Commentary

This transcript has been edited for clarity. The transcript and an accompanying video first appeared on Medscape.com.

This is Mark Kris from chilly New York and Memorial Sloan Kettering. Today I want to talk about a recent article in the Journal of Clinical Oncology that reported a study of a new neurokinin-1 antagonist called fosnetupitant. This was a well-conducted trial that demonstrates the noninferiority of IV fosnetupitant when compared with IV fosaprepitant. By their study criteria, fosnetupitant was not inferior.

But my reason for discussing this is that the paper and the trial miss the point for the field right now. Although the authors talk about the prevention of nausea and vomiting in the introduction, in the paper itself and in the abstract results section, there’s not a single mention about the medication’s ability to control nausea, which is the critical issue for our patients today. You have to go into the supplementary data to find it mentioned, and what you find is that the prevention of nausea is 50% for both the control and this new drug. We control nausea in only half of the patients who receive cisplatin in 2022. That is a huge issue.

When you ask patients what are the effects of cancer treatment that they fear most, that concerns them most, it’s nausea and emesis; indeed, nausea has replaced emesis as the biggest concern. And although this trial used emesis as the main endpoint, and it was useful in defining the drug, it was not useful in coming up with a new treatment that addresses a huge need. Further, the authors talk about an advantage to fosnetupitant based on infusion reactions, but it is a difference of 0.3% vs. 3%. They talk about that sort of thing in the abstract and in the discussion section but don’t include nausea as part of the key endpoint of this trial. Again, you had to dig deeply to find out that, frankly, fosnetupitant was no better than the drugs we already have.

The other concerning point is that we do have another drug that works well. If you go to the American Society of Clinical Oncology or National Comprehensive Cancer Network guidelines for patients receiving high dosages of cisplatin, you find a four-drug regimen, including olanzapine, and that was not used here. Why is olanzapine so critical? It’s an available drug, it’s an inexpensive drug, it’s a safe drug, and it improves nausea by 15%.

So they did this huge trial to show noninferiority, and they neglected to give a drug that could deal with the most serious side effect of cancer therapy – nausea – and improve things by 15%.

A challenge to people in this field: We have to do better. Nausea is a big problem. While noninferiority trials can be helpful for drug development, they’re not really helpful for the field. With a problem of this magnitude, we need better drugs to control nausea. In the meantime, I urge you all to follow the guidelines for high doses of cisplatin. Please use the four-drug regimen that is recommended in the guidelines and widely used in the United States. Going forward, make sure that when we expend huge amounts of energy to develop new agents and report them in our medical journals, that we look for ways to advance care where there are significant gaps in our ability to deliver what we want. Delivering better control of nausea is something we all need to be committed to. It’s a huge unmet need, and I hope future trials will address that need. Our patients will be better for it and we’ll be better in that we’re delivering what patients deserve, what they need, and what they ask for.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. He reported serving as a director, officer, partner, employee, adviser, consultant, or trustee for AstraZeneca, Roche/Genentech, and Ariad Pharmaceuticals, and has received research grants from Pfizer, PUMA, and Roche/Genentech.

This transcript has been edited for clarity. The transcript and an accompanying video first appeared on Medscape.com.

This is Mark Kris from chilly New York and Memorial Sloan Kettering. Today I want to talk about a recent article in the Journal of Clinical Oncology that reported a study of a new neurokinin-1 antagonist called fosnetupitant. This was a well-conducted trial that demonstrates the noninferiority of IV fosnetupitant when compared with IV fosaprepitant. By their study criteria, fosnetupitant was not inferior.

But my reason for discussing this is that the paper and the trial miss the point for the field right now. Although the authors talk about the prevention of nausea and vomiting in the introduction, in the paper itself and in the abstract results section, there’s not a single mention about the medication’s ability to control nausea, which is the critical issue for our patients today. You have to go into the supplementary data to find it mentioned, and what you find is that the prevention of nausea is 50% for both the control and this new drug. We control nausea in only half of the patients who receive cisplatin in 2022. That is a huge issue.

When you ask patients what are the effects of cancer treatment that they fear most, that concerns them most, it’s nausea and emesis; indeed, nausea has replaced emesis as the biggest concern. And although this trial used emesis as the main endpoint, and it was useful in defining the drug, it was not useful in coming up with a new treatment that addresses a huge need. Further, the authors talk about an advantage to fosnetupitant based on infusion reactions, but it is a difference of 0.3% vs. 3%. They talk about that sort of thing in the abstract and in the discussion section but don’t include nausea as part of the key endpoint of this trial. Again, you had to dig deeply to find out that, frankly, fosnetupitant was no better than the drugs we already have.

The other concerning point is that we do have another drug that works well. If you go to the American Society of Clinical Oncology or National Comprehensive Cancer Network guidelines for patients receiving high dosages of cisplatin, you find a four-drug regimen, including olanzapine, and that was not used here. Why is olanzapine so critical? It’s an available drug, it’s an inexpensive drug, it’s a safe drug, and it improves nausea by 15%.

So they did this huge trial to show noninferiority, and they neglected to give a drug that could deal with the most serious side effect of cancer therapy – nausea – and improve things by 15%.

A challenge to people in this field: We have to do better. Nausea is a big problem. While noninferiority trials can be helpful for drug development, they’re not really helpful for the field. With a problem of this magnitude, we need better drugs to control nausea. In the meantime, I urge you all to follow the guidelines for high doses of cisplatin. Please use the four-drug regimen that is recommended in the guidelines and widely used in the United States. Going forward, make sure that when we expend huge amounts of energy to develop new agents and report them in our medical journals, that we look for ways to advance care where there are significant gaps in our ability to deliver what we want. Delivering better control of nausea is something we all need to be committed to. It’s a huge unmet need, and I hope future trials will address that need. Our patients will be better for it and we’ll be better in that we’re delivering what patients deserve, what they need, and what they ask for.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. He reported serving as a director, officer, partner, employee, adviser, consultant, or trustee for AstraZeneca, Roche/Genentech, and Ariad Pharmaceuticals, and has received research grants from Pfizer, PUMA, and Roche/Genentech.

This transcript has been edited for clarity. The transcript and an accompanying video first appeared on Medscape.com.

This is Mark Kris from chilly New York and Memorial Sloan Kettering. Today I want to talk about a recent article in the Journal of Clinical Oncology that reported a study of a new neurokinin-1 antagonist called fosnetupitant. This was a well-conducted trial that demonstrates the noninferiority of IV fosnetupitant when compared with IV fosaprepitant. By their study criteria, fosnetupitant was not inferior.

But my reason for discussing this is that the paper and the trial miss the point for the field right now. Although the authors talk about the prevention of nausea and vomiting in the introduction, in the paper itself and in the abstract results section, there’s not a single mention about the medication’s ability to control nausea, which is the critical issue for our patients today. You have to go into the supplementary data to find it mentioned, and what you find is that the prevention of nausea is 50% for both the control and this new drug. We control nausea in only half of the patients who receive cisplatin in 2022. That is a huge issue.

When you ask patients what are the effects of cancer treatment that they fear most, that concerns them most, it’s nausea and emesis; indeed, nausea has replaced emesis as the biggest concern. And although this trial used emesis as the main endpoint, and it was useful in defining the drug, it was not useful in coming up with a new treatment that addresses a huge need. Further, the authors talk about an advantage to fosnetupitant based on infusion reactions, but it is a difference of 0.3% vs. 3%. They talk about that sort of thing in the abstract and in the discussion section but don’t include nausea as part of the key endpoint of this trial. Again, you had to dig deeply to find out that, frankly, fosnetupitant was no better than the drugs we already have.

The other concerning point is that we do have another drug that works well. If you go to the American Society of Clinical Oncology or National Comprehensive Cancer Network guidelines for patients receiving high dosages of cisplatin, you find a four-drug regimen, including olanzapine, and that was not used here. Why is olanzapine so critical? It’s an available drug, it’s an inexpensive drug, it’s a safe drug, and it improves nausea by 15%.

So they did this huge trial to show noninferiority, and they neglected to give a drug that could deal with the most serious side effect of cancer therapy – nausea – and improve things by 15%.

A challenge to people in this field: We have to do better. Nausea is a big problem. While noninferiority trials can be helpful for drug development, they’re not really helpful for the field. With a problem of this magnitude, we need better drugs to control nausea. In the meantime, I urge you all to follow the guidelines for high doses of cisplatin. Please use the four-drug regimen that is recommended in the guidelines and widely used in the United States. Going forward, make sure that when we expend huge amounts of energy to develop new agents and report them in our medical journals, that we look for ways to advance care where there are significant gaps in our ability to deliver what we want. Delivering better control of nausea is something we all need to be committed to. It’s a huge unmet need, and I hope future trials will address that need. Our patients will be better for it and we’ll be better in that we’re delivering what patients deserve, what they need, and what they ask for.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. He reported serving as a director, officer, partner, employee, adviser, consultant, or trustee for AstraZeneca, Roche/Genentech, and Ariad Pharmaceuticals, and has received research grants from Pfizer, PUMA, and Roche/Genentech.

An otherwise healthy 55-year-old male, with no previous psychiatric or medical history, sought care with a family medicine physician for the first time in decades.

Medical symptoms began Oct. 9, 2021, with “some leg weakness and mild sniffles.” Since he was going to be at a public event, he decided to take a PCR test for the SARS-CoV-2 virus on Oct. 13. The patient tested positive.

His symptoms continued to worsen, and he experienced severe body fatigue, sleep disturbance, and lethargy. “A few days after my positive test, the cognitive and physical symptoms dramatically ramped up,” the patient recalled.

Because of those worsening symptoms, on Oct. 20, the patient obtained a new patient appointment with a family medicine physician. After a telemedicine evaluation, the family medicine physician began a multifaceted early outpatient COVID-19 treatment protocol,¹ as I (C.M.W.) and colleagues wrote about late last year. However, this treatment began late in the course because of the patient’s initial resistance to seek care.

This early outpatient treatment protocol for COVID-19 included vitamin D3 125 mcg (5,000 ICU), N-acetylcysteine (NAC) 600 mg every day x 30 days; acetylsalicylic acid 325 mg every day x 30 days; azithromycin 250 mg b.i.d. before every meal x 10 days; hydroxychloroquine sulfate 200 mg b.i.d. x 10 days; ivermectin 3 mg, 5 pills daily x 10 days; zinc sulfate 220 mg (50 mg elemental) every day x 30 days; and a prednisone taper (30 mg daily x 3 days, tapering down 5 mg every 3 days). Hydroxyzine 50 mg at bedtime as needed was added for sleep. The patient did not comment to the family physician on any of the psychological or psychiatric symptoms and responded appropriately to questions during the Oct. 20 initial evaluation.

However, he later described that around the time the PCR was positive, “COVID twisted my brain. I could not think straight. Every thought required 50 times the effort.” For example, he was watching a simple YouTube video for work and “everything was confusing me ... it rattled me, and I couldn’t understand it.” He described his COVID-19 mind as: “The words in my head would come out in a jumbled order, like the message from the words in my brain to my mouth would get crossed. I had trouble spelling and texting. Total cognitive breakdown. I couldn’t do simple mathematics.”

Despite his physical exhaustion, he endured a 3-day period of sleep deprivation. During this time, he recalled looking up at the roof and thinking, “I need to jump off the roof” or thinking, “I might want to throw myself under a bus.” He did not initially reveal his suicidal thoughts to his family medicine physician. After beginning COVID-19 treatment, the patient had two nights of sleep and felt notably improved, and his physical symptoms began to remit. However, the sleeplessness quickly returned “with a vengeance” along with “silly suicidal thoughts.” The thoughts took on a more obsessional quality. For example, he repeatedly thought of jumping out of his second-story bedroom to the living room below and was preoccupied by continually looking at people’s roofs and thinking about jumping. Those thoughts intensified and culminated in his “going missing,” leading his wife to call the police. It was discovered that he had driven to a local bridge and was contemplating jumping off.

After that “going missing” incident, the patient and his wife reached out to their family medicine physician. He reevaluated the patient and, given the new information about the psychiatric symptoms, strongly recommended stat crisis and psychiatric consultation. After discussing the case on the same day, both the family medicine physician and the psychiatrist recommended stat hospital emergency department (ED) assessment on Oct. 29. In the ED, a head CT without contrast at the recommendation of both psychiatrist and family physician, routine electrolytes, CBC with differential, and EKG all were within normal limits. The ED initially discharged him home after crisis evaluation, deciding he was not an imminent risk to himself or others.

The next day, the psychiatrist spoke on the phone with the patient, family medicine physician, and the patient’s wife to arrange an initial assessment. At that time, it remained unclear to all whether the obsessional thoughts had resolved to such a degree that the patient could resist acting upon them. Further, the patient’s sleep architecture had not returned to normal. All agreed another emergency ED assessment was indicated. Ultimately, after voluntary re-evaluation and a difficult hold in the crisis unit, the patient was admitted for psychiatric hospitalization on Oct. 29 and discharged on Nov. 4.

In the psychiatric hospital, venlafaxine XR was started and titrated to 75 mg. The patient was discovered to be hypertensive, and hydrochlorothiazide was started. The discharge diagnosis was major depressive disorder, single episode, severe, without psychotic features.
 

Posthospitalization course

The patient’s clinical course cleared remarkably. He was seen for his initial psychiatric outpatient assessment postpsychiatric hospitalization on Nov. 9, as he had not yet been formally evaluated by the psychiatrist because of the emergency situation.

Gabapentin 300 mg by mouth at bedtime was started, and his sleep architecture was restored. The initial plan to titrate venlafaxine XR into dual selective norepinephrine reuptake inhibitor dose range was terminated, and his psychiatrist considered tapering and discontinuing the venlafaxine XR. A clinical examination, additional history, and collateral data no longer necessarily pointed to an active major depressive disorder or even unspecified depressive disorder, though to be sure, the patient was taking 75 mg of venlafaxine XR. While there were seasonal stressors, historically, nothing had risen to the level of MDD.

The obsessions driving his thoughts to jump off buildings and bridges had completely remitted. His cognitive ability returned to baseline with an ability to focus and perform the complicated tasks of his high-intensity work by the Dec. 8 psychiatric examination, where he was accompanied by his wife. He described feeling like, “I snapped back to like I was before this crazy stuff happened.” His mood was reported as, “Very good; like my old self” and this was confirmed by his wife. His affect was calmer and less tense. He was now using gabapentin sparingly for sleep. We continued to entertain discontinuing the venlafaxine XR, considering this recent severe episode likely driven by the COVID-19 virus. The decision was made to continue venlafaxine XR through the winter rather than discontinuing, remaining on the conservative side of treatment. The patient’s diagnosis was changed from “MDD, single episode,” to “mood disorder due to known physiologic condition (COVID-19) (F06.31) with depressive features; resolving.” At the patient’s follow-up examination on Jan. 5, 2022, he was continuing to do well, stating, “The whole series of crazy events happened to someone else.” The hydrochlorothiazide had been discontinued, and the patient’s blood pressure and pulse were normal at 119/81 and 69, respectively. He had made strategic changes at work to lessen stressors during the typically difficult months.
 

Discussion

Literature has discussed neuropsychiatric sequelae of COVID-19.² The cited example questions whether psychiatric symptoms are tied directly to the viral infection or to the “host’s immune response.” We believe our case represents a direct neurocognitive/neuropsychiatric insult due to the COVID-19 infection.

This case presents a 55-year-old male with no previous psychiatric or medical history with new onset significant and debilitating cognitive impairment and obsessive thoughts of throwing himself from his bedroom balcony ending up at a bridge struggling with an irrational thought of jumping; ultimately requiring psychiatric hospitalization for acute suicidal thoughts. The patient’s psychiatric symptoms arose prior to any and all medication treatment. The obsessive thoughts correlated both with the onset of SARS-CoV-2 infection and a period of sleep deprivation subsequent to the infection. A course of steroid treatment and taper were started after the onset of neurocognitive-psychiatric symptoms, though there is close timing. We submit that the patient experienced, as part of the initial neurocognitive psychiatric initiating cascade, a COVID-19–induced sleep deprivation that was not etiologic but part of the process; since, even when sleep returned to normal, it was still several weeks before full cognitive function returned to baseline.

An argument could be made for possible MDD or unspecified depressive disorder, as historically there had been work-related stressors for the patient at this time of year because of the chronological nature of his work; though previously nothing presented with obsessional suicidal thinking and nothing with any cognitive impairment – let alone to this incapacitating degree.

The patient describes his seasonal work much like an accountant’s work at the beginning of each year. In the patient’s case, the months of September and October are historically “nonstop, working days,” which then slow down in the winter months for a period of recuperation. In gathering his past history of symptoms, he denied neurovegetative symptoms to meet full diagnostic criteria for MDD or unspecified depressive disorder, absent this episode in the presence of SARS-CoV-2 infection.

We could also consider a contributory negative “organic push” by the viral load and prednisone helping to express an underlying unspecified depression or MDD, but for the profound and unusual presentation. There was little prodrome of depressive symptoms (again, he reported his “typical” extraordinary work burden for this time of year, which is common in his industry).

In this patient, the symptoms have remitted completely. However, the patient is currently taking venlafaxine XR 75 mg. We have considered tapering and discontinuing the venlafaxine – since it is not entirely clear that he needs to be on this medication – so this question remains an open one. We did decide, however, to continue the venlafaxine until after the winter months and to reassess at that time.
 

Conclusion

The patient presented with new onset psychological and psychiatric symptoms in addition to physiologic symptoms; the former symptoms were not revealed prior to initial family medicine evaluation. As the symptoms worsened, he and his wife sought additional consultation with family physician, psychiatrists, and ED. Steroid treatment may have played a part in exacerbation of symptoms, but the neuropsychiatric cognitive symptoms were present prior to initiation of all pharmacologic and medical treatment. The successful outcome of this case was based upon quick action and collaboration between the family medicine physician, the psychiatrist, and the ED physician. The value of communication, assessment, and action via phone call and text cannot be overstated. Future considerations include further large-scale evaluation of multifaceted early treatment of patients with COVID-19 within the first 72 hours of symptoms to prevent not only hospitalization, morbidity, and mortality, but newly recognized psychological and psychiatric syndromes.^3,4

Lastly, fluvoxamine might have been a better choice for adjunctive early treatment of COVID-19.⁵ As a matter of distinction, if a lingering mood disorder or obsessive-compulsive disorder remain a result of SARS-CoV-2 or if one were to start an antidepressant during the course of illness, it would be reasonable to consider fluvoxamine as a potential first-line agent.

