Confusion about MRSA reaching epidemic proportions

MRSA outbreaks are nothing compared to the outbreak of media distortion about MRSA. The latest barrage was sparked by the report of the MRSA related death of a Virginia high school student as well as this paper in JAMA which updates the epidemiology of MRSA.

In an attempt to parse what’s going on let’s start with the story of the Virginia high school student. The Associated Press report reads:

BEDFORD, Va. (AP) — A high school student who was hospitalized for more than a week with an antibiotic-resistant staph infection has died. After a student protest, officials shut down 21 schools for cleaning to keep the illness from spreading.

Ashton Bonds, 17, a senior at Staunton River High School, died Monday after being diagnosed with Methicillin-resistant Staphylococcus aureus, or MRSA, his mother said.

Although we have no information about the infecting strain, be it the “old MRSA” typified by the USA100 strain or the “new MRSA” typified by USA300 (although pulsed-field typing was probably not done in this case the strain could easily have been inferred from the sensitivity pattern for antibiotics other than methicillin as I explained here) it was most likely the former.

The significance of the JAMA article is that it is the most systematic analysis of the epidemiology of invasive MRSA in the U.S. to date and despite its limitations suggests that the infection is more widespread than had been appreciated. The paper is “busy” with data and somewhat confusing categorizations. (An editorial in the same issue provides clarity). Infections were classified on the basis of site of onset (health care or community) and on the basis of risk factor associations (health care or community). Pulsed field typing was available for a minority of isolates. Considerable overlap among all 3 methods of categorization suggests limitations on the popular designations “community associated” and “health care associated”. Nevertheless MRSA comprises at least two different beasts with important clinical associations, best typified by pulsed field types USA100 and USA300 and usually distinguishable to clinicians by characteristic antimicrobial sensitivity patterns. While I decry the media’s “killer superbug” hype I did point out, almost 2 years ago, that the “new” MRSA had unique potential for increased transmissibility and severe necrotizing infections.

Now let’s examine some of the media distortion. I did a Google News search for MRSA and had difficulty finding articles that provided appropriate perspective. This Q and A piece defines MRSA as “a type of staph bacterium that is resistant to common antibiotics such as penicillin.” Not quite. Penicillin sensitivity is rare even among non-MRSA isolates.

Many articles talked about schools closing for a good scrubbing down following the reports of MRSA infections in Aston Bonds and other students. However, given the importance of person to person spread of MRSA it’s unlikely that environmental sanitation measures would have much impact. This article implies that poor hospital cleaning was responsible for MRSA sepsis and death in a newborn. But almost a year ago I cited a lack of evidence of correlation between hospital cleanliness and MRSA bacteremia. In hospitals hand washing and proper use of isolation procedures, rather than environmental cleanliness, will make the most impact. Equally important are sanitation measures for infected patients to follow after hospital discharge, which I provided here.

This superbug article declares:

All schools should be disinfected. Regularly. And we need to educate ourselves about this increasingly aggressive disease that few drugs can defeat.

There may be good reasons for environmental disinfection, but such measures won’t contain MRSA. Kids bring these bugs form home and pass them to others via direct contact or sharing of items of personal hygiene, also brought from home in many cases. Utensils and items of athletic equipment are reasonable areas of focus for schools.

It’s simplistic to characterize the “new” MRSA, the one that’s getting all the attention in schools, as a problem of increasing antimicrobial resistance. For milder cases several antibiotics are effective, including a few old ones (Bactrim, tetracyclines). The problem is these are not the same old antibiotics (cephalexin, diclox) we’ve been used to using to treat community acquired skin infections. To make it a bit more challenging, the ones that work for the new MRSA aren’t effective against group A strep which is still a common cause of skin infections. The new MRSA happens to be susceptible to more antibiotics than the old MRSA that’s been quietly making the rounds in hospitals for years.

There’s plenty more hype, but I’ll stop there. I can imagine how the reporter felt as she researched her daughter’s ordeal with MRSA: “I became a mouse-click medical expert. The more I read, the more I feared”.

The emphasis on core quality measures is dumbing down the practice of medicine

That’s because “quality” measures as they are now promulgated reflect a simplistic view of clinical science, distract from things in medicine that really matter and encourage health care providers to “play for the test”.

Bob Wachter over at Wachter’s World sees some interesting parallels with the unintended consequences of outcome based education and the No Child Left Behind law. In primary and secondary education, emphasis on the core skills of math and reading has relegated the humanities and other important subjects to the status of “soft” content. (Wachter presents data from the San Diego schools!).

Whether in primary and secondary education or in medicine, one hazard of adopting core measures is that the achievement of minimum standards trumps the pursuit of excellence. One of the many consequences in medicine may be the demise of the master clinicians, the Proctor Harveys of the world. Wachter agrees and shares an anecdote about one of UCSF’s master diagnosticians, Gurpreet “Goop” Dhaliwal, concluding:

I’m afraid that Goop’s diagnostic acumen might well be healthcare’s music class: extraordinarily impressive, really quite beautiful in a way, but way off the measurement radar screen. If our students get the message that Goop's kind of clinical intelligence and diagnostic ability are unimportant (after all, they don’t seem to be part of what we’re calling “quality”), I think you can guess what will happen over time. Clinical "artists and musicians" will become extinct.

Rapid response teams: promoted but not evidence based

Rapid response teams, though promoted by Joint Commission and IHI have not been supported by high level evidence. The latest analysis, a systematic review recently published in Critical Care Medicine, offers little more in the way of evidentiary support for RRTs.

RRTs were marginally effective in preventing cardiac arrest in the pooled analysis of observational studies but not in the only randomized controlled trial (RCT). RRTs had no impact on mortality in any level of study (neither in observational studies nor in the two RCTs). This is consistent with what was known before. Despite these negative findings Joint Commission urges hospitals to use “Rapid Response Systems to Save Lives” and the IHI declares that the use of RRTs is “perhaps the most dramatic of the six strategies at the heart of IHI’s 100,000 Lives Campaign”.

The authors of the systematic review conclude that “Large randomized controlled trials are needed to clarify the efficacy of rapid response systems before they should become standard of care.”

Unreasonable expectations for new type 2 diabetes drugs

Physiology and clinical epidemiology give us no reason to expect that glycemic control with any drug should prevent heart attacks or strokes (macrovascular benefit). In fact, the most time tested and trusted class of oral agents for type 2 diabetes is associated with macrovascular harm. Had macrovascular benefit been the standard for approval of drugs for type 2 diabetes all along we would now have only two drugs available: metformin and pioglitazone.

Of course all this got started as a result of the Avandia bru-ha-ha. I‘ve ranted about this macrovascular issue here and elsewhere. Here’s an expert who seems to agree, commenting in a recent issue of DOC News:

But as a medical community, do we want to prove that our agents to treat type 2 diabetes improve heart attack and stroke risk before approval?

I think not.

Deceptive promotion by hospitals and health care systems

---while commonplace, hasn’t gotten the criticism it deserves. Earlier this year I wondered why the outrage about direct to consumer advertising was so selective and quoted Dr. David Oxman’s article:

By now Americans are accustomed to seeing advertisements for medical goods and services. The steady supply of direct-to-consumer TV advertisements by the pharmaceutical industry is probably the most high-profile example. But while much has been written about the negative effects of these advertisements, the impact of healthcare service advertising---by hospitals as well as by individual physicians---receives comparatively little attention and almost no debate.

A survey of hospitals from the Archives of Internal Medicine a couple of years ago, referenced in Oxman’s article, uncovered conflicts of interest, non-evidence based promotions, disease promotion and “freebies”. Worse, these promotions were found in 16 of the 17 “America’s Best Hospitals”.

