The Avandia meta-analysis: critical appraisal versus hype

Musings of a Distractible Mind shared some Thoughts on Avandia today (via Kevin M.D.) and is rightfully concerned that irresponsible popular media coverage seems to be guiding scientific discussion. In discussing some of the flaws of the meta-analysis he notes this:

We had an endocrinologist in our office a few days ago (not representing GSK) and we discussed this issue, and his comment was that Dr. Nissen is “the Michael Moore of the medical industry.” Strong words. Mr. Moore is a crusader against the big and rich for the protection of the little guy (in his opinion). The problem is (in my opinion) that Mr. Moore does not always come to conclusions based on evidence, but starts with a conclusion and finds evidence to support this. This is precisely the danger of a meta-analysis of the sort that was done in this case.

But the Medscape piece he cites seems to portray the writers of the related NEJM editorial, Psaty and Furberg, as the real crusaiders:

Dr Steven Haffner (University of Texas Health Science Center, San Antonio), who was involved in the ADOPT study of rosiglitazone, said the paper needed to be published, but it should have undergone a more extensive review, and there should have been a different editorial with more emphasis on the flaws of the study. “The NEJM was irresponsible to go to [Drs Bruce] Psaty and [Curt] Furberg for the editorial--they were always going to emphasize concerns about drug safety; that’s what they do," he commented.

Dr. Robert Califf of Duke University commented on the harmful effect of scientific discussions being played out in popular media:

“It would be better if we had a system of postmarketing signal detection in which signals were vetted scientifically rather than splashed over TV and newspapers. I can't help but wonder if the NEJM is functioning more like the mainstream press than a scientific journal at this point, since many potential peer reviewers seem to feel that Dr Nissen's analyses are missing key elements that could have been added."

Points I’ve made many times in these pages.

Clinical pharmacists as members of the health care team

The latest MedGenMed video editorial reminds us of the importance of the clinical pharmacist. It’s worth viewing and makes valid points. I’m wondering, though, if it’s part of a promotional campaign. It’s the third MedGenMed video editorial in just over a month telling us not to forget the clinical pharmacist. I think I get the message.

Stinging rebuke of the Avandia meta-analysis

In my humble opinion a bad meta-analysis belongs at the bottom of the evidence based medicine hierarchy. The Avandia meta-analysis has been accepted uncritically by the media but how good is it, really? The Angry Pharmacist has some questions. The entire post is compelling reading, but I was most interested in the part about the conflict of interest disclosure, a point the popular media missed entirely: Dr. Nissen reports receiving research support to perform clinical trials through the Cleveland Clinic Cardiovascular Coordinating Center from Pfizer, AstraZeneca, Daiichi Sankyo, Roche, Takeda, Sanofi-Aventis, and Eli Lilly.

It’s an impressive list of Glaxo’s competitors, including Takeda, the maker of Avandia’s most direct competitor, Actose. Well, how about that!

Via Kevin M.D.

Acute decompensated heart failure: management in 2007

A review article in the March 13 2007 issue of CMAJ covers the initial evaluation and management and cites the supporting literature. A few points of interest follow.

Loop diuretics: Mainstay of initial therapy; should be combined with other modalities.

Peripheral venous ultrafiltration: Promising, with role in the general care of acute heart failure to be determined.

Nitroglycerine intravenously: Beneficial for patients with adequate blood pressure, underutilized.

Nesiritide: Controversial. Large mortality and cost effectiveness trial about to begin.

CPAP, BiPAP: Now considered first line as initial short term therapy in acute cardiogenic pulmonary edema. (Invasive mechanical ventilation may be more appropriate in some patients presenting with acute myocardial infarction).

Inotropes, PDE inhibitors: Generally avoided and limited to short term palliative use. May increase mortality.

“What to do with long-term ß-blocker therapy in the setting of acute decompensated heart failure remains a clinical conundrum. Our practice is to reduce the dose proportionate to the degree of hemodynamic compromise; the ß-blocker dose may be decreased by about half in patients with evidence of hypoperfusion, and stopped in patients with frank cardiogenic shock, although there is little evidence to support this approach. Following an episode of acute decompensated heart failure, ß-blocker therapy should be titrated upward slowly.”

ER Pocketbooks

ER Pocketbooks is a non-anonymous blog which posts clinical images. It’s the latest subject of the recent flurry of posts which relate, in one way or another, to the hazards of blogging. The site got the attention of KNSD, channels 7/39, San Diego which ran this: A North County emergency room doctor is generating controversy by posting X-rays and pictures of patients' injuries on his Web site, NBC 7/39 medical correspondent Peggy Pico reported.

Although a hospital where the blogger works as an emergency physician was concerned about how the images were obtained the KNSD report concludes there were no HIPPA violations since the images contained no patient identifying information.

The blogging fears that have been expressed recently have been all over the map, it seems to me, without a really consistent theme. After all, the individual blog shutdowns occurred for different reasons. That makes it difficult to know just what is the lesson of Black Wednesday.

At any rate, regardless of where one weighs in on the controversy, ER Pocketbooks looks like a site worth checking out for its educational value. Here, for example, he presents a well discussed and well referenced case of an underappreciated entity: Wellens syndrome.

Rosiglitazone (Avandia) in perspective

Today the New England Journal of Medicine released, on line ahead of print, a meta-analysis of 42 trials looking at the effect of rosiglitazone on cardiovascular outcomes. The use of rosiglitazone, compared against placebo or other regimens for type 2 diabetes, was associated with a statistically significant increase in myocardial infarction and a non-statistically significant trend toward increased cardiovascular mortality.

This finding begs the question of whether the apparent adverse effect is a class effect of thiazolidinediones (TZDs) or is unique to rosiglitazone. The meta-analysis findings are in contrast to the PROactive study of the other TZD approved in the U.S., pioglitazone, which showed improved cardiovascular outcomes. I commented on PROactive here, here and here. A new analysis of PROactive published in the Journal of the American College of Cardiology (JACC), looking at recurrent MI in the cohort of patients with previous MI (2,445, just under half of the PROactive population) showed a statistically significant reduction in the pioglitazone group. The official PROactive web page contains updates.

Is there an explanation for these apparently disparate effects? It may lie in the fact that while rosiglitazone is a pure PPAR gamma agonist pioglitazone is a mixed PPAR gamma and PPAR alpha agonist. PPAR alpha agonism may confer more favorable lipid effects on pioglitazone. Specifically, while both drugs raise HDLC, pioglitazone has little or no effect on LDLC while rosiglitazone raises LDLC. Pioglitazone seems to lower triglycerides more effectively than does rosiglitazone.

Psaty and Furberg commented on the meta-analysis findings in this editorial. They point out that although ongoing trials may shed favorable light on rosiglitazone, a lack of positive outcome data in the long period since approval in 1999 is concerning, and reach this sobering conclusion: “On the basis of this meta-analysis, however, the possibility of cardiovascular benefit associated with the use of rosiglitazone seems remote.”

More from Kevin M.D.

Panda Bear challenges the conventional wisdom

Panda Bear is a medical blog I discovered today, thanks to Kevin. Panda Bear seeks to challenge the politically correct dogma of an elitist medical establishment he refers to as “The Man”. His contrarian ways of looking at medicine and society are refreshing. Here’s a sampling from recent posts:

The conventional wisdom is that the American health care system is broken. This is the party line parroted by the various media organs of the dependocracy in their attempt to stampede an excitable public towards socialized medicine. Like a lot of the conventional wisdom, the idea of a broken health care system gets repeated so often that it has become a cliche, something that people spout in a self-righteous reflex. It is certainly a pleasant metaphor and an easy one for the people to get a handle on without having to think about the real complexities of delivering zero-defect medical care to a largely non-compliant public….


We pay lip service to the idea of patient-centered health care of course, and including the patient as an equal partner in medical decisions is the New Religion. In our society however, where a physician can get sued for not having written on the discharge instructions for a dead crack dealer, “Return to Emergency Department if chest pain returns,” well, there just isn’t as much equal partnering as you’d like to believe.