Dr. Kohanski is a fellowship trained forensic psychiatrist and a diplomate of the American Board of Psychiatry & Neurology. She maintains a private practice in Somerset, N.J., and is a frequent media commentator and medical podcaster. Dr. Kohanski has no conflicts of interest. Dr. Wax is a residency-trained osteopathic family medicine physician in independent private practice in Mullica Hill, N.J. He has authored multiple papers over 2 decades on topics such as SARS-CoV-2 and COVID-19 early treatment. He has been a speaker and media host over 2 decades and served on the National Physicians Council on Healthcare Policy’s congressional subcommittee. Dr. Wax has no conflicts of interest.

References

1. Rev Cardiovasc Med. 2020 Dec 30;21(4):517-30.

2. Brain Behav Immun. 2020 Jul;87:34-9.

3. Trav Med Infect Dis. 2020 May-Jun 35;10738.

4. Kirsch S. “Early treatment for COVID is key to better outcomes.” Times of India. 2021 May 21.

5. Lancet. 2022 Jan 1;10(1):E42-E51.

An otherwise healthy 55-year-old male, with no previous psychiatric or medical history, sought care with a family medicine physician for the first time in decades.

Medical symptoms began Oct. 9, 2021, with “some leg weakness and mild sniffles.” Since he was going to be at a public event, he decided to take a PCR test for the SARS-CoV-2 virus on Oct. 13. The patient tested positive.

His symptoms continued to worsen, and he experienced severe body fatigue, sleep disturbance, and lethargy. “A few days after my positive test, the cognitive and physical symptoms dramatically ramped up,” the patient recalled.

Because of those worsening symptoms, on Oct. 20, the patient obtained a new patient appointment with a family medicine physician. After a telemedicine evaluation, the family medicine physician began a multifaceted early outpatient COVID-19 treatment protocol,¹ as I (C.M.W.) and colleagues wrote about late last year. However, this treatment began late in the course because of the patient’s initial resistance to seek care.

This early outpatient treatment protocol for COVID-19 included vitamin D3 125 mcg (5,000 ICU), N-acetylcysteine (NAC) 600 mg every day x 30 days; acetylsalicylic acid 325 mg every day x 30 days; azithromycin 250 mg b.i.d. before every meal x 10 days; hydroxychloroquine sulfate 200 mg b.i.d. x 10 days; ivermectin 3 mg, 5 pills daily x 10 days; zinc sulfate 220 mg (50 mg elemental) every day x 30 days; and a prednisone taper (30 mg daily x 3 days, tapering down 5 mg every 3 days). Hydroxyzine 50 mg at bedtime as needed was added for sleep. The patient did not comment to the family physician on any of the psychological or psychiatric symptoms and responded appropriately to questions during the Oct. 20 initial evaluation.

However, he later described that around the time the PCR was positive, “COVID twisted my brain. I could not think straight. Every thought required 50 times the effort.” For example, he was watching a simple YouTube video for work and “everything was confusing me ... it rattled me, and I couldn’t understand it.” He described his COVID-19 mind as: “The words in my head would come out in a jumbled order, like the message from the words in my brain to my mouth would get crossed. I had trouble spelling and texting. Total cognitive breakdown. I couldn’t do simple mathematics.”

Despite his physical exhaustion, he endured a 3-day period of sleep deprivation. During this time, he recalled looking up at the roof and thinking, “I need to jump off the roof” or thinking, “I might want to throw myself under a bus.” He did not initially reveal his suicidal thoughts to his family medicine physician. After beginning COVID-19 treatment, the patient had two nights of sleep and felt notably improved, and his physical symptoms began to remit. However, the sleeplessness quickly returned “with a vengeance” along with “silly suicidal thoughts.” The thoughts took on a more obsessional quality. For example, he repeatedly thought of jumping out of his second-story bedroom to the living room below and was preoccupied by continually looking at people’s roofs and thinking about jumping. Those thoughts intensified and culminated in his “going missing,” leading his wife to call the police. It was discovered that he had driven to a local bridge and was contemplating jumping off.

After that “going missing” incident, the patient and his wife reached out to their family medicine physician. He reevaluated the patient and, given the new information about the psychiatric symptoms, strongly recommended stat crisis and psychiatric consultation. After discussing the case on the same day, both the family medicine physician and the psychiatrist recommended stat hospital emergency department (ED) assessment on Oct. 29. In the ED, a head CT without contrast at the recommendation of both psychiatrist and family physician, routine electrolytes, CBC with differential, and EKG all were within normal limits. The ED initially discharged him home after crisis evaluation, deciding he was not an imminent risk to himself or others.

The next day, the psychiatrist spoke on the phone with the patient, family medicine physician, and the patient’s wife to arrange an initial assessment. At that time, it remained unclear to all whether the obsessional thoughts had resolved to such a degree that the patient could resist acting upon them. Further, the patient’s sleep architecture had not returned to normal. All agreed another emergency ED assessment was indicated. Ultimately, after voluntary re-evaluation and a difficult hold in the crisis unit, the patient was admitted for psychiatric hospitalization on Oct. 29 and discharged on Nov. 4.

In the psychiatric hospital, venlafaxine XR was started and titrated to 75 mg. The patient was discovered to be hypertensive, and hydrochlorothiazide was started. The discharge diagnosis was major depressive disorder, single episode, severe, without psychotic features.
 

Posthospitalization course

The patient’s clinical course cleared remarkably. He was seen for his initial psychiatric outpatient assessment postpsychiatric hospitalization on Nov. 9, as he had not yet been formally evaluated by the psychiatrist because of the emergency situation.

Gabapentin 300 mg by mouth at bedtime was started, and his sleep architecture was restored. The initial plan to titrate venlafaxine XR into dual selective norepinephrine reuptake inhibitor dose range was terminated, and his psychiatrist considered tapering and discontinuing the venlafaxine XR. A clinical examination, additional history, and collateral data no longer necessarily pointed to an active major depressive disorder or even unspecified depressive disorder, though to be sure, the patient was taking 75 mg of venlafaxine XR. While there were seasonal stressors, historically, nothing had risen to the level of MDD.

The obsessions driving his thoughts to jump off buildings and bridges had completely remitted. His cognitive ability returned to baseline with an ability to focus and perform the complicated tasks of his high-intensity work by the Dec. 8 psychiatric examination, where he was accompanied by his wife. He described feeling like, “I snapped back to like I was before this crazy stuff happened.” His mood was reported as, “Very good; like my old self” and this was confirmed by his wife. His affect was calmer and less tense. He was now using gabapentin sparingly for sleep. We continued to entertain discontinuing the venlafaxine XR, considering this recent severe episode likely driven by the COVID-19 virus. The decision was made to continue venlafaxine XR through the winter rather than discontinuing, remaining on the conservative side of treatment. The patient’s diagnosis was changed from “MDD, single episode,” to “mood disorder due to known physiologic condition (COVID-19) (F06.31) with depressive features; resolving.” At the patient’s follow-up examination on Jan. 5, 2022, he was continuing to do well, stating, “The whole series of crazy events happened to someone else.” The hydrochlorothiazide had been discontinued, and the patient’s blood pressure and pulse were normal at 119/81 and 69, respectively. He had made strategic changes at work to lessen stressors during the typically difficult months.
 

Discussion

Literature has discussed neuropsychiatric sequelae of COVID-19.² The cited example questions whether psychiatric symptoms are tied directly to the viral infection or to the “host’s immune response.” We believe our case represents a direct neurocognitive/neuropsychiatric insult due to the COVID-19 infection.

This case presents a 55-year-old male with no previous psychiatric or medical history with new onset significant and debilitating cognitive impairment and obsessive thoughts of throwing himself from his bedroom balcony ending up at a bridge struggling with an irrational thought of jumping; ultimately requiring psychiatric hospitalization for acute suicidal thoughts. The patient’s psychiatric symptoms arose prior to any and all medication treatment. The obsessive thoughts correlated both with the onset of SARS-CoV-2 infection and a period of sleep deprivation subsequent to the infection. A course of steroid treatment and taper were started after the onset of neurocognitive-psychiatric symptoms, though there is close timing. We submit that the patient experienced, as part of the initial neurocognitive psychiatric initiating cascade, a COVID-19–induced sleep deprivation that was not etiologic but part of the process; since, even when sleep returned to normal, it was still several weeks before full cognitive function returned to baseline.

An argument could be made for possible MDD or unspecified depressive disorder, as historically there had been work-related stressors for the patient at this time of year because of the chronological nature of his work; though previously nothing presented with obsessional suicidal thinking and nothing with any cognitive impairment – let alone to this incapacitating degree.

The patient describes his seasonal work much like an accountant’s work at the beginning of each year. In the patient’s case, the months of September and October are historically “nonstop, working days,” which then slow down in the winter months for a period of recuperation. In gathering his past history of symptoms, he denied neurovegetative symptoms to meet full diagnostic criteria for MDD or unspecified depressive disorder, absent this episode in the presence of SARS-CoV-2 infection.

We could also consider a contributory negative “organic push” by the viral load and prednisone helping to express an underlying unspecified depression or MDD, but for the profound and unusual presentation. There was little prodrome of depressive symptoms (again, he reported his “typical” extraordinary work burden for this time of year, which is common in his industry).

In this patient, the symptoms have remitted completely. However, the patient is currently taking venlafaxine XR 75 mg. We have considered tapering and discontinuing the venlafaxine – since it is not entirely clear that he needs to be on this medication – so this question remains an open one. We did decide, however, to continue the venlafaxine until after the winter months and to reassess at that time.
 

Conclusion

The patient presented with new onset psychological and psychiatric symptoms in addition to physiologic symptoms; the former symptoms were not revealed prior to initial family medicine evaluation. As the symptoms worsened, he and his wife sought additional consultation with family physician, psychiatrists, and ED. Steroid treatment may have played a part in exacerbation of symptoms, but the neuropsychiatric cognitive symptoms were present prior to initiation of all pharmacologic and medical treatment. The successful outcome of this case was based upon quick action and collaboration between the family medicine physician, the psychiatrist, and the ED physician. The value of communication, assessment, and action via phone call and text cannot be overstated. Future considerations include further large-scale evaluation of multifaceted early treatment of patients with COVID-19 within the first 72 hours of symptoms to prevent not only hospitalization, morbidity, and mortality, but newly recognized psychological and psychiatric syndromes.^3,4

Lastly, fluvoxamine might have been a better choice for adjunctive early treatment of COVID-19.⁵ As a matter of distinction, if a lingering mood disorder or obsessive-compulsive disorder remain a result of SARS-CoV-2 or if one were to start an antidepressant during the course of illness, it would be reasonable to consider fluvoxamine as a potential first-line agent.

Dr. Kohanski is a fellowship trained forensic psychiatrist and a diplomate of the American Board of Psychiatry & Neurology. She maintains a private practice in Somerset, N.J., and is a frequent media commentator and medical podcaster. Dr. Kohanski has no conflicts of interest. Dr. Wax is a residency-trained osteopathic family medicine physician in independent private practice in Mullica Hill, N.J. He has authored multiple papers over 2 decades on topics such as SARS-CoV-2 and COVID-19 early treatment. He has been a speaker and media host over 2 decades and served on the National Physicians Council on Healthcare Policy’s congressional subcommittee. Dr. Wax has no conflicts of interest.

References

1. Rev Cardiovasc Med. 2020 Dec 30;21(4):517-30.

2. Brain Behav Immun. 2020 Jul;87:34-9.

3. Trav Med Infect Dis. 2020 May-Jun 35;10738.

4. Kirsch S. “Early treatment for COVID is key to better outcomes.” Times of India. 2021 May 21.

5. Lancet. 2022 Jan 1;10(1):E42-E51.

An otherwise healthy 55-year-old male, with no previous psychiatric or medical history, sought care with a family medicine physician for the first time in decades.

Medical symptoms began Oct. 9, 2021, with “some leg weakness and mild sniffles.” Since he was going to be at a public event, he decided to take a PCR test for the SARS-CoV-2 virus on Oct. 13. The patient tested positive.

His symptoms continued to worsen, and he experienced severe body fatigue, sleep disturbance, and lethargy. “A few days after my positive test, the cognitive and physical symptoms dramatically ramped up,” the patient recalled.

Because of those worsening symptoms, on Oct. 20, the patient obtained a new patient appointment with a family medicine physician. After a telemedicine evaluation, the family medicine physician began a multifaceted early outpatient COVID-19 treatment protocol,¹ as I (C.M.W.) and colleagues wrote about late last year. However, this treatment began late in the course because of the patient’s initial resistance to seek care.

This early outpatient treatment protocol for COVID-19 included vitamin D3 125 mcg (5,000 ICU), N-acetylcysteine (NAC) 600 mg every day x 30 days; acetylsalicylic acid 325 mg every day x 30 days; azithromycin 250 mg b.i.d. before every meal x 10 days; hydroxychloroquine sulfate 200 mg b.i.d. x 10 days; ivermectin 3 mg, 5 pills daily x 10 days; zinc sulfate 220 mg (50 mg elemental) every day x 30 days; and a prednisone taper (30 mg daily x 3 days, tapering down 5 mg every 3 days). Hydroxyzine 50 mg at bedtime as needed was added for sleep. The patient did not comment to the family physician on any of the psychological or psychiatric symptoms and responded appropriately to questions during the Oct. 20 initial evaluation.

However, he later described that around the time the PCR was positive, “COVID twisted my brain. I could not think straight. Every thought required 50 times the effort.” For example, he was watching a simple YouTube video for work and “everything was confusing me ... it rattled me, and I couldn’t understand it.” He described his COVID-19 mind as: “The words in my head would come out in a jumbled order, like the message from the words in my brain to my mouth would get crossed. I had trouble spelling and texting. Total cognitive breakdown. I couldn’t do simple mathematics.”

Despite his physical exhaustion, he endured a 3-day period of sleep deprivation. During this time, he recalled looking up at the roof and thinking, “I need to jump off the roof” or thinking, “I might want to throw myself under a bus.” He did not initially reveal his suicidal thoughts to his family medicine physician. After beginning COVID-19 treatment, the patient had two nights of sleep and felt notably improved, and his physical symptoms began to remit. However, the sleeplessness quickly returned “with a vengeance” along with “silly suicidal thoughts.” The thoughts took on a more obsessional quality. For example, he repeatedly thought of jumping out of his second-story bedroom to the living room below and was preoccupied by continually looking at people’s roofs and thinking about jumping. Those thoughts intensified and culminated in his “going missing,” leading his wife to call the police. It was discovered that he had driven to a local bridge and was contemplating jumping off.

After that “going missing” incident, the patient and his wife reached out to their family medicine physician. He reevaluated the patient and, given the new information about the psychiatric symptoms, strongly recommended stat crisis and psychiatric consultation. After discussing the case on the same day, both the family medicine physician and the psychiatrist recommended stat hospital emergency department (ED) assessment on Oct. 29. In the ED, a head CT without contrast at the recommendation of both psychiatrist and family physician, routine electrolytes, CBC with differential, and EKG all were within normal limits. The ED initially discharged him home after crisis evaluation, deciding he was not an imminent risk to himself or others.

The next day, the psychiatrist spoke on the phone with the patient, family medicine physician, and the patient’s wife to arrange an initial assessment. At that time, it remained unclear to all whether the obsessional thoughts had resolved to such a degree that the patient could resist acting upon them. Further, the patient’s sleep architecture had not returned to normal. All agreed another emergency ED assessment was indicated. Ultimately, after voluntary re-evaluation and a difficult hold in the crisis unit, the patient was admitted for psychiatric hospitalization on Oct. 29 and discharged on Nov. 4.

In the psychiatric hospital, venlafaxine XR was started and titrated to 75 mg. The patient was discovered to be hypertensive, and hydrochlorothiazide was started. The discharge diagnosis was major depressive disorder, single episode, severe, without psychotic features.
 

Posthospitalization course

The patient’s clinical course cleared remarkably. He was seen for his initial psychiatric outpatient assessment postpsychiatric hospitalization on Nov. 9, as he had not yet been formally evaluated by the psychiatrist because of the emergency situation.

Gabapentin 300 mg by mouth at bedtime was started, and his sleep architecture was restored. The initial plan to titrate venlafaxine XR into dual selective norepinephrine reuptake inhibitor dose range was terminated, and his psychiatrist considered tapering and discontinuing the venlafaxine XR. A clinical examination, additional history, and collateral data no longer necessarily pointed to an active major depressive disorder or even unspecified depressive disorder, though to be sure, the patient was taking 75 mg of venlafaxine XR. While there were seasonal stressors, historically, nothing had risen to the level of MDD.

The obsessions driving his thoughts to jump off buildings and bridges had completely remitted. His cognitive ability returned to baseline with an ability to focus and perform the complicated tasks of his high-intensity work by the Dec. 8 psychiatric examination, where he was accompanied by his wife. He described feeling like, “I snapped back to like I was before this crazy stuff happened.” His mood was reported as, “Very good; like my old self” and this was confirmed by his wife. His affect was calmer and less tense. He was now using gabapentin sparingly for sleep. We continued to entertain discontinuing the venlafaxine XR, considering this recent severe episode likely driven by the COVID-19 virus. The decision was made to continue venlafaxine XR through the winter rather than discontinuing, remaining on the conservative side of treatment. The patient’s diagnosis was changed from “MDD, single episode,” to “mood disorder due to known physiologic condition (COVID-19) (F06.31) with depressive features; resolving.” At the patient’s follow-up examination on Jan. 5, 2022, he was continuing to do well, stating, “The whole series of crazy events happened to someone else.” The hydrochlorothiazide had been discontinued, and the patient’s blood pressure and pulse were normal at 119/81 and 69, respectively. He had made strategic changes at work to lessen stressors during the typically difficult months.
 

Discussion

Literature has discussed neuropsychiatric sequelae of COVID-19.² The cited example questions whether psychiatric symptoms are tied directly to the viral infection or to the “host’s immune response.” We believe our case represents a direct neurocognitive/neuropsychiatric insult due to the COVID-19 infection.

