Month: October 2021

FDA Advisory Committee Meeting on EUA for Moderna COVID-19 Vaccine Booster Today

Today I’m watching the FDA meeting on extending the Emergency Use Authorization (EUA) for Moderna COVID-19 Vaccine Booster application. Right now, I’m in-between presentations and I’ll be updating later this afternoon. I’m skipping the Open Public Hearing.

I’m wondering if the question to vote on will get changed like it did last month for the Pfizer booster. So far, today’s question is:

“10/14 Voting Question:

Question 1) Do available data support the safety and effectiveness of Moderna COVID-19 Vaccine for use under EUA as a booster dose (50 mcg mRNA-1273) at least 6 months after completion of a primary series in the following populations:

• Individuals 65 years of age and older,

• Individuals 18 through 64 years of age at high risk of severe COVID-19, and

• Individuals 18 through 64 years of age whose frequent institutional or occupational exposure to SARS-CoV-2 puts them at high risk of serious complications of COVID-19 including severe COVID-19.”

Dr. Arnold Monto is in fine form and has already starting limiting the number of questions participants can ask. But we’re ahead of schedule and he’s very pleased overall.

My wife, Sena, finally got her Pfizer booster this morning. It has been kind of complicated for her to schedule and she went through a telephone algorithm about a half dozen times. She showed up on the day scheduled a couple of days ago and the pharmacy manager cancelled it, saying it was too early for the 6-month mark (by 2 days) following her 2nd primary series dose. This morning he apologized for being the “Vaccine Nazi.”

My Moderna booster depends on what happens today, and after the CDC advisory committee makes its decision at their meeting next week Oct 20-21. If approved, I’d get half the dose I received during my primary series (50 mcg instead of 100 mcg)—provided I don’t run into the Vaccine Nazi.

Anyway, this morning’s meeting went fairly well; only 2 people forgot to unmute their microphones. The Israeli researchers gave a presentation on their updated booster program that impressed committee members, who called the data “compelling.” As I recall, last month, some people raised questions about their definition of COVID-19 disease severity, making it hard to judge how applicable their data results would be in the United States. This morning, they clarified that the disease severity criteria actually came from the NIH (slide 15).

Update around 2:15 PM today: The committee upvoted the question above unanimously.

Tomorrow the committee will take up the issues of J&J boosters and heterologous vaccinations.

Music Beat

We listen to the Music Choice Channel almost every night on our TV. I know that must sound odd, listening to a music channel on television. What makes it more interesting are the biographical sketches. The Light Classical Channel bios occasionally have typos and word usage oddities as well as eyebrow raising facts:

Mozart’s full name was Johannes Chrysostomas Wolfgangus Theophilus “Bud” Mozart.

Frederic Chopin is not pronounced “Choppin” as in his well-known tune “I’m Choppin’ Onions in My Stew and Crying Over Losing You.”

Edvard Grieg was taught the violin by Ole Bull, which is a lot of bull since, at least in Iowa, bulls go “mooooo” and chase red bandanas.

Antonin Dvorak spent a summer in Spillville, Iowa in 1893 where he drank beer and toppled into the Turkey River.

Riveting stuff like that is usual for the Music Choice Light Classical Channel. On the other hand, some months ago, I heard a song called “The Penguin” by somebody named Raymond Scott. I looked him up today and he was a jazz composer and Music Choice must have misfiled him.

I can’t really make fun of his bio because it’s eccentric enough by itself. His music ended up in a lot of cartoons, but he didn’t do that on purpose. Scott sold the publishing rights to his work to Warner Bros. Music in 1943. The music director at that time was Carl Stalling, who used a lot of Scott’s compositions in cartoons, such as Looney Tunes and many others.

Raymond Scott wasn’t even his real name. He looked it up in a phone book and used it partly because it sounded cool. The other reason is more complicated. His real name was Harry Warnow and he was playing piano in a radio orchestra conducted by his brother, Mark in the 1930s. The band started playing Harry’s off-beat compositions and, in order to avoid the appearance of nepotism, Harry adopted the new name.

