Rheumination

Direct to Trash Advertising

The Copenhagen summit might want to take a look at the state of pharmaceutical sponsored mailings. The boreal forests of Canada's north are likely dwindling due to the massive amount of paper used for uninvited conference updates and reports sent out to physicians of all specialties.  These throw-away journals and articles flood my in-box every week and I'm tempted to chuck them without a glance.  The problem is, and the advertising  industry of course knows it, is that it's hard to just throw away what looks like honest-to-goodness medical research.  We're simply drawn to information and if it's in a form that looks like a journal, well all the harder to ignore.  I must also admit, that although rare, some useful and unbiased stuff occasionally floats in, just enough to keep me looking at all the other junk.  Most of the time though, these publications are no more than  pharmaceutical  info-mercials..  Almost always there is a thin veneer of respectability, feebly attempted by throwing in the name of a competitor in a non-threatening study or even better, to show a non-pharma related article to suggest that this is really just an educational forum.

I've developed my own strategy for these publications.  If I'm busy, I chuck the lot.  This is the usual and undoubtedly the best approach.  If I've got a bit of time on my hands or need some bathroom reading, I will sometimes play the 'guess the sponsor' game. I browse through the publication's article titles, then try to guess the pharma sponsor of the publication based on the meagre information gleaned from the titles alone.  If I guess right, game over and into the recycling it goes.  If not, I may take a second look.  A second look is an exceedingly rare event. 

Celebrex Associated With Heart Attacks

 Well, the Canadian football season wrapped up this last weekend with another classic Grey Cup game.  I don't know what it is about the CFL but the Grey Cup game is almost never a disappointment.  This year may have been the best, especially if you are a Montreal fan.  As any Canadian surely knows by now, the game came down to the last seconds, with a field goal to win the game.  Nothing exceptional there, except that the first attempt was missed, only to be replayed after the opposition was penalized for too many men on the field.  I have personally never heard that call in the Canadian game.

From a rheumatological perspective, other than the fact that virtually everybody on the field will be seeing a rheumatologist in the coming years for their knee OA, is the fact that Pfizer sponsored the game with enough cash that all players from both teams wore a prominent celebrex patch on the front of their jerseys.  They got their money's worth as the game was so exciting that it broke TV watching records.  As one fan put it:

Louise Laroche, a season-ticket holder for the last five years, waved her arms and shouted as the parade rolled by.Asked how nervous she was in the final seconds of the game, she said she nearly had a heart attack.

So there you have it.   A clear association of Celebrex with heart attacks.  (Or at least near heart attacks)

A Lupus Success Story?

LymphoStatB.  Other than having a cool name, this drug has been a bit of a loser over the years.  It seems I've heard about it for years, but always at the end of a presentation on Lupus; a kind of add-on to make the presenter look knowledgeable about up and coming meds or to make it look like he/she wasn't talking up the pharma sponsor's drug alone.  

Other drugs have always been more interesting for some reason.  Mycophenolate mofetil (CellCept) made a bit of a splash, equalling but not besting cyclophoshamide. Not a huge step forward, but we all hate cyclophosphamide, so any little bit is appreciated.   Rituximab (Rituxan) has been the unchallenged darling for several years now, largely based on accumulated anecdotal evidence .  It was a huge disappointment though when actual science got in the way.  Both the EXPLORER and LUNAR trials in SLE and SLE nephritis respectively, failed to  show  significant results in any endpoints examined.  This was fairly startling to all of us, and lead to a weird spectacle wherebye diehard evidence-based types would swear that the stuff works, it's just that SLE is too darned hard to study because of its many manifestations and unpredictable course.  This was fairly believable, I must say, until the recent results of our old and nearly forgotten wallflower, LymphoStatB.  Since I last heard of it, it has changed its name to the far less cool, much more feminine name, Benlysta (belimumab), and has gone out and done what was said could not be done, get positive results in a Lupus trial .  They now report,(the company Human Genome Sciences that is),  that their trial of 819 patients over 76 weeks showed significant improvement in the primary endpoints, 40-43% in treated patients vs 33% in controls, as well a several secondary endpoints.  It'll be nice to see the details, and of course, being published would be a good start.

Sounds good, and as a bonus, seems to put to rest the idea that SLE patients are impossible to study.

More Disco-Supplementation

A premiere orthopaedic and joint replacement hospital, Jewish Hospital physicians are leaders in the field who train other doctors... Focusing on a complete joint program that includes outstanding patient care, pre-operative joint care, pre-therapy and disco-supplementation.

Because there is nothing better for osteoarthritis of the knee than a little disco.

from AARP.ORG

H1N1 and the Color of Phlegm

from  www.newsteamtexas.com/. ../2009/09/flu.jpg

A while ago I wrote a post about my experience with phlegm and how it helped me eliminate respirology as a potential career.  A follow-up post linked to a site that included a color choice labeled 'phlegm' and how I disagreed with the color choice.  It was, as you can imagine, just a joke, but these posts have been some of my most looked up posts of all time.  All last winter I would get regular visits from anxious people the world around trying to figure out if I could help them diagnose what they were harking out. I couldn't.  The visits dwindled out throughout the summer and I thought that was the end of it.  I didn't mind.  It was a bit rude that one of my most successful posts had nothing to do with rheumatology.   