This case presents a 55-year-old male with no previous psychiatric or medical history with new onset significant and debilitating cognitive impairment and obsessive thoughts of throwing himself from his bedroom balcony ending up at a bridge struggling with an irrational thought of jumping; ultimately requiring psychiatric hospitalization for acute suicidal thoughts. The patient’s psychiatric symptoms arose prior to any and all medication treatment. The obsessive thoughts correlated both with the onset of SARS-CoV-2 infection and a period of sleep deprivation subsequent to the infection. A course of steroid treatment and taper were started after the onset of neurocognitive-psychiatric symptoms, though there is close timing. We submit that the patient experienced, as part of the initial neurocognitive psychiatric initiating cascade, a COVID-19–induced sleep deprivation that was not etiologic but part of the process; since, even when sleep returned to normal, it was still several weeks before full cognitive function returned to baseline.

An argument could be made for possible MDD or unspecified depressive disorder, as historically there had been work-related stressors for the patient at this time of year because of the chronological nature of his work; though previously nothing presented with obsessional suicidal thinking and nothing with any cognitive impairment – let alone to this incapacitating degree.

The patient describes his seasonal work much like an accountant’s work at the beginning of each year. In the patient’s case, the months of September and October are historically “nonstop, working days,” which then slow down in the winter months for a period of recuperation. In gathering his past history of symptoms, he denied neurovegetative symptoms to meet full diagnostic criteria for MDD or unspecified depressive disorder, absent this episode in the presence of SARS-CoV-2 infection.

We could also consider a contributory negative “organic push” by the viral load and prednisone helping to express an underlying unspecified depression or MDD, but for the profound and unusual presentation. There was little prodrome of depressive symptoms (again, he reported his “typical” extraordinary work burden for this time of year, which is common in his industry).

In this patient, the symptoms have remitted completely. However, the patient is currently taking venlafaxine XR 75 mg. We have considered tapering and discontinuing the venlafaxine – since it is not entirely clear that he needs to be on this medication – so this question remains an open one. We did decide, however, to continue the venlafaxine until after the winter months and to reassess at that time.
 

Conclusion

The patient presented with new onset psychological and psychiatric symptoms in addition to physiologic symptoms; the former symptoms were not revealed prior to initial family medicine evaluation. As the symptoms worsened, he and his wife sought additional consultation with family physician, psychiatrists, and ED. Steroid treatment may have played a part in exacerbation of symptoms, but the neuropsychiatric cognitive symptoms were present prior to initiation of all pharmacologic and medical treatment. The successful outcome of this case was based upon quick action and collaboration between the family medicine physician, the psychiatrist, and the ED physician. The value of communication, assessment, and action via phone call and text cannot be overstated. Future considerations include further large-scale evaluation of multifaceted early treatment of patients with COVID-19 within the first 72 hours of symptoms to prevent not only hospitalization, morbidity, and mortality, but newly recognized psychological and psychiatric syndromes.^3,4

Lastly, fluvoxamine might have been a better choice for adjunctive early treatment of COVID-19.⁵ As a matter of distinction, if a lingering mood disorder or obsessive-compulsive disorder remain a result of SARS-CoV-2 or if one were to start an antidepressant during the course of illness, it would be reasonable to consider fluvoxamine as a potential first-line agent.

Dr. Kohanski is a fellowship trained forensic psychiatrist and a diplomate of the American Board of Psychiatry & Neurology. She maintains a private practice in Somerset, N.J., and is a frequent media commentator and medical podcaster. Dr. Kohanski has no conflicts of interest. Dr. Wax is a residency-trained osteopathic family medicine physician in independent private practice in Mullica Hill, N.J. He has authored multiple papers over 2 decades on topics such as SARS-CoV-2 and COVID-19 early treatment. He has been a speaker and media host over 2 decades and served on the National Physicians Council on Healthcare Policy’s congressional subcommittee. Dr. Wax has no conflicts of interest.

References

1. Rev Cardiovasc Med. 2020 Dec 30;21(4):517-30.

2. Brain Behav Immun. 2020 Jul;87:34-9.

3. Trav Med Infect Dis. 2020 May-Jun 35;10738.

4. Kirsch S. “Early treatment for COVID is key to better outcomes.” Times of India. 2021 May 21.

5. Lancet. 2022 Jan 1;10(1):E42-E51.

All else being equal, I’d prefer to do nothing. Whether this is nihilism, laziness, or experience is a matter of debate. The American College of Chest Physicians (CHEST) Guidelines on therapy for venous thromboembolism (VTE) opened a door for withholding treatment for isolated subsegmental pulmonary embolism (ISSPE) in 2016 and kept it open in 2021. I was happy to walk through it and withhold therapy if it wasn’t indicated.

ISSPE is truly a conundrum. With advances in technology, the distal vessels in the lung became visible on commercial CT a little more than 10 years ago. The subsegmental branches are located after the fourth bifurcation of the pulmonary arterial system, and the new technology offered resolution adequate to identify clot in these vessels. But the new technology told us nothing about how to manage clot isolated to the subsegmental vasculature.

Autopsy data say clot in these vessels is common, even in patients who were never diagnosed with VTE while they were alive. To some degree then, the pulmonary arterial system is thought to serve as a filter to prevent clot from crossing to the systemic circulation and causing stroke. This led some to speculate that the subsegmental pulmonary arteries are supposed to contain clot and that we simply couldn’t see it before now. If this theory is correct, the practice of providing anticoagulation for ISSPE could increase bleeding without reducing the risk for VTE recurrence.

Management studies generally supported this concept. In 2007, a trial that was published in JAMA randomized patients to two different diagnostic strategies: ventilation-perfusion (VQ) and CT. CT detected more clot than VQ did, so more anticoagulation was given in the CT arm. Yet, the VTE rate during follow-up was not significantly different between arms. The implication? Some of the clots detected by CT were of lesser clinical significance and didn’t need to be treated.

Meta-analytic data from management trials also suggested that some pulmonary emboli (PE) need not be treated. Data also show when compared with patients who have more proximal PE, those with ISSPE have lower pretest probability for VTE, are less symptomatic, and have a lower burden of coexistent lower extremity thrombosis (deep vein thrombosis [DVT]).

In response to this data, the CHEST Guidelines began cautiously providing the option for withholding therapy in patients who were diagnosed with ISSPE in 2016. Their recommendations stated that patients should be stratified for recurrence risk and have lower extremity ultrasonography performed to rule out DVT. A patient with ISSPE, a low recurrence risk, and a negative ultrasound can have anticoagulation withheld. This made perfect sense to me based on what I thought I knew at the time.

Recently published data cast doubt on my nihilism. The first prospective study designed specifically to assess the safety of withholding therapy for ISSPE suggests that this practice could be dangerous. How did this happen? The trial was very well done, and the authors enrolled the right population. All of the patients had ISSPE, low recurrence risk, and negative lower extremity ultrasound. The authors were anticipating a 1% VTE rate at 90 days based on prior data but instead found a rate of 3.1% (1.6%-6.1%). They point out that this rate is not different from those seen in patients with more proximal PE who are treated with anticoagulation. However, they acknowledge that it is higher than what’s considered acceptable and warrants therapeutic anticoagulation.

So what should we do now? We treat ISSPE, that’s what. All the arguments for withholding therapy remain valid, the recurrence rate is reasonably low, and none of the recurrent VTEs in the new study were fatal. There’s still no doubt that some patients with PE won’t benefit from anticoagulation. Unfortunately, we currently lack the tools to identify them. The risk-benefit ratio for recurrence versus bleeding will be tighter with ISSPE, particularly when there’s only one clot. Unless the bleeding risk is elevated though, the ratio still favors treatment.

Aaron B. Holley, MD, is an associate professor of medicine at Uniformed Services University and program director of pulmonary and critical care medicine at Walter Reed National Military Medical Center.

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

All else being equal, I’d prefer to do nothing. Whether this is nihilism, laziness, or experience is a matter of debate. The American College of Chest Physicians (CHEST) Guidelines on therapy for venous thromboembolism (VTE) opened a door for withholding treatment for isolated subsegmental pulmonary embolism (ISSPE) in 2016 and kept it open in 2021. I was happy to walk through it and withhold therapy if it wasn’t indicated.

ISSPE is truly a conundrum. With advances in technology, the distal vessels in the lung became visible on commercial CT a little more than 10 years ago. The subsegmental branches are located after the fourth bifurcation of the pulmonary arterial system, and the new technology offered resolution adequate to identify clot in these vessels. But the new technology told us nothing about how to manage clot isolated to the subsegmental vasculature.

Autopsy data say clot in these vessels is common, even in patients who were never diagnosed with VTE while they were alive. To some degree then, the pulmonary arterial system is thought to serve as a filter to prevent clot from crossing to the systemic circulation and causing stroke. This led some to speculate that the subsegmental pulmonary arteries are supposed to contain clot and that we simply couldn’t see it before now. If this theory is correct, the practice of providing anticoagulation for ISSPE could increase bleeding without reducing the risk for VTE recurrence.

Management studies generally supported this concept. In 2007, a trial that was published in JAMA randomized patients to two different diagnostic strategies: ventilation-perfusion (VQ) and CT. CT detected more clot than VQ did, so more anticoagulation was given in the CT arm. Yet, the VTE rate during follow-up was not significantly different between arms. The implication? Some of the clots detected by CT were of lesser clinical significance and didn’t need to be treated.

Meta-analytic data from management trials also suggested that some pulmonary emboli (PE) need not be treated. Data also show when compared with patients who have more proximal PE, those with ISSPE have lower pretest probability for VTE, are less symptomatic, and have a lower burden of coexistent lower extremity thrombosis (deep vein thrombosis [DVT]).

In response to this data, the CHEST Guidelines began cautiously providing the option for withholding therapy in patients who were diagnosed with ISSPE in 2016. Their recommendations stated that patients should be stratified for recurrence risk and have lower extremity ultrasonography performed to rule out DVT. A patient with ISSPE, a low recurrence risk, and a negative ultrasound can have anticoagulation withheld. This made perfect sense to me based on what I thought I knew at the time.

Recently published data cast doubt on my nihilism. The first prospective study designed specifically to assess the safety of withholding therapy for ISSPE suggests that this practice could be dangerous. How did this happen? The trial was very well done, and the authors enrolled the right population. All of the patients had ISSPE, low recurrence risk, and negative lower extremity ultrasound. The authors were anticipating a 1% VTE rate at 90 days based on prior data but instead found a rate of 3.1% (1.6%-6.1%). They point out that this rate is not different from those seen in patients with more proximal PE who are treated with anticoagulation. However, they acknowledge that it is higher than what’s considered acceptable and warrants therapeutic anticoagulation.

So what should we do now? We treat ISSPE, that’s what. All the arguments for withholding therapy remain valid, the recurrence rate is reasonably low, and none of the recurrent VTEs in the new study were fatal. There’s still no doubt that some patients with PE won’t benefit from anticoagulation. Unfortunately, we currently lack the tools to identify them. The risk-benefit ratio for recurrence versus bleeding will be tighter with ISSPE, particularly when there’s only one clot. Unless the bleeding risk is elevated though, the ratio still favors treatment.

Aaron B. Holley, MD, is an associate professor of medicine at Uniformed Services University and program director of pulmonary and critical care medicine at Walter Reed National Military Medical Center.

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

All else being equal, I’d prefer to do nothing. Whether this is nihilism, laziness, or experience is a matter of debate. The American College of Chest Physicians (CHEST) Guidelines on therapy for venous thromboembolism (VTE) opened a door for withholding treatment for isolated subsegmental pulmonary embolism (ISSPE) in 2016 and kept it open in 2021. I was happy to walk through it and withhold therapy if it wasn’t indicated.

ISSPE is truly a conundrum. With advances in technology, the distal vessels in the lung became visible on commercial CT a little more than 10 years ago. The subsegmental branches are located after the fourth bifurcation of the pulmonary arterial system, and the new technology offered resolution adequate to identify clot in these vessels. But the new technology told us nothing about how to manage clot isolated to the subsegmental vasculature.

Autopsy data say clot in these vessels is common, even in patients who were never diagnosed with VTE while they were alive. To some degree then, the pulmonary arterial system is thought to serve as a filter to prevent clot from crossing to the systemic circulation and causing stroke. This led some to speculate that the subsegmental pulmonary arteries are supposed to contain clot and that we simply couldn’t see it before now. If this theory is correct, the practice of providing anticoagulation for ISSPE could increase bleeding without reducing the risk for VTE recurrence.

Management studies generally supported this concept. In 2007, a trial that was published in JAMA randomized patients to two different diagnostic strategies: ventilation-perfusion (VQ) and CT. CT detected more clot than VQ did, so more anticoagulation was given in the CT arm. Yet, the VTE rate during follow-up was not significantly different between arms. The implication? Some of the clots detected by CT were of lesser clinical significance and didn’t need to be treated.

Meta-analytic data from management trials also suggested that some pulmonary emboli (PE) need not be treated. Data also show when compared with patients who have more proximal PE, those with ISSPE have lower pretest probability for VTE, are less symptomatic, and have a lower burden of coexistent lower extremity thrombosis (deep vein thrombosis [DVT]).

In response to this data, the CHEST Guidelines began cautiously providing the option for withholding therapy in patients who were diagnosed with ISSPE in 2016. Their recommendations stated that patients should be stratified for recurrence risk and have lower extremity ultrasonography performed to rule out DVT. A patient with ISSPE, a low recurrence risk, and a negative ultrasound can have anticoagulation withheld. This made perfect sense to me based on what I thought I knew at the time.

Recently published data cast doubt on my nihilism. The first prospective study designed specifically to assess the safety of withholding therapy for ISSPE suggests that this practice could be dangerous. How did this happen? The trial was very well done, and the authors enrolled the right population. All of the patients had ISSPE, low recurrence risk, and negative lower extremity ultrasound. The authors were anticipating a 1% VTE rate at 90 days based on prior data but instead found a rate of 3.1% (1.6%-6.1%). They point out that this rate is not different from those seen in patients with more proximal PE who are treated with anticoagulation. However, they acknowledge that it is higher than what’s considered acceptable and warrants therapeutic anticoagulation.

So what should we do now? We treat ISSPE, that’s what. All the arguments for withholding therapy remain valid, the recurrence rate is reasonably low, and none of the recurrent VTEs in the new study were fatal. There’s still no doubt that some patients with PE won’t benefit from anticoagulation. Unfortunately, we currently lack the tools to identify them. The risk-benefit ratio for recurrence versus bleeding will be tighter with ISSPE, particularly when there’s only one clot. Unless the bleeding risk is elevated though, the ratio still favors treatment.

Aaron B. Holley, MD, is an associate professor of medicine at Uniformed Services University and program director of pulmonary and critical care medicine at Walter Reed National Military Medical Center.

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

One clinic morning in an office visit, I stood next to the door talking, hand on the doorknob ready to exit. My elderly patient was sitting in the chair next to the door, family member in another, as I attempted my exit. Suddenly, as if looking for something, my patient locked her gaze to my abdomen and began to slowly advance herself forward, eyes squinting for a better view. She had found something. Poke, poke, poke. Three pokes in quick succession into my apparently protruding abdomen stoked an internal horror that I dared not release onto my face. How in the hell could she know? My heart sank – the signs were still there. 

“There’s something in there,” she said with a seasoned certainty.

“No there’s not,” I said trying hard to hide any emotion. 

“Yes, there is,” she said flatly. 

“Grannie, no there isn’t,” her family member interrupted, unknowingly saving me. I thanked them again and quickly left the room. 

My patient had the ongoings of slowly progressing dementia. Little did she know she was right. Maybe she had known something in another time and space. Either way, I wasn’t prepared to tell the story. She wasn’t prepared to fully understand. 

I tried to forge on to see the next patient. Tears began welling in both eyes. I tilted my head back slightly to prevent the water from falling. I wanted to feel offended, but she couldn’t have known the war my body was fighting at the time. I had not yet shared the pregnancy news with this particular patient, and yet her knowing was telling in a sense. I’m learning that the old folks always know. 

I was at work, actively having yet another miscarriage. This was the second of two. This most recent time, we found out at 9 weeks that our baby had stopped growing about a week or so earlier. Cue the denial. Cue the rage. Cue the devastation. 

Thinking back, with each pregnancy discovery, we did not wait the customary 3 months before telling anyone. Just about everyone knew. We were immediately excited to start sharing with friends, family, coworkers, and even patients early on. We knew the risks in my 40-something age group but were quintessentially optimistic. 

I am a family medicine physician with expert-level knowledge and clinical experiences in women’s health counseling, contraception, conception, and pregnancy. In my training, I’ve delivered babies, been elbow-deep searching for wayward tissue from bleeding uteri, and sutured gaping vaginal lacerations. I’ve cried with new mothers at the end of long labors. I’ve been bear-hugged by doting new fathers. I have an abundance of medical knowledge, and yet the pain and struggle of miscarriage over the past 2.5 years has twice reduced me to absolute pieces. There was no course to teach me how to navigate loss within my own body, no textbook to study so that I could test out of the experience. Life hit us dead-on, and I was broken.

I can say that the experience of a miscarriage does not get easier with each subsequent loss. At least for me, the emotions were always raw and tender. Each one was a new gash to my emotional and physical health. My sanity bled out. I was physically exhausted. The struggles of being a health care worker in the midst of a global pandemic I’m sure did not help the situation. My first miscarriage was just before the start of the pandemic. I was in New York visiting family and after dinner at Tavern on the Green, of all places, when I began showing signs. Two days later, I was at the coffee station in our clinic cafeteria adding my cream and sugar when my ob.gyn.’s office called. The hCG levels were probably too low; a miscarriage was likely. I kept my composure, walked out of the cafeteria, got my car keys, went to my car, and proceeded to scream at the top of my lungs for a few minutes. Afterward, I went back to finish up my work and canceled my clinic for the rest of the day. 

For my second miscarriage, I was laying in my doctor’s office getting an ultrasound. I had started bleeding the previous day but thought that the subchorionic hemorrhage noted on the last ultrasound might be the culprit. The bleeding was light. That’s the thing about being a pregnant physician: We know too much. The image on the screen looked abnormal, the remnants a ghost of its former self. I knew something was wrong but held out some hope. She searched and turned and pressed the transducer into my belly for a seemingly better view. She apologized for not finding the heartbeat. How is this happening again?

