cambridge, England, 2010).
The UCSF program provides patient guides in English and Spanish with suggestions of ways to reduce chemical exposures at work and at home.
Limits in the data
Michael Eisenberg, MD, a urologist and director of male reproductive medicine and surgery at Stanford (Calif.) University Medical Center, often gets questions from patients about how lifestyle and environmental exposures affect male fertility. (In her book, Dr. Swan also discusses how factors such as diet, exercise, smoking, and stress can affect male and female fertility.)
He found the evidence convincing that certain chemicals impact fertility – although, of course, it isn’t ethically possible to do randomized, controlled trials in which some people are intentionally exposed to chemicals to measure the effects. Along with adopting other healthy habits, he advised patients to avoid chemical exposures.
“It’s reasonable to try to eat organic and be mindful of where some of these exposures come from and try to minimize them to the extent possible,” he said.
Rebecca Sokol, MD, MPH, an endocrinologist and expert in male reproductive health, demonstrated the toxic effects of lead on sperm production in studies conducted on rats. But she views low-dose chemical exposure from everyday products as just one aspect of modern reproductive risks, some of which have stronger associations. For example, testosterone therapy impairs sperm production, and finasteride (a medication for male pattern baldness) has been linked to a reversible decline in sperm count.
“When it comes to these ubiquitous chemicals like phthalate and BPA, we explain to the patient that maybe they’re harmful, but we can’t say for sure,” because of the lack of causal data, said Dr. Sokol, professor emerita at the University of Southern California, who was on the panel that drafted the American Urological Association and American Society of Reproductive Medicine guideline on the diagnosis and treatment of male infertility.
Nonetheless, she advised patients to try to reduce exposures. “I don’t see us eradicating all the chemicals that might be bad for us unless we go back to another era. But we can do the best we can to avoid what we can.”
A call to action
Dr. Swan likened awareness of the health threat of chemical exposures to the gradual recognition of the climate crisis as a global imperative. Yet in some ways, the scientific work on chemical effects is even more daunting. The Environmental Protection Agency lists more than 86,000 chemicals on its inventory of chemical substances manufactured or imported into the United States.
Little is known about the potential effects of many chemicals that we inhale, ingest or absorb through our skin, Dr. Swan said. In her book, she noted the impact on wildlife – for example, reproductive abnormalities in frogs, alligators, and birds that were exposed to EDCs.
Yet Dr. Swan also takes solace in the lessons from the animal kingdom. Decades after the pesticide DDT, a neurotoxin and endocrine-disruptor, was banned in the United States in 1972, the bald eagle has made a comeback from near-extinction. She also pointed to a 2018 study which found that, while mice exposed to bisphenols passed on reproductive effects to offspring, when the exposures stopped, the effects disappeared after several generations.
“If we stop poisoning ourselves, we can turn this around,” said Dr. Swan. “That’s what I want people to know.”
Count Down frames the issues in language that is much starker than typically found in academic publications. But that is what’s necessary to draw attention to the effects of chemical exposures on human health and reproduction, Dr. Swan said. “I’m saying this in fairly extreme terms to alarm people, to make them realize it is a crisis and they have to act.”
No disclosures were reported.
Implementation of a Pharmacist-Managed Transitions of Care Tool
Effective transitions of care (TOC) are essential to ensure quality continuity of care after hospital discharge. About 20 to 30% of patients experience an adverse event (AE) in the peridischarge period when discharged to the community.1 Additionally, about two-thirds of AEs are preventable.1 The Joint Commission has identified various breakdowns in care that are associated with poor outcomes, including a lack of standardized discharge procedures, limited time dedicated to discharge planning and processes, and patients who lack the necessary resources or skills to implement discharge care plans.2
Background
The most impactful TOC programs are those that target patients who are at high risk for readmission or adverse outcomes.3 Factors such as advanced age, polypharmacy, cognitive impairment, and lack of social support are patient characteristics that have been associated with unfavorable outcomes after discharge.4 To identify this subset of high-risk individuals, various risk assessment scores have been developed, ranging from those that are used locally at the facility level to those that are nationally validated. The LACE score (Length of hospital stay; Acuity of the admission; Comorbidities measured with the Charlson comorbidity index score; and Emergency department visits within the past 6 months) is a validated index scoring tool that is used to identify medical and surgical patients at risk for readmission or death within 30 days of hospital discharge. On a 19-point scale, a score of ≥ 10 is considered high risk.5 Specific to the US Department of Veterans Affairs (VA), the Care Assessment Needs (CAN) score was developed to risk stratify the veteran population. The CAN score is generated using information including patient demographics, medical conditions, VA health care utilization, vital signs, laboratory values, medications, and socioeconomic status. This score is expressed as a percentile that compares the probability of death or admission among veterans at 90 days and 1 year postdischarge. Veterans in the 99th percentile have a 74% risk for these adverse outcomes at 1 year.6
The Joint Commission states that a fundamental component to assuring safe and effective TOC is medication management, which includes the involvement of pharmacists.2 TOC programs with pharmacist involvement have shown significant improvements related to reduced 30-day hospital readmissions and health care costs in addition to significant medication-related interventions.7-9 While this body of evidence continues to grow and demonstrates that pharmacists are an integral component of the TOC process, there is no gold standard program. Brantley and colleagues noted that a weakness of many TOC programs is that they are one dimensional, meaning that they focus on only 1 element of care transitions or 1 specific patient population or disease.10
There is well-supported evidence of high-impact interventions for pharmacists involved early in the admission process, but data are less robust on the discharge process. 11,12 Therefore, the primary focus of this project was to develop a pharmacist-based TOC program and implement a process for communicating high-risk patients who are discharging from our hospital across the continuum of care.
Setting
The Richard L. Roudebush VA Medical Center (RLRVAMC) is a tertiary care referral center for veterans in Indiana and eastern Illinois. Acute care clinical pharmacists are fully integrated into the acute care teams and practice under a comprehensive care model. Pharmacists attend daily patient care rounds and conduct discharge medication reconciliation for all patients with additional bedside counseling for patients who are being discharged home.
Primary care services are provided by patient aligned care teams (PACTs), multidisciplinary teams composed of physicians, advanced practice nurses, pharmacists, mental health care providers, registered nurses, dieticians, and care coordinators. Ambulatory Care or PACT clinical pharmacists are established within each RLRVAMC PACT clinic and provide comprehensive care management through an independent scope of practice for several chronic diseases, including hypertension, type 2 diabetes mellitus (T2DM), dyslipidemia, hypothyroidism, and tobacco cessation. Prior to this project implementation, there was no formalized or standardized method for facilitating routine communication of patients between acute care and PACT pharmacists in the TOC process.
Pilot Study
In 2017, RLRVAMC implemented a TOC pharmacy program pilot. A pharmacy resident and both acute care and PACT clinical pharmacy specialists (CPSs) developed the service. The pilot program was conducted from September 1, 2017 to March 1, 2018. The initial phase consisted of the development of an electronic TOC tool to standardize communication between acute care and PACT pharmacists. The TOC tool was created on a secure site accessible only to pharmacy personnel and not part of the formal medical record. (Figure 1).
The acute care pharmacist identified high-risk patients through calculated CAN and LACE scores during the discharge process and offered PACT pharmacist follow-up to the patient during bedside discharge counseling. Information was then entered into the TOC tool, including patient identifiers and a message with specific information outlining the reason for referral. PACT pharmacists routinely reviewed the tool and attempted to phone each patient within 7 days of discharge. Follow-up included medication reconciliation and chronic disease management as warranted at the discretion of the PACT pharmacist. All postdischarge follow-up appointments were created and documented in the electronic health record. A retrospective chart review was completed on patients who were entered into the TOC tool.
Patients were eligible for referral if they were discharged during the study period with primary care established in one of the facility’s PACT clinics. Additionally, patients had to meet ≥ 1 of the following criteria, deeming them a high risk for readmission: LACE score ≥ 10, CAN score ≥ 90th percentile, or be considered high risk based on the discretion of the acute care pharmacist. Patients were included in the analysis if they met the CAN or LACE score requirement. Patients were excluded if they received primary care from a site other than a RLRVAMC PACT clinic. This included non-VA primary care, home-based primary care, or VA community-based outpatient clinics (CBOCs). Patients also were excluded if they required further institutional care postdischarge (ie, subacute rehabilitation, extended care facility, etc), discharged to hospice, or against medical advice.
The average referral rate per month during the pilot study was 19 patients, with 113 total referrals during the 6-month study period. Lower rates of index emergency department (ED) visits (5.3% vs 23.3%) and readmissions (1% vs 6.7%) were seen in the group of patients who received PACT pharmacist follow-up postdischarge compared with those who did not. Additionally, PACT pharmacists were able to make > 120 interventions, averaging 1.7 interventions per patient. Of note, these results were not statistically analyzed and were assessed as observational data to determine whether the program had the potential to be impactful. The results of the pilot study demonstrated positive outcomes associated with having a pharmacist-based TOC process and led to the desire for further development and implementation of the TOC program at the RLRVAMC. These positive results prompted a second phase project to address barriers, make improvements, and ensure sustainability.
Methods
Phase 2 was a quality improvement initiative; therefore, institutional review board approval was not needed. The aim of phase 2 was to improve, expand, and sustain the TOC program that was implemented in the pilot study. Barriers identified after discussion with acute care and PACT pharmacists included difficulty in making referrals due to required entry of cumbersome readmission risk factor calculations, limiting inclusion to patients who receive primary care at the main hospital facility, and the expansion of pharmacy staff with new pharmacists who were not knowledgeable of the referral process.
Design
To overcome barriers, 4 main targeted interventions were needed: streamlining the referral process, enhancing pharmacy staff education, updating the discharge note template, and expanding the criteria to include patients who receive care at VA CBOCs. The referral process was streamlined by removing required calculated readmission risk scores, allowing pharmacist judgement to take precedence for referrals. Focused face-to-face education was provided to acute care and PACT pharmacists about the referral process and inclusion criteria to increase awareness and provide guidance of who may benefit from entry into the tool. Unlike the first phase of the study, education was provided for outpatient staff pharmacists responsible for discharging patients on the weekends. Additionally, the pharmacists received a printed quick reference guide of the information covered during the education sessions (Figure 2). Referral prompts were embedded into the standard pharmacy discharge note template to serve as a reminder to discharging pharmacists to assess patients for inclusion into the tool and provided a direct link to the tool. Expansion to include VA CBOCs occurred postpilot study, allowing increased patient access to this TOC service. All other aspects of the program were continued from the pilot phase.
Patients were eligible if they were discharged from RLRVAMC between October 1, 2018 and February 28, 2019. Additionally, the patient had to be established in a PACT clinic for primary care and have been referred to the tool based on the discretion of an acute care pharmacist. Patients were excluded if they were discharged against medical advice or to any facility where the patient and/or caregiver would not be responsible for medication administration (eg, subacute rehabilitation, extended care facility), or if the patient refused pharmacy follow-up.
Outcomes
The primary outcomes assessed were all-cause and index ED visits and readmissions within 30 days of discharge. All-cause ED visits and readmissions were defined as a second visit to RLRVAMC , regardless of readmission diagnosis. Index ED visits and readmissions were defined as those that were related to the initial admission diagnosis. Additional data collected and analyzed included the number of patients referred by pharmacists, number and type of medication discrepancies, medication changes, counseling interventions, time to follow-up postdischarge, and number of patients added to the PACT pharmacist’s clinic schedule for further management. A discrepancy identified by a PACT pharmacist was defined as a difference between the discharge medication list and the patient-reported medication list at the time of follow-up. Patients who were referred to the TOC tool but were unable to be reached by telephone served as the control group for this study.
Data Collection
A retrospective chart review was completed on patients entered into the tool. Data were collected and kept in a secured Microsoft Excel workbook. Baseline characteristics were analyzed using either a χ2 for nominal data or Student t test for continuous data. The primary outcomes were analyzed using a χ2 test. All statistical tests were analyzed using MiniTab 19 Statistical Software.
Results
Pharmacists added 172 patients into the TOC tool; 139 patients met inclusion criteria. Of those excluded, most were because the PACT pharmacist did not attempt to contact the patient since they already had a primary care visit scheduled postdischarge (Table 1). Of the 139 patients who met the inclusion criteria, 99 were successfully contacted by a PACT pharmacist. Most patients were aged in their 60s, male, and white. Both groups had a similar quantity of outpatient medications on admission and medication changes made at discharge. Additionally, both groups had a similar number of patients with hospitalizations and/or ED visits in the 3 months before hospital admission that resulted in TOC tool referral (Table 2).
Hospital Readmission
Hospital 30-day readmission rates for patients who were successfully followed by pharmacy compared with those who were not were 5.1% vs 15.0% (P = .049) for index readmissions and 8.1% vs 27.5% (P = .03) for all-cause readmissions. No statistically significant difference existed between those patients with follow-up compared with those without follow-up for either index (10.1% vs 12.5%, respectively; P = .68) or for all-cause ED visit rates (15.2% vs 20.0%, respectively; P = .49).
Patient Encounters
The average time to follow-up was 8.8 days, which was above the predetermined goal of contact within 7 days. Additionally, this was a decline from the initial pilot study, which had an average time to reach of 4.7 days. All patients reached by a pharmacist received medication reconciliation, with ≥ 28% of patients having ≥ 1 discrepancy. There were 43 discrepancies among all patients. Of the discrepancies, 25 were reported as errors performed by the patient, and 18 were from an error during the discharge process. The discrepancies that resulted from patient error were primarily patients who took the wrong dose of prescribed medications. Other patient discrepancies included taking medications not as scheduled, omitting medications (both intentionally and mistakenly), continuing to take medications that had been discontinued by a health care provider and improper administration technique. Examples of provider errors that occurred during the discharge process included not ordering medications for patient to pick up at discharge, not discontinuing a medication from the patient’s profile, and failure to renew expired prescriptions.
Additional counseling was provided to 75% of patients: The most common reason for counseling was T2DM, hypertension, and dyslipidemia management. PACT pharmacists changed medication regimens for 27.3% of patients for improved control of chronic diseases or relief of medication AEs.
At the end of each visit, patients were assessed to determine whether they could benefit from additional pharmacy follow-up. Thirty-seven patients were added to the pharmacist schedules for disease management appointments. The most common conditions for these appointments were T2DM, hypertension, tobacco cessation, and hyperlipidemia. Among the 37 patients who had pharmacy follow-up, there were 137 additional pharmacy appointments within the study period.
Program Referrals
After expansion to include the VA CBOCs, elimination of the elevated LACE or CAN score requirement, and additional staff education, the rate of referrals per month increased during phase 2 in comparison to the pilot study (Figure 3). There were a mean (SD) of 34 (10) referrals per month. Although not statistically analyzed, it is an objective increase in comparison to a mean 19 referrals per month in the pilot study.
Discussion
The continued development and use of a pharmacist-driven TOC tool at RLRVAMC increased communication and follow-up of high-risk patients, demonstrated the ability of pharmacists to identify and intervene in medication-related issues postdischarge, and successfully reduce 30-day readmissions. This program emphasized pharmacist involvement during the discharge process and created a standardized mechanism for TOC follow-up, addressing multiple areas that were identified by The Joint Commission as being associated with poor outcomes. The advanced pharmacy practice model at RLRVAMC allowed for a multidimensional program, including prospective patient identification and multiple pharmacy touchpoints. This is unique in comparison to many of the one-dimensional programs described in the literature.
Polypharmacy has been identified as a major predictor of medication discrepancies postdischarge, and patients with ≥ 10 active medications have been found to be at highest risk.13,14 Patients in this study had a mean 13 active medications on admission, with a mean 5 medication changes at discharge. PACT pharmacists documented 28 of 99 patients with ≥ 1 medication-related discrepancy at postdischarge reconciliation. This 28% discrepancy rate is consistent with discrepancy rates previously reported in the literature, which ranged from 14 to 45% in large meta-analyses.14,15 The majority of these discrepancies (58%) were related to patients who took the wrong dose of a prescribed medication.
Targeted interventions to overcome barriers in the pilot study increased the referral rates to the TOC tool; however, the increase in referral rate was associated with increased time to follow up by ambulatory care pharmacists. The extended follow-up times were seen most often in the 2 busiest primary care clinics, one of which is considered a teaching clinic for medical residents. Pharmacists were required to integrate these calls into their normal work schedule and were not provided additional time for calling, allowing for an increased follow-up time. The increased follow-up time likely contributed to the increased number of patients excluded due to already having PACT follow-up, giving more time for the primary care provider to have an appointment with the patient. The ambulatory care pharmacist could then determine whether further intervention was needed. In the summer of 2018, a decrease in referral rates occurred for a short time, but this is likely explained by incoming new residents and staff within the pharmacy department and decreased awareness among the new staff. The enhanced staff education took place during September 2018 and lead to increased referral rates compared with those seen in months prior.
PACT pharmacists were not only able to identify discrepancies, but also provide timely intervention on a multitude of medication-related issues by using their scope of practice (SOP). Most interventions were related to medication or disease counseling, including lifestyle, device, and disease education. The independent SOP of our PACT pharmacists is a unique aspect of this program and allowed pharmacists to independently adjust many aspects of a patient’s medication regimen during follow-up visits.
The outcomes of 30-day index and all-cause readmissions, as well as index and all-cause ED visit rates, were lower in the subset of patients who received PACT pharmacist follow-up after discharge (Table 3). The difference was most pronounced in the all-cause readmission rates: Only 8.1% of patients who received PACT follow-up experienced a readmission compared with 27.5% of those who did not. The difference between the groups regarding ED visit rates were not as pronounced, but this may be attributed to a limited sample size. These data indicate that the role of the pharmacist in identifying discrepancies and performing interventions at follow-up may play a clinically significant part in reducing both ED visit rates and hospital readmissions.
Limitations
There are some limitations identified within this study. Although the referral criteria were relaxed from the pilot study and enhanced education was created, continued education regarding appropriate referral of TOC patients continues to be necessary given intermittent staff changeover, incorporation of pharmacy trainees, and modifications to clinic workflow. Patients who were discharged to facilities were not included. This ensured that appropriate and consistent PACT pharmacist follow-up would be available, but likely reduced our sample size.
Although performing this study in a closed health care system with pharmacists who have independent SOPs is a strength of our study, also it can limit generalizability. Not all facilities house both acute care and ambulatory care in one location with wide SOPs to allow for comprehensive and continued care. Last, this study used convenience sampling, potentially introducing selection bias, as patients unable to be reached by PACT pharmacists may inherently be at increased risk for hospital readmission. However, in the 3 months preceding the hospital admission that resulted in TOC tool referral, both groups had a similar number of patients with hospital admissions and ED visits.
The TOC tool has become fully integrated into the daily workflow for both acute care and PACT pharmacists. After the conclusion of the study period, the referral rates into the tool have been maintained at a steady level, even surpassing the rates seen during the study period. In comparison with the pilot study, PACT pharmacists reported a subjective increase in referrals placed for procedures such as medication reconciliation or adherence checks. This is likely because acute care pharmacists were able to use their clinical judgement rather than to rely solely on calculated readmission risk scores for TOC tool referral.
The success of the TOC program led to the expansion to other specialty areas. ED pharmacists now refer patients from the ED who were not admitted to the hospital but would benefit from PACT follow-up. Additionally, the option to refer hematology and oncology patients was added to allow these patients to be followed up by our hematology/oncology CPSs by phone appointments. Unique reasons for follow-up for this patient population include concerns about delayed chemotherapy cycles or chemotherapy-associated AEs.
Conclusions
This study outlines the creation and continued improvement of a pharmacist-based TOC program. The program was designed as a method of communication between acute care and PACT pharmacists about high-risk patients. The creation of this program allowed PACT pharmacists not only to identify discrepancies and make interventions on high-risk patients, but also demonstrate that having pharmacists involved in these programs may have a positive impact on readmissions and ED visits. The success of the TOC tool at the RLRVAMC has led to its expansion and is now an integral part of the daily workflow for both acute care and PACT pharmacists.
1. Forster AJ, Murff HJ, Peterson JF, Gandhi TK, Bates DW. The incidence and severity of adverse effects affecting patients after discharge from the hospital. Ann Intern Med. 2003;138(3):161-167. doi:10.7326/0003-4819-138-3-200302040-00007
2. The Joint Commission. Transitions of care: the need for collaboration across entire care continuum. Published February 2013. Accessed February 25, 2021. http://www.jointcommission.org/assets/1/6/TOC_Hot_Topics.pdf
3. Leppin AL, Gionfriddo MR, Kessler M, et al. Preventing 30-day hospital readmissions: a systematic review and meta-analysis of randomized trials. JAMA Intern Med. 2014;174(7):1095-1107. doi:10.1001/jamainternmed.2014.1608
4. Medicare Hospital Compare. Readmissions and deaths. Accessed February 25, 2021. https://www.cms.gov/Medicare/Quality-Initiatives-Patient-Assessment-Instruments/HospitalQualityInits/VA-Data
5. van Walraven C, Dhalla IA, Bell C, et al. Derivation and validation of an index to predict early death or unplanned readmission after discharge from hospital to the community. CMAJ. 2010;182(6):551-557. doi:10.1503/cmaj.091117
6. US Department of Veteran Affairs. Care Assessment Needs (CAN) score report. Updated May 14, 2019. Accessed February 25, 2021. https://www.va.gov/HEALTHCAREEXCELLENCE/about/organization/examples/care-assessment-needs.asp
7. Schnipper JL, Kirwin JL, Cotugno MC, et al. Role of pharmacist counseling in preventing adverse drug events after hospitalization. Arch Intern Med. 2006;166(5):565-571. doi:10.1001/archinte.166.5.565
8. Phatak A, Prusi R, Ward B, et al. Impact of pharmacist involvement in the transitional care of high-risk patients through medication reconciliation, medication education, and post-discharge call-backs. J Hosp Med. 2016;11(1):40-44. doi:10.1002/jhm.2493
9. Coleman EA, Min SJ, Chomiak A, Kramer AM. Posthospital care transitions: patterns, complications, and risk identification. Health Serv Res. 2004;39(5):1449-1465. doi:10.1111/j.1475-6773.2004.00298.x
10. Brantley AF, Rossi DM, Barnes-Warren S, Francisco JC, Schatten I, Dave V. Bridging gaps in care: implementation of a pharmacist-led transitions of care program. Am J Health Syst Pharm. 2018;75(5)(suppl 1):S1-S5. doi:10.2146/ajhp160652
11. Scarsi KK, Fotis MA, Noskin GA. Pharmacist participation in medical rounds reduces medical errors. Am J Health Syst Pharm. 2002;59(21):2089-2092. doi:10.1093/ajhp/59.21.2089
12. Pevnick JM, Nguyen C, Jackevicius CA, et al. Improving admission medication reconciliation with pharmacists or pharmacy technicians in the emergency department: a randomised controlled trial. BMJ Qual Saf. 2018;27:512-520. doi:10.1136/bmjqs-2017-006761.
13. Kirwin J, Canales AE, Bentley ML, et al; American College of Clinical Pharmacy. Process indicators of quality clinical pharmacy services during transitions of care. Pharmacotherapy. 2012;32(11):e338-e347. doi:10.1002/phar.1214
14. Kwan JL, Lo L, Sampson M, et al. Medication reconciliation during transitions of care as a patient safety strategy: a systematic review. Ann Intern Med. 2013;158(5, part 2):397-403. doi:10.7326/0003-4819-158-5-201303051-00006
15. Stitt DM, Elliot DP, Thompson SN. Medication discrepancies identified at time of hospital discharge in a geriatric population. Am J Geriatr Pharmacother. 2011;9(4):234-240. doi:10.1016/j.amjopharm.2011.06.002
Effective transitions of care (TOC) are essential to ensure quality continuity of care after hospital discharge. About 20 to 30% of patients experience an adverse event (AE) in the peridischarge period when discharged to the community.1 Additionally, about two-thirds of AEs are preventable.1 The Joint Commission has identified various breakdowns in care that are associated with poor outcomes, including a lack of standardized discharge procedures, limited time dedicated to discharge planning and processes, and patients who lack the necessary resources or skills to implement discharge care plans.2
Background
The most impactful TOC programs are those that target patients who are at high risk for readmission or adverse outcomes.3 Factors such as advanced age, polypharmacy, cognitive impairment, and lack of social support are patient characteristics that have been associated with unfavorable outcomes after discharge.4 To identify this subset of high-risk individuals, various risk assessment scores have been developed, ranging from those that are used locally at the facility level to those that are nationally validated. The LACE score (Length of hospital stay; Acuity of the admission; Comorbidities measured with the Charlson comorbidity index score; and Emergency department visits within the past 6 months) is a validated index scoring tool that is used to identify medical and surgical patients at risk for readmission or death within 30 days of hospital discharge. On a 19-point scale, a score of ≥ 10 is considered high risk.5 Specific to the US Department of Veterans Affairs (VA), the Care Assessment Needs (CAN) score was developed to risk stratify the veteran population. The CAN score is generated using information including patient demographics, medical conditions, VA health care utilization, vital signs, laboratory values, medications, and socioeconomic status. This score is expressed as a percentile that compares the probability of death or admission among veterans at 90 days and 1 year postdischarge. Veterans in the 99th percentile have a 74% risk for these adverse outcomes at 1 year.6
The Joint Commission states that a fundamental component to assuring safe and effective TOC is medication management, which includes the involvement of pharmacists.2 TOC programs with pharmacist involvement have shown significant improvements related to reduced 30-day hospital readmissions and health care costs in addition to significant medication-related interventions.7-9 While this body of evidence continues to grow and demonstrates that pharmacists are an integral component of the TOC process, there is no gold standard program. Brantley and colleagues noted that a weakness of many TOC programs is that they are one dimensional, meaning that they focus on only 1 element of care transitions or 1 specific patient population or disease.10
There is well-supported evidence of high-impact interventions for pharmacists involved early in the admission process, but data are less robust on the discharge process. 11,12 Therefore, the primary focus of this project was to develop a pharmacist-based TOC program and implement a process for communicating high-risk patients who are discharging from our hospital across the continuum of care.
Setting
The Richard L. Roudebush VA Medical Center (RLRVAMC) is a tertiary care referral center for veterans in Indiana and eastern Illinois. Acute care clinical pharmacists are fully integrated into the acute care teams and practice under a comprehensive care model. Pharmacists attend daily patient care rounds and conduct discharge medication reconciliation for all patients with additional bedside counseling for patients who are being discharged home.
Primary care services are provided by patient aligned care teams (PACTs), multidisciplinary teams composed of physicians, advanced practice nurses, pharmacists, mental health care providers, registered nurses, dieticians, and care coordinators. Ambulatory Care or PACT clinical pharmacists are established within each RLRVAMC PACT clinic and provide comprehensive care management through an independent scope of practice for several chronic diseases, including hypertension, type 2 diabetes mellitus (T2DM), dyslipidemia, hypothyroidism, and tobacco cessation. Prior to this project implementation, there was no formalized or standardized method for facilitating routine communication of patients between acute care and PACT pharmacists in the TOC process.
Pilot Study
In 2017, RLRVAMC implemented a TOC pharmacy program pilot. A pharmacy resident and both acute care and PACT clinical pharmacy specialists (CPSs) developed the service. The pilot program was conducted from September 1, 2017 to March 1, 2018. The initial phase consisted of the development of an electronic TOC tool to standardize communication between acute care and PACT pharmacists. The TOC tool was created on a secure site accessible only to pharmacy personnel and not part of the formal medical record. (Figure 1).
The acute care pharmacist identified high-risk patients through calculated CAN and LACE scores during the discharge process and offered PACT pharmacist follow-up to the patient during bedside discharge counseling. Information was then entered into the TOC tool, including patient identifiers and a message with specific information outlining the reason for referral. PACT pharmacists routinely reviewed the tool and attempted to phone each patient within 7 days of discharge. Follow-up included medication reconciliation and chronic disease management as warranted at the discretion of the PACT pharmacist. All postdischarge follow-up appointments were created and documented in the electronic health record. A retrospective chart review was completed on patients who were entered into the TOC tool.
Patients were eligible for referral if they were discharged during the study period with primary care established in one of the facility’s PACT clinics. Additionally, patients had to meet ≥ 1 of the following criteria, deeming them a high risk for readmission: LACE score ≥ 10, CAN score ≥ 90th percentile, or be considered high risk based on the discretion of the acute care pharmacist. Patients were included in the analysis if they met the CAN or LACE score requirement. Patients were excluded if they received primary care from a site other than a RLRVAMC PACT clinic. This included non-VA primary care, home-based primary care, or VA community-based outpatient clinics (CBOCs). Patients also were excluded if they required further institutional care postdischarge (ie, subacute rehabilitation, extended care facility, etc), discharged to hospice, or against medical advice.
The average referral rate per month during the pilot study was 19 patients, with 113 total referrals during the 6-month study period. Lower rates of index emergency department (ED) visits (5.3% vs 23.3%) and readmissions (1% vs 6.7%) were seen in the group of patients who received PACT pharmacist follow-up postdischarge compared with those who did not. Additionally, PACT pharmacists were able to make > 120 interventions, averaging 1.7 interventions per patient. Of note, these results were not statistically analyzed and were assessed as observational data to determine whether the program had the potential to be impactful. The results of the pilot study demonstrated positive outcomes associated with having a pharmacist-based TOC process and led to the desire for further development and implementation of the TOC program at the RLRVAMC. These positive results prompted a second phase project to address barriers, make improvements, and ensure sustainability.
Methods
Phase 2 was a quality improvement initiative; therefore, institutional review board approval was not needed. The aim of phase 2 was to improve, expand, and sustain the TOC program that was implemented in the pilot study. Barriers identified after discussion with acute care and PACT pharmacists included difficulty in making referrals due to required entry of cumbersome readmission risk factor calculations, limiting inclusion to patients who receive primary care at the main hospital facility, and the expansion of pharmacy staff with new pharmacists who were not knowledgeable of the referral process.
Design
To overcome barriers, 4 main targeted interventions were needed: streamlining the referral process, enhancing pharmacy staff education, updating the discharge note template, and expanding the criteria to include patients who receive care at VA CBOCs. The referral process was streamlined by removing required calculated readmission risk scores, allowing pharmacist judgement to take precedence for referrals. Focused face-to-face education was provided to acute care and PACT pharmacists about the referral process and inclusion criteria to increase awareness and provide guidance of who may benefit from entry into the tool. Unlike the first phase of the study, education was provided for outpatient staff pharmacists responsible for discharging patients on the weekends. Additionally, the pharmacists received a printed quick reference guide of the information covered during the education sessions (Figure 2). Referral prompts were embedded into the standard pharmacy discharge note template to serve as a reminder to discharging pharmacists to assess patients for inclusion into the tool and provided a direct link to the tool. Expansion to include VA CBOCs occurred postpilot study, allowing increased patient access to this TOC service. All other aspects of the program were continued from the pilot phase.
Patients were eligible if they were discharged from RLRVAMC between October 1, 2018 and February 28, 2019. Additionally, the patient had to be established in a PACT clinic for primary care and have been referred to the tool based on the discretion of an acute care pharmacist. Patients were excluded if they were discharged against medical advice or to any facility where the patient and/or caregiver would not be responsible for medication administration (eg, subacute rehabilitation, extended care facility), or if the patient refused pharmacy follow-up.