To me it’s a case of the pot calling the kettle black as physician leaders at these and other academic medical centers talk about “professionalism” and rail against pharmaceutical industry promotion while tolerating such ethical breaches by their own institutions.

That may be changing. In yesterday’s issue of JAMA, faculty from two medical centers addressed a novel aspect of self-promotion: hospitals, eager to take advantage of rising public interest in quality and transparency, are now couching their promotions in scientific terms by presenting them as “data”. The problem is they are doing this independently of any form of external validation, without appropriate statistical analysis and with bias.

Dr. Robert Wachter, one of the paper’s authors, talks about it on his blog.

Mycosis fungoides

It’s a great mimicker. Be sure to think of it. A review appeared in the British Journal of Dermatology, via Medscape.

ITP---not always idiopathic

When clinical conditions warrant consider these underlying diseases:

SLE

Antipholpholipid syndrome

H. pylori infection---here the association is controversial, but some studies indicate a high rate of improvement or remission of thrombocytopenia following eradication.

Hepatitis C---screen all patients with chronic thrombocytopenia for hep C. Thrombocytopenia may improve with treatment of the underlying disease.

HIV

Via Current Opinion in Hematology

Another hazard of systematic reviews

---is that they go out of date, as this paper in the Annals of Internal Medicine reminds us.

So what, you’re thinking to yourself. All medical literature goes out of date!

OK, here’s what: Some EBM mavens worship the systematic review. Most EBM resources rate systematic reviews at the top of the evidence hierarchy, thus encouraging clinicians to preferentially seek systematic reviews to answer clinical questions. Many contain links that search only systematic reviews

Search strategies which focus on systematic reviews ignore randomized controlled trials published since the latest review and thus may not yield the best and most current evidence.

A quick Google image search reveals that the vast majority (although not all) evidence pyramids rank the systematic review at the top.

Why is tPA for stroke still so controversial 12 years after NINDS?

Because of all the screaming. Plenty of it on both sides.

On the affirmative side are false claims (“it saves lives”), egregious media spin and hyped up expert testimony.

On the negative side are knee jerk cries of “conflict of interest”.

What’s a doctor to do?

We need an objective analysis that cuts through all the noise and gives us a balanced perspective.

I think I’ve found such an analysis: Joseph Lex’s presentation at the FERNE 2007 Brain Illness and Injury Course.

Bottom line: Patient selection is difficult, therapeutic window is narrow and informed consent is crucial. Know how to inform patients and families. This presentation shows how.

Modest effects of pneumococcal vaccination in adults

Polysaccharide pneumococcal vaccination has been designated a core quality measure despite the fact that it does not prevent pneumonia and from the standpoint of absolute risk reduction its effects on the complications of pneumococcal infection are modest.

This study, reported in the Archives of Internal Medicine, compared vaccinated and unvaccinated patients hospitalized with community acquired pneumonia and found a reduction in a composite outcome of death or admission to the ICU in vaccinated patients. Buried in the body of the paper is the statement that the entire effect was due to the reduction in ICU admissions. There was no effect on mortality.

So, when you administer pneumococcal vaccine to your patients at discharge you won’t prevent pneumonia and probably won’t help them live longer, but you’ll decrease the likelihood of admission to ICU next episode.

The polysaccharide pneumococcal vaccine, which is the only kind approved for adults, is a weak sister compared to the conjugate vaccine approved for kids. We need a conjugate vaccine for adults. Is anybody out there working on it?

Massive pulmonary embolism leading to cardiac arrest

Emergency surgery may be an option. (Texas Heart Institute Journal).

Is your medical reading getting too dry?

Try Striped Giraffe Press. “…a publishing company dedicated to teaching medical knowledge in an offbeat fashion.”

The site appears to be under construction. Not much there yet, but could be interesting.

Core measures and P4P: rank-and-file doctors aren’t buying in

Bob Wachter used an electronic audience response system to poll over 500 attendees (mainly hospitalists) about this topic at his recent UCSF/SHM sponsored Hospital Medicine Course. Among physician groups, you’d think hospitalists would be the cheerleaders of the quality movement. But these doctors were overwhelmingly skeptical. Wachter presents the poll results here and euphemistically concludes: The bottom line: everybody’s got a lot of work to do if we’re going to get this thing right.

More discussion on intensive glycemic control in hospitalized patients

A review in Chest addressed the controversies on this topic and summarized results of clinical studies done up to the time of submission of the manuscript. Several tables display summaries of available data on the basis of duration of the intervention, types of outcomes and types of populations.

An accompanying editorial is linked here.

Early Goal Directed Therapy of sepsis

---from the perspective of an Emergency physician. Via Emergency Medicine News.

Remembering Proctor Harvey

W. Proctor Harvey, M.D., M.A.C.C., passed away on Sept. 26 at the age of 89. He was widely renowned as a master clinician and teacher of cardiac auscultation. His teaching sessions were legendary. I had the good fortune to attend a few of them at CME meetings through the years. Harvey taught, and demonstrated to his students repeatedly, that most cardiovascular disease could be diagnosed at the bedside.

Nowadays the abuse (wasteful, ineffective use, sometimes to the harm of patients) of sophisticated technology, especially in cardiovascular medicine, is common. That’s because medicine has lost the legacy of Proctor Harvey: the importance of basic clinical skills. Another master teacher, J. Willis Hurst, has said that unless one masters low technology (basic clinical skills) one is bound to abuse high technology. He said it here in this way:

When low technology, consisting of the history, physical examination, electrocardiogram, and chest x-ray film, is used poorly it is very likely that high technology will be used poorly. It is not possible to take a second step (high technology) without taking a well placed first step (low technology).

During my training it seemed there was never quite enough time to teach basic skills properly. Today there is even less time, given the many new and competing demands of medical education, not to mention all the fluff and woo. Now as in years past practicing physicians must teach and reteach themselves these skills.

Dr. Harvey realized that fact and at one of his CME presentations announced a collaboration with engineer David C. Canfield and Roche pharmaceuticals to capture live recordings of heart sounds from hundreds of patients, put them on cassette tapes along with a set of booklets to be distributed as freebies by drug reps to interested physicians. (Dr. Harvey, true to his reputation for humility, didn’t think it beneath himself to collaborate with a drug company to make this wonderful educational resource available!).

A tribute to Dr. Harvey in the Texas Heart Institute Journal described the project:

In recognition of the importance of his message, numerous educational grants have enabled the distribution of his writings to American medical students and physicians. Roche Pharmaceutical company alone is responsible for distributing 75,000 copies of Clinical Auscultation of the Cardiovascular System, a work that includes 10 high-fidelity audio cassettes of various heart sounds and murmurs, recorded from more than 450 patients, together with a text that describes the compendium of acoustic findings and their significance. Harvey's voice is heard throughout the cassettes as he sprinkles in his “cardiac pearls.”

I still have my set, pictured here.

Shamelessly and with no sense of “reciprocal obligation” I would like to express my thanks to Roche Laboratories for making this wonderful resource available.

For those who would like to feel morally superior by paying for this resource, last time I looked one was being sold on ebay.

Meet the newest member of the trauma team: the reiki master!

I considered not writing about this because I’m a little late for the party. Orac has already covered it extensively and Kevin has posted a link. But the incredible story on the introduction of reiki to the University of Maryland’s Shock Trauma program deserves exposure, and the more we can give it the better. It represents infusion of pseudoscience into mainstream academic medicine (a trend I’ve followed on this blog for some time) taken to a new level. Not only is reiki among the wooiest of woo, it’s being introduced into the (up to now) pristine specialty area of emergency and trauma medicine!

