Should we throw the bums (drug reps) out?

The medical blogging about the dispute between No Free Lunch and the American Academy of Family Physicians has been mostly favorable to No Free Lunch. I am glad to see that AAFP has finally decided to allow No Free Lunch (NFL) to exhibit and I hope ACP follows suit next year. I believe in a free market place of ideas, and theirs deserve to see the light of day.

I said before that while I agree with the basic premise of NFL (“that pharmaceutical promotion should not guide clinical practice”) I am concerned that some of their positions are extreme, or are taken to extremes by their supporters. My intention here is to state my specific areas of concern and issue a call for moderation. (Disclaimer: try as I will to avoid the straw man argument, I could be perceived as misstating the NFL position. NFL has eloquently stated its principles, but with the possible exception of the pledge these principles have not been codified in any formal way. As I express my concerns I realize that the opinions of NFL supporters occupy a spectrum. If this shoe doesn’t fit don’t wear it).

One of my differences with NFL lies in the distinction between skepticism and cynicism. At a recent CME conference at McGill Dr. Jerome Hoffman, professor of emergency medicine at UCLA and a supporter of NFL, pointed out the difference between these two approaches to evaluating claims and evidence. The cynic, he said, seeks to knock everything down; the skeptic, by contrast, thinks critically and questions claims, but all the while with an open mind. Webster defines the cynic as “contemptuously distrustful of human nature and motives” (italics mine). My perspective about the pharmaceutical industry is skeptical, while I view the attitude of many NFL supporters as cynical.

The cynic’s position might be that the drug companies care only about their stock holders, never have the public good in mind and that their interests are always in conflict with those of patients. The cynic might feel that the medical profession should have no interaction with the industry and never believe anything they say.

As a skeptic I believe that while there are conflicts of interest, in perception and in fact, the interests of the drug companies are sometimes but not always in conflict with good patient care. (Good patient outcomes can help increase profits). Unlike the cynic I believe win-win situations are possible. My skepticism says not to believe everything they claim and to always check primary sources. However, out of hand rejection of every claim based solely on source (the ad hominem fallacy) is unreasonable.

What about the practical consequences of the NFL objections? Are we ready to give up industry supported CME? I enjoy attending CME meetings. Although I can do without the pharmaceutical company exhibits, were it not for partial industry support the registration fees would be prohibitively expensive for many meetings. Not all physicians are wealthy. Those who attend AAFP and ACP meetings are among the least likely to be wealthy. I dare say many would not be able to attend at all without industry support.

There are other examples. Many of us enjoy (and often link to) emedicine and Medscape. I don’t want those free resources to go away. What about all the open access medical journals which would not survive without pharmaceutical advertising?

So to those who want to “throw the bums out” I urge caution. This highly nuanced issue does not lend itself to simplistic ideas.

Another nail in the coffin of a medical myth

Tradition has it that parenteral therapy is necessary to treat vitamin B-12 malabsorption. In recent years accumulating evidence has suggested the effectiveness of oral treatment. Much of the evidence has been in the form of case control and case series studies. This was the subject of a recent Cochrane review which found two RCTs of oral versus parenteral vitamin replacement, totaling 108 participants. 1000 to 2000 mcg of oral B-12 daily was found equal to a standard parenteral regimen.

Two recent narrative reviews of vitamin B-12 deficiency are linked here. [1] [2] They explain the physiologic rationale for oral replacement and highlight the only recently appreciated and most common cause of B-12 deficiency, known as food-cobalamin malabsorption syndrome. Now believed to be more common than classic pernicious anemia, food-cobalamin malabsorption syndrome is largely a disorder of the elderly. As explained in these reviews a common form of age related gastric atrophy results in deficient secretion of acid and pepsin, which are necessary to strip cobalamin from food protein. Patients with this common disorder can absorb B-12 from pills, but not food. Such patients have a normal Schilling’s test. The disorder is poorly understood, and some cases may be the result of longstanding H. pylori infection.

