Saturday, December 31, 2005

Top ten issues in hospital medicine for 2005------issue 3

Emerging infections

1) Avian flu. Is it a big deal? Yes. Are we prepared? Not yet. Has it been hyped? Definitely. I have posted several times on this topic through the course of the year. [1] [2] [3] [4] [5] [6] Unanswered questions include: When will it arrive? Will the genetic shift necessary for efficient human to human transmission also weaken its virulence? (Let’s hope so. That’s what happened with two of the three pandemics this century).

2) Community associated methicillin resistant Staphylococcus aureus. It’s different from the old MRSA. The resistance pattern and the genome are distinct. Although we’ve had a friendly debate here on the blogosphere about the clinical significance (or lack thereof) of certain unique virulence factors, the clinical profile is different, with more skin and soft tissue infections, occasional necrotizing fasciitis, a possible increased threat of necrotizing pneumonia, and increased transmissibility. On the other hand the risk of intravascular and bone and joint infections may be less. Here are my previous posts on the topic. [7] [8] [9] [10]

3) New profiles of Clostridium difficile infection. I blogged previously about the outbreak of a new strain of C. diff in Quebec. An alarmingly higher mortality compared to usual infections was noted, attributable to a mutation in a regulator gene which controls toxin production, resulting in production of 15-20 times more toxin than usual. The reports from Canadian Medical Association Journal which I cited suggested that shared bathrooms in outmoded hospital facilities was the most important risk factor. Subsequently, two reports [11] [12] and an accompanying editorial in NEJM described outbreaks in the U.S. as well as the Quebec outbreak. It appears that the U.S. outbreak is similar to the Quebec outbreak, in that both are due to a strain that contains the toxin regulator gene deletion and has the ability to produce a previously uncommon binary toxin. The virulence potential of the regulator gene mutation is well known, while the significance of the binary toxin is less clear. The NEJM editorial by J. Bartlett summarizes the problem nicely, and points to two curious features of the severe cases, those being leukemoid reactions and hypoalbuminemia.

Top 10 issues in hospital medicine for 2005------issue 4

Controversies in hypercoagulability

Recent guidelines have recommended testing certain patients for hypercoagulable states following an episode of venous thromboembolism (VTE) and others suggest how such test results might influence treatment decisions. But controversy arose last May with the publication of this study in JAMA of patients who underwent thrombophilia testing after an episode of VTE. The study showed that certain clinical factors, but not laboratory testing, were predictive of recurrent VTE events. The popular spin, simplistic as always, was that thrombophilia testing be abandoned.

How can this seemingly disparate evidence be integrated with what was known before? Older data, upon which the guidelines were based, had established that thrombophilia testing was predictive of the relative risk for initial VTE. The situation is completely different for patients who have already had a spontaneous VTE. Why? It has long been known that patients with spontaneous VTE are hypercoagulable, (untreated recurrence rates of 2% to 5% per year) no matter the result of thrombophilia testing. In part this is because comprehensive laboratory testing of clinically thrombophilic patients will yield negative results---no “laboratory lesion”--- in about 30%-40% of cases. The thinking is that those patients have a thrombophilic state that hasn’t been discovered yet. To keep it in perspective, remember that the concept of hereditary thrombophilia has been around since the discovery, in 1963, of antithrombin deficiency (Egeberg O: Inherited antithrombin deficiency causing thrombophilia. Thrombosis Diathesis Haemorrhagica 1963; 13: 516) but it was not until about a decade ago that the most common hereditary thrombophilia, Factor V Leiden, was discovered. The field will mature and as additional disorders are characterized thrombophilia testing will become more “evidence based.”

In a related controversy “NORVIT: Randomised trial of homocysteine-lowering with B vitamins for secondary prevention of cardiovascular disease after acute myocardial infarction” was presented at the European Society of Cardiology this year. The media spin---that the homocysteine hypothesis is a “bust”---was irresponsible. Forget the media reports and view the presentation slides. What the study actually did was to suggest that the popular notion of an upper “safe” limit of homocysteine for cardiovascular health of 9 or 10 may not be valid. It also debunked the popular practice (which was never evidence based in the first place) of giving everyone combination B vitamins for secondary prevention. Homocysteine testing and selective use of folic acid and/or B6 may be clinically valid.