So how does one get through the loss of multiple pregnancies? I know my husband and I worked hard to get through each loss. We did all the right things a good therapist would recommend: Be present in the moment, go with your feelings, allow yourself to feel everything. There were no wrong emotions. Little by little we grieved and healed, grieved and healed. Having a successful pregnancy did help. Miracles are not promised but I believe we were sent one, and her name is Giavonna Barbara. Bookended by miscarriages, she has made me realize just how precious and delicate life really is. She is our absolute world and joy. 

I’ve learned twice now that men mourn differently than women. Not any less, just in a different way. There is a pain in the silence that often goes unvocalized, but it is of no less value. My husband and I allowed each other to heal in our own unique ways, and that has made all of the difference. I think I knew I was doing okay when one day I found something funny and I let out the heartiest laugh my belly could muster. A different purpose was renewed. Tears were harder to come by. Hope for the future again sprung eternal. Life went on and so did we. 

Looking back, I realize that having a miscarriage and working as a physician in the middle of a global pandemic pushed me to my emotional and physical limits. There is a second-guessing of sorts that occurs. Did the miscarriage happen because I was under so much stress at work? It had happened in the past, was this going to continue to happen? 

I can say that I was great at compartmentalizing emotions. I’d try and box them away until I got off of work and then turn them on like a switch once I hit the driver’s seat. It’s easy as a busy physician with so many patients to see, messages to return, notes to write, students and residents to teach, and programs to run to completely tune out the thought of mourning. Temporarily anyway. Work was actually a welcome distraction at times. A purpose. The journey to healing is individualized and can’t be rushed. I like to think that I heal a little bit more every day thinking about the losses and gains that I’ve had. I’m grateful for the experience and growth. 

In 2022, I’m looking forward to continuing my healing journey among the twists and turns of the pandemic. I now bring a different level of understanding and empathy to my patients who are undergoing or who have undergone a miscarriage. There will always be a piece of me that viscerally mourns with them. We have a hidden shared experience. I believe I am a better physician because of those lessons learned from my own personal tragedy. Now, I look forward to sharing big belly laughs with my family and friends and savoring the small, quiet moments with my husband and daughter. 

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

One clinic morning in an office visit, I stood next to the door talking, hand on the doorknob ready to exit. My elderly patient was sitting in the chair next to the door, family member in another, as I attempted my exit. Suddenly, as if looking for something, my patient locked her gaze to my abdomen and began to slowly advance herself forward, eyes squinting for a better view. She had found something. Poke, poke, poke. Three pokes in quick succession into my apparently protruding abdomen stoked an internal horror that I dared not release onto my face. How in the hell could she know? My heart sank – the signs were still there. 

“There’s something in there,” she said with a seasoned certainty.

“No there’s not,” I said trying hard to hide any emotion. 

“Yes, there is,” she said flatly. 

“Grannie, no there isn’t,” her family member interrupted, unknowingly saving me. I thanked them again and quickly left the room. 

My patient had the ongoings of slowly progressing dementia. Little did she know she was right. Maybe she had known something in another time and space. Either way, I wasn’t prepared to tell the story. She wasn’t prepared to fully understand. 

I tried to forge on to see the next patient. Tears began welling in both eyes. I tilted my head back slightly to prevent the water from falling. I wanted to feel offended, but she couldn’t have known the war my body was fighting at the time. I had not yet shared the pregnancy news with this particular patient, and yet her knowing was telling in a sense. I’m learning that the old folks always know. 

I was at work, actively having yet another miscarriage. This was the second of two. This most recent time, we found out at 9 weeks that our baby had stopped growing about a week or so earlier. Cue the denial. Cue the rage. Cue the devastation. 

Thinking back, with each pregnancy discovery, we did not wait the customary 3 months before telling anyone. Just about everyone knew. We were immediately excited to start sharing with friends, family, coworkers, and even patients early on. We knew the risks in my 40-something age group but were quintessentially optimistic. 

I am a family medicine physician with expert-level knowledge and clinical experiences in women’s health counseling, contraception, conception, and pregnancy. In my training, I’ve delivered babies, been elbow-deep searching for wayward tissue from bleeding uteri, and sutured gaping vaginal lacerations. I’ve cried with new mothers at the end of long labors. I’ve been bear-hugged by doting new fathers. I have an abundance of medical knowledge, and yet the pain and struggle of miscarriage over the past 2.5 years has twice reduced me to absolute pieces. There was no course to teach me how to navigate loss within my own body, no textbook to study so that I could test out of the experience. Life hit us dead-on, and I was broken.

I can say that the experience of a miscarriage does not get easier with each subsequent loss. At least for me, the emotions were always raw and tender. Each one was a new gash to my emotional and physical health. My sanity bled out. I was physically exhausted. The struggles of being a health care worker in the midst of a global pandemic I’m sure did not help the situation. My first miscarriage was just before the start of the pandemic. I was in New York visiting family and after dinner at Tavern on the Green, of all places, when I began showing signs. Two days later, I was at the coffee station in our clinic cafeteria adding my cream and sugar when my ob.gyn.’s office called. The hCG levels were probably too low; a miscarriage was likely. I kept my composure, walked out of the cafeteria, got my car keys, went to my car, and proceeded to scream at the top of my lungs for a few minutes. Afterward, I went back to finish up my work and canceled my clinic for the rest of the day. 

For my second miscarriage, I was laying in my doctor’s office getting an ultrasound. I had started bleeding the previous day but thought that the subchorionic hemorrhage noted on the last ultrasound might be the culprit. The bleeding was light. That’s the thing about being a pregnant physician: We know too much. The image on the screen looked abnormal, the remnants a ghost of its former self. I knew something was wrong but held out some hope. She searched and turned and pressed the transducer into my belly for a seemingly better view. She apologized for not finding the heartbeat. How is this happening again?

So how does one get through the loss of multiple pregnancies? I know my husband and I worked hard to get through each loss. We did all the right things a good therapist would recommend: Be present in the moment, go with your feelings, allow yourself to feel everything. There were no wrong emotions. Little by little we grieved and healed, grieved and healed. Having a successful pregnancy did help. Miracles are not promised but I believe we were sent one, and her name is Giavonna Barbara. Bookended by miscarriages, she has made me realize just how precious and delicate life really is. She is our absolute world and joy. 

I’ve learned twice now that men mourn differently than women. Not any less, just in a different way. There is a pain in the silence that often goes unvocalized, but it is of no less value. My husband and I allowed each other to heal in our own unique ways, and that has made all of the difference. I think I knew I was doing okay when one day I found something funny and I let out the heartiest laugh my belly could muster. A different purpose was renewed. Tears were harder to come by. Hope for the future again sprung eternal. Life went on and so did we. 

Looking back, I realize that having a miscarriage and working as a physician in the middle of a global pandemic pushed me to my emotional and physical limits. There is a second-guessing of sorts that occurs. Did the miscarriage happen because I was under so much stress at work? It had happened in the past, was this going to continue to happen? 

I can say that I was great at compartmentalizing emotions. I’d try and box them away until I got off of work and then turn them on like a switch once I hit the driver’s seat. It’s easy as a busy physician with so many patients to see, messages to return, notes to write, students and residents to teach, and programs to run to completely tune out the thought of mourning. Temporarily anyway. Work was actually a welcome distraction at times. A purpose. The journey to healing is individualized and can’t be rushed. I like to think that I heal a little bit more every day thinking about the losses and gains that I’ve had. I’m grateful for the experience and growth. 

In 2022, I’m looking forward to continuing my healing journey among the twists and turns of the pandemic. I now bring a different level of understanding and empathy to my patients who are undergoing or who have undergone a miscarriage. There will always be a piece of me that viscerally mourns with them. We have a hidden shared experience. I believe I am a better physician because of those lessons learned from my own personal tragedy. Now, I look forward to sharing big belly laughs with my family and friends and savoring the small, quiet moments with my husband and daughter. 

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

One clinic morning in an office visit, I stood next to the door talking, hand on the doorknob ready to exit. My elderly patient was sitting in the chair next to the door, family member in another, as I attempted my exit. Suddenly, as if looking for something, my patient locked her gaze to my abdomen and began to slowly advance herself forward, eyes squinting for a better view. She had found something. Poke, poke, poke. Three pokes in quick succession into my apparently protruding abdomen stoked an internal horror that I dared not release onto my face. How in the hell could she know? My heart sank – the signs were still there. 

“There’s something in there,” she said with a seasoned certainty.

“No there’s not,” I said trying hard to hide any emotion. 

“Yes, there is,” she said flatly. 

“Grannie, no there isn’t,” her family member interrupted, unknowingly saving me. I thanked them again and quickly left the room. 

My patient had the ongoings of slowly progressing dementia. Little did she know she was right. Maybe she had known something in another time and space. Either way, I wasn’t prepared to tell the story. She wasn’t prepared to fully understand. 

I tried to forge on to see the next patient. Tears began welling in both eyes. I tilted my head back slightly to prevent the water from falling. I wanted to feel offended, but she couldn’t have known the war my body was fighting at the time. I had not yet shared the pregnancy news with this particular patient, and yet her knowing was telling in a sense. I’m learning that the old folks always know. 

I was at work, actively having yet another miscarriage. This was the second of two. This most recent time, we found out at 9 weeks that our baby had stopped growing about a week or so earlier. Cue the denial. Cue the rage. Cue the devastation. 

Thinking back, with each pregnancy discovery, we did not wait the customary 3 months before telling anyone. Just about everyone knew. We were immediately excited to start sharing with friends, family, coworkers, and even patients early on. We knew the risks in my 40-something age group but were quintessentially optimistic. 

I am a family medicine physician with expert-level knowledge and clinical experiences in women’s health counseling, contraception, conception, and pregnancy. In my training, I’ve delivered babies, been elbow-deep searching for wayward tissue from bleeding uteri, and sutured gaping vaginal lacerations. I’ve cried with new mothers at the end of long labors. I’ve been bear-hugged by doting new fathers. I have an abundance of medical knowledge, and yet the pain and struggle of miscarriage over the past 2.5 years has twice reduced me to absolute pieces. There was no course to teach me how to navigate loss within my own body, no textbook to study so that I could test out of the experience. Life hit us dead-on, and I was broken.

I can say that the experience of a miscarriage does not get easier with each subsequent loss. At least for me, the emotions were always raw and tender. Each one was a new gash to my emotional and physical health. My sanity bled out. I was physically exhausted. The struggles of being a health care worker in the midst of a global pandemic I’m sure did not help the situation. My first miscarriage was just before the start of the pandemic. I was in New York visiting family and after dinner at Tavern on the Green, of all places, when I began showing signs. Two days later, I was at the coffee station in our clinic cafeteria adding my cream and sugar when my ob.gyn.’s office called. The hCG levels were probably too low; a miscarriage was likely. I kept my composure, walked out of the cafeteria, got my car keys, went to my car, and proceeded to scream at the top of my lungs for a few minutes. Afterward, I went back to finish up my work and canceled my clinic for the rest of the day. 

For my second miscarriage, I was laying in my doctor’s office getting an ultrasound. I had started bleeding the previous day but thought that the subchorionic hemorrhage noted on the last ultrasound might be the culprit. The bleeding was light. That’s the thing about being a pregnant physician: We know too much. The image on the screen looked abnormal, the remnants a ghost of its former self. I knew something was wrong but held out some hope. She searched and turned and pressed the transducer into my belly for a seemingly better view. She apologized for not finding the heartbeat. How is this happening again?

So how does one get through the loss of multiple pregnancies? I know my husband and I worked hard to get through each loss. We did all the right things a good therapist would recommend: Be present in the moment, go with your feelings, allow yourself to feel everything. There were no wrong emotions. Little by little we grieved and healed, grieved and healed. Having a successful pregnancy did help. Miracles are not promised but I believe we were sent one, and her name is Giavonna Barbara. Bookended by miscarriages, she has made me realize just how precious and delicate life really is. She is our absolute world and joy. 

I’ve learned twice now that men mourn differently than women. Not any less, just in a different way. There is a pain in the silence that often goes unvocalized, but it is of no less value. My husband and I allowed each other to heal in our own unique ways, and that has made all of the difference. I think I knew I was doing okay when one day I found something funny and I let out the heartiest laugh my belly could muster. A different purpose was renewed. Tears were harder to come by. Hope for the future again sprung eternal. Life went on and so did we. 

Looking back, I realize that having a miscarriage and working as a physician in the middle of a global pandemic pushed me to my emotional and physical limits. There is a second-guessing of sorts that occurs. Did the miscarriage happen because I was under so much stress at work? It had happened in the past, was this going to continue to happen? 

I can say that I was great at compartmentalizing emotions. I’d try and box them away until I got off of work and then turn them on like a switch once I hit the driver’s seat. It’s easy as a busy physician with so many patients to see, messages to return, notes to write, students and residents to teach, and programs to run to completely tune out the thought of mourning. Temporarily anyway. Work was actually a welcome distraction at times. A purpose. The journey to healing is individualized and can’t be rushed. I like to think that I heal a little bit more every day thinking about the losses and gains that I’ve had. I’m grateful for the experience and growth. 

In 2022, I’m looking forward to continuing my healing journey among the twists and turns of the pandemic. I now bring a different level of understanding and empathy to my patients who are undergoing or who have undergone a miscarriage. There will always be a piece of me that viscerally mourns with them. We have a hidden shared experience. I believe I am a better physician because of those lessons learned from my own personal tragedy. Now, I look forward to sharing big belly laughs with my family and friends and savoring the small, quiet moments with my husband and daughter. 

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

“I believe that this nation should commit itself to achieving the goal, before the decade is out, of landing a man on the Moon and returning him safely to Earth.”

President John F. Kennedy, May 25, 1961

Despite significant progress, there remain many unmet needs in psychiatry. These include a granular understanding of the neurobiology of various psychopathologies, an objective and valid diagnostic schema, and disease-modifying treatments for chronic and disabling psychiatric disorders. Several moonshots are needed to address those festering needs.

A “moonshot” is an extremely ambitious, dramatic, imaginative, and inspiring goal. Landing on the Moon was generally believed to be impossible when President Kennedy boldly set that as a goal for the United States in 1961. Yet, 8 short years later, on July 20, 1969, Neil Armstrong stepped off the lunar module ladder onto the Moon’s surface, a feat that captured the imagination of the nation and the world. I distinctly remember watching it on television with amazement as a young boy. It was a surreal experience. That’s what achieving a moonshot feels like.

Successful organizations should always have 1 or more moonshots (American Psychiatric Association and National Institute of Mental Health [NIMH], are you listening?). Setting lofty goals that require monumental determination and effort to accomplish will have a transformative, long-lasting impact. The construction of the Panama Canal to connect 2 oceans and the Manhattan Project to develop the first nuclear bomb, which ended World War II, are examples of moonshots that continue to reverberate. A more recent moonshot is the driverless car, which in the past was a laughable idea but is now a reality that will change society and the world in many ways. Innovative billionaire moguls now speak loudly about colonizing Mars, which sounds improbable and highly risky, but it’s a moonshot that may be achieved within a few years. Establishing world peace is a moonshot that requires collective Kennedy-esque vision and motivation among world leaders, which currently is sadly lacking.

So, for contemporary psychiatry, what is the equivalent of landing on the Moon? Here is the list that pops in my brain’s mind (let us know which of these would be your top 3 moonshots by taking our survey at https://bit.ly/3qkKqTa):

• A cure for schizophrenia (across positive, negative, and cognitive symptom domains)
• A cure for mood disorders, unipolar and bipolar (including suicide)
• A cure for anxiety disorders
• A cure for obsessive-compulsive disorder
• A cure for posttraumatic stress disorder
• A cure for alcoholism/addiction
• A cure for autism
• A cure for Alzheimer’s disease and other dementias
• A cure for personality disorders, especially antisocial and borderline
• A cure for the visceral hatred across political parties that permeates our society (obviously not a psychiatric category, but perhaps it should be added to DSM because it is so destructive).

Those moonshots may be regarded as absurd, and totally unachievable, but so was landing on the Moon, until it was accomplished. Psychiatry must stop thinking small and being content with tiny advances (which is like changing the chairs to more comfortable sofas on the deck of the Titanic and calling it “progress…”). Psychiatry needs to be unified under the flag of “moonshot thinking” by several visionary and transformative leaders to start believing in a miraculously better future for our patients. But to pave the way for moonshots in psychiatry, the leading organizations must collaborate closely to open the door for unprecedented scientific and medical breakthroughs of a moonshot by:

1. Lobbying effectively to secure massive funding for research from federal, state, corporate, and foundation sources (perhaps convincing the Gates Foundation that schizophrenia is as devastating worldwide as malaria may bring a few badly needed billions into psychiatric brain research).
2. Reminding members of Congress that in the United States, costs associated with psychiatric brain disorders total an estimated $700 billion annually,¹ and that this must be addressed by boosting the meager NIMH budget by at least an order of magnitude. The NIMH should disproportionately invest its resources on severe brain disorders such as schizophrenia because breakthrough advances in its neurobiology will provide unprecedented insights to the pathophysiology of other severe psychiatric brain disorders.
3. Partnering intimately with the pharmaceutical industry in a powerful public-private coalition to exploit the extensive research infrastructure of this industry.
4. Creating the necessary army of researchers (physician-scientists) by providing huge incentives to medical students and psychiatric residents to pursue careers in neuroscience research. Incentives can include paying for an individual’s entire medical education and research training, and providing generous salaries that match or exceed the income of a very successful clinical practice.
5. Convincing all psychiatric clinicians to support research by referring patients to research projects. Clinical psychiatrists are badly needed to care for the population, but they must be reminded that every treatment they are using today was a research project in the past, and that the research of today will evolve into the treatments (or cures) of tomorrow.

Pursuing lofty moonshots via innovative research is very likely to enhance serendipity and lead to unexpected discoveries along the way. As Louis Pasteur said, “chance only favors the prepared mind.”² Moonshot thinking in psychiatry today is more feasible than ever before because of the many advances in research methods (neuroimaging, pluripotent cells, optogenetics, CRISPR, etc) and complex data management technologies (big data, machine learning, artificial intelligence), each of which qualifies as a preparatory moonshot in its own right.

