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Wednesday, December 17, 2014

RxNT in Progress

I thought I'd follow up my previous EPCS post to let you know how things are going with RxNT.

I had a bit of a problem setting up the soft token, which is generated by an app called, Safenet Mobilepass. In order to get started, you need to send in an activation code, which shows up on your phone screen. The instructions tell you to take a screenshot so you don't lose the code. My iPhone takes screenshots by pressing the little round button and the top right button simultaneously. My timing was a little off on my first attempt, and I lost the screen. I tried to go back one step, but it wouldn't let me, and I had to get out and start over. It worked the second time, but gave me a new ID. I still can't get rid of the original ID, "Token 1", but I can't use it, either.

My first attempt at sending in a prescription for a controlled substance didn't work. It seemed to go through fine on my end, but then the pharmacy called and said they were getting a message that I wasn't set up for controlled substances. So I emailed support at RxNT, etc. Turns out, the problem was on the pharmacy's end.

Support got back to me the next morning-so that was good. they suggested I delete the "Token 1" ID, but didn't tell me how. I wrote back that I had already tried, and there's no obvious way to do it. Haven't heard back from them on that point yet.

Suffice it to say, all beginnings are difficult.

Other topics of interest:

There's no way to pay RxNT online. No PayPal or anything like that. You have to email or fax a credit card form. That seems like a pretty easy thing to rectify. I mean, I even take PayPal in my office.

There's a "recent rx" tab that lists recent prescriptions (duh) if you click on it. But I can't figure out how to set a date range for how recent I want it. It seems to default to the 4 most recent. You can generate a Rx Report, where you can set the date range as you see fit. But that's just for a reportnot the "recent rx" page.

Similarly, I can't find a screen that simply lists my patients alphabetically. I don't have the EHR set up, so that may be the reason.

Refill requests don't have a direct link to editing. I had to go through the patient link to edit. Maybe I need to practice more, here, and there's something I'm not noticing.

I get a "data could not be loaded" message a lot. But then the data seems to load normally, so I'm just ignoring it.

Finally, this is my silly hangup, but the app icon for the soft token:



Reminds me uncomfortably of the logo for Panera Bread:





I don't know why this bothers me. Something about the relationship between a big, mediocre food chain, and the company that allows me to prescribe controlled substances.



Sunday, December 14, 2014

Ziprasidone and DRESS

In case you haven't seen it, the FDA released a safety communication about Ziprasidone (Geodon) induced Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). The FDA reviewed 6 worldwide cases of DRESS temporally associated with initiation of Ziprasidone, specifically, within 11 and 30 days of initiation of treatment. There were no fatalities. In 3 of the cases, Ziprasidone was initiated, the patients developed DRESS, Ziprasidone was discontinued and later restarted, at which point, the patients re-developed DRESS, only faster than the first time around. 3 cases reported concomitant use of other drugs associated with DRESS. (I believe, based on the ambiguous FDA description, that) all 6 cases were hospitalized.

To review, mostly from UpToDate, DRESS is rare-anywhere from 1-5/10,000 in patients taking carbamazepine and phenytoin, and 1/300 adults or 1/100 children taking lamotrigine. Mortality is 10%. The most common associated agents are carbamazepine, phenytoin, lamotrigine, phenobarbital, and allopurinol. Etiology is unclear. Reactivation of Herpesvirus or EBV infection concurrent with drug hypersensitivity is common.

DRESS usually begins within 2-6 weeks of drug initiation, and most commonly presents with fever, malaise, lymphadenopathy, and skin eruption. There is liver involvement in 60-80% of patients. Kidney and lung are also frequently involved. Hematologic abnormalities include leukocytosis with eosinophilia and/or atypical lymphocytosis.

Treatment consists primarily of withdrawing the offending agent, with systemic corticosteroids for severe cases of tubulointerstitial nephritis or interstitial pneumonitis. Skin eruption and visceral involvement resolve gradually, within 6-9 weeks. In up to 20% of cases, the disease persists for several months, with a succession of remissions and relapses. The long-term, natural course consists of spontaneous flares.

One more thing to discuss with patients before starting them on ziprasidone.

Tuesday, December 9, 2014

App Review: NbNomenclature

A while back, I wrote a post called, What's In A Name?, about a proposed 5-Axis drug nomenclature system. The idea was that our current system of describing psychoactive medication involves terms like "Antidepressant" and "Antipsychotic", even though antidepressants are sometimes prescribed for anxiety, and antipsychotics for depression, and this is confusing, especially to patients.

Instead, the new system has a different way of describing drug class, along with mechanism of action,  indications uses, and relevant side effects, as well as neurobiology.

I had some concerns about how this system would be used, and by whom. There was talk of a future merge with DSM, whatever that would mean. It was created by people with strong ties to industry. The claim is that it would be a collaborative model, and I wondered what the charge for that collaboration would be. And I also wondered if reporting off-label uses as part of the drug description would influence future drug indication.