In fact, there’s none to speak of where it counts. Not an artery hardens or liver fails without a physician somewhere, somehow being blamed.

There are many versions of the Hippocratic Oath and it is continuously edited to suit the demands of political correctness.

…..it is not a requirement that physicians be social activists or professional busy-bodies.

Maybe a hundred years ago you could make a case for magic potions and mysterious cures from the East but today we should know better and only don’t because of a combination of scientific illiteracy and an ingrained bias against rational Western thought.

I’m adding Panda Bear to my blogroll. Stat.

Pay attention to the patient’s body language in evaluating chest pain

The pointing sign has negative predictive value for ischemic heart disease. Other gestures are less helpful diagnostically.

Non-evidence based heart failure management

Here’s yet another study to add to the growing literature showing underutilization of proven drug treatments.

Classification of diabetes

---with discussion of some of the atypical forms. From Clinical Diabetes.

ACLS drugs

Pharmacotherapy Considerations in Advanced Cardiac Life Support, published in the journal Pharmacotherapy, comprehensively reviews ACLS drugs and their 2005 guideline recommendations. Treatment of beta blocker, calcium blocker and digoxin overdose as well as hyperkalemia and hypokalemia are also reviewed.

Cervical spine manipulation and stroke

Southern Medical Journal reports a case of fatal posterior circulation stroke following chiropractic manipulation of the cervical spine and discusses the literature. The authors conclude:

Since there is a large amount of evidence from many reports regarding an association between neurologic damage and cervical manipulation, and because there are no identifiable risk factors, anyone who receives CSMT can be at risk of neurologic damage. It is important for patients to be well informed before undergoing this kind of procedure and for physicians to recognize the early symptoms of this complication so that catastrophic consequences can be avoided.

Stroke update

What the physician on the front line needs to know. Via Patient Care.

Multiple beneficial effects of statins

To Retired Doc’s roundup of possible extravascular benefits of statin drugs I add this: a report from Pharmacotherapy on a reduction in fatal pneumonia.

Impending doom?

Among the blogospheric reactions to the departures of Flea and Fat Doctor I found this one interesting over at Stranger than you can imagine: I think the risks are too high. I think that all of the medical bloggers are going to disappear or go private in a month or less.

OK, start the countdown. 30 days.

Taking woo to a new level at the NIH

You can read about it in this press release from the NIH (hat tip to the Health Fraud List). According to the release, woo is nothing new at NIH:

CAM is not a new concept at the NIH Clinical Center. The Clinical Center’s Pain and Palliative Care Service and the Rehabilitation Medicine Department offer acupuncture, Reiki, hypnosis, guided imagery, massage therapy, acupuncture, tai chi, and qi gong training.

But now woo will get more respect with the opening of the NIH Clinical Center’s Integrative Medicine Consult service.

Use of meropenem in penicillin allergic patients

Despite evidence that imipenem frequently cross reacts with penicillin and the general belief that all “penems” should be avoided in penicillin allergic patients, meropenem seldom cross reacted in this study. Nevertheless, the authors recommend skin testing before using meropenem in penicillin allergic patients.

Related: Cehpalosporin use in penicillin allergic patients.

How does your state Medicaid program measure up?

Public Citizen rates them here.

Need help with boards?

Clinical Cases and Images has some great tips and resource links.

Learn woo from the Dream Healer and get CME credit

---at the Body Heals Conference. The bio describes Adam the Dream Healer as a “distant energy healer” who “uses energy healing in a unique way to merge the auras of all participants with healing intentions. Then he uses holographic views to energetically affect through intention those present.” Before you dismiss these methods note: “We would like to impress upon everyone that what Adam does is not mystical or magical. It is all based on science.”

There’s more. Learn the secrets of youthful aging from Dr. Norm Shealy. “Those with the essential healthy attitude and lifestyle will live an average of 100 years, and the wisest will choose habits to add another 40 years.”

And if you really want to pursue wellness, get a horse! Sandra Wallin, MA, RCC, BSc, Bed introduces the Equine Apothecary.

Additional sessions cover Qi Gong, homeopathic weapons against the coming influenza pandemic, the “fluoride deception” and cancer as a “moral illness.” I don’t think I’ve seen so much woo packed into one CME activity. My head is swimming.

Via the Health Fraud list.

Chronic tachycardia mediated cardiomyopathy cured by ablation

In a population of patients with dilated cardiomyopathy and atrial fibrillation, maintenance of sinus rhythm via ablation (mainly pulmonary vein isolation) was associated with nearly universal improvement in left ventricular systolic dysfunction with normalization in most patients. The study, recently published in the Journal of Cardiovascular Electrophysiology, adds to the growing evidence for the existence of chronic tachycardia mediated cardiomyopathy as a distinct and important clinical entity.

Opioid treatment of chronic back pain

In this systematic review efficacy was unclear beyond 16 weeks and “aberrant medication-taking behaviors” (translate seeking, abuse) was noted in up to 24% of patients. That finding certainly differs from the current pain management dogma that “addiction is rare.”

Characteristic CT findings in methanol intoxication

A case report and brief commentary in CMAJ.

Can complementary and alternative medicine be subjected to scientific scrutiny?

It’s often said that the debates over alternative medicine are pointless because there is really no alternative medicine; there’s only medicine that has been proven to work and medicine that hasn’t. At first glance the notion seems sound. Simply subject an alternative claim to scientific investigation. If it proves out it becomes mainstream, otherwise it is rejected. If only it were so simple! The reality is that little has been settled despite many years and hundreds of millions of dollars devoted to alternative medicine research. I offer examples here of why this is so.

Promoters of unscientific claims often reject ordinary scientific standards for experimental design and evidence
The American Medical Student Association, the largest and most influential organization of medical students, promotes many unproven methods. In their web pages on integrative, complementary and alternative medicine they suggest that currently accepted scientific methods may not be optimal to study alternative medicine. Moreover, they imply that complementary and alternative medicine should be adopted now, without waiting for definitive evidence, with this statement: “For most CAM therapies, the final word is not yet in on their effectiveness. But the medical community cannot wait for the final word; they need to know what patients are using now and if it is effective. Many primary care doctors are opening clinics with CAM practitioners. These integrated medical centers provide one of the best learning tools for current physicians and may be the most efficient and effective way to blend conventional and unconventional medicine.”

Even government funded CAM research is troubled with serious methodologic flaws
Perhaps the best example of such flawed design is the National Center for Complementary and Alternative Medicine’s ongoing Trial to Assess Chelation Therapy as a treatment for atherosclerosis. As I pointed out in this post, many of the study sites appear to be tainted by a lack of objectivity and dubious scientific qualifications. That lack of objectivity is especially concerning because the investigators are not securely blinded.

Research on complementary and alternative methods is conducted without regard to biologic plausibility
Numerous subjects of CAM “research” are so implausible they would require rewriting the chemistry and physics books. These include claims that a mystical force remains in water after solute is diluted out (homeopathy), imaginary claims of “energy fields” which can’t be measured or detected (various energy healing modalities) and purported energy channels that have no basis in anatomy (the meridians of acupuncture and related methods). It’s as if the NCCAM is willing to “study” any claim, no matter how preposterous, if there’s consumer interest and available funding.

Why is this problematic? Because the test of plausibility is an important safeguard, without which baseless health claims can be subject to clinical studies, occasionally passing the test of statistical significance and yielding “positive” results by chance variation. That might not be a major problem were it not for positive publication bias in quackery promoting journals which receive favorable consideration for Medline indexing, thus inflating dubious claims subjected to meta-analyses, which rely heavily on Medline searching. (See below). In consequence, woo based claims get the trappings of evidence based medicine. My principle for plausibility testing is crude but vivid: “evidence based” woo is still woo!