Outcomes
The primary outcomes assessed were all-cause and index ED visits and readmissions within 30 days of discharge. All-cause ED visits and readmissions were defined as a second visit to RLRVAMC , regardless of readmission diagnosis. Index ED visits and readmissions were defined as those that were related to the initial admission diagnosis. Additional data collected and analyzed included the number of patients referred by pharmacists, number and type of medication discrepancies, medication changes, counseling interventions, time to follow-up postdischarge, and number of patients added to the PACT pharmacist’s clinic schedule for further management. A discrepancy identified by a PACT pharmacist was defined as a difference between the discharge medication list and the patient-reported medication list at the time of follow-up. Patients who were referred to the TOC tool but were unable to be reached by telephone served as the control group for this study.
Data Collection
A retrospective chart review was completed on patients entered into the tool. Data were collected and kept in a secured Microsoft Excel workbook. Baseline characteristics were analyzed using either a χ2 for nominal data or Student t test for continuous data. The primary outcomes were analyzed using a χ2 test. All statistical tests were analyzed using MiniTab 19 Statistical Software.
Results
Pharmacists added 172 patients into the TOC tool; 139 patients met inclusion criteria. Of those excluded, most were because the PACT pharmacist did not attempt to contact the patient since they already had a primary care visit scheduled postdischarge (Table 1). Of the 139 patients who met the inclusion criteria, 99 were successfully contacted by a PACT pharmacist. Most patients were aged in their 60s, male, and white. Both groups had a similar quantity of outpatient medications on admission and medication changes made at discharge. Additionally, both groups had a similar number of patients with hospitalizations and/or ED visits in the 3 months before hospital admission that resulted in TOC tool referral (Table 2).
Hospital Readmission
Hospital 30-day readmission rates for patients who were successfully followed by pharmacy compared with those who were not were 5.1% vs 15.0% (P = .049) for index readmissions and 8.1% vs 27.5% (P = .03) for all-cause readmissions. No statistically significant difference existed between those patients with follow-up compared with those without follow-up for either index (10.1% vs 12.5%, respectively; P = .68) or for all-cause ED visit rates (15.2% vs 20.0%, respectively; P = .49).
Patient Encounters
The average time to follow-up was 8.8 days, which was above the predetermined goal of contact within 7 days. Additionally, this was a decline from the initial pilot study, which had an average time to reach of 4.7 days. All patients reached by a pharmacist received medication reconciliation, with ≥ 28% of patients having ≥ 1 discrepancy. There were 43 discrepancies among all patients. Of the discrepancies, 25 were reported as errors performed by the patient, and 18 were from an error during the discharge process. The discrepancies that resulted from patient error were primarily patients who took the wrong dose of prescribed medications. Other patient discrepancies included taking medications not as scheduled, omitting medications (both intentionally and mistakenly), continuing to take medications that had been discontinued by a health care provider and improper administration technique. Examples of provider errors that occurred during the discharge process included not ordering medications for patient to pick up at discharge, not discontinuing a medication from the patient’s profile, and failure to renew expired prescriptions.
Additional counseling was provided to 75% of patients: The most common reason for counseling was T2DM, hypertension, and dyslipidemia management. PACT pharmacists changed medication regimens for 27.3% of patients for improved control of chronic diseases or relief of medication AEs.
At the end of each visit, patients were assessed to determine whether they could benefit from additional pharmacy follow-up. Thirty-seven patients were added to the pharmacist schedules for disease management appointments. The most common conditions for these appointments were T2DM, hypertension, tobacco cessation, and hyperlipidemia. Among the 37 patients who had pharmacy follow-up, there were 137 additional pharmacy appointments within the study period.
Program Referrals
After expansion to include the VA CBOCs, elimination of the elevated LACE or CAN score requirement, and additional staff education, the rate of referrals per month increased during phase 2 in comparison to the pilot study (Figure 3). There were a mean (SD) of 34 (10) referrals per month. Although not statistically analyzed, it is an objective increase in comparison to a mean 19 referrals per month in the pilot study.
Discussion
The continued development and use of a pharmacist-driven TOC tool at RLRVAMC increased communication and follow-up of high-risk patients, demonstrated the ability of pharmacists to identify and intervene in medication-related issues postdischarge, and successfully reduce 30-day readmissions. This program emphasized pharmacist involvement during the discharge process and created a standardized mechanism for TOC follow-up, addressing multiple areas that were identified by The Joint Commission as being associated with poor outcomes. The advanced pharmacy practice model at RLRVAMC allowed for a multidimensional program, including prospective patient identification and multiple pharmacy touchpoints. This is unique in comparison to many of the one-dimensional programs described in the literature.
Polypharmacy has been identified as a major predictor of medication discrepancies postdischarge, and patients with ≥ 10 active medications have been found to be at highest risk.13,14 Patients in this study had a mean 13 active medications on admission, with a mean 5 medication changes at discharge. PACT pharmacists documented 28 of 99 patients with ≥ 1 medication-related discrepancy at postdischarge reconciliation. This 28% discrepancy rate is consistent with discrepancy rates previously reported in the literature, which ranged from 14 to 45% in large meta-analyses.14,15 The majority of these discrepancies (58%) were related to patients who took the wrong dose of a prescribed medication.
Targeted interventions to overcome barriers in the pilot study increased the referral rates to the TOC tool; however, the increase in referral rate was associated with increased time to follow up by ambulatory care pharmacists. The extended follow-up times were seen most often in the 2 busiest primary care clinics, one of which is considered a teaching clinic for medical residents. Pharmacists were required to integrate these calls into their normal work schedule and were not provided additional time for calling, allowing for an increased follow-up time. The increased follow-up time likely contributed to the increased number of patients excluded due to already having PACT follow-up, giving more time for the primary care provider to have an appointment with the patient. The ambulatory care pharmacist could then determine whether further intervention was needed. In the summer of 2018, a decrease in referral rates occurred for a short time, but this is likely explained by incoming new residents and staff within the pharmacy department and decreased awareness among the new staff. The enhanced staff education took place during September 2018 and lead to increased referral rates compared with those seen in months prior.
PACT pharmacists were not only able to identify discrepancies, but also provide timely intervention on a multitude of medication-related issues by using their scope of practice (SOP). Most interventions were related to medication or disease counseling, including lifestyle, device, and disease education. The independent SOP of our PACT pharmacists is a unique aspect of this program and allowed pharmacists to independently adjust many aspects of a patient’s medication regimen during follow-up visits.
The outcomes of 30-day index and all-cause readmissions, as well as index and all-cause ED visit rates, were lower in the subset of patients who received PACT pharmacist follow-up after discharge (Table 3). The difference was most pronounced in the all-cause readmission rates: Only 8.1% of patients who received PACT follow-up experienced a readmission compared with 27.5% of those who did not. The difference between the groups regarding ED visit rates were not as pronounced, but this may be attributed to a limited sample size. These data indicate that the role of the pharmacist in identifying discrepancies and performing interventions at follow-up may play a clinically significant part in reducing both ED visit rates and hospital readmissions.
Limitations
There are some limitations identified within this study. Although the referral criteria were relaxed from the pilot study and enhanced education was created, continued education regarding appropriate referral of TOC patients continues to be necessary given intermittent staff changeover, incorporation of pharmacy trainees, and modifications to clinic workflow. Patients who were discharged to facilities were not included. This ensured that appropriate and consistent PACT pharmacist follow-up would be available, but likely reduced our sample size.
Although performing this study in a closed health care system with pharmacists who have independent SOPs is a strength of our study, also it can limit generalizability. Not all facilities house both acute care and ambulatory care in one location with wide SOPs to allow for comprehensive and continued care. Last, this study used convenience sampling, potentially introducing selection bias, as patients unable to be reached by PACT pharmacists may inherently be at increased risk for hospital readmission. However, in the 3 months preceding the hospital admission that resulted in TOC tool referral, both groups had a similar number of patients with hospital admissions and ED visits.
The TOC tool has become fully integrated into the daily workflow for both acute care and PACT pharmacists. After the conclusion of the study period, the referral rates into the tool have been maintained at a steady level, even surpassing the rates seen during the study period. In comparison with the pilot study, PACT pharmacists reported a subjective increase in referrals placed for procedures such as medication reconciliation or adherence checks. This is likely because acute care pharmacists were able to use their clinical judgement rather than to rely solely on calculated readmission risk scores for TOC tool referral.
The success of the TOC program led to the expansion to other specialty areas. ED pharmacists now refer patients from the ED who were not admitted to the hospital but would benefit from PACT follow-up. Additionally, the option to refer hematology and oncology patients was added to allow these patients to be followed up by our hematology/oncology CPSs by phone appointments. Unique reasons for follow-up for this patient population include concerns about delayed chemotherapy cycles or chemotherapy-associated AEs.
Conclusions
This study outlines the creation and continued improvement of a pharmacist-based TOC program. The program was designed as a method of communication between acute care and PACT pharmacists about high-risk patients. The creation of this program allowed PACT pharmacists not only to identify discrepancies and make interventions on high-risk patients, but also demonstrate that having pharmacists involved in these programs may have a positive impact on readmissions and ED visits. The success of the TOC tool at the RLRVAMC has led to its expansion and is now an integral part of the daily workflow for both acute care and PACT pharmacists.
Effective transitions of care (TOC) are essential to ensure quality continuity of care after hospital discharge. About 20 to 30% of patients experience an adverse event (AE) in the peridischarge period when discharged to the community.1 Additionally, about two-thirds of AEs are preventable.1 The Joint Commission has identified various breakdowns in care that are associated with poor outcomes, including a lack of standardized discharge procedures, limited time dedicated to discharge planning and processes, and patients who lack the necessary resources or skills to implement discharge care plans.2
Background
The most impactful TOC programs are those that target patients who are at high risk for readmission or adverse outcomes.3 Factors such as advanced age, polypharmacy, cognitive impairment, and lack of social support are patient characteristics that have been associated with unfavorable outcomes after discharge.4 To identify this subset of high-risk individuals, various risk assessment scores have been developed, ranging from those that are used locally at the facility level to those that are nationally validated. The LACE score (Length of hospital stay; Acuity of the admission; Comorbidities measured with the Charlson comorbidity index score; and Emergency department visits within the past 6 months) is a validated index scoring tool that is used to identify medical and surgical patients at risk for readmission or death within 30 days of hospital discharge. On a 19-point scale, a score of ≥ 10 is considered high risk.5 Specific to the US Department of Veterans Affairs (VA), the Care Assessment Needs (CAN) score was developed to risk stratify the veteran population. The CAN score is generated using information including patient demographics, medical conditions, VA health care utilization, vital signs, laboratory values, medications, and socioeconomic status. This score is expressed as a percentile that compares the probability of death or admission among veterans at 90 days and 1 year postdischarge. Veterans in the 99th percentile have a 74% risk for these adverse outcomes at 1 year.6
The Joint Commission states that a fundamental component to assuring safe and effective TOC is medication management, which includes the involvement of pharmacists.2 TOC programs with pharmacist involvement have shown significant improvements related to reduced 30-day hospital readmissions and health care costs in addition to significant medication-related interventions.7-9 While this body of evidence continues to grow and demonstrates that pharmacists are an integral component of the TOC process, there is no gold standard program. Brantley and colleagues noted that a weakness of many TOC programs is that they are one dimensional, meaning that they focus on only 1 element of care transitions or 1 specific patient population or disease.10
There is well-supported evidence of high-impact interventions for pharmacists involved early in the admission process, but data are less robust on the discharge process. 11,12 Therefore, the primary focus of this project was to develop a pharmacist-based TOC program and implement a process for communicating high-risk patients who are discharging from our hospital across the continuum of care.
Setting
The Richard L. Roudebush VA Medical Center (RLRVAMC) is a tertiary care referral center for veterans in Indiana and eastern Illinois. Acute care clinical pharmacists are fully integrated into the acute care teams and practice under a comprehensive care model. Pharmacists attend daily patient care rounds and conduct discharge medication reconciliation for all patients with additional bedside counseling for patients who are being discharged home.
Primary care services are provided by patient aligned care teams (PACTs), multidisciplinary teams composed of physicians, advanced practice nurses, pharmacists, mental health care providers, registered nurses, dieticians, and care coordinators. Ambulatory Care or PACT clinical pharmacists are established within each RLRVAMC PACT clinic and provide comprehensive care management through an independent scope of practice for several chronic diseases, including hypertension, type 2 diabetes mellitus (T2DM), dyslipidemia, hypothyroidism, and tobacco cessation. Prior to this project implementation, there was no formalized or standardized method for facilitating routine communication of patients between acute care and PACT pharmacists in the TOC process.
Pilot Study
In 2017, RLRVAMC implemented a TOC pharmacy program pilot. A pharmacy resident and both acute care and PACT clinical pharmacy specialists (CPSs) developed the service. The pilot program was conducted from September 1, 2017 to March 1, 2018. The initial phase consisted of the development of an electronic TOC tool to standardize communication between acute care and PACT pharmacists. The TOC tool was created on a secure site accessible only to pharmacy personnel and not part of the formal medical record. (Figure 1).
The acute care pharmacist identified high-risk patients through calculated CAN and LACE scores during the discharge process and offered PACT pharmacist follow-up to the patient during bedside discharge counseling. Information was then entered into the TOC tool, including patient identifiers and a message with specific information outlining the reason for referral. PACT pharmacists routinely reviewed the tool and attempted to phone each patient within 7 days of discharge. Follow-up included medication reconciliation and chronic disease management as warranted at the discretion of the PACT pharmacist. All postdischarge follow-up appointments were created and documented in the electronic health record. A retrospective chart review was completed on patients who were entered into the TOC tool.
Patients were eligible for referral if they were discharged during the study period with primary care established in one of the facility’s PACT clinics. Additionally, patients had to meet ≥ 1 of the following criteria, deeming them a high risk for readmission: LACE score ≥ 10, CAN score ≥ 90th percentile, or be considered high risk based on the discretion of the acute care pharmacist. Patients were included in the analysis if they met the CAN or LACE score requirement. Patients were excluded if they received primary care from a site other than a RLRVAMC PACT clinic. This included non-VA primary care, home-based primary care, or VA community-based outpatient clinics (CBOCs). Patients also were excluded if they required further institutional care postdischarge (ie, subacute rehabilitation, extended care facility, etc), discharged to hospice, or against medical advice.
The average referral rate per month during the pilot study was 19 patients, with 113 total referrals during the 6-month study period. Lower rates of index emergency department (ED) visits (5.3% vs 23.3%) and readmissions (1% vs 6.7%) were seen in the group of patients who received PACT pharmacist follow-up postdischarge compared with those who did not. Additionally, PACT pharmacists were able to make > 120 interventions, averaging 1.7 interventions per patient. Of note, these results were not statistically analyzed and were assessed as observational data to determine whether the program had the potential to be impactful. The results of the pilot study demonstrated positive outcomes associated with having a pharmacist-based TOC process and led to the desire for further development and implementation of the TOC program at the RLRVAMC. These positive results prompted a second phase project to address barriers, make improvements, and ensure sustainability.
Methods
Phase 2 was a quality improvement initiative; therefore, institutional review board approval was not needed. The aim of phase 2 was to improve, expand, and sustain the TOC program that was implemented in the pilot study. Barriers identified after discussion with acute care and PACT pharmacists included difficulty in making referrals due to required entry of cumbersome readmission risk factor calculations, limiting inclusion to patients who receive primary care at the main hospital facility, and the expansion of pharmacy staff with new pharmacists who were not knowledgeable of the referral process.
Design
To overcome barriers, 4 main targeted interventions were needed: streamlining the referral process, enhancing pharmacy staff education, updating the discharge note template, and expanding the criteria to include patients who receive care at VA CBOCs. The referral process was streamlined by removing required calculated readmission risk scores, allowing pharmacist judgement to take precedence for referrals. Focused face-to-face education was provided to acute care and PACT pharmacists about the referral process and inclusion criteria to increase awareness and provide guidance of who may benefit from entry into the tool. Unlike the first phase of the study, education was provided for outpatient staff pharmacists responsible for discharging patients on the weekends. Additionally, the pharmacists received a printed quick reference guide of the information covered during the education sessions (Figure 2). Referral prompts were embedded into the standard pharmacy discharge note template to serve as a reminder to discharging pharmacists to assess patients for inclusion into the tool and provided a direct link to the tool. Expansion to include VA CBOCs occurred postpilot study, allowing increased patient access to this TOC service. All other aspects of the program were continued from the pilot phase.
Patients were eligible if they were discharged from RLRVAMC between October 1, 2018 and February 28, 2019. Additionally, the patient had to be established in a PACT clinic for primary care and have been referred to the tool based on the discretion of an acute care pharmacist. Patients were excluded if they were discharged against medical advice or to any facility where the patient and/or caregiver would not be responsible for medication administration (eg, subacute rehabilitation, extended care facility), or if the patient refused pharmacy follow-up.
Outcomes
The primary outcomes assessed were all-cause and index ED visits and readmissions within 30 days of discharge. All-cause ED visits and readmissions were defined as a second visit to RLRVAMC , regardless of readmission diagnosis. Index ED visits and readmissions were defined as those that were related to the initial admission diagnosis. Additional data collected and analyzed included the number of patients referred by pharmacists, number and type of medication discrepancies, medication changes, counseling interventions, time to follow-up postdischarge, and number of patients added to the PACT pharmacist’s clinic schedule for further management. A discrepancy identified by a PACT pharmacist was defined as a difference between the discharge medication list and the patient-reported medication list at the time of follow-up. Patients who were referred to the TOC tool but were unable to be reached by telephone served as the control group for this study.
Data Collection
A retrospective chart review was completed on patients entered into the tool. Data were collected and kept in a secured Microsoft Excel workbook. Baseline characteristics were analyzed using either a χ2 for nominal data or Student t test for continuous data. The primary outcomes were analyzed using a χ2 test. All statistical tests were analyzed using MiniTab 19 Statistical Software.
Results
Pharmacists added 172 patients into the TOC tool; 139 patients met inclusion criteria. Of those excluded, most were because the PACT pharmacist did not attempt to contact the patient since they already had a primary care visit scheduled postdischarge (Table 1). Of the 139 patients who met the inclusion criteria, 99 were successfully contacted by a PACT pharmacist. Most patients were aged in their 60s, male, and white. Both groups had a similar quantity of outpatient medications on admission and medication changes made at discharge. Additionally, both groups had a similar number of patients with hospitalizations and/or ED visits in the 3 months before hospital admission that resulted in TOC tool referral (Table 2).
Hospital Readmission
Hospital 30-day readmission rates for patients who were successfully followed by pharmacy compared with those who were not were 5.1% vs 15.0% (P = .049) for index readmissions and 8.1% vs 27.5% (P = .03) for all-cause readmissions. No statistically significant difference existed between those patients with follow-up compared with those without follow-up for either index (10.1% vs 12.5%, respectively; P = .68) or for all-cause ED visit rates (15.2% vs 20.0%, respectively; P = .49).
Patient Encounters
The average time to follow-up was 8.8 days, which was above the predetermined goal of contact within 7 days. Additionally, this was a decline from the initial pilot study, which had an average time to reach of 4.7 days. All patients reached by a pharmacist received medication reconciliation, with ≥ 28% of patients having ≥ 1 discrepancy. There were 43 discrepancies among all patients. Of the discrepancies, 25 were reported as errors performed by the patient, and 18 were from an error during the discharge process. The discrepancies that resulted from patient error were primarily patients who took the wrong dose of prescribed medications. Other patient discrepancies included taking medications not as scheduled, omitting medications (both intentionally and mistakenly), continuing to take medications that had been discontinued by a health care provider and improper administration technique. Examples of provider errors that occurred during the discharge process included not ordering medications for patient to pick up at discharge, not discontinuing a medication from the patient’s profile, and failure to renew expired prescriptions.
Additional counseling was provided to 75% of patients: The most common reason for counseling was T2DM, hypertension, and dyslipidemia management. PACT pharmacists changed medication regimens for 27.3% of patients for improved control of chronic diseases or relief of medication AEs.
At the end of each visit, patients were assessed to determine whether they could benefit from additional pharmacy follow-up. Thirty-seven patients were added to the pharmacist schedules for disease management appointments. The most common conditions for these appointments were T2DM, hypertension, tobacco cessation, and hyperlipidemia. Among the 37 patients who had pharmacy follow-up, there were 137 additional pharmacy appointments within the study period.
Program Referrals
After expansion to include the VA CBOCs, elimination of the elevated LACE or CAN score requirement, and additional staff education, the rate of referrals per month increased during phase 2 in comparison to the pilot study (Figure 3). There were a mean (SD) of 34 (10) referrals per month. Although not statistically analyzed, it is an objective increase in comparison to a mean 19 referrals per month in the pilot study.
Discussion
The continued development and use of a pharmacist-driven TOC tool at RLRVAMC increased communication and follow-up of high-risk patients, demonstrated the ability of pharmacists to identify and intervene in medication-related issues postdischarge, and successfully reduce 30-day readmissions. This program emphasized pharmacist involvement during the discharge process and created a standardized mechanism for TOC follow-up, addressing multiple areas that were identified by The Joint Commission as being associated with poor outcomes. The advanced pharmacy practice model at RLRVAMC allowed for a multidimensional program, including prospective patient identification and multiple pharmacy touchpoints. This is unique in comparison to many of the one-dimensional programs described in the literature.
Polypharmacy has been identified as a major predictor of medication discrepancies postdischarge, and patients with ≥ 10 active medications have been found to be at highest risk.13,14 Patients in this study had a mean 13 active medications on admission, with a mean 5 medication changes at discharge. PACT pharmacists documented 28 of 99 patients with ≥ 1 medication-related discrepancy at postdischarge reconciliation. This 28% discrepancy rate is consistent with discrepancy rates previously reported in the literature, which ranged from 14 to 45% in large meta-analyses.14,15 The majority of these discrepancies (58%) were related to patients who took the wrong dose of a prescribed medication.
Targeted interventions to overcome barriers in the pilot study increased the referral rates to the TOC tool; however, the increase in referral rate was associated with increased time to follow up by ambulatory care pharmacists. The extended follow-up times were seen most often in the 2 busiest primary care clinics, one of which is considered a teaching clinic for medical residents. Pharmacists were required to integrate these calls into their normal work schedule and were not provided additional time for calling, allowing for an increased follow-up time. The increased follow-up time likely contributed to the increased number of patients excluded due to already having PACT follow-up, giving more time for the primary care provider to have an appointment with the patient. The ambulatory care pharmacist could then determine whether further intervention was needed. In the summer of 2018, a decrease in referral rates occurred for a short time, but this is likely explained by incoming new residents and staff within the pharmacy department and decreased awareness among the new staff. The enhanced staff education took place during September 2018 and lead to increased referral rates compared with those seen in months prior.
PACT pharmacists were not only able to identify discrepancies, but also provide timely intervention on a multitude of medication-related issues by using their scope of practice (SOP). Most interventions were related to medication or disease counseling, including lifestyle, device, and disease education. The independent SOP of our PACT pharmacists is a unique aspect of this program and allowed pharmacists to independently adjust many aspects of a patient’s medication regimen during follow-up visits.
The outcomes of 30-day index and all-cause readmissions, as well as index and all-cause ED visit rates, were lower in the subset of patients who received PACT pharmacist follow-up after discharge (Table 3). The difference was most pronounced in the all-cause readmission rates: Only 8.1% of patients who received PACT follow-up experienced a readmission compared with 27.5% of those who did not. The difference between the groups regarding ED visit rates were not as pronounced, but this may be attributed to a limited sample size. These data indicate that the role of the pharmacist in identifying discrepancies and performing interventions at follow-up may play a clinically significant part in reducing both ED visit rates and hospital readmissions.
Limitations
There are some limitations identified within this study. Although the referral criteria were relaxed from the pilot study and enhanced education was created, continued education regarding appropriate referral of TOC patients continues to be necessary given intermittent staff changeover, incorporation of pharmacy trainees, and modifications to clinic workflow. Patients who were discharged to facilities were not included. This ensured that appropriate and consistent PACT pharmacist follow-up would be available, but likely reduced our sample size.
Although performing this study in a closed health care system with pharmacists who have independent SOPs is a strength of our study, also it can limit generalizability. Not all facilities house both acute care and ambulatory care in one location with wide SOPs to allow for comprehensive and continued care. Last, this study used convenience sampling, potentially introducing selection bias, as patients unable to be reached by PACT pharmacists may inherently be at increased risk for hospital readmission. However, in the 3 months preceding the hospital admission that resulted in TOC tool referral, both groups had a similar number of patients with hospital admissions and ED visits.
The TOC tool has become fully integrated into the daily workflow for both acute care and PACT pharmacists. After the conclusion of the study period, the referral rates into the tool have been maintained at a steady level, even surpassing the rates seen during the study period. In comparison with the pilot study, PACT pharmacists reported a subjective increase in referrals placed for procedures such as medication reconciliation or adherence checks. This is likely because acute care pharmacists were able to use their clinical judgement rather than to rely solely on calculated readmission risk scores for TOC tool referral.
The success of the TOC program led to the expansion to other specialty areas. ED pharmacists now refer patients from the ED who were not admitted to the hospital but would benefit from PACT follow-up. Additionally, the option to refer hematology and oncology patients was added to allow these patients to be followed up by our hematology/oncology CPSs by phone appointments. Unique reasons for follow-up for this patient population include concerns about delayed chemotherapy cycles or chemotherapy-associated AEs.
Conclusions
This study outlines the creation and continued improvement of a pharmacist-based TOC program. The program was designed as a method of communication between acute care and PACT pharmacists about high-risk patients. The creation of this program allowed PACT pharmacists not only to identify discrepancies and make interventions on high-risk patients, but also demonstrate that having pharmacists involved in these programs may have a positive impact on readmissions and ED visits. The success of the TOC tool at the RLRVAMC has led to its expansion and is now an integral part of the daily workflow for both acute care and PACT pharmacists.
1. Forster AJ, Murff HJ, Peterson JF, Gandhi TK, Bates DW. The incidence and severity of adverse effects affecting patients after discharge from the hospital. Ann Intern Med. 2003;138(3):161-167. doi:10.7326/0003-4819-138-3-200302040-00007
2. The Joint Commission. Transitions of care: the need for collaboration across entire care continuum. Published February 2013. Accessed February 25, 2021. http://www.jointcommission.org/assets/1/6/TOC_Hot_Topics.pdf
3. Leppin AL, Gionfriddo MR, Kessler M, et al. Preventing 30-day hospital readmissions: a systematic review and meta-analysis of randomized trials. JAMA Intern Med. 2014;174(7):1095-1107. doi:10.1001/jamainternmed.2014.1608
4. Medicare Hospital Compare. Readmissions and deaths. Accessed February 25, 2021. https://www.cms.gov/Medicare/Quality-Initiatives-Patient-Assessment-Instruments/HospitalQualityInits/VA-Data
5. van Walraven C, Dhalla IA, Bell C, et al. Derivation and validation of an index to predict early death or unplanned readmission after discharge from hospital to the community. CMAJ. 2010;182(6):551-557. doi:10.1503/cmaj.091117
6. US Department of Veteran Affairs. Care Assessment Needs (CAN) score report. Updated May 14, 2019. Accessed February 25, 2021. https://www.va.gov/HEALTHCAREEXCELLENCE/about/organization/examples/care-assessment-needs.asp
7. Schnipper JL, Kirwin JL, Cotugno MC, et al. Role of pharmacist counseling in preventing adverse drug events after hospitalization. Arch Intern Med. 2006;166(5):565-571. doi:10.1001/archinte.166.5.565
8. Phatak A, Prusi R, Ward B, et al. Impact of pharmacist involvement in the transitional care of high-risk patients through medication reconciliation, medication education, and post-discharge call-backs. J Hosp Med. 2016;11(1):40-44. doi:10.1002/jhm.2493
9. Coleman EA, Min SJ, Chomiak A, Kramer AM. Posthospital care transitions: patterns, complications, and risk identification. Health Serv Res. 2004;39(5):1449-1465. doi:10.1111/j.1475-6773.2004.00298.x
10. Brantley AF, Rossi DM, Barnes-Warren S, Francisco JC, Schatten I, Dave V. Bridging gaps in care: implementation of a pharmacist-led transitions of care program. Am J Health Syst Pharm. 2018;75(5)(suppl 1):S1-S5. doi:10.2146/ajhp160652
11. Scarsi KK, Fotis MA, Noskin GA. Pharmacist participation in medical rounds reduces medical errors. Am J Health Syst Pharm. 2002;59(21):2089-2092. doi:10.1093/ajhp/59.21.2089
12. Pevnick JM, Nguyen C, Jackevicius CA, et al. Improving admission medication reconciliation with pharmacists or pharmacy technicians in the emergency department: a randomised controlled trial. BMJ Qual Saf. 2018;27:512-520. doi:10.1136/bmjqs-2017-006761.
13. Kirwin J, Canales AE, Bentley ML, et al; American College of Clinical Pharmacy. Process indicators of quality clinical pharmacy services during transitions of care. Pharmacotherapy. 2012;32(11):e338-e347. doi:10.1002/phar.1214
14. Kwan JL, Lo L, Sampson M, et al. Medication reconciliation during transitions of care as a patient safety strategy: a systematic review. Ann Intern Med. 2013;158(5, part 2):397-403. doi:10.7326/0003-4819-158-5-201303051-00006
15. Stitt DM, Elliot DP, Thompson SN. Medication discrepancies identified at time of hospital discharge in a geriatric population. Am J Geriatr Pharmacother. 2011;9(4):234-240. doi:10.1016/j.amjopharm.2011.06.002
1. Forster AJ, Murff HJ, Peterson JF, Gandhi TK, Bates DW. The incidence and severity of adverse effects affecting patients after discharge from the hospital. Ann Intern Med. 2003;138(3):161-167. doi:10.7326/0003-4819-138-3-200302040-00007
2. The Joint Commission. Transitions of care: the need for collaboration across entire care continuum. Published February 2013. Accessed February 25, 2021. http://www.jointcommission.org/assets/1/6/TOC_Hot_Topics.pdf
3. Leppin AL, Gionfriddo MR, Kessler M, et al. Preventing 30-day hospital readmissions: a systematic review and meta-analysis of randomized trials. JAMA Intern Med. 2014;174(7):1095-1107. doi:10.1001/jamainternmed.2014.1608
4. Medicare Hospital Compare. Readmissions and deaths. Accessed February 25, 2021. https://www.cms.gov/Medicare/Quality-Initiatives-Patient-Assessment-Instruments/HospitalQualityInits/VA-Data
5. van Walraven C, Dhalla IA, Bell C, et al. Derivation and validation of an index to predict early death or unplanned readmission after discharge from hospital to the community. CMAJ. 2010;182(6):551-557. doi:10.1503/cmaj.091117
6. US Department of Veteran Affairs. Care Assessment Needs (CAN) score report. Updated May 14, 2019. Accessed February 25, 2021. https://www.va.gov/HEALTHCAREEXCELLENCE/about/organization/examples/care-assessment-needs.asp
7. Schnipper JL, Kirwin JL, Cotugno MC, et al. Role of pharmacist counseling in preventing adverse drug events after hospitalization. Arch Intern Med. 2006;166(5):565-571. doi:10.1001/archinte.166.5.565
8. Phatak A, Prusi R, Ward B, et al. Impact of pharmacist involvement in the transitional care of high-risk patients through medication reconciliation, medication education, and post-discharge call-backs. J Hosp Med. 2016;11(1):40-44. doi:10.1002/jhm.2493
9. Coleman EA, Min SJ, Chomiak A, Kramer AM. Posthospital care transitions: patterns, complications, and risk identification. Health Serv Res. 2004;39(5):1449-1465. doi:10.1111/j.1475-6773.2004.00298.x
10. Brantley AF, Rossi DM, Barnes-Warren S, Francisco JC, Schatten I, Dave V. Bridging gaps in care: implementation of a pharmacist-led transitions of care program. Am J Health Syst Pharm. 2018;75(5)(suppl 1):S1-S5. doi:10.2146/ajhp160652
11. Scarsi KK, Fotis MA, Noskin GA. Pharmacist participation in medical rounds reduces medical errors. Am J Health Syst Pharm. 2002;59(21):2089-2092. doi:10.1093/ajhp/59.21.2089
12. Pevnick JM, Nguyen C, Jackevicius CA, et al. Improving admission medication reconciliation with pharmacists or pharmacy technicians in the emergency department: a randomised controlled trial. BMJ Qual Saf. 2018;27:512-520. doi:10.1136/bmjqs-2017-006761.