This was over a year ago.

More recently, Clinical Psychiatry News reported the launch of the drug terminology overhaul. The launch was accompanied by the release of a paperback book, as well as a new app, NbNomenclature, available for free download on iTunes App store and google play.  See also Nigella's comments on The Practical Psychosomaticist.

Not sure why Nigella had difficulty downloading it. Maybe because she was using an ipad. I put it on my iphone, and it does work. I haven't attempted an ipad yet.

So  I thought I'd share some of my thoughts. The home screen looks like this:





If I type in say, nortriptyline, I get this (the screen shot is missing the neurobiology section, down at the bottom, but I'll get to that):


It gives the official indication as Major Depressive Disorder, under the check mark (or tick, if you're British), but the + sign gives you the conditions it's used for.

Common and serious side effects under the - sign, that's useful.

What it doesn't give you is what you do get on something like Epocrates, dosing:


(Yes, I get crappy signal. Thanks, Verizon)

This lack of further information is strange in light of what I read in the app's stated mission:

"This proposed nomenclature aims to reflect the current pharmacological knowledge base and cannot necessarily represent the ultimate scientific truth...we feel that it's better to present a cutting-edge scientific interpretation than to wait for the definitive conclusion. We need to treat our patients now, and we cannot postpone treatment until all the facts are known.

Therefore this nomenclature is based on:

1. The need to treat now.

2. Updated neuroscience insights.

3. The judgement of the members of the task force." (italics mine)


With all this emphasis on the need to treat NOW, it would be nice to know how to dose the patient sitting in front of me, and what dosing forms are available for writing a prescription.

Maybe the Nb people didn't think that was important since we'll all be using electronic prescribing software that will tell us dosing options and forms. But for me, it keeps the app from being really useful, except perhaps to medical students who don't prescribe anything and don't need to know dosages. (Don't freak. I do remember most dosage forms, but there are some meds I don't prescribe very often, and I look those up just to be sure. Also, when titrating or tapering, sometimes you need weird, in-between dosage strengths.)


One nice feature is that if you're looking at a drug, and you swipe left, you get a similar drug. One left swipe from nortriptyline takes me to amoxapine.

Curious about this feature, I looked up Strattera, which it lists as a norepinephrine reuptake inhibitor (NE-RI in the app's abbreviation system). One left swipe takes me to desipramine, another NE-RI, then to lofepramine, maprotiline, and reboxetine, all indicated for Major Depression, unlike Strattera. So the new classification system is based strictly on mode of action.

Again, my question-who is going to use this? If I'm looking up Strattera, then presumably I want a medication for ADHD. If I'm looking for an alternative, I don't want to end up with an antidepressant. As an experienced clinician, I already know what other ADHD meds are out there. For an inexperienced clinician, this could cause a lot of problems. Or maybe the idea is for doctors to experiment based on mode of action.

Okay, so I couldn't find another ADHD med by swiping. I went back to the home page, clicked on "approved indication", and looked up ADHD. I got two hits: amphetamine and lisdexamfetamine. Aren't they missing a few? It turns out, they have several categories of ADHD. The one I checked was just ADHD. ADHD in children in Canada gives me guanfacine, ADHD in children >6y in the US gives me clonidine, and ADHD in children >6y and adults gives me methylphenidate and atomoxetine, right back where I started. Those are all the ADHDs they had.

In contrast, looking up ADHD in Epocrates gives me a list of 31 drugs, from Adderall to Zenzedi. Kinda easier to find alternatives.

As for the neurobiology section, nortriptyline looks like this:


Those highlighted phrases don't link to anything. Maybe they will down the line.

Bottom line: I can't think why this would be useful to anyone who already prescribes medications. And I'm not sure what the long term implications of a system like this are.

If an app rating consists of "A", "AP", and "APP", from worst to best, I rate it a "A".

Thursday, December 4, 2014

Behind the Violence

(Note: This post was written a week earlier than published, but did not save properly so I had to rewrite it. Sorry for the delay)

There was an article in the NY Times last week entitled, Adam Lanza's Mental Problems 'Completely Untreated' Before Newtown Shootings, Report Says. It linked to a report released by the Connecticut Office of the Child Advocate (OCA) on November 21st of this year, Shooting at Sandy Hook Elementary School. This is a 114 page report produced by the OCA to, "...focus on Adam Lanza (hereinafter referred to as AL)  and [to] include a review of the circumstances that pre-dated his commission of mass murder...The charge was to develop any recommendations for public health system improvement that emanated from the review. Authors of this report focused on AL's developmental, educational, and mental health profile over time, the services he received from various community providers, and ultimately his condition prior to his actions on December 14, 2012."