The proponents and funders of alternative medicine research do not accept negative results
Despite, for example, negative results in the National Center for Complementary and Alternative Medicine supported trail on echinacea the NCCAM apparently didn’t believe the results and wants to do it over again. Worse yet, last year the director and deputy director of the Office of Clinical and Regulatory Affairs of NCCAM published this editorial suggesting that multiple negative results from NCCAM supported studies should not be accepted. More recently, NCCAM has decided to seek funding for the performance of “omics analysis” on previous negative studies of CAM modalities.


Government oversight is biased in favor of complementary and alternative medicine
Dr. Wallace Sampson, Emeritus Clinical Professor of Medicine at Stanford University, has extensively researched the procedures of journal selection by the National Library of Medicine for indexing in Medline and uncovered enormous bias in favor of CAM oriented journals which are largely promotional, uncritical and agenda driven. The whole process, it seems, is corrupted by conflicts of interest. Moreover, the FDA has a lax double standard which is favorable to the development of herbal remedies.

Evidence based medicine (EBM) has failed to remedy the many problems in CAM research. It cannot adequately address the massive agenda which drives much of the research and pays too little regard to biologic plausibility. This is due to misappropriation and misunderstanding of EBM more than any inherent failings of EBM.

Case based learning on the web

In the February issue of Mayo Clinic Proceedings is a review of case based learning resources for internists on the web. It contains a huge collection of links. It’s behind access controls now, but will be open access in August.

Not all of the sites offer CME credit, and of those which do some charge for the CME processing although the content is free.

Here are just a few:

Baylor GI rounds
UCSF chest cases
Hopkins CPCs
Cleveland Clinic Image Quizes


No listing of case based learning resources would be complete without mentioning one of our favorite blogs, Clinical Cases and Images.

Docs submit fake postings to Rate MDs

Dr. Keith Thompson became frustrated at the false anonymous comments about himself and his colleagues. He tried to work with the site’s owners to change commenting procedures. That didn’t work, so----

"I spammed the site because I was upset with what I saw about colleagues that I knew was false and because I saw the site as being no more valid than an MSN chat room," Dr Thompson told NRM by email. "I have consistently tried to make my point that ratings or comments need to be available to registered users only...

Via National Review of Medicine. Read the rest.

UK health system gets bad report card from Karolinska Institute

High cancer mortality due to lack of access to new drugs noted. Check it out here.

Bloggers’ reactions:

Blue Crab Boulevard

Captain’s Quarters

Finally, Socialized Medicine weighs in with some reflections on single payer health---

The other thing that worries me about socialized medicine is that there is no incentive there for the best-and-the-brightest to undertake the arduous work (and heavy cost) of obtaining medical degrees, so that they can be under the power of the Government, rather than allowed to strike out on their own. Then who will be our next doctors? The second tier students? The third? Socialism too often is a showcase for mediocrity. It doesn't work. The private sector is imperfect, and there are certainly issues within our health care system that need addressing, particularly for the un-insured, but throwing us into this fresh hell is not the answer.

Self promotion by the VA health system

The McClatchy Newspapers have been doing some investigative reporting on VA health care. “The Department of Veterans Affairs has habitually exaggerated the record of its medical system, inflating its achievements in ways that make it appear more successful than it is, a McClatchy Newspapers study shows.” The report cites doctoring of appointment records to show shorter wait times and more.

Via The Health Care Blog and Kevin M.D.

When and how did presidential candidate Dennis Kucinich find out about the systematic review on Canada and U.S. health outcomes?

I recently posted this criticism of a systematic review of health outcomes in Canada and the U.S. and wondered if the paper was politically motivated. Other bloggers, including DB, Health Care Renewal, Medpundit and Kevin weighed in about the paper, published in the inaugural issue of Open Medicine.

On May 3 Scientific American posted an article about the paper which was predictably uncritical and largely unrevealing until the last paragraph:

This research may already be having an impact on policy debate: According to Woolhandler, Ohio democratic congressman and presidential candidate Dennis Kucinich has plans to circulate the results of this study to Congress. Woolhandler herself would like to see this study play a part in a slightly different debate—one over whether it it [sic] is better to be sick and insured in the U.S. or in Canada. "I'd like to see politicians giving up on this mythology that the quality of care for sick people in the U.S. is unique."

Woolhandler, of course, is one of the authors of the Open Medicine paper and, like the other authors I profiled here, an admirer of Canada’s health care system and an activist for adoption of a similar system in the U.S.

Dennis Kucinich is a Democratic presidential candidate. Moreover he’s a supporter of single payer health care and the co-author of HR 676, a plan for a “universal, single payer, not for profit health care system”. In principle Kucinich’s proposal is similar to Woolhandler’s and not unlike Canada’s system.

So, let’s look at a possible time line. The Scientific American article was posted May 3. Since it’s an on line article and not a post on their blog the editorial process between submission and posting likely took several days. We must then ask how many days before submission did the interview with Woolhandler take place and, how long before the interview did she know of Kucinich’s plans to distribute the study results to congress? Since Open Medicine was not launched until April 18 that didn’t give Kucinich much time to find out about the paper. How could he have searched for it? Open Medicine isn’t listed in PubMed yet. Did he search the blogs? With his busy campaign schedule and congressional duties would he have had time to do that?

Does Woolhandler have any association with Kucinich? What’s the nature of any conversations they may have had? And dare we ask: Did Kucinich learn about the paper with the help of one of its authors? The big question, and one I raised in my previous post, is whether or not this paper was submitted with political intent. The Scientific American piece lends further credence to that question.

Does lethal injection constitute cruel and unusual punishment?

Maybe so according to a paper in PLoS Medicine: Lethal Injection for Execution: Chemical Asphyxiation? The authors looked at execution records from 2 states, examined eyewitness accounts of execution by lethal injection and examined the relevant pharmacology. They write:

We were able to analyze only a limited number of executions. However, our findings suggest that current lethal injection protocols may not reliably effect death through the mechanisms intended, indicating a failure of design and implementation. If thiopental and potassium chloride fail to cause anesthesia and cardiac arrest, potentially aware inmates could die through pancuronium-induced asphyxiation. Thus the conventional view of lethal injection leading to an invariably peaceful and painless death is questionable.

In other words the effect of thiopental as it is used in execution protocols may not be strong or long lasting enough to eliminate awareness of the pancuronium-induced respiratory paralysis or the intense pain resulting from injection of concentrated potassium chloride.

The article also cites eyewitness accounts suggesting inmates’ suffering and points out that execution by lethal injection doesn’t have nearly the research underpinning or ethical oversight that is applied to animal euthanasia. This paper may result in increased pressure for states to open their execution records and may be a stimulus for legal challenges against execution by lethal injection.

Now for some personal disclosures and reflections. I oppose capital punishment. I also, as regular readers know, believe that scientific discussions can be corrupted when mixed with political debate. When such discussions overlap, as they inevitably must, safeguards are necessary. First, while science can legitimately inform political discussions (in the case of lethal injection, the authors clearly show us that we had better understand a little pharmacology before we can argue about whether it’s humane) it should not be the other way around. Second, appropriate disclosure of significant political affiliations or leanings is essential. To the credit of PloS Medicine appropriate disclosure seems to have been made. We are informed that one of the authors practices capital defense, another has been a paid expert in death penalty litigation and all the editors at PLoS Medicine oppose the death penalty. Other journals should take note.

MTHFR testing to assess risk of VTE recurrence---don’t bother

The MTHFR 677C-T polymorphism increases homocysteine levels. Meta-analyses have demonstrated a weak association of the 677TT genotype with risk of VTE, although these data may be troubled by publication bias. In this large population-based case-control study the genotype was not associated with increased risk of recurrence. MTHFR gene testing is not recommended although homocysteine testing is reasonable.

Industry support for CME

Mayo Clinic investigators surveyed attendees of 4 of their own Internal Medicine CME programs, 2 of which received pharmaceutical industry support and two of which did not. Respondents’ attitudes regarding industry sponsorship were evaluated. The results were not surprising. Overall, a majority (about 58%) had no general preference as to whether an event received sponsorship or not. On the other hand, a similar majority (62%) believed that a CME program should accept support it would reduce the cost for attendees.