13. Kirwin J, Canales AE, Bentley ML, et al; American College of Clinical Pharmacy. Process indicators of quality clinical pharmacy services during transitions of care. Pharmacotherapy. 2012;32(11):e338-e347. doi:10.1002/phar.1214
14. Kwan JL, Lo L, Sampson M, et al. Medication reconciliation during transitions of care as a patient safety strategy: a systematic review. Ann Intern Med. 2013;158(5, part 2):397-403. doi:10.7326/0003-4819-158-5-201303051-00006
15. Stitt DM, Elliot DP, Thompson SN. Medication discrepancies identified at time of hospital discharge in a geriatric population. Am J Geriatr Pharmacother. 2011;9(4):234-240. doi:10.1016/j.amjopharm.2011.06.002
What’s the future of telehealth? It’s ‘complicated’
pre-AAD meeting.
“We have seen large numbers of children struggle with access to school and access to health care because of lack of access to devices, challenges of broadband Internet access, culture, language, and educational barriers – just having trouble being comfortable with this technology,” said Natalie Pageler, MD, a pediatric intensivist and chief medical information officer at Stanford Children’s Health, Palo Alto, Calif.
“There are also privacy concerns, especially in situations where there are multiple families within a household. Finally, it’s important to remember that policy and reimbursement issues may have a significant effect on some of the socioeconomic barriers,” she added. “For example, many of our families who don’t have access to audio and video may be able to do a telephone call, but it’s important that telephone calls be considered a form of telehealth and be reimbursed to help increase the access to health care by these families. It also makes it easier to facilitate coordination of care. All of this leads to decreased time and costs for patients, families, and providers.”
Within the first few weeks of the pandemic, Dr. Pageler and colleagues at Stanford Children’s Health observed an increase from about 20 telehealth visits per day to more than 700 per day, which has held stable. While the benefits of telehealth are clear, many perceived barriers exist. In a study conducted prior to the COVID-19 pandemic, researchers identified a wide variety of barriers to implementation of telehealth, led by reimbursement, followed by poor business model sustainability, lack of provider time, and provider interest.
“Some of the barriers, like patient preferences for inpatient care, lack of provider interest in telehealth, and lack of provider time were easily overcome during the COVID pandemic,” Dr. Pageler said. “We dedicated the time to train immediately, because the need was so great.”
In 2018, Patrick McMahon, MD, and colleagues at Children’s Hospital of Philadelphia, launched a teledermatology program that provided direct-to-patient “E-visits” and recently pivoted to using this service only for acne patients through a program called “Acne Express.” The out-of-pocket cost to patients is $50 per consult and nearly 1,500 cases have been completed since 2018, which has saved patients and their parents an estimated 65,000 miles driving to the clinic.
“In the last year we have piloted something called “E-Consults,” which is a provider-to-provider, store-and-forward service,” said Dr. McMahon, a pediatric dermatologist and director of teledermatology at CHOP. “That service is not currently reimbursable, but it’s funded through our hospital. We also have live video visits between provider and patient. That is reimbursable. We have done about 7,500 of those.”
In a 2020 unpublished membership survey of SPD members, Dr. McMahon and colleagues posed the question, “How has teledermatology positively impacted your practice over the past year?” The top three responses were that teledermatology was safe during COVID-19, it provided easy access for follow-up, and it was convenient. In response to the question, “What is the most fundamental change needed for successful delivery of pediatric teledermatology?” the top three responses were reimbursement, improved technology, and regulatory changes.
“When we asked about struggles and difficulties, a lot of responses surrounded the lack of connectivity, both from a technological standpoint and also that lack of connectivity we would feel in person – a lack of rapport,” Dr. McMahon said. “There’s also the inability for us to touch and feel when we examine, and we worry about misdiagnosing. There are also concerns about disparities and for us being sedentary – sitting in one place staring at a screen.”
To optimize the teledermatology experience, he suggested four pillars: educate, optimize, reach out, and tailor. “I think we need to draw upon some of the digital education we already have, including a handout for patients [on the SPD website] that offers tips on taking a clear photograph on their smartphones,” he said. “We’re also trying to use some of the cases and learnings from our teledermatology experiences to teach the providers. We are setting up CME modules that are sort of a flashcard-based teaching mechanism.”
To optimize teledermatology experiences, he continued, tracking demographics, diagnoses, number of cases, and turnaround time is helpful. “We can then track who’s coming in to see us at follow-up after a new visit through telehealth,” Dr. McMahon said. “This helps us repurpose things, pivot as needed, and find any glitches. Surveying the families is also critical. Finally, we need clinical support to tee-up visits and to ensure photos are submitted and efficient, and to match diagnoses and family preference with the right modality.”
Another panelist, Justin M. Ko, MD, MBA, who chairs the American Academy of Dermatology’s Task Force on Augmented Intelligence, said that digitally enabled and artificial intelligence (AI)-augmented care delivery offers a “unique opportunity” for increasing access and increasing the value of care delivered to patients.
“The role that we play as clinicians is central, and I think we can make significant strides by doing two things,” said Dr. Ko, chief of medical dermatology for Stanford (Calif.) Health Care. “One: extending the reach of our expertise, and the second: scaling the impact of the care we deliver by clinician-driven, patient-centered, digitally-enabled, AI-augmented care delivery innovation. This opportunity for digital care transformation is more than just a transition from in-person visits to video visits. We have to look at this as an opportunity to leverage the unique aspects of digital capabilities and fundamentally reimagine how we deliver care.”
The AAD’s Position Statement on Augmented Intelligence was published in 2019.
Between March and June of 2021, Neil S. Prose, MD, conducted about 300 televisits with patients. “I had a few spectacular visits where, for example, a teenage patient who had been challenging showed me all of her artwork and we became instantly more connected,” said Dr. Prose, professor of dermatology, pediatrics, and global health at Duke University, Durham, N.C. “Then there’s the potential for a long-term improvement in health care for some patients.”
But there were also downsides to the process, he said, including dropped connections, poor picture and sound quality, patient no-shows, and patients reporting they were unable to schedule a telemedicine visit. “The problems I was experiencing were not just between me and my patients; the problems are systemic, and they have to do with various factors: the portal, the equipment, Internet access, and inadequate or no health insurance,” said Dr. Prose, past president of the SPD.
Portal-related challenges include a lack of focus on culture, literacy, and numeracy, “and these worsen inequities,” he said. “Another issue related to portal design has to do with language. Very few of the portals allow patients to participate in Spanish. This has been particularly difficult for those of us who use Epic. The next issue has to deal with the devices the patients are using. Cell phone visits can be very problematic. Unfortunately, lower-income Americans have a lower level of technology adoption, and many are relying on smartphones for their Internet access. That’s the root of some of our problems.”
To achieve digital health equity, Dr. Prose emphasized the need for federal mandates for tools for digital health access usable by underserved populations and federal policies that increase broadband access and view it as a human right. He also underscored the importance of federal policies that ensure continuation of adequate telemedicine reimbursement beyond the pandemic and urged health institutions to invest in portals that address the needs of the underserved.
“What is the future of telemedicine? The answer is complicated,” said Dr. Prose, who recommended a recently published article in JAMA on digital health equity. “There have been several rumblings of large insurers who plan to pull the rug on telemedicine as soon as the pandemic is more or less over. So, all of our projections about this being a wonderful trend for the future may be for naught if the insurers don’t step up to the table.”
None of the presenters reported having financial disclosures.
pre-AAD meeting.
“We have seen large numbers of children struggle with access to school and access to health care because of lack of access to devices, challenges of broadband Internet access, culture, language, and educational barriers – just having trouble being comfortable with this technology,” said Natalie Pageler, MD, a pediatric intensivist and chief medical information officer at Stanford Children’s Health, Palo Alto, Calif.
“There are also privacy concerns, especially in situations where there are multiple families within a household. Finally, it’s important to remember that policy and reimbursement issues may have a significant effect on some of the socioeconomic barriers,” she added. “For example, many of our families who don’t have access to audio and video may be able to do a telephone call, but it’s important that telephone calls be considered a form of telehealth and be reimbursed to help increase the access to health care by these families. It also makes it easier to facilitate coordination of care. All of this leads to decreased time and costs for patients, families, and providers.”
Within the first few weeks of the pandemic, Dr. Pageler and colleagues at Stanford Children’s Health observed an increase from about 20 telehealth visits per day to more than 700 per day, which has held stable. While the benefits of telehealth are clear, many perceived barriers exist. In a study conducted prior to the COVID-19 pandemic, researchers identified a wide variety of barriers to implementation of telehealth, led by reimbursement, followed by poor business model sustainability, lack of provider time, and provider interest.
“Some of the barriers, like patient preferences for inpatient care, lack of provider interest in telehealth, and lack of provider time were easily overcome during the COVID pandemic,” Dr. Pageler said. “We dedicated the time to train immediately, because the need was so great.”
In 2018, Patrick McMahon, MD, and colleagues at Children’s Hospital of Philadelphia, launched a teledermatology program that provided direct-to-patient “E-visits” and recently pivoted to using this service only for acne patients through a program called “Acne Express.” The out-of-pocket cost to patients is $50 per consult and nearly 1,500 cases have been completed since 2018, which has saved patients and their parents an estimated 65,000 miles driving to the clinic.
“In the last year we have piloted something called “E-Consults,” which is a provider-to-provider, store-and-forward service,” said Dr. McMahon, a pediatric dermatologist and director of teledermatology at CHOP. “That service is not currently reimbursable, but it’s funded through our hospital. We also have live video visits between provider and patient. That is reimbursable. We have done about 7,500 of those.”
In a 2020 unpublished membership survey of SPD members, Dr. McMahon and colleagues posed the question, “How has teledermatology positively impacted your practice over the past year?” The top three responses were that teledermatology was safe during COVID-19, it provided easy access for follow-up, and it was convenient. In response to the question, “What is the most fundamental change needed for successful delivery of pediatric teledermatology?” the top three responses were reimbursement, improved technology, and regulatory changes.
“When we asked about struggles and difficulties, a lot of responses surrounded the lack of connectivity, both from a technological standpoint and also that lack of connectivity we would feel in person – a lack of rapport,” Dr. McMahon said. “There’s also the inability for us to touch and feel when we examine, and we worry about misdiagnosing. There are also concerns about disparities and for us being sedentary – sitting in one place staring at a screen.”
To optimize the teledermatology experience, he suggested four pillars: educate, optimize, reach out, and tailor. “I think we need to draw upon some of the digital education we already have, including a handout for patients [on the SPD website] that offers tips on taking a clear photograph on their smartphones,” he said. “We’re also trying to use some of the cases and learnings from our teledermatology experiences to teach the providers. We are setting up CME modules that are sort of a flashcard-based teaching mechanism.”
To optimize teledermatology experiences, he continued, tracking demographics, diagnoses, number of cases, and turnaround time is helpful. “We can then track who’s coming in to see us at follow-up after a new visit through telehealth,” Dr. McMahon said. “This helps us repurpose things, pivot as needed, and find any glitches. Surveying the families is also critical. Finally, we need clinical support to tee-up visits and to ensure photos are submitted and efficient, and to match diagnoses and family preference with the right modality.”
Another panelist, Justin M. Ko, MD, MBA, who chairs the American Academy of Dermatology’s Task Force on Augmented Intelligence, said that digitally enabled and artificial intelligence (AI)-augmented care delivery offers a “unique opportunity” for increasing access and increasing the value of care delivered to patients.
“The role that we play as clinicians is central, and I think we can make significant strides by doing two things,” said Dr. Ko, chief of medical dermatology for Stanford (Calif.) Health Care. “One: extending the reach of our expertise, and the second: scaling the impact of the care we deliver by clinician-driven, patient-centered, digitally-enabled, AI-augmented care delivery innovation. This opportunity for digital care transformation is more than just a transition from in-person visits to video visits. We have to look at this as an opportunity to leverage the unique aspects of digital capabilities and fundamentally reimagine how we deliver care.”
The AAD’s Position Statement on Augmented Intelligence was published in 2019.
Between March and June of 2021, Neil S. Prose, MD, conducted about 300 televisits with patients. “I had a few spectacular visits where, for example, a teenage patient who had been challenging showed me all of her artwork and we became instantly more connected,” said Dr. Prose, professor of dermatology, pediatrics, and global health at Duke University, Durham, N.C. “Then there’s the potential for a long-term improvement in health care for some patients.”
But there were also downsides to the process, he said, including dropped connections, poor picture and sound quality, patient no-shows, and patients reporting they were unable to schedule a telemedicine visit. “The problems I was experiencing were not just between me and my patients; the problems are systemic, and they have to do with various factors: the portal, the equipment, Internet access, and inadequate or no health insurance,” said Dr. Prose, past president of the SPD.
Portal-related challenges include a lack of focus on culture, literacy, and numeracy, “and these worsen inequities,” he said. “Another issue related to portal design has to do with language. Very few of the portals allow patients to participate in Spanish. This has been particularly difficult for those of us who use Epic. The next issue has to deal with the devices the patients are using. Cell phone visits can be very problematic. Unfortunately, lower-income Americans have a lower level of technology adoption, and many are relying on smartphones for their Internet access. That’s the root of some of our problems.”
To achieve digital health equity, Dr. Prose emphasized the need for federal mandates for tools for digital health access usable by underserved populations and federal policies that increase broadband access and view it as a human right. He also underscored the importance of federal policies that ensure continuation of adequate telemedicine reimbursement beyond the pandemic and urged health institutions to invest in portals that address the needs of the underserved.
“What is the future of telemedicine? The answer is complicated,” said Dr. Prose, who recommended a recently published article in JAMA on digital health equity. “There have been several rumblings of large insurers who plan to pull the rug on telemedicine as soon as the pandemic is more or less over. So, all of our projections about this being a wonderful trend for the future may be for naught if the insurers don’t step up to the table.”
None of the presenters reported having financial disclosures.
pre-AAD meeting.
“We have seen large numbers of children struggle with access to school and access to health care because of lack of access to devices, challenges of broadband Internet access, culture, language, and educational barriers – just having trouble being comfortable with this technology,” said Natalie Pageler, MD, a pediatric intensivist and chief medical information officer at Stanford Children’s Health, Palo Alto, Calif.
“There are also privacy concerns, especially in situations where there are multiple families within a household. Finally, it’s important to remember that policy and reimbursement issues may have a significant effect on some of the socioeconomic barriers,” she added. “For example, many of our families who don’t have access to audio and video may be able to do a telephone call, but it’s important that telephone calls be considered a form of telehealth and be reimbursed to help increase the access to health care by these families. It also makes it easier to facilitate coordination of care. All of this leads to decreased time and costs for patients, families, and providers.”
Within the first few weeks of the pandemic, Dr. Pageler and colleagues at Stanford Children’s Health observed an increase from about 20 telehealth visits per day to more than 700 per day, which has held stable. While the benefits of telehealth are clear, many perceived barriers exist. In a study conducted prior to the COVID-19 pandemic, researchers identified a wide variety of barriers to implementation of telehealth, led by reimbursement, followed by poor business model sustainability, lack of provider time, and provider interest.
“Some of the barriers, like patient preferences for inpatient care, lack of provider interest in telehealth, and lack of provider time were easily overcome during the COVID pandemic,” Dr. Pageler said. “We dedicated the time to train immediately, because the need was so great.”
In 2018, Patrick McMahon, MD, and colleagues at Children’s Hospital of Philadelphia, launched a teledermatology program that provided direct-to-patient “E-visits” and recently pivoted to using this service only for acne patients through a program called “Acne Express.” The out-of-pocket cost to patients is $50 per consult and nearly 1,500 cases have been completed since 2018, which has saved patients and their parents an estimated 65,000 miles driving to the clinic.
“In the last year we have piloted something called “E-Consults,” which is a provider-to-provider, store-and-forward service,” said Dr. McMahon, a pediatric dermatologist and director of teledermatology at CHOP. “That service is not currently reimbursable, but it’s funded through our hospital. We also have live video visits between provider and patient. That is reimbursable. We have done about 7,500 of those.”
In a 2020 unpublished membership survey of SPD members, Dr. McMahon and colleagues posed the question, “How has teledermatology positively impacted your practice over the past year?” The top three responses were that teledermatology was safe during COVID-19, it provided easy access for follow-up, and it was convenient. In response to the question, “What is the most fundamental change needed for successful delivery of pediatric teledermatology?” the top three responses were reimbursement, improved technology, and regulatory changes.
“When we asked about struggles and difficulties, a lot of responses surrounded the lack of connectivity, both from a technological standpoint and also that lack of connectivity we would feel in person – a lack of rapport,” Dr. McMahon said. “There’s also the inability for us to touch and feel when we examine, and we worry about misdiagnosing. There are also concerns about disparities and for us being sedentary – sitting in one place staring at a screen.”
To optimize the teledermatology experience, he suggested four pillars: educate, optimize, reach out, and tailor. “I think we need to draw upon some of the digital education we already have, including a handout for patients [on the SPD website] that offers tips on taking a clear photograph on their smartphones,” he said. “We’re also trying to use some of the cases and learnings from our teledermatology experiences to teach the providers. We are setting up CME modules that are sort of a flashcard-based teaching mechanism.”
To optimize teledermatology experiences, he continued, tracking demographics, diagnoses, number of cases, and turnaround time is helpful. “We can then track who’s coming in to see us at follow-up after a new visit through telehealth,” Dr. McMahon said. “This helps us repurpose things, pivot as needed, and find any glitches. Surveying the families is also critical. Finally, we need clinical support to tee-up visits and to ensure photos are submitted and efficient, and to match diagnoses and family preference with the right modality.”
Another panelist, Justin M. Ko, MD, MBA, who chairs the American Academy of Dermatology’s Task Force on Augmented Intelligence, said that digitally enabled and artificial intelligence (AI)-augmented care delivery offers a “unique opportunity” for increasing access and increasing the value of care delivered to patients.
“The role that we play as clinicians is central, and I think we can make significant strides by doing two things,” said Dr. Ko, chief of medical dermatology for Stanford (Calif.) Health Care. “One: extending the reach of our expertise, and the second: scaling the impact of the care we deliver by clinician-driven, patient-centered, digitally-enabled, AI-augmented care delivery innovation. This opportunity for digital care transformation is more than just a transition from in-person visits to video visits. We have to look at this as an opportunity to leverage the unique aspects of digital capabilities and fundamentally reimagine how we deliver care.”
The AAD’s Position Statement on Augmented Intelligence was published in 2019.
Between March and June of 2021, Neil S. Prose, MD, conducted about 300 televisits with patients. “I had a few spectacular visits where, for example, a teenage patient who had been challenging showed me all of her artwork and we became instantly more connected,” said Dr. Prose, professor of dermatology, pediatrics, and global health at Duke University, Durham, N.C. “Then there’s the potential for a long-term improvement in health care for some patients.”
But there were also downsides to the process, he said, including dropped connections, poor picture and sound quality, patient no-shows, and patients reporting they were unable to schedule a telemedicine visit. “The problems I was experiencing were not just between me and my patients; the problems are systemic, and they have to do with various factors: the portal, the equipment, Internet access, and inadequate or no health insurance,” said Dr. Prose, past president of the SPD.
Portal-related challenges include a lack of focus on culture, literacy, and numeracy, “and these worsen inequities,” he said. “Another issue related to portal design has to do with language. Very few of the portals allow patients to participate in Spanish. This has been particularly difficult for those of us who use Epic. The next issue has to deal with the devices the patients are using. Cell phone visits can be very problematic. Unfortunately, lower-income Americans have a lower level of technology adoption, and many are relying on smartphones for their Internet access. That’s the root of some of our problems.”
To achieve digital health equity, Dr. Prose emphasized the need for federal mandates for tools for digital health access usable by underserved populations and federal policies that increase broadband access and view it as a human right. He also underscored the importance of federal policies that ensure continuation of adequate telemedicine reimbursement beyond the pandemic and urged health institutions to invest in portals that address the needs of the underserved.
“What is the future of telemedicine? The answer is complicated,” said Dr. Prose, who recommended a recently published article in JAMA on digital health equity. “There have been several rumblings of large insurers who plan to pull the rug on telemedicine as soon as the pandemic is more or less over. So, all of our projections about this being a wonderful trend for the future may be for naught if the insurers don’t step up to the table.”
None of the presenters reported having financial disclosures.
FROM THE SPD PRE-AAD MEETING
Gastrointestinal Symptoms and Lactic Acidosis in a Chronic Marijuana User
A 57-year-old woman with a history of traumatic brain injury, posttraumatic stress disorder, depression, migraines, hypothyroidism, and a hiatal hernia repair presented to the emergency department with a 1-day history of nausea, vomiting, and diffuse abdominal pain. She reported that her symptoms were relieved by hot showers. She also reported having similar symptoms and a previous gastric-emptying study that showed a slow-emptying stomach. Her history also consisted of frequent cannabis use for mood and appetite stimulation along with eliminating meat and fish from her diet, an increase in consumption of simple carbohydrates in the past year, and no alcohol use. Her medications included topiramate 100 mg and clonidine 0.3 mg nightly for migraines; levothyroxine 200 mcg daily for hypothyroidism; tizanidine 4 mg twice a day for muscle spasm; famotidine 40 mg twice a day as needed for gastric reflux; and bupropion 50 mg daily, citalopram 20 mg daily, and lamotrigine 25 mg nightly for mood.
The patient’s physical examination was notable for bradycardia (43 beats/min) and epigastric tenderness. Admission laboratory results were notable for an elevated lactic acid level of 4.8 (normal range, 0.50-2.20) mmol/L and a leukocytosis count of 10.8×109 cells/L. Serum alcohol level and blood cultures were negative. Liver function test, hemoglobin A1c, and lipase test were unremarkable. Her electrocardiogram showed an unchanged right bundle branch block. Chest X-ray, computed tomography (CT) of her abdomen/pelvis and echocardiogram were unremarkable.
What is your diagnosis?
How would you treat this patient?
This patient was diagnosed with gastrointestinal beriberi. Because of her dietary changes, lactic acidosis, and bradycardia, thiamine deficiency was suspected after ruling out other possibilities on the differential diagnosis (Table). The patient’s symptoms resolved after administration of high-dose IV thiamine 500 mg 3 times daily for 4 days. Her white blood cell count and lactic acid level normalized. Unfortunately, thiamine levels were not obtained for the patient before treatment was initiated. After administration of IV thiamine, her plasma thiamine level was > 1,200 (normal range, 8-30) nmol/L.
Her differential diagnosis included infectious etiology. Given her leukocytosis and lactic acidosis, vancomycin and piperacillin/tazobactam were started on admission. One day later, her leukocytosis count doubled to 20.7×109 cells/L. However, after 48 hours of negative blood cultures, antibiotics were discontinued.
Small bowel obstruction was suspected due to the patient’s history of abdominal surgery but was ruled out with CT imaging. Similarly, pancreatitis was ruled out based on negative CT imaging and the patient’s normal lipase level. Gastroparesis also was considered because of the patient’s history of hypothyroidism, tobacco use, and her prior gastric-emptying study. The patient was treated for gastroparesis with a course of metoclopramide and erythromycin without improvement in symptoms. Additionally, gastroparesis would not explain the patient’s leukocytosis.
Cannabinoid hyperemesis syndrome (CHS) was suspected because the patient’s symptoms improved with cannabis discontinuation and hot showers.1 In chronic users, however, tetrahydrocannabinol levels have a half-life of 5 to 13 days.2 Although lactic acidosis and leukocytosis have been previously reported with cannabis use, it is unlikely that the patient would have such significant improvement within the first 4 days after discontinuation.1,3,4 Although the patient had many psychiatric comorbidities with previous hospitalizations describing concern for somatization disorder, her leukocytosis and elevated lactic acid levels were suggestive of an organic rather than a psychiatric etiology of her symptoms.
Discussion
Gastrointestinal beriberi has been reported in chronic cannabis users who present with nausea, vomiting, epigastric pain, leukocytosis, and lactic acidosis; all these symptoms rapidly improve after thiamine administration.5,6 The patient’s dietary change also eliminated her intake of vitamin B12, which compounded her condition. Thiamine deficiency produces lactic acidosis by disrupting pyruvate metabolism.7 Bradycardia also can be a sign of thiamine deficiency, although the patient’s use of clonidine for migraines is a confounder.8
Chronically ill patients are prone to nutritional deficiencies, including deficiencies of thiamine.7,9 Many patients with chronic illnesses also use cannabis to ameliorate physical and neuropsychiatric symptoms.2 Recent reports suggest cannabis users are prone to gastrointestinal beriberi and Wernicke encephalopathy.5,10 Treating gastrointestinal symptoms in these patients can be challenging to diagnose because gastrointestinal beriberi and CHS share many clinical manifestations.
The patient’s presentation is likely multifactorial resulting from the combination of gastrointestinal beriberi and CHS. However, thiamine deficiency seems to play the dominant role.
There is no standard treatment regimen for thiamine deficiency with neurologic deficits, and patients only retain about 10 to 15% of intramuscular (IM) injections of cyanocobalamin.11,12 The British Committee for Standards in Haematology recommends IM injections of 1,000 mcg of cyanocobalamin 3 times a week for 2 weeks and then reassess the need for continued treatment.13 The British Columbia guidelines also recommend IM injections of 1,000 mcg daily for 1 to 5 days before transitioning to oral repletion.14 European Neurology guidelines for the treatment of Wernicke encephalopathy recommend IV cyanocobalamin 200 mg 3 times daily.15 Low-level evidence with observational studies informs these decisions and is why there is variation.
The patient’s serum lactate and leukocytosis normalized 1 day after the administration of thiamine. Thiamine deficiency classically causes Wernicke encephalopathy and wet beriberi.16 The patient did not present with Wernicke encephalopathy’s triad: ophthalmoplegia, ataxia, or confusion. She also was euvolemic without signs or symptoms of wet beriberi.
Conclusions
Thiamine deficiency is principally a clinical diagnosis. Thiamine laboratory testing may not be readily available in all medical centers, and confirming a diagnosis of thiamine deficiency should not delay treatment when thiamine deficiency is suspected. This patient’s thiamine levels resulted a week after collection. The administration of thiamine before sampling also can alter the result as it did in this case. Additionally, laboratories may offer whole blood and serum testing. Whole blood testing is more accurate because most bioactive thiamine is found in red blood cells.17
1. Price SL, Fisher C, Kumar R, Hilgerson A. Cannabinoid hyperemesis syndrome as the underlying cause of intractable nausea and vomiting. J Am Osteopath Assoc. 2011;111(3):166-169. doi:10.7556/jaoa.2011.111.3.166
2. Sharma P, Murthy P, Bharath MM. Chemistry, metabolism, and toxicology of cannabis: clinical implications. Iran J Psychiatry. 2012;7(4):149-156.
3. Antill T, Jakkoju A, Dieguez J, Laskhmiprasad L. Lactic acidosis: a rare manifestation of synthetic marijuana intoxication. J La State Med Soc. 2015;167(3):155.
4. Sullivan S. Cannabinoid hyperemesis. Can J Gastroenterol. 2010;24(5):284-285. doi:10.1155/2010/481940
5. Duca J, Lum CJ, Lo AM. Elevated lactate secondary to gastrointestinal beriberi. J Gen Intern Med. 2016;31(1):133-136. doi:10.1007/s11606-015-3326-2
6. Prakash S. Gastrointestinal beriberi: a forme fruste of Wernicke’s encephalopathy? BMJ Case Rep. 2018;bcr2018224841. doi:10.1136/bcr-2018-224841
7. Friedenberg AS, Brandoff DE, Schiffman FJ. Type B lactic acidosis as a severe metabolic complication in lymphoma and leukemia: a case series from a single institution and literature review. Medicine (Baltimore). 2007;86(4):225-232. doi:10.1097/MD.0b013e318125759a
8. Liang CC. Bradycardia in thiamin deficiency and the role of glyoxylate. J Nutrition Sci Vitaminology. 1977;23(1):1-6. doi:10.3177/jnsv.23.1
9. Attaluri P, Castillo A, Edriss H, Nugent K. Thiamine deficiency: an important consideration in critically ill patients. Am J Med Sci. 2018;356(4):382-390. doi:10.1016/j.amjms.2018.06.015
10. Chaudhari A, Li ZY, Long A, Afshinnik A. Heavy cannabis use associated with Wernicke’s encephalopathy. Cureus. 2019;11(7):e5109. doi:10.7759/cureus.5109
11. Stabler SP. Vitamin B12 deficiency. N Engl J Med. 2013;368(2):149-160. doi:10.1056/NEJMcp1113996
12. Green R, Allen LH, Bjørke-Monsen A-L, et al. Vitamin B12 deficiency. Nat Rev Dis Primers. 2017;3(1):17040. doi:10.1038/nrdp.2017.40
13. Devalia V, Hamilton MS, Molloy AM. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. 2014;166(4):496-513. doi:10.1111/bjh.12959
14. British Columbia Ministry of Health; Guidelines and Protocols and Advisory Committee. Guidelines and protocols cobalamin (vitamin B12) deficiency–investigation & management. Effective January 1, 2012. Revised May 1, 2013. Accessed March 10, 2021. https://www2.gov.bc.ca/gov/content/health/practitioner-professional-resources/bc-guidelines/vitamin-b12
15. Galvin R, Brathen G, Ivashynka A, Hillbom M, Tanasescu R, Leone MA. EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol. 2010;17(12):1408-1418. doi:10.1111/j.1468-1331.2010.03153.x
16. Wiley KD, Gupta M. Vitamin B1 thiamine deficiency (beriberi). In: StatPearls. StatPearls Publishing LLC; 2019.
17. Jenco J, Krcmova LK, Solichova D, Solich P. Recent trends in determination of thiamine and its derivatives in clinical practice. J Chromatogra A. 2017;1510:1-12. doi:10.1016/j.chroma.2017.06.048
A 57-year-old woman with a history of traumatic brain injury, posttraumatic stress disorder, depression, migraines, hypothyroidism, and a hiatal hernia repair presented to the emergency department with a 1-day history of nausea, vomiting, and diffuse abdominal pain. She reported that her symptoms were relieved by hot showers. She also reported having similar symptoms and a previous gastric-emptying study that showed a slow-emptying stomach. Her history also consisted of frequent cannabis use for mood and appetite stimulation along with eliminating meat and fish from her diet, an increase in consumption of simple carbohydrates in the past year, and no alcohol use. Her medications included topiramate 100 mg and clonidine 0.3 mg nightly for migraines; levothyroxine 200 mcg daily for hypothyroidism; tizanidine 4 mg twice a day for muscle spasm; famotidine 40 mg twice a day as needed for gastric reflux; and bupropion 50 mg daily, citalopram 20 mg daily, and lamotrigine 25 mg nightly for mood.
