Popular bias about nesiritide

Remember the brouhaha almost two years ago about the JAMA meta-analysis on 30 day mortality with the use of nesiritide? The increased mortality observed with nesiritide was not statistically significant, but based on popular reaction you would have thought it was cyanide. So, why the silence about these two recent papers?

In brief, the February 13 issue of JACC contains this report of a randomized double blind trial of nesiritide after coronary artery bypass in patients with left ventricular systolic dysfunction, showing that nesiritide was associated with improved renal function, decreased length of stay and lower 180 day mortality.

This meta-analysis from American Heart Journal (posted on Medscape February 7), arguably methodologically stronger than the aforementioned JAMA meta-analysis, showed no difference in mortality between nesiritide and comparison groups in 7 studies. For an analysis of the strengths and weaknesses of the two meta-analyses read the discussion section of the American Heart Journal paper particularly in reference to the heavier use of inotropes in the neseritide treated patients in the JAMA paper. (It’s well known that inotropes increase mortality in heart failure).

I’m lukewarm on neseritide and there are enough remaining questions about its efficacy and safety to keep it off the front line, at least for now. For acute cardiogenic pulmonary edema I prefer an approach utilizing nitroglycerine, loop diuretics and CPAP or NPPV. (A randomized controlled trial of nesiritide to evaluate for mortality, renal function and cost effectiveness will begin this year).

Anticoagulant bridging with low molecular weight heparin before surgery

A popular practice in anticoagulant bridging with enoxaparin is to continue it in full therapeutic doses (1mg/kg Q 12 H) through the evening before surgery and hold it the morning of. This paper suggests that might not be a good idea.

Dolly’s legacy

A decade after the birth of Dolly the cloned sheep CMAJ reflects on the state of the science.

DB’s video editorial

DB of Med Rants offers some inspiring words on being a great physician. Put a face with a name and watch his Medscape Webcast Video Editorial.

On Lyme disease and woo

It was a first for this blog. I removed a comment in reference to my post on Lyme disease activism. I appreciate and learn from commenters who criticize me. By exposing weaknesses in my positions they help me refine my arguments. But I will remove comments containing personal attacks and gratuitous foul language. Such comments generate more heat than light. Besides, scientific discussions are corrupted when attached to strong emotions or someone’s agenda. At their best discussions of science are sterile and sometimes even seem boring.

The post in question, in essence, applauded the new IDSA guidelines and suggested that Lyme disease can be quack fodder. Why quack fodder? Diagnostic guidelines from the International Lyme and Associated Disease Society, recently cited by Dinosaur, allow a diagnosis of “chronic Lyme disease” in the absence of any abnormal physical or laboratory findings. And the symptoms on which the diagnosis can be made are vague, overlapping sufficiently with other diseases or even the normal population to be meaningless. So, you have statements like this: Available data suggest that objective evidence alone is inadequate to make treatment decisions, because a significant number of chronic Lyme disease cases may occur in symptomatic patients without objective features on examination or confirmatory laboratory testing. Well, in the absence of objective findings how do we know those patients have Lyme disease in the first place?

That’s just another way of saying the diagnosis of chronic Lyme disease is subjective, isn’t it? That’s why it’s potential quack fodder. Any patient with vague symptoms can be declared to have chronic Lyme disease and be subjected to all sorts of woo.

The Infectious Disease Society of America (IDSA) recognizes that there are some patients who “remain unwell” following completion of standard courses of antibiotic treatment for Lyme disease. I’m willing to reserve judgment about such patients, currently the subject of randomized controlled trials. I will not summarily dismiss the notion of chronic Lyme disease as long as it is under investigation. Unfortunately such patients, until the condition is better defined, are all too vulnerable to the purveyors of woo.

The Beatles’ gift to medicine

It’s an underappreciated fact that The Beatles played an important role in delivering the CT scan to clinical medicine and making it ready for prime time. When I began residency in St. Louis in 1975 there were only two CT scanners, then known as EMI scanners, in the city. EMI was Electronic and Musical Industries, the company that manufactured the scanners in the early days. It was also the parent company of The Beatles’ two record labels, Capitol Records and Apple Records.

