Sometimes "Failure is the best way to learn" but here's hoping it's not the only way.

This isn't the first topic that I thought I would write about but I do think it's important.  Unfortunately I also think it's totally nebulous, not straight forward, might not help anyone. It's got to do with making decisions about your care. My hope is that if you have a rare disease my experiences might help you whether the roads I've taken were the best or not.

I can't tell you how many times my doctors have told me that I spend too much time researching; my medications, side effects, symptoms, therapies, concocting theories with a liberal arts degree and the internet.  They actually think it's detrimental to my mental health and they want to see me enjoy my life as much as I can for however long I have left. The thing is, I think it's foolish to not investigate this stuff and ask questions and make sure all the t's are crossed to ones satisfaction.  For me it helps build confidence in treatment strategy so I believe in what I'm doing even when it makes me nauseus for months and I can't eat for a week.  If you've read any of my previous posts on this blog you'll know I'm a huge fan of Viktor Frankl whose thoughts on purpose in ones life really resonate with me.  Having a better grasp on my treatment helps me define that purpose.

Anyway the reason I decided to write this post was actually because of an article I saw on the front page of reddit - The FDA buries evidence of fraud in medical trials. My students and I dug it up. - Please don't think I'm going to go on a conspiracy rant. This article just stirred up a line of thinking that was originally ignited by my sister when she began sending me quotes from a book by Jerome Groopman called How Doctors Think. They are sort of two sides of the same coin that is finding out how to treat these fragile jars of clay we inhabit; how do I get my doctors to a proper state of empathy and, conversely, how do we use this understanding to find the right exogenous supports.  

So on one side of the coin I need to get my doctors on the same page as me.  They have to understand my complaints often beyond just lab results. For that matter we need some measure of proper communication to make sure the right tests get ordered in the first place.  Personally, I have often felt like I've had a hard time accurately communicating with my doctors and I wasn't really getting my concerns through. Or, worse yet, they were getting through and being thrown right out the door.  That's where lines like this gem would ring so powerfully with me:

"Statistics cannot substitute for the human being before you; statistics embody averages, not individuals.  Numbers can only complement a physician's personal experience with a drug, or a procedure, as well as his knowledge of whether a "best" therapy from a clinical trial fits a patient's particular needs and values."

I believe medication like antibiotics or chemotherapies can save peoples lives, but each person reacts differently and we've yet to come far enough (by a long shot) to understand how an individual is going to react to something before administering it.  There's a story of a woman in the beginning of How Doctors Think that describes a woman who had a chronic illness for over a decade and because none of the doctors were able to properly diagnose what was wrong, they labeled most of her problem as psychological.  I can personally relate to this from a number of different examples but here's a short one:

I had a pulmonary infection shortly after my Bronchiolitis Obliterens (BOS) diagnosis (probably because of prednisone*...) of Asperggillus Terrace and the go to drug for it was Voriconozole.  It has a lot of weird side effects like visual hallucinations.  Now at this point it had been 2+ years since my transplant and on top of bactrim, the transplant, the GvH and other meds I had to stay out of the sunlight.  Voriconozole increased my risk of skin cancer which added further reason to stay out of the sun. Obviously I had concerns about this, as did my physicians, but "do or die" had once again visited my doorstep.  My doctors however, were overly concerned about the concurrent mycobacterial infection I had and this influenced my treatment. 

For one, they didn't pay very much attention to the fact that my Voriconozole levels were never therapeutic.  Second, despite it constantly showing up on my bronchs and the low blood serum levels they were sure A.Terrace was being treated and would just take time.  Third, they ignored my perisistent questions about the Flovent I was taking and the fact that I lived in a moldy house in Florida and the possibility these were promoting it's growth/sticking around.  It took a few months** before they decided to try and raise my Voriconozole levels by increasing my dose.  After 2 more months of doing this they finally realized that I was rare yet again and metabolized Voriconzole so quickly we were approaching toxic dosing and still not in therapeutic range.  The Infectious Disease doctors changed to a newly released formulation of Posiconozole, my BOS pulm specialist agreed it might be smart to try dropping my Flovent to 1 puff twice a day instead of 2, and we had to move out of our house.