The patient’s physical examination was notable for bradycardia (43 beats/min) and epigastric tenderness. Admission laboratory results were notable for an elevated lactic acid level of 4.8 (normal range, 0.50-2.20) mmol/L and a leukocytosis count of 10.8×109 cells/L. Serum alcohol level and blood cultures were negative. Liver function test, hemoglobin A1c, and lipase test were unremarkable. Her electrocardiogram showed an unchanged right bundle branch block. Chest X-ray, computed tomography (CT) of her abdomen/pelvis and echocardiogram were unremarkable.
What is your diagnosis?
How would you treat this patient?
This patient was diagnosed with gastrointestinal beriberi. Because of her dietary changes, lactic acidosis, and bradycardia, thiamine deficiency was suspected after ruling out other possibilities on the differential diagnosis (Table). The patient’s symptoms resolved after administration of high-dose IV thiamine 500 mg 3 times daily for 4 days. Her white blood cell count and lactic acid level normalized. Unfortunately, thiamine levels were not obtained for the patient before treatment was initiated. After administration of IV thiamine, her plasma thiamine level was > 1,200 (normal range, 8-30) nmol/L.
Her differential diagnosis included infectious etiology. Given her leukocytosis and lactic acidosis, vancomycin and piperacillin/tazobactam were started on admission. One day later, her leukocytosis count doubled to 20.7×109 cells/L. However, after 48 hours of negative blood cultures, antibiotics were discontinued.
Small bowel obstruction was suspected due to the patient’s history of abdominal surgery but was ruled out with CT imaging. Similarly, pancreatitis was ruled out based on negative CT imaging and the patient’s normal lipase level. Gastroparesis also was considered because of the patient’s history of hypothyroidism, tobacco use, and her prior gastric-emptying study. The patient was treated for gastroparesis with a course of metoclopramide and erythromycin without improvement in symptoms. Additionally, gastroparesis would not explain the patient’s leukocytosis.
Cannabinoid hyperemesis syndrome (CHS) was suspected because the patient’s symptoms improved with cannabis discontinuation and hot showers.1 In chronic users, however, tetrahydrocannabinol levels have a half-life of 5 to 13 days.2 Although lactic acidosis and leukocytosis have been previously reported with cannabis use, it is unlikely that the patient would have such significant improvement within the first 4 days after discontinuation.1,3,4 Although the patient had many psychiatric comorbidities with previous hospitalizations describing concern for somatization disorder, her leukocytosis and elevated lactic acid levels were suggestive of an organic rather than a psychiatric etiology of her symptoms.
Discussion
Gastrointestinal beriberi has been reported in chronic cannabis users who present with nausea, vomiting, epigastric pain, leukocytosis, and lactic acidosis; all these symptoms rapidly improve after thiamine administration.5,6 The patient’s dietary change also eliminated her intake of vitamin B12, which compounded her condition. Thiamine deficiency produces lactic acidosis by disrupting pyruvate metabolism.7 Bradycardia also can be a sign of thiamine deficiency, although the patient’s use of clonidine for migraines is a confounder.8
Chronically ill patients are prone to nutritional deficiencies, including deficiencies of thiamine.7,9 Many patients with chronic illnesses also use cannabis to ameliorate physical and neuropsychiatric symptoms.2 Recent reports suggest cannabis users are prone to gastrointestinal beriberi and Wernicke encephalopathy.5,10 Treating gastrointestinal symptoms in these patients can be challenging to diagnose because gastrointestinal beriberi and CHS share many clinical manifestations.
The patient’s presentation is likely multifactorial resulting from the combination of gastrointestinal beriberi and CHS. However, thiamine deficiency seems to play the dominant role.
There is no standard treatment regimen for thiamine deficiency with neurologic deficits, and patients only retain about 10 to 15% of intramuscular (IM) injections of cyanocobalamin.11,12 The British Committee for Standards in Haematology recommends IM injections of 1,000 mcg of cyanocobalamin 3 times a week for 2 weeks and then reassess the need for continued treatment.13 The British Columbia guidelines also recommend IM injections of 1,000 mcg daily for 1 to 5 days before transitioning to oral repletion.14 European Neurology guidelines for the treatment of Wernicke encephalopathy recommend IV cyanocobalamin 200 mg 3 times daily.15 Low-level evidence with observational studies informs these decisions and is why there is variation.
The patient’s serum lactate and leukocytosis normalized 1 day after the administration of thiamine. Thiamine deficiency classically causes Wernicke encephalopathy and wet beriberi.16 The patient did not present with Wernicke encephalopathy’s triad: ophthalmoplegia, ataxia, or confusion. She also was euvolemic without signs or symptoms of wet beriberi.
Conclusions
Thiamine deficiency is principally a clinical diagnosis. Thiamine laboratory testing may not be readily available in all medical centers, and confirming a diagnosis of thiamine deficiency should not delay treatment when thiamine deficiency is suspected. This patient’s thiamine levels resulted a week after collection. The administration of thiamine before sampling also can alter the result as it did in this case. Additionally, laboratories may offer whole blood and serum testing. Whole blood testing is more accurate because most bioactive thiamine is found in red blood cells.17
A 57-year-old woman with a history of traumatic brain injury, posttraumatic stress disorder, depression, migraines, hypothyroidism, and a hiatal hernia repair presented to the emergency department with a 1-day history of nausea, vomiting, and diffuse abdominal pain. She reported that her symptoms were relieved by hot showers. She also reported having similar symptoms and a previous gastric-emptying study that showed a slow-emptying stomach. Her history also consisted of frequent cannabis use for mood and appetite stimulation along with eliminating meat and fish from her diet, an increase in consumption of simple carbohydrates in the past year, and no alcohol use. Her medications included topiramate 100 mg and clonidine 0.3 mg nightly for migraines; levothyroxine 200 mcg daily for hypothyroidism; tizanidine 4 mg twice a day for muscle spasm; famotidine 40 mg twice a day as needed for gastric reflux; and bupropion 50 mg daily, citalopram 20 mg daily, and lamotrigine 25 mg nightly for mood.
The patient’s physical examination was notable for bradycardia (43 beats/min) and epigastric tenderness. Admission laboratory results were notable for an elevated lactic acid level of 4.8 (normal range, 0.50-2.20) mmol/L and a leukocytosis count of 10.8×109 cells/L. Serum alcohol level and blood cultures were negative. Liver function test, hemoglobin A1c, and lipase test were unremarkable. Her electrocardiogram showed an unchanged right bundle branch block. Chest X-ray, computed tomography (CT) of her abdomen/pelvis and echocardiogram were unremarkable.
What is your diagnosis?
How would you treat this patient?
This patient was diagnosed with gastrointestinal beriberi. Because of her dietary changes, lactic acidosis, and bradycardia, thiamine deficiency was suspected after ruling out other possibilities on the differential diagnosis (Table). The patient’s symptoms resolved after administration of high-dose IV thiamine 500 mg 3 times daily for 4 days. Her white blood cell count and lactic acid level normalized. Unfortunately, thiamine levels were not obtained for the patient before treatment was initiated. After administration of IV thiamine, her plasma thiamine level was > 1,200 (normal range, 8-30) nmol/L.
Her differential diagnosis included infectious etiology. Given her leukocytosis and lactic acidosis, vancomycin and piperacillin/tazobactam were started on admission. One day later, her leukocytosis count doubled to 20.7×109 cells/L. However, after 48 hours of negative blood cultures, antibiotics were discontinued.
Small bowel obstruction was suspected due to the patient’s history of abdominal surgery but was ruled out with CT imaging. Similarly, pancreatitis was ruled out based on negative CT imaging and the patient’s normal lipase level. Gastroparesis also was considered because of the patient’s history of hypothyroidism, tobacco use, and her prior gastric-emptying study. The patient was treated for gastroparesis with a course of metoclopramide and erythromycin without improvement in symptoms. Additionally, gastroparesis would not explain the patient’s leukocytosis.
Cannabinoid hyperemesis syndrome (CHS) was suspected because the patient’s symptoms improved with cannabis discontinuation and hot showers.1 In chronic users, however, tetrahydrocannabinol levels have a half-life of 5 to 13 days.2 Although lactic acidosis and leukocytosis have been previously reported with cannabis use, it is unlikely that the patient would have such significant improvement within the first 4 days after discontinuation.1,3,4 Although the patient had many psychiatric comorbidities with previous hospitalizations describing concern for somatization disorder, her leukocytosis and elevated lactic acid levels were suggestive of an organic rather than a psychiatric etiology of her symptoms.
Discussion
Gastrointestinal beriberi has been reported in chronic cannabis users who present with nausea, vomiting, epigastric pain, leukocytosis, and lactic acidosis; all these symptoms rapidly improve after thiamine administration.5,6 The patient’s dietary change also eliminated her intake of vitamin B12, which compounded her condition. Thiamine deficiency produces lactic acidosis by disrupting pyruvate metabolism.7 Bradycardia also can be a sign of thiamine deficiency, although the patient’s use of clonidine for migraines is a confounder.8
Chronically ill patients are prone to nutritional deficiencies, including deficiencies of thiamine.7,9 Many patients with chronic illnesses also use cannabis to ameliorate physical and neuropsychiatric symptoms.2 Recent reports suggest cannabis users are prone to gastrointestinal beriberi and Wernicke encephalopathy.5,10 Treating gastrointestinal symptoms in these patients can be challenging to diagnose because gastrointestinal beriberi and CHS share many clinical manifestations.
The patient’s presentation is likely multifactorial resulting from the combination of gastrointestinal beriberi and CHS. However, thiamine deficiency seems to play the dominant role.
There is no standard treatment regimen for thiamine deficiency with neurologic deficits, and patients only retain about 10 to 15% of intramuscular (IM) injections of cyanocobalamin.11,12 The British Committee for Standards in Haematology recommends IM injections of 1,000 mcg of cyanocobalamin 3 times a week for 2 weeks and then reassess the need for continued treatment.13 The British Columbia guidelines also recommend IM injections of 1,000 mcg daily for 1 to 5 days before transitioning to oral repletion.14 European Neurology guidelines for the treatment of Wernicke encephalopathy recommend IV cyanocobalamin 200 mg 3 times daily.15 Low-level evidence with observational studies informs these decisions and is why there is variation.
The patient’s serum lactate and leukocytosis normalized 1 day after the administration of thiamine. Thiamine deficiency classically causes Wernicke encephalopathy and wet beriberi.16 The patient did not present with Wernicke encephalopathy’s triad: ophthalmoplegia, ataxia, or confusion. She also was euvolemic without signs or symptoms of wet beriberi.
Conclusions
Thiamine deficiency is principally a clinical diagnosis. Thiamine laboratory testing may not be readily available in all medical centers, and confirming a diagnosis of thiamine deficiency should not delay treatment when thiamine deficiency is suspected. This patient’s thiamine levels resulted a week after collection. The administration of thiamine before sampling also can alter the result as it did in this case. Additionally, laboratories may offer whole blood and serum testing. Whole blood testing is more accurate because most bioactive thiamine is found in red blood cells.17
1. Price SL, Fisher C, Kumar R, Hilgerson A. Cannabinoid hyperemesis syndrome as the underlying cause of intractable nausea and vomiting. J Am Osteopath Assoc. 2011;111(3):166-169. doi:10.7556/jaoa.2011.111.3.166
2. Sharma P, Murthy P, Bharath MM. Chemistry, metabolism, and toxicology of cannabis: clinical implications. Iran J Psychiatry. 2012;7(4):149-156.
3. Antill T, Jakkoju A, Dieguez J, Laskhmiprasad L. Lactic acidosis: a rare manifestation of synthetic marijuana intoxication. J La State Med Soc. 2015;167(3):155.
4. Sullivan S. Cannabinoid hyperemesis. Can J Gastroenterol. 2010;24(5):284-285. doi:10.1155/2010/481940
5. Duca J, Lum CJ, Lo AM. Elevated lactate secondary to gastrointestinal beriberi. J Gen Intern Med. 2016;31(1):133-136. doi:10.1007/s11606-015-3326-2
6. Prakash S. Gastrointestinal beriberi: a forme fruste of Wernicke’s encephalopathy? BMJ Case Rep. 2018;bcr2018224841. doi:10.1136/bcr-2018-224841
7. Friedenberg AS, Brandoff DE, Schiffman FJ. Type B lactic acidosis as a severe metabolic complication in lymphoma and leukemia: a case series from a single institution and literature review. Medicine (Baltimore). 2007;86(4):225-232. doi:10.1097/MD.0b013e318125759a
8. Liang CC. Bradycardia in thiamin deficiency and the role of glyoxylate. J Nutrition Sci Vitaminology. 1977;23(1):1-6. doi:10.3177/jnsv.23.1
9. Attaluri P, Castillo A, Edriss H, Nugent K. Thiamine deficiency: an important consideration in critically ill patients. Am J Med Sci. 2018;356(4):382-390. doi:10.1016/j.amjms.2018.06.015
10. Chaudhari A, Li ZY, Long A, Afshinnik A. Heavy cannabis use associated with Wernicke’s encephalopathy. Cureus. 2019;11(7):e5109. doi:10.7759/cureus.5109
11. Stabler SP. Vitamin B12 deficiency. N Engl J Med. 2013;368(2):149-160. doi:10.1056/NEJMcp1113996
12. Green R, Allen LH, Bjørke-Monsen A-L, et al. Vitamin B12 deficiency. Nat Rev Dis Primers. 2017;3(1):17040. doi:10.1038/nrdp.2017.40
13. Devalia V, Hamilton MS, Molloy AM. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. 2014;166(4):496-513. doi:10.1111/bjh.12959
14. British Columbia Ministry of Health; Guidelines and Protocols and Advisory Committee. Guidelines and protocols cobalamin (vitamin B12) deficiency–investigation & management. Effective January 1, 2012. Revised May 1, 2013. Accessed March 10, 2021. https://www2.gov.bc.ca/gov/content/health/practitioner-professional-resources/bc-guidelines/vitamin-b12
15. Galvin R, Brathen G, Ivashynka A, Hillbom M, Tanasescu R, Leone MA. EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol. 2010;17(12):1408-1418. doi:10.1111/j.1468-1331.2010.03153.x
16. Wiley KD, Gupta M. Vitamin B1 thiamine deficiency (beriberi). In: StatPearls. StatPearls Publishing LLC; 2019.
17. Jenco J, Krcmova LK, Solichova D, Solich P. Recent trends in determination of thiamine and its derivatives in clinical practice. J Chromatogra A. 2017;1510:1-12. doi:10.1016/j.chroma.2017.06.048
1. Price SL, Fisher C, Kumar R, Hilgerson A. Cannabinoid hyperemesis syndrome as the underlying cause of intractable nausea and vomiting. J Am Osteopath Assoc. 2011;111(3):166-169. doi:10.7556/jaoa.2011.111.3.166
2. Sharma P, Murthy P, Bharath MM. Chemistry, metabolism, and toxicology of cannabis: clinical implications. Iran J Psychiatry. 2012;7(4):149-156.
3. Antill T, Jakkoju A, Dieguez J, Laskhmiprasad L. Lactic acidosis: a rare manifestation of synthetic marijuana intoxication. J La State Med Soc. 2015;167(3):155.
4. Sullivan S. Cannabinoid hyperemesis. Can J Gastroenterol. 2010;24(5):284-285. doi:10.1155/2010/481940
5. Duca J, Lum CJ, Lo AM. Elevated lactate secondary to gastrointestinal beriberi. J Gen Intern Med. 2016;31(1):133-136. doi:10.1007/s11606-015-3326-2
6. Prakash S. Gastrointestinal beriberi: a forme fruste of Wernicke’s encephalopathy? BMJ Case Rep. 2018;bcr2018224841. doi:10.1136/bcr-2018-224841
7. Friedenberg AS, Brandoff DE, Schiffman FJ. Type B lactic acidosis as a severe metabolic complication in lymphoma and leukemia: a case series from a single institution and literature review. Medicine (Baltimore). 2007;86(4):225-232. doi:10.1097/MD.0b013e318125759a
8. Liang CC. Bradycardia in thiamin deficiency and the role of glyoxylate. J Nutrition Sci Vitaminology. 1977;23(1):1-6. doi:10.3177/jnsv.23.1
9. Attaluri P, Castillo A, Edriss H, Nugent K. Thiamine deficiency: an important consideration in critically ill patients. Am J Med Sci. 2018;356(4):382-390. doi:10.1016/j.amjms.2018.06.015
10. Chaudhari A, Li ZY, Long A, Afshinnik A. Heavy cannabis use associated with Wernicke’s encephalopathy. Cureus. 2019;11(7):e5109. doi:10.7759/cureus.5109
11. Stabler SP. Vitamin B12 deficiency. N Engl J Med. 2013;368(2):149-160. doi:10.1056/NEJMcp1113996
12. Green R, Allen LH, Bjørke-Monsen A-L, et al. Vitamin B12 deficiency. Nat Rev Dis Primers. 2017;3(1):17040. doi:10.1038/nrdp.2017.40
13. Devalia V, Hamilton MS, Molloy AM. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. 2014;166(4):496-513. doi:10.1111/bjh.12959
14. British Columbia Ministry of Health; Guidelines and Protocols and Advisory Committee. Guidelines and protocols cobalamin (vitamin B12) deficiency–investigation & management. Effective January 1, 2012. Revised May 1, 2013. Accessed March 10, 2021. https://www2.gov.bc.ca/gov/content/health/practitioner-professional-resources/bc-guidelines/vitamin-b12
15. Galvin R, Brathen G, Ivashynka A, Hillbom M, Tanasescu R, Leone MA. EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol. 2010;17(12):1408-1418. doi:10.1111/j.1468-1331.2010.03153.x
16. Wiley KD, Gupta M. Vitamin B1 thiamine deficiency (beriberi). In: StatPearls. StatPearls Publishing LLC; 2019.
17. Jenco J, Krcmova LK, Solichova D, Solich P. Recent trends in determination of thiamine and its derivatives in clinical practice. J Chromatogra A. 2017;1510:1-12. doi:10.1016/j.chroma.2017.06.048
The Natural History of a Patient With COVID-19 Pneumonia and Silent Hypoxemia
In less than a year, COVID-19 has infected nearly 100 million people worldwide and caused more than 2 million deaths and counting. Although the infection fatality rate is estimated to be 1% and the case fatality rate between 2% and 3%, COVID-19 has had a disproportionate effect on the older population and those with comorbidities. Some of these findings are mirrored in the US Department of Veterans Affairs (VA) population, which has seen a higher case fatality rate.1-4
As a respiratory tract infection, the most dreaded presentation is severe pneumonia with acute hypoxemia, which may rapidly deteriorate to acute respiratory distress syndrome (ARDS) and respiratory failure.5-7 This possibility has led to early intubation strategies aimed at preempting this rapid deterioration and minimizing viral exposure to health care workers. Intubation rates have varied widely with extremes of 6 to 88%.8,9
However, this early intubation strategy has waned as some of the rationale behind its endorsement has been called into question. Early intubation bypasses alternatives to intubation; high-flow nasal cannula oxygen, noninvasive ventilation, and awake proning are all effective maneuvers in the appropriate patient.10,11 The use of first-line high-flow nasal cannula oxygen and noninvasive ventilation has been widely reported. Reports of first-line use of high-flow nasal cannula oxygen has not demonstrated inferior outcomes, nor has the timing of intubation, suggesting a significant portion of patients could benefit from a trial of therapy and eventually avoid intubation.11-14 Other therapies, such as systemic corticosteroids, confer a mortality benefit in those patients with COVID-19 who require oxygen or mechanical ventilation, but their impact on the progression of respiratory failure and need for intubation are undetermined.
There also are reports of patients who report no signs of respiratory distress or dyspnea with their COVID-19 pneumonia despite profound hypoxemia or high oxygen requirements. Various terms, including silent hypoxemia or happy hypoxia, are descriptive of the demeanor of these patients, and treatment has invariably included oxygen.15,16 Nevertheless, low oxygen measurements have generally prompted higher levels of supplemental oxygen or more invasive therapies.
Treatment rendered may obscure the trajectory of response, which is important to understand to better position options for invasive therapies and other therapeutics. We recently encountered a patient with a course of illness that represented the natural history of COVID-19 pneumonia with low oxygen levels (referred to as hypoxemia for consistency) that highlighted several issues of management.
Case Presentation
A 62-year-old undomiciled woman with morbid obesity, prediabetes mellitus, long-standing schizophrenia, and bipolar disorder presented to our facility for evaluation of dry cough and need for tuberculosis clearance for admittance to a shelter. She appeared comfortable and was afebrile with blood pressure 111/74 mm Hg, heart rate 82 beats per minute. Her respiratory rate was 18 breaths per minute, but the pulse oximetry showed oxygen saturation of 70 to 75% on room air at rest. A chest X-ray showed bibasilar infiltrates (Figure 1), and a rapid COVID-19 nasopharyngeal polymerase chain reaction (PCR) test returned positive, confirmed by a second PCR test. Baseline inflammatory markers were elevated (Figure 2). In addition, the serum interleukin-6 also was elevated to 66.1 pg/mL (normal < 5.0), erythrocyte sedimentation rate elevated to 69 mm/h, but serum procalcitonin was essentially normal (0.22 ng/mL; normal < 20 ng/mL) as was the serum lactate (1.4 mmol/L).
The patient was admitted to the intensive care unit (ICU) for close monitoring in anticipation of the possibility of decompensation based on her age, hypoxia, and elevated inflammatory markers.17 Besides a subsequent low-grade fever (100.4 oF) and lymphopenia (manual count 550/uL), she remained clinically unchanged. Throughout her hospitalization, she maintained a persistent psychotic delusion that she did not have COVID-19, refusing all medical interventions, including a peripheral IV line and supplemental oxygen for the entire duration. Extensive efforts to identify family or a surrogate decision maker were unsuccessful. After consultation with Psychiatry, Bio-Ethics, and hospital leadership, the patient was deemed to lack decision-making capacity regarding treatment or disposition and was placed on a psychiatric hold. However, since any interventions against her will would require sedation, IV access, and potentially increase the risk of nosocomial COVID-19 transmission, she was allowed to remain untreated and was closely monitored for symptoms of worsening respiratory failure.
Over the next 2 weeks, her hypoxemia, inflammatory markers, and the infiltrates on imaging resolved (Figure 2). The lowest daily awake room air pulse oximetry readings are reported, initially with consistent readings in the low 80% range, but on day 12, readings were > 90% and remained > 90% for the remainder of her hospitalization. Therefore, shortly after hospital day 12, she was clinically stable for discharge from acute care to a subacute facility, but this required documentation of the clearance of her viral infection. She refused to undergo a subsequent nasopharyngeal swab but allowed an oropharyngeal COVID-19 PCR swab, which was negative. She remained stable and unchanged for the remainder of her hospitalization, awaiting identification of a receiving facility and was able to be discharged to transitional housing on day 38.
Discussion
The initial reports of COVID-19 pneumonia focused on ARDS and respiratory failure requiring mechanical ventilation with less emphasis on those with lower severity of illness. This was heightened by health care systems that were overwhelmed with large number of patients while faced with limited supplies and equipment. Given the risk to patients and providers of crash intubations, some recommended early intubation strategies.3 However, the natural history of COVID-19 pneumonia and the threshold for intubation of these patients remain poorly defined despite the creation of prognostic tools.17 This patient’s persistent hypoxemia and elevated inflammatory markers certainly met markers of disease associated with a high risk of progression.
The greatest concern would have been her level of hypoxemia. Acceptable thresholds of hypoxemia vary, but general consensus would classify pulse oximetry < 90% as hypoxemia and a threshold for administering supplemental oxygen. It is important to recognize how pulse oximetry readings translate to partial pressure of oxygen (PaO2) measurements (Table 1). Pulse oximetry readings of 90% corresponds to a PaO2 readings of 60 mm Hg in ideal conditions without the influence of acidosis, PaCO2, or temperature. While lower readings are of concern, these do not represent absolute indications for assisted ventilatory support as lower levels are well tolerated in a variety of conditions. A common example are patients with chronic obstructive pulmonary disease. Long-term mortality benefits of continuous supplemental oxygen are well established in specific populations, but the threshold for correction in the acute setting remains a case-by-case decision. This decision is complex and is based on more than an absolute number or the amount of oxygen required to achieve a threshold level of oxygenation.
The PaO2/FIO2 (fraction of inspired oxygen) is a common measure used to address severity of disease and oxygen requirements. It also has been used to define the severity of ARDS, but the ratio is based on intubated and mechanically ventilated patients and may not translate well to those not on assisted ventilation. Treatment with supplemental oxygen also involves entrained air with associated imprecision in oxygen delivery.18 For this discussion, the patient’s admission PaO2/FIO2 on room air would have been between 190 and 260. Coupled with the bilateral infiltrates on imaging, there was justified concern for progression to severe ARDS. Her presentation would have met most of the epidemiologic criteria used in initial case finding for severe COVID-19 cases, including a blood oxygen saturation ≤ 93%, PaO2/FIO2 < 300 with infiltrates involving close to if not exceeding 50% of the lung.
With COVID-19 pneumonia, the pathologic injury to the alveoli resembles that of any viral pneumonia with recruitment of predominantly lymphocytic inflammatory cells that fill the alveoli, derangements in ventilation/perfusion mismatch as the core mechanism of hypoxemia with interstitial edema and shuntlike physiology developing at the extremes of involvement. In later stages, the histologic appearance is similar to ARDS, including hyaline membrane formation and thickened alveolar septa with perivascular lymphocytic-plasmocytic infiltration. In addition, there also are findings of organizing pneumonia with fibroblastic proliferation, thrombosis, and diffuse alveolar damage, a constellation of findings similar to that seen in the latter stages of ARDS.2
Although these histologic findings resemble ARDS, many patients with respiratory failure due to COVID-19 have a different physiologic profile compared with those with typical ARDS, with the most striking finding of lungs with low elastance or high compliance. From the critical care standpoint, this meant that the lungs were relatively easy to ventilate with lower peak airway and plateau pressures and low driving pressures. This condition suggested that there was relatively less lung that could be recruited with positive end expiratory pressure; therefore, a somewhat different entity from that associated with ARDS.19 These findings were often noted early in the course of respiratory failure, and although there is debate about whether this represents a different phenotype or timepoint in the spectrum of disease, it clearly represents a subset that is distinct from that which had been previously encountered.
On the other hand, the clinical features seen in those patients with COVID-19 pneumonia who progressed to advanced respiratory failure were essentially indistinguishable from those patients with traditional ARDS. Other explanations for this respiratory failure have included a disrupted vasoregulatory response to hypoxemia with failed hypoxic vasoconstriction, intravascular microthrombi, and impaired diffusion, all contributing to impaired gas exchange and hypoxemia.19-21 This can lead to shuntlike conditions that neither respond well to supplemental oxygen nor manifest the type of physiologic response seen with other causes of hypoxemia.
The severity of hypoxemia manifested by this patient may have elicited additional findings of respiratory distress, such as dyspnea and tachypnea. However, in patients with severe COVID-19 pneumonia, dyspnea was not a universal finding, reported in the 20 to 60% range of cohorts, higher in those with ARDS and mechanical ventilation, although some report near universal dyspnea in their series.1,4,8,22,23 Tachypnea is another symptom of interest. Using a threshold of > 24 breaths/min, tachypnea was noted in 16 to 29% of patients with a much greater proportion (63%) in nonsurvivors.6,24 Several explanations have been proposed for the discordance between the presence and severity of hypoxemia and lack of symptoms of dyspnea and tachypnea. It is important to recognize that misclassification of the severity of hypoxemia can occur due to technical issues and potential errors involving pulse oximetry measurement and shifts in the oxyhemoglobin dissociation curve. However, this is more pertinent for those with mild disease as the severity of hypoxemia in severe pneumonia is beyond what can be attributed to technical issues.
More important, the ventilatory response curve to hypoxemia may not be normal for some patients, blunted by as much as 50% in older patients, especially in those with diabetes mellitus.7,25,26 In addition, the ventilatory response varies widely even among normal individuals. This would translate to lower levels of minute ventilation (less tachypnea or respiratory effort) with hypoxemia. Hypocapnic hypoxemia also blunts the ventilatory response to hypoxemia. Subjects do not increase their minute ventilation if the PaCO2 remains low despite oxygen desaturation to < 70%, especially if PaCO2 < 30 mm Hg or alternatively, increases in minute ventilation are not seen until the PaCO2 exceeds 39 mm Hg.27 Both scenarios occur in those with COVID-19 pneumonia and provide another explanation for the absence of respiratory symptoms or signs of respiratory distress in some patients.
The observation of more compliant lungs may help in the understanding of the variable presentation of these patients. Compliant lungs do not require the increased pressure needed to achieve a specific tidal volume that, in turn, may increase the work of breathing. This may add to the explanation of seemingly paradoxical silent hypoxemia in those patients where the combination of a blunted ventilatory response, hypocapnia, shunt physiology, and normal respiratory system compliance is represented by the absence of increased breathing effort despite severe hypoxemia.
If not for the patient’s refusal of medical services, this patient quite possibly would have been intubated due to hypoxemia and health care providers’ concern for her risk of deterioration. Reported intubation and mechanical ventilation rates have varied widely from extremes of from < 5 to 88% in severely ill patients.9,22 About 75% will need oxygen, but many can be treated and recover without the need for intubation and mechanical ventilation.
As previously mentioned, options for treatment include standard and high-flow oxygen delivery, noninvasive ventilation, and awake prone ventilation. Their role in patient management has been recently outlined, and instead of an early intubation strategy, represents gradual escalation of support that may be sufficient to treat hypoxemia and avoid the need for intubation and mechanical ventilation (Table 2).
In addition, the patient’s hospital course was notable for the decline in known markers of active inflammation that mirrored the resolution of her hypoxemia and pneumonia. This included elevated lactate dehydrogenase, D-dimer, ferritin, and C-reactive protein with all but the latter rising and decreasing over 2 weeks. These findings provide additional information of the time for recovery and supports the use of these markers to monitor the course of pneumonia.
The patient declined all intervention, including oxygen, and recovered to her presumed prehospitalization condition. This experiment of nature due to unique circumstances may shed light on the natural time course of untreated hypoxemic COVID-19 pneumonia that has not previously been well appreciated. It is important to recognize that recovery occurred over 2 weeks. This is close to the observed and expected time for recovery that has been reported for those with severe COVID-19 pneumonia.
Conclusions
Since the emergence of the COVID-19, evidence has accumulated for the benefit of several adjunctive therapies in the treatment of this type of pneumonia, with corticosteroids providing a mortality benefit. Although unknown whether this patient’s experience can be generalized to others or whether it represents her unique response, this case provides another perspective for comparison of treatments and reinforces the need for prospective, randomized clinical trials to establish treatment efficacy. The exact nature of silent hypoxemia of COVID-19 remains incompletely understood; however, this case highlights the importance of treating the individual instead of clinical markers and provides a time course for recovery from pneumonia and severe hypoxemia that occurs without oxygen or any other treatment over about 2 weeks.
