Hepatitis C: Beware the Jabberwok

 Hepatitis C:  Beware the Jabberwok

Through the Looking Glass

‘Twas brillig, and the slithy toves
Did gyre and gimble in the wabe:
All mimsy were the borogoves,
And the mome raths outgrabe.

‘Beware the Jabberwock, my son!
The jaws that bite, the claws that catch!
Beware the Jubjub bird, and shun
The frumious Bandersnatch!’

He took his vorpal sword in hand:
Long time the manxome foe he sought 
So rested he by the Tumtum tree,
And stood a while in thought.

And, as in uffish thought he stood,
The Jabberwock, with eyes of flame,
Came whiffling through the tulgey wood,
And burbled as it came!

One two! One two! And through and through
The vorpal blade went snicker-snack!
He left it dead, and with its head
He went galumphing back.

‘And hast thou slain the Jabberwock?
Come to my arms, my beamish boy!
Oh frabjous day! Callooh! Callay!’
He chortled in his joy.

‘Twas brillig, and the slithy toves
Did gyre and gimble in the wabe:
All mimsy were the borogoves,
And the mome raths outgrabe.    

  

If you listen to a scientific lecture for an hour, you can begin to believe nonsense is science, but don’t.

I believe that the average Hep C patient (whoever that is) has a triple cross to bear.     1. You feel like shit on a stick  2. You have to go to unimaginable places like a liver biopsy suite and 3.You are thrown into a parallel universe where the language is almost understandable, but not really. It’s Jabberwok.

I was listening to a lecture yesterday on Hepatitis A through E. I was reading the slides as Dr. Nice Lady from pharmacy was talking.  And then I heard it:Hepatitis B and C are predominately associated with percutaneous and permucosal transmission”.  Translation:  Hep B and C can be caught through blood and through sexual contact.  Permucosal  is medical lingo for via mucous membranes.  The problem was that fifty pharmacists were about to  leave the lecture and tell their worlds that you can catch Hep C through sex.  I couldn’t let that happen so I said through the chat box “Hep C can be caught through sexual contact?  Is this new information?”  She said no, you are right to point that out, it is not transmitted that way.  So why did she say it?  The slide looked better that way.

In reality, the way one gets Hep C through sex is through rough sex and I mean rough.  Percutaneous means blood transmission.  I will pause here so that you create your own image.

Now I was willing to let it slide when she said that Hepatitis A and E were transmitted through the oral-fecal route.  In reality it is fecal-oral route.  Think about that for a moment.  But my point is that there is a lot of slightly non-true information out there.  What can you do about it?  Ask questions wherever you go.  Even if you have asked the same question before.  Remember how your doctor’s office always has that sign in English and Spanish that says Questions/Pregunta?  They really want you to ask.

Boy, did spellcheck light up Jabberwok!

http://en.wikipedia.org/wiki/Jabberwocky

Lewis Carroll Through the Looking Glass

Viral Hepatitis:  Keeping Your Patients Safe www.freece.com

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I Pooped Today, Things to Track with Hepatitis C Treatment

“I Pooped Today”  Important information to track while on Hepatitis C treatment

If you choose to participate in a drug study while being treated for Hepatitis C, be prepared to keep a diary.  Most of these examples are from round one.  You know what they say about experience:  There are those that got it and those that are going to get it.  I’ve been both.  During round two, I knew a lot of holes were out there and walked around them.  Or paved them in advanced.  I did find new ones.

Dear Diary:

How many bowel movements have you had since your last visit? What color is it? I think this is a test to see if I am fixated on poop.  BTW Your family doesn’t want to know about your poop even if they pretend to.  Most people on treatment have frequent stools but not me.  See, don’t you wish you didn’t know?

Get comfortable discussing your bodily functions with everyone in a white coat. You haven’t had dignity for a while. How dark is your urine? I don’t know, it’s diluted when it hits the toilet bowl. Does it smell? I really want to make a nose joke here.

How’s your eating? Food smells and tastes like pennies and my stomach burns. Have you tried not eating spicy foods? I am only eating buttered noodles and Little Debbie Oatmeal Cakes.  Oh.

Brain fog “Loss of ability to concentrate. Memory loss”   How has your memory been?Huh?    Non-participative.  Try to write everything down in one place.  I can’t seem to find my notebook, so I start another. Kinda makes it worse.Try to hold a job let alone a career with that side effect.

Did I take my medicine? When did I take my medicine? Did I take it in lemon duck? Did I take it with a eunuch?  Did I take it on my death-bed?  Did it make me see a dragon’s head?  Write it all down, you won’t remember.  (ref Brain Fog)

Try to get as much sleep as you can. Brilliant. Now I lay me down to sleep, to lie awake with Lil Bo Peep.  Okay, a bit too much rhyming.  But today my brain wants to rhyme. 