Given the tragic consequences of psychiatric brain disorders, it is imperative that we “think big.” Humanity expects us to do that. We must envision the future of psychiatry as dramatically different from the present. Moonshot thinking is the indispensable vehicle to take us there.

“I believe that this nation should commit itself to achieving the goal, before the decade is out, of landing a man on the Moon and returning him safely to Earth.”

President John F. Kennedy, May 25, 1961

Despite significant progress, there remain many unmet needs in psychiatry. These include a granular understanding of the neurobiology of various psychopathologies, an objective and valid diagnostic schema, and disease-modifying treatments for chronic and disabling psychiatric disorders. Several moonshots are needed to address those festering needs.

A “moonshot” is an extremely ambitious, dramatic, imaginative, and inspiring goal. Landing on the Moon was generally believed to be impossible when President Kennedy boldly set that as a goal for the United States in 1961. Yet, 8 short years later, on July 20, 1969, Neil Armstrong stepped off the lunar module ladder onto the Moon’s surface, a feat that captured the imagination of the nation and the world. I distinctly remember watching it on television with amazement as a young boy. It was a surreal experience. That’s what achieving a moonshot feels like.

Successful organizations should always have 1 or more moonshots (American Psychiatric Association and National Institute of Mental Health [NIMH], are you listening?). Setting lofty goals that require monumental determination and effort to accomplish will have a transformative, long-lasting impact. The construction of the Panama Canal to connect 2 oceans and the Manhattan Project to develop the first nuclear bomb, which ended World War II, are examples of moonshots that continue to reverberate. A more recent moonshot is the driverless car, which in the past was a laughable idea but is now a reality that will change society and the world in many ways. Innovative billionaire moguls now speak loudly about colonizing Mars, which sounds improbable and highly risky, but it’s a moonshot that may be achieved within a few years. Establishing world peace is a moonshot that requires collective Kennedy-esque vision and motivation among world leaders, which currently is sadly lacking.

So, for contemporary psychiatry, what is the equivalent of landing on the Moon? Here is the list that pops in my brain’s mind (let us know which of these would be your top 3 moonshots by taking our survey at https://bit.ly/3qkKqTa):

• A cure for schizophrenia (across positive, negative, and cognitive symptom domains)
• A cure for mood disorders, unipolar and bipolar (including suicide)
• A cure for anxiety disorders
• A cure for obsessive-compulsive disorder
• A cure for posttraumatic stress disorder
• A cure for alcoholism/addiction
• A cure for autism
• A cure for Alzheimer’s disease and other dementias
• A cure for personality disorders, especially antisocial and borderline
• A cure for the visceral hatred across political parties that permeates our society (obviously not a psychiatric category, but perhaps it should be added to DSM because it is so destructive).

Those moonshots may be regarded as absurd, and totally unachievable, but so was landing on the Moon, until it was accomplished. Psychiatry must stop thinking small and being content with tiny advances (which is like changing the chairs to more comfortable sofas on the deck of the Titanic and calling it “progress…”). Psychiatry needs to be unified under the flag of “moonshot thinking” by several visionary and transformative leaders to start believing in a miraculously better future for our patients. But to pave the way for moonshots in psychiatry, the leading organizations must collaborate closely to open the door for unprecedented scientific and medical breakthroughs of a moonshot by:

1. Lobbying effectively to secure massive funding for research from federal, state, corporate, and foundation sources (perhaps convincing the Gates Foundation that schizophrenia is as devastating worldwide as malaria may bring a few badly needed billions into psychiatric brain research).
2. Reminding members of Congress that in the United States, costs associated with psychiatric brain disorders total an estimated $700 billion annually,¹ and that this must be addressed by boosting the meager NIMH budget by at least an order of magnitude. The NIMH should disproportionately invest its resources on severe brain disorders such as schizophrenia because breakthrough advances in its neurobiology will provide unprecedented insights to the pathophysiology of other severe psychiatric brain disorders.
3. Partnering intimately with the pharmaceutical industry in a powerful public-private coalition to exploit the extensive research infrastructure of this industry.
4. Creating the necessary army of researchers (physician-scientists) by providing huge incentives to medical students and psychiatric residents to pursue careers in neuroscience research. Incentives can include paying for an individual’s entire medical education and research training, and providing generous salaries that match or exceed the income of a very successful clinical practice.
5. Convincing all psychiatric clinicians to support research by referring patients to research projects. Clinical psychiatrists are badly needed to care for the population, but they must be reminded that every treatment they are using today was a research project in the past, and that the research of today will evolve into the treatments (or cures) of tomorrow.

Pursuing lofty moonshots via innovative research is very likely to enhance serendipity and lead to unexpected discoveries along the way. As Louis Pasteur said, “chance only favors the prepared mind.”² Moonshot thinking in psychiatry today is more feasible than ever before because of the many advances in research methods (neuroimaging, pluripotent cells, optogenetics, CRISPR, etc) and complex data management technologies (big data, machine learning, artificial intelligence), each of which qualifies as a preparatory moonshot in its own right.

Given the tragic consequences of psychiatric brain disorders, it is imperative that we “think big.” Humanity expects us to do that. We must envision the future of psychiatry as dramatically different from the present. Moonshot thinking is the indispensable vehicle to take us there.

“I believe that this nation should commit itself to achieving the goal, before the decade is out, of landing a man on the Moon and returning him safely to Earth.”

President John F. Kennedy, May 25, 1961

Despite significant progress, there remain many unmet needs in psychiatry. These include a granular understanding of the neurobiology of various psychopathologies, an objective and valid diagnostic schema, and disease-modifying treatments for chronic and disabling psychiatric disorders. Several moonshots are needed to address those festering needs.

A “moonshot” is an extremely ambitious, dramatic, imaginative, and inspiring goal. Landing on the Moon was generally believed to be impossible when President Kennedy boldly set that as a goal for the United States in 1961. Yet, 8 short years later, on July 20, 1969, Neil Armstrong stepped off the lunar module ladder onto the Moon’s surface, a feat that captured the imagination of the nation and the world. I distinctly remember watching it on television with amazement as a young boy. It was a surreal experience. That’s what achieving a moonshot feels like.

Successful organizations should always have 1 or more moonshots (American Psychiatric Association and National Institute of Mental Health [NIMH], are you listening?). Setting lofty goals that require monumental determination and effort to accomplish will have a transformative, long-lasting impact. The construction of the Panama Canal to connect 2 oceans and the Manhattan Project to develop the first nuclear bomb, which ended World War II, are examples of moonshots that continue to reverberate. A more recent moonshot is the driverless car, which in the past was a laughable idea but is now a reality that will change society and the world in many ways. Innovative billionaire moguls now speak loudly about colonizing Mars, which sounds improbable and highly risky, but it’s a moonshot that may be achieved within a few years. Establishing world peace is a moonshot that requires collective Kennedy-esque vision and motivation among world leaders, which currently is sadly lacking.

So, for contemporary psychiatry, what is the equivalent of landing on the Moon? Here is the list that pops in my brain’s mind (let us know which of these would be your top 3 moonshots by taking our survey at https://bit.ly/3qkKqTa):

• A cure for schizophrenia (across positive, negative, and cognitive symptom domains)
• A cure for mood disorders, unipolar and bipolar (including suicide)
• A cure for anxiety disorders
• A cure for obsessive-compulsive disorder
• A cure for posttraumatic stress disorder
• A cure for alcoholism/addiction
• A cure for autism
• A cure for Alzheimer’s disease and other dementias
• A cure for personality disorders, especially antisocial and borderline
• A cure for the visceral hatred across political parties that permeates our society (obviously not a psychiatric category, but perhaps it should be added to DSM because it is so destructive).

Those moonshots may be regarded as absurd, and totally unachievable, but so was landing on the Moon, until it was accomplished. Psychiatry must stop thinking small and being content with tiny advances (which is like changing the chairs to more comfortable sofas on the deck of the Titanic and calling it “progress…”). Psychiatry needs to be unified under the flag of “moonshot thinking” by several visionary and transformative leaders to start believing in a miraculously better future for our patients. But to pave the way for moonshots in psychiatry, the leading organizations must collaborate closely to open the door for unprecedented scientific and medical breakthroughs of a moonshot by:

1. Lobbying effectively to secure massive funding for research from federal, state, corporate, and foundation sources (perhaps convincing the Gates Foundation that schizophrenia is as devastating worldwide as malaria may bring a few badly needed billions into psychiatric brain research).
2. Reminding members of Congress that in the United States, costs associated with psychiatric brain disorders total an estimated $700 billion annually,¹ and that this must be addressed by boosting the meager NIMH budget by at least an order of magnitude. The NIMH should disproportionately invest its resources on severe brain disorders such as schizophrenia because breakthrough advances in its neurobiology will provide unprecedented insights to the pathophysiology of other severe psychiatric brain disorders.
3. Partnering intimately with the pharmaceutical industry in a powerful public-private coalition to exploit the extensive research infrastructure of this industry.
4. Creating the necessary army of researchers (physician-scientists) by providing huge incentives to medical students and psychiatric residents to pursue careers in neuroscience research. Incentives can include paying for an individual’s entire medical education and research training, and providing generous salaries that match or exceed the income of a very successful clinical practice.
5. Convincing all psychiatric clinicians to support research by referring patients to research projects. Clinical psychiatrists are badly needed to care for the population, but they must be reminded that every treatment they are using today was a research project in the past, and that the research of today will evolve into the treatments (or cures) of tomorrow.

Pursuing lofty moonshots via innovative research is very likely to enhance serendipity and lead to unexpected discoveries along the way. As Louis Pasteur said, “chance only favors the prepared mind.”² Moonshot thinking in psychiatry today is more feasible than ever before because of the many advances in research methods (neuroimaging, pluripotent cells, optogenetics, CRISPR, etc) and complex data management technologies (big data, machine learning, artificial intelligence), each of which qualifies as a preparatory moonshot in its own right.

Given the tragic consequences of psychiatric brain disorders, it is imperative that we “think big.” Humanity expects us to do that. We must envision the future of psychiatry as dramatically different from the present. Moonshot thinking is the indispensable vehicle to take us there.

February is National Cancer Prevention Month. With approximately 4.8 million new cases and 3.4 million deaths worldwide annually, GI cancers represent roughly a quarter of the global cancer incidence and over a third of all cancer-related deaths, according to one study.

In this month’s issue of GI & Hepatology News, we feature timely content relevant to prevention and early detection of GI cancers, which remains a central focus of our clinical and endoscopic practice as gastroenterologists. This includes important studies that demonstrate the value of upper endoscopy in reducing GI cancer mortality, illustrate the potential promise of artificial intelligence in improving early detection of gastric cancer, and link adenoma detection rate to long-term survival in patients who undergo CRC screening with flexible sigmoidoscopy. We also report on a focused update from the U.S. Multi-Society Task Force on colorectal cancer, which thoughtfully reviews the data supporting a shift in the age of initiation of average-risk CRC screening from 50 to 45 years.

On the policy front, AGA and its partners have worked tirelessly for many years to eliminate financial barriers to colorectal cancer (CRC) screening through national advocacy efforts. These efforts resulted in closure of the so-called Medicare “colonoscopy loophole” through legislation included in the COVID-19 relief bill – as a result, out-of-pocket costs for patients undergoing a screening colonoscopy that results in polypectomy are disallowed as of January 2022. The Biden Administration recently issued guidance in January in response to multisociety advocacy efforts: Private insurers must provide coverage without cost sharing for a follow-up colonoscopy after a positive stool-based CRC screening test for plan or policy years starting on or after May 31, 2022. Removing these financial barriers to care is particularly critical to efforts to improve CRC screening rates among medically underserved communities.

These achievements highlight the power of physician advocacy in inspiring policy changes that directly improve the health and well-being of our patients. I encourage you to visit the AGA website to learn how you can contribute to ongoing advocacy efforts.

Megan A. Adams, MD, JD, MSc
Editor in Chief

February is National Cancer Prevention Month. With approximately 4.8 million new cases and 3.4 million deaths worldwide annually, GI cancers represent roughly a quarter of the global cancer incidence and over a third of all cancer-related deaths, according to one study.

In this month’s issue of GI & Hepatology News, we feature timely content relevant to prevention and early detection of GI cancers, which remains a central focus of our clinical and endoscopic practice as gastroenterologists. This includes important studies that demonstrate the value of upper endoscopy in reducing GI cancer mortality, illustrate the potential promise of artificial intelligence in improving early detection of gastric cancer, and link adenoma detection rate to long-term survival in patients who undergo CRC screening with flexible sigmoidoscopy. We also report on a focused update from the U.S. Multi-Society Task Force on colorectal cancer, which thoughtfully reviews the data supporting a shift in the age of initiation of average-risk CRC screening from 50 to 45 years.

On the policy front, AGA and its partners have worked tirelessly for many years to eliminate financial barriers to colorectal cancer (CRC) screening through national advocacy efforts. These efforts resulted in closure of the so-called Medicare “colonoscopy loophole” through legislation included in the COVID-19 relief bill – as a result, out-of-pocket costs for patients undergoing a screening colonoscopy that results in polypectomy are disallowed as of January 2022. The Biden Administration recently issued guidance in January in response to multisociety advocacy efforts: Private insurers must provide coverage without cost sharing for a follow-up colonoscopy after a positive stool-based CRC screening test for plan or policy years starting on or after May 31, 2022. Removing these financial barriers to care is particularly critical to efforts to improve CRC screening rates among medically underserved communities.

These achievements highlight the power of physician advocacy in inspiring policy changes that directly improve the health and well-being of our patients. I encourage you to visit the AGA website to learn how you can contribute to ongoing advocacy efforts.

Megan A. Adams, MD, JD, MSc
Editor in Chief

February is National Cancer Prevention Month. With approximately 4.8 million new cases and 3.4 million deaths worldwide annually, GI cancers represent roughly a quarter of the global cancer incidence and over a third of all cancer-related deaths, according to one study.

In this month’s issue of GI & Hepatology News, we feature timely content relevant to prevention and early detection of GI cancers, which remains a central focus of our clinical and endoscopic practice as gastroenterologists. This includes important studies that demonstrate the value of upper endoscopy in reducing GI cancer mortality, illustrate the potential promise of artificial intelligence in improving early detection of gastric cancer, and link adenoma detection rate to long-term survival in patients who undergo CRC screening with flexible sigmoidoscopy. We also report on a focused update from the U.S. Multi-Society Task Force on colorectal cancer, which thoughtfully reviews the data supporting a shift in the age of initiation of average-risk CRC screening from 50 to 45 years.

On the policy front, AGA and its partners have worked tirelessly for many years to eliminate financial barriers to colorectal cancer (CRC) screening through national advocacy efforts. These efforts resulted in closure of the so-called Medicare “colonoscopy loophole” through legislation included in the COVID-19 relief bill – as a result, out-of-pocket costs for patients undergoing a screening colonoscopy that results in polypectomy are disallowed as of January 2022. The Biden Administration recently issued guidance in January in response to multisociety advocacy efforts: Private insurers must provide coverage without cost sharing for a follow-up colonoscopy after a positive stool-based CRC screening test for plan or policy years starting on or after May 31, 2022. Removing these financial barriers to care is particularly critical to efforts to improve CRC screening rates among medically underserved communities.

These achievements highlight the power of physician advocacy in inspiring policy changes that directly improve the health and well-being of our patients. I encourage you to visit the AGA website to learn how you can contribute to ongoing advocacy efforts.

Megan A. Adams, MD, JD, MSc
Editor in Chief

I’m in a crowded commercial kitchen, and everywhere I look I see bottles of colorful drinks and jars holding faded vegetables suspended in brine. The smell of fermented cabbage permeates the room. I open a mason jar, which lets out a loud hiss. I’d spent months researching the gut-brain axis during my PhD, hoping to understand the role that fermented food may play in our mental health. So I enrolled in a class on how to make fermented foods.

The teacher is praising these ancient foods as a magical cure for every ailment you can imagine. I’m uncomfortable – not because of the smell, but because I’ve never found a scientific article that definitively supported this idea. I’m subconsciously applying a fact filter and wondering what the other unsuspecting students must think. I let this slide, since I’m here to learn the art of fermentation. I bravely take a spoonful of sauerkraut. The salty brine overwhelms my senses. Gulp!

If you’ve ever eaten sauerkraut, kimchi, tempeh, kombucha, or kefir, then you’ve had a fermented food (or drink). The first time I gave them a proper go (with a mind open to enjoying them), I noticed the sour, vinegar-like taste and the noticeable absence of sugar. It didn’t take me long to get used to the taste. After a while of drinking my bubbly kombucha, I noticed that my palate had adapted and sweet flavors felt overpowering.

Fermentation is a natural process of curdling or culturing that has been used for thousands of years to preserve foods. Fermented foods and drinks are made through “desired microbial growth and enzymatic conversions of food components” (as opposed to undesirable microbial growth, which happens when your food spoils). Fermented foods are made either by the bacteria and yeast already present in the environment/food material or by introducing bacteria or yeast to help start the fermentation process.

For example, when I made sauerkraut, I shredded the cabbage, added salt, then pummeled and squeezed the cabbage until it released its own juices, which also allowed the “probiotic” lactic acid bacteria in the cabbage to kickstart the fermentation process. Probiotic bacteria like Lactobacillus and Bifidobacterium are considered probiotic good bugs, and are also present in many yogurts and cheeses.

We can’t necessarily call our sauerkraut a “probiotic food” because we don’t know the exact probiotic strains that are in our sauerkraut and whether they are present in the correct “probiotic” dose. It’s also worth noting that foods and drinks that are produced by fermentation don’t necessarily need to have live bacteria in them when you eat them to still be considered a fermented food. For example, sourdough is born from a bubbly live starter culture that contains yeast and bacteria, but once cooked it might no longer have any live bacteria in it.

So, what about the health claims?