Another reason for me to weigh in is that Orac, it seems, is beginning to feel a little lonely and frustrated in his battle to restore scientific integrity to academic medicine:

I'm beginning to wonder if I should just give up this quixotic battle to try to insist on evidence-based medicine in academic medical centers. I'm clearly losing the battle, and sooner or later I'll be relegated to the sidelines along with the other dinosaurs who advocate scientific medicine over unproven, non-evidence-based therapies. If I were to join the Dark Side, I could probably attract a bunch of grants to fund clinical trials to look at whatever the woo du jour is. I'd never do that, of course, if only because as a former skeptic I'd represent a truly valuable scalp for the world of non-evidence-based medicine, but I feel as though I'm increasingly alone in holding out.

Yes, it must get a little lonesome. Out here in the hinterlands I can only wonder what’s going on in academic medicine these days. Is there anyone there for whom the standards of science mean anything at all? Well, there must be. There are plenty of people who teach and write about evidence based medicine. And how about the rising chorus of voices calling for the purging from academic medicine of the biased influence of drug companies? They claim to stand for scientific purity, so why do they (with the notable exception of Arnold Relman) remain silent about woo?

What conflicts of interest might be involved? It’s partly about money. Consumers demand woo and to an astonishing degree pay for it out of pocket. There’s also the ever more lucrative pipeline of government grants to promote and “research” woo. And, as Orac pointed out, there is the dinosaur phenomenon. Increasing pseudoscientific indoctrination of medical students over the last few years means changing priorities and values for the academic medical center as these students become faculty members. As the culture of the academic medical center becomes more and more steeped in woo it must be getting difficult to stand up for science. It takes courage to risk the dinosaur label.

So, for what it’s worth, I’m weighing in. As Orac points out, not only is reiki unsupported by evidence but, even worse, it’s utterly implausible. Its purported mechanisms involve a mysterious, undocumented energy which can traverse time and space provided the proper symbols are used. (That would be mighty handy if it worked. The reiki master wouldn’t even have to show up). Such credulity in academic medicine is astonishing. What’s going on?

At the University of Maryland, as well as, I suspect, other academic medical centers, there appears to be a new standard. Alternative medicine modalities, unlike pharmaceutical agents, no longer have to be evaluated with the measuring stick of science. A different standard has been adopted, one which was articulated by the University of Maryland’s own director of integrative medicine, Dr. Brian Berman, in his BMJ editorial from a few years ago. His statement is telling (emphasis mine):

When in 1992 we developed a complementary and alternative therapy curriculum at the University of Maryland we thought it was important to present the therapies in the context of their own philosophies and models of health and illness.

The Baltimore Sun piece quotes Berman as saying patients’ reactions to reiki therapy make it “ripe for study”. And I had to laugh at this:

At Shock Trauma, a clinical research study is under way to look at the effectiveness of acupuncture on trauma patients, to see whether it lessens a patient's reliance on drugs. A reiki study could follow, which might quiet skeptics who still wonder whether its power is little more than one of suggestion.

Well, I’ve got news for reporter Stephanie Desmon. It’ll take more than “a study” to quiet the skeptics and move reiki out of the category of extreme woo, especially considering the type of study that’s most likely to be conducted. In order to evaluate reiki’s energy based claims, and test whether it’s anything more than a relaxation technique it would have to be compared with those same techniques. It would require a control group of patients undergoing an equivalent form of relaxation, stripped of the name “reiki” and all its associated energy and religious woo. It might also be necessary to blind patients to the fact that there is a comparison group. (Suppose you told the control patients they were only receiving “reiki light” and being compared with patients getting the real thing. What would that do to the placebo effect?). Suppose reiki demonstrated a positive effect. What then? Well, reiki is an extraordinary claim. The results would need to be duplicated at other study centers, preferably those (if they exist) which have no interest in promoting woo. If a robust effect were observed repeatedly then the basic scientists would need to get to work in search of a mechanism.

Like Orac, I lament the fact that woo seems to be running rampant in academic medicine. I know there are leaders there who share my concerns. I hope they’ll comment here. I’d like to know why they remain largely silent and what, if anything, they are doing to stand against this trend in their own institutions.

Does mainstream medicine treat the whole patient?

I have a certain hesitation in talking about the “whole patient”. As important as the notion is, in recent years it seems to have lost some of its meaning, at least in popular usage. That’s because it’s been hijacked by the boosters of alternative medicine who relentlessly accuse the mainstream of focusing on the disease and organ system at the expense of the person who has the disease. The American Medical Student Association, for example, in its promotional web page on Integrative, Complementary and Alternative Medicine, says this:

The above examples suggest that CAM fills a hole in conventional medicine. Michael Cohen describes the biomedical vs. holistic paradigms. Conventional medicine has almost perfected the biomedical approach. This system views the body as a machine and reduces the body to its components. The biomedical paradigm works well for emergency problems or diseases with one specific cause. The holistic paradigm, embraced by many CAM practitioners, sees the body as more than the sum of all of its parts. It emphasizes lifestyle changes, stress reduction and nutrition to enhance the patient's healing process. Biomedicine often falls short in treating chronic problems, while many patients with chronic problems find some relief with the holistic approach of CAM therapies.

Half truths and innuendo of this sort are pervasive in alternative medicine literature. Such “whole patient” promotions generally mislead and have the potential for great harm because they drive widespread uncritical acceptance of non-evidence based health claims.

But do they have a point? Has the mainstream become too reductionistic? The answer, in part, is that external barriers have caused a disconnect between real world practice and the teachings and ideals of mainstream medicine.

Mainstream medicine has always taught that doctors must treat the whole person. My favorite medical school mentor, the late Thomas E. Brittingham, pounded the notion into students’ heads. In his annual introductory letter to incoming third year students about to begin their medicine clerkship he wrote:

I expect you to spend time with each one of your patients after the initial workup in establishing rapport with him, obtaining an extensive personal history by indirect and easy means, and in showing the patient that you have a keen interest in him as a person and friend as well as a disease.

Dr. Brittingham wasn’t pushing some altie agenda. (There was no room for that in medical school in those days!). He was teaching the fundamentals of mainstream medicine. And despite the unfortunate fact that quackery is making its way into the curricula of MD granting schools today, the “mainstream” teachers in these schools still emphasize a comprehensive approach that treats the patient and not just the disease. One of our favorite “mainstream” bloggers, DB of DB’s Medical Rants, teaches this philosophy to students and house staff at the University of Alabama School of Medicine. For a sample of his writing on this subject check out his last two blog entries.

But, as I alluded to above, physicians encounter difficulty translating this principle into real world practice. Economic incentives force doctors to see too many patients in too little time. Perfunctory “quality” measures distract from things that really matter in patient care. The ever present threat of litigation makes the patient a potential adversary. These dehumanizing forces are significant obstacles to treating patients as whole persons.

There are no easy fixes, but at both the individual and the system level we in medicine must continually oppose these barriers to our professionalism. Without knowledge and skill in the humanistic dimensions of medicine we cannot be effective clinicians, but “integrative” medicine is not the answer. We can spend all the time in the world learning about the patient’s psychological make up, temperament and social interactions, but when we’re not grounded in the biomedical model we become incompetent.

We as doctors need to appreciate patients as people, but guess what? We also need to know about organs. And diseases. Our thought leaders do well to teach about the healing of whole persons. But they must also insist that the principles of Western science be rigorously applied to the healing of those persons.

Screening for coronary artery disease with CT calcium scoring and carotid intima media thickness: ready for prime time?