A synthesis of current recommendations regarding industry CME support by the AMA, ACP and ACCME was given by the authors, who believe that adherence to such guidelines will substantially reduce inappropriate industry influence and bias. In effect these recommendations call for unrestricted grants, conflict of interest disclosure by speakers, no industry role in determining content, support given to program organizers rather than the participants and safeguards against bias. I agree.

Deaths following treatment at Portland integrative medicine clinic

Three patients recently died shortly after receiving intravenous injections of colchicine provided by an integrative medicine clinic in Portland Oregon. It was discovered that the batch of colchicine, obtained from ApothéCure Inc., was 10 times as potent as labeled. Two of the deaths have been officially determined to be due to the faulty preparation while the third is under investigation. Colchicine was being used for the off label indication of chronic neck and back pain.

ApothéCure, while purportedly a compounding pharmacy, may in fact have been functioning as a drug company by selling batches of drugs for use in multiple patients. But if it’s a drug company it’s not mainstream. The Autism Diva offers this expose of compounding pharmacies and in this post characterizes them as “un-Big-Pharma”:

It's amazing how people are willing to believe the worst about Big Pharma (which is guilty of some amazing abuses, to be sure) but they are also willing to give un-Big-Pharma a free pass on what they are doing and selling and how much profit they are making.

ApothéCure, it seems, has been investigated before. Dr. Geoffrey Wiss, a Portland emergency physician, was a partner in the integrative medicine clinic and noted that although colchicine was available from manufacturers the clinic ordered it from ApothéCure because it was less expensive. It is unclear who prescribed the colchicine. Although the patients were under the care of naturopaths, Wiss and other M.D.s collaborate in the clinic. Naturopathic physicians have prescriptive privileges in Oregon. Dr. Wiss, profiled here, joined the clinic in 2005 to learn about alternative medicine by working with naturopathic physicians. He was credited with recognizing the pattern of deaths and alerting authorities.

These deaths raise many questions. Were naturopaths, generally loathe to use prescription drugs and whose mantra is first do no harm, involved in the administration of the highly toxic drug colchicine? Well, I guess it is “natural”. After all, it’s an alkaloid.

Perspectives on industry and the sepsis guidelines

A commentary on this ongoing controversy, Is Industry Guiding the Sepsis Guidelines? A Perspective, appeared in a recent issue of Critical Care Medicine. (I’ve had a thing or two to say about it here, here and here).

Author Charles Durbin, M.D. notes the unacceptably high mortality in sepsis, the potential for multiple evidence based modalities to impact this mortality and the universal gap between publication of evidence and clinical implementation. The Surviving Sepsis Campaign (SSC) was conceived to try and close this gap. The task, unfortunately, took extensive resources, resources not available from public funding. Although Eli Lilly supported the logistics of the campaign the company had no role in the development of the guidelines.

The Society of Critical Care Medicine (SCCM) undertook the process of sepsis guideline revision last year without industry sponsorship in order to avoid unwarranted criticism. Durbin hints that the revised guidelines and bundles will not substantially change, thus supporting the work of the 2004 authors.

He concludes:

Viewed pragmatically, the SSC under the stewardship of respected medical societies is a fundamentally sound and promising endeavor to improve patient care. The premises of the Campaign remain vital: 1) the mortality rate for severe sepsis is unacceptably high; 2) practice guidelines, developed through a rigorous evidence-based review of the literature, must be translated into practice; and 3) research questions about the efficacy of a bundle approach in severe sepsis and the differential impact of combining sepsis therapies must be answered. SCCM strongly supports the call for the creation of public funding mechanisms to accomplish translational research. In the meantime, the Campaign will press forward to reduce mortality attributable to severe sepsis with the resources available.

The more vocal guideline critics seem mainly to be screaming about the role of industry, offering little in the way of constructive criticism. One wonders whether they’re concerned with anything more than industry bashing. If they want to help doctors take better care of patients with sepsis they should discuss the evidence on its own merits. If the guidelines are hopelessly flawed they should help develop better ones. Everyone will get along better and patients will benefit.

Newly discovered blog for hospitalists

The comment thread in Aggravated DocSurg’s recent hospitalist rant pointed me to The Hospitalist Blog, written by IPC hospitalist company leader Adam Singer, M.D. This blog has been up and running about a year, but is new to me. I shall browse with interest.

Fair use, copyright and other legal traps for bloggers

Aviva Directory discusses some legal issues bloggers should know. This dovetails with our recent discussions on blogging and fair use.

Via Follow Me Here.

Blogroll update

This is long overdue. I haven’t had nearly enough time to properly tend to this blog. Check out the new links. Listing on this blogroll does not imply agreement or endorsement. What it does mean is that these blogs post content of interest to me often enough to warrant inclusion here. More to come as time permits.

More discussion on the hospitalist movement

Not long ago Aggravated DocSurg wrote a very negative post about the hospitalist model of care. I responded here and acknowledged that DocSurg had raised some important issues that hospitalist leaders need to address. Then Flea weighed in with these two posts and said:

There is no more stinging indictment of the hospitalist phenomenon than this: The patients hate it. They want to be cared for by their own doctors. When will the peeps speak up and tell the hospitals they hate the hospitalists? If the powers that be won't listen to the fleas, perhaps they'll listen to the customers.

I must respectfully question that assertion and again point out that a collection of anecdotes does not equal evidence. The best evidence that I’m aware of comes from this systematic review of hospitalist outcomes. Of the 19 papers in the review 4 reported on patient satisfaction. In all 4 of those studies no difference in patient satisfaction was found between the hospitalist model and the traditional care model. From the patient’s point of view the disadvantage of hospitalist care, discontinuity, may be counterbalanced by the fact that the hospitalist is “there” all day, can make frequent re-visits when necessary and may be more accessible to families.

“I sleep with a drug rep”

----is one of several conflict of interest disclosures given by Thomas P. Stossel, a participant in Medical Progress Today’s conflict of interest symposium. You can view a text only or slide version of his presentation. Although not against reasonable safeguards he effectively shatters some of the simplistic and extreme positions now being put forth concerning the interaction between medicine and industry.

Appropriate and reasonable concern about the influence of industry on science has swung to an unhealthy extreme. He notes “In the past we named sponsors of our research and education efforts to honor them. Now, all disclaimers to the contrary, we are forced to itemize sponsors so that the beholder can discount our words and our work and to satisfy a prurient interest in our earnings.”

Though Stossel isn’t advocating for non-disclosure he notes adverse consequences of our obsession with industry connections: “Nothing better illustrates how what we disclose demeans us than the call to have only the second best and the not so bright, persons free from all commercial interests, serve in advisory roles.” Is there support for this implication that exclusion of experts with industry connections leaves us with “second best and not so bright”? It was certainly true in the experience of New England Journal editors in 2002 who found they had to relax their policy banning commercial interests in order to find qualified authors for their drug therapy series.

Stossel addresses the selective outrage about conflicts of interest with this: “Interestingly, these authorities exempt the principal source of money exchange in medicine—clinical practice—from the segregation of production and promotion, even though promotion of clinical services is routine.”

It’s worth the read in its entirety.

Therapeutic hypothermia after cardiac arrest: practical aspects

The 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiac Care have incorporated new recommendations for the application of therapeutic hypothermia in the post resuscitation period. External cooling applied to comatose patients upon return of spontaneous circulation (ROSC) who are hemodynamically stable results in increased survival and better neurologic outcomes. Out of hospital cardiac arrest in which the initial rhythm was VF carries a Class IIa recommendation. In hospital cardiac arrest and out of hospital non VF arrest carry a IIb recommendation.

There are details to attend to in real world implementation of the recommendations. Patient selection is difficult, and many patients will not be candidates. This concise review in CMAJ covers some of the practical aspects such as cooling methods, temperature goals, patient selection and complications.