Microbial fermentation may interact with health through multiple different biological pathways. It can enhance the nutritional composition of the final food, create bioactive compounds, and change the composition of the gut microbiota (potentially outcompeting harmful pathogens). The lactic acid bacteria in fermented food might also help to influence your immune system and strengthen your intestinal barrier. Some fermented foods, like tempeh, also contain prebiotics; these are fibers that escape your digestion and are broken down by your gut bacteria, including your lactic acid bacteria, which feed off prebiotic fiber to help grow their colonies. In a recent diet experiment, a high-fiber diet was compared with a diet high in fermented foods (eg, yogurt, fermented vegetables, kefir, fermented cheese); those who ate higher fermented food had lower markers of inflammation and an increased diversity of gut microbiota (which is thought to be a good thing in adults). So, in theory, fermented foods sound good.

Still wanting to understand more, and dispel a few myths, a team of researchers and I investigated what’s known about the link between fermented foods and mental health. We looked at the pathways by which fermented foods might affect mental health, such as by reducing inflammation and strengthening the intestinal barrier. These pathways are relevant because they might reduce your brain’s exposure to certain inflammatory molecules that can impact brain function and mental health.

Fermented foods also contain neurotransmitters that are important to mental health. Research about fermented food and mental health is still in its early infancy. Animal studies provide experimental evidence that fermented foods can help with symptoms of depression and anxiety – but that’s in animals. The problem is in knowing how the animal findings relate to our human experience.

We found eight studies in humans that experimented with fermented foods (for example, fermented milk products) to measure their impact on depression, anxiety, and stress in adults, but the studies were all so different that we were unable to make firm conclusions. It is still difficult to know what the active ingredient in fermented foods is. Is it the microbes? Is it the byproducts? Is it the nutrition? And how much of each is needed, and what are safe levels of each? We really need more studies, with detailed descriptions of exactly what is in each food being tested. At this stage, there is not enough human evidence to make firm clinical recommendations for eating fermented food to improve mental health symptoms.

I’ve since moved on from sauerkraut to making sourdough bread as a COVID lockdown project (as this involves a fermented starter culture). When my delicious fresh bread comes out of the oven, my world is paused for a few minutes, and my family mill around to enjoy the warm, fresh bread. While it may be too soon to tell whether fermented foods help our mental health, my sourdough itself has sure helped us.

Dr. Dawson is a nutritionist and bioinformatician research fellow at the Food & Mood Centre at Deakin University, Geelong, Australia. She disclosed no relevant financial relationships.

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

I’m in a crowded commercial kitchen, and everywhere I look I see bottles of colorful drinks and jars holding faded vegetables suspended in brine. The smell of fermented cabbage permeates the room. I open a mason jar, which lets out a loud hiss. I’d spent months researching the gut-brain axis during my PhD, hoping to understand the role that fermented food may play in our mental health. So I enrolled in a class on how to make fermented foods.

The teacher is praising these ancient foods as a magical cure for every ailment you can imagine. I’m uncomfortable – not because of the smell, but because I’ve never found a scientific article that definitively supported this idea. I’m subconsciously applying a fact filter and wondering what the other unsuspecting students must think. I let this slide, since I’m here to learn the art of fermentation. I bravely take a spoonful of sauerkraut. The salty brine overwhelms my senses. Gulp!

If you’ve ever eaten sauerkraut, kimchi, tempeh, kombucha, or kefir, then you’ve had a fermented food (or drink). The first time I gave them a proper go (with a mind open to enjoying them), I noticed the sour, vinegar-like taste and the noticeable absence of sugar. It didn’t take me long to get used to the taste. After a while of drinking my bubbly kombucha, I noticed that my palate had adapted and sweet flavors felt overpowering.

Fermentation is a natural process of curdling or culturing that has been used for thousands of years to preserve foods. Fermented foods and drinks are made through “desired microbial growth and enzymatic conversions of food components” (as opposed to undesirable microbial growth, which happens when your food spoils). Fermented foods are made either by the bacteria and yeast already present in the environment/food material or by introducing bacteria or yeast to help start the fermentation process.

For example, when I made sauerkraut, I shredded the cabbage, added salt, then pummeled and squeezed the cabbage until it released its own juices, which also allowed the “probiotic” lactic acid bacteria in the cabbage to kickstart the fermentation process. Probiotic bacteria like Lactobacillus and Bifidobacterium are considered probiotic good bugs, and are also present in many yogurts and cheeses.

We can’t necessarily call our sauerkraut a “probiotic food” because we don’t know the exact probiotic strains that are in our sauerkraut and whether they are present in the correct “probiotic” dose. It’s also worth noting that foods and drinks that are produced by fermentation don’t necessarily need to have live bacteria in them when you eat them to still be considered a fermented food. For example, sourdough is born from a bubbly live starter culture that contains yeast and bacteria, but once cooked it might no longer have any live bacteria in it.

So, what about the health claims?

Microbial fermentation may interact with health through multiple different biological pathways. It can enhance the nutritional composition of the final food, create bioactive compounds, and change the composition of the gut microbiota (potentially outcompeting harmful pathogens). The lactic acid bacteria in fermented food might also help to influence your immune system and strengthen your intestinal barrier. Some fermented foods, like tempeh, also contain prebiotics; these are fibers that escape your digestion and are broken down by your gut bacteria, including your lactic acid bacteria, which feed off prebiotic fiber to help grow their colonies. In a recent diet experiment, a high-fiber diet was compared with a diet high in fermented foods (eg, yogurt, fermented vegetables, kefir, fermented cheese); those who ate higher fermented food had lower markers of inflammation and an increased diversity of gut microbiota (which is thought to be a good thing in adults). So, in theory, fermented foods sound good.

Still wanting to understand more, and dispel a few myths, a team of researchers and I investigated what’s known about the link between fermented foods and mental health. We looked at the pathways by which fermented foods might affect mental health, such as by reducing inflammation and strengthening the intestinal barrier. These pathways are relevant because they might reduce your brain’s exposure to certain inflammatory molecules that can impact brain function and mental health.

Fermented foods also contain neurotransmitters that are important to mental health. Research about fermented food and mental health is still in its early infancy. Animal studies provide experimental evidence that fermented foods can help with symptoms of depression and anxiety – but that’s in animals. The problem is in knowing how the animal findings relate to our human experience.

We found eight studies in humans that experimented with fermented foods (for example, fermented milk products) to measure their impact on depression, anxiety, and stress in adults, but the studies were all so different that we were unable to make firm conclusions. It is still difficult to know what the active ingredient in fermented foods is. Is it the microbes? Is it the byproducts? Is it the nutrition? And how much of each is needed, and what are safe levels of each? We really need more studies, with detailed descriptions of exactly what is in each food being tested. At this stage, there is not enough human evidence to make firm clinical recommendations for eating fermented food to improve mental health symptoms.

I’ve since moved on from sauerkraut to making sourdough bread as a COVID lockdown project (as this involves a fermented starter culture). When my delicious fresh bread comes out of the oven, my world is paused for a few minutes, and my family mill around to enjoy the warm, fresh bread. While it may be too soon to tell whether fermented foods help our mental health, my sourdough itself has sure helped us.

Dr. Dawson is a nutritionist and bioinformatician research fellow at the Food & Mood Centre at Deakin University, Geelong, Australia. She disclosed no relevant financial relationships.

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

I’m in a crowded commercial kitchen, and everywhere I look I see bottles of colorful drinks and jars holding faded vegetables suspended in brine. The smell of fermented cabbage permeates the room. I open a mason jar, which lets out a loud hiss. I’d spent months researching the gut-brain axis during my PhD, hoping to understand the role that fermented food may play in our mental health. So I enrolled in a class on how to make fermented foods.

The teacher is praising these ancient foods as a magical cure for every ailment you can imagine. I’m uncomfortable – not because of the smell, but because I’ve never found a scientific article that definitively supported this idea. I’m subconsciously applying a fact filter and wondering what the other unsuspecting students must think. I let this slide, since I’m here to learn the art of fermentation. I bravely take a spoonful of sauerkraut. The salty brine overwhelms my senses. Gulp!

If you’ve ever eaten sauerkraut, kimchi, tempeh, kombucha, or kefir, then you’ve had a fermented food (or drink). The first time I gave them a proper go (with a mind open to enjoying them), I noticed the sour, vinegar-like taste and the noticeable absence of sugar. It didn’t take me long to get used to the taste. After a while of drinking my bubbly kombucha, I noticed that my palate had adapted and sweet flavors felt overpowering.

Fermentation is a natural process of curdling or culturing that has been used for thousands of years to preserve foods. Fermented foods and drinks are made through “desired microbial growth and enzymatic conversions of food components” (as opposed to undesirable microbial growth, which happens when your food spoils). Fermented foods are made either by the bacteria and yeast already present in the environment/food material or by introducing bacteria or yeast to help start the fermentation process.

For example, when I made sauerkraut, I shredded the cabbage, added salt, then pummeled and squeezed the cabbage until it released its own juices, which also allowed the “probiotic” lactic acid bacteria in the cabbage to kickstart the fermentation process. Probiotic bacteria like Lactobacillus and Bifidobacterium are considered probiotic good bugs, and are also present in many yogurts and cheeses.

We can’t necessarily call our sauerkraut a “probiotic food” because we don’t know the exact probiotic strains that are in our sauerkraut and whether they are present in the correct “probiotic” dose. It’s also worth noting that foods and drinks that are produced by fermentation don’t necessarily need to have live bacteria in them when you eat them to still be considered a fermented food. For example, sourdough is born from a bubbly live starter culture that contains yeast and bacteria, but once cooked it might no longer have any live bacteria in it.

So, what about the health claims?

Microbial fermentation may interact with health through multiple different biological pathways. It can enhance the nutritional composition of the final food, create bioactive compounds, and change the composition of the gut microbiota (potentially outcompeting harmful pathogens). The lactic acid bacteria in fermented food might also help to influence your immune system and strengthen your intestinal barrier. Some fermented foods, like tempeh, also contain prebiotics; these are fibers that escape your digestion and are broken down by your gut bacteria, including your lactic acid bacteria, which feed off prebiotic fiber to help grow their colonies. In a recent diet experiment, a high-fiber diet was compared with a diet high in fermented foods (eg, yogurt, fermented vegetables, kefir, fermented cheese); those who ate higher fermented food had lower markers of inflammation and an increased diversity of gut microbiota (which is thought to be a good thing in adults). So, in theory, fermented foods sound good.

Still wanting to understand more, and dispel a few myths, a team of researchers and I investigated what’s known about the link between fermented foods and mental health. We looked at the pathways by which fermented foods might affect mental health, such as by reducing inflammation and strengthening the intestinal barrier. These pathways are relevant because they might reduce your brain’s exposure to certain inflammatory molecules that can impact brain function and mental health.

Fermented foods also contain neurotransmitters that are important to mental health. Research about fermented food and mental health is still in its early infancy. Animal studies provide experimental evidence that fermented foods can help with symptoms of depression and anxiety – but that’s in animals. The problem is in knowing how the animal findings relate to our human experience.

We found eight studies in humans that experimented with fermented foods (for example, fermented milk products) to measure their impact on depression, anxiety, and stress in adults, but the studies were all so different that we were unable to make firm conclusions. It is still difficult to know what the active ingredient in fermented foods is. Is it the microbes? Is it the byproducts? Is it the nutrition? And how much of each is needed, and what are safe levels of each? We really need more studies, with detailed descriptions of exactly what is in each food being tested. At this stage, there is not enough human evidence to make firm clinical recommendations for eating fermented food to improve mental health symptoms.

I’ve since moved on from sauerkraut to making sourdough bread as a COVID lockdown project (as this involves a fermented starter culture). When my delicious fresh bread comes out of the oven, my world is paused for a few minutes, and my family mill around to enjoy the warm, fresh bread. While it may be too soon to tell whether fermented foods help our mental health, my sourdough itself has sure helped us.

Dr. Dawson is a nutritionist and bioinformatician research fellow at the Food & Mood Centre at Deakin University, Geelong, Australia. She disclosed no relevant financial relationships.

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

When 2021 began, there appeared to be light at the end of the long and dark COVID-19 pandemic. A vaccine was introduced, the “curve” had been flattened, and by spring, businesses were slowly starting to open. Whereas the medical literature of 2020 seemed to be almost entirely focused on COVID-19, medical writers, researchers, and educators seemed to slowly start turning more attention back to non–COVID-related topics in 2021.

Unfortunately, as I write this, the Omicron variant of the coronavirus is in full swing, and much of our attention has once again turned back to COVID-19. However, we are able to look back on 2021 and acknowledge a wealth of fantastic original research articles and guidelines which have improved patient care in many ways. In this annual recap of my favorite articles of the past year, I will focus on what I believe every acute care physician should read and know, as they will improve patient care.

Specifically, I have chosen articles that did not appear to gain widespread notoriety in emergency medicine but are, nevertheless, worthy of your time and attention. Note that this write-up serves as a summary only, and I encourage interested readers to peruse the full manuscripts for further details. I am limiting my recap to two articles.
 

Recommendations on difficult airway management

Emergency physicians are well trained in airway management, and a major part of that training includes the preintubation anatomic assessment of the airway. However, there are few recommendations on the physiological considerations for airway management.

A set of recommendations from the Society for Airway Management was written primarily with anesthesiologists in mind, but many of the recommendations listed below are very relevant to emergency physicians as well. The authors make recommendations for patients who are hypoxic or hypotensive prior to induction, for patients with right ventricular dysfunction, for patients with severe metabolic acidosis, and for neurologically injured patients. Some of the key pearls follow.
 

Patients with hypoxemia

• The importance of preoxygenation before intubation is once again emphasized, and this can be performed using high-flow oxygen for at least 3 minutes, or (in a cooperative patient) with eight vital capacity breaths.
• Maintenance of oxygenation during the apneic period should be continued. Apneic oxygenation can be provided with a nasal cannula at 15 liters per minute or with a high-flow nasal oxygen system at 40-70 LPM.
• For patients with significant shunt physiology or reduced functional residual capacity (for example, late pregnancy, obesity, or acute respiratory distress syndrome), preoxygenation should be performed with positive end expiratory pressure (PEEP) using noninvasive positive pressure ventilation or bag-valve mask ventilation with a PEEP valve. When higher levels of PEEP are required, an extraglottic device should be considered during preoxygenation.
• For patients with refractory hypoxemia, awake intubation to maintain spontaneous respirations should be considered.
• Patients should be preoxygenated in the upright position when possible.
• Ramped-up position (head elevated so as to bring the external auditory canal in the same horizontal line as the sternal notch) should be performed when possible in order to improve the grade of view, improve oxygenation, and reduce aspiration.

Patients with hypotension

• Patients should be screened for high risk for hemodynamic collapse prior to administration of induction medications and intubation by assessing the stroke index. A stroke index greater than 0.7 predicts a high risk. These patients should receive hemodynamic optimization (for example, intravenous fluids, administration of vasopressors) whenever possible, prior to administration of induction medications and intubation.
• Vasopressor infusions are preferable to bolus-dosed vasopressors. However, if vasopressor infusions are not possible, bolus-dosed vasopressors should be available and used to maintain systemic pressure during and after the intubation until an infusion can be started. When bolus-dosed vasopressors are used, diluted epinephrine should be considered as the vasopressor of choice in patients with depressed myocardial function.

Patients with right ventricular (RV) dysfunction

• Patients should be screened for significant RV dysfunction prior to intubation because of their high risk for hemodynamic decompensation with positive pressure ventilation.
• RV dysfunction may sometimes worsen with fluid administration. Fluid-intolerant patients may instead need RV afterload reduction with inhaled or intravenous pulmonary vasodilators.
• Patients with RV failure–induced shock should be considered for preintubation extracorporeal membrane oxygenation if available.
• Patients with RV volume overload should receive diuresis prior to intubation.
• Ventilator settings should aim to avoid hypercapnia, maintain low airway pressures, and use a higher PEEP to avoid atelectasis.

Patients with severe metabolic acidosis

• Patients with severe metabolic acidosis are at high risk for decompensation after intubation because of volume depletion and inadequate alveolar ventilation, resulting in profound acidosis.
• Patients with high minute ventilation prior to intubation should be considered for awake intubation to maintain spontaneous respirations. Otherwise, consider a spontaneous breathing mode after intubation with a high minute ventilation (that is, use a higher-than-normal respiratory rate on the ventilator in order to reproduce the preintubation minute ventilation). Apnea time should be minimized in order to minimize worsening acidosis.
• Preintubation bicarbonate boluses to prevent worsening acidosis are controversial and lack data showing any benefit.

Neurologically injured patients

• Eucapnia and normoxia should be maintained before, during, and after intubation to maintain stable cerebral blood flow.
• Hemodynamically neutral induction agents should be used.
• Patients should be positioned with the head of bed elevated to 30° upright when possible.
• Limit PEEP post intubation in order to promote venous drainage.

Evidence update for the treatment of anaphylaxis

The treatment of anaphylaxis is considered bread and butter in emergency and acute care medicine, but a great deal of what we have learned over the years is not well supported by the literature. In an article published in Resuscitation, the Anaphylaxis Working Group of the Resuscitation Council of the United Kingdom performed an evidence review regarding the emergency treatment of anaphylaxis.

A summary of key points includes:

• Anaphylaxis is defined as a systemic hypersensitivity reaction, usually rapid in onset, with potentially life-threatening compromise in airway, breathing, and/or circulation.
• The most important treatment is epinephrine (EPI), with an initial recommended dose in adults of 0.5 mg administered via the intramuscular (IM) route. Up to 10% of patients have a suboptimal response to one dose, but 98% will respond by the third dose; therefore, these authors recommend repeating the IM EPI every 5 minutes, if needed, up to three doses. There is no evidence to support any alternative or additional vasopressors, and so they should only be used if EPI is ineffective. Intravenous EPI is not recommended initially except in the perioperative setting where close monitoring can be performed. If intravenous EPI is used, the authors recommend an intravenous infusion rather than bolus dosing.
• Intravenous fluid bolus dosing is recommended in the majority of cases of anaphylaxis, regardless of presence or absence of hemodynamic compromise, because of the profound reduction in venous tone and third-spacing that typically occurs.
• Antihistamines are not recommended in early treatment. They are only effective for reversing skin manifestations of anaphylaxis (which EPI treats as well), and the sedation they produce can confound the proper ongoing evaluation of the patient. Furthermore, the use of antihistamines early in the treatment of anaphylaxis has been found to produce delays in proper use of EPI.
• Steroids are not recommended in early treatment. They help only with the late phase of inflammatory response, but despite that, there is no good evidence that they decrease the biphasic response of anaphylaxis. There is some emerging evidence that the use of steroids may actually be associated with increased morbidity even after correcting for anaphylaxis severity. The authors recommended the use of steroids in anaphylaxis only for patients with poorly controlled asthma and possibly for patients with refractory anaphylaxis. Inhaled beta-agonists are recommended in anaphylaxis only for patients with lower respiratory tract symptoms caused by anaphylaxis, but warned that the inhaled beta-agonists should not delay proper use of EPI.
• The optimal observation period before discharge for stable patients is unknown. The authors noted the recommendations of the Joint Task Force on Practice Parameters of the American Academy of Allergy, Asthma, & Immunology and the American College of Allergy, Asthma, and Immunology: Biphasic reactions were more common in patients with severe initial symptoms – for example, those requiring more than one dose of EPI; therefore, these patients are recommended to have “extended observation.” Lower-risk patients with resolved symptoms of anaphylaxis can be observed for 1 hour, which would capture 95% of biphasic reactions in this group of patients.