Prevention guidelines for cardiovascular disease have advocated treatment guided by the assessment of traditional risk factors. The Framingham risk score is often used for this purpose. Recently, interest has grown in the use of noninvasive imaging to assess risk in asymptomatic patients, particularly CT calcium scoring and ultrasound measurement of carotid intima media thickness (IMT), due to accumulating evidence of superior predictive power of these modalities. Risk assessment strategies have not been studied head to head for clinical outcomes. And, unfortunately, they’re not likely to be anytime soon:

That appears unlikely, at least for now, said Dr. Diane Bild, a medical officer at the National Heart, Lung, and Blood Institute, the logical agency to conduct such research. She said specialists there have already rejected the idea of a head-to-head study looking at how patients who received the high-tech screening fared long term, compared with those screened using more traditional methods.

The institute, Bild said, ``has a lot of competing priorities, and this type of study would be very expensive to conduct, and it just hasn't reached that level where we've gone forward with it."

(Competing priorities indeed. Like the multimillion dollar promotion of quackery by the NCCAM which, like NHLBI, is also a subsidiary of the NIH. But I digress). Needless to say we won’t have the benefit of outcome based trials to guide in the assessment of patients. For the foreseeable future we must settle for lower level evidence. Does that mean we can’t make evidence based decisions? No. Evidence based medicine would have us apply clinical judgment and expertise to come up with the best synthesis of evidence we can, even when this evidence is “low level”. But when a group of experts with special interest in cardiac imaging attempted to do just that and promulgated their own guidelines a firestorm of controversy erupted.

This controversy bears careful examination for several reasons, not the least of which is the nagging question of how best to stem the epidemic of cardiovascular disease. It also impacts broader areas of guideline development relating to potential conflicts of interest and disagreement with other guidelines.

The new guidelines, known as the SHAPE guidelines, expand the recommendations for imaging modalities to screen patients, calling for the use of CT calcium scoring or ultrasound IMT measurement for all asymptomatic men ages 45-75 and women ages 55-75 except for those defined as very low risk. This represents a radical departure from the American College of Cardiology Foundation/American Heart Association expert consensus document, just updated this year to recommend screening only for those patients deemed to be at intermediate risk.

Publication of the guidelines in a supplement to the American Journal of Cardiology was supported by Pfizer pharmaceuticals, eliciting the usual knee-jerk cries of “conflict of interest”. (Joining the chorus were medical thought leaders Arnold Relman and Jerome Kassirer. Do those guys ever miss a chance to pounce on the drug companies?).

Dr. Steven Nissen, no stranger to controversy and hyperbole, also chimed in with:

This issue is not about the conservatism of the ACC and AHA, it’s about the practice of evidence-based medicine. The AEHA is a group of shameless self-promoters who have no scientific basis for their assertions.

The controversy was nicely covered in a point counterpoint in the Cleveland Clinic Journal of Medicine. While I believe Nissen was wrong to say the guideline authors had no scientific basis for their assertions I have chosen not to take sides in this controversy. A reasonable clinician could take either view. All physicians involved in preventive medicine should familiarize themselves with both sides of this debate. These tests are being promoted to patients, who will come to their appointments with questions.

In defense of traditional lecture based CME

Right now I’m feeling a little morose as Bob Wachter over at Wachter’s World posts bittersweet reminders of the fact that I missed this year’s just completed UCSF Hospital Medicine Conference in San Francisco. It’s one of several high quality CME courses I repeat on a rotating basis, chock-full of updates and thoughtful presentations on this ever more complex field.

As I console myself thinking “maybe next year” I‘m a little concerned about an emerging threat to the existence of this type of meeting. There are people out there, people in high places, who would like nothing more than the end of traditional didactic CME conferences as we now know them. A rising chorus of voices calls for the end of pharmaceutical company support for CME activities, without which many conferences of the high caliber exemplified by the UCSF meeting would simply cease to exist. Others call for a virtual end of all traditional didactic CME, including Dr. Jordan Cohen, former president of the AAMC.

Wachter addresses these criticisms in the concluding paragraph of his post:

People wonder about whether CME does any good, either because content taught in big lectures tends not to stick or because many CME courses are golf-laden boondoggles. It is now Saturday morning, and 90% of our registrants are still here (and they’ve already received their CME certificates and it is gorgeous day in San Francisco – lots of excuses to play hookie). I admire their commitment, and, though I can’t prove it, I think we’re saving a few lives here in the Fairmont Hotel.

No, he can’t prove it, but having attended a couple of Bob’s past conferences I suspect he’s right. I come home from courses like this, read and re-read the syllabus, look up related material and primary sources on the Internet, then return to work with batteries charged, newly inspired to try and make a difference.

As far as "proof" of efficacy of CME goes, some critics of traditional programs insist that accreditation somehow be based on verification that each content element be correlated directly with a change in physician “behavior”. For a more lengthy rant of mine on what’s wrong with that thinking click here.

New and noteworthy medical blog

One of the latest additions to the growing medical blogosphere is Wachter’s World, Robert Wachter’s new blog devoted to hospital medicine. The subtitle reads Lively and iconoclastic ruminations on hospitals, hospitalists, quality, safety and more… Having heard Wachter speak many times I have no doubt that he’ll deliver on that promise. Stop by for a dose of healthy skepticism on the hospitalist movement along with the latest buzz on hospital medicine. I’ll be linking from there often. It’ll be on my blog roll once I get around to the next update.

Media credulity towards alternative medicine

If woomeisters put the good name of academic medicine behind their claims those claims must be true. If they admit that quackery really does exist they must be appropriately skeptical. Right? Wrong, but don’t tell that to CNN which recently published this credulous piece: 5 Alternative Medicine Treatments That Work.

The article well illustrates two things I’ve been harping on for a while, these being the harm done when academic medicine promotes quackery and the distortion of health issues by popular media. Needless to say it would have been fun to write a debunking piece about this article. I thought about it the other night but was just too tired. Fortunately Mark Hoofnagle and Orac came through. Although both posts are worth reading in their entirety Orac’s conclusion best summarizes what’s really wrong with the recent infusion of pseudoscience into academic medicine:

The bottom line is that the infiltration of woo into academic medicine is a threat to evidence-based medicine because it lends the prestige of scientific medicine to modalities that are not evidence-based, thereby promoting the belief that they are on an equal footing, even though the vast majority of them are not. In so doing, it blurs the line between science and non-science, between scientifically supported treatments and quackery. Moreover, the faculty of the institutes, divisions, and departments dedicated to CAM in medical schools are, by and large, not made up of skeptics, but of true believers, be they M.D.s or not, who apply a veneer of skepticism and science to their studies and curriculae and then give interviews to credulous reporters like Elizabeth Cohen to publish on CNN.com.

Controversies in antiphospholipid syndrome

Terminology can be confusing. Diagnostic and treatment strategies are evolving. This update in Current Opinion in Hematology is timely.

Noteworthy points:

Among antiphospholipid antibodies, those which prolong the aPTT (so called Lupus anticoagulants) may carry a higher risk of thrombosis than anticardiolipin antibodies (OR 11.0 and 1.6 respectively). This marked difference may be biased by inclusion in the meta-analyses on which these data are based of patients with low titer anticardiolipin antibodies which are of doubtful clinical significance and do not meet current diagnostic criteria for antiphospholipid syndrome.

A common scenario is the need to evaluate a patient for thrombophilia after anticoagulants have been started. Lupus anticoagulant assays can be done on such patients but require special handling and advance notification to the laboratory.

Patients with antiphospholipid antibodies and venous thrombosis, following acute treatment with some form of heparin overlapped with warfarin, should be treated with warfarin adjusted to an INR of 2.0-3.0 long term for a duration of one year to indefinitely.

Data are less clear for patients with stroke and antiphospholipid antibodies. Absent another indication for anticoagulation warfarin adjusted to an INR of 1.4-2.8 or aspirin is suggested. For non-cerebral arterial thrombosis warfarin adjusted to an INR of 2.0-3.0 is recommended.