It's a pretty extensive review, written by six main reviewers, 8 additional contributors, and with the assistance of the Connecticut State Police, the FBI, and the US Attorney's Office, among others.

Typically, the Times goes for the sensational, "Completely Untreated". To me, that conjures up an image of a child who is visibly deteriorating, and ignored by everyone in his life. And that is so not what happened.

I read the report, and before I describe my impressions, let me convey what prompted me to bother reading the whole thing. As you probably know, on November 18th, two armed Palestinian men entered a synagogue in Jerusalem, and murdered 4 of the men who were praying there. A fifth man, a police officer, later died of his wounds. The two Palestinian men were killed at the scene.

One of the men murdered while praying was a cousin of mine. Not a first cousin, but not a very distant cousin, either. I probably hadn't seen him since I was a child, so I don't mourn for him personally, although my heart goes out to those of his family and friends who do. But the killing does feel personal to me.
This blog is not a forum for discussion of politics in the Middle East, and I will refrain from sharing any of my opinions on that subject. But my professional life involves trying to understand why people feel what they feel, think what they think, and do what they do. Since I never expect to have access to that information about the men who murdered my cousin, I find it helpful to know that many people took the time to try to understand AL and the horror in Newtown, CT.

The authors of the study were very good about emphasizing the fact that no one incident or condition or lapse in treatment has a direct line to the outcome of a mass shooting. They stressed this repeatedly, in boldface. Unsurprisingly, one of their main conclusions was that guns are dangerous.

There is no clear evidence of bullying. The closest anything came to a history of bullying is the comment by someone who knew him and was interviewed that to his knowledge, AL was not bullied, but he wouldn't be surprised to learn that he had been. There are indications that many people, including fellow students, were kind to him.

It was clear from very early on that AL had difficulties with communication. In the early years of elementary school, he received speech and language tutoring to help with articulation. The report noted that this tutoring did not focus on AL's other communication difficulties, i.e. the social ones. So once he mastered the articulation issues, the tutoring stopped.

This type of help is characteristic of one of the difficulties in what happened with AL. He had problems. People in his life knew about these problems and tried to help with them. The school was involved. Bits and pieces of the problems got addressed, with a notable focus on helping AL navigate his academic requirements. No one regularly involved with AL had a grip on, or was able to address the bigger picture.

Overall, AL did okay in elementary school. He was a decent student, if odd. But there was one red flag noted in the report. In 5th grade, AL had a school assignment that involved writing some sort of comic book. He collaborated with a classmate, and they wrote, The Big Book of Granny, about a female caregiver and her grandchild. According to the report, the book was extremely violent, way out of proportion to what would be expected of a 5th grade boy. They didn't include any details.

I think this is a red flag in retrospect. If you're a 5th grade teacher, and one of your students hands in something like The Big Book of Granny, you might be concerned. You might even show it to the school psychologist. Or, you might just say, "Well, that's a bit extreme, but he's not a violent child. He doesn't get into fights. He's not disruptive in class. He's a good student. So what if he has a violent imagination?"

Even if you were quite concerned, what would you do? Insist that he be in therapy because of a homework assignment? And in the absence of other evidence of violence? I can't imagine that every 11 year old boy with violent fantasies goes on to become a mass murderer. And in fact, the boy who co-authored the book now has some serious psychiatric illness, but he's never killed anyone.

Middle school was more difficult for AL, given the changing social environment for early adolescents. He switched to a different school, and later stopped going to school entirely. His anxiety levels had skyrocketed.

At this point, his mother took him to an ER in Danbury, ostensibly to get a note excusing him from attending school due to his anxiety. The hospital suggested further testing and evaluation, but Mrs. Lanza declined, stating the experience was too stressful for AL ("torture" was the word she used), and in any case, he was to begin seeing a community psychiatrist in a couple weeks. The ER wrote a note indicating that AL should stay home from school for 3 days.

AL did begin working with a community psychiatrist, who wrote a note to the school stating that AL could not return to school at that point, and might never be able to return to school.

This is where AL's life really begins to unravel, and we start to see the other characteristic problem in attempts to help him begin to unfold. Mrs. Lanza, who no doubt had her own troubles with anxiety, tried to fit the world to AL, rather than to help AL adjust to the world. She seems to have gotten the community psychiatrist to collude with her. This man is no longer in practice, due to allegations about sexual misconduct with patients, but nowhere in the report is there any indication that AL was one of his victims. However, one wonders about his ability to maintain boundaries with his patients, and their families.
The school classified AL as "homebound" rather than "homeschooled". "Homeschooling" is what it sounds like. But "homebound" means that the student is expected to return to school, and there is a specific plan, with a timeframe, for getting him back to school. This is one of the places the school dropped the ball. Any plan that existed was vague. And as far as I could tell, there was no real discussion of moving AL to a therapeutic school, or any other kind of school setting.