Avoid undue excitement. You mean like my brain running The Fifth Element  Flossing Paradise 24/7? We can prescribe sleep medications. Why didn’t you tell me that 6 months ago?

We recommend aerobic exercise 15-20 minutes/day. Are you shitting me? Do I keep track if you are shitting me?

How many times did you have a blinding H/A this week? How many not so blinding?  Let me see, I cry a couple of times a day.  Crying results in a blinding headache.  So I hold in the crying.  The result, “not blinding” headache.  I’m not sure if I am crying on the inside or outside.

Rashes and skin changes. Is that because of medications or just old spots?  What about the ones that are 3-D?

My skin itches. Take an antihistamine. I did. Take Benadryl 50 mg. Spit will fall out of my mouth if I have any secretions Can I see a dermatologist about this?  Sure but it will be weeks before we can get you in.  WTF is a dermatologist so busy doing?

How has your mental health been since your last visit? Can you draw a line on this form to show the change? I can’t give you any more instructions, even if you don’t understand this (silly) form.  The -Y axis is not long enough to document  the rate of my decline.

Do you think we should put you on antidepressants? I don’t know who I am much less what I need. Have you had suicidal or homicidal thoughts? I can’t remember. With or without headaches?

It is Tuesday, time for my weekly injection. Just when I was feeling up line dancing in a circle (props go Dos XX commercial). Where was your injection site last week? In my forehead with a silver bullet.

Because my Hemoglobin (HgB) is so low, I can’t walk  from the parking structure to my work appointments. Can I get a Handicap Placard? No one has ever asked for one before. So can I get one? Bring us the form. The Dr. will have to sign it.

License branch information booth: Do I have to stand in the long line with the masses? If I could stand that long I wouldn’t need a Handicap placard. Then bring someone to stand in line for you. Next

Adverse Events in Treatment: If it’s you, it’s minor. If it’s me, it’s major

Adverse Events and Reactions

There are conflicting definitions here because there are conflicting definitions in science and medicine.

A Side Effect (SE) is when a drug does something besides what you are treating. Rogaine was initially a drug for hypertension that had a side effect (SE) causing hair to grow on your head.  It was predictable.  Talk about a marketing turn-around. That  pharmaceutical guy is probably still hailed as a hero. What? Me judge? 

Minoxidil is an antihypertensive vasodilator medication which also slows or stops hair loss and promotes hair regrowth.

Ooh ah, chemistry structure. 

Why is it that I can understand how this crosses the epidermis but I cannot understand how house plans will look as a house?

An Adverse Drug Event (ADE) is something that is dose independent and causes harm.  Wow, the definitions are wide open.

I went to the Veterans Administration (VA) website:   No clear definition  from their panel of experts

I went to the NIH:  The National Institutes of Health (NIH) Blah Blah Blah ”  WTF? I stopped there.  These people had no intention of helping me get  a clear definition. 

 Wikipedia, that bastion of scientific rigor says:

http://en.wikipedia.org/wiki/Adverse_drug_reactions

An adverse drug reaction (abbreviated ADR) is an expression that describes harm associated with the use of given medications at a normal dosage during normal use. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs. The meaning of this expression differs from the meaning of “side effect“, as this last expression might also imply that the effects can be beneficial.[1] The study of ADRs is the concern of the field known as pharmacovigilanceNo shit.  Just what we need, splitting more ill-defined hairs.

An adverse drug event (abbreviated ADE) refers to any injury caused by the drug (at normal dosage and/or due to overdose) and any harm associated with the use of drug (e.g. discontinuation of drug therapy).[2] ADRs are a special type of ADEs.

  • Type A: Augmented pharmacologic effects – dose dependent and predictable
    • Intolerance: Severe decrease in red blood cells (RBCs) with ribavirin.  Decrease dose of ribavirin.
    • Side Effects. Immobilizing depression .  Anti-depression agents can help.

     My question to you and your doctor is “Why not start antidepressants in advance of hepatitis C therapy?”  I did the 2nd time around and I wasn’t on another planet every day.  Only sometimes.

  • Type B: Bizarre effects (or idiosyncratic) – dose independent and unpredictable.

Congratulations!  You are 1 in 100,000 whose teeth fall out.  It is a rare occurrence, 1 in 100,000.  But if you are the one, it is 1 in 1 (100%).  I apologize, I do not remember where I got this mask rendering.  Please don’t sue me.

  • Type C: Chronic effects: You keep taking that boy ,and you will go blind.
  • Type D: Delayed effects:  We didn’t realize that three weeks into treatment your butt hole would fail to shut.  Awkward!
  • Type E: End-of-treatment effects: Seriously, , Ribavirin stays in red blood cells (RBCs) for 6 months after treatment causing teratogenic effects (birth defects)  in non mammals.  Even if only the sire is taking the drug.
  • Type F: Failure of therapy The operation was a success but the patient died.
  • Type G: Genetic reactions OOPs,  you went deaf because you don’t have the enzyme to pee out that drug. Are your parents from Lapland?