Top ten issues in hospital medicine for 2005------issue 5

Emergency cardiac care

New guidelines were published late this year which place greater emphasis on cardiac compressions. I anticipated these changes in a blogpost last October which details the science behind the new emphasis on compressions. The guidelines came short of full implementation of the changes suggested by the group at the University of Arizona which has done pioneering work in this area.

Top ten issues in hospital medicine for 2005, ------issue 6

Electronic medical records and computerized physician order entry
Electronic medical records (EMR) and computerized physician order entry (CPOE) hold great promise, and hospitalists are expected to be leaders in the adoption of these technologies. The news this year, however, was not all good. As I posted earlier this month, adoption of EMR in Hawaii has been problematic. In March there was this study in JAMA suggesting that CPOE may actually increase errors. Meanwhile the system at Vanderbilt seems to be working well as reported in this podcast interview at Soundpractice.

Perhaps Medpundit summed it up best this year in saying “Successful implementation an electronic medical record requires a tremendous amount of cooperation and consultation with the people who are going to be using it. The bigger the group, the harder that's going to be.”

Friday, December 30, 2005

Top 10 issues in hospital medicine for 2005, issue 8

Quality, accountability and P4P

With the Institute of Medicine’s publication in 2000 of “To Err is Human” the spotlight was placed on hospital quality and safety. Although the report’s claim that errors cause 44,000 to 98,000 hospital deaths each year is controversial it put patient safety initiatives in high gear. Since that time consumer activists have been demanding change. Although there has been some evidence that quality is improving, studies continue to show significant deviation from recommended practices. This study published in NEJM in 2003 suggested that adherence to recommended processes was just over 50% for acute care, suggesting significant room for improvement in hospital quality.

Meanwhile, data on hospital quality indicators is increasingly being made public as in, for example, the department of HHS Hospital Compare project and the independent health care rating company Healthgrades. (Although most of the information in Healthgrades is behind access control the hospital quality reports are open access).

Pay-for-performance (P4P) is one of the latest buzz words in the quality movement. The ultimate impact and sustainability of P4P is unknown, but this recent study in JAMA was not encouraging.

Although the concept of hospital quality is not new, the issue gained considerable momentum and was a major concern for hospitalists in 2005.

Thursday, December 29, 2005

Top 10 issues in hospital medicine for 2005, issue 9

Inpatient glycemic control

Although this issue has been out there a few years it continued to be a major focus of interest among hospitalists in 2005. Thinking was changed after ground breaking investigation was published in NEJM in 2001. This study of critically ill patients in a surgical intensive care unit demonstrated reduced morbidity and mortality attributable to tight post operative glycemic control. Of interest, only 13% of the patients had a prior history of diabetes. Now intensive insulin therapy in hospitalized patients had become an intervention to reduce mortality and complications. Subsequent studies have validated the intervention across a wider spectrum of hospitalized patients. I previously blogged and cited additional references here.

Top ten issues in hospital medicine for 2005

As the year draws to a close I will be writing a series of posts on the major issues of the year in the field of hospital medicine. Disclaimer: This list reflects solely the biases of a committee of one (me). The reverse numerical order of posting does not necessarily reflect the order of importance. I have blogged about some, but not all of the issues before.

Issue 10: The diagnosis of pulmonary embolism.
The long awaited results of PIOPED II were announced at the close of last year at the Radiological Society of North America national meeting. There was also some discussion of the results at Chest 2004. To the best of my knowledge the results have not yet been published. Despite hopes that CT would emerge as the clear diagnostic modality of choice the PIOPED II results suggested otherwise: the best approach is individualized, and usually based on the integration of multiple modalities and clinical data. I presented my thoughts on the issue earlier this year. That post has more information on the PIOPED II findings, which will not be repeated here.

I think Gregory S. Martin, speaking about PIOPED II at Chest 2004, sums it up best: Based on these results, the use of PE-protocol CT cannot be advocated as a stand-alone procedure for diagnosing PE.

Wednesday, December 28, 2005

Creighton University Alternative Medicine Links

Their web site on Voodoo describes the theory and methods. Though falling just short of promoting Voodoo in its entirety the article maintains that Voodoo pharmaceuticals are effective. Concerning the spiritual dimensions of Voodoo healing it takes a non critical stance: “As a philosophical and cosmological system, with its emphasis on spiritual reality, it is regarded by science with doubt and derision. Yet, this may be due, as mentioned earlier, to their disparate paradigms and may merely be a reflection of the conceptual prejudices of Western science.”