Scott also invented electronic musical instruments, and after a while, he spent most of his time doing that, working with engineers on many inventions.

I haven’t heard him on the Light Classical Channel for a long while now. Maybe Music Choice finally got him filed to the Jazz Channel.

Heeeeeere’s Arnie—at the FDA Advisory Committee Meeting

I got a big kick out of Acting Chair of the FDA’s Vaccine and Related Biological Products Advisory Committee. Dr. Arnold Monto at the FDA meeting last month for the Pfizer COVID-19 vaccine booster. Everybody else did too, I bet. They all called him Arnie. I’m looking forward to seeing Arnie in action again this week for the meeting on the other boosters, Moderna and J&J. They’ll also discuss mixing and matching vaccine boosters—if Arnie lets them.

Arnie is pretty good at keeping speakers on a timeline. Everybody has a short leash. “That’s all you can ask.” “Keep it short, or I’ll cut you off.” “Hurry up, people want to get out in their gardens.” (He actually said something like that toward the end of the last meeting). The end of the meeting was abrupt. Arnie evidently expected the Advisory Committee on Immunization Practices (ACIP) to tidy up the regulatory decision with which the FDA committee seemed to struggle regarding the Pfizer booster.

I’m not the only one who notices Arnie’s preference for terseness. I found the article “Hearing Without Listening” by David S. Hilzenrath, who posted it on the web, December 16, 2020 on POGO.

I think Hilzenrath was a little hard on Arnie. People do tend to talk too much at meetings and that can interfere with getting things done.

I wonder what Arnie thinks about the Moderna and J&J boosters and the heterologous vaccination dosing strategies (“mixing and matching”)? My impression of what I read in the news is that different experts might be purposely jazzing up the topic, sending readers in different directions decorated with teaser headlines and leading statements. One might say something like, sure, the booster does what it’s supposed to do, which is boost—but does it boost enough? Another might say the boosters are barely needed. Many of them tend to be identified as “former” directors of something or other.

I’m not sure I’ll pay much attention to the hour long open public hearing, 3-minute-long diatribes per speaker on the miraculous properties of lemon-freshened Ivermectin gummies, including breathless accounts of also witnessing armies of Bigfoot hacking hairballs at armies of Gray Aliens doing impressions of Elvis (“thank ya-thank ya very much”) all on the head of a pin. If YouTube is kicking out purveyors of COVID-19 vaccine misinformation, why can’t the FDA and CDC advisory committees do the same?

I wonder if Arnie will rush the upcoming meeting because has a butternut squash garden he wants to get back to as soon as possible?

OK, we’re done here. You need to pick your pumpkins.

Thoughts on Transplant Psychiatry

I see in the news that organ transplant centers have removed a few patients from wait lists because they refuse COVID-19 vaccines. It may seem odd, but this reminds me of an even more difficult situation in organ transplantation. What do you do about those who just refuse organ transplant altogether?

I used to be a psychiatric consultant and that meant providing psychiatric consultations to the organ transplant service as well.

As anyone can imagine, refusing a transplant is uncommon. But it happens.

There are strong contraindications to transplant, among them severe psychiatric illness, medical noncompliance, absent social support, and active substance use.

There are not enough organs to go around. Many transplant candidates die every year while on the waiting list. Graft survival rates are usually shorter than survival rates, meaning some patients will need more than one transplant.

This means that selection criteria for candidates must be fair and realistic. More than 95% of transplant programs require psychosocial evaluations. There are usually not enough transplant psychiatrists to do this so a team approach is used in which social workers, nurse practitioners, psychologists, substance use disorders experts, and psychiatric consultants collaborate.