IVIG for severe sepsis?

Promising but not ready for prime time.

PCP prophylaxis---not just for patients with HIV

What other patients should receive prophylaxis for Pneumocystis jiroveci (formerly Pneumocystis carinii) infection? You may be surprised.

See this study and accompanying editorial in Mayo Clinic Proceedings. These articles (both open access full text) are dated but may be news to some.

New concepts in the evaluation of syncope

Reviewed in PACE.

Want to promote woo?

U.S. medical schools are more than glad to help. “Ayurveda is set to make a landmark entry into mainstream U.S. medical education” according to this report.

The course is the result of four years' hard work by Riverdale, Md.-based urologist Navin Shah, who took on the challenge of bringing Ayurveda to mainstream U.S. medical education after a request from erstwhile Indian Prime Minister Atal Behari Vajpayee, he told India-West.

"Vajpayee wanted me to propagate Ayurveda," he said. "I told him the best way is to go through the medical schools, because we want to enter through the main door of the mainstream, which is (the) medical
school."

The med schools came through. Several are preparing to offer courses to medical students and house officers. Dr. Shah even foresees Ayurveda achieving subspecialty status in the field of Internal Medicine.

Blogiversary roundup

How about a cybertoast to three pioneering medical bloggers who note blogiversaries this month!

Gruntdoc celebrated his fifth on May 2.

Kevin M.D. celebrates his fourth today.

DB’s fifth is coming up May 19.

These bloggers have been sources of inspiration and encouragement to me. Here’s wishing them many more.

It’s springtime, when a med student’s fancy turns to thoughts of woo

If woo is your fancy, the American Medical Student Association sponsored Humanistic Elective in Alternative Medicine, Activism and Reflective Transformation, held last month, did not disappoint. What’s more, the woo was accredited.

As in last year’s elective, a variety of woo based methods were featured, including, according to the sample schedule, homeopathy, TCM, Native American Healing, and Ayruveda.

The course web page reflects the antithesis of the Western scientific world view with this statement: It is only with the heart that one can see clearly; what is essential is invisible to the eyes….

Should you turn your patients over to hospitalists?

It’s all a matter of what works best for you and your patients. Although physicians who juggle the responsibilities of office and hospital practice seem to be a dying breed there are many who do it well.

The January 19 issue of Medical Economics offers a point-counterpoint.

Hospitalists: Why I don’t use them.

Hospitalists: How I make it work.

Systematic review of troponin elevation in critical illness

Via Archives of Internal Medicine.

Antiquated hospital plumbing linked to Pseudomonas deaths in Canada hospital

This is according to a report on a Pseudomonas aeruginosa outbreak that took place on a neonatal ward in a Montreal hospital in 2004-2005. After disinfection efforts failed to stem the outbreak the ward was closed. Pseudomonas, which likes stagnant water, was found, according to the investigation, festering in the sinks on the wards because the sinks did not drain properly.

There’s a pattern emerging. Outmoded facilities constitute an infection control problem. Canada faced a similar issue with the new highly virulent Clostridium difficile strain which broke out in Quebec hospitals. A study in CMAJ described the outbreak and highlighted the high attributable mortality. That paper concluded: The lack of investment in our hospitals infrastructure over several decades, with shared bathrooms being the rule rather than the exception, may have facilitated the transmission of this spore-forming pathogen, which can survive on environmental surfaces for months. Providing modern medical care within hospitals built a century ago is no longer acceptable.

An accompanying editorial noted we need to begin long-neglected upgrades in hospitals infrastructure, as there is a lag of almost a decade between the intention to build and the completion of projects and cited the related observation that the risk of nosocomial acquisition of methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci and C. difficile was reduced 4-fold after the medical teaching unit at the Foothills Medical Centre in Calgary moved from a 5:1 to a 1:1 bed-toilet ratio.

Controversy over electronic medical records

Does the medical profession deserve the Luddite label as DB suggests? The Dinosaur doesn’t think he does even though he is skeptical about the benefits of electronic medical records (EMRs). I’m not a Luddite—I’m a computerphile. I was one of the first kids on my block to go on line with medical searching, way back before the days of the World Wide Web. But I share much of Dinosaur’s skepticism. I place myself in the middle ground on this debate.

Let’s look at a couple of Dinosaur’s objections, which addressed some of the popular myths about EMRs. First, do they really improve legibility? That depends, of course, on the quality of the doctor’s handwriting, and whether or not the doctor dictates his/her notes. But Dinosaur makes an important point about readability problems inherent in EMRs which rings true in my own experience: computer template generated clinical notes have a very low signal to noise ratio. For the doctor the signal is clinical information. The noise consists of all the clinically useless clutter which serves no purpose but to keep the insurance coders happy. Template generated progress notes make it nigh unto impossible to communicate a doctor’s thinking or tell a patient’s story in a meaningful narrative form.

Do EMRs save time? There’s probably not an “evidence based” answer to this, but the overwhelming subjective experience seems to be that EMRs are a net consumer of time, at least for a year or two after implementation.

Do they improve reimbursement? Dinosaur addresses P4P and points out that any P4P rewards gained from EMRs are nominal. Do they improve E&M coding, thus improving reimbursement? The potential is certainly there. I’ve encountered software that prompts me to “add one more system to the review of systems and two more to the physical exam to code one level higher.” This ensures that the documentation will support the coding but is it ethical? If the patient has a cold does he/she need a complete system review? A great deal of template generated “documentation” appears gratuitous to me.

Do EMRs improve quality? Many studies report soft outcomes. An EMR may increase the rate of documentation of patients’ hemoglobin A1C levels from 75% to 83%, but what about error rates and clinical outcomes? Although EMRs may intercept certain types of errors they increase others. Data on hard clinical outcomes are sparse, but at least one study showed an increase in mortality related to computerized physician order entry.

How can this debate be resolved? The answer is “it depends”. In a MedGenMed Video Editorial last year opinion leader Robert Wachter, M.D. gave a sober assessment. He cautioned that Computer systems must be implemented carefully, with unforeseen consequences not only sought but anticipated. Systems should be launched on a pilot unit, and should be extensively vetted by user groups before going live. Staff must be educated, and swarms of real-time problem solvers should be immediately available after implementation. The computerization of healthcare will ultimately improve the quality, safety, and efficiency of care. But the road will be full of bumps and curves. It’s not a matter of “just doing it”.

The DocSurg is aggravated with the hospitalist movement

At my place of work surgeons and hospitalists enjoy a mutually respectful and beneficial relationship. So, I was surprised to read this rant from Aggravated DocSurg, a general surgeon and one of my favorite medical bloggers. He’s underwhelmed with the hospitalists who came to fill the vacuum in his community resulting from all the internists giving up hospital medicine. These hosptialists don’t provide him the help he needs. Consequently he’s having to “tune up” his surgical patients and manage their post operative medical complications. In short he’s functioning as a flea (a pejorative term for Internist) and, thanks to global surgical fees, not getting reimbursed for it.

He writes “How can a middle aged guy who has spent the last 19 years training and then working as a general surgeon be a flea underneath his scrubs? I am afraid that it is because the economics of medicine, and the lifestyle choices of (many) physicians, have foisted the hospitalist era upon us.” He laments that the hospitalist program at his institution is inefficient and that other surgeons he networks with across the country feel the same way. Citing several possible reasons for this he notes, concerning hospitalists “…but in my experience they are folks who did not flourish in the world of office practice seemingly due to an inability to address patient problems in a time efficient manner.” Ouch. He goes on with “Additionally, one of the unspoken problems with the hospitalist system is that many patients are so P.O.ed at not being able to see their ‘real’ doctor that they develop an intense animosity towards the hospitalists called in to see them....and then fire them.” Yikes. And finally “I manage a whole host of perioperative medical problems because I can now do it more expediently, more safely, and with a better degree of success than my patients could get the same care through the system that has been handed to us. When cardiac problems get out of my league, I call a cardiologist ---- just like the hospitalists do. Ditto for pulmonary issues.” Blistering.