Two emerging outdoorsy infections

Naegleria fowleri---it’s the brain eating Amoeba we’ve been hearing about, with 6 infections reported this year in contrast with 23 reported in a 9 year period. Think of it if your patient has been swimming, has an illness resembling meningitis and has a negative CSF gram stain.

Rabies---early recognition is now more important because it may not be hopeless. Think of it in any patient with undiagnosed neurologic disease. An article beginning on page 17 of this issue of The Hospitalist tells you what a hospitalist needs to know about it.

The electrocardiogram in heart failure

The Resting Electrocardiogram in the Management of Patients with Congestive Heart Failure: Established Applications and New Insights, originally published in PACE, has many useful and fascinating pearls about information that can be teased out of the electrocardiograms of patients with heart failure. Via Medscape.

Vitamin K for warfarin reversal

Following early confusing but dramatic case reports of severe systemic reactions to parenteral vitamin K there has been a persistent and widely promulgated notion that it causes anaphylaxis.

In a recent article in Emergency Medicine News Dr. James Roberts critically examines this claim and attempts to make sense of the evidence. He concludes that there is reason for caution although the mechanism of the reaction, the degree of risk and any relation to prior vitamin K exposure is unclear. Although the problem may be overblown there is likely some risk. Oral vitamin K appears to be safer and should be used when possible.

Clostridium difficile

Another review published in Pharmacotherapy, via Medscape.

Practical aspects of early treatment of sepsis

Some nuts and bolts from Emergency Medicine News concerning antibiotic choices, EGDT and activated protein C. There’s also a hint concerning the results of CORTICUS and how they may change our use of corticosteroids.

What can turn an $800 medical encounter into a $4000 encounter?

Defensive medicine and the fear of litigation, that’s what. RangelMD gives an example. Compelling reading.

Via Kevin M.D.

Conflicting views about disclosure

Medical journals are becoming increasingly strict in their disclosure requirements concerning authors’ financial conflicts of interest. Dr. Jerome Kassirer addresses the problem in a recent MedGenMed Webcast Video Editorial. He correctly points out that disclosure, while necessary, does not “fix” the problem of potential bias in practice guidelines and journal reviews. But the focus of this editorial is inappropriately narrow, singling out financial ties with drug companies while ignoring multiple other important conflicts.

Concerning disclosure, Kassirer states:

Disclosure may alert readers of possible bias, but it requires them to become mind readers. Did the author pen an unvarnished manuscript? Were his opinions subtly influenced by consulting or speakers' fees? Did he intentionally bias the material to satisfy the company whose fees help to pay for his daughter's college tuition? Interpreting the opinions and recommendations of financially conflicted authors in editorials and review articles is more akin to reading a mystery novel than reading a scientific paper.

Mind readers? Absurd as that seems some of the harshest cynics seem to think they can read authors’ minds. For the rest of us, disclosure alerts to possible bias and suggests the direction of such bias. While this doesn’t require mind reading it prompts discerning readers to look critically at the authors’ recommendations and to check primary sources. Those are skills doctors learned, or should have learned, in training.

Kassirer concludes with a call to go beyond disclosure and eliminate conflicts by finding “unconflicted experts”. But isn’t that an oxymoron? Anyone with expertise in a field is likely to have a personal stake. As Thomas Stossel recently pointed out, excluding all experts with potential personal or commercial interest risks leaving us with “the second best and not so bright”. The New England Journal of Medicine realized this in 2002 when editors found they had to relax their conflict of interest policy in order to find qualified experts.

The focus on drug company ties represents selective outrage in the debate over conflicts of interest. Drug company influence is only one of many conflicts, financial and otherwise, which may bias reviews and practice guidelines. A fair and intellectually honest approach to the issue should question all conflicts of interest that might impact conclusions and recommendations drawn from medical research. Should gastroenterologists, for example, who might gain financially from doing procedures, write guidelines on the indications for endoscopy and who should perform it? Should invasive cardiologists participate in the writing of guidelines for cardiac catheterization and stent implantation? As this list goes on and on one has to wonder how many “unconflicted experts” even exist.

Activated protein C in severe sepsis: patient selection is getting harder

A meta-analysis recently published in BioMed Central Anesthesiology raised troubling questions on the use of recombinant human activated protein C (rhAPC) in severe sepsis.

First a little background. Sepsis is defined by known or suspected infection in the presence of the systemic inflammatory response syndrome (SIRS). Sepsis is defined as being severe when accompanied by dysfunction of at least one organ system. For decision making purposes clinicians attempt to further subdivide cases of severe sepsis into those with a lower risk of death and those with the highest risk of death.

Since rhAPC was approved in 2001 it has been the subject of controversy because its approval was based on a subset analysis of a single randomized controlled trial, PROWESS. The patients in PROWESS determined to have the highest risk of death based on an APACHE-II score of at least 25 or involvement of 2 or more organs accounted for the reduction in mortality associated with rhAPC.

The FDA required a follow up study of rhAPC in patients with severe sepsis defined as having a lower risk of death. This study, ADDRESS, was halted early due to futility. On the basis of PROWESS and ADDRESS rhAPC was recommended only for patients with severe sepsis who had a high risk of death.

ENHANCE was a single arm open label post marketing study to evaluate the efficacy and safety of rhAPC in conditions resembling real world clinical practice, using patient selection criteria similar to PROWESS. No distinction was made among patients with severe sepsis between those having a high or low risk of death although the vast majority of patients had dysfunction of 2 or more organs. The mortality in ENHANCE was almost identical to that observed in the PROWESS treatment arm although the rate of bleeding complications was higher. A notable finding in ENHANCE was that patients treated within the first 24 hours of the first evidence of organ dysfunction had a lower mortality than those treated later.

The BioMed Central Anesthesia meta-analysis raised concerns about the efficacy of rhAPC and proper patient selection. The authors performed a pooled analysis of PROWESS and ADDRESS to assess the effect on mortality, and included several other studies in a cost effectiveness analysis. There was no statistically significant overall effect on mortality (RR .93, CI .69-1.26). That finding represents the overall patient population and is not particularly surprising considering that the less severely ill ADDRESS patients, for whom rhAPC is off label, were included.

But that’s not all. The subgroup analysis produced worrisome findings. In order to understand the subgroup analysis it is important to emphasize that the ADDRESS cohort of less ill patients contained some with APACHE-II scores over 25 and some with multiple organ dysfunction. That confusing situation arose because labeling criteria for defining patients at high risk of death, which were used to select patients for ADDRESS, tended to be vague and varied among participating countries.

Here’s the graphic representation of the subgroup analysis for the pooled results of ADDRESS and PROWESS. The findings of interest were these:

APACHE-II score of 25 or greater: RR .9, CI .54-1.49.
Two or more dysfunctional organs: RR .84, CI .70-1.00

These results may be skewed by the patients in address with APACHE-II scores of 25 or greater, in which the RR was 1.19 (CI .83-1.71).

How can the different results in the ADDRESS patients with multiple organ dysfunction or high APACHE-II scores be explained? First, these were probably less severely ill patients than those in PROWESS. Secondly, ADDRESS study sites included many smaller community hospitals where the level of investigator expertise may have been low. Complex and potentially dangerous drugs like rhAPC generally perform better in the hands of expert clinical trialists than they do in the community.

In light of this new information, what is the status of rhAPC (Xigris) today? My impressions are as follows:

1) Xigris can ethically be considered for additional clinical trials.
2) Xigris is a niche drug for more gravely ill patients with severe sepsis. A simple formulaic approach to patient selection based on the APACHE-II score is not sufficient. The APACHE-II score must be coupled with clinical judgment. Suitable candidates might include patients with both a high APACHE-II score and multiple organ dysfunction.
3) Clinical expertise is important for optimal use of Xigris. Hospitals and health care systems may wish to restrict its use to critical care specialists.
4) Early use of Xigris is important for optimal results. Benefits diminish beyond 24 hours after the first evidence of organ dysfunction.
5) Although Xigris has a role in patients with severe sepsis and can be a life saving drug when used in the optimal patient population and with appropriate expertise it should not, in my opinion, be considered standard of care.
6) New information about rhAPC presents a difficult challenge to the writers of the next version of the Surviving Sepsis guidelines.