Summary and other honorable mentions

There you have it. My two favorite practice-changing (non–COVID-19) articles of 2021. Not surprisingly, both articles deal largely with airway and hemodynamic concerns – the ABC’s of emergency medicine. Although these bulleted pearls provide key points from these two articles, the full discussions of those key points in the articles would provide a great deal more education than I can provide in this brief write-up, and so I strongly encourage everyone to read the full articles.

I also encourage readers to peruse the following “honorable mention” articles: Stiell and colleagues published a “Best Practices Checklist” on behalf of the Canadian Association of Emergency Physicians pertaining to the management of acute atrial fibrillation and atrial flutter; and on behalf of the American Heart Association (in collaboration with several other major organizations), Gulati and colleagues published the 2021 Guideline for the Evaluation and Diagnosis of Chest Pain. Both publications show us how we should strive to manage atrial fibrillation and chest pain, respectively, in the emergency department for years to come.

Amal Mattu, MD, is a professor, vice chair of education, and codirector of the emergency cardiology fellowship in the department of emergency medicine at the University of Maryland, Baltimore.

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

When 2021 began, there appeared to be light at the end of the long and dark COVID-19 pandemic. A vaccine was introduced, the “curve” had been flattened, and by spring, businesses were slowly starting to open. Whereas the medical literature of 2020 seemed to be almost entirely focused on COVID-19, medical writers, researchers, and educators seemed to slowly start turning more attention back to non–COVID-related topics in 2021.

Unfortunately, as I write this, the Omicron variant of the coronavirus is in full swing, and much of our attention has once again turned back to COVID-19. However, we are able to look back on 2021 and acknowledge a wealth of fantastic original research articles and guidelines which have improved patient care in many ways. In this annual recap of my favorite articles of the past year, I will focus on what I believe every acute care physician should read and know, as they will improve patient care.

Specifically, I have chosen articles that did not appear to gain widespread notoriety in emergency medicine but are, nevertheless, worthy of your time and attention. Note that this write-up serves as a summary only, and I encourage interested readers to peruse the full manuscripts for further details. I am limiting my recap to two articles.
 

Recommendations on difficult airway management

Emergency physicians are well trained in airway management, and a major part of that training includes the preintubation anatomic assessment of the airway. However, there are few recommendations on the physiological considerations for airway management.

A set of recommendations from the Society for Airway Management was written primarily with anesthesiologists in mind, but many of the recommendations listed below are very relevant to emergency physicians as well. The authors make recommendations for patients who are hypoxic or hypotensive prior to induction, for patients with right ventricular dysfunction, for patients with severe metabolic acidosis, and for neurologically injured patients. Some of the key pearls follow.
 

Patients with hypoxemia

• The importance of preoxygenation before intubation is once again emphasized, and this can be performed using high-flow oxygen for at least 3 minutes, or (in a cooperative patient) with eight vital capacity breaths.
• Maintenance of oxygenation during the apneic period should be continued. Apneic oxygenation can be provided with a nasal cannula at 15 liters per minute or with a high-flow nasal oxygen system at 40-70 LPM.
• For patients with significant shunt physiology or reduced functional residual capacity (for example, late pregnancy, obesity, or acute respiratory distress syndrome), preoxygenation should be performed with positive end expiratory pressure (PEEP) using noninvasive positive pressure ventilation or bag-valve mask ventilation with a PEEP valve. When higher levels of PEEP are required, an extraglottic device should be considered during preoxygenation.
• For patients with refractory hypoxemia, awake intubation to maintain spontaneous respirations should be considered.
• Patients should be preoxygenated in the upright position when possible.
• Ramped-up position (head elevated so as to bring the external auditory canal in the same horizontal line as the sternal notch) should be performed when possible in order to improve the grade of view, improve oxygenation, and reduce aspiration.

Patients with hypotension

• Patients should be screened for high risk for hemodynamic collapse prior to administration of induction medications and intubation by assessing the stroke index. A stroke index greater than 0.7 predicts a high risk. These patients should receive hemodynamic optimization (for example, intravenous fluids, administration of vasopressors) whenever possible, prior to administration of induction medications and intubation.
• Vasopressor infusions are preferable to bolus-dosed vasopressors. However, if vasopressor infusions are not possible, bolus-dosed vasopressors should be available and used to maintain systemic pressure during and after the intubation until an infusion can be started. When bolus-dosed vasopressors are used, diluted epinephrine should be considered as the vasopressor of choice in patients with depressed myocardial function.

Patients with right ventricular (RV) dysfunction

• Patients should be screened for significant RV dysfunction prior to intubation because of their high risk for hemodynamic decompensation with positive pressure ventilation.
• RV dysfunction may sometimes worsen with fluid administration. Fluid-intolerant patients may instead need RV afterload reduction with inhaled or intravenous pulmonary vasodilators.
• Patients with RV failure–induced shock should be considered for preintubation extracorporeal membrane oxygenation if available.
• Patients with RV volume overload should receive diuresis prior to intubation.
• Ventilator settings should aim to avoid hypercapnia, maintain low airway pressures, and use a higher PEEP to avoid atelectasis.

Patients with severe metabolic acidosis

• Patients with severe metabolic acidosis are at high risk for decompensation after intubation because of volume depletion and inadequate alveolar ventilation, resulting in profound acidosis.
• Patients with high minute ventilation prior to intubation should be considered for awake intubation to maintain spontaneous respirations. Otherwise, consider a spontaneous breathing mode after intubation with a high minute ventilation (that is, use a higher-than-normal respiratory rate on the ventilator in order to reproduce the preintubation minute ventilation). Apnea time should be minimized in order to minimize worsening acidosis.
• Preintubation bicarbonate boluses to prevent worsening acidosis are controversial and lack data showing any benefit.

Neurologically injured patients

• Eucapnia and normoxia should be maintained before, during, and after intubation to maintain stable cerebral blood flow.
• Hemodynamically neutral induction agents should be used.
• Patients should be positioned with the head of bed elevated to 30° upright when possible.
• Limit PEEP post intubation in order to promote venous drainage.

Evidence update for the treatment of anaphylaxis

The treatment of anaphylaxis is considered bread and butter in emergency and acute care medicine, but a great deal of what we have learned over the years is not well supported by the literature. In an article published in Resuscitation, the Anaphylaxis Working Group of the Resuscitation Council of the United Kingdom performed an evidence review regarding the emergency treatment of anaphylaxis.

A summary of key points includes:

• Anaphylaxis is defined as a systemic hypersensitivity reaction, usually rapid in onset, with potentially life-threatening compromise in airway, breathing, and/or circulation.
• The most important treatment is epinephrine (EPI), with an initial recommended dose in adults of 0.5 mg administered via the intramuscular (IM) route. Up to 10% of patients have a suboptimal response to one dose, but 98% will respond by the third dose; therefore, these authors recommend repeating the IM EPI every 5 minutes, if needed, up to three doses. There is no evidence to support any alternative or additional vasopressors, and so they should only be used if EPI is ineffective. Intravenous EPI is not recommended initially except in the perioperative setting where close monitoring can be performed. If intravenous EPI is used, the authors recommend an intravenous infusion rather than bolus dosing.
• Intravenous fluid bolus dosing is recommended in the majority of cases of anaphylaxis, regardless of presence or absence of hemodynamic compromise, because of the profound reduction in venous tone and third-spacing that typically occurs.
• Antihistamines are not recommended in early treatment. They are only effective for reversing skin manifestations of anaphylaxis (which EPI treats as well), and the sedation they produce can confound the proper ongoing evaluation of the patient. Furthermore, the use of antihistamines early in the treatment of anaphylaxis has been found to produce delays in proper use of EPI.
• Steroids are not recommended in early treatment. They help only with the late phase of inflammatory response, but despite that, there is no good evidence that they decrease the biphasic response of anaphylaxis. There is some emerging evidence that the use of steroids may actually be associated with increased morbidity even after correcting for anaphylaxis severity. The authors recommended the use of steroids in anaphylaxis only for patients with poorly controlled asthma and possibly for patients with refractory anaphylaxis. Inhaled beta-agonists are recommended in anaphylaxis only for patients with lower respiratory tract symptoms caused by anaphylaxis, but warned that the inhaled beta-agonists should not delay proper use of EPI.
• The optimal observation period before discharge for stable patients is unknown. The authors noted the recommendations of the Joint Task Force on Practice Parameters of the American Academy of Allergy, Asthma, & Immunology and the American College of Allergy, Asthma, and Immunology: Biphasic reactions were more common in patients with severe initial symptoms – for example, those requiring more than one dose of EPI; therefore, these patients are recommended to have “extended observation.” Lower-risk patients with resolved symptoms of anaphylaxis can be observed for 1 hour, which would capture 95% of biphasic reactions in this group of patients.

Summary and other honorable mentions

There you have it. My two favorite practice-changing (non–COVID-19) articles of 2021. Not surprisingly, both articles deal largely with airway and hemodynamic concerns – the ABC’s of emergency medicine. Although these bulleted pearls provide key points from these two articles, the full discussions of those key points in the articles would provide a great deal more education than I can provide in this brief write-up, and so I strongly encourage everyone to read the full articles.

I also encourage readers to peruse the following “honorable mention” articles: Stiell and colleagues published a “Best Practices Checklist” on behalf of the Canadian Association of Emergency Physicians pertaining to the management of acute atrial fibrillation and atrial flutter; and on behalf of the American Heart Association (in collaboration with several other major organizations), Gulati and colleagues published the 2021 Guideline for the Evaluation and Diagnosis of Chest Pain. Both publications show us how we should strive to manage atrial fibrillation and chest pain, respectively, in the emergency department for years to come.

Amal Mattu, MD, is a professor, vice chair of education, and codirector of the emergency cardiology fellowship in the department of emergency medicine at the University of Maryland, Baltimore.

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

When 2021 began, there appeared to be light at the end of the long and dark COVID-19 pandemic. A vaccine was introduced, the “curve” had been flattened, and by spring, businesses were slowly starting to open. Whereas the medical literature of 2020 seemed to be almost entirely focused on COVID-19, medical writers, researchers, and educators seemed to slowly start turning more attention back to non–COVID-related topics in 2021.

Unfortunately, as I write this, the Omicron variant of the coronavirus is in full swing, and much of our attention has once again turned back to COVID-19. However, we are able to look back on 2021 and acknowledge a wealth of fantastic original research articles and guidelines which have improved patient care in many ways. In this annual recap of my favorite articles of the past year, I will focus on what I believe every acute care physician should read and know, as they will improve patient care.

Specifically, I have chosen articles that did not appear to gain widespread notoriety in emergency medicine but are, nevertheless, worthy of your time and attention. Note that this write-up serves as a summary only, and I encourage interested readers to peruse the full manuscripts for further details. I am limiting my recap to two articles.
 

Recommendations on difficult airway management

Emergency physicians are well trained in airway management, and a major part of that training includes the preintubation anatomic assessment of the airway. However, there are few recommendations on the physiological considerations for airway management.

A set of recommendations from the Society for Airway Management was written primarily with anesthesiologists in mind, but many of the recommendations listed below are very relevant to emergency physicians as well. The authors make recommendations for patients who are hypoxic or hypotensive prior to induction, for patients with right ventricular dysfunction, for patients with severe metabolic acidosis, and for neurologically injured patients. Some of the key pearls follow.
 

Patients with hypoxemia

• The importance of preoxygenation before intubation is once again emphasized, and this can be performed using high-flow oxygen for at least 3 minutes, or (in a cooperative patient) with eight vital capacity breaths.
• Maintenance of oxygenation during the apneic period should be continued. Apneic oxygenation can be provided with a nasal cannula at 15 liters per minute or with a high-flow nasal oxygen system at 40-70 LPM.
• For patients with significant shunt physiology or reduced functional residual capacity (for example, late pregnancy, obesity, or acute respiratory distress syndrome), preoxygenation should be performed with positive end expiratory pressure (PEEP) using noninvasive positive pressure ventilation or bag-valve mask ventilation with a PEEP valve. When higher levels of PEEP are required, an extraglottic device should be considered during preoxygenation.
• For patients with refractory hypoxemia, awake intubation to maintain spontaneous respirations should be considered.
• Patients should be preoxygenated in the upright position when possible.
• Ramped-up position (head elevated so as to bring the external auditory canal in the same horizontal line as the sternal notch) should be performed when possible in order to improve the grade of view, improve oxygenation, and reduce aspiration.

Patients with hypotension

• Patients should be screened for high risk for hemodynamic collapse prior to administration of induction medications and intubation by assessing the stroke index. A stroke index greater than 0.7 predicts a high risk. These patients should receive hemodynamic optimization (for example, intravenous fluids, administration of vasopressors) whenever possible, prior to administration of induction medications and intubation.
• Vasopressor infusions are preferable to bolus-dosed vasopressors. However, if vasopressor infusions are not possible, bolus-dosed vasopressors should be available and used to maintain systemic pressure during and after the intubation until an infusion can be started. When bolus-dosed vasopressors are used, diluted epinephrine should be considered as the vasopressor of choice in patients with depressed myocardial function.

Patients with right ventricular (RV) dysfunction

• Patients should be screened for significant RV dysfunction prior to intubation because of their high risk for hemodynamic decompensation with positive pressure ventilation.
• RV dysfunction may sometimes worsen with fluid administration. Fluid-intolerant patients may instead need RV afterload reduction with inhaled or intravenous pulmonary vasodilators.
• Patients with RV failure–induced shock should be considered for preintubation extracorporeal membrane oxygenation if available.
• Patients with RV volume overload should receive diuresis prior to intubation.
• Ventilator settings should aim to avoid hypercapnia, maintain low airway pressures, and use a higher PEEP to avoid atelectasis.

Patients with severe metabolic acidosis

• Patients with severe metabolic acidosis are at high risk for decompensation after intubation because of volume depletion and inadequate alveolar ventilation, resulting in profound acidosis.
• Patients with high minute ventilation prior to intubation should be considered for awake intubation to maintain spontaneous respirations. Otherwise, consider a spontaneous breathing mode after intubation with a high minute ventilation (that is, use a higher-than-normal respiratory rate on the ventilator in order to reproduce the preintubation minute ventilation). Apnea time should be minimized in order to minimize worsening acidosis.
• Preintubation bicarbonate boluses to prevent worsening acidosis are controversial and lack data showing any benefit.

Neurologically injured patients

• Eucapnia and normoxia should be maintained before, during, and after intubation to maintain stable cerebral blood flow.
• Hemodynamically neutral induction agents should be used.
• Patients should be positioned with the head of bed elevated to 30° upright when possible.
• Limit PEEP post intubation in order to promote venous drainage.

Evidence update for the treatment of anaphylaxis

The treatment of anaphylaxis is considered bread and butter in emergency and acute care medicine, but a great deal of what we have learned over the years is not well supported by the literature. In an article published in Resuscitation, the Anaphylaxis Working Group of the Resuscitation Council of the United Kingdom performed an evidence review regarding the emergency treatment of anaphylaxis.

A summary of key points includes:

• Anaphylaxis is defined as a systemic hypersensitivity reaction, usually rapid in onset, with potentially life-threatening compromise in airway, breathing, and/or circulation.
• The most important treatment is epinephrine (EPI), with an initial recommended dose in adults of 0.5 mg administered via the intramuscular (IM) route. Up to 10% of patients have a suboptimal response to one dose, but 98% will respond by the third dose; therefore, these authors recommend repeating the IM EPI every 5 minutes, if needed, up to three doses. There is no evidence to support any alternative or additional vasopressors, and so they should only be used if EPI is ineffective. Intravenous EPI is not recommended initially except in the perioperative setting where close monitoring can be performed. If intravenous EPI is used, the authors recommend an intravenous infusion rather than bolus dosing.
• Intravenous fluid bolus dosing is recommended in the majority of cases of anaphylaxis, regardless of presence or absence of hemodynamic compromise, because of the profound reduction in venous tone and third-spacing that typically occurs.
• Antihistamines are not recommended in early treatment. They are only effective for reversing skin manifestations of anaphylaxis (which EPI treats as well), and the sedation they produce can confound the proper ongoing evaluation of the patient. Furthermore, the use of antihistamines early in the treatment of anaphylaxis has been found to produce delays in proper use of EPI.
• Steroids are not recommended in early treatment. They help only with the late phase of inflammatory response, but despite that, there is no good evidence that they decrease the biphasic response of anaphylaxis. There is some emerging evidence that the use of steroids may actually be associated with increased morbidity even after correcting for anaphylaxis severity. The authors recommended the use of steroids in anaphylaxis only for patients with poorly controlled asthma and possibly for patients with refractory anaphylaxis. Inhaled beta-agonists are recommended in anaphylaxis only for patients with lower respiratory tract symptoms caused by anaphylaxis, but warned that the inhaled beta-agonists should not delay proper use of EPI.
• The optimal observation period before discharge for stable patients is unknown. The authors noted the recommendations of the Joint Task Force on Practice Parameters of the American Academy of Allergy, Asthma, & Immunology and the American College of Allergy, Asthma, and Immunology: Biphasic reactions were more common in patients with severe initial symptoms – for example, those requiring more than one dose of EPI; therefore, these patients are recommended to have “extended observation.” Lower-risk patients with resolved symptoms of anaphylaxis can be observed for 1 hour, which would capture 95% of biphasic reactions in this group of patients.