While it can be unsettling to remove a patient from the wait list, few people outside of the transplant center realize it can be even more upsetting to hear a patient say “no” to transplant. In all cases, the patient’s life probably has been saved many times. Often, all members of the team have invested a great deal of emotional energy to keeping the patient in the game.

There is also another incentive for transplant centers which must, in all fairness, be acknowledged. The government requires centers to do a certain number of transplant surgeries a year to retain their transplant Medicare certification. The procedure itself costs hundreds of thousands of dollars.

One typical letter from a transplant center can look like this:

“…specific outcome requirements must be met by transplant centers as outlined by the Centers for Medicare and Medicaid Services.  Programs are required to notify their patients if these requirements are not met.  Currently, Hospital X meets all requirements for transplant centers.”

There is a report by the Scientific Registry of Transplant Recipients (SRTR) which updates transplant statistics for all transplant programs. Anyone can look at the numbers.

This can become a point of pride and possibly some competition between centers. The older reference below is an example:

“Does Competition Among Transplant Centers Lead to Efficient Organ Allocation?” Scanlon D, Ubel PA, Loh E; Academy for Health Services Research and Health Policy. Meeting. Abstr Acad Health Serv Res Health Policy Meet. 2001; 18: 17. Short answer is-probably not, rather leads to inappropriate listing.

This means that an ethics consultation would be a good idea in many complicated organ transplant cases. The University of Washington has a “4 Boxes” tool that I used as a guide for years. The contextual features box merits close examination.

Anyhow, the patient who outright refuses transplant presents the transplant team with a singular question. Does this patient want to die? Usually that triggers a call to the psychiatric consultant. My role as an interdisciplinary collaborator was to focus on identifying psychosocial challenges to address in order to maximize postoperative chances of successful outcomes. That sentence was from the team’s perspective. However, my real goal was to listen to the patient and try to understand. In fact, I had a dual role. My main role, from the point of view of the transplant team, was to enhance the suitability of the patient for transplant—from a psychiatric standpoint.

It was never that easy, especially when the patient didn’t want a transplant. Suitability was out the window. Also, there are more or less discrete phases of transplant.

The Evaluation Phase in which the patient is usually very sick, faced with a terminal illness, and eager to be transplanted.

The Waiting for Donor Phase, often a very stressful time, frequently marked by demoralization as others get transplanted sooner.

The Surgery and Postop Course Phase, which could be marked by difficulty accepting the new organ, fantasies about the life and death of the donor, and fear that one will take on the traits or identity of the donor.

Prior to coming up on the wait list, some factors which may influence transplant refusal:

  • Depression or grief
  • Denial
  • Delirium and dementia
  • Fear of transplant surgery or negative past experiences with surgeries
  • Concerns about postop quality of life
  • Ambivalence about surgery and/or survival
  • Acceptance of inevitability of death
    • Frierson, R. L., J. B. Tabler, et al. (1990). “Patients who refuse heart transplantation.” J Heart Transplant 9(4): 385-91.

Ambivalence is one factor that has been studied. It has been described as the tension between the wish for an extended life for which transplant holds out a promise as contrasted with the:

  • Need to confront the desperate seriousness of their situation
  • Need to fathom undergoing an operation which will remove the very organ physically and symbolically sustaining life
  • Need to accept postop quality of life that could be less than acceptable because of the amount of suffering it could inflict
    • Difficulty facing seriousness of situation
    • Fear of the surgery
    • Quality of life concerns

The tasks for the patients:

  • Realize they have a terminal illness
  • Accept the idea that a transplant is necessary to preserve life
  • Endure the uncertainty about acceptance or rejection for transplantation
  • Assimilate an enormous amount of information in a short period of time
  • Emotionally reinvest in the possibility of an extension of their lives

Even the normal person feels, as it were, two souls in his breast.”

E. Bleuler

How would this be addressed in a busy transplant center intent on saving lives and retaining certification?