This paper gives me yet another reason to appreciate BioMed Central: it’s apparently off the radar screen for popular media outlets such as the New York Times. Thankfully, nobody there seems to have noticed the paper, which could have been published in NEJM or JAMA. If it had, the media would have pounced on it. I can just see the headline: “Eli Lilly’s expensive sepsis drug ineffective”.

Sepsis review from Hospital Physician

This review on the diagnosis and management of sepsis from the June 2007 issue of Hospital Physician covers multiple aspects of treatment including practical application of the Surviving Sepsis Guidelines.

Of special note, the section on early goal directed therapy (EGDT, the Rivers protocol) emphasizes the underappreciated point that EGDT is time dependent. As such it is an emergency department protocol which commences as soon as severe sepsis or septic shock is recognized, and is carried out during the first 6 hours. The article appropriately cautions that EGDT should not wait until arrival in the ICU.

This caveat is supported by largely forgotten evidence that goal directed therapy which commenced in the ICU (late goal directed therapy, when a pulmonary artery catheter could be inserted) was ineffective.

If you treat patients with sepsis this is a must

Add the MUST Guide to your bookmarks.

Prison time for a medication error?

That’s what may happen to an Ohio pharmacist.

The neutraceutical-industrial complex

Herbal woo is a big money industry. It’s coming on strong, largely unchallenged. Compared to the rigorous scrutiny of Big Pharma the N-I complex is getting a free ride. This article from Clinical Pharmacology and Therapeutics is a fascinating exposé:

In conclusion, the N-I complex is rapidly growing despite limited proven value of the products they produce, no known benefit in most cases, and even harmful effects in some instances. Its distribution models often prey on the poor and naive, and the industry is a master of misinformation, confusing the public with many techniques, some described above. Moreover, for reasons one can only speculate about, our culture has created and continues to propagate this powerful meme, which, sadly, is probably aided by missteps in marketing and drug development as well as other serious issues plaguing the pharmaceutical industry.

Read the rest.

Hospital efficiency tips

If you’re part of a hospitalist program you can bet your administration will be tracking your length of stay and charges per case. Hospitals tend to lose money on Medicare inpatients, and hospitalists can help stop the bleeding.

That’s why an article in the American College of Physicians publication ACP Hospitalist is timely. It contains tips for efficient care of hospitalized patients and was written by Dr. Robert M. Centor, better known to many of us as DB of DB’s Med Rants. Very helpful stuff.

Sphygmomanometer on the verge of extinction

The way things are going there may come a time when you have to visit the Mütter Museum in order to see one. If you don’t believe me, next time you’re on the ward ask the nursing staff for one and note the blank stares.

Dr. Wes muses about the vanishing sphygmomanometer and laments that the phenomenon is symptomatic of declining basic clinical skills. He’s a little conflicted, though, because it’s good for business if you’re an electrophysiologist.

I don’t particularly mind the newer electronic BP machines (all you have to do is push the button) except when I need to check a patient for pulsus paradoxicus.

Avandia and Actose: Are there lessons for diabetes care and drug safety?

In light of new developments in the thiazolidinedione (TZD) controversy now might be a good time to take stock of where we are in drug therapy of type 2 diabetes. First there’s the latest spin from the New York Times, an article worth reading principally as an example of popular media distortion.

It mentions two new studies in JAMA and notes a doubling of heart failure risk from Avandia without making a clear distinction between TZD associated heart failure and Avandia associated myocardial infarction (MI). TZD associated heart failure exacerbation was reviewed in the Cleveland Clinic Journal of Medicine. The review makes this statement:

The incidence of congestive heart failure reported in clinical trials is less than 1% and appears to be related to underlying dysfunction, with decompensation caused by sodium retention and fluid accumulation rather than a direct cardiac suppressive effect.

This important distinction from drugs which are truly cardiotoxic is known to physicians but not to most Times readers, who might think Avandia is a cardiac poison like adriamycin. The distortion gets worse. One of the JAMA authors is quoted as saying that Avandia causes blindness and doubles the rate of fractures in women. The Times doesn’t bother to elaborate or even cite primary sources. As the statement stands it’s a half truth.

The blindness comment refers to macular edema. The primary source is here in a report from CMAJ. According to that report macular edema due to Avandia is believed to be rare, may reverse with drug discontinuation, may be anticipated by the development of peripheral edema, and does not invariably lead to blindness. The New York Times article left out another detail---insulin therapy in patients with type 2 diabetes is an established risk factor for macular edema. [1] [2].

And the fractures? Because the article provides no elaboration or background, readers might naturally assume these are hip or spine fractures. But the primary source, a study in NEJM from last December, reveals no increased rate of hip or spine fractures. The problem was confined to arm and foot fractures. That finding, although worrisome and in need of better understanding, is less concerning than what would naturally be inferred from the Times story, which confuses more than it informs. Unfortunately this type of sound bite coverage will again hijack scientific debate on the findings of the new JAMA studies.

In refreshing contrast is a discussion between Steven Nissen, author of the controversial NEJM Avandia meta-analysis, and Robert Califf, a cardiologist and Professor of Medicine at Duke University. The video and transcript are linked at Medscape Diabetes and Endocrinology. The Medscape editor explains the importance of this resource in the introduction:

The May 2007 online publication of the meta-analysis "Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death From Cardiovascular Causes," in The New England Journal of Medicine (NEJM) launched a controversy that has been difficult to navigate. In an attempt to clarify the debate, our colleagues at theheart.org organized a videotaped conversation between Steven E. Nissen, MD, MACC, Medical Director, Cleveland Clinic Cardiovascular Coordinating Center, Cleveland, Ohio -- and co-author of the NEJM article -- and Robert M. Califf, MD, Professor of Medicine, Vice-Chancellor for Clinical Research, and Director, Translational Medicine Institute, Duke University, Durham, North Carolina. Drs. Nissen and Cardiff review the meta-analysis and the US Food and Drug Administration (FDA) advisory panel hearing, as well as discuss the wide-ranging implications of the ongoing clinical and political debate. It is a thoughtful, collegial conversation that helps parse this controversy and what it means for clinical practice and public policy.

It’s must viewing for anyone who wants the fair and balanced version of this debate but so far it’s been drowned out by sensationalistic media coverage.

The New York Times distortion centered around two studies and an accompanying editorial published in the most recent issue of JAMA. One of the papers, another rosiglitazone (Avandia) meta-analysis, reached the same conclusion as Nissen’s NEJM study. The JAMA meta-analysis, which differed from the NEJM study in that it restricted papers for inclusion to those which reported long term follow up and had a pre-specified intention of looking at adverse cardiovascular outcomes, showed a relative risk for myocardial infarction of 1.42 (1.06-1.91) associated with rosiglitazone and no increased risk of mortality.

Although not mentioned as a potential conflict of interest, the paper could be interpreted as more ammunition against the FDA. One of its authors, Curt Furberg, has been critical of the FDA’s approval and safety monitoring procedures and has had conflict with the agency. When removed form an FDA advisory panel meeting on arthritis drugs in 2004 Furberg expressed concern that agency officials were trying to silence him. The same Washington Post article quotes from an FDA official:

Sandra Kweder, deputy director of the FDA Office of New Drugs, said it was not unusual for advisory panel members to be kept from participating in a meeting if they have clear financial interests or intellectual positions that could keep them from being objective.