What about the generalizability of DocSurg’s experience? He no doubt could provide a collection of anecdotes to back up his impressions, but these do not equal evidence. The evidence regarding the hospitalist movement right now is mixed. DB recently pointed out that there will be good hospitalists and not so good hospitalists. Moreover, from an organizational point of view there are good and not so good hospitalist programs. DocSurg has pointed out some quality concerns that hospitalist leaders need to address. I hope they’re tuned in.

Kevin weighs in here.

Canada’s health care is at least as good as in the U.S., and that’s evidence based!

The inaugural issue of Open Medicine published a systematic review of health outcomes in Canada and the U.S. which purported to show that “…although Canadian outcomes were more often superior to US outcomes than the reverse, neither the United States nor Canada can claim hegemony in terms of quality of medical care and the resultant patient-important outcomes.” This despite the fact, as the authors point out, that the U.S. spends nearly twice as much per capita on health care as Canada. At face value it doesn’t speak well for the U.S. free market model. Although several bloggers jumped on this sound bite uncritically it’s worth digging deeper.

First, the conflict of interest disclosure reads “Competing interests: None declared.” That may be literally true but it’s deceptive. No conflicts were declared but they certainly do exist. Not very open for an open medical journal, I’d say. It took some serious Googling on my part to find the conflicts.

What I found was that several of the authors are political activists and staunch advocates for the Canadian model. Co-author Steffie Woolhandler, for example, was profiled thusly in the New York Times: “Her plan is simple. Get rid of the private health insurance industry and abolish Medicaid, the government's health insurance program for the poor. In their stead, set up a national health insurance system that would cover all Americans by expanding Medicare, the old-style Medicare, to include everyone from birth to death.” A co-founder of Physicians for a National Health Program, (PNHP) she’s also on their speaker’s bureau and a board member of the organization. The John Goodman Health Blog had this to say about her: “Not if you're Steffie Woolhandler, who along with her husband, David Himmelstein, has spent years urging Americans to adopt Canada's healthcare system.” Himmelstein by the way is another of the co-authors of the paper. Kevin had a few choice words about an earlier Woolhandler study here.

Lead author Gordon Guyatt appears to have a similar conflict. He’s been a political candidate for the socialist-leaning New Democratic Party which advocates for government health care and the end of privatization. He was taken to task before for not declaring this obvious competing interest.

Another of the authors, Armine Yalnizyan, has been a vigorous advocate for the Canadian model as evidenced by these writings.

The methods session of the paper is no more open than the conflict of interest statement. We are told that “Interested readers can obtain the detailed protocol for this review from the corresponding author.” That’s right; you have to email the authors to get the search strategy. It would appear, though, that the search strategy was not predetermined; rather, it was “iterative”, almost as if they made it up as they went along. Then they culled the list of retrieved citations down from 4923 down to 38. We’re not told exactly how this was done or by whom, but it appears to have been a complicated procedure, and to the reader it’s somewhat mysterious.

Even if this review is valid it’s nothing new. No one is claiming that patients in the U.S. live longer. This paper, from where I sit, smacks of activism for single payer health care disguised as research.

Another resource for bloggers on fair use

Page 3.14, the editorial blog of Science Blogs, has started a continually updating post and comment thread about fair use with experts expected to weigh in. Add this to the list of resources.

New open access journal will increase the transparency of pharmaceutical industry studies

Wiley-Blackwell publishing has announced the launch of Archives of Drug Information. The journal will publish inconclusive and negative trials as well as positive trials.

C. Michael Stein, M.D. of Vanderbilt University School of Medicine, the editor of the new journal, was interviewed in the March 23 edition of the Vanderbilt Reporter.
“’The pharmaceutical industry is under a lot of pressure to publish information about the studies they perform,’ said Stein, professor of Medicine and Pharmacology, and associate director of the Division of Clinical Pharmacology. ‘But it's actually very difficult for them to do so because most scientific journals select the highest impact articles for publication, and many of the studies performed in drug development do not have a high scientific priority for medical journals.’

As a result, ‘whenever there are problems with a drug later on, there are often allegations that information was in some way hidden,’ he said.”

More on the flap over RateMDs in Canada

---from CMAJ.

Inflamatory abdominal aortic aneurysm

It accounts for about 5%-10% of all abdominal aortic aneurysms and is under appreciated. Its unique clinical features, including its association with retroperitoneal fibrosis, are reviewed in Grand Rounds at the Johns Hopkins Bayview Medical Center.

What did we learn today about fair use?

Science blogger Shelley Batts got into a little tiff with Wiley publishers over reproducing a figure from a Wiley journal in one of her blog posts, raising all sorts of questions about fair use. The blogosphere responded with an avalanche of posts and emails, overwhelmingly in Shelley’s favor. Today Shelley reports a happy resolution. The publisher issued an apology of sorts and gave Shelley written permission to use the figure. What is not clear from the publisher’s response is whether it was really OK with them that she used the figure without permission in the first place. The fair use question was thus dodged.

What can we learn from the many blog posts and comment threads that ensued? I haven’t read them all. From what I’ve seen so far, while most commenters, with varying levels of expertise, seem to think Shelley was within the bounds of fair use, the concept is fuzzy and if you really want a final answer you would have to test the legal waters and see what a judge would say. But, needless to say, the issue was thoroughly hashed out and those interested might want to bookmark a few of these threads for reference. One commenter pointed to this web site devoted to the issue.

On a side note, Drug Monkey ended his post on this subject with an expression of disgust over the reactionary nature of the scientific blogosphere: This is not a “win”. This is a “loss” in which the blogos look like emotional nutcases willing to go ballistic before all the facts are in and/or considered rationally. That may be okay for the political ranters but surely scientific bloggers can do a bit better? Indeed. Let’s leave the caterwauling to the political bloggers.

Medical and surgical treatment of peripheral vascular disease

A concise review in American Family Physician.

Prescription drug deaths soar in Tennessee

They exceed illicit drug deaths and nearly equal murders according to this article in the Tennessean. Narcotic pain relievers are the major culprits and leading the list, of course, is methadone.

Cystic fibrosis: what the internist needs to know

Review in CCJM.

What’s fair use?

An Orac post and the ensuing comment thread examine the case of another Science Blogger who reproduced a figure in her report on a paper from a Wiley Interscience nutrition journal. (BTW, Wiley journals are very closed access—as closed as they come, as in locked up tighter than a drum).

Within a day of her report she received a letter from Wiley demanding that the figure be removed, and threatening legal action. As Orac asks, isn’t the inclusion of the figure, with its appropriate attribution and its use for the purpose of criticism, an example of fair use? And doesn’t the “amount and substantiality” of the reproduced content (one figure---it’s not as if she reproduced the whole thing) fall within the boundaries of fair use?

This should be of great interest to bloggers, who do this sort of thing a lot. As this gets passed around the blogosphere the reaction is likely to be overwhelmingly negative. Let’s hope some experts weigh in and let’s hope Wiley notices.

I’ve been away and computerless for the last few days

So today I surveyed some of the medical blogs for recent interesting posts and these (in no particular order) caught my eye:

Retired Doc comments about Joint Commission’s recent decision to change the four hour antibiotic rule for pneumonia treatment to six hours. They just don’t get it. (The updated and recently published guidelines promulgated jointly by the ATS and the IDSA have eliminated all specific timing recommendations for the administration of initial antibiotic doses, citing the potential for abuse of antibiotics and flaws in the evidence upon which the original four hour rule was based. “Guideline concordant therapy” for community acquired pneumonia should include the administration of antibiotics as soon as possible, and in most cases in the ER, but no longer incorporates rigid time rules).