Here is a crystal therapy page which explains all about Chakras.

Here is their craniosacral therapy page.

Monday, December 26, 2005

Do not miss this diagnosis!

Here’s one of those medical mysteries from a New England Journal CPC. Although it should never actually be a mystery---it’s easy to diagnose if you think about it---it remains under appreciated. It’s a must not miss diagnosis.

If you haven’t read the CPC, test yourself. To play the game it’s enough to know that this patient presented in cardiac arrest. Without peeking (that is don’t scroll down too far) click on Figure 1 and click again to zoom. You should have the correct diagnosis in mind in seconds.

This is not a typical CPC case because it’s a look-see diagnosis. Although the discussant goes through the obligatory long differential diagnosis (and a brilliant discussion it is!) he indicates from the start that the exercise isn’t really necessary. He opens his discussion of differential diagnosis by saying “Although I am aware of the diagnosis in this case……..” It is, of course, Brugada syndrome.

Here are some additional useful resources. [1] [2] These latter are open access full text in case you can’t access the NEJM CPC.

Saturday, December 24, 2005

Doctors are becoming more selective in antibiotic prescribing

This is good news from AHRQ. Doctors are following the evidence and prescribing fewer antibiotics to children.

Thursday, December 22, 2005

Community acquired MRSA in athletes

This review from the American Journal of Sports Medicine reminds us of the increasing problem of outbreaks of community acquired methicillin resistant Staphylococcus aureus in contact sports teams. I have blogged on the subject previously. [1] [2] [3].

Wednesday, December 21, 2005

Autoimmune bradyarrhythmias

The autoimmune pathogenesis of cardiac conduction system disease is reviewed here (European Heart Journal 2001). The well known association between congenital heart block and maternal antinuclear antibodies (SSA/Ro and SSB/La) is discussed. Less well appreciated conditions are antibodies to sino-atrial node and atrio-ventricular node tissues and their clinical associations with bradycardia, sick sinus syndrome and heart block and the increased incidence of AV block in HLA B-27 positive individuals.

Tuesday, December 20, 2005

Docs ignore black box warnings

The large Harvard study is reported here via Medscape. We already knew this, as I blogged some time ago. In this study, compliance with black box warnings was variable. Doctors ignored the warnings almost half the time for some drugs. The study was published in Pharmacoepidemiol Drug Safety. 2005;14:1-18.
Through the years we’ve seen many drugs taken off the market as well as some class action law suits against drug companies. But studies like this should cause us to reconsider our views on drug safety. It’s simplistic to merely categorize drugs as good versus bad, safe versus dangerous. Some drug disasters are more related to inappropriate use. That’s exactly what happened to cisapride ---not inherently a bad drug, just a relatively unforgiving drug that saw widespread contraindicated prescribing. Public opinion placed far too much of the blame on the FDA and the drug company.

There are similar lessons in the Phen-Fen case. Though there was no black box warning, the two weight loss drugs were never approved by the FDA nor were they promoted by the drug companies for combination use. Nevertheless the combination became the rage in obesity treatment. A weight loss industry was born and large numbers of doctors inappropriately prescribed the cocktail. But what did the trial lawyers do? They followed Sutton’s Law and went where the money was. It had to be more cost effective to file a class action suit against a large company than to go after all those doctors individually.

What are the solutions to the problem of contraindicated prescribing? The author of the Harvard study suggests incorporating better information into the black box warnings and the use of alerts and warnings built into electronic medical records.

Monday, December 19, 2005

Food-cobalamin malabsorption syndrome

I recently blogged and cited references about this underappreciated yet most common form of vitamin B12 deficiency in the elderly. Another paper with similar conclusions has recently appeared in the American Journal of Medicine. Here are some of its key points.

1) Food-cobalamin malabsorption (FCM) is the most common form of B12 deficiency in the elderly, with classic pernicious anemia (PA) being seen in a minority.
2) The criteria for FCM are low B12 levels, normal Schilling test (using free cobalamin, not egg yolk bound cobalamin), absence of auto-antibodies and adequate dietary cobalamin intake.
3) These patients can absorb free (pill form) cobalamin but not food-borne cobalamin.
4) A spectrum of biochemical, hematologic and neurologic manifestations is seen, which may be milder than that seen in PA.
5) Oral B12 was effective. The investigators used 125mcg-1000mcg daily.