My two favorite terms are Bizarre and Idiosyncratic. Bizarre we recognize. Sort of. Idiosyncratic means we have no effing clue. Idiosyncratic is more palatable than ” no effing clue”. 

The Food and Drug Administration (FDA to their friends) says An ADR should not be labeled as ‘certain’ unless the ADR abates with a challenge-dechallenge-rechallenge protocol (stopping and starting the drug). Now, I don’t know about you, but I am probably not going to volunteer to restart a drug that I had to stop because of  a bad experience.  At least not any more.

Both Interferon and Ribavirin warn about severe depression, suicide, homicide, and  crazy thinking.  I got the D and CT.  These are predictable SEs

  From the Interferon (Pegasys) package Insert

http://www.accessdata.fda.gov/drugsatfda_docs/label/2002/pegihof101602LB.htm#cont

BOXED WARNING 

 Alpha interferons, including PEGASYS, may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Patients with persistently severe or worsening signs or symptoms of these conditions should be withdrawn from therapy. In many, but not all cases, these disorders resolve after stopping PEGASYS therapy (see WARNINGS and ADVERSE REACTIONS).

Neuropsychiatric

Life-threatening neuropsychiatric reactions may manifest in patients receiving therapy with PEGASYS. Depression, suicidal ideation, and suicidal attempt may occur in patients with and without previous psychiatric illness.

PEGASYS should be used with extreme caution in patients who report a history of depression. Neuropsychiatric adverse events observed with alpha interferon treatment include relapse of drug addiction, drug overdose, aggressive behavior, psychoses, hallucinations, bipolar disorders and mania.   Almost all patients with hepatitis c have a history of depression.  It goes with the territory. 

ADVERSE REACTIONS

Nearly all patients in clinical trials experienced one or more adverse events. The most commonly reported adverse reactions were psychiatric reactions, including depression, irritability, anxiety, and flu-like symptoms such as fatigue, pyrexia, myalgia, headache and rigors. The most common reason for dose modification or withdrawal from studies was hematologic abnormalities.

Ribavirin  http://en.wikipedia.org/wiki/Ribavirin  It is more difficult to get a straight package insert regarding Ribavirin as there are multiple manufacturers.  Of note, Ribavirin has shown teratogenicity in non mammals.  You will have to sign many forms to document that you grasp this.

 I am not the suicide type.  As a kid, I stumbled on my mom trying to kill herself.  Pills, cut wrists, head in gaseous oven.  I would call an ambulance then my Aunt Sudie.   Aunt Sudie kept  my brother and me during hospital stays.  I packed our school stuff in a  cardboard box and waited for her.  We stayed there till Mom promised the psych doctors that she’s better and wouldn’t try suicide again.  Back then you would whisper “She’s had a nervous breakdown”.  You don’t hear that anymore.

It was weird at Aunt Sudie’s house.  It was quiet , clean and ran on a schedule.  They had ice cream all the time  and a freezer that kept it frozen.   My cousins  Gary and Randy would have to room together so my brother  and I could have a bed.  I put every effort into making sure Tim and I were no trouble. Little Orphan Annie has come to our house to stay.  To wash the cups and saucers up and brush the crumbs away…  J W Riley.  This thinking came from me.  Aunt Sudie didn’t expect me to work for my keep.

 When my period  started, Randy’s dog , Lady, shredded my Kotex all over the dining room floor and they saw it.   I died quietly.  At home no one shredded my Kotex stuff.   No matter how bad it is at home, there are some plusses.

Back then there was no Valium or Prozac.  Only Thorazine.  Which Mom used to for suicide attempts. See a pattern?    Mom later found an alternative.  She began drinking with my dad.  I became grown up on duty (GOD) when I was about eleven.

Partial Responders with Hepatitis C

All Hepatitis C studies are not created equal. Duh

I used to see myself as smarter than the average bear.  Not so much now.

Being me, I was not passive when searching for a Hep C study.  But I was mistaken.   I assumed. Don’t make an assumption.  I knew better.   My mom taught me this.  Every time some of us kids got in trouble, she pulled me aside and said, “You know better”.  It was years before it dawned on me that other kids knew better too.  My mom was once a kid.  In fact she was still a kid when she had me.  In 1951 it was not cool to have a baby out-of-wedlock.  My biological father passed on marriage and she had to go back home to Harlan County, Ky.   This is where I was born.  Papaw told me to say I was from “Bloody Harlan” because of the bloody mine strikes.   So that is what I told my teacher.  Papaw and all Moms’ brothers were coal miners.  We didn’t make moonshine (the other career path)

I learned that the TV show Justified   is about Harlan County.  I don’t watch it myself.  Makes me jumpy.