Sir Godfrey Hounsfield, whose BMJ obit is here, worked as an engineer for EMI and was the inventor of the CT scan (PubMed citation here). According to this article from Whittington Hospital: Having sold 200 million of the Fab Four’s singles, (at seven inches, almost enough vinyl to stretch the length of the equator) the Beatles’ record company, EMI, was able to fund Hounsfield to do his research and the scanner was ready be used in hospitals in the 1970’s.

Image source: The Library of Congress

The Canadian Medical Association Journal one year after its “collapse”

About this time last year a New England Journal of Medicine Perspective piece announced the “collapse” of the Canadian Medical Association Journal (CMAJ). Not long after, departed CMAJ editors revealed plans for a new open access journal of their own.

So what’s happened in the ensuing year? CMAJ is still doing very well, thank you. If the journal is indeed on life support you wouldn’t know it from this optimistic piece featuring the new Editor-in-Chief. And the new journal? It has a web site and a title but no content.

Ten myths about EHRs

From Family Practice Management.

Via Medpundit.

What is Big Pharma’s most lavish gift to the medical profession?

It’s not the expensive meals, junkets or honoraria. It’s the fact that the drug companies are taking a huge public relations and financial beating for our mistakes! A case in point is Fen-Phen, a once popular anti-obesity drug cocktail found, about 10 years ago, to be associated with valvular heart disease and pulmonary hypertension. Class action product liability suits followed and American Home Products Corporation settled for about $4 billion, taking the monkey off the back of untold numbers of doctors who engaged in contraindicated prescribing of the two drugs in combination. The company did not promote combined use of the two drugs.

A more recent example is the pro-motility drug cisapride (Propulsid, or Prepulsid in Canada) withdrawn from the market a few months after a well publicized case of fatal cardiac arrhythmia (presumably torsade de pointes) despite the fact that the drug was being taken against product labeling. As reviewed in this article form CMAJ Johnson and Johnson, facing huge lawsuits regarding adverse cisapride related events, contended that physicians improperly used the drug. That contention was evidence based (as it is for many drugs); nevertheless, the company settled for $90 million.

Now cisapride’s in the news again as a class action suit gets underway against Canada’s Johnson and Johnson subsidiary. Again the company maintains, correctly, I believe, that “the drug ‘is a safe and effective medicine when prescribed appropriately.’" But, doctors, worry not. They’ll settle.

I wrote about this very problem in our fourth Medscape Roundtable Discussion on how to stay current on prescription drugs. So, doctors, it ain’t rocket science. Just read the product labeling. (If you got your copy of the product labeling from a drug rep be sure and wash your hands 10 times after handling).

Anti-Pharma bias

Doctors who gratuitously bash the drug companies have a little help from the media, it appears.

Via Kevin MD

Thought provoking

I’ve been tagged by Angry Doctor to spread the meme (originated, appropriately enough, here) of blogs that make me think. These are blogs that challenge me, sometimes by disagreeing with me, always in a collegial way. Here are some---not an all inclusive list by any means.

DB’s Medical Rants – thought provoking discussions on teaching, learning and health policy.

Retired Doc – critical discussions of issues in Internal Medicine which often challenge popular simplistic assumptions.

Orac – incisive criticism of pseudoscientific woo---and some really funny stuff.

Kevin MD – something intriguing just about every day. How does he do it?

Clinical Cases and Images – a great repository of Web based resources that challenge me on my quest of lifelong learning.

OK, consider yourself tagged. You know the drill.

Another New York Times “puzzler”

The patient had resistant hypertension, with no assignable cause of secondary hypertension despite “scores of tests” and evaluation by numerous doctors at Yale’s specialty clinic. It was known that she had a murmur and bruits as well as claudications and absent ankle pulses. What’s the final answer? Coarctation of the aorta, finally revealed by an echocardiogram.

It’s an important clinical lesson (always think of coarct when you’re looking for secondary hypertension) but there’s a little something wrong with this story. Either the NYT account is simplistic or the folks at Yale made some sophomoric mistakes. (I suspect the former).