3 WEEKS later I was in the hospital for a Stenotrophomonas infection and the bronch then showed I had cleared the A.Terrace infection... 6 months of Voriconzole, 3 WEEKS on Posiconozole.  In those previous 6 months I continually brought up my concerns about Florida, my house, Flovent, Vori...but my doctors just reiterated to me the danger and importance of my continued use of the prescribed medication.  

I know I am not the best communicator and have even seen my physicians notes sometimes marking me as some kind of spazzy basket case.  Honestly it's the worst kind of feeling when it's as if nobody understands you. Why do they think this?  The only reason I've gotten from my doctors is that I am not concise enough and I try to let my doctors know EVERYTHING that's going on.  I realize that can be a problem and that there's simply too much that I keep track of that distracts them from doing their job.  It's tricky though...for example:

Bronchiolitis Obliterans (BOS)

Every winter since I started chemo at the end of 2009 I'd noticed a slight pain in my upper chest cavity upon deep inspiratory breaths.  This didn't really bother anybody as I had Bleomycin during my first line Hodgkin's treatment (ABVD).  This is known to cause lung problems and this was really pretty minor.  It persisted every winter and I brought it up but no worries.  During 2011 I got my autologus stem cell transplant and, probably in the beginning of 2012, I noticed I was really getting short of breath when I went on my walks.  I brought it up and considering the downtime I've had from the chemo before during and after transplant, the antibiotics, the GvH, addressing the hypothyroidism, the steroids, the difficulty in maintaining caloric intake...it takes quite a toll so we thought I was probably just deconditioned.  

I wish to God I had pushed harder and we had done a Pulmonary Function Test (PFT) at the time but there was already a lot going on so it slipped under the radar.  It continued to get worse and that winter, when that inspiratory pain returned, I noticed a wheeze along with it.  This prompted me to be more vigilant in my inquiry.  They sent me to a pulmonologist, did a PFT and discovered that my FEV1 (forced exhalation volume over 1 sec) had decreased to something like 36% if I recall correctly.  Along with the other numbers in the PFT the diagnosis was pretty clear; Bronchiolitis Obliterans (BOS).  

I don't blame anyone because you could say it was my fault for not being more persistent, or not noticing the severity of dyspnea (I find my body adapts to things or I get used to them so something insidious occurring over 16 odd months isn't as noticeable as a broken bone).  Or say my doctors were to blame for not catching the signs; it's extremely rare for GvH to cause BOS and there were definitely other more plausible explanations.  But it was missed and because of that it effects how I think of things.  It has made someone already sensitive to changes and side effects MUCH more so and it has not made interaction with my doctors any easier EXCEPT with the doctor that was with me when we were late on the BOS diagnosis (my primary doctor).  He understands me better than anyone and this event has only helped him take my concerns even more seriously and help me better explain myself to other doctors so they do as well.  

The Heart, The Thyroid And Lots Of Theorizing

This is an example of what happened after I was diagnosed with BOS (and then the Mycobacterium Abscessus and Aspergillus Terrace infections). I go in and say, "Hey doc, my heart has been feeling weak for a number of months."  He ordered an echo, an EKG some bloodwork and even a consult with a cardiologist.  That's above and beyond! With my luck though we didn't find anything but something in my left ventricle that is common in patients that have had chemotherapy; nothing of concern I was told.  Something popped into my head about previously reading how the Thyroid is important in heart health and I bring it up and a consult is scheduled with an Endocrinologist so I can express concerns about how maybe my T4 only supplementation (synthroid) might not be enough for me. I had been on thyroid supplementation since it was discovered I had hypothyroidism about a year after my stem cell transplant (very common so make sure you regularly check your TSH levels if you get one).  During this time my doctors at the NIH, on a hunch, discovered that after my years on prednisone* my adrenals were not making cortisol. 