DB cites a clinical vignette from the New York Times presented by columnist and Yale internist Lisa Sanders, M.D. The patient, who presented to the ER with abdominal pain, hypotension and profound bradycardia was ultimately “cured” by the urology resident. The sequence of events was that this patient, despite a lack of prior urinary symptoms, was in acute urinary retention which led to renal failure, hyperkalemia and, consequently, depression of cardiac function. The case is instructional and interesting on several levels. Could application of the Prostate Symptom Score have averted the crisis? Although it’s an intriguiging question, Dr. Sanders’s self flagellation seems unwarranted.

The Patient’s Doctor has a couple of items concerning Wal-Mart, headquartered just down the street from where I sit. The Washington Post reports Wal-Mart’s plan to open 400 in-store clinics. IHealthBeat reports on remarks by Wal-Mart’s CEO on the role of business in transforming U.S. healthcare.

The Dinosaur presented a case puzzler here, and the solution here. One commenter was partially correct and everyone else missed it a mile. The patient had an uncommon presentation of a common disease (peptic ulcer). The lesson? Perhaps it’s the old saw (that I think I remember once reading in Cliff Meador’s Little Book of Doctors’ Rules) that you can not diagnose that which is not in your differential diagnosis, assuming you generated one in the first place. Or maybe that it’s occasionally appropriate to order an imaging study without a focused clinical question, other than just to “see what’s going on.”

For a little gallows humor here are some politically incorrect mnemonics being kicked around at the Student Doctor Forum (via Kevin).

The blogosphere was screaming after the U.S. Supreme Court decision to uphold the Partial-Birth Abortion Ban Act of 2003, even calling it shameful and incomprehensible, apparently so incomprehensible that no medical blogs I could find provided a link to the original document. For those interested and who think they can comprehend the nuances, it’s here.

Simplistic thinking about conflicts of interest

I’ve commented before about simplistic and one sided thinking concerning conflicts of interest in the medical profession. Medical Progress Today has published a symposium which takes a more skeptical, nuanced look at the issue. The introduction says this: “The fiduciary standards companies owe their shareholders are surely compatible with producing the highest quality products and research possible given existing technologies. Companies that made products that routinely harmed patients or produced deceptive marketing materials for physicians would find themselves punished by investors, physicians, courts and regulators in very short order.” Drug company marketing is biased and yes, there are potential conflicts of interest, but in the final analysis they have an interest in good patient outcomes. I’ll be covering some of the individual articles in this series in future posts.

NCCAM’s latest ploy to keep the bucks flowing

Secondary omics analysis of CAM trials.

Via the Health Fraud List.

Lipid lowering therapy

Open access topic review in the Texas Heart Institute Journal.

Interview with Michael Crichton

Crichton was interviewed at The Daily Ablution. Here’s a snippet of what he had to say about the global warming debate: Any departure from environmental orthodoxy is marked by ad hominem attack, vigorous spread of false information, claims of criminality and mental derangement, and general nastiness. Apparently this is one area where reasonable people cannot disagree.

There’s much more, as well as this link to his web site.

Critical illness in morbidly obese patients

This topic was recently reviewed in Critical Care Medicine. (Via Medscape).

Hypocrisy about direct to consumer advertising

If you’re a health care professional who likes to rail against direct to consumer advertising by drug companies do you market your services to consumers or remain silent when the hospital or clinic where you work does the same thing? I wrote about this problem last month and the Dinosaur weighed in the other day saying Medical marketing is bullshit; even more so than direct-to-consumer pharma advertising. He’s right!

More on NSAIDs and cardiovascular risk

The portrayal of COX-2 inhibiting NSAIDs as cardiotoxic and older NSAIDs as safe is simplistic and irresponsible, as I demonstrated here. Now there’s this study, published ahead of print in the Annals of Rheumatic Disease on line, suggesting that ibuprofen is associated with higher cardiovascular risk, over 8 fold in high risk aspirin users, than the COX-2 inhibitor lumiracoxib.

Aortic dissection

Updated in Resident and Staff Physician.

Annals of Internal Medicine on research fraud

Safeguards announced.

Addressing conflicts of interest that matter

Mention conflict of interest in medicine and the knee jerk response is likely to be a diatribe about drug company gifts to doctors. This selective outrage is misdirected. Drug company gifts, though ubiquitous, are modest these days, and any potential conflicts of interest they create for doctors are trivial in comparison to other conflicts in day to day professional life, especially compensation incentives.

Physician compensation plans in the U.S. are varied and complex but almost all, with perhaps the notable exception of the V.A.’s, contain financial incentives that can influence practice patterns and clinical decisions. This NEJM Career Center article on compensation plans notes (italics mine) “’Compensation plans in the 1990s were very complicated, and included such things as participation in the group and patient satisfaction, which involved very complex formulas. Today, they [models] are moving back to a focus on productivity, efficiency, and the amount of dollars a physician brings in’”. Though these positive cost incentives are the norm today the negative incentives of capitation common in the managed care era still prevail in some regions according to the NEJM report. Both types of incentive can influence clinical practice away form what’s best for patients and away from the dictates of evidence based medicine.

The effects of compensation in clinical practice are more pervasive than those of drug company gifts because they go beyond drug prescribing. Pressure to see more patients in less time as well as incentives to overuse ancillaries and do more procedures all have potential to harm patients.

What is the evidence that compensation incentives influence doctors? Jason Shafrin, the blogger at Healthcare Economist, discusses his recent paper on physician compensation here (h/t to Kevin). The post contains a link to the actual draft of the paper, which reviews previous research linking compensation plans to physician behavior and presents new data showing that switching from capitation to fee-for-service compensation increases surgery rates by 155%! Now that represents a lot of surgery. Think of all the pens and lunches that could be funded by those extra fees!

What’s a doctor to do? There’s no pat answer in the real world. We’re not all alike, and not equally susceptible to perverse incentives. Most of us would strive to adhere to first principles. Patients come first. But there are some who take a more radical position. The folks at No Free Lunch apparently believe that the only way to deal with conflicts of interest is to avoid them altogether. By selectively addressing drug company gifts they are focusing on the easiest conflict to avoid. It costs virtually nothing. But any consistent application of the avoidance principle must also take into account the conflicts inherent in compensation incentives. Avoidance of such conflicts is possible, but often at great personal sacrifice. Those doctors who sign the No Free Lunch pledge to avoid conflicts of interest should consider this cost and be willing to disclose their compensation incentives.

We (doctors) don’t know Jack

----according to this Medscape Video Editorial by Linda Casebeer, PhD. But there’s hope that online CME can help. She cites (as yet unpublished) data showing that it improves decision accuracy, and offers some tips for on line searching.

10 acid-base pearls

From Resident and Staff Physician.

Evidence based woo

The National Center for Complementary and Alternative Medicine, which I will henceforth refer to as the National Center for the Promotion of Pseudoscience (NCPP), has just released a study claiming that Tai Chi boosts immunity against HVZ (Shingles) virus. There’s something in this paper to make all the alties happy. The anti vaccination crowd will be excited to learn that Tai Chi worked as well as vaccination. For the integrative medicine enthusiasts there was the finding that Tai Chi combined with vaccination worked better than either treatment alone.

If you ignore the obvious problem of biologic implausibility (the “mechanism” of Tai Chi is said to be the unblocking of the flow of the vital energy Qi along the body’s meridians) the paper appears sound at first glance. With its prospective randomized design, p values and prestigious institutional representation (UCLA and UCSD) it has all the trappings of science. But the ever diligent Orac, in contrast to the sound bite style of the popular media and much of the blogosphere, looked beyond the abstract and, digging deep into the methods section of the paper, discovered that this study proved nothing whatsoever about the effect of Tai Chi on the immune system. Because the control subjects merely “sat on their behinds in a class” the study suggests only that exercise might boost immunity. As Orac points out, to prove any unique effect of Tai Chi a comparison group treated with conventional exercise at a comparable aerobic level, or Tai Chi exercises with the “wrong moves” (a valid Tai Chi placebo for most subjects unschooled in the ways of woo) would have been necessary.

That is a patently obvious, huge, huge design flaw! Why was this study conceived in this way and why was it accepted for publication? Orac suggests a significant conflict of interest: woo is sexy these days, it sells, and it gets funded.