Ironically, by acknowledging that refusal of transplant is an acceptable choice. Ambivalence is not necessarily a sign of mental illness. It’s probably fine to avoid trying to talk the patient into going ahead with the transplant. You can see that the psychiatric consultant is supposed to be the advocate for the patient, not necessarily always for the transplant team.

Try to help the transplant team tolerate their own emotional turmoil as well as the patient’s. Try to create a space in which the transplant team can debrief and grieve those “who choose not to be saved.”

  • Frierson, R.L., et al., Patients who refuse heart transplantation. J Heart Transplant, 1990. 9(4): p. 385-91.
  • Kuhn, W.F., B. Myers, and M.H. Davis, Ambivalence in cardiac transplantation candidates. Int J Psychiatry Med, 1988. 18(4): p. 305-14.

Stay in the chair.

FDA Advisory Committee Meetings on COVID-19 Vaccine EUA Amendments for Moderna, J&J Boosters and Heterologous Boosters, Pfizer Vaccine for Children

The FDA Advisory Committee will hold a meeting October 14-15 to discuss amendments to the Emergency Use Authorization (EUA) for Moderna and J&J COVID-19 boosters as well as heterologous boosting (mix and match). New data is available, including NIH preliminary results on the mix and match study.

The FDA also announced a meeting to discuss Pfizer COVID-19 vaccine for children age 5-11, which is scheduled for October 26, 2021.

Links to the livestream meetings details are in the press announcement (link above).

Meeting materials are posted here.

Get This Book: Every Deep-Drawn Breath

I just got Wes Ely’s new book, Every Deep-Drawn Breath. You do need to buy this book to learn about delirium, Post-Intensive Care Syndrome (PICS) and what Dr. Ely and colleagues are doing to prevent it. PICS is a syndrome patients suffer after being hospitalized with severe medical illness in critical care units. It includes impairments in cognitive skills (impaired executive functioning), emotional functioning (depression, anxiety, post-traumatic stress disorder), and physical function (weakness, myopathy, and neuropathy). 

Reading the prologue and first chapter reminded me of my early years in medical school and residency. It also reminded me of my frustrations when I was working as a psychiatric consultant trying to teach my colleagues about delirium, which a large percentage of patients suffer in the intensive care unit (ICU). I retired a little over a year ago.

Dr. Ely’s book also reminded me that I wrote an article about delirium 10 years ago, which was published in Psychiatric Times. I can still find it on line. The title is “Psychiatrists Can Help Prevent Delirium.” Prevention is the key because once delirium sets in, the challenge to offset the neurocognitive impairment becomes far greater.

A couple of years before I wrote it, I had tried working in private practice in Wisconsin. Aside from gaining weight from the good food there, I didn’t adjust well and quickly returned to Iowa City. I did make a consultation visit to a primary care clinic where I worked, which was a welcome surprised to the clinician who asked for help. You can take the psychiatric consultant out of the hospital, but you can’t take the hospital out of the psychiatric consultant.

I also met Dr. Ely around that time as well, because I kidded him about what he wrote in another book, Delirium in Critical Care (2011). There was a couple of paragraphs in a section called “Psychiatrists and delirium.” I’m going to risk somebody rapping my knuckles about copyright rules, but I’ll quote the sentence that usually made me chuckle: “Should we, or should we not, call the psychiatrist? Can we replace them with a screening tool and then use haloperidol freely?”

I think that was meant to be funny—and it was in an ironic way. Every psychiatric consultant knows that the main treatment for delirium is not haloperidol, but treating the underlying medical illnesses. Anyway, I poked a little fun at that book section in a blog post (which I no longer have, called “The Practical Psychosomaticist”) and shortly thereafter, he emailed me, asking me to write a few posts highlighting the serious and important research he and others were conducting about delirium. I learned a lot.

Eventually, I actually met Dr. Ely, at meeting of the American Delirium Society in Indianapolis. I respect and admire him. He’s a brilliant doctor and a caring man. And you should buy his book.