Food-cobalamin malabsorption is to be distinguished from classic pernicious anemia, an autoimmune disease characterized by antibodies to parietal cells and intrinsic factor. The effectiveness of oral B-12 replacement in such patients is less well understood, but apparently there is an alternate pathway of absorption which is independent of intrinsic factor. The absorptive mechanism is simple diffusion and requires a high concentration gradient, which is provided by the large daily oral doses of 1000-2000 mcg used in the studies.

As suggested in the Cochrane review this evidence, if put into widespread practice, could ease a substantial burden on health care resources. (The clinical effects may be more modest in those patients who derive substantial placebo effect from B-12 shots---anecdotal observation).

A few caveats:
1) The number of patients studied is small. The number with classic PA is smaller still.
2) The effective oral dose is high---1000 to 2000mcg daily.
3) Parenteral therapy has stood the test of time and may be preferable in patients with questionable compliance.
4) If oral treatment is elected the patient should be followed carefully in the short and long term for resolution of neurologic, hematologic and metabolic abnormalities including monitoring of the hemogram, reticulocyte response, homocysteine and methylmalonic acid levels.

Fetal pain round three

Well, we finally got disclosure about the fetal pain article, but wouldn’t it be better if the authors had provided it themselves? We shouldn’t have to rely on the media to do it for us. The National Right to Life Committee (NRLC) did some homework and came up two more items of note about Dr. Eleanor A. Drey, one of the paper’s authors. I previously noted that she is an abortion provider. The NRLC linked to the March 31 2004 issue of the San Fransisco Chronicle which informs us that she was head of San Fransisco’s largest abortion clinic and testified against the Partial-Birth Abortion Ban Act of 2003.

The September 2004 issue of the Physicians for Reproductive Choice and Health newsletter, also linked from the NRLC web site, profiles Dr. Drey as an activist whose passion on the issue is intense. Concerning a woman’s choice, she is quoted “It’s already an emotional decision, and to make it that much more difficult really infuriates me.” It infuriates her. Wow. With such intense emotion driving her opposition to fetal pain legislation could she have been objective in selecting and interpreting studies for a scientific review of the topic? The newsletter goes on to quote “It makes me feel really good that I can do something very immediate to serve women’s medical and emotional welfare while working in a political sense to train future providers, do research, and hopefully broaden women’s access to abortion and reproductive care. I am very lucky because I get to train residents and medical students, and I really do feel that it’s a type of activism.” (Italics mine).

This speaks volumes. There was clearly an agenda surrounding the fetal pain paper, and JAMA readers needed to know.

Heliox for asthma exacerbation

The popularity of heliox has outpaced its evidentiary basis. Here’s some interesting evidence in favor of heliox from this month’s Academic Emergency Medicine.

Another important cause of dilated cardiomyopathy

On July 27 I discussed familial dilated cardiomyopathy (DCM). There is another under-appreciated form of DCM that must not be missed because it can be completely reversible. I’ll start with a case. This is not a real patient, but a composite of some memorable ones I’ve seen.

A 66 yo male presents with dyspnea and leg edema, progressive over three weeks. He had no prior history of heart disease, diabetes or hypertension and had never consumed alcohol. Physical exam revealed bilateral lung crackles, lower extremity edema, ascites, neck vein distension and an S3 gallop. The electrocardiogram revealed rapid atrial fibrillation. The patient was not aware of his irregular cardiac rhythm.

He was admitted and underwent diuresis, rate control and anticoagulation with subsequent clinical improvement. An echocardiogram showed global hypokinesis, an ejection fraction of 15%, and no significant valvular abnormalities. The patient was discharged on digoxin, furosemide, warfarin and potassium supplement. (This was before the era of ACE inhibitors and beta blockers!).