Caveat: All the patients in this study had FCM. Although oral cobalamin can also be used to treat PA, higher daily doses (1000mcg-2000mcg) are recommended. Oral vitamin B12 replacement is less well validated in patients with PA than in those with FCM.

Hypokalemia and hyponatremia from thiazides

Reported here in the British Journal of Clinical Pharmacology. This is occasionally severe enough to land people in the hospital. I think I’ve seen more of it since ALLHAT.

Sunday, December 18, 2005

Influenza pandemics

NEJM has this open access review of the subject.

Antipsychotic drugs and diabetes

This study in the Journal of Psychopharmacology examines the mechanism at the level of the beta cell.

A contrarian view of evidence based medicine

Evidence based medicine (EBM) intrigues and challenges me. While I embrace its principles I am concerned when some proponents take ideas to extremes.

Norman Latov, M.D, Ph.D, professor of neurology at Cornell thinks the zealots of EBM have gone too far. His recent article in the Journal of American Physicians and Surgeons takes them to task. Many proponents of EBM eschew expertise, case reports and physiologic rationale which, Latov points out, were important in the pioneering work of Harvey, Pasteur and Osler.

I don’t agree with all of Latov’s statements (e.g., his implications that guidelines do more harm than good, that EBM makes no allowance for physician judgment, or that guideline adherence has not been shown to impact outcomes) but he makes many valid points.

Latov effectively challenges the orthodoxy of EBM, much of which is dogma rather than science. Counter-arguments such as his should help us refine and balance our views of EBM.

Saturday, December 17, 2005

Rheumatology labs

The bewildering array of serologic tests for connective tissue disease is nicely summarized in this update from Clinical Medicine and Research. I found what I believe to be one small error in the paper. The anti-Sm antibody, an anti-nuclear antibody highly specific for systemic lupus, is referred to incorrectly as “anti-smooth muscle” antibody. It actually stands for “anti-Smith antibody”. Anti-smooth muscle antibody, not relevant to this article, is used to test for certain forms of autoimmune hepatitis.

Hyponatremia: must reads for hospital physicians

An excellent review (via Medscape) on hyponatremia appeared recently in Clinical Endocrinology. Other general reviews of note are linked here (open access full text) [1 ] [2 ]. This review from a few years ago in Archives of Internal Medicine addresses the underappreciated distinction between osmololarity and tonicity as well as the related concepts of effective and ineffective osmoles (not light reading but important—a classic article worth having in the original).

article from CMAJ, though dated, is important in that it highlights selective serotonin reuptake inhibitors as an under recognized cause of hyponatremia.

Finally there is the problem of post operative hyponatremia. Although it occurs in a variety of post operative settings, hyponatremia after orthopedic surgery is of particular interest to hospitalists for a couple of reasons. First, there has been recent interest in hospitalist collaboration in the management of orthopedic surgical patients. Secondly, hyponatremia after orthopedic surgery has been noted sufficiently frequently to warrant special attention [3].
It seems to be more of a problem in female patients and is often aggravated by recent thiazide diuretic use.

The difficult patient

In the November 15 issue of American Family Physician is a review entitled Management of the Difficult Patient. It offers an insightful analysis of the problem and some useful suggestions for primary care physicians. I spent about 20 years as a traditional office based internist before becoming a hospitalist. The article has a ring of truth, many of its points reminding me of things I learned from that experience.

It categorizes difficulties in the doctor-patient relationship into the areas of system problems, patient problems, and physician problems. System problems in primary care are all too well known, driven largely by financial pressures which translate into time constraints. Patient problems may be due to psychopathology in the patients themselves, often in the form of a personality disorder. Finally if you, the physician, think all or most patients are “difficult” you may have issues of your own to face.

Friday, December 16, 2005

The emerging association of anemia and heart failure

November’s issue of the Cleveland Clinic Journal of Medicine contains a review on the links between anemia and heart failure. Anemia occurs with increased frequency in heart failure by a variety of mechanisms, and is associated with increased mortality. There is evidence to support treatment of anemia in heart failure with iron and erythropoietin, but the level of evidence is low and does not support a firm recommendation.

There has been a lot of recent noise about anemia and heart failure. This review sums it up nicely and is worth reading in its entirety.

Thursday, December 15, 2005

Public Citizen opposes liability protection for vaccines

Why am I not surprised? Check it out here. They even have a canned letter you can send to your senators and representatives with a click of the mouse.