But then came the fall and the visitors returned. I realized that it coincided with the onset of H1N1 in the USA and sure enough, the numbers of visitors continues to rise.  It seems that my post is an H1N1 meter.

Fair enough.  I guess even rheumatologists and others interested in rheumatology get a cough now and again and their phlegm conundrum might lead them to this site.  All the better.  As for me, well I got my vaccine this week so I'm hoping my own sputum will remain pristine.  Mind you, a week in bed might have increased my posting productivity.

Groopman's Wrist

Jerome Groopman is discussed again over at DB's Medical Rants.  I'm sure just about all of you know of Groopman and his book, How Doctors Think.  This book, which discusses how MDs go about their business of making, or missing diagnoses, was the talk of the blogosphere when it first came out in 2007 and seems to pop up regularly since.  I must admit, while the book was an interesting read, his chapter on his own wrist problem lead me wonder exactly how Groopman thinks.

His wrist problem is discussed in mechanical terms, with multiple small traumas, but the problem evolved to the point where it would regularly become "hot, beet red, and swollen".  Now this is the classic triad of inflammatory joint pain, generally seen in arthritic, not orthopaedic conditions.  I would have to think of crystal arthropathy like pseudogout or gout, maybe even palindromic rheumatism.  Instead, it seems like Groopman visits half the orthopedic surgeons on the East coast and discovers, to the surprise of exactly nobody, that surgeons, when they aren't sure what to do, like to operate.  Although the man is an internist, there is no mention of visiting one of his rheumatology buddies who might have done the appropriate diagnostic  procedure, which is a simple joint tap during an attack.

 Sure, maybe it was mechanical, as he suggests by chapters end, but with those symptoms he might have avoided a lot of grief  by staying in the internal medicine wing of the hospital.  For all I know, he's still suffering from pseudogout with an underlying metabolic disease like hemochromatosis.  Just hope he takes the walk  down the corridor to his local rheumatologist.

 

HLA B-27 to the Rescue?

The discovery, in 1973, of the association between ankylosing spondylitis and the Human Leukocyte Antigen HLA B27  raised two still unanswered questions.  The first,  the holy grail of spondyloarthropathy research, is simply; how does the B27 gene confer risk of developing the disease, and the second, somewhat  less funded question; why the hell does this nasty piece of DNA still exist.  Why haven't the Mendelian garbage collectors tossed this unwelcome gene onto the trash heap of failed genetic experiments.

Recent events have rekindled my interest in the latter question.  The H1N1 influenza virus is upon us again and for unknown reasons appears to attack native populations with disproportionate ferocity.  In Canada, many native communities have suffered greatly once the virus touches down.  There is a higher number of affected and a much higher rate of severe infection.  In some respects, it reminds me of the arrival of  Europeans to the continent and their tallships laden with viruses which proved lethal to untold numbers of the original inhabitants.  While the numbers vary wildly, it is suggested that up to 80% of the aboriginal population succumbed to one of the many waves of infectious diseases from abroad.  Given this massive assault, it's possible that a small genetic survival advantage may have had a huge impact.  Could that advantage have been the HLA B27?  I'm starting to wonder.  The clues that lead me to this suggestion start with the inordinately high rate of B27 amongst North American native populations.  While most of the Northern native populations have higher rates of B27, the rate can run as high as 50% in some populations, such as the Haida of the west coast of Canada.  And it isn't because they are immune to the arthritogenic potential of the gene.  20% of the men carrying the gene showed evidence of sacroiliitis on x-ray.  Spondyloarthropathy would likely have  been  a brutal disease among these not-so-long-ago hunter-gatherer peoples, so why is it so prevalent?  Could it be that the B27 gene somehow protected these vulnerable populations from the many plagues that followed the arrival of Europeans? The survivors, though cursed with this unfortunate gene may then have passed it on to future generations.  

Sure, but it's just one of many possibilities.  After all, B27 may simply be linked to any other gene with survival qualities,  like hunting skills or negotiating with ethically challenged governments.  On the other hand, there is some evidence that resisting infections is part of the B27 advantage.  Recent studies have shown that HLA B27 has a protective effect in both HIV and Hepatitis C infections.  While nobody suspects that either of these viruses had anything to do with the massive casualties post Columbus, it makes me wonder whether any of the other diseases such as smallpox or influenza were also less fatal among B27 carriers.  It is known that HLA B27 is involved in the immune response to Influenza A, but I don't know whether this confers any survival advantage.  In fact, it would be a very good study question.  It might even be a good study question for the scary virus flying around the planet today.  

Who knows.  Maybe we'll all be begging for a B27 allele before the end of this modern day pandemic.  

Fibromyalgia Breakthrough

Well, about as big  a breakthrough as has occurred  in the recorded history of fibromyalgia research, which pretty well sets the low end of the scale for scientific breakthroughs.  In fact, the published abstract doesn't even mention fibromyalgia, but hey, you get your good fibromyalgia news where you can.