Summary and other honorable mentions

There you have it. My two favorite practice-changing (non–COVID-19) articles of 2021. Not surprisingly, both articles deal largely with airway and hemodynamic concerns – the ABC’s of emergency medicine. Although these bulleted pearls provide key points from these two articles, the full discussions of those key points in the articles would provide a great deal more education than I can provide in this brief write-up, and so I strongly encourage everyone to read the full articles.

I also encourage readers to peruse the following “honorable mention” articles: Stiell and colleagues published a “Best Practices Checklist” on behalf of the Canadian Association of Emergency Physicians pertaining to the management of acute atrial fibrillation and atrial flutter; and on behalf of the American Heart Association (in collaboration with several other major organizations), Gulati and colleagues published the 2021 Guideline for the Evaluation and Diagnosis of Chest Pain. Both publications show us how we should strive to manage atrial fibrillation and chest pain, respectively, in the emergency department for years to come.

Amal Mattu, MD, is a professor, vice chair of education, and codirector of the emergency cardiology fellowship in the department of emergency medicine at the University of Maryland, Baltimore.

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

Here we are. Again. It’s cold and it’s gray. The sun rises late and sets early, so that it feels like midnight by 8 p.m. Indoor venues are risky with the highly contagious Omicron variant, and I feel like we are all pushing the replay button on 2021’s miserable winter.

In some ways, it’s worse: In 2021 we had the hope that vaccines would pull us out of the pandemic and we had guidance on all that we should not be doing. In January, we were gaming the various Internet sites to get a coveted vaccine for ourselves or our family and friends, then lining up to get jabbed. We did not yet know that it wouldn’t be enough – that we’d need boosters, that Delta and Omicron would defy the vaccines. Yes, the vaccines work miracles to prevent severe disease and death, but the worry of passing the virus to someone who is vulnerable or unvaccinated(!), or both, remains – and now we can wonder how we’ll ever get out of this mess with hopeful talk of an endemic, while we wait on the next variant. I like certainty, and this pandemic is one big screaming reminder that certainty about anything is just a pleasant notion, death and taxes excluded, of course.

PeopleImages/E+/Getty Images

Kris Lukish, vice president of human resources at Johns Hopkins Hospital in Baltimore, started an update to the hospital employees with: “As we begin 2022, it feels like we are experiencing dejà vu, or ‘Groundhog Day,’ or ‘50 First Dates.’ In ‘50 First Dates,’ Drew Barrymore wakes up each day reliving one specific day. It never changes. I realize our world may seem a little like that right now. We thought we’d turned a corner with COVID, and instead we saw a rapid rise in cases and hospitalizations due to the Omicron variant, higher than in previous surges.”

In 2021, many of us skipped holiday travel and ate outdoors. My morning coffee group moved to Zoom and it wasn’t until late spring, when community rates of COVID nose-dived, that I began seeing patients in my office for the first time in over a year. Since many of my patients are over 60, I tested myself with a home antigen test before going into the office. I changed my schedule so sessions began on the half-hour to be sure the suite’s waiting room would be empty, and I purchased an air purifier, cracked the window open, and figured everyone was as safe as we could reasonably be.

By the first Monday in January 2022, the positivity rate in Maryland was just shy of 30%. Twitter circulated anecdotes about false negatives with the home antigen test kits, and I decided it was safest to return to all-virtual appointments.

Mona Masood, DO, is cofounder of the Physician Support Line, a call-in service for doctors that started in March 2020. She has noted a change in the problems physicians face.

“We’re seeing a lot of empathy fatigue,” Dr. Masood said. “It’s not unexpected with a prolonged situation like this – the trauma has doctors in survival mode and they need to be present for themselves, their families, and their patients. People are emotionally drained, and we’re stretching them to the limit. Now at the front lines, doctors are getting a lot of backlash. There are the conspiracy theories, and people who challenge their knowledge and training and it leads them to ask if they should be doing this work. Some callers are thinking about leaving medicine and asking: ‘Is this what I signed up for?’ and these are large decisions that are being made in a specific context.

“The other thing we’re hearing is from trainees – residents and fellows – who are expected to carry a lot of work on the COVID units. Some are being told that they can’t graduate because they haven’t finished their other training requirements. This type of systemic issue produces moral injury.”

Dr. Masood talked about what running the support line has been like for her. “I know people want to give more in a catastrophe, and I was realistic that the enthusiasm might die off. I would go as long as psychiatrists volunteer, and the most incredible thing is that it hasn’t stopped. Some of the original people are no longer with us, but others have come aboard, and it’s been incredible to be a part of this.”

In her Jan. 26, 2022, newsletter, epidemiologist Katelyn Jetelina, PhD, MPH, tried to be reassuring about the future. “In order to know how this will end, we need to look at how other pandemics ended,” Dr. Jetelina wrote. “First, recognize the last part of that sentence ... pandemics end. Every epi curve comes down. This pandemic will end, too. Hold that fact close to you.”

She wrote about the three ways that pandemics end. The SARS pandemic of 2002 lasted 1.5 years as public health measures were effective, in large part because the disease was spread only by symptomatic patients. Vaccines offer a second way to end pandemics, as they have for polio and smallpox. “If the globe works together, we could possibly eradicate SARS-CoV-2 with vaccines. [Now that we have numerous animal reservoirs, though, this is close to impossible.]”

Finally, Dr. Jetelina noted that the 1918 flu changed from a pandemic situation to being endemic. “Over time, the virus attenuated, it became less severe.” Society acclimates to a virus with a low mortality rate. “The vast majority of scientists think an endemic state is the future of SARS-CoV-2. I agree.” And she goes on to define endemic as a steady state, but not the absence of suffering. She likens it to malaria and tuberculosis, illnesses with high global mortality.

“An endemic will come without an announcement or headlines, we won’t know we’re there until well after we’ve arrived.” She wrote of the uncertainty that faces us moving forward: We don’t know how much, or how long, immunity from Omicron infections will last, or if future variants will cause more or less severe disease. She casted her vote for global vaccinations, boosters, masks, better ventilation, communication, empathy, and tolerance to end the pandemic.

In Maryland, hospitalizations and positivity are starting to decline from the postholiday surge. I have figured out that I am not good at predicting what will happen next, and the experts don’t seem to be much better. I’d like a headline ending, the kind we looked to be heading toward last June.

I’ve told my patients who want to come in person that I will reassess in March. We have written our own rules, and mine are somewhere in the middle – I don’t go to public indoor spaces unmasked, but I do see vaccinated family and friends in our homes without masks. I don’t want to be responsible for transmitting a potentially fatal illness to a vulnerable patient. Honestly, this makes no sense, but since there is a video option, I feel I should not risk passing a potentially lethal virus to my patients. I just hope I’m not writing this same article again in January 2023.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins. Dr. Miller has no conflicts of interest.

Here we are. Again. It’s cold and it’s gray. The sun rises late and sets early, so that it feels like midnight by 8 p.m. Indoor venues are risky with the highly contagious Omicron variant, and I feel like we are all pushing the replay button on 2021’s miserable winter.

In some ways, it’s worse: In 2021 we had the hope that vaccines would pull us out of the pandemic and we had guidance on all that we should not be doing. In January, we were gaming the various Internet sites to get a coveted vaccine for ourselves or our family and friends, then lining up to get jabbed. We did not yet know that it wouldn’t be enough – that we’d need boosters, that Delta and Omicron would defy the vaccines. Yes, the vaccines work miracles to prevent severe disease and death, but the worry of passing the virus to someone who is vulnerable or unvaccinated(!), or both, remains – and now we can wonder how we’ll ever get out of this mess with hopeful talk of an endemic, while we wait on the next variant. I like certainty, and this pandemic is one big screaming reminder that certainty about anything is just a pleasant notion, death and taxes excluded, of course.

PeopleImages/E+/Getty Images

Kris Lukish, vice president of human resources at Johns Hopkins Hospital in Baltimore, started an update to the hospital employees with: “As we begin 2022, it feels like we are experiencing dejà vu, or ‘Groundhog Day,’ or ‘50 First Dates.’ In ‘50 First Dates,’ Drew Barrymore wakes up each day reliving one specific day. It never changes. I realize our world may seem a little like that right now. We thought we’d turned a corner with COVID, and instead we saw a rapid rise in cases and hospitalizations due to the Omicron variant, higher than in previous surges.”

In 2021, many of us skipped holiday travel and ate outdoors. My morning coffee group moved to Zoom and it wasn’t until late spring, when community rates of COVID nose-dived, that I began seeing patients in my office for the first time in over a year. Since many of my patients are over 60, I tested myself with a home antigen test before going into the office. I changed my schedule so sessions began on the half-hour to be sure the suite’s waiting room would be empty, and I purchased an air purifier, cracked the window open, and figured everyone was as safe as we could reasonably be.

By the first Monday in January 2022, the positivity rate in Maryland was just shy of 30%. Twitter circulated anecdotes about false negatives with the home antigen test kits, and I decided it was safest to return to all-virtual appointments.

Mona Masood, DO, is cofounder of the Physician Support Line, a call-in service for doctors that started in March 2020. She has noted a change in the problems physicians face.

“We’re seeing a lot of empathy fatigue,” Dr. Masood said. “It’s not unexpected with a prolonged situation like this – the trauma has doctors in survival mode and they need to be present for themselves, their families, and their patients. People are emotionally drained, and we’re stretching them to the limit. Now at the front lines, doctors are getting a lot of backlash. There are the conspiracy theories, and people who challenge their knowledge and training and it leads them to ask if they should be doing this work. Some callers are thinking about leaving medicine and asking: ‘Is this what I signed up for?’ and these are large decisions that are being made in a specific context.

“The other thing we’re hearing is from trainees – residents and fellows – who are expected to carry a lot of work on the COVID units. Some are being told that they can’t graduate because they haven’t finished their other training requirements. This type of systemic issue produces moral injury.”

Dr. Masood talked about what running the support line has been like for her. “I know people want to give more in a catastrophe, and I was realistic that the enthusiasm might die off. I would go as long as psychiatrists volunteer, and the most incredible thing is that it hasn’t stopped. Some of the original people are no longer with us, but others have come aboard, and it’s been incredible to be a part of this.”

In her Jan. 26, 2022, newsletter, epidemiologist Katelyn Jetelina, PhD, MPH, tried to be reassuring about the future. “In order to know how this will end, we need to look at how other pandemics ended,” Dr. Jetelina wrote. “First, recognize the last part of that sentence ... pandemics end. Every epi curve comes down. This pandemic will end, too. Hold that fact close to you.”

She wrote about the three ways that pandemics end. The SARS pandemic of 2002 lasted 1.5 years as public health measures were effective, in large part because the disease was spread only by symptomatic patients. Vaccines offer a second way to end pandemics, as they have for polio and smallpox. “If the globe works together, we could possibly eradicate SARS-CoV-2 with vaccines. [Now that we have numerous animal reservoirs, though, this is close to impossible.]”

Finally, Dr. Jetelina noted that the 1918 flu changed from a pandemic situation to being endemic. “Over time, the virus attenuated, it became less severe.” Society acclimates to a virus with a low mortality rate. “The vast majority of scientists think an endemic state is the future of SARS-CoV-2. I agree.” And she goes on to define endemic as a steady state, but not the absence of suffering. She likens it to malaria and tuberculosis, illnesses with high global mortality.

“An endemic will come without an announcement or headlines, we won’t know we’re there until well after we’ve arrived.” She wrote of the uncertainty that faces us moving forward: We don’t know how much, or how long, immunity from Omicron infections will last, or if future variants will cause more or less severe disease. She casted her vote for global vaccinations, boosters, masks, better ventilation, communication, empathy, and tolerance to end the pandemic.

In Maryland, hospitalizations and positivity are starting to decline from the postholiday surge. I have figured out that I am not good at predicting what will happen next, and the experts don’t seem to be much better. I’d like a headline ending, the kind we looked to be heading toward last June.

I’ve told my patients who want to come in person that I will reassess in March. We have written our own rules, and mine are somewhere in the middle – I don’t go to public indoor spaces unmasked, but I do see vaccinated family and friends in our homes without masks. I don’t want to be responsible for transmitting a potentially fatal illness to a vulnerable patient. Honestly, this makes no sense, but since there is a video option, I feel I should not risk passing a potentially lethal virus to my patients. I just hope I’m not writing this same article again in January 2023.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins. Dr. Miller has no conflicts of interest.

Here we are. Again. It’s cold and it’s gray. The sun rises late and sets early, so that it feels like midnight by 8 p.m. Indoor venues are risky with the highly contagious Omicron variant, and I feel like we are all pushing the replay button on 2021’s miserable winter.

In some ways, it’s worse: In 2021 we had the hope that vaccines would pull us out of the pandemic and we had guidance on all that we should not be doing. In January, we were gaming the various Internet sites to get a coveted vaccine for ourselves or our family and friends, then lining up to get jabbed. We did not yet know that it wouldn’t be enough – that we’d need boosters, that Delta and Omicron would defy the vaccines. Yes, the vaccines work miracles to prevent severe disease and death, but the worry of passing the virus to someone who is vulnerable or unvaccinated(!), or both, remains – and now we can wonder how we’ll ever get out of this mess with hopeful talk of an endemic, while we wait on the next variant. I like certainty, and this pandemic is one big screaming reminder that certainty about anything is just a pleasant notion, death and taxes excluded, of course.

PeopleImages/E+/Getty Images

Kris Lukish, vice president of human resources at Johns Hopkins Hospital in Baltimore, started an update to the hospital employees with: “As we begin 2022, it feels like we are experiencing dejà vu, or ‘Groundhog Day,’ or ‘50 First Dates.’ In ‘50 First Dates,’ Drew Barrymore wakes up each day reliving one specific day. It never changes. I realize our world may seem a little like that right now. We thought we’d turned a corner with COVID, and instead we saw a rapid rise in cases and hospitalizations due to the Omicron variant, higher than in previous surges.”

In 2021, many of us skipped holiday travel and ate outdoors. My morning coffee group moved to Zoom and it wasn’t until late spring, when community rates of COVID nose-dived, that I began seeing patients in my office for the first time in over a year. Since many of my patients are over 60, I tested myself with a home antigen test before going into the office. I changed my schedule so sessions began on the half-hour to be sure the suite’s waiting room would be empty, and I purchased an air purifier, cracked the window open, and figured everyone was as safe as we could reasonably be.

By the first Monday in January 2022, the positivity rate in Maryland was just shy of 30%. Twitter circulated anecdotes about false negatives with the home antigen test kits, and I decided it was safest to return to all-virtual appointments.

Mona Masood, DO, is cofounder of the Physician Support Line, a call-in service for doctors that started in March 2020. She has noted a change in the problems physicians face.

“We’re seeing a lot of empathy fatigue,” Dr. Masood said. “It’s not unexpected with a prolonged situation like this – the trauma has doctors in survival mode and they need to be present for themselves, their families, and their patients. People are emotionally drained, and we’re stretching them to the limit. Now at the front lines, doctors are getting a lot of backlash. There are the conspiracy theories, and people who challenge their knowledge and training and it leads them to ask if they should be doing this work. Some callers are thinking about leaving medicine and asking: ‘Is this what I signed up for?’ and these are large decisions that are being made in a specific context.

“The other thing we’re hearing is from trainees – residents and fellows – who are expected to carry a lot of work on the COVID units. Some are being told that they can’t graduate because they haven’t finished their other training requirements. This type of systemic issue produces moral injury.”

Dr. Masood talked about what running the support line has been like for her. “I know people want to give more in a catastrophe, and I was realistic that the enthusiasm might die off. I would go as long as psychiatrists volunteer, and the most incredible thing is that it hasn’t stopped. Some of the original people are no longer with us, but others have come aboard, and it’s been incredible to be a part of this.”

In her Jan. 26, 2022, newsletter, epidemiologist Katelyn Jetelina, PhD, MPH, tried to be reassuring about the future. “In order to know how this will end, we need to look at how other pandemics ended,” Dr. Jetelina wrote. “First, recognize the last part of that sentence ... pandemics end. Every epi curve comes down. This pandemic will end, too. Hold that fact close to you.”

She wrote about the three ways that pandemics end. The SARS pandemic of 2002 lasted 1.5 years as public health measures were effective, in large part because the disease was spread only by symptomatic patients. Vaccines offer a second way to end pandemics, as they have for polio and smallpox. “If the globe works together, we could possibly eradicate SARS-CoV-2 with vaccines. [Now that we have numerous animal reservoirs, though, this is close to impossible.]”

Finally, Dr. Jetelina noted that the 1918 flu changed from a pandemic situation to being endemic. “Over time, the virus attenuated, it became less severe.” Society acclimates to a virus with a low mortality rate. “The vast majority of scientists think an endemic state is the future of SARS-CoV-2. I agree.” And she goes on to define endemic as a steady state, but not the absence of suffering. She likens it to malaria and tuberculosis, illnesses with high global mortality.

“An endemic will come without an announcement or headlines, we won’t know we’re there until well after we’ve arrived.” She wrote of the uncertainty that faces us moving forward: We don’t know how much, or how long, immunity from Omicron infections will last, or if future variants will cause more or less severe disease. She casted her vote for global vaccinations, boosters, masks, better ventilation, communication, empathy, and tolerance to end the pandemic.

In Maryland, hospitalizations and positivity are starting to decline from the postholiday surge. I have figured out that I am not good at predicting what will happen next, and the experts don’t seem to be much better. I’d like a headline ending, the kind we looked to be heading toward last June.

I’ve told my patients who want to come in person that I will reassess in March. We have written our own rules, and mine are somewhere in the middle – I don’t go to public indoor spaces unmasked, but I do see vaccinated family and friends in our homes without masks. I don’t want to be responsible for transmitting a potentially fatal illness to a vulnerable patient. Honestly, this makes no sense, but since there is a video option, I feel I should not risk passing a potentially lethal virus to my patients. I just hope I’m not writing this same article again in January 2023.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins. Dr. Miller has no conflicts of interest.