Wednesday, December 14, 2005

Is this the antimicrobial magic bullet?

Not quite, but tigecycline (Tygacil), a new tetracycline derivative (glycycycline) approved by the FDA in June 2005 and marketed by Wyeth pharmaceuticals is active against a wide spectrum of organisms and promises to be a useful addition to the antimicrobial arsenal. FDA approval processes are lengthy and drug companies, anxious to get products to the market, tend to launch antibiotics after approval of a limited number of indications that are restrictive when compared to the drug’s true range of efficacy. This invariably (and often appropriately) leads to “off label” use of antibiotics. Such may be true of tigecycline, approved only for complicated skin and soft tissue infections and complicated intra-abdominal infections. Certain pharmacokinetic advantages and a broad spectrum of activity suggest a wider range of potential use, but what other uses might be appropriate?

This review in the Journal of Antimicrobial Chemotherapy addresses the question by covering the basics of tigecycline’s antimicrobial activity and the relevant pharmacokinetics. As promising as tigecycline is, the article notes these caveats: 1) Gaps in the gram negative spectrum include Pseudomonas aeruginosa and the family Proteeae (the genera Proteus, Morganella, and Providencia). 2) Excellent tissue penetration occurs at the price of a very large volume of distribution and consequent low serum levels, raising concerns about its efficacy in bacteremic infections. 3) Predominant biliary excretion results in low urinary levels, limiting the efficacy in urinary tract infections. 4) Emergent resistance of some gram negative species was seen in phase three trials, serving to warn against indiscriminate use.

The article concludes “Whether or not significant resistance threats ultimately do emerge (and experience shows that they usually do!), it is excellent news to have a new agent with increased activity against Gram-negative as well as Gram-positive bacteria. Few others will come this decade” (Italics mine—I have previously blogged about the waning antibiotic development pipeline).

Polymerase chain reaction demystified

Well, not quite, but I found this review in Advances in Physiology Education helpful.

The importance of the electrocardiographic P wave

J. Willis Hurst of Emory University School of Medicine has written a great deal about electrocardiography, including this piece in Clinical Cardiology outlining pet peeves he terms “electrocardiographic crotchets”, or common irritating errors in interpretation. One of his crotchets is the failure to appreciate the importance of P wave abnormalities. P waves may reflect conduction abnormalities in the right or left atrium caused by atrioventricular (mitral or tricuspid) valve disorders or by disorders (hypertrophy or dilatation) of the right or left ventricle, respectively. It is important to note that the atrial conduction abnormality may or may not reflect hypertrophy or dilatation of the atrium. Thus it is proper to speak of right or left atrial abnormality as an electrocardiographic finding, but not enlargement or hypertrophy. The atrial abnormality is more telling about the corresponding valve or ventricle than the atrium itself. Regarding the importance of P waves he writes “To ignore P-wave abnormalities or to refer to them as being due to atrial enlargement or hypertrophy are crotchets.”

To the growing importance of P wave abnormalities we can now add findings from this recent paper in Stroke. Electrocardiographic left atrial abnormality (defined as dimensions of the terminal P wave component in V1 >40ms*mm) was associated with increased risk of ischemic stroke (OR 2.32) in this case-control study.

By the way---those with a scholarly interest in electrocardiography should read Hurst’s paper in the original.

Tuesday, December 13, 2005

The American Medical Student Association Promotes Chelation Therapy

The American Medical Student Association (AMSA) has launched the PharmFree campaign which encourages doctors and med students to distance themselves from drug companies and their representatives by refusing gifts, support and promotional materials. In this way, so they claim, they intend to change the culture of medicine toward higher ethical standards, increased professionalism and evidence based medicine. I would applaud such lofty goals, but there’s a problem. The AMSA’s promotion of pseudoscience and unproven health methods belies its stated ideals and one has to wonder what the true agenda of the PharmFree campaign is. I recently posted an overview of this hypocrisy and today will focus on chelation therapy, just one of the questionable health claims promoted by AMSA.

Though chelation’s proponents claim its effectiveness against cardiovascular disease and a variety of other disorders there is no supporting evidence or rationale except for the treatment of heavy metal poisoning. The American College of Cardiology’s position statement recommends against chelation therapy for cardiovascular disease. The Federal Trade Commission charged one group with false advertising for its claims that chelation therapy was effective in treating atherosclerosis. Although a large scale NIH sponsored study of chelation is in progress, researchers have for decades been unable to demonstrate clinical effectiveness or physiologic rationale. The most recently published evidence regarding chelation therapy is a systematic review which failed to find evidence of effectiveness.