1. Ioannou GN, Locke E, Green P, et al. Risk factors for hospitalization, mechanical ventilation, or death among 10131 US veterans with SARS-CoV-2 infection. JAMA Netw Open. 2020;3(9):e2022310. doi:10.1001/jamanetworkopen.2020.22310
2. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA. 2020;324(8):782-793. doi:10.1001/jama.2020.12839
3. Alhazzani W, Moller MH, Arabi YM, et al. Surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Crit Care Med. 2020;48(6):e440-e469. doi:10.1097/CCM.0000000000004363
4. Ziehr DR, Alladina J, Petri CR, et al. Respiratory pathophysiology of mechanically ventilated patients with COVID-19: a cohort study. Am J Respir Crit Care Med. 2020;201(12):1560-1564. doi:10.1164/rccm.202004-1163LE
5. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):1239-1242. doi:10.1001/jama.2020.2648
6. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-1062. doi:10.1016/S01406736(20)30566-3
7. Tobin MJ, Laghi F, Jubran A. Why COVID-19 silent hypoxemia is baffling to physicians. Am J Respir Crit Care Med. 2020;202(3):356-360. doi:10.1164/rccm.202006-2157CP
8. Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708-1720. doi:10.1056/NEJMoa2002032
9. Grasselli G, Zangrillo A, Zanella A, et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020;323(16):1574-1581. doi:10.1001/jama.2020.5394
10. Raoof S, Nava S, Carpati C, Hill NS. High-flow, noninvasive ventilation and awake (nonintubation) proning in patients with coronavirus disease 2019 with respiratory failure. Chest. 2020;158(5):1992-2002. doi:10.1016/j.chest.2020.07.013
11. Ackermann M, Mentzer SJ, Jonigk D. Pulmonary vascular pathology in COVID-19. Reply. N Engl J Med. 2020;383(9):888-889. doi:10.1056/NEJMc2022068
12. McDonough G, Khaing P, Treacy T, McGrath C, Yoo EJ. The use of high-flow nasal oxygen in the ICU as a first-line therapy for acute hypoxemic respiratory failure secondary to coronavirus disease 2019. Crit Care Explor. 2020;2(10):e0257. doi:10.1097/CCE.0000000000000257
13. Hernandez-Romieu AC, Adelman MW, et al. Timing of intubation and mortality among critically ill coronavirus disease 2019 patients: a single-center cohort study. Crit Care Med. 2020;48(11):e1045-e1053. doi:10.1097/CCM.0000000000004600
14. Cummings MJ, Baldwin MR, Abrams D, et al. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. Lancet. 2020;395(10239):1763-1770. doi:10.1016/S0140-6736(20)31189-2
15. Dhont S, Derom E, Van Braeckel E, Depuydt P, Lambrecht BN. The pathophysiology of ‘happy’ hypoxemia in COVID-19. Respir Res. 2020;21(1):198. doi:10.1186/s12931-020-01462-5
16. Wilkerson RG, Adler JD, Shah NG, Brown R. Silent hypoxia: a harbinger of clinical deterioration in patients with COVID-19. Am J Emerg Med. 2020;38(10):2243.e5-2243.e6. doi:10.1016/j.ajem.2020.05.044
17. Gong J, Ou J, Qiu X, et al. A tool for early prediction of severe coronavirus disease 2019 (COVID-19): a multicenter study using the risk nomogram in Wuhan and Guangdong, China. Clin Infect Dis. 2020;71(15):833-840. doi:10.1093/cid/ciaa443
18. Force ADT, Ranieri VM, Rubenfeld GD, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307(23):2526-2533. doi:10.1001/jama.2012.5669
19. Marini JJ, Gattinoni L. Management of COVID-19 respiratory distress. JAMA. 2020;323(22):2329-2330. doi:10.1001/jama.2020.6825
20. Schaller T, Hirschbuhl K, Burkhardt K, et al. Postmortem examination of patients with COVID-19. JAMA. 2020;323(24):2518-2520. doi:10.1001/jama.2020.8907
21. Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med. 2020;383(2):120-128. doi:10.1056/NEJMoa2015432
22. Wu C, Chen X, Cai Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020;180(7):934-943. doi:10.1001/jamainternmed.2020.0994. Published correction appeared May 11, 2020. Errors in data and units of measure. doi:10.1001/jamainternmed.2020.1429
23. Yang J, Zheng Y, Gou X, et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int J Infect Dis. 2020;94:91-95. doi:10.1016/j.ijid.2020.03.017
24. Richardson S, Hirsch JS, Narasimhan M, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA. 2020;323(20):2052-2059. doi:10.1001/jama.2020.6775
25. Tobin MJ, Jubran A, Laghi F. Misconceptions of pathophysiology of happy hypoxemia and implications for management of COVID-19. Respir Res. 2020;21(1):249. doi:10.1186/s12931-020-01520-y
26. Bickler PE, Feiner JR, Lipnick MS, McKleroy W. “Silent” presentation of hypoxemia and cardiorespiratory compensation in COVID-19. Anesthesiology. 2020;134(2):262-269. doi:10.1097/ALN.0000000000003578
27. Jounieaux V, Parreira VF, Aubert G, Dury M, Delguste P, Rodenstein DO. Effects of hypocapnic hyperventilation on the response to hypoxia in normal subjects receiving intermittent positive-pressure ventilation. Chest. 2002;121(4):1141-1148. doi:10.1378/chest.121.4.1141
In less than a year, COVID-19 has infected nearly 100 million people worldwide and caused more than 2 million deaths and counting. Although the infection fatality rate is estimated to be 1% and the case fatality rate between 2% and 3%, COVID-19 has had a disproportionate effect on the older population and those with comorbidities. Some of these findings are mirrored in the US Department of Veterans Affairs (VA) population, which has seen a higher case fatality rate.1-4
As a respiratory tract infection, the most dreaded presentation is severe pneumonia with acute hypoxemia, which may rapidly deteriorate to acute respiratory distress syndrome (ARDS) and respiratory failure.5-7 This possibility has led to early intubation strategies aimed at preempting this rapid deterioration and minimizing viral exposure to health care workers. Intubation rates have varied widely with extremes of 6 to 88%.8,9
However, this early intubation strategy has waned as some of the rationale behind its endorsement has been called into question. Early intubation bypasses alternatives to intubation; high-flow nasal cannula oxygen, noninvasive ventilation, and awake proning are all effective maneuvers in the appropriate patient.10,11 The use of first-line high-flow nasal cannula oxygen and noninvasive ventilation has been widely reported. Reports of first-line use of high-flow nasal cannula oxygen has not demonstrated inferior outcomes, nor has the timing of intubation, suggesting a significant portion of patients could benefit from a trial of therapy and eventually avoid intubation.11-14 Other therapies, such as systemic corticosteroids, confer a mortality benefit in those patients with COVID-19 who require oxygen or mechanical ventilation, but their impact on the progression of respiratory failure and need for intubation are undetermined.
There also are reports of patients who report no signs of respiratory distress or dyspnea with their COVID-19 pneumonia despite profound hypoxemia or high oxygen requirements. Various terms, including silent hypoxemia or happy hypoxia, are descriptive of the demeanor of these patients, and treatment has invariably included oxygen.15,16 Nevertheless, low oxygen measurements have generally prompted higher levels of supplemental oxygen or more invasive therapies.
Treatment rendered may obscure the trajectory of response, which is important to understand to better position options for invasive therapies and other therapeutics. We recently encountered a patient with a course of illness that represented the natural history of COVID-19 pneumonia with low oxygen levels (referred to as hypoxemia for consistency) that highlighted several issues of management.
Case Presentation
A 62-year-old undomiciled woman with morbid obesity, prediabetes mellitus, long-standing schizophrenia, and bipolar disorder presented to our facility for evaluation of dry cough and need for tuberculosis clearance for admittance to a shelter. She appeared comfortable and was afebrile with blood pressure 111/74 mm Hg, heart rate 82 beats per minute. Her respiratory rate was 18 breaths per minute, but the pulse oximetry showed oxygen saturation of 70 to 75% on room air at rest. A chest X-ray showed bibasilar infiltrates (Figure 1), and a rapid COVID-19 nasopharyngeal polymerase chain reaction (PCR) test returned positive, confirmed by a second PCR test. Baseline inflammatory markers were elevated (Figure 2). In addition, the serum interleukin-6 also was elevated to 66.1 pg/mL (normal < 5.0), erythrocyte sedimentation rate elevated to 69 mm/h, but serum procalcitonin was essentially normal (0.22 ng/mL; normal < 20 ng/mL) as was the serum lactate (1.4 mmol/L).
The patient was admitted to the intensive care unit (ICU) for close monitoring in anticipation of the possibility of decompensation based on her age, hypoxia, and elevated inflammatory markers.17 Besides a subsequent low-grade fever (100.4 oF) and lymphopenia (manual count 550/uL), she remained clinically unchanged. Throughout her hospitalization, she maintained a persistent psychotic delusion that she did not have COVID-19, refusing all medical interventions, including a peripheral IV line and supplemental oxygen for the entire duration. Extensive efforts to identify family or a surrogate decision maker were unsuccessful. After consultation with Psychiatry, Bio-Ethics, and hospital leadership, the patient was deemed to lack decision-making capacity regarding treatment or disposition and was placed on a psychiatric hold. However, since any interventions against her will would require sedation, IV access, and potentially increase the risk of nosocomial COVID-19 transmission, she was allowed to remain untreated and was closely monitored for symptoms of worsening respiratory failure.
Over the next 2 weeks, her hypoxemia, inflammatory markers, and the infiltrates on imaging resolved (Figure 2). The lowest daily awake room air pulse oximetry readings are reported, initially with consistent readings in the low 80% range, but on day 12, readings were > 90% and remained > 90% for the remainder of her hospitalization. Therefore, shortly after hospital day 12, she was clinically stable for discharge from acute care to a subacute facility, but this required documentation of the clearance of her viral infection. She refused to undergo a subsequent nasopharyngeal swab but allowed an oropharyngeal COVID-19 PCR swab, which was negative. She remained stable and unchanged for the remainder of her hospitalization, awaiting identification of a receiving facility and was able to be discharged to transitional housing on day 38.
Discussion
The initial reports of COVID-19 pneumonia focused on ARDS and respiratory failure requiring mechanical ventilation with less emphasis on those with lower severity of illness. This was heightened by health care systems that were overwhelmed with large number of patients while faced with limited supplies and equipment. Given the risk to patients and providers of crash intubations, some recommended early intubation strategies.3 However, the natural history of COVID-19 pneumonia and the threshold for intubation of these patients remain poorly defined despite the creation of prognostic tools.17 This patient’s persistent hypoxemia and elevated inflammatory markers certainly met markers of disease associated with a high risk of progression.
The greatest concern would have been her level of hypoxemia. Acceptable thresholds of hypoxemia vary, but general consensus would classify pulse oximetry < 90% as hypoxemia and a threshold for administering supplemental oxygen. It is important to recognize how pulse oximetry readings translate to partial pressure of oxygen (PaO2) measurements (Table 1). Pulse oximetry readings of 90% corresponds to a PaO2 readings of 60 mm Hg in ideal conditions without the influence of acidosis, PaCO2, or temperature. While lower readings are of concern, these do not represent absolute indications for assisted ventilatory support as lower levels are well tolerated in a variety of conditions. A common example are patients with chronic obstructive pulmonary disease. Long-term mortality benefits of continuous supplemental oxygen are well established in specific populations, but the threshold for correction in the acute setting remains a case-by-case decision. This decision is complex and is based on more than an absolute number or the amount of oxygen required to achieve a threshold level of oxygenation.
The PaO2/FIO2 (fraction of inspired oxygen) is a common measure used to address severity of disease and oxygen requirements. It also has been used to define the severity of ARDS, but the ratio is based on intubated and mechanically ventilated patients and may not translate well to those not on assisted ventilation. Treatment with supplemental oxygen also involves entrained air with associated imprecision in oxygen delivery.18 For this discussion, the patient’s admission PaO2/FIO2 on room air would have been between 190 and 260. Coupled with the bilateral infiltrates on imaging, there was justified concern for progression to severe ARDS. Her presentation would have met most of the epidemiologic criteria used in initial case finding for severe COVID-19 cases, including a blood oxygen saturation ≤ 93%, PaO2/FIO2 < 300 with infiltrates involving close to if not exceeding 50% of the lung.
With COVID-19 pneumonia, the pathologic injury to the alveoli resembles that of any viral pneumonia with recruitment of predominantly lymphocytic inflammatory cells that fill the alveoli, derangements in ventilation/perfusion mismatch as the core mechanism of hypoxemia with interstitial edema and shuntlike physiology developing at the extremes of involvement. In later stages, the histologic appearance is similar to ARDS, including hyaline membrane formation and thickened alveolar septa with perivascular lymphocytic-plasmocytic infiltration. In addition, there also are findings of organizing pneumonia with fibroblastic proliferation, thrombosis, and diffuse alveolar damage, a constellation of findings similar to that seen in the latter stages of ARDS.2
Although these histologic findings resemble ARDS, many patients with respiratory failure due to COVID-19 have a different physiologic profile compared with those with typical ARDS, with the most striking finding of lungs with low elastance or high compliance. From the critical care standpoint, this meant that the lungs were relatively easy to ventilate with lower peak airway and plateau pressures and low driving pressures. This condition suggested that there was relatively less lung that could be recruited with positive end expiratory pressure; therefore, a somewhat different entity from that associated with ARDS.19 These findings were often noted early in the course of respiratory failure, and although there is debate about whether this represents a different phenotype or timepoint in the spectrum of disease, it clearly represents a subset that is distinct from that which had been previously encountered.
On the other hand, the clinical features seen in those patients with COVID-19 pneumonia who progressed to advanced respiratory failure were essentially indistinguishable from those patients with traditional ARDS. Other explanations for this respiratory failure have included a disrupted vasoregulatory response to hypoxemia with failed hypoxic vasoconstriction, intravascular microthrombi, and impaired diffusion, all contributing to impaired gas exchange and hypoxemia.19-21 This can lead to shuntlike conditions that neither respond well to supplemental oxygen nor manifest the type of physiologic response seen with other causes of hypoxemia.
The severity of hypoxemia manifested by this patient may have elicited additional findings of respiratory distress, such as dyspnea and tachypnea. However, in patients with severe COVID-19 pneumonia, dyspnea was not a universal finding, reported in the 20 to 60% range of cohorts, higher in those with ARDS and mechanical ventilation, although some report near universal dyspnea in their series.1,4,8,22,23 Tachypnea is another symptom of interest. Using a threshold of > 24 breaths/min, tachypnea was noted in 16 to 29% of patients with a much greater proportion (63%) in nonsurvivors.6,24 Several explanations have been proposed for the discordance between the presence and severity of hypoxemia and lack of symptoms of dyspnea and tachypnea. It is important to recognize that misclassification of the severity of hypoxemia can occur due to technical issues and potential errors involving pulse oximetry measurement and shifts in the oxyhemoglobin dissociation curve. However, this is more pertinent for those with mild disease as the severity of hypoxemia in severe pneumonia is beyond what can be attributed to technical issues.
More important, the ventilatory response curve to hypoxemia may not be normal for some patients, blunted by as much as 50% in older patients, especially in those with diabetes mellitus.7,25,26 In addition, the ventilatory response varies widely even among normal individuals. This would translate to lower levels of minute ventilation (less tachypnea or respiratory effort) with hypoxemia. Hypocapnic hypoxemia also blunts the ventilatory response to hypoxemia. Subjects do not increase their minute ventilation if the PaCO2 remains low despite oxygen desaturation to < 70%, especially if PaCO2 < 30 mm Hg or alternatively, increases in minute ventilation are not seen until the PaCO2 exceeds 39 mm Hg.27 Both scenarios occur in those with COVID-19 pneumonia and provide another explanation for the absence of respiratory symptoms or signs of respiratory distress in some patients.
The observation of more compliant lungs may help in the understanding of the variable presentation of these patients. Compliant lungs do not require the increased pressure needed to achieve a specific tidal volume that, in turn, may increase the work of breathing. This may add to the explanation of seemingly paradoxical silent hypoxemia in those patients where the combination of a blunted ventilatory response, hypocapnia, shunt physiology, and normal respiratory system compliance is represented by the absence of increased breathing effort despite severe hypoxemia.
If not for the patient’s refusal of medical services, this patient quite possibly would have been intubated due to hypoxemia and health care providers’ concern for her risk of deterioration. Reported intubation and mechanical ventilation rates have varied widely from extremes of from < 5 to 88% in severely ill patients.9,22 About 75% will need oxygen, but many can be treated and recover without the need for intubation and mechanical ventilation.
As previously mentioned, options for treatment include standard and high-flow oxygen delivery, noninvasive ventilation, and awake prone ventilation. Their role in patient management has been recently outlined, and instead of an early intubation strategy, represents gradual escalation of support that may be sufficient to treat hypoxemia and avoid the need for intubation and mechanical ventilation (Table 2).
In addition, the patient’s hospital course was notable for the decline in known markers of active inflammation that mirrored the resolution of her hypoxemia and pneumonia. This included elevated lactate dehydrogenase, D-dimer, ferritin, and C-reactive protein with all but the latter rising and decreasing over 2 weeks. These findings provide additional information of the time for recovery and supports the use of these markers to monitor the course of pneumonia.
The patient declined all intervention, including oxygen, and recovered to her presumed prehospitalization condition. This experiment of nature due to unique circumstances may shed light on the natural time course of untreated hypoxemic COVID-19 pneumonia that has not previously been well appreciated. It is important to recognize that recovery occurred over 2 weeks. This is close to the observed and expected time for recovery that has been reported for those with severe COVID-19 pneumonia.
Conclusions
Since the emergence of the COVID-19, evidence has accumulated for the benefit of several adjunctive therapies in the treatment of this type of pneumonia, with corticosteroids providing a mortality benefit. Although unknown whether this patient’s experience can be generalized to others or whether it represents her unique response, this case provides another perspective for comparison of treatments and reinforces the need for prospective, randomized clinical trials to establish treatment efficacy. The exact nature of silent hypoxemia of COVID-19 remains incompletely understood; however, this case highlights the importance of treating the individual instead of clinical markers and provides a time course for recovery from pneumonia and severe hypoxemia that occurs without oxygen or any other treatment over about 2 weeks.
In less than a year, COVID-19 has infected nearly 100 million people worldwide and caused more than 2 million deaths and counting. Although the infection fatality rate is estimated to be 1% and the case fatality rate between 2% and 3%, COVID-19 has had a disproportionate effect on the older population and those with comorbidities. Some of these findings are mirrored in the US Department of Veterans Affairs (VA) population, which has seen a higher case fatality rate.1-4
As a respiratory tract infection, the most dreaded presentation is severe pneumonia with acute hypoxemia, which may rapidly deteriorate to acute respiratory distress syndrome (ARDS) and respiratory failure.5-7 This possibility has led to early intubation strategies aimed at preempting this rapid deterioration and minimizing viral exposure to health care workers. Intubation rates have varied widely with extremes of 6 to 88%.8,9
However, this early intubation strategy has waned as some of the rationale behind its endorsement has been called into question. Early intubation bypasses alternatives to intubation; high-flow nasal cannula oxygen, noninvasive ventilation, and awake proning are all effective maneuvers in the appropriate patient.10,11 The use of first-line high-flow nasal cannula oxygen and noninvasive ventilation has been widely reported. Reports of first-line use of high-flow nasal cannula oxygen has not demonstrated inferior outcomes, nor has the timing of intubation, suggesting a significant portion of patients could benefit from a trial of therapy and eventually avoid intubation.11-14 Other therapies, such as systemic corticosteroids, confer a mortality benefit in those patients with COVID-19 who require oxygen or mechanical ventilation, but their impact on the progression of respiratory failure and need for intubation are undetermined.
There also are reports of patients who report no signs of respiratory distress or dyspnea with their COVID-19 pneumonia despite profound hypoxemia or high oxygen requirements. Various terms, including silent hypoxemia or happy hypoxia, are descriptive of the demeanor of these patients, and treatment has invariably included oxygen.15,16 Nevertheless, low oxygen measurements have generally prompted higher levels of supplemental oxygen or more invasive therapies.
Treatment rendered may obscure the trajectory of response, which is important to understand to better position options for invasive therapies and other therapeutics. We recently encountered a patient with a course of illness that represented the natural history of COVID-19 pneumonia with low oxygen levels (referred to as hypoxemia for consistency) that highlighted several issues of management.
Case Presentation
A 62-year-old undomiciled woman with morbid obesity, prediabetes mellitus, long-standing schizophrenia, and bipolar disorder presented to our facility for evaluation of dry cough and need for tuberculosis clearance for admittance to a shelter. She appeared comfortable and was afebrile with blood pressure 111/74 mm Hg, heart rate 82 beats per minute. Her respiratory rate was 18 breaths per minute, but the pulse oximetry showed oxygen saturation of 70 to 75% on room air at rest. A chest X-ray showed bibasilar infiltrates (Figure 1), and a rapid COVID-19 nasopharyngeal polymerase chain reaction (PCR) test returned positive, confirmed by a second PCR test. Baseline inflammatory markers were elevated (Figure 2). In addition, the serum interleukin-6 also was elevated to 66.1 pg/mL (normal < 5.0), erythrocyte sedimentation rate elevated to 69 mm/h, but serum procalcitonin was essentially normal (0.22 ng/mL; normal < 20 ng/mL) as was the serum lactate (1.4 mmol/L).
The patient was admitted to the intensive care unit (ICU) for close monitoring in anticipation of the possibility of decompensation based on her age, hypoxia, and elevated inflammatory markers.17 Besides a subsequent low-grade fever (100.4 oF) and lymphopenia (manual count 550/uL), she remained clinically unchanged. Throughout her hospitalization, she maintained a persistent psychotic delusion that she did not have COVID-19, refusing all medical interventions, including a peripheral IV line and supplemental oxygen for the entire duration. Extensive efforts to identify family or a surrogate decision maker were unsuccessful. After consultation with Psychiatry, Bio-Ethics, and hospital leadership, the patient was deemed to lack decision-making capacity regarding treatment or disposition and was placed on a psychiatric hold. However, since any interventions against her will would require sedation, IV access, and potentially increase the risk of nosocomial COVID-19 transmission, she was allowed to remain untreated and was closely monitored for symptoms of worsening respiratory failure.
Over the next 2 weeks, her hypoxemia, inflammatory markers, and the infiltrates on imaging resolved (Figure 2). The lowest daily awake room air pulse oximetry readings are reported, initially with consistent readings in the low 80% range, but on day 12, readings were > 90% and remained > 90% for the remainder of her hospitalization. Therefore, shortly after hospital day 12, she was clinically stable for discharge from acute care to a subacute facility, but this required documentation of the clearance of her viral infection. She refused to undergo a subsequent nasopharyngeal swab but allowed an oropharyngeal COVID-19 PCR swab, which was negative. She remained stable and unchanged for the remainder of her hospitalization, awaiting identification of a receiving facility and was able to be discharged to transitional housing on day 38.
Discussion
The initial reports of COVID-19 pneumonia focused on ARDS and respiratory failure requiring mechanical ventilation with less emphasis on those with lower severity of illness. This was heightened by health care systems that were overwhelmed with large number of patients while faced with limited supplies and equipment. Given the risk to patients and providers of crash intubations, some recommended early intubation strategies.3 However, the natural history of COVID-19 pneumonia and the threshold for intubation of these patients remain poorly defined despite the creation of prognostic tools.17 This patient’s persistent hypoxemia and elevated inflammatory markers certainly met markers of disease associated with a high risk of progression.
The greatest concern would have been her level of hypoxemia. Acceptable thresholds of hypoxemia vary, but general consensus would classify pulse oximetry < 90% as hypoxemia and a threshold for administering supplemental oxygen. It is important to recognize how pulse oximetry readings translate to partial pressure of oxygen (PaO2) measurements (Table 1). Pulse oximetry readings of 90% corresponds to a PaO2 readings of 60 mm Hg in ideal conditions without the influence of acidosis, PaCO2, or temperature. While lower readings are of concern, these do not represent absolute indications for assisted ventilatory support as lower levels are well tolerated in a variety of conditions. A common example are patients with chronic obstructive pulmonary disease. Long-term mortality benefits of continuous supplemental oxygen are well established in specific populations, but the threshold for correction in the acute setting remains a case-by-case decision. This decision is complex and is based on more than an absolute number or the amount of oxygen required to achieve a threshold level of oxygenation.
The PaO2/FIO2 (fraction of inspired oxygen) is a common measure used to address severity of disease and oxygen requirements. It also has been used to define the severity of ARDS, but the ratio is based on intubated and mechanically ventilated patients and may not translate well to those not on assisted ventilation. Treatment with supplemental oxygen also involves entrained air with associated imprecision in oxygen delivery.18 For this discussion, the patient’s admission PaO2/FIO2 on room air would have been between 190 and 260. Coupled with the bilateral infiltrates on imaging, there was justified concern for progression to severe ARDS. Her presentation would have met most of the epidemiologic criteria used in initial case finding for severe COVID-19 cases, including a blood oxygen saturation ≤ 93%, PaO2/FIO2 < 300 with infiltrates involving close to if not exceeding 50% of the lung.
With COVID-19 pneumonia, the pathologic injury to the alveoli resembles that of any viral pneumonia with recruitment of predominantly lymphocytic inflammatory cells that fill the alveoli, derangements in ventilation/perfusion mismatch as the core mechanism of hypoxemia with interstitial edema and shuntlike physiology developing at the extremes of involvement. In later stages, the histologic appearance is similar to ARDS, including hyaline membrane formation and thickened alveolar septa with perivascular lymphocytic-plasmocytic infiltration. In addition, there also are findings of organizing pneumonia with fibroblastic proliferation, thrombosis, and diffuse alveolar damage, a constellation of findings similar to that seen in the latter stages of ARDS.2
Although these histologic findings resemble ARDS, many patients with respiratory failure due to COVID-19 have a different physiologic profile compared with those with typical ARDS, with the most striking finding of lungs with low elastance or high compliance. From the critical care standpoint, this meant that the lungs were relatively easy to ventilate with lower peak airway and plateau pressures and low driving pressures. This condition suggested that there was relatively less lung that could be recruited with positive end expiratory pressure; therefore, a somewhat different entity from that associated with ARDS.19 These findings were often noted early in the course of respiratory failure, and although there is debate about whether this represents a different phenotype or timepoint in the spectrum of disease, it clearly represents a subset that is distinct from that which had been previously encountered.
On the other hand, the clinical features seen in those patients with COVID-19 pneumonia who progressed to advanced respiratory failure were essentially indistinguishable from those patients with traditional ARDS. Other explanations for this respiratory failure have included a disrupted vasoregulatory response to hypoxemia with failed hypoxic vasoconstriction, intravascular microthrombi, and impaired diffusion, all contributing to impaired gas exchange and hypoxemia.19-21 This can lead to shuntlike conditions that neither respond well to supplemental oxygen nor manifest the type of physiologic response seen with other causes of hypoxemia.
The severity of hypoxemia manifested by this patient may have elicited additional findings of respiratory distress, such as dyspnea and tachypnea. However, in patients with severe COVID-19 pneumonia, dyspnea was not a universal finding, reported in the 20 to 60% range of cohorts, higher in those with ARDS and mechanical ventilation, although some report near universal dyspnea in their series.1,4,8,22,23 Tachypnea is another symptom of interest. Using a threshold of > 24 breaths/min, tachypnea was noted in 16 to 29% of patients with a much greater proportion (63%) in nonsurvivors.6,24 Several explanations have been proposed for the discordance between the presence and severity of hypoxemia and lack of symptoms of dyspnea and tachypnea. It is important to recognize that misclassification of the severity of hypoxemia can occur due to technical issues and potential errors involving pulse oximetry measurement and shifts in the oxyhemoglobin dissociation curve. However, this is more pertinent for those with mild disease as the severity of hypoxemia in severe pneumonia is beyond what can be attributed to technical issues.
More important, the ventilatory response curve to hypoxemia may not be normal for some patients, blunted by as much as 50% in older patients, especially in those with diabetes mellitus.7,25,26 In addition, the ventilatory response varies widely even among normal individuals. This would translate to lower levels of minute ventilation (less tachypnea or respiratory effort) with hypoxemia. Hypocapnic hypoxemia also blunts the ventilatory response to hypoxemia. Subjects do not increase their minute ventilation if the PaCO2 remains low despite oxygen desaturation to < 70%, especially if PaCO2 < 30 mm Hg or alternatively, increases in minute ventilation are not seen until the PaCO2 exceeds 39 mm Hg.27 Both scenarios occur in those with COVID-19 pneumonia and provide another explanation for the absence of respiratory symptoms or signs of respiratory distress in some patients.
The observation of more compliant lungs may help in the understanding of the variable presentation of these patients. Compliant lungs do not require the increased pressure needed to achieve a specific tidal volume that, in turn, may increase the work of breathing. This may add to the explanation of seemingly paradoxical silent hypoxemia in those patients where the combination of a blunted ventilatory response, hypocapnia, shunt physiology, and normal respiratory system compliance is represented by the absence of increased breathing effort despite severe hypoxemia.
If not for the patient’s refusal of medical services, this patient quite possibly would have been intubated due to hypoxemia and health care providers’ concern for her risk of deterioration. Reported intubation and mechanical ventilation rates have varied widely from extremes of from < 5 to 88% in severely ill patients.9,22 About 75% will need oxygen, but many can be treated and recover without the need for intubation and mechanical ventilation.
As previously mentioned, options for treatment include standard and high-flow oxygen delivery, noninvasive ventilation, and awake prone ventilation. Their role in patient management has been recently outlined, and instead of an early intubation strategy, represents gradual escalation of support that may be sufficient to treat hypoxemia and avoid the need for intubation and mechanical ventilation (Table 2).
In addition, the patient’s hospital course was notable for the decline in known markers of active inflammation that mirrored the resolution of her hypoxemia and pneumonia. This included elevated lactate dehydrogenase, D-dimer, ferritin, and C-reactive protein with all but the latter rising and decreasing over 2 weeks. These findings provide additional information of the time for recovery and supports the use of these markers to monitor the course of pneumonia.
The patient declined all intervention, including oxygen, and recovered to her presumed prehospitalization condition. This experiment of nature due to unique circumstances may shed light on the natural time course of untreated hypoxemic COVID-19 pneumonia that has not previously been well appreciated. It is important to recognize that recovery occurred over 2 weeks. This is close to the observed and expected time for recovery that has been reported for those with severe COVID-19 pneumonia.
Conclusions
Since the emergence of the COVID-19, evidence has accumulated for the benefit of several adjunctive therapies in the treatment of this type of pneumonia, with corticosteroids providing a mortality benefit. Although unknown whether this patient’s experience can be generalized to others or whether it represents her unique response, this case provides another perspective for comparison of treatments and reinforces the need for prospective, randomized clinical trials to establish treatment efficacy. The exact nature of silent hypoxemia of COVID-19 remains incompletely understood; however, this case highlights the importance of treating the individual instead of clinical markers and provides a time course for recovery from pneumonia and severe hypoxemia that occurs without oxygen or any other treatment over about 2 weeks.