When I read a story like this I’m in the “quiz mode.” It’s different in the hectic, mind numbing, day to day clinical world. But it’s not rocket science to check for radiofemoral delay and take upper and lower extremity blood pressures. It’s hypertension 101 to perform these maneuvers and think of coarctation. And this was a specialty clinic. Equally strange is that she had had all these tests including rennin profiling, magnetic resonance imaging and angiography before getting a simple echo.

I can hardly imagine this happened at Yale’s hypertension clinic. Did the New York Times feel the need to dumb the presentation down for the lay public?

Methadone deaths increasing

JAMA News reports that methadone deaths are increasing far faster than deaths from other types of poisoning, a trend observed between 1999 and 2004.

Now that timeline, showing methadone deaths to rise 7 times faster than all poison deaths, is an interesting one. It speaks volumes. A Substance Abuse and Mental Health Services Administration report concluded that it reflects increased use of methadone as a prescription analgesic rather than a treatment for opiate addiction.

1999 was about the time pain management became politicized and activists were beating up on doctors for under treating pain. They pummeled us with arguments based 90% on dogma and 10% on science. They told us that the patient’s numeric rating of pain was “the fifth vital sign.” They redefined the concept of addiction to suit their agenda and told us that most instances of drug seeking behavior were in fact “pseudo addiction”, supposedly an indication to give more narcotics. A stable patient verbalizing “eight out of ten” pain was a medical emergency and a mandate for narcotics. Respiratory hazards were downplayed.

Around the time Joint Commission launched their pain initiative they held a panel discussion with Q&A. A pulmonologist asked “Aren’t you concerned about an increased incidence of respiratory depression?” The panel’s answer was, in effect, “It’s your problem. Your hospital needs to draft policies and procedures for respiratory assessment.”

Methadone seemed appealing for chronic pain management because it was cheap and its pharmacokinetic profile was thought to limit its abuse potential. Now we’re seeing the consequences of our zeal. True, not many years ago we under treated pain, but the pendulum has swung too far.

Many of us anticipated respiratory deaths from methadone, but the problem of cardiotoxicity was below the radar screen until the drug began enjoying heavy use as an analgesic.

Background:
Methadone’s proarrhythmic effects reviewed.
Methadone’s new FDA warning.
Methadone and the death of Anna Nicole Smith’s son.

More healthy skepticism about P4P

----from Retired Doc.

The Dinosaur gets a dose of Lyme disease activism

…and does a nice job of parsing the issue of “chronic Lyme disease.” I had a similar experience a while back.

Google in medicine: Is it all that?

Medical Economics recently interviewed several experts regarding Google as a tool for medicine and the responses were mixed. Google is all the rage, but as handy as it is there are weaknesses. Google is powerful but imprecise and may be dumbing down our searching skills.

Everyone remembers the fabled BMJ paper demonstrating how Google helped lead doctors to the correct NEJM case record diagnosis in 15 of 26 cases. As interesting as that is one has to ask how it would compare with other on line differential diagnosis resources such as Isabel or Dxplain.

Dr. Eamon Armstrong, a teacher of EBM, expressed concern about the imprecision of Google and noted “’I can't think of a single person in the EBM field who would use Google on a regular basis.’”

The article drew my attention to one Google enhancement I hadn’t noted before which is the category links at the top of the results page. (This may be under development, as I found the feature for some, but not all medical searches I tried). A search of Brugada syndrome, for example, yielded this page displaying the first of 261,000 hits.



That’s too large a number to be very useful, but by using the category links at the top you can narrow the search. Clicking on “for health professionals” narrows the results down to a more manageable 386 hits.

Also note that the health professionals page provides additional categories of interest to doctors such as “CME” and “practice guidelines.”

Still, it’s imprecise. Because you never know exactly what you’re getting or how the results are chosen Google can never be better than “pretty darn good” as termed by internist and Google product manager Roni Zeiger. Because Google’s searching methods are proprietary there’s a lack of transparency, and although there are books written about numerous “hacks” you never quite know. There’s always something dark and mysterious about Google.