fig 1.Me, Mom in the white car coat, dad that raised me, Mamaw, Papaw, and aunts. Harlan County, KY. My mom has the big nose like Papaw.  She waited to get a nose job after Papaw died

Coal tipple loads rail road cars 1

When I was a curly headed baby
My daddy sat me down upon his knee
He said, “Boy, you go to school and learn your letters
Don’t you be a dirty miner like me”

I used to think my daddy was a black man
With script enough to buy the company store
Now he goes downtown with empty pockets
And his face is white as a February snow

I was born and raised in the mouth of the Hazard Hollow
Coal cars rambled past my door
Now they’re standin’ in a rusty row all empty
And the L & N
Don’t stop here anymore

http://www.sing365.com/music/lyric.nsf/The-L-amp-N-Don’t-Stop-Here-Anymore-lyrics-Johnny-Cash/6B378501111ECA5D48256DEA000A5308

I love this song but never heard it until I moved to Texas

Where was I?    Okay brain get back on track.  Let me recommend that you do not have your driver’s license photo taken while on treatment. Very scary.

I chose to participate in a Multi Centered, Randomized, Placebo Controlled, Double Blinded study, evaluating Standard of Care (SOC) Interferon and Ribavirin (which had been my only choice all these years) vs. SOC and telaprevir for round one.  In fact I sought out this study. There were three arms, two with study drug.  I had a 66.7% chance of receiving study drug.  As I learned later, I was not randomized to study drug (telaprevir).  I assumed SOC included addressing anemia and other life threatening events.  In this case, SOC did not include blood transfusions or red blood cell (RBC) stimulant injections such as Procrit.  Standards of care have not caught up to current practices. Step one was to reduce the Ribavirin dose.  .  My hemoglobin (HgB) was 8.9 and the guideline minimum for taking Ribavirin is 10.0. Normal HgB range for females is 11.5-15.8 mg/dL.   My Ribavirin dose was decreased. Hemoglobin got slightly better but I paid for it later by not clearing the virus. In order to treat the anemia I would have to walk away from the study.  Dang it!   I quickly lost the ability to walk down a hallway, climb stairs or lift baggage without major shortness of breath (SOB) and the ability to complete a thought, all necessary for my job (oops, career). More about that later.

After treatment completion, an individual is assessed for response to measure viral load. If there is virus remaining but a reduction of disease by 30% or more  – it is called a partial response.   Partial response (PR) implies further treatment  required.  www.about.com   I moved from treatment naïve to partial responder.  Here I had saved myself for newer treatments but still got the same treatment that was available years ago.  Plus no treatment for the anemia.  How did a smart girl like me get in a dumb box like this?  I hung in there and finished the (long) 48 week trial.  Not only did I not have red blood cells (RBCs) or white blood cells (WBCs), but then the virus that was left was a stronger warrior.   Not good.  Here is the part where my education went out the window.  I was so depressed that I couldn’t function.  Every little thing was monumental.  I should have quit the study when my blood chemistry went to hell.  But I couldn’t think clearly enough to look at the situation logically.  All my decisions were made by a scared little girl.  See fig 1

You know I wanted to blame insurance companies.  It is so easy to blame insurance companies.  I wanted to blame pharmaceutical companies and the FDA.  They are easy targets too.  In reality, I, more than most, understand the study requirements and commitments. Sort of. I have been a research pharmacist for a couple of decades.  The data must be unsullied from outside forces like blood transfusions that will make it impossible to evaluate the toxicity.  That is the point of the study, not patient care.  Don’t misunderstand me.  Patients are well cared for. A patient can get treated without a study but a study cannot evaluate a treatment without patients

FYI, HgB is the molecule in the blood that carries oxygen, (O2) from your lungs to your blood and carbon dioxide (CO2) to your lungs so you can exhale this gas.  Speaking of HgB, it is a bucket brigade that carries water to a fire.  Even if you have plenty of water, if you don’t have enough buckets, the barn burns down.  Wait, that wasn’t a great example.  It wasn’t completely accurate either.  Never mind.  It’s just that I spent all these years learning this stuff; I want to get my money’s worth.  Kurt Vonnegut said only hermaphrodites use a semi colon; .Sort of.  While metaphorically I don’t relate to that, he did say it.   I didn’t pay Kurt Vonnegut, God rest your soul Mr. Rosewater.  Anyway my WORD grammar check said uses it.  I think I paid for that.  Yes of course I did.

Telaprevir (Incivek) and boceprevir (Victrelis) are now available to add to Standard of Care (SOC).  In fact by now they may be a part of SOC.  Glad I contributed to the body of knowledge that is clinical research.  Really I am.  But I wouldn’t repeat round one for nothing, not no way, not no how. It was two years before I was well enough to go for round two of treatment.  My career never recovered.