1. Ioannou GN, Locke E, Green P, et al. Risk factors for hospitalization, mechanical ventilation, or death among 10131 US veterans with SARS-CoV-2 infection. JAMA Netw Open. 2020;3(9):e2022310. doi:10.1001/jamanetworkopen.2020.22310
2. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA. 2020;324(8):782-793. doi:10.1001/jama.2020.12839
3. Alhazzani W, Moller MH, Arabi YM, et al. Surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Crit Care Med. 2020;48(6):e440-e469. doi:10.1097/CCM.0000000000004363
4. Ziehr DR, Alladina J, Petri CR, et al. Respiratory pathophysiology of mechanically ventilated patients with COVID-19: a cohort study. Am J Respir Crit Care Med. 2020;201(12):1560-1564. doi:10.1164/rccm.202004-1163LE
5. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):1239-1242. doi:10.1001/jama.2020.2648
6. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-1062. doi:10.1016/S01406736(20)30566-3
7. Tobin MJ, Laghi F, Jubran A. Why COVID-19 silent hypoxemia is baffling to physicians. Am J Respir Crit Care Med. 2020;202(3):356-360. doi:10.1164/rccm.202006-2157CP
8. Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708-1720. doi:10.1056/NEJMoa2002032
9. Grasselli G, Zangrillo A, Zanella A, et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020;323(16):1574-1581. doi:10.1001/jama.2020.5394
10. Raoof S, Nava S, Carpati C, Hill NS. High-flow, noninvasive ventilation and awake (nonintubation) proning in patients with coronavirus disease 2019 with respiratory failure. Chest. 2020;158(5):1992-2002. doi:10.1016/j.chest.2020.07.013
11. Ackermann M, Mentzer SJ, Jonigk D. Pulmonary vascular pathology in COVID-19. Reply. N Engl J Med. 2020;383(9):888-889. doi:10.1056/NEJMc2022068
12. McDonough G, Khaing P, Treacy T, McGrath C, Yoo EJ. The use of high-flow nasal oxygen in the ICU as a first-line therapy for acute hypoxemic respiratory failure secondary to coronavirus disease 2019. Crit Care Explor. 2020;2(10):e0257. doi:10.1097/CCE.0000000000000257
13. Hernandez-Romieu AC, Adelman MW, et al. Timing of intubation and mortality among critically ill coronavirus disease 2019 patients: a single-center cohort study. Crit Care Med. 2020;48(11):e1045-e1053. doi:10.1097/CCM.0000000000004600
14. Cummings MJ, Baldwin MR, Abrams D, et al. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. Lancet. 2020;395(10239):1763-1770. doi:10.1016/S0140-6736(20)31189-2
15. Dhont S, Derom E, Van Braeckel E, Depuydt P, Lambrecht BN. The pathophysiology of ‘happy’ hypoxemia in COVID-19. Respir Res. 2020;21(1):198. doi:10.1186/s12931-020-01462-5
16. Wilkerson RG, Adler JD, Shah NG, Brown R. Silent hypoxia: a harbinger of clinical deterioration in patients with COVID-19. Am J Emerg Med. 2020;38(10):2243.e5-2243.e6. doi:10.1016/j.ajem.2020.05.044
17. Gong J, Ou J, Qiu X, et al. A tool for early prediction of severe coronavirus disease 2019 (COVID-19): a multicenter study using the risk nomogram in Wuhan and Guangdong, China. Clin Infect Dis. 2020;71(15):833-840. doi:10.1093/cid/ciaa443
18. Force ADT, Ranieri VM, Rubenfeld GD, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307(23):2526-2533. doi:10.1001/jama.2012.5669
19. Marini JJ, Gattinoni L. Management of COVID-19 respiratory distress. JAMA. 2020;323(22):2329-2330. doi:10.1001/jama.2020.6825
20. Schaller T, Hirschbuhl K, Burkhardt K, et al. Postmortem examination of patients with COVID-19. JAMA. 2020;323(24):2518-2520. doi:10.1001/jama.2020.8907
21. Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med. 2020;383(2):120-128. doi:10.1056/NEJMoa2015432
22. Wu C, Chen X, Cai Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020;180(7):934-943. doi:10.1001/jamainternmed.2020.0994. Published correction appeared May 11, 2020. Errors in data and units of measure. doi:10.1001/jamainternmed.2020.1429
23. Yang J, Zheng Y, Gou X, et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int J Infect Dis. 2020;94:91-95. doi:10.1016/j.ijid.2020.03.017
24. Richardson S, Hirsch JS, Narasimhan M, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA. 2020;323(20):2052-2059. doi:10.1001/jama.2020.6775
25. Tobin MJ, Jubran A, Laghi F. Misconceptions of pathophysiology of happy hypoxemia and implications for management of COVID-19. Respir Res. 2020;21(1):249. doi:10.1186/s12931-020-01520-y
26. Bickler PE, Feiner JR, Lipnick MS, McKleroy W. “Silent” presentation of hypoxemia and cardiorespiratory compensation in COVID-19. Anesthesiology. 2020;134(2):262-269. doi:10.1097/ALN.0000000000003578
27. Jounieaux V, Parreira VF, Aubert G, Dury M, Delguste P, Rodenstein DO. Effects of hypocapnic hyperventilation on the response to hypoxia in normal subjects receiving intermittent positive-pressure ventilation. Chest. 2002;121(4):1141-1148. doi:10.1378/chest.121.4.1141
1. Ioannou GN, Locke E, Green P, et al. Risk factors for hospitalization, mechanical ventilation, or death among 10131 US veterans with SARS-CoV-2 infection. JAMA Netw Open. 2020;3(9):e2022310. doi:10.1001/jamanetworkopen.2020.22310
2. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA. 2020;324(8):782-793. doi:10.1001/jama.2020.12839
3. Alhazzani W, Moller MH, Arabi YM, et al. Surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Crit Care Med. 2020;48(6):e440-e469. doi:10.1097/CCM.0000000000004363
4. Ziehr DR, Alladina J, Petri CR, et al. Respiratory pathophysiology of mechanically ventilated patients with COVID-19: a cohort study. Am J Respir Crit Care Med. 2020;201(12):1560-1564. doi:10.1164/rccm.202004-1163LE
5. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):1239-1242. doi:10.1001/jama.2020.2648
6. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-1062. doi:10.1016/S01406736(20)30566-3
7. Tobin MJ, Laghi F, Jubran A. Why COVID-19 silent hypoxemia is baffling to physicians. Am J Respir Crit Care Med. 2020;202(3):356-360. doi:10.1164/rccm.202006-2157CP
8. Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708-1720. doi:10.1056/NEJMoa2002032
9. Grasselli G, Zangrillo A, Zanella A, et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020;323(16):1574-1581. doi:10.1001/jama.2020.5394
10. Raoof S, Nava S, Carpati C, Hill NS. High-flow, noninvasive ventilation and awake (nonintubation) proning in patients with coronavirus disease 2019 with respiratory failure. Chest. 2020;158(5):1992-2002. doi:10.1016/j.chest.2020.07.013
11. Ackermann M, Mentzer SJ, Jonigk D. Pulmonary vascular pathology in COVID-19. Reply. N Engl J Med. 2020;383(9):888-889. doi:10.1056/NEJMc2022068
12. McDonough G, Khaing P, Treacy T, McGrath C, Yoo EJ. The use of high-flow nasal oxygen in the ICU as a first-line therapy for acute hypoxemic respiratory failure secondary to coronavirus disease 2019. Crit Care Explor. 2020;2(10):e0257. doi:10.1097/CCE.0000000000000257
13. Hernandez-Romieu AC, Adelman MW, et al. Timing of intubation and mortality among critically ill coronavirus disease 2019 patients: a single-center cohort study. Crit Care Med. 2020;48(11):e1045-e1053. doi:10.1097/CCM.0000000000004600
14. Cummings MJ, Baldwin MR, Abrams D, et al. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. Lancet. 2020;395(10239):1763-1770. doi:10.1016/S0140-6736(20)31189-2
15. Dhont S, Derom E, Van Braeckel E, Depuydt P, Lambrecht BN. The pathophysiology of ‘happy’ hypoxemia in COVID-19. Respir Res. 2020;21(1):198. doi:10.1186/s12931-020-01462-5
16. Wilkerson RG, Adler JD, Shah NG, Brown R. Silent hypoxia: a harbinger of clinical deterioration in patients with COVID-19. Am J Emerg Med. 2020;38(10):2243.e5-2243.e6. doi:10.1016/j.ajem.2020.05.044
17. Gong J, Ou J, Qiu X, et al. A tool for early prediction of severe coronavirus disease 2019 (COVID-19): a multicenter study using the risk nomogram in Wuhan and Guangdong, China. Clin Infect Dis. 2020;71(15):833-840. doi:10.1093/cid/ciaa443
18. Force ADT, Ranieri VM, Rubenfeld GD, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307(23):2526-2533. doi:10.1001/jama.2012.5669
19. Marini JJ, Gattinoni L. Management of COVID-19 respiratory distress. JAMA. 2020;323(22):2329-2330. doi:10.1001/jama.2020.6825
20. Schaller T, Hirschbuhl K, Burkhardt K, et al. Postmortem examination of patients with COVID-19. JAMA. 2020;323(24):2518-2520. doi:10.1001/jama.2020.8907
21. Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med. 2020;383(2):120-128. doi:10.1056/NEJMoa2015432
22. Wu C, Chen X, Cai Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020;180(7):934-943. doi:10.1001/jamainternmed.2020.0994. Published correction appeared May 11, 2020. Errors in data and units of measure. doi:10.1001/jamainternmed.2020.1429
23. Yang J, Zheng Y, Gou X, et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int J Infect Dis. 2020;94:91-95. doi:10.1016/j.ijid.2020.03.017
24. Richardson S, Hirsch JS, Narasimhan M, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA. 2020;323(20):2052-2059. doi:10.1001/jama.2020.6775
25. Tobin MJ, Jubran A, Laghi F. Misconceptions of pathophysiology of happy hypoxemia and implications for management of COVID-19. Respir Res. 2020;21(1):249. doi:10.1186/s12931-020-01520-y
26. Bickler PE, Feiner JR, Lipnick MS, McKleroy W. “Silent” presentation of hypoxemia and cardiorespiratory compensation in COVID-19. Anesthesiology. 2020;134(2):262-269. doi:10.1097/ALN.0000000000003578
27. Jounieaux V, Parreira VF, Aubert G, Dury M, Delguste P, Rodenstein DO. Effects of hypocapnic hyperventilation on the response to hypoxia in normal subjects receiving intermittent positive-pressure ventilation. Chest. 2002;121(4):1141-1148. doi:10.1378/chest.121.4.1141
Bariatric surgery may cut cancer in obesity with liver disease
In a large cohort of insured working adults with severe obesity and nonalcoholic fatty liver disease (NAFLD), the rate of incident cancer was lower during a 10-month median follow-up period among those who underwent bariatric surgery. The rate was especially lower with regard to obesity-related cancers. The risk reduction was greater among patients with cirrhosis.
Among almost 100,000 patients with severe obesity (body mass index >40 kg/m2) and NAFLD, those who underwent bariatric surgery had an 18% and 35% lower risk of developing any cancer or obesity-related cancer, respectively.
Bariatric surgery was associated with a significantly lower risk of being diagnosed with colorectal, pancreatic, endometrial, and thyroid cancer, as well as hepatocellular carcinoma and multiple myeloma (all obesity-related cancers). The findings are from an observational study by Vinod K. Rustgi, MD, MBA, and colleagues, which was published online March 17, 2021, in Gastroenterology.
It was not surprising that bariatric surgery is effective in reducing the malignancy rate among patients with cirrhosis, the researchers wrote, because the surgery results in long-term weight loss, resolution of nonalcoholic steatohepatitis (NASH), and regression of fibrosis.
“Cirrhosis can happen from fatty liver disease or NASH,” Dr. Rustgi, a hepatologist at Robert Wood Johnson Medical School, New Brunswick, N.J., explained to this news organization. “It’s becoming the fastest growing indication for liver transplant, but also the reason for increased rates of hepatocellular carcinoma.”
Current treatment for patients with obesity and fatty liver disease begins with lifestyle changes to lose weight, he continued. “As people lose 10% of their weight, they actually start to see regression of fibrosis in the liver that is correlated with [lower rates of] malignancy outcomes and other deleterious outcomes.” But long-lasting weight loss is extremely difficult to achieve.
Future studies “may identify new targets and treatments, such as antidiabetic-, satiety-, or GLP-1-based medications, for chemoprevention in NAFLD/NASH,” the investigators suggested. However, pharmaceutical agents will likely be very expensive when they eventually get marketed, Dr. Rustgi observed.
Although “bariatric surgery is a more aggressive approach than lifestyle modifications, surgery may provide additional benefits, such as improved quality of life and decreased long-term health care costs,” he and his coauthors concluded.
Rising rates of fatty liver disease, obesity
An estimated 30% of the population of the United States has NAFLD, the most common chronic liver disease, the researchers noted in their article. The prevalence of NAFLD increased 2.8-fold in the United States between 2003 and 2011, in parallel with increasing obesity.
NAFLD is more common among male patients with obesity and diabetes and Hispanic patients; “70% of [patients with diabetes] may have fatty liver disease, according to certain surveys,” Dr. Rustgi noted.
Cancer is the second greatest cause of mortality among patients with obesity and NAFLD, he continued, after cardiovascular disease. Cancer mortality is higher than mortality from liver disease.
Obesity-related cancers include adenocarcinoma of the esophagus, cancers of the breast (in postmenopausal women), colon, rectum, endometrium (corpus uterus), gallbladder, gastric cardia, kidney (renal cell), liver, ovary, pancreas, and thyroid, as well as meningioma and multiple myeloma, according to a 2016 report from the International Agency for Research on Cancer working group.
Obesity-related cancer accounted for 40% of all cancer in the United States in 2014 – 55% of cancers in women, and 24% of cancers in men, according to a study published in Morbidity and Mortality Weekly Report in 2017, as previously reported by this news organization.
Several studies, including one presented at Obesity Week in 2019 and later published, have shown that bariatric surgery is linked with a lower risk for cancer in general populations.
One meta-analysis reported that NAFLD is an independent risk factor for cholangiocarcinoma and colorectal, breast, gastric, pancreatic, prostate, and esophageal cancers. In another study, NAFLD was associated with a twofold increased risk for hepatocellular carcinoma and uterine, stomach, pancreatic, and colon cancers, Dr. Rustgi and colleagues noted.
Until now, the impact of bariatric surgery on the risk for cancer among patients with obesity and NAFLD was unknown.
Does bariatric surgery curb cancer risk in liver disease?
The researchers examined insurance claims data from the national MarketScan database from Jan. 1, 2007, to Dec. 31, 2017, for patients aged 18-64 years who had health insurance from 350 employers and 100 insurers. They identified 98,090 patients with severe obesity who were newly diagnosed with NAFLD during 2008-2017.
Roughly a third of the cohort (33,435 patients) underwent bariatric surgery. From 2008 to 2017, laparoscopic sleeve gastrectomies increased from 4% of bariatric procedures to 68% of all surgeries. Laparoscopic adjustable gastric band and laparoscopic Roux-en-Y gastric bypass procedures fell from 35% to less than 1% and from 49% to 28%, respectively.
Patients who underwent bariatric surgery were younger (mean age, 44 vs. 46 years), were more likely to be women (74% vs. 62%), and were less likely to have a history of smoking (6% vs. 10%).
During a mean follow-up of 22 months (and a median follow-up of 10 months), there were 911 incident cases of obesity-related cancers. These included cancer of the colon (116 cases), rectum (15), breast (in postmenopausal women; 131), kidney (120), esophagus (16), gastric cardia (8), gallbladder (4), pancreas (44), ovaries (74), endometrium (135), and thyroid (143), as well as hepatocellular carcinoma (49), multiple myeloma (50), and meningioma (6). There were 1,912 incident cases of other cancers, such as brain and lung cancers and leukemia.
A total of 258 patients who underwent bariatric surgery developed an obesity-related cancer (an incidence of 3.83 per 1,000 person-years), compared with 653 patients who did not have bariatric surgery (an incidence of 5.63 per 1,000 person-years).
The researchers noted that study limitations include the fact that it was restricted to privately insured individuals aged 18-64 years with severe obesity. In addition, “the short median follow-up may underestimate the full effect of bariatric surgery on cancer risk,” they wrote.
The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a large cohort of insured working adults with severe obesity and nonalcoholic fatty liver disease (NAFLD), the rate of incident cancer was lower during a 10-month median follow-up period among those who underwent bariatric surgery. The rate was especially lower with regard to obesity-related cancers. The risk reduction was greater among patients with cirrhosis.
Among almost 100,000 patients with severe obesity (body mass index >40 kg/m2) and NAFLD, those who underwent bariatric surgery had an 18% and 35% lower risk of developing any cancer or obesity-related cancer, respectively.
Bariatric surgery was associated with a significantly lower risk of being diagnosed with colorectal, pancreatic, endometrial, and thyroid cancer, as well as hepatocellular carcinoma and multiple myeloma (all obesity-related cancers). The findings are from an observational study by Vinod K. Rustgi, MD, MBA, and colleagues, which was published online March 17, 2021, in Gastroenterology.
It was not surprising that bariatric surgery is effective in reducing the malignancy rate among patients with cirrhosis, the researchers wrote, because the surgery results in long-term weight loss, resolution of nonalcoholic steatohepatitis (NASH), and regression of fibrosis.
“Cirrhosis can happen from fatty liver disease or NASH,” Dr. Rustgi, a hepatologist at Robert Wood Johnson Medical School, New Brunswick, N.J., explained to this news organization. “It’s becoming the fastest growing indication for liver transplant, but also the reason for increased rates of hepatocellular carcinoma.”
Current treatment for patients with obesity and fatty liver disease begins with lifestyle changes to lose weight, he continued. “As people lose 10% of their weight, they actually start to see regression of fibrosis in the liver that is correlated with [lower rates of] malignancy outcomes and other deleterious outcomes.” But long-lasting weight loss is extremely difficult to achieve.
Future studies “may identify new targets and treatments, such as antidiabetic-, satiety-, or GLP-1-based medications, for chemoprevention in NAFLD/NASH,” the investigators suggested. However, pharmaceutical agents will likely be very expensive when they eventually get marketed, Dr. Rustgi observed.
Although “bariatric surgery is a more aggressive approach than lifestyle modifications, surgery may provide additional benefits, such as improved quality of life and decreased long-term health care costs,” he and his coauthors concluded.
Rising rates of fatty liver disease, obesity
An estimated 30% of the population of the United States has NAFLD, the most common chronic liver disease, the researchers noted in their article. The prevalence of NAFLD increased 2.8-fold in the United States between 2003 and 2011, in parallel with increasing obesity.
NAFLD is more common among male patients with obesity and diabetes and Hispanic patients; “70% of [patients with diabetes] may have fatty liver disease, according to certain surveys,” Dr. Rustgi noted.
Cancer is the second greatest cause of mortality among patients with obesity and NAFLD, he continued, after cardiovascular disease. Cancer mortality is higher than mortality from liver disease.
Obesity-related cancers include adenocarcinoma of the esophagus, cancers of the breast (in postmenopausal women), colon, rectum, endometrium (corpus uterus), gallbladder, gastric cardia, kidney (renal cell), liver, ovary, pancreas, and thyroid, as well as meningioma and multiple myeloma, according to a 2016 report from the International Agency for Research on Cancer working group.
Obesity-related cancer accounted for 40% of all cancer in the United States in 2014 – 55% of cancers in women, and 24% of cancers in men, according to a study published in Morbidity and Mortality Weekly Report in 2017, as previously reported by this news organization.
Several studies, including one presented at Obesity Week in 2019 and later published, have shown that bariatric surgery is linked with a lower risk for cancer in general populations.
One meta-analysis reported that NAFLD is an independent risk factor for cholangiocarcinoma and colorectal, breast, gastric, pancreatic, prostate, and esophageal cancers. In another study, NAFLD was associated with a twofold increased risk for hepatocellular carcinoma and uterine, stomach, pancreatic, and colon cancers, Dr. Rustgi and colleagues noted.
Until now, the impact of bariatric surgery on the risk for cancer among patients with obesity and NAFLD was unknown.
Does bariatric surgery curb cancer risk in liver disease?
The researchers examined insurance claims data from the national MarketScan database from Jan. 1, 2007, to Dec. 31, 2017, for patients aged 18-64 years who had health insurance from 350 employers and 100 insurers. They identified 98,090 patients with severe obesity who were newly diagnosed with NAFLD during 2008-2017.
Roughly a third of the cohort (33,435 patients) underwent bariatric surgery. From 2008 to 2017, laparoscopic sleeve gastrectomies increased from 4% of bariatric procedures to 68% of all surgeries. Laparoscopic adjustable gastric band and laparoscopic Roux-en-Y gastric bypass procedures fell from 35% to less than 1% and from 49% to 28%, respectively.
Patients who underwent bariatric surgery were younger (mean age, 44 vs. 46 years), were more likely to be women (74% vs. 62%), and were less likely to have a history of smoking (6% vs. 10%).
During a mean follow-up of 22 months (and a median follow-up of 10 months), there were 911 incident cases of obesity-related cancers. These included cancer of the colon (116 cases), rectum (15), breast (in postmenopausal women; 131), kidney (120), esophagus (16), gastric cardia (8), gallbladder (4), pancreas (44), ovaries (74), endometrium (135), and thyroid (143), as well as hepatocellular carcinoma (49), multiple myeloma (50), and meningioma (6). There were 1,912 incident cases of other cancers, such as brain and lung cancers and leukemia.
A total of 258 patients who underwent bariatric surgery developed an obesity-related cancer (an incidence of 3.83 per 1,000 person-years), compared with 653 patients who did not have bariatric surgery (an incidence of 5.63 per 1,000 person-years).
The researchers noted that study limitations include the fact that it was restricted to privately insured individuals aged 18-64 years with severe obesity. In addition, “the short median follow-up may underestimate the full effect of bariatric surgery on cancer risk,” they wrote.
The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a large cohort of insured working adults with severe obesity and nonalcoholic fatty liver disease (NAFLD), the rate of incident cancer was lower during a 10-month median follow-up period among those who underwent bariatric surgery. The rate was especially lower with regard to obesity-related cancers. The risk reduction was greater among patients with cirrhosis.
Among almost 100,000 patients with severe obesity (body mass index >40 kg/m2) and NAFLD, those who underwent bariatric surgery had an 18% and 35% lower risk of developing any cancer or obesity-related cancer, respectively.
Bariatric surgery was associated with a significantly lower risk of being diagnosed with colorectal, pancreatic, endometrial, and thyroid cancer, as well as hepatocellular carcinoma and multiple myeloma (all obesity-related cancers). The findings are from an observational study by Vinod K. Rustgi, MD, MBA, and colleagues, which was published online March 17, 2021, in Gastroenterology.
It was not surprising that bariatric surgery is effective in reducing the malignancy rate among patients with cirrhosis, the researchers wrote, because the surgery results in long-term weight loss, resolution of nonalcoholic steatohepatitis (NASH), and regression of fibrosis.
“Cirrhosis can happen from fatty liver disease or NASH,” Dr. Rustgi, a hepatologist at Robert Wood Johnson Medical School, New Brunswick, N.J., explained to this news organization. “It’s becoming the fastest growing indication for liver transplant, but also the reason for increased rates of hepatocellular carcinoma.”
Current treatment for patients with obesity and fatty liver disease begins with lifestyle changes to lose weight, he continued. “As people lose 10% of their weight, they actually start to see regression of fibrosis in the liver that is correlated with [lower rates of] malignancy outcomes and other deleterious outcomes.” But long-lasting weight loss is extremely difficult to achieve.
Future studies “may identify new targets and treatments, such as antidiabetic-, satiety-, or GLP-1-based medications, for chemoprevention in NAFLD/NASH,” the investigators suggested. However, pharmaceutical agents will likely be very expensive when they eventually get marketed, Dr. Rustgi observed.
Although “bariatric surgery is a more aggressive approach than lifestyle modifications, surgery may provide additional benefits, such as improved quality of life and decreased long-term health care costs,” he and his coauthors concluded.
Rising rates of fatty liver disease, obesity
An estimated 30% of the population of the United States has NAFLD, the most common chronic liver disease, the researchers noted in their article. The prevalence of NAFLD increased 2.8-fold in the United States between 2003 and 2011, in parallel with increasing obesity.
NAFLD is more common among male patients with obesity and diabetes and Hispanic patients; “70% of [patients with diabetes] may have fatty liver disease, according to certain surveys,” Dr. Rustgi noted.
Cancer is the second greatest cause of mortality among patients with obesity and NAFLD, he continued, after cardiovascular disease. Cancer mortality is higher than mortality from liver disease.
Obesity-related cancers include adenocarcinoma of the esophagus, cancers of the breast (in postmenopausal women), colon, rectum, endometrium (corpus uterus), gallbladder, gastric cardia, kidney (renal cell), liver, ovary, pancreas, and thyroid, as well as meningioma and multiple myeloma, according to a 2016 report from the International Agency for Research on Cancer working group.
Obesity-related cancer accounted for 40% of all cancer in the United States in 2014 – 55% of cancers in women, and 24% of cancers in men, according to a study published in Morbidity and Mortality Weekly Report in 2017, as previously reported by this news organization.
Several studies, including one presented at Obesity Week in 2019 and later published, have shown that bariatric surgery is linked with a lower risk for cancer in general populations.
One meta-analysis reported that NAFLD is an independent risk factor for cholangiocarcinoma and colorectal, breast, gastric, pancreatic, prostate, and esophageal cancers. In another study, NAFLD was associated with a twofold increased risk for hepatocellular carcinoma and uterine, stomach, pancreatic, and colon cancers, Dr. Rustgi and colleagues noted.
Until now, the impact of bariatric surgery on the risk for cancer among patients with obesity and NAFLD was unknown.
Does bariatric surgery curb cancer risk in liver disease?
The researchers examined insurance claims data from the national MarketScan database from Jan. 1, 2007, to Dec. 31, 2017, for patients aged 18-64 years who had health insurance from 350 employers and 100 insurers. They identified 98,090 patients with severe obesity who were newly diagnosed with NAFLD during 2008-2017.
Roughly a third of the cohort (33,435 patients) underwent bariatric surgery. From 2008 to 2017, laparoscopic sleeve gastrectomies increased from 4% of bariatric procedures to 68% of all surgeries. Laparoscopic adjustable gastric band and laparoscopic Roux-en-Y gastric bypass procedures fell from 35% to less than 1% and from 49% to 28%, respectively.
Patients who underwent bariatric surgery were younger (mean age, 44 vs. 46 years), were more likely to be women (74% vs. 62%), and were less likely to have a history of smoking (6% vs. 10%).
During a mean follow-up of 22 months (and a median follow-up of 10 months), there were 911 incident cases of obesity-related cancers. These included cancer of the colon (116 cases), rectum (15), breast (in postmenopausal women; 131), kidney (120), esophagus (16), gastric cardia (8), gallbladder (4), pancreas (44), ovaries (74), endometrium (135), and thyroid (143), as well as hepatocellular carcinoma (49), multiple myeloma (50), and meningioma (6). There were 1,912 incident cases of other cancers, such as brain and lung cancers and leukemia.
A total of 258 patients who underwent bariatric surgery developed an obesity-related cancer (an incidence of 3.83 per 1,000 person-years), compared with 653 patients who did not have bariatric surgery (an incidence of 5.63 per 1,000 person-years).
The researchers noted that study limitations include the fact that it was restricted to privately insured individuals aged 18-64 years with severe obesity. In addition, “the short median follow-up may underestimate the full effect of bariatric surgery on cancer risk,” they wrote.
The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Creating a Sustainable and Reliable Emergency Preparedness Program to Promote Appropriate Health Care Resources Use
Over the past decade, natural disasters and health care emergencies have increased 74%, averaging 400 documented events per year.1 These unpredictable and sometimes devastating events negatively impact the physical and mental health of communities, taxing already stretched health care system resources and the economy.2,3 During many of these events, patients inappropriately use hospitals, emergency departments (EDs), and critical care resources for chronic disease and elective health care management, resulting in medication shortages, health care access concerns, and treatment delays.4
Most available emergency preparedness programs rely solely on volunteers and/or public health providers to address the resultant coverage gap; however, instability in state and federal funding can make it difficult to maintain and sustain focused preparedness and response efforts. Alaska’s vast geography, low population density (1.2 people per square mile), and access limitations (about 200 villages only reachable by air or boat) make it especially challenging to provide reliable and sustained emergency preparedness and response support. Therefore, all eligible health care providers (HCPs) in Alaska must be involved in preparedness and response efforts.
Despite being the most accessible HCPs, pharmacists and student pharmacists, have not been actively involved in statewide emergency preparedness planning and disaster management efforts in Alaska. In preparation for and during disasters, for example, pharmacists may administer vaccinations, conduct point of care testing, dispense emergency medications, provide emergency medication refills, help mitigate medication shortages, and provide reliable health information to other health care professionals, patients, and their families as they prepare for and manage care during the event.4
The goal of this paper is to share the experience at the University of Alaska Anchorage/Idaho State University College of Pharmacy (UAA/ISU) in the development and implementation of a sustainable emergency preparedness and response support network (EPRSN) model; leveraging an established university student leadership structure and Doctor of Pharmacy (PharmD) students to support sharing of information among community pharmacies, state emergency response teams, and community members.
2018 Alaska Earthquake
On November 30, 2018, southcentral Alaska experienced a magnitude 7.1 earthquake, affecting nearly 295,000 people (approximately 40% of Alaska’s population) damaging roads, buildings, homes, and health care facilities. Emergency response efforts were quickly overwhelmed and hospital EDs became overburdened with patients seeking not only emergent, but also chronic care along with requests for prescription refills.
During disasters, disruptions in medication access and adherence are common. Disruptions can lead to disease exacerbation or progression, hospitalization, and/or death; all of which further contribute to the health care system and economic health burden. For example, after Hurricane Katrina, 46% of patients on hypertension medications had less than perfect adherence due to a variety of reasons (eg, not bringing any or enough medications during evacuation, lack of access to refills).5 Nonadherence to prescription hypertension medication specifically can lead to stroke, heart attack, and more rapidly progressing kidney dysfunction. Patients with diabetes mellitus (DM) also experience negative consequences due to disruptions in medication adherence.6 Lack of access to medications and supplies for DM can likewise lead to significant health sequelae, including acute hyperglycemic events, which can be life-threatening; ongoing hyperglycemia can lead to higher rates of cardiovascular disease, kidney disease, nerve damage, and diabetic retinopathy.7 However, the long-term effects of a natural disaster on health in terms of morbidity and mortality often go unreported, and their impact on chronic health conditions may be underestimated and last for years after the event.
As future health care professionals, student pharmacists continually seek opportunities to engage with and support communities; including preparing for, responding to, mitigating against, and recovering from disasters that affect the health care system and access to needed drug therapies. After the earthquake, student pharmacists reached out to state and local emergency response programs detailed within The State of Alaska Emergency Operations Plan to find opportunities to volunteer.
Agencies contacted included the Office of Emergency Management (OEM) for the Municipality of Anchorage. OEM partners with local health, fire, and police departments, the Alaska Department of Health and Social Services and Emergency Management, the Federal Emergency Management Agency, Centers for Disease Control and Prevention, American Red Cross, and the Salvation Army. It is important to note, due to lack of funding, Alaska no longer has a Medical Reserve Corps, which significantly impacts community emergency response and resilience efforts. After the earthquake, the emergency program manager extended an invitation to student pharmacists to join the joint medical emergency conference call, where local HCPs discuss emergency protocols, identify gaps, and work together to identify solutions.
During this call there was a consensus among HCPs that many patients were inappropriately seeking to fill and refill prescription medications in the ED, and staff were ill-prepared to guide patients to the appropriate services, unaware of which pharmacies were impacted by the earthquake; therefore unable to direct patients to still-operational pharmacies in the area. Together faculty and students discussed how student pharmacists could be involved in filling these identified information gaps and enhance communication among HCPs and entities. It was determined that if student pharmacists established and maintained open lines of communication with community pharmacists, they could efficiently determine which pharmacies were open and operational after disasters and disseminate that information to EDs and health care facilities in order to better direct patients to appropriate health care services.
Observations
A question/answer format and time line approach was used to review the steps leading to EPRSN program development and establishment of project/model deliverables.