The importance of the potential conflict is underscored in this analysis by the fact that only 4 studies out of 140 were selected. Despite this caution the analysis must be taken seriously. It agrees with other research findings and when combined with other reports it strengthens the “signal” for macro vascular harm associated with Avandia.

The other paper, though conflicted due to co-author Steven Nissen’s ties with Takeda pharmaceuticals, the makers of the study drug, also confirms previously known findings. Pioglitazone (Actose), Avandia’s competitor and companion TZD, was found in a meta-analysis to be associated with a reduction in the primary composite outcome of death, myocardial infarction and stroke. This is in line with the controversial PROactive study. Thus it would appear, surprisingly enough, that the two approved members of the TZD class have divergent effects on macro vascular health, once again challenging simplistic assumptions about class effect. (Mea culpa!).

The accompanying editorial gives a helpful clinical perspective and makes suggestions for change at the FDA. Unfortunately label revisions and black box warnings are not enough. As the editorial points out and as I wrote in a previous Medscape Roundtable it has been demonstrated again and again that doctors ignore such warnings. This has not only led to untold instances of direct patient harm but has also deprived patients of beneficial therapy due to the withdrawal of effective drugs form he market. It has unfairly tarnished the reputations of drug companies and the FDA.

Unfortunately this debate has been fueled by a fundamental and pervasive misunderstanding of diabetes treatment. The problem is an inappropriate expectation that anti-diabetes drugs should improve macro vascular outcomes. Myocardial infarction and stroke are examples of macro vascular outcomes. While it’s well established that glycemic control improves micro vascular outcomes (e.g. retinopathy, neuropathy and nephropathy) clinical epidemiologists have been telling us for years that not even the strictest glycemic targets produce macro vascular benefits. In fact it has been known long before the advent of TZDs that drug treatment for type 2 diabetes is associated with macro vascular harm. This fact was recognized decades ago when the University Group Diabetes Program (UGDP) reported increased cardiovascular mortality in association with first generation sulfonylureas.

Although the UGDP study was criticized its findings have been supported in subsequent reports such as this recent analysis of a large Canadian health care database. Not only first generation but also second generation sulfonylureas were associated with cardiovascular death, and the association was dose related. These alarming findings, published last year, went largely unnoticed in the arena of public debate. Where was the outrage? Where was the New York Times? There can only be one explanation. The fact is, these are old, off patent drugs from decades ago. That makes it difficult to bash drug companies and the FDA. While the findings are much more important (because patient deaths are involved) than the Avandia results there’s low potential for hype. Clearly the popular media hysteria is more about finger pointing than patient care.

In order to improve macro vascular health in type 2 diabetes you can’t just lower blood glucose. You have to do something else. What is that “something else”? It is, at the risk of oversimplification, treatment of the metabolic syndrome, the principal dyslipidemia of type 2 diabetes. Such treatment is generally multimodal, based on hygienic measures (diet and exercise) often in conjunction with lipid regulating drugs. Glycemic control doesn’t accomplish this goal, and glucose controlling drugs are ineffective unless they exert additional direct effects on one or more adverse components of the metabolic syndrome. For a glucose controlling drug this is not the norm. When it occurs it’s a bonus. Thus far only two drugs in the vast array of diabetes medications appear promising in this regard: pioglitazone and metformin. Realistically the best we can expect for most diabetes drugs is a neutral effect on macro vascular health.

Background: Here’s the FDA warning for a popular sulfonylurea (Amaryl).

Vancomycin tips

Not too many years ago the adage was “say no to vanco.” That has changed in the CA-MRSA era as vancomycin assumes front line status for many patients. Today’s Hospitalist discusses current trends.

Varicella-zoster virus and the nervous system

CCJM has a full text review outlining clinical features, diagnosis and treatment.

Churg-Strauss syndrome and related disorders

The spectrum of pulmonary vasculitis, notably Churg-Strauss syndrome, Wegener’s gramulomatosis and microscopic polyangiitis, is reviewed in Current Opinion in Pulmonary Medicine.

Catecholaminergic polymorphic ventricular tachycardia

It’s another genetic cause of ventricular arrhythmias and sudden death. It’s not Torsades---the QT interval is not prolonged and the tachycardia morphology is typically a bidirectional alternans type of tachycardia rather than twisting about an isoelectric point. It’s reviewed here in the Journal of Cardiovascular Electrophysiology, via Medscape. The mechanism is believed to relate to excessive myocardial cytosolic calcium.

An analogous situation is seen in digitalis toxic ventricular ectopy, classically presenting as bidirectional tachycardia, also believed related to intracellular calcium excess. Digitalis exerts its inotropic effect by increasing the delivery of calcium to the contractile proteins.

By the way, UpToDate has an excellent discussion of CPVT in a section on the polymorphic VTs with normal QT intervals which, for obvious reasons, I can’t link here.

Erythropoietin treatment in critical illness

Transfusion of red cells has been associated with adverse outcomes. The search for a safer alternative to red cell transfusion in critically ill patients has led to great interest in the use of erythropoietin to help patients maintain appropriate hemoglobin concentrations. A study in NEJM demonstrates again that evidence often tempers enthusiasm for appealing ideas. The EPO Critical Care Trials Group reported, in the September 6 issue, on the use of erythropoietin in critically ill patients. In the treatment group there was no reduction in the use of red cell transfusions and no significant improvement in mortality except in a subset of trauma patients. An increase in the rate of thromboembolism was seen in the erythropoietin group.

Deborah Cook and Mark Crowther in an accompanying editorial warned against premature conclusion that erythropoietin is beneficial in critically ill trauma patients. The absolute benefit was small and the relatively high incidence of VTE in trauma patients may result in a smaller number needed to harm than was reported for the overall group. They concluded:

Without a clear indication for initiating erythropoietin in all critically ill patients, new prescriptions for this drug should be restricted to randomized trials with independent research oversight carefully examining fatal and nonfatal clinically important outcomes.

Whither practice guidelines?

How helpful are clinical practice guidelines (CPGs)? How are they most effectively used? A couple of my blogging colleagues have been examining this issue. In a recent series of posts DB examines biases in guideline development, guidelines written with complexity inappropriate for a generalist audience, and the difficulty in applying single disease guidelines to elderly patients with multiple complex problems.

Today Orac provided a useful perspective on CPGs and evidence based medicine (EBM), centering his comments around a paper in PLOS Medicine which on the surface could be construed as diminishing the value of EBM. But that interpretation, though likely to be trumpeted by the popular media and the alties, is not a fair rendering of what the paper actually said, as Orac went to considerable length to explain. The paper was not critical of EBM. What it did do is question the ability of CPGs to help clinicians practice EBM. The authors evaluated randomized controlled trials (RCTs) on which guidelines were based and found a disturbingly low number (about a third) that met two criteria: applicability to the patient populations targeted in the guidelines and reporting of “hard” clinical outcomes. The study may not be generalizable because of its narrow focus on a limited number of guideline recommendations. The authors were circumspect:

In conclusion, our finding that less than one-third of treatment recommendations (and less than half of those citing RCTs in support of the advocated treatment) were based on high-quality evidence in national evidence-based guidelines for common conditions should sound a note of caution to consumers of clinical practice guidelines who assume that the sobriquet “evidence based” means that all recommendations contained therein are derived from high-quality evidence.

For me this paper is a reminder that slavish adherence to CPGs is not the same thing as practicing EBM although it is popularly assumed to be so. The true steps of EBM are rigorous and time consuming as I have outlined before. Here I discussed the general steps of EBM and gave some case examples. In a more recent post I expanded on the first step of EBM (formulating a focused clinical question to be translated into search terms) by introducing the PICO acronym. The P in PICO stands for population and refers to the need to define the specific patient population that corresponds to your patient, and specifying the relevant characteristics in the focused clinical question and the search terms. That addresses one of the problems, cited by the authors of the paper, inherent in the use of CPGs by helping ensure that the evidence applied to the clinical problem at hand matches the attributes of the patient.