To oversimplify, you need cortisol to convert T4 to T3 and both (along with others) are closely linked to testosterone.  My bloodwork showed low T3, low TSH, high T4 and low testosterone.*** Since this was the same time my doctors found zero cortisol in my blood we started hydrocortisone supplementation and those numbers even out a bit but my heart still "feels weak" with the left ventricle explanation not getting any attention.  So to me I'm thinking about how all these hormones are important in regulating themselves, converting one another into needed chemical formations and I  start to think that, as little info as I seem to be able to get out of my Endocrinologists and online about even the FUNCTION of T1, T2, their subgroups and calcitonin I figure maybe there are other things that I'm not making that might help optimize my thyroid supplementation.  

Sad thing was the only thyroid related symptoms that the Endo's would consider were that my testicles were perpetually freezing cold and crammed up into my perineum, my hair was thinning, I was always tired, and often depressed/apathetic.  The hair thinning and fatigue often being attributed to GvH and depression/apathy to pretty much anything from predispotion, medication, situation, etc..  I read about dessicated thyroid which is extracted from pigs and contains all of the same hormones that the human thyroid makes.  After many months of pestering people I get a prescription and find an Endo that will work with me in trying this "experiment."  My thyroid numbers varied a bit as we go from Synthroid (T4 only) to Armour (dessicated) but that's actually expected with dessicated as it historically doesn't give as consistent bloodwork as T4 only supplementation and is one of the main reasons it's not used so much.  I notice in a few weeks however that my testicles got a little warmth in them and they started to relax.  About a month later I feel a little less...weary of dealing with being sick and tired. Maybe a month later I noticed my heart stops "feeling weak."  Bonus! Months after that I had to do an Echo again to test for a PFO because I was having hemiplegic migraines and there is no comment about my left ventricle… 

Those were just two examples of things that have gone on in trying to get this body healthy.  Symptoms brushed off versus symptoms deeply analyzed.  I could go on and on with examples where I've been overly concerned about something that ended up resolving on its own.  On the other hand, I just learned this last Friday I might have another problem that's gone on for too long and might become another very serious problem because I let my doctors assuage my concerns with their experience.  

That's one side of the coin in making decisions about treatment and it segues into the other side with a specific drug that I and my primary doctor were thinking of trying to combat both my GvH as well as the BOS.  

The Other Side Of The Coin

My primary doctor had recently been to Italy were he had been told how they have empirically seen good results treating BOS with Rituximab.  No studies to support it yet though.  I did a little research on it and read about how it has been known to cause pulmonary fibrosing, albeit very rarely.  I asked my primary about it and he actually had one patient years ago that had this reaction and died because of it.  This, obviously, bugged me.  

I was blessed to go to my primary because he had personal and extensive experience with a new chemo that we used when I relapsed after my transplant.  He is by far the best doctor I've worked with in the last 6 years and his experience and opinion has become very important to me.  But, on this course we disagreed.   I wanted to double check all that we could before trying it out and asked if he could find out if there was anything out there that showed patients with previous lung disease like BOS, COPD or CF that increased the chances of pulmonary fibrosis. 

This is where that article on the FDA comes into play.  There wasn't any research available to my doctor so he contacted Genentech, the manufacturers. They have people to help find this kind of thing out.  My primary said they sort of gave him the run around for a bit and finally sent out a representative to talk with him...where nothing was accomplished.  More talk, no numbers and no data.  I went up to the NIH for another followup on some of the trials I'm on and spoke with the BOS specialist up there and she informed me that they've seen the opposite - no benefit using it versus the methods they use (flovent, azithromycin and cingulair) to treat BOS nor for the prevailing GvH symptoms that I had (eyes, mouth, musculoskeletal and possibly neurological).****

It's All Madness!