Identified gaps
Chronic disease management. According to interviews conducted by the National Center for Disaster Preparedness, people often inappropriately use EDs during disasters.8 EDs do not stock enough medications to refill prescriptions for patients outside of their emergent care needs and are typically ill-suited for patients’ chronic disease management. At the time of the earthquake in Alaska no specific place/organization had been established to collect, store, or disseminate information regarding available pharmacy resources in an emergency. Had such a system been in place to actively inform HCPs and community members which pharmacies were open and operational, it is likely that many negative consequences related to health care utilization could have been reduced or avoided, including the number of people inappropriately using EDs for chronic prescription medication refills. This would not only reduce the burden on the health care system but allow for patients with both emergency and chronic needs to be seen quickly and prevent unnecessary health care costs.
Pharmacists play a vital role in managing chronic diseases.9 Due to extensive education and training, they are considered medication experts, ideally suited to manage chronic medication therapy, help prevent or minimize disease exacerbation and/or progression, reduce preventable health care costs, improve patient quality of life, and reduce morbidity and mortality.9 Pharmacists are accessible and strategically located throughout communities and provide patients with continuity of care other HCPs may be unable to provide. For example, during the COVID-19 pandemic, pharmacies remained open when other primary care providers (PCPs) were not. In addition, during times of natural disasters pharmacies tend to remain open unless there are extenuating circumstances (eg, unsafe building infrastructure, unsafe drug supply).
Emergency Response. To determine the role pharmacists play in emergency preparedness efforts we looked initially to the peer-reviewed literature (search terms: emergency preparedness, natural disasters, pharmacy/pharmacies) then turned to materials and research produced by organizations outside of the traditional commercial and academic publishing channels; however, most emergency preparedness protocols and standard operating procedures (SOPs) did not pertain to pharmacies or acknowledge the contribution of pharmacists. Researchers urge both state and federal governments to foster relationships with and use community pharmacist’s expertise and expanded roles in order to improve the nation’s public health.10
Historically, pharmacists within the US Public Health Service (PHS) have responded alongside local HCPs to meet the needs of communities during public health emergencies. Pharmacists were pivotal in the 2009 response to H1N1 influenza and the 2015 Ebola response, both abroad and within the United States.6 Pharmacists screened and triaged patients, provided life-saving vaccinations, and supported community and health care system education initiatives. However, as the COVID-19 pandemic has demonstrated, responding to a public health crisis takes more than the 1,000 pharmacists serving in the PHS.11 The American Society of Health-System Pharmacists argues that all pharmacists should be involved in working with public health planners.12
Community and health-systems pharmacists are vital to current and future public health responses and represent a largely untapped resource. Pharmacists across the country, especially in rural and underserved communities, have the potential to significantly impact emergency preparedness and response efforts. The > 319,000 US pharmacists comprise a sizable portion of the population and can play vital roles during emergency situations or disasters.13 Often after catastrophic events, community pharmacists provide first-aid, emergency refills, medication counseling, point of care testing, triage patients and serve on emergency response teams.14 However, pharmacists alone cannot address all medication-related patient needs and student pharmacists likewise have a role in emergency preparedness and response efforts. By participating in these efforts and learning these roles as students, they are better prepared to engage in emergency efforts as pharmacists.
Student pharmacist support. There are more than 140 accredited pharmacy schools across the United States, employing > 6,500 pharmacy faculty, and teaching > 63,000 student pharmacists.15 The majority of schools provide free and volunteer-based health care services and collaborate with local, regional, and national entities such as state boards of pharmacy, professional pharmacy organizations, and the American Pharmacist Association (APhA). Through the APhA Academy of Student Pharmacists (ASP), in 2018 and 2019 Operation Heart Campaign, 4,239 patients were referred to a PCP for follow-up care, 117,251 patients received health and wellness services, and 2,772,179 patients were educated regarding cardiovascular disease, the most common noncommunicable disease in the United States.16,17 Also, in 2018 and 2019, APhA-ASPs Operation Diabetes Campaign referred 3,785 patients to their PCP, provided health and wellness services to 36,334 patients, and educated 1,114,281 patients regarding DM.18
Student pharmacists are positioned across the country with reach to rural and underserved communities and have student organizational structures in place to manage student volunteers and support health care service opportunities. These structures could readily be used to augment and provide emergency pharmacy services and the coordination of chronic care services during times of emergency or disaster. Student leaders are well situated to coordinate communication and cooperation across health care disciplines and to facilitate local community pharmacy resource information collection and distribution.
Emergency Preparation Program
To address gaps in emergency preparedness and response, student pharmacists at UAA/ISU took the following steps to develop the EPRSN. Planning involved a multistep process. Step 1 identified important uncaptured data (eg, operational status, staffing, hours of operation, continuity and safety of drug supply chain, building/parking lot damage) required to direct patients to the appropriate medication-related care during an emergency. For step 2, student pharmacists obtained a list of the 138 pharmacies in Alaska from the state board of pharmacy. Pharmacies were contacted by student pharmacists using an established telephone script and updated contact information collected was stored on a secure, online drive accessible to UAA/ISU College of Pharmacy faculty and students using their UAA/ISU email address. In step 3, the APhA-ASP president elect and 3 leaders in each of the 16 APhA-ASP operation in charge of the EPRSN Alaska initiative, surveyed student leaders to determine student willingness to participate. Step 4 was to develop an organizational structure using established leadership structure to collect, capture, update, and share pharmacy data with state emergency response teams. Sustainability from year to year will be ensured through incorporation into the APhA-ASP student engagement framework (eg, annual training led by the president elect, contact information updated biyearly by student leaders, and oversight provided by College of Pharmacy faculty). Step 5 was to create SOPs, flowcharts, telephone scripts, talking points, and student training materials. And in the final preparatory step, plan documents and deliverables were provided to faculty administration and advisors within the College of Pharmacy for initial approval and presented to the student leadership for final approval.
EPRSN will be activated in the case of a natural disaster or state of emergency. Pharmacy students will contact all pharmacies within the designated area to collect up-to-date vital information (eg, operational status, staffing, hours of operation, safe drug supply, building/parking lot damage). Collected information will be disseminated to appropriate community members, HCPs, health care facilities, and emergency preparedness officials, under the direction of the Emergency Program Manager.
Discussion
In order to make informed and timely decisions during emergency situations, patients, HCPs, and health care systems must have appropriate situational awareness. The ability of decision makers to respond is directly dependent on timeliness and relevance of the information collected and shared and greatly contributes to this awareness. Accurate, effective, and consistent information collection has historically been one of the greatest challenges to situational awareness. This is particularly important in times of disaster when necessary emergency situation data may not exist, tools to collect data are inefficient and/or ineffective, and/or current data are inaccessible to relevant parties.19 This was the case in the Alaska earthquake of 2018 and more recently the COVID-19 pandemic of 2020 where information sharing deficits and structural barriers became even more evident.
Transfer of knowledge and information is especially critical during an emergency situation. Ineffective communication and information sharing results in transfer gaps. Gaps that result from inadequate transfers of care between HCPs are referred to as hand-off gaps. Training gaps result from inadequate preparation on the part of HCPs and civic leaders as well as in public health policies and procedures and in understanding of needs in emergent situations. Organization gaps occur when an individual changes positions or leaves a given institution and the acquired knowledge is not shared with others before departure or the replacement individual does not receive necessary training.
In both the Alaska earthquake and the COVID-19 pandemic, gaps in hand-offs, training, and organization were identified. Pharmacists were involved in the solution, providing care, addressing unmet health needs, and supporting the health care system. Many patients and HCPs remain unaware of the services pharmacists are capable and willing to provide, but at even a more basic level they are unsure of what services may be needed in emergency situations. Pharmacists are often used and considered vital HCPs after natural disasters or emergency situations, providing services that extend beyond their normal duties, yet remain within their SOP and expertise and address the medication management needs of their patients, ensuring safe, effective, and continuous access to needed pharmaceuticals.
It is vital that pharmacists and student pharmacists take an active role in emergency preparedness, that students get involved early in outreach and engagement initiatives for which they are ideally suited to coordinate in their communities, and that College of Pharmacy faculty support student pharmacist efforts to continue to highlight the professional roles of pharmacists, in routine health care as well as during times of crisis or disaster. It is important to note that an indirect but important cause of patient mortality related to an emergency event is the inability to access routine health care. If pharmacists and student pharmacists were more involved in emergency preparedness and response efforts, they could play an even greater role in providing much needed health care to patients during times when the health care system is overtaxed (facilitating medication refills and providing administrative and health care support).
Conclusions
Emergency and disaster preparedness are vital to promote the appropriate use of health care resources and prevent health-related complications. Student pharmacists represent a sustainable resource, uniquely positioned to identify community needs, support emergency efforts, coordinate with local pharmacies, and work with pharmacists and others to ensure patients receive the care they need. This work has the potential to improve utilization of health care resources and service delivery during natural disasters and emergencies, on a local, state, and regional level, with the overall goal of maintaining patient health and well-being.
1. Ritchie H, Roser M. Natural disasters. Updated November 2019. Accessed March 12, 2021. https://ourworldindata.org/natural-disasters
2. Freedy JR, Simpson WM Jr. Disaster-related physical and mental health: a role for the family physician. Am Fam Physician. 2007;75(6):841-846.
3. Martin U. Health after disaster: a perspective of psychological/health reactions to disaster. Cogent Psychol. 2015;2(1):1053741. doi:10.1080/23311908.2015.1053741
4. Joy K. Ripple effect: how hurricanes and other disasters affect hospital care. Published September 11, 2017. Accessed March 12, 2021. https://labblog.uofmhealth.org/industry-dx/ripple-effect-how-hurricanes-and-other-disasters-affect-hospital-care
5. Krousel-Wood MA, Islam T, Muntner P, et al. Medication adherence in older clinic patients with hypertension after Hurricane Katrina: implications for clinical practice and disaster management. Am J Med Sci. 2008;336(2):99-104. doi:10.1097/MAJ.0b013e318180f14f
6. Cefalu WT, Smith SR, Blonde L, Fonseca V. The Hurricane Katrina aftermath and its impact on diabetes care: observations from “ground zero”: lessons in disaster preparedness of people with diabetes. Diabetes Care. 2006;29(1):158-160. doi:10.2337/diacare.29.1.158
7. Fonseca VA, Smith H, Kuhadiya N, et al. Impact of a natural disaster on diabetes: exacerbation of disparities and long-term consequences. Diabetes Care. 2009;32(9):1632-1638. doi:10.2337/dc09-0670
8. Suneja A, Chandler TE, Schlegelmilch J, May M, Redlener IE; Columbia University Earth Institute. Chronic disease after natural disasters: public health, policy, and provider perspectives. Published November 12, 2018. Accessed March 12, 2021. doi:10.7916/D8ZP5Q23
9. Kehrer JP, Eberhart G, Wing M, Horon K. Pharmacy’s role in a modern health continuum. Can Pharm J (Ott). 2013;146(6):321-324. doi:10.1177/1715163513506370
10. Shearer MP, Geleta A, Adalja A, Gronvall GK; Johns Hopkins Bloomberg School of Public Health Center for Health Security. Serving the greater good: public health & community pharmacy partnerships. Published October 2017. Accessed March 12, 2021. https://www.centerforhealthsecurity.org/our-work/pubs_archive/pubs-pdfs/2017/public-health-and-community-pharmacy-partnerships-report.pdf
11. Flowers L, Wick J, Figg WD Sr, et al. U.S. Public Health Service Commissioned Corps pharmacists: making a difference in advancing the nation’s health. J Am Pharm Assoc (2003). 2009;49(3):446-452. doi:10.1331/JAPhA.2009.08036
12. American Society of Health-System Pharmacists. ASHP Statement on the Role of Health-System Pharmacists in Public Health. Am J Health Syst Pharm. 2008;65(5):462-467. doi:10.2146/ajhp070399
13. Deloitte. Data USA: pharmacists. Accessed June 2, 2020. https://datausa.io/profile/soc/pharmacists
14. Menighan TE. Pharmacists have major role in emergency response. Pharmacy Today. 2016;22(8):8. doi:10.1016/j.ptdy.2016.07.009
15. American Association of Colleges of Pharmacy. Academic pharmacy’s vital statistics. Updated July 2020. Accessed March 12, 2021. https://www.aacp.org/article/academic-pharmacys-vital-statistics
16. American Pharmacists Association. APhA-ASP Operation Heart. Accessed March 12, 2021. https://www.pharmacist.com/apha-asp-operation-heart
17. World Health Organization. Noncommunicable diseases. Updated June 1, 2018. Accessed March 12, 2021. https://www.who.int/en/news-room/fact-sheets/detail/noncommunicable-diseases
18. American Pharmacists Association. APhA-ASP Operation Diabetes. Accessed March 12, 2021. https://www.pharmacist.com/apha-asp-operation-diabetes
19. Reeve M, Wizemann T, Altevogt B. Enabling Rapid and Sustainable Public Health Research During Disasters: Summary of a Joint Workshop by the Institute of Medicine and the U.S. Department of Health and Human Services. National Academies Press; 2015.
Over the past decade, natural disasters and health care emergencies have increased 74%, averaging 400 documented events per year.1 These unpredictable and sometimes devastating events negatively impact the physical and mental health of communities, taxing already stretched health care system resources and the economy.2,3 During many of these events, patients inappropriately use hospitals, emergency departments (EDs), and critical care resources for chronic disease and elective health care management, resulting in medication shortages, health care access concerns, and treatment delays.4
Most available emergency preparedness programs rely solely on volunteers and/or public health providers to address the resultant coverage gap; however, instability in state and federal funding can make it difficult to maintain and sustain focused preparedness and response efforts. Alaska’s vast geography, low population density (1.2 people per square mile), and access limitations (about 200 villages only reachable by air or boat) make it especially challenging to provide reliable and sustained emergency preparedness and response support. Therefore, all eligible health care providers (HCPs) in Alaska must be involved in preparedness and response efforts.
Despite being the most accessible HCPs, pharmacists and student pharmacists, have not been actively involved in statewide emergency preparedness planning and disaster management efforts in Alaska. In preparation for and during disasters, for example, pharmacists may administer vaccinations, conduct point of care testing, dispense emergency medications, provide emergency medication refills, help mitigate medication shortages, and provide reliable health information to other health care professionals, patients, and their families as they prepare for and manage care during the event.4
The goal of this paper is to share the experience at the University of Alaska Anchorage/Idaho State University College of Pharmacy (UAA/ISU) in the development and implementation of a sustainable emergency preparedness and response support network (EPRSN) model; leveraging an established university student leadership structure and Doctor of Pharmacy (PharmD) students to support sharing of information among community pharmacies, state emergency response teams, and community members.
2018 Alaska Earthquake
On November 30, 2018, southcentral Alaska experienced a magnitude 7.1 earthquake, affecting nearly 295,000 people (approximately 40% of Alaska’s population) damaging roads, buildings, homes, and health care facilities. Emergency response efforts were quickly overwhelmed and hospital EDs became overburdened with patients seeking not only emergent, but also chronic care along with requests for prescription refills.
During disasters, disruptions in medication access and adherence are common. Disruptions can lead to disease exacerbation or progression, hospitalization, and/or death; all of which further contribute to the health care system and economic health burden. For example, after Hurricane Katrina, 46% of patients on hypertension medications had less than perfect adherence due to a variety of reasons (eg, not bringing any or enough medications during evacuation, lack of access to refills).5 Nonadherence to prescription hypertension medication specifically can lead to stroke, heart attack, and more rapidly progressing kidney dysfunction. Patients with diabetes mellitus (DM) also experience negative consequences due to disruptions in medication adherence.6 Lack of access to medications and supplies for DM can likewise lead to significant health sequelae, including acute hyperglycemic events, which can be life-threatening; ongoing hyperglycemia can lead to higher rates of cardiovascular disease, kidney disease, nerve damage, and diabetic retinopathy.7 However, the long-term effects of a natural disaster on health in terms of morbidity and mortality often go unreported, and their impact on chronic health conditions may be underestimated and last for years after the event.
As future health care professionals, student pharmacists continually seek opportunities to engage with and support communities; including preparing for, responding to, mitigating against, and recovering from disasters that affect the health care system and access to needed drug therapies. After the earthquake, student pharmacists reached out to state and local emergency response programs detailed within The State of Alaska Emergency Operations Plan to find opportunities to volunteer.
Agencies contacted included the Office of Emergency Management (OEM) for the Municipality of Anchorage. OEM partners with local health, fire, and police departments, the Alaska Department of Health and Social Services and Emergency Management, the Federal Emergency Management Agency, Centers for Disease Control and Prevention, American Red Cross, and the Salvation Army. It is important to note, due to lack of funding, Alaska no longer has a Medical Reserve Corps, which significantly impacts community emergency response and resilience efforts. After the earthquake, the emergency program manager extended an invitation to student pharmacists to join the joint medical emergency conference call, where local HCPs discuss emergency protocols, identify gaps, and work together to identify solutions.
During this call there was a consensus among HCPs that many patients were inappropriately seeking to fill and refill prescription medications in the ED, and staff were ill-prepared to guide patients to the appropriate services, unaware of which pharmacies were impacted by the earthquake; therefore unable to direct patients to still-operational pharmacies in the area. Together faculty and students discussed how student pharmacists could be involved in filling these identified information gaps and enhance communication among HCPs and entities. It was determined that if student pharmacists established and maintained open lines of communication with community pharmacists, they could efficiently determine which pharmacies were open and operational after disasters and disseminate that information to EDs and health care facilities in order to better direct patients to appropriate health care services.
Observations
A question/answer format and time line approach was used to review the steps leading to EPRSN program development and establishment of project/model deliverables.
Identified gaps
Chronic disease management. According to interviews conducted by the National Center for Disaster Preparedness, people often inappropriately use EDs during disasters.8 EDs do not stock enough medications to refill prescriptions for patients outside of their emergent care needs and are typically ill-suited for patients’ chronic disease management. At the time of the earthquake in Alaska no specific place/organization had been established to collect, store, or disseminate information regarding available pharmacy resources in an emergency. Had such a system been in place to actively inform HCPs and community members which pharmacies were open and operational, it is likely that many negative consequences related to health care utilization could have been reduced or avoided, including the number of people inappropriately using EDs for chronic prescription medication refills. This would not only reduce the burden on the health care system but allow for patients with both emergency and chronic needs to be seen quickly and prevent unnecessary health care costs.
Pharmacists play a vital role in managing chronic diseases.9 Due to extensive education and training, they are considered medication experts, ideally suited to manage chronic medication therapy, help prevent or minimize disease exacerbation and/or progression, reduce preventable health care costs, improve patient quality of life, and reduce morbidity and mortality.9 Pharmacists are accessible and strategically located throughout communities and provide patients with continuity of care other HCPs may be unable to provide. For example, during the COVID-19 pandemic, pharmacies remained open when other primary care providers (PCPs) were not. In addition, during times of natural disasters pharmacies tend to remain open unless there are extenuating circumstances (eg, unsafe building infrastructure, unsafe drug supply).
Emergency Response. To determine the role pharmacists play in emergency preparedness efforts we looked initially to the peer-reviewed literature (search terms: emergency preparedness, natural disasters, pharmacy/pharmacies) then turned to materials and research produced by organizations outside of the traditional commercial and academic publishing channels; however, most emergency preparedness protocols and standard operating procedures (SOPs) did not pertain to pharmacies or acknowledge the contribution of pharmacists. Researchers urge both state and federal governments to foster relationships with and use community pharmacist’s expertise and expanded roles in order to improve the nation’s public health.10
Historically, pharmacists within the US Public Health Service (PHS) have responded alongside local HCPs to meet the needs of communities during public health emergencies. Pharmacists were pivotal in the 2009 response to H1N1 influenza and the 2015 Ebola response, both abroad and within the United States.6 Pharmacists screened and triaged patients, provided life-saving vaccinations, and supported community and health care system education initiatives. However, as the COVID-19 pandemic has demonstrated, responding to a public health crisis takes more than the 1,000 pharmacists serving in the PHS.11 The American Society of Health-System Pharmacists argues that all pharmacists should be involved in working with public health planners.12
Community and health-systems pharmacists are vital to current and future public health responses and represent a largely untapped resource. Pharmacists across the country, especially in rural and underserved communities, have the potential to significantly impact emergency preparedness and response efforts. The > 319,000 US pharmacists comprise a sizable portion of the population and can play vital roles during emergency situations or disasters.13 Often after catastrophic events, community pharmacists provide first-aid, emergency refills, medication counseling, point of care testing, triage patients and serve on emergency response teams.14 However, pharmacists alone cannot address all medication-related patient needs and student pharmacists likewise have a role in emergency preparedness and response efforts. By participating in these efforts and learning these roles as students, they are better prepared to engage in emergency efforts as pharmacists.
Student pharmacist support. There are more than 140 accredited pharmacy schools across the United States, employing > 6,500 pharmacy faculty, and teaching > 63,000 student pharmacists.15 The majority of schools provide free and volunteer-based health care services and collaborate with local, regional, and national entities such as state boards of pharmacy, professional pharmacy organizations, and the American Pharmacist Association (APhA). Through the APhA Academy of Student Pharmacists (ASP), in 2018 and 2019 Operation Heart Campaign, 4,239 patients were referred to a PCP for follow-up care, 117,251 patients received health and wellness services, and 2,772,179 patients were educated regarding cardiovascular disease, the most common noncommunicable disease in the United States.16,17 Also, in 2018 and 2019, APhA-ASPs Operation Diabetes Campaign referred 3,785 patients to their PCP, provided health and wellness services to 36,334 patients, and educated 1,114,281 patients regarding DM.18
Student pharmacists are positioned across the country with reach to rural and underserved communities and have student organizational structures in place to manage student volunteers and support health care service opportunities. These structures could readily be used to augment and provide emergency pharmacy services and the coordination of chronic care services during times of emergency or disaster. Student leaders are well situated to coordinate communication and cooperation across health care disciplines and to facilitate local community pharmacy resource information collection and distribution.
Emergency Preparation Program
To address gaps in emergency preparedness and response, student pharmacists at UAA/ISU took the following steps to develop the EPRSN. Planning involved a multistep process. Step 1 identified important uncaptured data (eg, operational status, staffing, hours of operation, continuity and safety of drug supply chain, building/parking lot damage) required to direct patients to the appropriate medication-related care during an emergency. For step 2, student pharmacists obtained a list of the 138 pharmacies in Alaska from the state board of pharmacy. Pharmacies were contacted by student pharmacists using an established telephone script and updated contact information collected was stored on a secure, online drive accessible to UAA/ISU College of Pharmacy faculty and students using their UAA/ISU email address. In step 3, the APhA-ASP president elect and 3 leaders in each of the 16 APhA-ASP operation in charge of the EPRSN Alaska initiative, surveyed student leaders to determine student willingness to participate. Step 4 was to develop an organizational structure using established leadership structure to collect, capture, update, and share pharmacy data with state emergency response teams. Sustainability from year to year will be ensured through incorporation into the APhA-ASP student engagement framework (eg, annual training led by the president elect, contact information updated biyearly by student leaders, and oversight provided by College of Pharmacy faculty). Step 5 was to create SOPs, flowcharts, telephone scripts, talking points, and student training materials. And in the final preparatory step, plan documents and deliverables were provided to faculty administration and advisors within the College of Pharmacy for initial approval and presented to the student leadership for final approval.
EPRSN will be activated in the case of a natural disaster or state of emergency. Pharmacy students will contact all pharmacies within the designated area to collect up-to-date vital information (eg, operational status, staffing, hours of operation, safe drug supply, building/parking lot damage). Collected information will be disseminated to appropriate community members, HCPs, health care facilities, and emergency preparedness officials, under the direction of the Emergency Program Manager.
Discussion
In order to make informed and timely decisions during emergency situations, patients, HCPs, and health care systems must have appropriate situational awareness. The ability of decision makers to respond is directly dependent on timeliness and relevance of the information collected and shared and greatly contributes to this awareness. Accurate, effective, and consistent information collection has historically been one of the greatest challenges to situational awareness. This is particularly important in times of disaster when necessary emergency situation data may not exist, tools to collect data are inefficient and/or ineffective, and/or current data are inaccessible to relevant parties.19 This was the case in the Alaska earthquake of 2018 and more recently the COVID-19 pandemic of 2020 where information sharing deficits and structural barriers became even more evident.
Transfer of knowledge and information is especially critical during an emergency situation. Ineffective communication and information sharing results in transfer gaps. Gaps that result from inadequate transfers of care between HCPs are referred to as hand-off gaps. Training gaps result from inadequate preparation on the part of HCPs and civic leaders as well as in public health policies and procedures and in understanding of needs in emergent situations. Organization gaps occur when an individual changes positions or leaves a given institution and the acquired knowledge is not shared with others before departure or the replacement individual does not receive necessary training.
In both the Alaska earthquake and the COVID-19 pandemic, gaps in hand-offs, training, and organization were identified. Pharmacists were involved in the solution, providing care, addressing unmet health needs, and supporting the health care system. Many patients and HCPs remain unaware of the services pharmacists are capable and willing to provide, but at even a more basic level they are unsure of what services may be needed in emergency situations. Pharmacists are often used and considered vital HCPs after natural disasters or emergency situations, providing services that extend beyond their normal duties, yet remain within their SOP and expertise and address the medication management needs of their patients, ensuring safe, effective, and continuous access to needed pharmaceuticals.
It is vital that pharmacists and student pharmacists take an active role in emergency preparedness, that students get involved early in outreach and engagement initiatives for which they are ideally suited to coordinate in their communities, and that College of Pharmacy faculty support student pharmacist efforts to continue to highlight the professional roles of pharmacists, in routine health care as well as during times of crisis or disaster. It is important to note that an indirect but important cause of patient mortality related to an emergency event is the inability to access routine health care. If pharmacists and student pharmacists were more involved in emergency preparedness and response efforts, they could play an even greater role in providing much needed health care to patients during times when the health care system is overtaxed (facilitating medication refills and providing administrative and health care support).
Conclusions
Emergency and disaster preparedness are vital to promote the appropriate use of health care resources and prevent health-related complications. Student pharmacists represent a sustainable resource, uniquely positioned to identify community needs, support emergency efforts, coordinate with local pharmacies, and work with pharmacists and others to ensure patients receive the care they need. This work has the potential to improve utilization of health care resources and service delivery during natural disasters and emergencies, on a local, state, and regional level, with the overall goal of maintaining patient health and well-being.
Over the past decade, natural disasters and health care emergencies have increased 74%, averaging 400 documented events per year.1 These unpredictable and sometimes devastating events negatively impact the physical and mental health of communities, taxing already stretched health care system resources and the economy.2,3 During many of these events, patients inappropriately use hospitals, emergency departments (EDs), and critical care resources for chronic disease and elective health care management, resulting in medication shortages, health care access concerns, and treatment delays.4
Most available emergency preparedness programs rely solely on volunteers and/or public health providers to address the resultant coverage gap; however, instability in state and federal funding can make it difficult to maintain and sustain focused preparedness and response efforts. Alaska’s vast geography, low population density (1.2 people per square mile), and access limitations (about 200 villages only reachable by air or boat) make it especially challenging to provide reliable and sustained emergency preparedness and response support. Therefore, all eligible health care providers (HCPs) in Alaska must be involved in preparedness and response efforts.
Despite being the most accessible HCPs, pharmacists and student pharmacists, have not been actively involved in statewide emergency preparedness planning and disaster management efforts in Alaska. In preparation for and during disasters, for example, pharmacists may administer vaccinations, conduct point of care testing, dispense emergency medications, provide emergency medication refills, help mitigate medication shortages, and provide reliable health information to other health care professionals, patients, and their families as they prepare for and manage care during the event.4
The goal of this paper is to share the experience at the University of Alaska Anchorage/Idaho State University College of Pharmacy (UAA/ISU) in the development and implementation of a sustainable emergency preparedness and response support network (EPRSN) model; leveraging an established university student leadership structure and Doctor of Pharmacy (PharmD) students to support sharing of information among community pharmacies, state emergency response teams, and community members.
2018 Alaska Earthquake
On November 30, 2018, southcentral Alaska experienced a magnitude 7.1 earthquake, affecting nearly 295,000 people (approximately 40% of Alaska’s population) damaging roads, buildings, homes, and health care facilities. Emergency response efforts were quickly overwhelmed and hospital EDs became overburdened with patients seeking not only emergent, but also chronic care along with requests for prescription refills.
During disasters, disruptions in medication access and adherence are common. Disruptions can lead to disease exacerbation or progression, hospitalization, and/or death; all of which further contribute to the health care system and economic health burden. For example, after Hurricane Katrina, 46% of patients on hypertension medications had less than perfect adherence due to a variety of reasons (eg, not bringing any or enough medications during evacuation, lack of access to refills).5 Nonadherence to prescription hypertension medication specifically can lead to stroke, heart attack, and more rapidly progressing kidney dysfunction. Patients with diabetes mellitus (DM) also experience negative consequences due to disruptions in medication adherence.6 Lack of access to medications and supplies for DM can likewise lead to significant health sequelae, including acute hyperglycemic events, which can be life-threatening; ongoing hyperglycemia can lead to higher rates of cardiovascular disease, kidney disease, nerve damage, and diabetic retinopathy.7 However, the long-term effects of a natural disaster on health in terms of morbidity and mortality often go unreported, and their impact on chronic health conditions may be underestimated and last for years after the event.
As future health care professionals, student pharmacists continually seek opportunities to engage with and support communities; including preparing for, responding to, mitigating against, and recovering from disasters that affect the health care system and access to needed drug therapies. After the earthquake, student pharmacists reached out to state and local emergency response programs detailed within The State of Alaska Emergency Operations Plan to find opportunities to volunteer.
Agencies contacted included the Office of Emergency Management (OEM) for the Municipality of Anchorage. OEM partners with local health, fire, and police departments, the Alaska Department of Health and Social Services and Emergency Management, the Federal Emergency Management Agency, Centers for Disease Control and Prevention, American Red Cross, and the Salvation Army. It is important to note, due to lack of funding, Alaska no longer has a Medical Reserve Corps, which significantly impacts community emergency response and resilience efforts. After the earthquake, the emergency program manager extended an invitation to student pharmacists to join the joint medical emergency conference call, where local HCPs discuss emergency protocols, identify gaps, and work together to identify solutions.
During this call there was a consensus among HCPs that many patients were inappropriately seeking to fill and refill prescription medications in the ED, and staff were ill-prepared to guide patients to the appropriate services, unaware of which pharmacies were impacted by the earthquake; therefore unable to direct patients to still-operational pharmacies in the area. Together faculty and students discussed how student pharmacists could be involved in filling these identified information gaps and enhance communication among HCPs and entities. It was determined that if student pharmacists established and maintained open lines of communication with community pharmacists, they could efficiently determine which pharmacies were open and operational after disasters and disseminate that information to EDs and health care facilities in order to better direct patients to appropriate health care services.
Observations
A question/answer format and time line approach was used to review the steps leading to EPRSN program development and establishment of project/model deliverables.
Identified gaps
Chronic disease management. According to interviews conducted by the National Center for Disaster Preparedness, people often inappropriately use EDs during disasters.8 EDs do not stock enough medications to refill prescriptions for patients outside of their emergent care needs and are typically ill-suited for patients’ chronic disease management. At the time of the earthquake in Alaska no specific place/organization had been established to collect, store, or disseminate information regarding available pharmacy resources in an emergency. Had such a system been in place to actively inform HCPs and community members which pharmacies were open and operational, it is likely that many negative consequences related to health care utilization could have been reduced or avoided, including the number of people inappropriately using EDs for chronic prescription medication refills. This would not only reduce the burden on the health care system but allow for patients with both emergency and chronic needs to be seen quickly and prevent unnecessary health care costs.