Public Citizen: Celebrex ad “dangerous and misleading”

After a long moratorium, Pfizer resumed television advertisements for Celebrex last week. The Public Citizen Health Research Group, declaring the ad “dangerous and misleading”, is petitioning the FDA to ban the spot, which you can view here. Decide for yourself whether it’s misleading or dangerous. The Public Citizen letter also strikes me as a little misleading. The ad, the essential messages of which are that “Celebrex is an option” and “get your doctor’s advice,” makes cautious claims.

The ad points out that all NSAIDS are now required by the FDA to carry the same cardiovascular warning. Public Citizen believes this statement is misleading, claiming that the cardiovascular risks of COX-2 inhibitors exceed those of traditional NSAIDS. The Pfizer ad makes no claim about the safety of COX-2 inhibitors relative to other NSAIDS, but merely states that the notion that traditional NSAIDS are free of cardiovascular risk is “not clear.”

Public Citizen cites this BMJ meta-analysis which found no difference in cardiovascular risk between COX-2’s and older generation NSAIDS overall with the singular exception of naproxen which was associated with lower risk. The Public Citizen letter emphasized the difference in naproxen but neglected to mention the overall equivalency in risk between COX-2’s and older generation NSAIDS. The letter also conspicuously neglected to mention this large study in the European Heart Journal showing that the risk of MI was equally increased by COX-2’s and older generation NSAIDS.

We knew about the adverse cardio-renal effects of NSAIDS long before the COX-2 inhibitors. Although the COX-2’s arrived with a claim of increased GI tolerability there was no claim, by the drug companies or anyone else, of improved cardiovascular safety. In fact, substantial medical literature raised early concerns about cardiovascular risks. If the pharmaceutical industry concealed information about adverse cardiovascular events they should be held accountable. Nevertheless there were plenty of warnings, published in peer reviewed medical journals for all to see, about adverse cardio-renal effects of COX-2’s. Had these warnings been heeded there would have been far fewer prescriptions for Vioxx in patients with increased cardiovascular risk, the very patients in whom the absolute risk of cardiovascular harm was higher, and we might have avoided the Vioxx debacle.

It’s not fair to pick on the COX-2’s. All NSAIDS are problematic. I confess, I hate NSAIDS, old and new, and have for years. As an internist who treats many patients with cardiovascular risk factors and renal disease they are a class of drugs I love to hate.

We haven’t always embraced woo

In fact, our love and affection for quackery is a relatively recent development. As I’ve pointed out before Franz Mesmer, thoroughly discredited in the eighteenth century for his magnetic energy woo, might be on faculty at a medical school in today’s climate. Snake oil salesman John R. Brinkley, virtually run out of the country in 1930, would be making millions doing infomercials today.

As recently as 1959, as illustrated in this video from the Internet Archive (hat tip to the Health Fraud List) we were not afraid to use the Q word.

Intensive glycemic control in patients undergoing cardiac surgery

It may be worthwhile in the post operative period but not intraoperatively according to this single center study in Annals of Internal Medicine.

Diabetic foot disorders

As a hospitalist I wind up getting involved in the care of diabetic foot problems much more than I ever anticipated. Internal Medicine World Report has a little blurb based on an interview with John M. Guirini, DPM, of the Joslin Diabetes Center.

According to Dr Giurini, “There is no one person who can take care of diabetic foot problems by him or herself. It involves the cooperation of a foot and ankle surgeon, a visiting nurse, an endocrinologist, and sometimes a vascular surgeon and infectious disease specialist.” Trying to take care of these problems on their own, “from soup to nuts” is “probably one of the worst things that physicians can do,” he warns.

A world of information about the diabetic foot can be found in the newly released guidelines of the American College of Foot and Ankle Surgeons.

It has a certain symmetry to it

China is moving from traditional TCM to Western evidence based medicine while the U.S. increasingly embraces woo, observes Orac.

Backlash against drug reps gathering momentum

Kevin MD linked this from CNN. The public relations campaign against drug company to doctor promotions seems to be effective. More and more doctors---in some regions up to 50% according to the CNN piece---are saying no to drug reps.

The most publicized effect is the massive laying off of drug reps. Less well appreciated is the increase in direct to consumer advertising that is bound to occur as drug companies divert their marketing resources. I guess the lay consumers are supposed to be better information filters than those morally bankrupt, self-deceptive doctors.

Contraindicated prescribing claims two more casualties: Permax and Zelnorm

According to Pharm Aid contraindicated prescribing is responsible for the withdrawal of these two drugs from the market. You can bet the trial lawyers are interested and they’ll be going after the drug companies, not the doctors. The drug companies will also take the public relations hit. Contraindicated prescribing not only causes direct harm to patients but also, by causing good drugs to be yanked, deprives many patients of beneficial therapies.

I’ve previously blogged this very point here and here and discussed it in the Medscape Roundtable here.

Review of medical Web 2.0 applications from BMC Medical Education

The Patient’s Doctor points us to a BMC Medical Education review of medical blogs, wikis and podcasts which outlines the principles, advantages and disadvantages of web 2.0 applications and cites numerous examples.

Among those mentioned:

Clinical Cases and Images

Flu Wiki

Ganfyd

Johns Hopkins Medicine Podcasts

Cardiovascular Multimedia Information Network Podcasts

Doctors, do you know you’re morally bankrupt?

No Free Lunch is an organization concerned with pharmaceutical companies and their influence on the medical profession. They believe scientific evidence, rather than industry promotion, should guide clinical practice. Most of us would agree with that. The problem, though, arises with what the blogger at Pharm Aid considers to be a paternalistic position which assumes that doctors, because they can be “bought” with a slice of pizza or a free pen, are morally bankrupt. That radical idea, proclaimed by a vocal minority, has been subject to little in the way of critical examination. Maybe that’s because its purveyors are more interested in spreading hype than examining evidence and its opponents don’t take it seriously. In any case it’s an increasingly visible public perception as illustrated by New York Times articles cited by Pharm Aid here and here.

The “paternalists”, notes Pharm Aid, argue that because doctors are morally bankrupt their judgment can’t be trusted unless they are shielded from the pharmaceutical industry. Such shielding may take the form of an institutional ban on drug company lunches or a self imposed ban such as the No Free Lunch pledge. The pledge is purported to publicly separate those doctors who base their practice on evidence from those who base it on promotion by posting a web listing of doctors who signed on. It’s as if the true test of evidence based medicine is whether or not a doctor takes the pledge. Absurd though the notion seems there’s been little effort to challenge it.

The web listing of No Free Lunch pledge adherents has yet to appear on line despite having been promised on the site for several years. One wonders if more than a small handful of doctors has taken the pledge. Indeed on close examination very few practicing physicians, at least in the United States, could honestly sign the pledge because of this requirement: “to avoid conflicts of interest in my practice….” That pretty well disqualifies most doctors who practice medicine for a living. Depending on our compensation model most of us practice under either positive or negative financial incentives. These incentives influence the types and numbers of patients we see, the procedures we do, the tests we order and our referral patterns. Compared to the measly drug company pens, note pads and lunches these conflicts are much more powerful. They’re about real money and they impact each and every patient encounter.

Conflicts of interest are pervasive in medical practice and take many forms. Those inherent in doctors’ interactions with drug companies are small in the grand scope of things. If the paternalists are really interested in conflicts that matter why do they focus selectively on the pharmaceutical companies?

Regarding No Free Lunch, Pharm Aid writes: “This organization urges physicians to avoid any interaction with pharmaceutical companies, including pens, lunches, etc. However, their disdain of drug companies doesn’t seem to apply to anyone else (including insurance companies) trying to influence their physician’s prescribing patterns, the diagnostic tests they order and the medical procedures they perform.”

Are we morally bankrupt as a profession? Perhaps. And if we think holding ourselves at arms length from the pharmaceutical companies will cure our moral turpitude we are also profoundly self-deceptive.