After a few weeks of anticoagulation he returned for cardioversion followed by cardiac catheterization, which showed an ejection fraction of 20% and no significant coronary artery disease. He was diagnosed as “idiopathic dilated cardiomyopathy, possibly due to viral myocarditis.”

During long term follow up he maintained sinus rhythm and clinical improvement, and was able to have his diuretic discontinued. At one year all manifestations of his heart failure seemed to have disappeared and a repeat echo was totally normal, with an ejection fraction of 65%. What’s going on? What is the most likely etiology of his cardiomyopathy?

Answer: chronic tachycardia-induced cardiomyopathy.

Here’s a review of the topic from the American Journal of Medicine (only the abstract linked here is available for free; the full text is well worth the read if you can obtain it). This phenomenon was occasionally reported for decades but remained largely under the radar screen until publication of series like this one from the Mayo Clinic in 1992. (American Journal of Cardiology). These patients, some of whom were on the transplant list, were thought to have atrial fibrillation secondary to idiopathic DCM. The interesting finding in the series was that after rate or rhythm control the patients exhibited striking reversibility. Instead of atrial fibrillation secondary to DCM, the reverse appeared to be true. These patients likely started out with nothing more than “lone” atrial fibrillation. Is there anything unique about certain atrial fibrillation patients that predisposes them to this complication? Perhaps it’s that they lack tachycardia awareness, thus allowing them to maintain the arrhythmia for long periods without seeking medical attention. (That seemed to be a common thread in the Mayo series).

As explained in the American Journal of Medicine review, animal models of this condition produced by prolonged rapid pacing have demonstrated evidence of chronic myocardial energy depletion and numerous ultrastructural changes, all reversible after cessation of pacing.

What are the take home points?
1) When your new case of “idiopathic” DCM happens to have atrial fibrillation don’t be hasty and write it off as irreversible.
2) Chronic tachycardia can be the sole etiology of DCM (which may have originated as merely lone atrial fibrillation in a patient lacking tachycardia awareness) or a contributing etiology (in which case aggressive rate control will improve the patient’s heart failure).

Will the Lancet review be the death knell for homeopathy?

Maybe not. Here’s an article the investigators appear to have overlooked! :-)

The lost art of electrocardiography

Retired Doc recently lamented the lack of skill in ECG interpretation among internal medicine and emergency medicine residents. Perhaps in the present era of high technology electrocardiography has become a lost art much like physical examination. J. Willis Hurst has written extensively about the reasons, and possible remedies, for the decline in skill in electrocardiography. [1] [2]. He cites various weaknesses in postgraduate teaching, as well as the failure to understand basic electrophysiologic principles. Sadly, there is a lack of formal training. Learning by osmosis is not very effective.

There are a few decent web based learning resources. The best I’ve found is ECG Wave-Maven. This site is cased based, somewhat interactive, and has annotations with literature citations. Medscape’s ECG of the Week (free access after registration) is also somewhat helpful. Unfortunately, another of my favorites, the American College of Cardiology ECG of the month, has gone behind access controls.

Opinion writing disguised as medical research

In my recent post about the controversial JAMA article on fetal pain I suggested that financial relationships with pharmaceutical companies are not the only conflicts of interest that need to be disclosed. What else should be disclosed? The fetal pain article raised issues about two of the authors. We learned from the New York times that Dr. Eleanor Drey held opinions against proposed fetal pain legislation which could constitute bias. The Chicago Tribune also reported that she was an abortion provider. Another author, Susan Lee, had worked as an attorney for an abortion rights group. Though some disclosure was clearly needed it is unclear how it should have been accomplished. Readers needed to know about an author’s role as an abortion rights activist and another author’s role (and perhaps opinions) as a provider. But what other questions should be asked? Do we need to know about an author’s religious beliefs, or how an author voted in the last election? Certainly the notion of disclosure could be carried to undesirable extremes.