Pharmacists play a vital role in managing chronic diseases.9 Due to extensive education and training, they are considered medication experts, ideally suited to manage chronic medication therapy, help prevent or minimize disease exacerbation and/or progression, reduce preventable health care costs, improve patient quality of life, and reduce morbidity and mortality.9 Pharmacists are accessible and strategically located throughout communities and provide patients with continuity of care other HCPs may be unable to provide. For example, during the COVID-19 pandemic, pharmacies remained open when other primary care providers (PCPs) were not. In addition, during times of natural disasters pharmacies tend to remain open unless there are extenuating circumstances (eg, unsafe building infrastructure, unsafe drug supply).
Emergency Response. To determine the role pharmacists play in emergency preparedness efforts we looked initially to the peer-reviewed literature (search terms: emergency preparedness, natural disasters, pharmacy/pharmacies) then turned to materials and research produced by organizations outside of the traditional commercial and academic publishing channels; however, most emergency preparedness protocols and standard operating procedures (SOPs) did not pertain to pharmacies or acknowledge the contribution of pharmacists. Researchers urge both state and federal governments to foster relationships with and use community pharmacist’s expertise and expanded roles in order to improve the nation’s public health.10
Historically, pharmacists within the US Public Health Service (PHS) have responded alongside local HCPs to meet the needs of communities during public health emergencies. Pharmacists were pivotal in the 2009 response to H1N1 influenza and the 2015 Ebola response, both abroad and within the United States.6 Pharmacists screened and triaged patients, provided life-saving vaccinations, and supported community and health care system education initiatives. However, as the COVID-19 pandemic has demonstrated, responding to a public health crisis takes more than the 1,000 pharmacists serving in the PHS.11 The American Society of Health-System Pharmacists argues that all pharmacists should be involved in working with public health planners.12
Community and health-systems pharmacists are vital to current and future public health responses and represent a largely untapped resource. Pharmacists across the country, especially in rural and underserved communities, have the potential to significantly impact emergency preparedness and response efforts. The > 319,000 US pharmacists comprise a sizable portion of the population and can play vital roles during emergency situations or disasters.13 Often after catastrophic events, community pharmacists provide first-aid, emergency refills, medication counseling, point of care testing, triage patients and serve on emergency response teams.14 However, pharmacists alone cannot address all medication-related patient needs and student pharmacists likewise have a role in emergency preparedness and response efforts. By participating in these efforts and learning these roles as students, they are better prepared to engage in emergency efforts as pharmacists.
Student pharmacist support. There are more than 140 accredited pharmacy schools across the United States, employing > 6,500 pharmacy faculty, and teaching > 63,000 student pharmacists.15 The majority of schools provide free and volunteer-based health care services and collaborate with local, regional, and national entities such as state boards of pharmacy, professional pharmacy organizations, and the American Pharmacist Association (APhA). Through the APhA Academy of Student Pharmacists (ASP), in 2018 and 2019 Operation Heart Campaign, 4,239 patients were referred to a PCP for follow-up care, 117,251 patients received health and wellness services, and 2,772,179 patients were educated regarding cardiovascular disease, the most common noncommunicable disease in the United States.16,17 Also, in 2018 and 2019, APhA-ASPs Operation Diabetes Campaign referred 3,785 patients to their PCP, provided health and wellness services to 36,334 patients, and educated 1,114,281 patients regarding DM.18
Student pharmacists are positioned across the country with reach to rural and underserved communities and have student organizational structures in place to manage student volunteers and support health care service opportunities. These structures could readily be used to augment and provide emergency pharmacy services and the coordination of chronic care services during times of emergency or disaster. Student leaders are well situated to coordinate communication and cooperation across health care disciplines and to facilitate local community pharmacy resource information collection and distribution.
Emergency Preparation Program
To address gaps in emergency preparedness and response, student pharmacists at UAA/ISU took the following steps to develop the EPRSN. Planning involved a multistep process. Step 1 identified important uncaptured data (eg, operational status, staffing, hours of operation, continuity and safety of drug supply chain, building/parking lot damage) required to direct patients to the appropriate medication-related care during an emergency. For step 2, student pharmacists obtained a list of the 138 pharmacies in Alaska from the state board of pharmacy. Pharmacies were contacted by student pharmacists using an established telephone script and updated contact information collected was stored on a secure, online drive accessible to UAA/ISU College of Pharmacy faculty and students using their UAA/ISU email address. In step 3, the APhA-ASP president elect and 3 leaders in each of the 16 APhA-ASP operation in charge of the EPRSN Alaska initiative, surveyed student leaders to determine student willingness to participate. Step 4 was to develop an organizational structure using established leadership structure to collect, capture, update, and share pharmacy data with state emergency response teams. Sustainability from year to year will be ensured through incorporation into the APhA-ASP student engagement framework (eg, annual training led by the president elect, contact information updated biyearly by student leaders, and oversight provided by College of Pharmacy faculty). Step 5 was to create SOPs, flowcharts, telephone scripts, talking points, and student training materials. And in the final preparatory step, plan documents and deliverables were provided to faculty administration and advisors within the College of Pharmacy for initial approval and presented to the student leadership for final approval.
EPRSN will be activated in the case of a natural disaster or state of emergency. Pharmacy students will contact all pharmacies within the designated area to collect up-to-date vital information (eg, operational status, staffing, hours of operation, safe drug supply, building/parking lot damage). Collected information will be disseminated to appropriate community members, HCPs, health care facilities, and emergency preparedness officials, under the direction of the Emergency Program Manager.
Discussion
In order to make informed and timely decisions during emergency situations, patients, HCPs, and health care systems must have appropriate situational awareness. The ability of decision makers to respond is directly dependent on timeliness and relevance of the information collected and shared and greatly contributes to this awareness. Accurate, effective, and consistent information collection has historically been one of the greatest challenges to situational awareness. This is particularly important in times of disaster when necessary emergency situation data may not exist, tools to collect data are inefficient and/or ineffective, and/or current data are inaccessible to relevant parties.19 This was the case in the Alaska earthquake of 2018 and more recently the COVID-19 pandemic of 2020 where information sharing deficits and structural barriers became even more evident.
Transfer of knowledge and information is especially critical during an emergency situation. Ineffective communication and information sharing results in transfer gaps. Gaps that result from inadequate transfers of care between HCPs are referred to as hand-off gaps. Training gaps result from inadequate preparation on the part of HCPs and civic leaders as well as in public health policies and procedures and in understanding of needs in emergent situations. Organization gaps occur when an individual changes positions or leaves a given institution and the acquired knowledge is not shared with others before departure or the replacement individual does not receive necessary training.
In both the Alaska earthquake and the COVID-19 pandemic, gaps in hand-offs, training, and organization were identified. Pharmacists were involved in the solution, providing care, addressing unmet health needs, and supporting the health care system. Many patients and HCPs remain unaware of the services pharmacists are capable and willing to provide, but at even a more basic level they are unsure of what services may be needed in emergency situations. Pharmacists are often used and considered vital HCPs after natural disasters or emergency situations, providing services that extend beyond their normal duties, yet remain within their SOP and expertise and address the medication management needs of their patients, ensuring safe, effective, and continuous access to needed pharmaceuticals.
It is vital that pharmacists and student pharmacists take an active role in emergency preparedness, that students get involved early in outreach and engagement initiatives for which they are ideally suited to coordinate in their communities, and that College of Pharmacy faculty support student pharmacist efforts to continue to highlight the professional roles of pharmacists, in routine health care as well as during times of crisis or disaster. It is important to note that an indirect but important cause of patient mortality related to an emergency event is the inability to access routine health care. If pharmacists and student pharmacists were more involved in emergency preparedness and response efforts, they could play an even greater role in providing much needed health care to patients during times when the health care system is overtaxed (facilitating medication refills and providing administrative and health care support).
Conclusions
Emergency and disaster preparedness are vital to promote the appropriate use of health care resources and prevent health-related complications. Student pharmacists represent a sustainable resource, uniquely positioned to identify community needs, support emergency efforts, coordinate with local pharmacies, and work with pharmacists and others to ensure patients receive the care they need. This work has the potential to improve utilization of health care resources and service delivery during natural disasters and emergencies, on a local, state, and regional level, with the overall goal of maintaining patient health and well-being.
1. Ritchie H, Roser M. Natural disasters. Updated November 2019. Accessed March 12, 2021. https://ourworldindata.org/natural-disasters
2. Freedy JR, Simpson WM Jr. Disaster-related physical and mental health: a role for the family physician. Am Fam Physician. 2007;75(6):841-846.
3. Martin U. Health after disaster: a perspective of psychological/health reactions to disaster. Cogent Psychol. 2015;2(1):1053741. doi:10.1080/23311908.2015.1053741
4. Joy K. Ripple effect: how hurricanes and other disasters affect hospital care. Published September 11, 2017. Accessed March 12, 2021. https://labblog.uofmhealth.org/industry-dx/ripple-effect-how-hurricanes-and-other-disasters-affect-hospital-care
5. Krousel-Wood MA, Islam T, Muntner P, et al. Medication adherence in older clinic patients with hypertension after Hurricane Katrina: implications for clinical practice and disaster management. Am J Med Sci. 2008;336(2):99-104. doi:10.1097/MAJ.0b013e318180f14f
6. Cefalu WT, Smith SR, Blonde L, Fonseca V. The Hurricane Katrina aftermath and its impact on diabetes care: observations from “ground zero”: lessons in disaster preparedness of people with diabetes. Diabetes Care. 2006;29(1):158-160. doi:10.2337/diacare.29.1.158
7. Fonseca VA, Smith H, Kuhadiya N, et al. Impact of a natural disaster on diabetes: exacerbation of disparities and long-term consequences. Diabetes Care. 2009;32(9):1632-1638. doi:10.2337/dc09-0670
8. Suneja A, Chandler TE, Schlegelmilch J, May M, Redlener IE; Columbia University Earth Institute. Chronic disease after natural disasters: public health, policy, and provider perspectives. Published November 12, 2018. Accessed March 12, 2021. doi:10.7916/D8ZP5Q23
9. Kehrer JP, Eberhart G, Wing M, Horon K. Pharmacy’s role in a modern health continuum. Can Pharm J (Ott). 2013;146(6):321-324. doi:10.1177/1715163513506370
10. Shearer MP, Geleta A, Adalja A, Gronvall GK; Johns Hopkins Bloomberg School of Public Health Center for Health Security. Serving the greater good: public health & community pharmacy partnerships. Published October 2017. Accessed March 12, 2021. https://www.centerforhealthsecurity.org/our-work/pubs_archive/pubs-pdfs/2017/public-health-and-community-pharmacy-partnerships-report.pdf
11. Flowers L, Wick J, Figg WD Sr, et al. U.S. Public Health Service Commissioned Corps pharmacists: making a difference in advancing the nation’s health. J Am Pharm Assoc (2003). 2009;49(3):446-452. doi:10.1331/JAPhA.2009.08036
12. American Society of Health-System Pharmacists. ASHP Statement on the Role of Health-System Pharmacists in Public Health. Am J Health Syst Pharm. 2008;65(5):462-467. doi:10.2146/ajhp070399
13. Deloitte. Data USA: pharmacists. Accessed June 2, 2020. https://datausa.io/profile/soc/pharmacists
14. Menighan TE. Pharmacists have major role in emergency response. Pharmacy Today. 2016;22(8):8. doi:10.1016/j.ptdy.2016.07.009
15. American Association of Colleges of Pharmacy. Academic pharmacy’s vital statistics. Updated July 2020. Accessed March 12, 2021. https://www.aacp.org/article/academic-pharmacys-vital-statistics
16. American Pharmacists Association. APhA-ASP Operation Heart. Accessed March 12, 2021. https://www.pharmacist.com/apha-asp-operation-heart
17. World Health Organization. Noncommunicable diseases. Updated June 1, 2018. Accessed March 12, 2021. https://www.who.int/en/news-room/fact-sheets/detail/noncommunicable-diseases
18. American Pharmacists Association. APhA-ASP Operation Diabetes. Accessed March 12, 2021. https://www.pharmacist.com/apha-asp-operation-diabetes
19. Reeve M, Wizemann T, Altevogt B. Enabling Rapid and Sustainable Public Health Research During Disasters: Summary of a Joint Workshop by the Institute of Medicine and the U.S. Department of Health and Human Services. National Academies Press; 2015.
1. Ritchie H, Roser M. Natural disasters. Updated November 2019. Accessed March 12, 2021. https://ourworldindata.org/natural-disasters
2. Freedy JR, Simpson WM Jr. Disaster-related physical and mental health: a role for the family physician. Am Fam Physician. 2007;75(6):841-846.
3. Martin U. Health after disaster: a perspective of psychological/health reactions to disaster. Cogent Psychol. 2015;2(1):1053741. doi:10.1080/23311908.2015.1053741
4. Joy K. Ripple effect: how hurricanes and other disasters affect hospital care. Published September 11, 2017. Accessed March 12, 2021. https://labblog.uofmhealth.org/industry-dx/ripple-effect-how-hurricanes-and-other-disasters-affect-hospital-care
5. Krousel-Wood MA, Islam T, Muntner P, et al. Medication adherence in older clinic patients with hypertension after Hurricane Katrina: implications for clinical practice and disaster management. Am J Med Sci. 2008;336(2):99-104. doi:10.1097/MAJ.0b013e318180f14f
6. Cefalu WT, Smith SR, Blonde L, Fonseca V. The Hurricane Katrina aftermath and its impact on diabetes care: observations from “ground zero”: lessons in disaster preparedness of people with diabetes. Diabetes Care. 2006;29(1):158-160. doi:10.2337/diacare.29.1.158
7. Fonseca VA, Smith H, Kuhadiya N, et al. Impact of a natural disaster on diabetes: exacerbation of disparities and long-term consequences. Diabetes Care. 2009;32(9):1632-1638. doi:10.2337/dc09-0670
8. Suneja A, Chandler TE, Schlegelmilch J, May M, Redlener IE; Columbia University Earth Institute. Chronic disease after natural disasters: public health, policy, and provider perspectives. Published November 12, 2018. Accessed March 12, 2021. doi:10.7916/D8ZP5Q23
9. Kehrer JP, Eberhart G, Wing M, Horon K. Pharmacy’s role in a modern health continuum. Can Pharm J (Ott). 2013;146(6):321-324. doi:10.1177/1715163513506370
10. Shearer MP, Geleta A, Adalja A, Gronvall GK; Johns Hopkins Bloomberg School of Public Health Center for Health Security. Serving the greater good: public health & community pharmacy partnerships. Published October 2017. Accessed March 12, 2021. https://www.centerforhealthsecurity.org/our-work/pubs_archive/pubs-pdfs/2017/public-health-and-community-pharmacy-partnerships-report.pdf
11. Flowers L, Wick J, Figg WD Sr, et al. U.S. Public Health Service Commissioned Corps pharmacists: making a difference in advancing the nation’s health. J Am Pharm Assoc (2003). 2009;49(3):446-452. doi:10.1331/JAPhA.2009.08036
12. American Society of Health-System Pharmacists. ASHP Statement on the Role of Health-System Pharmacists in Public Health. Am J Health Syst Pharm. 2008;65(5):462-467. doi:10.2146/ajhp070399
13. Deloitte. Data USA: pharmacists. Accessed June 2, 2020. https://datausa.io/profile/soc/pharmacists
14. Menighan TE. Pharmacists have major role in emergency response. Pharmacy Today. 2016;22(8):8. doi:10.1016/j.ptdy.2016.07.009
15. American Association of Colleges of Pharmacy. Academic pharmacy’s vital statistics. Updated July 2020. Accessed March 12, 2021. https://www.aacp.org/article/academic-pharmacys-vital-statistics
16. American Pharmacists Association. APhA-ASP Operation Heart. Accessed March 12, 2021. https://www.pharmacist.com/apha-asp-operation-heart
17. World Health Organization. Noncommunicable diseases. Updated June 1, 2018. Accessed March 12, 2021. https://www.who.int/en/news-room/fact-sheets/detail/noncommunicable-diseases
18. American Pharmacists Association. APhA-ASP Operation Diabetes. Accessed March 12, 2021. https://www.pharmacist.com/apha-asp-operation-diabetes
19. Reeve M, Wizemann T, Altevogt B. Enabling Rapid and Sustainable Public Health Research During Disasters: Summary of a Joint Workshop by the Institute of Medicine and the U.S. Department of Health and Human Services. National Academies Press; 2015.
Lasting norovirus immunity may depend on T cells
Protection against norovirus gastroenteritis is supported in part by norovirus-specific CD8+ T cells that reside in peripheral, intestinal, and lymphoid tissues, according to investigators.
These findings, and the molecular tools used to discover them, could guide development of a norovirus vaccine and novel cellular therapies, according to lead author Ajinkya Pattekar, MD, of the University of Pennsylvania, Philadelphia, and colleagues.
“Currently, there are no approved pharmacologic therapies against norovirus, and despite several promising clinical trials, an effective vaccine is not available,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology, which may stem from an incomplete understanding of norovirus immunity, according to Dr. Pattekar and colleagues.
They noted that most previous research has focused on humoral immunity, which appears variable between individuals, with some people exhibiting a strong humoral response, while others mount only partial humoral protection. The investigators also noted that, depending on which studies were examined, this type of defense could last years or fade within weeks to months and that “immune mechanisms other than antibodies may be important for protection against noroviruses.”
Specifically, cellular immunity may be at work. A 2020 study involving volunteers showed that T cells were cross-reactive to a type of norovirus the participants had never been exposed to.
“These findings suggest that T cells may target conserved epitopes and could offer cross-protection against a broad range of noroviruses,” Dr. Pattekar and colleagues wrote.
To test this hypothesis, they first collected peripheral blood mononuclear cells (PBMCs) from three healthy volunteers with unknown norovirus exposure history. Then serum samples were screened for norovirus functional antibodies via the binding between virus-like particles (VLPs) and histo–blood group antigens (HBGAs). This revealed disparate profiles of blocking antibodies against various norovirus strains. While donor 1 and donor 2 had antibodies against multiple strains, donor 3 lacked norovirus antibodies. Further testing showed that this latter individual was a nonsecretor with limited exposure history.
Next, the investigators tested donor PBMCs for norovirus-specific T-cell responses with use of overlapping libraries of peptides for each of the three norovirus open reading frames (ORF1, ORF2, and ORF3). T-cell responses, predominantly involving CD8+ T cells, were observed in all donors. While donor 1 had the greatest response to ORF1, donors 2 and 3 had responses that focused on ORF2.
“Thus, norovirus-specific T cells targeting ORF1 and ORF2 epitopes are present in peripheral blood from healthy donors regardless of secretor status,” the investigators wrote.
To better characterize T-cell epitopes, the investigators subdivided the overlapping peptide libraries into groups of shorter peptides, then exposed serum to these smaller component pools. This revealed eight HLA class I restricted epitopes that were derived from a genogroup II.4 pandemic norovirus strain; this group of variants has been responsible for all six of the norovirus pandemics since 1996.
Closer examination of the epitopes showed that they were “broadly conserved beyond GII.4.” Only one epitope exhibited variation in the C-terminal aromatic anchor, and it was nondominant. The investigators therefore identified seven immunodominant CD8+ epitopes, which they considered “valuable targets for vaccine and cell-based therapies.
“These data further confirm that epitope-specific CD8+ T cells are a universal feature of the overall norovirus immune response and could be an attractive target for future vaccines,” the investigators wrote.
Additional testing involving samples of spleen, mesenteric lymph nodes, and duodenum from deceased individuals showed presence of norovirus-specific CD8+ T cells, with particular abundance in intestinal tissue, and distinct phenotypes and functional properties in different tissue types.
“Future studies using tetramers and intestinal samples should build on these observations and fully define the location and microenvironment of norovirus-specific T cells,” the investigators wrote. “If carried out in the context of a vaccine trial, such studies could be highly valuable in elucidating tissue-resident memory correlates of norovirus immunity.”
The study was funded by the National Institutes of Health, the Wellcome Trust, and Deutsche Forschungsgemeinschaft. The investigators reported no conflicts of interest.
Understanding the immune correlates of protection for norovirus is important for the development and evaluation of candidate vaccines and to better clarify the variation in host susceptibility to infection. 
Prior research on the human immune response to norovirus infection has largely focused on the antibody response. There is less known about the antinorovirus T cell response, which can target and clear virus-infected cells. Notably, anti-viral CD8+ T cells are critical for control of norovirus infection in mouse models, which suggests a similarly important role in humans. In this study by Dr. Pattekar and colleagues, the authors generated human norovirus-specific peptides covering the entire viral proteome, and then they used these peptides to identify and characterize norovirus-specific CD8+ T cells from the blood, spleen, lymph nodes, and intestinal lamina propria of human donors who were not actively infected by norovirus. The authors identified virus-specific memory T cells in the blood and intestines. Further, they found several HLA class I restricted virus epitopes that are highly conserved amongst the most commonly circulating GII.4 noroviruses. These norovirus-specific T cells represented about 0.5% of all cells and reveal that norovirus induces a durable population of memory T cells.
Further research is needed to determine whether norovirus-specific CD8+ T cells are necessary or sufficient for preventing norovirus infection and disease in people. This important study provides novel tools and increases our understanding of cell-mediated immunity to human norovirus infection that will influence future vaccine design and evaluation for this important human pathogen.
Craig B. Wilen, MD, PhD, is assistant professor of laboratory medicine and immunobiology at Yale University, New Haven, Conn. He does not have any conflicts to disclose.
Understanding the immune correlates of protection for norovirus is important for the development and evaluation of candidate vaccines and to better clarify the variation in host susceptibility to infection.
Prior research on the human immune response to norovirus infection has largely focused on the antibody response. There is less known about the antinorovirus T cell response, which can target and clear virus-infected cells. Notably, anti-viral CD8+ T cells are critical for control of norovirus infection in mouse models, which suggests a similarly important role in humans. In this study by Dr. Pattekar and colleagues, the authors generated human norovirus-specific peptides covering the entire viral proteome, and then they used these peptides to identify and characterize norovirus-specific CD8+ T cells from the blood, spleen, lymph nodes, and intestinal lamina propria of human donors who were not actively infected by norovirus. The authors identified virus-specific memory T cells in the blood and intestines. Further, they found several HLA class I restricted virus epitopes that are highly conserved amongst the most commonly circulating GII.4 noroviruses. These norovirus-specific T cells represented about 0.5% of all cells and reveal that norovirus induces a durable population of memory T cells.
Further research is needed to determine whether norovirus-specific CD8+ T cells are necessary or sufficient for preventing norovirus infection and disease in people. This important study provides novel tools and increases our understanding of cell-mediated immunity to human norovirus infection that will influence future vaccine design and evaluation for this important human pathogen.
Craig B. Wilen, MD, PhD, is assistant professor of laboratory medicine and immunobiology at Yale University, New Haven, Conn. He does not have any conflicts to disclose.
Understanding the immune correlates of protection for norovirus is important for the development and evaluation of candidate vaccines and to better clarify the variation in host susceptibility to infection.
Prior research on the human immune response to norovirus infection has largely focused on the antibody response. There is less known about the antinorovirus T cell response, which can target and clear virus-infected cells. Notably, anti-viral CD8+ T cells are critical for control of norovirus infection in mouse models, which suggests a similarly important role in humans. In this study by Dr. Pattekar and colleagues, the authors generated human norovirus-specific peptides covering the entire viral proteome, and then they used these peptides to identify and characterize norovirus-specific CD8+ T cells from the blood, spleen, lymph nodes, and intestinal lamina propria of human donors who were not actively infected by norovirus. The authors identified virus-specific memory T cells in the blood and intestines. Further, they found several HLA class I restricted virus epitopes that are highly conserved amongst the most commonly circulating GII.4 noroviruses. These norovirus-specific T cells represented about 0.5% of all cells and reveal that norovirus induces a durable population of memory T cells.
Further research is needed to determine whether norovirus-specific CD8+ T cells are necessary or sufficient for preventing norovirus infection and disease in people. This important study provides novel tools and increases our understanding of cell-mediated immunity to human norovirus infection that will influence future vaccine design and evaluation for this important human pathogen.
Craig B. Wilen, MD, PhD, is assistant professor of laboratory medicine and immunobiology at Yale University, New Haven, Conn. He does not have any conflicts to disclose.
Protection against norovirus gastroenteritis is supported in part by norovirus-specific CD8+ T cells that reside in peripheral, intestinal, and lymphoid tissues, according to investigators.
These findings, and the molecular tools used to discover them, could guide development of a norovirus vaccine and novel cellular therapies, according to lead author Ajinkya Pattekar, MD, of the University of Pennsylvania, Philadelphia, and colleagues.
“Currently, there are no approved pharmacologic therapies against norovirus, and despite several promising clinical trials, an effective vaccine is not available,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology, which may stem from an incomplete understanding of norovirus immunity, according to Dr. Pattekar and colleagues.
They noted that most previous research has focused on humoral immunity, which appears variable between individuals, with some people exhibiting a strong humoral response, while others mount only partial humoral protection. The investigators also noted that, depending on which studies were examined, this type of defense could last years or fade within weeks to months and that “immune mechanisms other than antibodies may be important for protection against noroviruses.”
Specifically, cellular immunity may be at work. A 2020 study involving volunteers showed that T cells were cross-reactive to a type of norovirus the participants had never been exposed to.
“These findings suggest that T cells may target conserved epitopes and could offer cross-protection against a broad range of noroviruses,” Dr. Pattekar and colleagues wrote.
To test this hypothesis, they first collected peripheral blood mononuclear cells (PBMCs) from three healthy volunteers with unknown norovirus exposure history. Then serum samples were screened for norovirus functional antibodies via the binding between virus-like particles (VLPs) and histo–blood group antigens (HBGAs). This revealed disparate profiles of blocking antibodies against various norovirus strains. While donor 1 and donor 2 had antibodies against multiple strains, donor 3 lacked norovirus antibodies. Further testing showed that this latter individual was a nonsecretor with limited exposure history.
Next, the investigators tested donor PBMCs for norovirus-specific T-cell responses with use of overlapping libraries of peptides for each of the three norovirus open reading frames (ORF1, ORF2, and ORF3). T-cell responses, predominantly involving CD8+ T cells, were observed in all donors. While donor 1 had the greatest response to ORF1, donors 2 and 3 had responses that focused on ORF2.
“Thus, norovirus-specific T cells targeting ORF1 and ORF2 epitopes are present in peripheral blood from healthy donors regardless of secretor status,” the investigators wrote.
To better characterize T-cell epitopes, the investigators subdivided the overlapping peptide libraries into groups of shorter peptides, then exposed serum to these smaller component pools. This revealed eight HLA class I restricted epitopes that were derived from a genogroup II.4 pandemic norovirus strain; this group of variants has been responsible for all six of the norovirus pandemics since 1996.
Closer examination of the epitopes showed that they were “broadly conserved beyond GII.4.” Only one epitope exhibited variation in the C-terminal aromatic anchor, and it was nondominant. The investigators therefore identified seven immunodominant CD8+ epitopes, which they considered “valuable targets for vaccine and cell-based therapies.
“These data further confirm that epitope-specific CD8+ T cells are a universal feature of the overall norovirus immune response and could be an attractive target for future vaccines,” the investigators wrote.
Additional testing involving samples of spleen, mesenteric lymph nodes, and duodenum from deceased individuals showed presence of norovirus-specific CD8+ T cells, with particular abundance in intestinal tissue, and distinct phenotypes and functional properties in different tissue types.
“Future studies using tetramers and intestinal samples should build on these observations and fully define the location and microenvironment of norovirus-specific T cells,” the investigators wrote. “If carried out in the context of a vaccine trial, such studies could be highly valuable in elucidating tissue-resident memory correlates of norovirus immunity.”
The study was funded by the National Institutes of Health, the Wellcome Trust, and Deutsche Forschungsgemeinschaft. The investigators reported no conflicts of interest.
Protection against norovirus gastroenteritis is supported in part by norovirus-specific CD8+ T cells that reside in peripheral, intestinal, and lymphoid tissues, according to investigators.
These findings, and the molecular tools used to discover them, could guide development of a norovirus vaccine and novel cellular therapies, according to lead author Ajinkya Pattekar, MD, of the University of Pennsylvania, Philadelphia, and colleagues.
“Currently, there are no approved pharmacologic therapies against norovirus, and despite several promising clinical trials, an effective vaccine is not available,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology, which may stem from an incomplete understanding of norovirus immunity, according to Dr. Pattekar and colleagues.
They noted that most previous research has focused on humoral immunity, which appears variable between individuals, with some people exhibiting a strong humoral response, while others mount only partial humoral protection. The investigators also noted that, depending on which studies were examined, this type of defense could last years or fade within weeks to months and that “immune mechanisms other than antibodies may be important for protection against noroviruses.”
Specifically, cellular immunity may be at work. A 2020 study involving volunteers showed that T cells were cross-reactive to a type of norovirus the participants had never been exposed to.
“These findings suggest that T cells may target conserved epitopes and could offer cross-protection against a broad range of noroviruses,” Dr. Pattekar and colleagues wrote.
To test this hypothesis, they first collected peripheral blood mononuclear cells (PBMCs) from three healthy volunteers with unknown norovirus exposure history. Then serum samples were screened for norovirus functional antibodies via the binding between virus-like particles (VLPs) and histo–blood group antigens (HBGAs). This revealed disparate profiles of blocking antibodies against various norovirus strains. While donor 1 and donor 2 had antibodies against multiple strains, donor 3 lacked norovirus antibodies. Further testing showed that this latter individual was a nonsecretor with limited exposure history.
Next, the investigators tested donor PBMCs for norovirus-specific T-cell responses with use of overlapping libraries of peptides for each of the three norovirus open reading frames (ORF1, ORF2, and ORF3). T-cell responses, predominantly involving CD8+ T cells, were observed in all donors. While donor 1 had the greatest response to ORF1, donors 2 and 3 had responses that focused on ORF2.
“Thus, norovirus-specific T cells targeting ORF1 and ORF2 epitopes are present in peripheral blood from healthy donors regardless of secretor status,” the investigators wrote.
To better characterize T-cell epitopes, the investigators subdivided the overlapping peptide libraries into groups of shorter peptides, then exposed serum to these smaller component pools. This revealed eight HLA class I restricted epitopes that were derived from a genogroup II.4 pandemic norovirus strain; this group of variants has been responsible for all six of the norovirus pandemics since 1996.
Closer examination of the epitopes showed that they were “broadly conserved beyond GII.4.” Only one epitope exhibited variation in the C-terminal aromatic anchor, and it was nondominant. The investigators therefore identified seven immunodominant CD8+ epitopes, which they considered “valuable targets for vaccine and cell-based therapies.
“These data further confirm that epitope-specific CD8+ T cells are a universal feature of the overall norovirus immune response and could be an attractive target for future vaccines,” the investigators wrote.
Additional testing involving samples of spleen, mesenteric lymph nodes, and duodenum from deceased individuals showed presence of norovirus-specific CD8+ T cells, with particular abundance in intestinal tissue, and distinct phenotypes and functional properties in different tissue types.
“Future studies using tetramers and intestinal samples should build on these observations and fully define the location and microenvironment of norovirus-specific T cells,” the investigators wrote. “If carried out in the context of a vaccine trial, such studies could be highly valuable in elucidating tissue-resident memory correlates of norovirus immunity.”
The study was funded by the National Institutes of Health, the Wellcome Trust, and Deutsche Forschungsgemeinschaft. The investigators reported no conflicts of interest.
FROM CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY