In the genes?

I'm starting to look into genetic testing to help my work with patients who have not responded well to multiple psychotropic medications. It feels like a desperate bid, but I'm not sure what other help I can offer.

There are three main testing products, that I could find:

Genesight

Genecept Assay

and

Genelex


I have three main questions about these products:

1. What do they tell me?

2. How accurate/helpful are they?

3. How easy are they to use?


Genesight

Genesight seems to be the one mentioned most by people I asked. Practically speaking, it involves a buccal swab sent to Genesight via prepaid FedEx, with access to results online 36 hours after the sample is received. They are covered by some insurance plans, and have a financial assistance program. And it looks like, in order to try out the test, you need to speak with one of their representatives-there's no way to order online.

In terms of how well it works, their claim is, "Patients with uncontrolled symptoms who switch off of genetically discordant medications show the greatest reduction in depressive symptoms."

They also claim that, "70% of patients who have failed at least one medication are currently taking a genetically sub-optimal medication," and that, "GeneSight testing may help avoid drug-drug interactions and compounding side effects."

Finally, for patients younger than 18, Genesight can help in decisions about efficacy, tolerability, and dosing.

They site a paper, A prospective, randomized, double-blind study assessing the clinical impact of integrated pharmacogenomic testing for major depressive disorder, the results of which were:

Between-group trends were observed with greater than double the likelihood of response and remission in the GeneSight group measured by HAMD-17 at week 10. Mean percent improvement in depressive symptoms on HAMD-17 was higher for the GeneSight group over TAU (30.8% vs 20.7%; p=0.28). TAU subjects who had been prescribed medications at baseline that were contraindicated based on the individual subject's genotype (i.e., red bin) had almost no improvement (0.8%) in depressive symptoms measured by HAMD-17 at week 10, which was far less than the 33.1% improvement (p=0.06) in the pharmacogenomic guided subjects who started on a red bin medication and the 26.4% improvement in GeneSight subjects overall (p=0.08).

You'll notice that they talk about "trends" without any statistics, and mean percent improvement showed no significant difference (p=0.28), even though they point out that improvement in the Genesight group was higher. Recall that p=0.28 means there is a 28% chance that the differences they found were due to chance alone.

The "red bin" is a reference to the way Genesight presents its results, which I find easy to understand, if not entirely illuminating. This is an example:

I don't get the impression that the results give me information about which drugs will be helpful, as much as which drugs won't be harmful.

How does the test work? Genesight measures polymorphisms among 5 genes, CYP2D6; CYP2C19; CYP1A2; the serotonin transporter gene, SLC6A4; and the serotonin 2A receptor gene, HTR2A.

The CYP genes are clearly measures of rates of metabolism. A repeat length polymorphism in the promoter of SLC6A4 has been shown to affect the rate of serotonin uptake. The implications of this fact are not clear to me, but according to Wikipedia, genetic variations in the SLC6A4 gene have resulted in phenotypic changes in mice, including increased anxiety. HTR2A influences serotonin transporter binding potential, and variations in the gene have been associated with variations in outcome in treatment with citalopram.

So the answers to my three questions, for Genesight, are:

1. It tells me which drugs are more and less safe and tolerable to use. And if I accept their conclusion that patients switched off red bin drugs improved significantly, then perhaps it tells me which drugs will be effective, but I'm skeptical about this part.

2. The results are less impressive than they'd like me to think.

3. Results are clear and easy to read.  Turnover time is good. Getting hold of a test is not that easy.



Genecept Assay

The genecept FAQ page is much more informative than the Genesight pages. The test can be ordered online or by phone. It's covered by most insurance and they have a patient assistance program. Turnaround time is 3-5 business days from receipt of the sample, also a buccal swab, and they provide expert staff to help interpret results.

The online order form also gives you the option of becoming a "Preferred Provider", which means they'll send patients who are looking for genetic testing to you.

As for function:

The Genecept Assay® report is intended to aid clinicians in making personalized treatment decisions tailored to a patient’s genetic background and helps to inform psychiatric treatments that:

Are more likely to be effective
Have lower risk for side effects and adverse events
Are dosed appropriately

The report consists of two pages, and looks like this:

So they look at more genes than Genesight, and they provide one report about what's safe to use, and another about what's potentially helpful.  And in all honesty, I don't have the energy right now to look up how believable their first page markers are in terms of efficacy, and I think I would need their help to interpret these results, but they do provide more information than Genesight.