I could only get the abstract from the Science on-line article but it's pretty intriguing.  In a study of chronic fatigue syndrome, researchers found the presence of retroviral DNA from xenotropic murine leukemia virus-related virus (XMRV), in 68 of 101 (67%) patients as compared to only 8 of 218 (3.7%) controls. Derek Lowe at In The Pipeline notes that the same group has now studied three hundred patients and has found the virus in 98%.  Pretty impressive numbers. Almost too impressive?

So what's this got to do with fibromyalgia.  First of all, CFS and fibromyalgia are very similar diseases. If you look at the criteria for CFS, you could be talking about any one of my fibromyalgia patients.  

The fatigue of CFS is accompanied by characteristic symptoms lasting at least six months. These symptoms include:

• difficulties with memory and concentration
• problems with sleep
• persistent muscle pain
• joint pain (without redness or swelling)
• headaches
• tender lymph nodes
• increased malaise (fatigue and sickness) following exertion
• sore throat

About the only difference is that the focus for CFS is fatigue and for fibromyalgia, it's pain.  Amongst 300 patients, I'd be surprised if there wasn't a lot of patients that would fulfill the criteria for fibromyalgia.  So, if 98% are positive for the virus, well maybe fibro patients will test positive as well.  In fact, the research institute which funded the study says as much, although without any numbers.

So we have here a study that's not about fibromyalgia, in abstract form alone, with no detail about study technique, concerning a virus that nobody has really heard about, from a private research institute with little track record, and nearly unbelievable numbers.

Well, in fibromyalgia terms, we call that progress.

Vioxx Populi 2009

September 30, 2004. 

Do you remember where you were that day?  I do.  I was at my office peeling off another prescription of Vioxx when my mother called with news that the drug had been withdrawn from the market.You know the reason, increased cardiovascular mortality which they apparently only then discovered.  Since then, of course,  all sorts of dirt has been exposed about the drug, and in particular, the company that produced and marketed it.  What made it more disturbing was the fact that I prescribed it a lot, even took it myself.  I gave talks to other physicians and undoubtedly convinced them to do the same.  All my colleagues did the same.  We were all taken in. 

 So now, every September 30 I pause to review my relationship with pharma.  I'm not a pharma basher.  I can't imagine how brutal rheumatology as a specialty would be without the new biologics and the other miracles they produce. But they are business, and their business is influencing my prescribing pattern, nothing else.  Every high powered guest speaker they bring in, every CME conference they sponsor, and every lunch or logo-laden pen they offer is to increase sales.  Much is so obvious that we laugh at the thought that it would influence us.  But we know it can.  Surely no physician wanted to hurt anybody with Vioxx, but somehow physicians were involved at every level.  Doctors involved in the studies must have been aware of the cardiovascular concerns, yet few sounded the alarm. Others allowed their name to be put on company produced research, though they had nothing to do with the trials.  Clinicians are  given speakers fees to spread the word of what we thought was a good product.  Guest speakers we couldn't dream of attracting without drug company money show up, but what are the chances they have a contrary message. None of the chain of physicians involved had any ill intent yet we all went for the ride...and crash.  

So now on September 30th of each year I'll re-read the following articles:

Ghost Management:  How Much of the Medical Literature is Shaped Behind the Scenes by the Pharmaceutical Industry?  

Guest Authorship and Ghostwriting in Publications Related to Rofecoxib 

The ADVANTAGE Seeding Trial: A Review of Internal Documents

Medical Journals are an Extension of the Marketing Arm of  Pharmaceutical Companies

Then I'll visit the Scientific Misconduct Blog for a bit. (Not too long, that's just depressing)

And tomorrow, my skeptic battery recharged, I'll be a wiser rheumatologist.

This was a re-post of last year's vioxx populi.  Since then there has been more dirt uncovered, something which I think we'll have to get used to.  The articles listed are still worth reading and there are many more I could add, but to keep the reading of unpleasantness down to a bare minimum, I would simply suggest that you check out PLOS  which regularly publishes articles related to pharmaceutical underhandedness, and Pharmagossip, a highly entertaining blog which nevertheless brings to the fore the latest pharma missteps.

 

A New Era

Things are a bit different around here these days.  Yes, the fact that I am actually posting again is something different, but the real difference is that our service has gone all university.  Since the summer we now have regular housestaff following us around.  It's quite a change after nearly twenty years of talking to myself between service rounds.  There are pros and cons to having residents about, some expected, others not so much, but overall I am quite happy with their arrival.  

The major pro is having young smart inquisitive people around asking questions and keeping me on my toes.  Even demonstrating the physical exam is amusing.  I'm not sure that that thrill will last after showing the knee exam for the hundredth time, but for now it's all good.

The biggest con is the distance residents put between me and my patients.  My longstanding patients now see different housestaff with every visit.  They have to go through a much longer history and physical each visit and when I do come in, the visit is often shorter. New patients are even more difficult.  I never feel like I know the patient as well when someone else takes the initial history and many of the subsequent visits are also with residents, so I never catch up.  

But it's all new.  I'm sure I'll figure out the balance between patient care and medical student care.  Just hope my patients can hang in there until I do.