So what all of that kerfuffle above is trying to say is that your treatment, my treatment, is all based upon a mix of scientific data, conjecture, gut feelings and experience.  Experience of the physicians as well as the patient.  What are you supposed to do when you're unsatisfied with what a doctor has told you and you tell them you want a second opinion.  If they're worth their salt they'll encourage it but what happens when the two opinions you get differ drastically?  What if you were only unsatisfied with the first doctor because they were in a rush and you felt they brushed you off but TRULY (and there's no way to actually KNOW this) they had the right course of action for treatment?  That's why I've made such a long winded post.  I figure the best way I can help is to show you what I've done and then you can make a decision. 

So, what do I do?

I pray.  A lot.  I listen to my body and even if there's some ludicrous idea that pops in my head I will absolutely investigate it (only ONE of my doctors believes that chocolate seems to have had an effect on my Liver Enzyme's because when my GvH was bad I had a hunch, I told him my suspicion and we tracked it).  I try my best to listen to what my doctors say even if my first impression is that it makes absolutely no sense and wait to go online to find out if indeed, they made no sense.  I do research until I feel satisfied with the course of action and I realize that 90% of the time I WILL NOT LIKE the course of action.  I ask lots and lots and lots of questions and come up with lots and lots of theories about how things might be interacting (it's surprising how on the mark we as patients can be about what's going on with our bodies if we just take note and think). I thank God every day for the things I can still do and what He's gotten me through.  I make bad decisions sometimes.  I have become an arguable degree of neurotic about many things. Knowing my doctors are fully aware of my history, my reactions, my concerns and my stubborn determination to do what is necessary, probably falls under that neurosis.  I apologize a lot for being difficult, both in my diseases and interactions.  

I remember that my doctors are human beings and every human being poops. And then I hit play.  


* I was on prednisone on and off for my Graft vs Host.  Mostly "on" sadly but as you have to ween off of it the doses were like a roller coaster. However,  I need to point out to anyone that gets BOS that I'm told prednisone does NOTHING for BOS but it does help with Cryptogenic Organizing Pneumonia [COP] which previously has been called Bronchiolitis Obliterans Organizing Pneumonia [BOOP] which is a misnomer.  Make sure your doctors are being very clear with you about this and that THEY know the distinction. I recommend getting in contact doctors at the NIH about their research that shows this.  There are great doctors in the Bone Marrow Transplant (BMT) area a part of the National Cancer Institute (NCI) with lots of BOS experience.  Be prepared to deal with differing opinions, treatment suggestions, and methods of care.  

** I say a few months for simplicity. These "few months" were after my entire Infectious Disease (ID) team was changed at the NIH and I was put on another clinical trial so I could have access to Clofazamine.  Interesting story.  Ya know I just wrote about how my doctors were overly concerned about the mycobacterium infection?  They originally told me that it was going to be at least 18 months of treatment because mycobacterium are really slow growing bacteria which means the antibiotics, as powerful as they are, are slow to act.  Despite this the ID doctor, about 5 months into treatment, wants to stop because of his concerns of toxicity (I still highly respect this doctor and am actually disappointed he's not still part of my care but you really can have "too many cooks...").  God forgive me, but I used a few expletives in trying to make sure my doctors understood that I had a very bad history of things coming back and wanted them to be absolutely sure this was the right decision. That I wasn't as concerned about toxicity as they were.  That I was willing to do whatever had to be done.  The only other person with BOS and M.Abscessus that they had seen had died from the combination and this was made clear to me so I didn't know why we were stopping.  Yes my CT was looking really good.  Yes my numbers were improving.  Yes I was breathing better.  But we didn't even do a bronch or a sputum culture to make sure it wasn't still present.  But I trusted their judgement and the hopes that my body would deal with the mycobacterium since, hey, that's what the human body is supposed to do, right?  And let's be honest, who wouldn't want to stop drugs that made you nauseous,  gave you migraines, and took up large portions of your day.  