Answers:

1. Safety, tolerability, and efficacy

2. I'm too tired to check

3. Easy to get the test, harder to interpret results


Genelex

Genelex allows you to order tests online, too. They claim there is some insurance coverage (See *, below), they have some fancy software that's supposed to be helpful, in addition to their report, and they have a 3-5 day turnaround time.

Genelex restricts itself to CYP450 genes, but it includes three that Genesight doesn't, 3A4, 3A5, and 2C9, but doesn't include 1A2. This is a link to a sample result, which is too long to include as an image. And like Genesight, it's mainly about what is and isn't safe or tolerable to take.*

*Actually, I just learned on the FAQ page that Genelex also includes CYP1A2; NAT2;DPD Enzyme; UGT1A1; 5HTT; and HLA-B*5701, but that these are generally not covered by insurance. I also couldn't figure out what data these additional tests provide.

Answers:

1. Safety, tolerability, maybe efficacy?

2. For the CYP tests, same as above, for others, I don't know

3. The software seems like overkill. The report is clear and moderately informative. You can order the test online.


That's it for this topic, for now, for me. I have yet to decide whether I'm going to use any testing.

Virtually Certified

A while back, I wrote about HealthTap, a platform that allows people to ask doctors questions in almost real time. The company was also developing a system for virtual care, and I recently received an email suggesting I take an online course, worth 2 CME credits, to be certified in said virtual care.

I was curious about the progress in this field, so I did take the course, and am now officially certified. I also accidentally clicked an  "okay" button, thinking it would allow me to print out my certificates. But it was the wrong button. The button I wanted said, "certificate only", but I didn't see it in time. The "okay" button indicated that I was allowing myself to be part of the HealthTap network of physicians. I didn't really want that, but I suppose it doesn't matter since I'm not going to do anything with it. So watch out for this if you decide to try it.

What I was mainly interested in, in the course, were the legal and regulatory issues related to virtual care. And I did learn a couple things. For instance, you do need to be licensed in your patient's state in order to provide virtual care. I don't know if that means the state where the patient resides, or just the state the patient is in when seeing you. I would guess the latter, since I can treat patients, in person, who live in neighboring New Jersey or Connecticut for example, where I'm not licensed, as long as they see me in my New York office.

Incidentally, you don't need to be licensed in any particular state to virtually treat patients outside the US.

The course referenced the Interstate Medical Licensure Compact, which, "Creates a new pathway to expedite the licensing of physicians seeking to practice medicine in multiple states. States participating in the Compact agree to share information with each other and work together in new ways to significantly streamline the licensing process."

A number of states have already enacted legislature that will allow this expedited pathway to proceed, and other states have introduced such legislation. Still others, such as New York, have done neither. One interesting point I noted is that in order to use this expedited system, you need to be primarily licensed in a state that has already enacted the legislature. So if I want to virtually care for patients in Montana, which has enacted this legislature, I can't, because I'm licensed in New York, which hasn't.

That point is irrelevant, though, since there is currently no administrative process for applying for this pathway, although they state that there, "...will be soon."

The video mentioned that there are CPT codes for virtual care, ranging from 99441 for a 5-10 minute telephone Eval/Management consultation, to a 99444 for an online E/M, to a 99446 inter-professional 5-10 minute consult, to a 99490 > 20 minutes of chronic care management. But most virtual care billing is done using the same CPT codes that would be used for a regular office visit, with a GT modifier, e.g. 99213 GT.

Most importantly, 25 states with parity laws, plus Washington DC, have enacted "...legislation requiring private insurers to pay for Virtual Care at the same level as equivalent in-person services, provided the care is deemed medically necessary."

According to this document, in New York, "The law requires telehealth parity under private insurance, Medicaid, and state employee health plans. The law does restrict the patient setting as a condition of payment."

This image depicts which states make it easy to provide virtual care (A is best), and which make it difficult (I'm not sure what the * means):

Aside from that, the course touts the virtues of virtual care, claiming that in some ways, it's superior to in-person care, and giving examples, such as the fact that patients have quicker access to virtual care. They also claim that many, if not most, common complaints can be treated virtually, and a lot of monitoring can be done at a distance, e.g. glucose. In addition, they mention the use of wearable devices for tracking activity, etc., and the up and coming virtual examination tools, like stethoscopes.