In the popular news media there is concern that opinion pieces are disguised as objective journalism. I wonder if a disclosure policy would help settle the debate about media bias and increase the credibility of news organizations. In medical literature we now have a similar concern that opinion writing could be disguised as research reporting. While the JAMA paper sparked particularly heated discussion there are many other examples of potential bias in medicine, largely under the radar screen and less emotionally charged.

In my own field of hospital medicine early studies suggested that the hospitalist model was associated with improved outcomes. But the fact that some of the papers were written by leaders in the hospitalist movement [1] [2] raises the possibility of bias. Similarly, papers which showed improved outcomes with a closed ICU model of care were authored by leaders in pulmonary-critical care medicine or published in journals affiliated with the specialty. This paper reported excessive rates of product withdrawal and post-marketing drug labeling changes, implying ineffective FDA procedures. Missing from the disclosure, however, was that one of the authors is an activist whose organization has a long history of lobbying on the issue.

Surprisingly little has been written about conflicts of interest in medical research except as they pertain to the influence of drug companies, although a few writers have acknowledged that there are other biases. Shaughnessy and Slawson for example, recognizing that expertise in a field creates bias, suggested that experts should not write reviews, and that we should not read papers written by experts. Sackett, similarly noting the bias of experts, wrote that as soon as one becomes an expert he or she should retire from teaching or writing in the field of expertise (whereupon he announced his retirement from teaching and writing about his field of evidence based medicine). This article on medical professionalism in NEJM took a broad view of bias and suggested for example that ophthalmologists or dermatologists rather than gastroenterologists should advocate for colon cancer screening.

These solutions seek to eliminate bias and are extreme. We can’t eliminate bias entirely. Disclosure, however, may heighten readers’ skepticism and provide a healthy opportunity for critical appraisal. I hope the debate surrounding the fetal pain article will not be hijacked by hate speech, but rather will broaden our awareness of bias and the importance of disclosure. It’s not just about the drug companies.

Personal reflections on the hospitalist movement

Published in the July/August 2005 issue of The Hospitalist is an abstract from the 2005 Society of Hospital Medicine annual meeting research competition that has received considerable attention around the medical blogosphere. It reports a large study of various outcomes of care by hospitalists compared with non-hospitalists in academic medical centers. In this first ever multi-center study there was no significant difference between hospitalists and non-hospitalists in outcomes. This was somewhat unexpected, since some earlier smaller studies suggested improved outcomes with hospitalist care.

Rather than try to critique the study (that’s been nicely done by DB, California Medicine Man and Clinical Cases and Images) I’ll offer my purely personal views as a hospitalist. First I disagree somewhat with Clinical Cases and Images that a well designed trial would solve the question of whether hospitalists are useful. To me the success of the hospitalist movement is driven by the growing demands and complexities of hospital medicine and a growing niche created by ever increasing numbers of primary care doctors choosing to practice exclusively ambulatory medicine. Personally I’m happy to fill that niche as long as it’s there. Although I’ve experienced more professional satisfaction since becoming a hospitalist I have no desire for the movement to “take over” hospital care.

The results don’t particularly surprise me. In fact they somewhat mirror my personal experience as I compare my numbers with those of my excellent local non-hospitalist peers. Many doctors in traditional primary care maintain excellent hospital skills. Their patients can get quality hospital care and at the same time maintain a measure of continuity---the best of both worlds.

Meanwhile a growing knowledge base in hospital medicine is creating a steep learning curve, and I enjoy ascending that curve. Maintaining this blog disciplines me to stay more abreast of this growing literature. In future posts I hope to accumulate a collection of hospital medicine “bookmarks” which will be useful not only to myself but to other physicians, in practice or training, with an interest in hospital medicine.

More about familial dilated cardiomyopathy

Over a month ago I blogged about this. Here’s another article on the topic from Cardiovascular Reviews and Reports via Medscape (free access after registration). Again the authors make the point that familial DCM is common, and that first degree relatives of patients with “idiopathic” DCM should be screened via echo and ECG.