Well low and behold, either because I was still on ineffectual Voriconozole and A.Terrace kept growing or the mycobacterium, without the presence of antibiotics, started growing again, I got worse.  They did a bronch, confirmed both were still there and declared I had relapsed. THAT is why they changed my physicians around.  It might've been for the best? If you notice in that wikipedia article on Clofazamine there is this gem of a pubmed article.  I have skin, joint AND mouth presentations of GvH from my transplant.  One might ask, "why didn't they put you on this at the onset?"  Good question.  Those "concerns about toxicity" and their persistence that M.Abscessus was going to kill me if I didn't treat it seem strange that they wouldn't try this earlier instead of stopping altogether. Turns out I learned later that even my impassioned verbal language didn't get through to them because part of the reason they stopped was because those "concerns about toxicity" were just because I was relaying to them the side effects that I was going through.  From my point of view I was giving information to help them decide if I was on the best course of therapy yet somehow from their point of view I was a whiney patient or some such nonsense. Frankly, one of them just didn't like me.   

*** What are those? Basically TSH is the current gold standard of measuring thyroid.  By measuring TSH (the Thyroid Stimulating Hormone released by the pituitary gland) Endocrinologists are able to tell wether your thyroid is producing adequate amounts of hormone.  If the TSH is high that means it's sort of shouting at the thyroid, "We need MOAR hormones!"  Low means the opposite.  T3 and T4 are the main hormones measured if the TSH is off but they are not the only ones.  Testosterone plays a big part in musculoskeletal development and hair growth.  Interestingly I could never find any information on HOW the thyroid effects testosterone but in every paper or study I found it just stated as fact that hypothyroid patients often also have low testosterone.  

**** In the above example we are STILL trying to figure out the best course of action.  That recent discovery was an ulcer biopsy on my tongue that took 6 weeks of gene studies at the Mayo in Rochester, NY to get a general idea that it might turn into Post Transplant Lymphoproliferative Disease (PTLD) but we're all hoping it won't.  Because of this pretty much all my immunosuppression is under more scrutiny.  The alternate drug we were considering to Rituximab was Rapamune, a drug I had taken previously to great effect.  The benefit being that Rapamune has possible anti-lymphoma properties that would hopefully combat the possible lymphoma that might arise from PTLD while it's ability to help fight fibrosing might help the BOS.  But the lung toxicity it can cause is markedly similar to the COP I already have that I can't take prednisone for because of the risk of infection.  I am currently pursuing stem cell regeneration though I feel a bit on my own.  I want to get some of the doctors like Dr. Jörg C. Gerlach who did the initial development of the SkinGun.  I'd love for them to talk with some of the doctors involved in pulmonary stem cell regeneration and see if there's any common ground they could find in figuring out how to regenerate damaged or scarred lung tissue.  This is my goal.  I just have to try and bring them together...or something. 

Some good quotes.

"But as a growing body of research shows, technical errors account for only a small fraction of our incorrect diagnoses and treatments.  Most errors are mistakes in thinking.  And part of what causes these cognitive errors is our inner feelings, feelings we do not readily admit to and often don't even recognize" - Dr. Jerome Groopman

"Patients and their loved ones swim together with physicians in a sea of feelings.  Each needs to keep an eye on a neutral shore where flags are planted to warn of perilous emotional currents. - Dr. Jerome Groopman

"To be neurotic – what good can that do? ... I myself have known more than one person who owed his whole usefulness and reason for existence to a neurosis, which prevented all the worst follies in his life and forced him to a mode of living that developed his valuable potentialities. These might have been stifled had not the neurosis, with iron grip, held him to the place where he belonged" - Carl Jung

"And if the Spirit of him who raised Jesus from the dead is living in you, he who raised Christ from the dead will also give life to your mortal bodies because of his Spirit who lives in you." - Romans 8:11

"I know the pieces fit, cause I watched them fall away" - Tool

"Failure is the best way to learn" - Kings of Convenience

A little vulgar, but pretty much. XKCD 931. And that's the lucky ones that don't have INSANE side effects from treatment or the secondary cancers that the treatment causes...

edited by Henry Toland

1 comment:

Andrew said...

Jhaysonn, you're an inspiration, buddy. Never stop being neurotic.