The video is careful to note situations which require in-person treatment, such as a wheezing infant, or chest and jaw pain in a 68 year old man.

A bit comical were the presentations. For a company that's promoting care via video-conferencing, they should probably have gotten better people to present in their video. One guy had shifty eyes, another had drooping eyelids and looked like he was falling asleep and forgetting what he needed to say, yet another guy looked like his shoulders were hiked up to the point of having no neck.

While I definitely prefer in-person work, I can see where psychiatry, and especially psychotherapy, are amenable to virtual care, probably more-so than specialties that require a physical examination. But given the regulatory and legal limitations, I'm not ready to go there, yet.

Orlando

The mass shooting in Florida has left me nearly speechless. But I want to post something because silence is the wrong response. 

Maybe I could write something useful about hate crimes or terrorism or psychotic enactments, but that would imply I have some understanding of this tragedy, and I don't. 

All I have is sadness, and my heart goes out to the victims and their loved ones. 

Film Review-In A Town This Size

I recently learned about a documentary, In a Town this Size, by photographer and filmmaker Patrick V Brown. It tells the story of the wealthy, Oklahoma oil town, Bartlesville, in which the pediatrician sexually abused many children over the course of many years. Brown, himself, was one of the victims.

I'm not really going to make this a review, as in, what did I like, what didn't I like, whether it's worth seeing. It is worth seeing, so please do. (That I know of, In a Town this Size is available on iTunes, on DVD from Netflix, and on Amazon Prime.) It addresses very important issues, aside from the obvious one of pedophilia. It addresses what it means to move from being a victim to being a survivor, to finding support, both within oneself and externally. It's also extremely well made, although quite simple-just interviews with a few interspersed pieces of footage and photographs. Mainly, I'm going to relate what it made me think about.

Dr. Bill Dougherty was a pediatrician and a prominent citizen in Bartlesville. He was friendly with the families of many of his patients, and was welcomed into their homes, and joined them on family vacations. Many of the adults considered him an "odd duck", because he had never married. Some assumed he was gay, but in that time and place, this was not a topic for discussion.

In the film, Brown interviews people who, as children, were abused by "Dr. Bill".  He also interviews their family members, including his own parents, as well as a few lawyers and therapists. Everyone who was interviewed was articulate and thoughtful. In part, this is a product of Brown's skillful interviewing-sensitive but appropriately direct. But I suspect it's also a product of the innate selection bias in who volunteers to be interviewed for a film like this, and what parts of the interviews made the final cut.

But the interviews did hit home the point for me that Bartlesville is a wealthy, educated town. There is footage of the Price Tower, the only skyscraper designed by Frank Lloyd Wright, and commissioned by Harold C. Price, of the H. C. Price oil company. There is also footage of the home of Harold Price, Jr., which looks like a Lloyd Wright structure to me. And Harold Price, Jr. is one of the interviewed parents.

The status of the town is what, perhaps, informed the title of the film. I couldn't tell if the idea was, "Who would believe something like this could happen in such a small town with so much money and power?" or, "Who would believe everyone didn't know about what was happening?" I suspect the ambiguity is intentional.

Which brings me to the topic of denial. Brown, himself, told his parents about the abuse after it had happened several times, starting when he was around 6 years old. But a child that young has neither the language nor the emotional wherewithal to describe sexual abuse, and the most he could come up with was, "He leaves his hands down there too long."

In their interviews, Brown's parents comment on their reactions. His father seemed to think he was talking about a normal genital exam, which is uncomfortable and embarrassing for everyone. His mother said that strange as it sounds now, maybe she'd heard of the word, "pedophile", but she couldn't imagine it applied to her family.

I was a bit outraged by their responses. I realize this is anachronistic of me, and their reactions to Brown's revelation were typical for the time, but even if you don't believe your child, don't you wonder? Aren't you at least a little suspicious? Don't you watch to see what your child's reaction is after the next pediatrician visit, or don't you insist on being present for the exam?

In fact, all but one of the parents interviewed say something along the lines of, "This sounds stupid now, but..."

Upon hearing that Dougherty had been accused of sexually abusing children, several of the parents went and comforted him. One ex-marine said he thought, "He's my friend. He'd never do that to me or my children. Besides, he knows I'd kill him."

Years later, after this man's sons revealed the abuse, his wife spent countless hours looking at photographs of her children from that period. The younger son's eyes are haunted. In retrospect, she says, she knew.