That’s why for more scholarly work or any search which needs to be exhaustive (e.g., has this or that type of case ever been reported in the world’s literature?) Pub Med is better. Pub Med, like Google, is powerful. But unlike Google there are no Pub Med secrets, so no hacks are necessary. It’s all out in the open and if you’re among the Pub Med uninitiated you can take their tutorial which will teach you formal search strategies. If you haven’t taken the tutorial you can still enter a simple free text search. Although that sacrifices searching power you can still know exactly what you got and how by viewing the strategy Pub Med used to retrieve your results. That’s done by clicking the details tab. Search results using the free text search syncope in patients with brugada syndrome are shown here. (I would not recommend this sloppy search statement for actual use of Pub Med but is it illustrative of how it works).

Clicking the details tab reveals what search strategy Pub Med actually used to get the results.

So which search engine is best? It depends on your objectives. Google doesn’t offer the precision of Pub Med but there are advantages, such as ability to search blogs, Wikis and emedicine. The two search engines are best viewed as complementary.

Medication wish list for Anna Nicole Smith

Fox News shows us a faxed request for medications (see pdf link) for “M. Chase”, Smith’s purported pseudonym. It includes dilaudid injectable, lorazepam liquid concentrate, soma, dalmane (2 qid---a sleeping med!), and methadone 20mg qid.

CPR guidelines represent a weakness of evidence based medicine

Note: I had the following post in preparation when Medpundit, Dr. Wes and Kevin M.D. commented on this issue.

At the Cleveland Clinic Heart-Brain Summitt Gordon Ewy, M.D., Chief of Cardiology at the University of Arizona College of Medicine and expert on resuscitation spoke on CPR and the 2005 AHA and ILCOR guidelines and made this statement: “An important reason for these continued poor outcomes is that both sets of guidelines, despite being updated in 2005, recommend an approach to out-of hospital cardiac arrest that is far from optimal.”

Ewy and his colleagues in Tucson have been telling us for years that our approach to CPR is fundamentally wrong. I first cited the evidence here and made follow up posts here and here. Simply put, the Arizona investigators recommend elimination of rescue breathing for adult out of hospital cardiac arrest (unless circumstances such as drowning or choking indicate a respiratory cause) and, for unwitnessed arrest, emphasize compressions rather than AED protocols as the initial modality of treatment. These new procedures have been implemented in public education programs and EMT protocols in Tucson. Ewy’s presentation summarizes and updates the evidence and is an excellent review of the topic.

Sometimes the wheels of EBM turn too slowly. The 2005 guideline authors, dutifully and painstakingly trying to be “evidence based”, largely ignored this evidence because it didn’t meet the EBM standard of randomized clinical trials. Nevertheless, the evidence is compelling, and subsequent studies continue to show marked survival improvement when the new protocols are used. I discussed this topic as an example of a failing of evidence based medicine in the last Medscape Roundtable Discussion on EBM.

Loss of procedures is another reason general Internal Medicine is on life support

Go read Retired Doc’s summary of an Annals of Internal Medicine survey of ACP general internist members and an accompanying editorial by two officials of the American Board of Internal Medicine (ABIM) concerning the marked decline in procedures done by general internists over the past two decades.

I’m not surprised by the decline in procedures but I found the ABIM editorial’s recommendations odd concerning what procedures general internists should be able to do versus merely talk about. I appreciate the comments by letter writer and Annals Associate Editor Michael LaCombe, who decries the committee approach to procedural competencies and calls for research on what procedures general internists should be trained to do. He concludes (italics mine) “Finally, a caveat to you young students out there: if such research is not funded, if this profound question is not answered by funded clinical research, if the question is sent to committee and therefore to certain death, continue to avoid general internal medicine at all costs, as you have been.”

Your pocket guide to woo from AMSA

Now you can access woo at the point of care. AMSA’s updated handbook, concise and trimmed down (and able to fit in your lab coat pocket), is still chock full of info on homeopathy, TCM, Tibetan medicine and much more.