Chelation is promoted on page 20 of AMSA’s Complementary Therapies Primer. This is not a balanced critical view of the treatment. The second paragraph makes the baseless claim that it improves blood flow and is helpful in the treatment of gangrene and intermittent claudications. The article also claims chelation is helpful for memory loss, arthritis, scleroderma and lupus. It goes on to say that oral chelation with either EDTA or penicillamine is useful as a “preventative measure” and lowers cholesterol.

This is patently absurd and destroys the credibility of the PharmFree campaign. It is also irresponsible. The AMSA needs to do some housecleaning of its own before pointing fingers at doctors for associating with the pharmaceutical companies.

Sunday, December 11, 2005

The hypocrisy of the American Medical Student Association

The American Medical Student Association (AMSA) was founded in 1950 as a subsidiary of the American Medical Association (AMA). Following “dramatic changes in the organization's objectives and philosophy” the organization severed ties with the AMA in 1967. In 1975, to further distance their image from the AMA they changed their name from the former Student AMA to the current AMSA. Among the association’s stated missions is the promotion of improvement in medical education. One of the education initiatives is the PharmFree campaign which encourages students to refuse gifts and support from drug companies which might influence them away from evidence based medicine. As I previously blogged, the campaign has recently received favorable press. The AMSA states on the campaign web site that PharmFree seeks to promote evidence based medicine and education about clinical guidelines, as well as foster honesty and integrity.

So far, so good----the AMSA says they’re all about science, evidence and ethics. But wait. Dig deeper and you find AMSA actively promoting quackery and pseudoscientific nonsense. Let’s look at a few links. Here we find that they advocate for complementary and alternative medical education. What does that mean? Well, they’ve just formed a naturopathic medicine interest group. (Here’s some reliable information on naturopathic medicine). They have also published a booklet entitled Between Heaven and Earth, a 46 page “Introduction to Integrative Approaches to Health Care.” Far from being a critical or scientific approach, the book actively promotes unscientific methods. Then there’s their Complementary Therapies Primer which teaches and actively promotes all sorts of nonsensical and outlandish claims. Included are promotions of chelation, homeopathy, aromatherapy, therapeutic touch, polarity therapy, rolfing, qigong and ayruvedic medicine.

The AMSA claims to promote evidence based medicine and ethical principles as exemplified by their PharmFree campaign. But their promotion of pseudoscientific nonsense (and, in my opinion, fraud), is neither evidence based nor ethical. It’s hypocritical and it’s outrageous. Thanks to the Health Fraud list for the links.

Update: Click here.

Saturday, December 10, 2005

Adopting electronic medical records: easier said than done

BMJ reports on Kaiser Permanente’s difficulties in Hawaii [1] [2]. And let’s not forget the disaster at Cedars-Sinai a few years ago.

Heparin Induced Thrombocytopenia

Here is a full text open access review in Thrombosis Journal. The take home points are:

1) There are two forms of thrombocytopenia related to heparin, and the nomenclature is confusing. A benign non-immune mediated form, little more than a laboratory phenomenon, reverses readily upon discontinuation of heparin. The more clinically important form is the immune mediated form. These have been known as HIT types I and II respectively. “HIT” often refers to HIT type II.
2) Immune mediated HIT is a state of extreme hypercoagulability, both arterial and venous. Hypercoagulability, not bleeding, dominates the clinical picture.
3) Mere cessation of heparin is insufficient. A non-heparin anticoagulant (danaparoid, lepirudin or argatroban) must be used. Low molecular weight heparin has cross reactivity and is therefore not appropriate. The synthetic pentasaccharide fondaparinux does not cross react and is therefore promising, but has not been adequately validated in clinical studies.
4) Mere substitution of warfarin is contraindicated. It must be overlapped with one of the non-heparin anticoagulants mentioned above. Otherwise the early depletion of protein C induced by warfarin would add one hypercoagulable state to another. Clinically, peripheral venous gangrene and warfarin skin necrosis have been observed after such inappropriate use of warfarin.