By all appearances in the film, Brown has a good relationship with his parents, and is working with his father, who is a lawyer, on changing the laws about the statute of limitations for reporting this kind of abuse. But I found myself outraged once more when he asked his father, "What made you finally believe me?"

The father's answer was that, as an attorney, he had gotten letters from other survivors of Dr. Bill's abuse, asking for legal help. He had to hear it from someone else in order to believe it.

Several of the survivors note that they don't feel angry at Dougherty. Some posit that this is because they don't have the self esteem to generate the anger. I wondered if their anger is threatening to them because it's not just towards Dougherty, it's towards their families, for not protecting them.

Based on the families interviewed, it seems like once it became clear, years after the fact, that the accusations of sexual abuse by Dr. Bill were true, the families did become very supportive of their children and of each other. The film, itself, is a testament to that.

My own reaction to Dougherty was interesting.  Generally, after I get over the initial horror of a story like this, my mind goes to, "What could possibly have happened to this man to have turned him into such a monster?" There's some sympathy involved, even if the crimes are inexcusable.

But I really don't have that much sympathy for Dougherty. There's something terribly opportunistic and psychopathic about him. Some of the survivors suggested that there was premeditation in his choice of pediatrics. My first thought about that was skeptical. I thought he probably felt an irresistible pull towards pediatrics, even though he knew this was a problem for him, and then rationalized the choice by convincing himself that he understood children, and that that would make him a good doctor. Apparently, when he wasn't abusing his patients, he was a good pediatrician.

As the film proceeded, I was less convinced by my argument. Atypically for a pedophile, he abused both boys and girls, although it seemed like there was a predilection for boys. His patterns of abuse also varied, and the choice of behavior seemed to vary with what he thought he could get away with. Several men report having been masturbated by him on the examining table. One woman reports having him take her on his lap and try to get her to masturbate him, while on vacation. On that same vacation he paraded in front of her and her sister in his underwear, showing his penis. It also seems that he sodomized a boy he knew to have psychiatric problems, and to me, that sounds like he thought the boy's story wouldn't be credible.

When Harold Price, who I mentioned above, visited him to offer support after he had been accused of the sodomy, Dougherty said something like, "That's absurd. I would never do that. Besides, he was ugly."

Such was Dougherty's power over these children that Brown seems to be in a minority in telling his parents about the abuse. Most of the kids didn't say anything to anyone. They didn't feel threatened, and they weren't told not to say anything, they just didn't.

Incidentally, after the truth about his abuse had come out, while the statute of limitations for criminal charges had run out, he did lose his medical license. However, he is still alive and living in Bartlesville, leaving his home only in disguise. He recently got married, for the first time, to a woman, at age 81.

The final point that struck me was about forgiveness, and its different meanings. The ex-marine father, who is a religious Christian, was torn for a long time between killing Dougherty and forgiving him. After reading a lot of scripture, and a lot of soul searching, he decided to forgive him. He says it is easier said than done. What puzzled me was the man's description of seeing Dougherty at a church with a woman and her sons, and thinking, There go those kids down the tubes. Does his forgiveness preclude speaking out against Dougherty to protect those children?

Brown's mother says she can't forgive him because he's shown no remorse. She and other's have written him many letters, and he has never responded. And Brown, himself, says he's not interested in forgiving Dougherty. It made me think about whether forgiveness is more for the one being forgiven, or the one forgiving.

In a Town this Size tells a horrifying story in a sensitive way. I think this approach has a further reach than a film that was more graphic and less forward-looking would have. The real strength of the film lies in the question Brown asks all the survivors, "How has the abuse impacted your life?" This simple question places the emphasis on where the survivors are now, and where they're headed, which is why this is a film about survivors, not victims.

One of the most powerful scenes takes place towards the end, where Brown goes to Bill Dougherty's house to confront him. He knocks on the door -forcefully, not timidly-, we hear a dog bark, but no one answers. Brown paces back and forth with his hands on his hips and knocks again. Still, no answer.

There is tremendous pathos in witnessing the courage it must have taken Brown to try to confront his abuser, only to be disappointed. But even if Brown didn't succeed in confronting the external version of Dougherty, I hope that In a Town this Size did succeed in helping him confront the internal version of the monster that is Dr. Bill.

A Tale of Two Hospitals

This is the story of two New York city hospitals, Mount Sinai, and Beth Israel.