Once the search is done and the studies are collected there remains the important step of critical appraisal, an additional check point for the quality and external validity (applicability to your patient) of the evidence.

Much of what is said to be EBM is not EBM at all. The true practice of EBM is onerous. In many situations clinicians lack the necessary time to practice pure EBM. Although the use of guidelines is not a valid substitute for EBM guidelines can be helpful to the time strapped physician when viewed with an appropriately critical eye.

Thiamine before dextrose

Is it a medical myth? Well, the evidence to support the practice is soft according to this article from Emergency Medicine News.

Out with Pharma, in with Woo---AMSA’s agenda for medical education

In researching the activities of the American Medical Student Association I ran across a couple of items highlighting their efforts to influence medical schools with a double standard for evaluating mainstream pharmaceuticals and alternative medicine. An article from DOTmed news and this post from Health Issues Unmasked both appeared within the past couple of weeks.

The DOTmed news piece describes how AMSA is stepping up the efforts of its PharmFree Campaign to try and rid the academic medical environment of the effects of industry promotions:

"It is important that we work to keep our medical schools and teaching hospitals free of the influence of pharmaceutical companies," said AMSA National President Jay Bhatt. "PharmFree medical students become PharmFree doctors and that commitment to evidence-based medicine benefits our patients and our colleagues."

Read that again. Note he said evidence-based medicine. It’s all well and good until you read the Health Issues Unmasked post from just days earlier describing AMSA’s other big initiative for med schools that’s not so evidence based:

The American Medical Student Association (AMSA) Foundation has just ended a pilot study designed to develop a curriculum for including complementary/ alternative medicine (CAM) training in MD and DO programs nationwide. The study, conducted at six medical schools, was financed with a $1.2 million grant from the National Institutes of Health (NIH)-National Center for Complementary and Alternative Medicin (NCCAM).

That’s right, they’re getting support from NCCAM. They trumpet the fact that they eschew all pharmaceutical industry sponsorship, in the name of evidence based medicine, while accepting a $1.2 million dollar grant from arguably the nation’s most organized and powerful promoter of pseudoscience.

The Health Issues blog post links to the AMSA website for its CAM educational initiatives where their guiding principle is explained:

Medicine today is experiencing a paradigm shift that involves the blending of two disparate philosophies of health and disease, the biomedical or scientific reductionist view and the clinical, experiential holistic view.

But you can’t blend scientific methods with “disparate philosophies”. Science is what it is only because certain absolute rules apply to how we interpret observations. The scientific foundations of medical education are undermined when they are blended with pseudoscience and metaphysical presuppositions. Abraham Flexner, almost a century ago, referred to such presuppositions as dogma and warned that medical schools must not compromise science with dogma. Medical education, influenced by the AMSA and its accomplices at NCCAM, is turning its back on Flexner’s warning.

Taken to task for my criticism of AMSA

Wednesday I criticized AMSA’s promotion of complementary and alternative medicine (CAM) and suggested that the organization might be just a wee bit disingenuous in its purported concern for evidence based medicine. This drew questions from two commenters.

Ladybird asked: “How do you know the chakra methods don't work?” That’s the wrong question because it shifts the burden of proof. The burden of proof should rest on those who make the claim. The appropriate questions should be “How do we know the chakra methods do work?” and “Can you show me an anatomic or physiologic basis for chakras?” Put another way, don’t CAM claims warrant the same burden of proof and degree of skepticism that we apply to the products of Big Pharma?

Paige Hatcher, a KU medical student and blogger who is taking an AMSA fellowship, cites a diversity of viewpoints within the membership of AMSA:

With over 10,000 pages on our website, and 70,000 members, there are many individual members and projects that may differ from AMSA's overall goal of teaching evidenced based medicine.

And this is supposed to explain away a double standard? It doesn’t. A standard of rigorous skepticism for the promotions of drug companies alongside one of nearly unconditional acceptance and credulity for numerous unproven, biologically implausible and even dangerous claims of alternative medicine sends a troubling double message.

Paige, as an enthusiastic participant in the leadership of AMSA you have a unique opportunity. I challenge you to make a difference. Encourage the boosters of CAM in your ranks to apply the same standards of evidence to their methods (e.g. chelation therapy, purging, fasting, homeopathy) as they would to the products of drug companies. This will help the cause of EBM and restore credibility to your organization.

Go Cards!

I spent Labor Day weekend visiting family in St. Louis. Last Saturday I indulged in one of my favorite pastimes as I watched the St. Louis Cardinals defeat the Cincinnati Reds 11-3. I took a few pictures which I’ll share here.

In pre-game ceremonies Cardinals manager Tony La Russa was honored for passing Hall of Famer Red Schoendienst’s all time managerial win record.




From left: Cardinal owner and managing partner Bill DeWitt; Schoendienst; La Russa.





Reds slugger Ken Griffey, Jr.

Cards first baseman Albert Pujols.

Cards win!

With Thursday’s win over the Pittsburg Pirates the cards are one game out of first place in the NL Central division. Will they win it all this year and have to apologize again?

The American Medical Student Association---a paradox of skepticism and credulity

The American Medical Student Association (AMSA) is in the news again with the roll out of a collaboration with Medical Letter (via Earth Times). The press release, titled “Medical Students Receive Free Evidence-Based Materials to Combat Marketing Paraphernalia” suggests that AMSA is all about EBM and critical thinking. It goes on to talk about professionalism and critical evaluation of therapies. The Medical Letter is a wonderful resource and should help students learn about rational drug therapy.

But cognitive dissonance sets in when the initiative is juxtaposed with AMSA’s numerous promotions of non-evidence based and implausible alternative medicine modalities. Page 4 of their handbook on Integrative, Complementary and Alternative Medicine for Providers of Primary Care claims, for example, that “Homeopathy is very cost effective over the long term”. The entire chapter on homeopathy in another AMSA alternative medicine publication, Between Heaven and Earth, is uncritical (pp. 34-36). The chapter on Therapeutic Touch explains the technique on the basis of chakras (p. 43):

Blockages of these chakras result in depletion of energy in the physical, emotional or mental dimensions associated with each. For example, a blockage of the root chakra can result in dysfunction in the physical energy layer, causing fatigue or ailments of the lower back, hips, legs and perineum.

It goes on.

What’s up with AMSA anyway? They’ll shun drug company support because they “don’t want to be bought”, demonstrate in front of a drug company’s headquarters by dumping thousands of advertising pens there, yet accept support from the American Holistic Medicine Association which promotes stuff like this.

Mechanical ventilation for ARDS

….is the subject of a State-of-the-Art Review in Chest. Not much new here. Low tidal volume ventilation, daily spontaneous breathing trials and protocols for liberation from mechanical ventilation were emphasized. Special modalities such as high peep may be useful rescue maneuvers in individual patients but are not considered evidence based for improving survival.

Continue statins as seamlessly as possible before and after vascular surgery

This study from the American Journal of Cardiology should be of interest to hospitalists, who are increasingly called on to help co-manage surgical patients. Interruption of statin use was associated with increased early postoperative cardiac events. A potential weakness of the study was the fact that those patents undergoing higher risk surgeries such as abdominal aortic procedures were the very patients likely to have longer interruptions in statin therapy due to being NPO for longer periods. The authors state they adjusted for that variable.

They suggest that administration of an extended release statin before surgery may help bridge the gap. Extended release statin use seemed to confer benefit in the study. Fluvastatin (Lescol XL) is the only extended release statin available.