From other literature:

The initiation of a non-heparin anticoagulant must be based on clinical grounds, since laboratory confirmation is often not immediately available. A point score system for the estimation of pretest probability for HIT appears promising for clinical decision making. (Free registration required to view abstracts and poster sessions of the 45th annual American Society of Hematology Meeting. Browse for item 1963 Preliminary Evaluation of a Clinical Scoring System for Estimating the Pretest Probability of Heparin-Induced Thrombocytopenia: The 4 T s . Session Type: Poster Session 134-II ).

Thrombocytopenia may occur as a result of the primary thromboembolic process itself, reflecting a consumptive phenomenon. Although usually mild it may be severe and be confused with HIT.

Antiarrhythmic drug therapy review

Although antiarrhythmic drug therapy has declined sharply in the post-CAST device therapy era, limited indications persist and are reviewed concisely here in the Texas Heart Institute Journal.

Friday, December 09, 2005

Podcast at

My podcast interview has been posted. If you have half an hour or so with nothing better to do, give it a listen.

Tuesday, December 06, 2005

Eye of newt, and toe of frog…

More pseudoscientific med school fluff

This time it’s the University of Manitoba medical school. According to this report from the school’s alternative medicine program “encourages future doctors to find ways to combine old medical philosophies with modern knowledge.” The curriculum, designed for second year students, features acupuncture, yoga, homeopathy and chiropractic. Students “sip ginseng tea while handling bags of dried gecko lizards and jars of toad droppings.”

Dr. Greg Chernish heads the program. “Chernish says combining the benefits of ancient medicine with modern science provides the best care for patients – a concept that surprised student Heather Nowosad. ‘The integration part was surprising for me, because I've always had this belief that it's sort of like people believe in one or the other,’ said Nowosad, who plans to become a family physician.” Don’t feel bad, Heather. Abraham Flexner had that belief too.

Systemic thrombolysis for submassive pulmonary embolism?

The accepted treatment for pulmonary embolism (PE) uncomplicated by hypotension or acute right ventricular failure is heparin (low molecular weight or unfractionated). When PE is complicated by hypotension (classified as massive) there is general acceptance of systemic thrombolysis in addition to heparin. More controversial is the intermediate situation, known as submassive PE, defined as PE with normal blood pressure but in the presence of acute right ventricular dysfunction. Right ventricular dysfunction is generally defined by echocardiography.

A randomized double blind placebo controlled trial in 2002 demonstrated that in submassive PE systemic thrombolysis added to heparin was associated with improved patient stability, less need to add hemodynamic support, but no difference in mortality. Controversy has persisted, and in the October 24 Archives of Internal Medicine are pro and con articles with rebuttals. [1] [2] [3] [4].

CA-MRSA in perspective

In his post today on Staphylococcal infections RangelMD says methicillin resistant staphylococcus aureus (MRSA) infections are not inherently worse than methicillin sensitive (MSSA) infections, community acquired MRSA (CA-MRSA) is not a “super bug”, and the press has sensationalized and distorted the issue. I agree partially---especially with the point about media distortion. I also agree that the “old fashioned” MRSA is not necessarily more virulent than MSSA, although it may be associated with poorer outcomes related to greater difficulty in treatment and greater comorbidities in MRSA infected populations.

Concerning CA-MRSA, however, I feel some need to elaborate since I have posted about its unique attributes before. [1] [2]. Although its predilection for causing minor skin infections often makes it more of a nuisance than a threat to life there is evidence of uniquely heightened virulence and transmissibility in some CA-MRSA clones. These characteristics are associated with the Panton-Vanentine leukocidin, (PVL) found more frequently in CA-MRSA than in other strains. The PVL gene is only rarely found in hospital associated MRSA and MSSA.

Although the somewhat heterogeneous nature of CA-MRSA makes it difficult to generalize, some trends are emerging which raise concerns about increased transmissibility and virulence.

Sunday, December 04, 2005

On the death of Lisa McPherson

Lisa McPherson was given Scientology’s “alternative” to psychiatry. On the tenth anniversary of her death under the care of Scientology staffers the Health Fraud List posts these links about the case. This article chronicles the tragedy and the subsequent legal wrangling. A large collection of links on the case is provided here. The wrongful death suit against Scientology lasted seven years and was finally settled last year.