Another point that came up in the report is Mrs. Lanza's ideas about her own health. She believed she had MS and was dying, but there was no evidence to support this conclusion.

During this period, the pediatrician's notes indicate obsessive compulsive behaviors, including hand-washing leading to excoriated skin. There is no documentation of the reasons for the behaviors being explored. He was prescribed an ointment for his skin. Again, a small, easily treatable problem is addressed, and the larger, more difficult problem is ignored.

High School was a little better for AL, at least at first. He managed to return to school, and took some high level classes. He even joined the Tech Club, and functioned well enough in it to host one of their events at his house. But by the end of 10th grade, his mother decided he'd be better off at home. He had increasingly severe OCD symptoms, would not touch anything handed to him directly, but would pull his sleeves over his hands to accept it. He also began influencing his mother in compulsive ways, such as insisting she stand a certain way.

Shortly after he started high school, his father sought an evaluation for him by the Yale Child Study Center, for his OCD and Asperger's symptoms. This evaluation expressed deep concern about the way his mother, in particular, shielded him from anything that might produce anxiety. Previously, when Mr. Lanza sought help for AL's social difficulties, Mrs. Lanza wrote (note? email?) that she had not focused on this aspect of AL's difficulties, and was, "More concerned with keeping [AL] as comfortable as possible and just getting through each day." The evaluation brought up the possibility of a therapeutic school, and made several other suggestions, including continued treatment at the Child Study Center, and intense parental guidance. AL had several sessions, but ultimately, Mrs. Lanza rejected their suggestions, defaulting to the community psychiatrist, who she felt knew him better. She also felt that their recommendations would be too great a strain on AL.

Mr. Lanza has stated that he was a "weekend father", even before he and Mrs. Lanza separated when AL was 9. He was concerned, and tried to get the school on board with the Yale recommendations, but there is no record that the school even had a copy of the evaluation. This is yet another instance of the limitations in the help AL received. His father was aware of difficulties, and tried to help in a constructive way, but was much less involved than his mother, and in any case, Mr. Lanza's attempts to get care coordinated with AL's school were thwarted.

There was a brief trial of medication, during which Mrs. Lanza reported that AL had complained of various side effects. AL or Mrs. Lanza or both decided to stop taking it.

The school misclassified AL's difficulties. He could have been classified as autistic, or having "emotional problems"-both of these classifications would have entitled AL to more extensive services  that addressed his social and emotional difficulties than he received. Instead, he was classified as Other health Impaired (OHI), a category that is intended for students with chronic or acute health problems impacting their education, and received 10 hours per week of tutoring. In general, the documentation by the school is terrible, and communication with other people involved in AL's care was, at best, fragmented. In addition, the community psychiatrist lost his records, but apparently treated AL for two years (based on payment records).

In 11th grade, AL left high school, but took classes at a local state college for high school credit, so he could graduate early, which he did, in 2009. AL's IEP (Individualized Education Program) stated that his "transition skills" were "age appropriate", while also noting his significant mental health disabilities, and without any plan to address these.

AL was severely isolated by this point. Mrs. Lanza attempted to adjust the world to fit him, rather than the other way around. In her defense, she was intensely involved in his care, anxious in her own right, and was attempting to support a son with very complicated problems. Her interchanges with the school indicate that both parties were trying to get AL through school, as he expressed a wish to be in school and treated normally. In the midst of this Herculean task, it must have been difficult to make room for considerations of his social/emotional disabilities. Mr. Lanza deferred educational decisions to Mrs. Lanza.

After high school, AL retreated even further. Towards the end of his life, he rarely left his room. He obsessively played hours of Dance Dance Revolution, becoming emaciated. His adult medical record notes nothing remarkable about his presentation, despite weighing 120 lbs. at 5'10". He refused any contact with his father. His mother appears not to have communicated the level of AL's deterioration to Mr. Lanza. He spent increasing time with an online community obsessed with mass murder.

It remains unclear what made him choose the particular day of his rampage. It was very carefully planned out, so he didn't just "snap". He was not considered psychotic by those who reviewed his records. His mother had recently informed him of her plan to move from Newtown, and had gone away to New Hampshire for several days, 2-3 days before the shooting. Prior to her trip, AL sustained a head injury, described by Mrs. Lanza as "bloody, bloody, bloody."

That's all we know.

This is a lot to take in. I don't feel like it's clear what led to the mass murder. AL's lifelong trajectory was poor, but I don't see anything about it that implies a direct line to the shooting. There could have been other outcomes. Maybe not towards the end of his life, but it seems like the Sandy Hook shooting was already being planned, then.

What can we learn? Maybe that various providers of care need to talk to each other clearly. That access to firearms is dangerous. That it's not only the whole child who needs to be considered, it's the child and his whole family. How fitting that poor communication between care providers took such a toll on a child who suffered from an inability to communicate.