According to Wikipedia. Mount Sinai was founded in 1852 as the Jews' Hospital, in response to discrimination against Jews by other hospitals, which would not treat or hire them. It is one of the oldest teaching hospitals in the US.

Also according to Wikipedia:


Beth Israel was incorporated in 1890 by a group of 40 Orthodox Jews on theLower East Side each of whom paid 25 cents to set up a hospital serving New York's Jewish immigrants, particularly newcomers. At the time New York's hospitals would not treat patients who had been in the city less than a year. It initially opened a dispensary on the Lower East Side. In 1891 it opened a 20-bed hospital and in 1892 expanded again and moved into a 115-bed hospital in 1902.^[2] In 1929 it moved into a 13-story, 500-bed building at its current location at the corner of Stuyvesant Square. It purchased its neighbor the Manhattan General Hospital in 1964 and renamed the complex Beth Israel Medical Center, located at First Avenue and 16th Street in Manhattan.


According to other verbal sources I've encountered, Beth Israel Hospital was founded in response to discrimination by Mount Sinai against poor Jewish immigrants on the lower east side. Mount Sinai would not treat them, but restricted its Jewish patients to middle- and higher-class Jewish immigrants from Germany.

I like to believe that this is the reason for the inscription on the entrance to the original Stuyvesant Square building:

It's a little hard to see, and it's in Hebrew, but roughly translated (by me) it reads:

Welcome! Welcome! From far and near. So says the Lord and his Healers. (Isaiah 57:19)

Hospitals in NYC are like 7th graders. They merge, split up, merge again with a different hospital, move around. For a while, Beth Israel belonged to a group of hospitals known as "Continuum," which included Albert Einstein Hospital, from which Beth Israel got its medical school affiliation. A few years back, Columbia Presbyterian joined up with New York Hospital Cornell, and became New York Presbyterian. These two hospitals are in very different parts of Manhattan, so the merger gave them access to a huge group of patients from diverse neighborhoods. My guess is that this was done for financial reasons. Then Mount Sinai decided to be even bigger, and subsumed Beth Israel, as well as St. Luke's/ Roosevelt (these two had merged years previously, and were formerly affiliated with Columbia).

For a little orientation, this is a map:

This gives you an idea of the current relationship statuses, which I've color coded. Mt. Sinai is the white star. Beth Israel, now called Mt. Sinai Beth Israel, is all the way downtown in red. It is the southern-most hospital in Manhattan.

Well, in case you didn't read it in the NY Times, Mt. Sinai Beth Israel Hospital in Manhattan Will Close to Rebuild Smaller.

The 825-bed Beth Israel will be closed over the next four years, to be replaced by a 70-bed hospital somewhere nearby, with an ER a few blocks away. Residents will be dispersed to other Mt. Sinai hospitals, union employees will be found new jobs. And according to an email I got from Mt. Sinai, where I'm affiliated, everyone else will be assisted in finding new employment. I suspect that's not precisely what will happen.

Ken Davis, President and CEO of the Mt. Sinai Health System (and former chair of psychiatry) explained that health care is too expensive, that Beth Israel lost $115 million last year and stood to lose $2 billion in the next 10 years, that hospitals are no longer the most efficient vehicles for delivering care, etc.

They plan to have 16 outpatient practice locations and 35 stand alone operating and procedure rooms.

Interestingly, from what I can tell, they plan to keep the psychiatry building, and expand its services. I assume the department actually makes some money, although I thought that was because of the rapid turnover on the Dual Diagnosis unit.

I worry about the impact on the community. There used to be 3 hospitals in Beth Israel's area, Beth Israel, itself, Cabrini, and St. Vincent's. Cabrini closed in 2008. St. Vincent's, much larger, and beloved by the community, closed in 2010. It's been replaced by some pretty fancy condos. Beth Israel is also situated in an extremely desirable neighborhood.

Going from 825 beds to 70? It may look like, what's the big deal, there are dozens of hospitals throughout NYC. But there are 8.5 million people living in NYC, plus people come in for treatment regularly from neighboring New Jersey and Connecticut.

Dr. Davis may be correct in stating that hospitals are not the future of medicine. But I don't believe 70 inpatient beds are adequate to the needs of all of lower Manhattan. We seem to have come full circle since 1890.

The word I translated above as "Welcome!" is Shalom, and the Hebrew word has multiple meanings. It can mean welcome, peace, and hello. It can also mean, "Goodbye."