Sloppy media coverage of avian flu

Popular media coverage of avian flu is confusing. This piece from WorldNetDaily is headlined “OUTBREAK! Has feared mutation of avian flu arrived? Doctors in Thailand, Indonesia see 1st signs of human-to-human spread.” The article reports that in Thailand two recent human flu cases can’t be traced to contact with birds. The cases were mild, and doctors speculate that waning virulence may have accompanied a mutation enabling human to human transmission. The problem is that the article cites no report of serologic analysis or evidence that the cases indeed represent the H5N1 avian variety. Moreover, no human disease contacts were mentioned. If there’s anything to this, the article certainly doesn’t inform us.

On down it says “Meanwhile, in Indonesia, the disease is spreading so rapidly, particularly in the capital of Jakarta, some health officials strongly suspect the long-dreaded mutation has already occurred.” Oh? They why does it say a few paragraphs below that only 13 avian flu cases have been confirmed in Indonesia?

And, if human to human transmission is the case here it’s not new. Human to human transmission of avian flu was well documented over a year ago.

The strange story of Dr. John R. Brinkley

Pseudoscientific health providers have a colorful history. They range from alternative practitioners who honestly believe in an unproven method to the purveyors of outright fraud. In this latter category was the fabled Dr. John Brinkley. Not only was he one of the better known “snake oil salesmen” in American history, but he may also be the originator of the infomercial 80 years ago in the early days of radio.

But it seems society in those days was less tolerant of the likes of Dr. Brinkley than now (those of Brinkley’s ilk today seem to be doing quite well). In 1930 both his medical license and his radio station license were revoked. Virtually run out of Kansas, he moved his operation to the Mexican border where he constructed one of the first Mexican border blaster radio stations. You can listen to an NPR report on Brinkley and border radio here. It contains excerpts from Brinkley’s infomercials and as a bonus, about 16 minutes in, an interview with Wolfman Jack, propelled to fame on the third and last incarnation of Brinkley’s station, XERF.

Friday, December 02, 2005

Clostridium difficile: the Quebec strain

DB blogged about a new face of C-diff earlier today—it’s been showing up in healthy members of the community, some of whom had no recent antibiotic exposure. There’s another aspect that is worth our attention and that’s the Quebec strain.

A hypervirulent strain of C. difficile has emerged there over the last three years. A study of the attributable mortality, an editorial and a news piece appear in the October issue of CMAJ.

What’s different about the strain? As reported in these articles: 1) it produces 15-20 times the amount of toxin as the ordinary strains, due to an altered repressor gene; 2) it’s more lethal, with 23% of patients dead at 30 days and an attributable mortality at one year of 16.7%.

The author of the study points out that some patients appear to have died of direct complications of the infection such as shock or perforation while others succumbed to secondary events such as myocardial infarction, venous thromboembolism or secondary infection.

Infection control implications are discussed and the papers offer conjecture about risk factors at the Quebec hospitals. There was no difference in patient characteristics compared to other regions of Canada or the United States (the strain has shown up at a few locations in the US), and no evident difference in the use of antibiotics. The only common thread seemed to be the use of shared bathrooms. The authors conclude: The lack of investment in our hospitals infrastructure over several decades, with shared bathrooms being the rule rather than the exception, may have facilitated the transmission of this spore-forming pathogen, which can survive on environmental surfaces for months. Providing modern medical care within hospitals built a century ago is no longer acceptable.

Wednesday, November 30, 2005

Medical students’ skulls being filled with mush

Student BMJ is a journal for medical students from the BMJ publishing group. In the November 2005 issue is an article on an alternative modality called Ayurvedic medicine. Ayruveda, the article says, is an ancient healing tradition with roots in India. It goes on to say that Ayruvedic tradition describes health and disease in terms of three fundamental constitutional principles called the doshas. Stephen Barrett’s expose on Ayruveda reports that “Ayurvedic proponents have claimed that the symptoms of disease are always related to the balance of the doshas, which can be determined by feeling the patient's wrist pulse or completing a questionnaire. Some proponents claim (incorrectly) that the pulse can be used to detect diabetes, cancer, musculoskeletal disease, asthma, and ‘imbalances at early stages when there may be no other clinical signs and when mild forms of intervention may suffice.’”
The BMJ publishing group, a division of the British Medical Association, says its mission is "To publish intellectually sound material that will serve the needs of doctors, members, other health professionals, the scientific community, and the public." Its premier journal, BMJ, is widely regarded as a champion of evidence based medicine. So why might a paper on an ancient healing art be published in Student BMJ? To increase students’ cultural awareness, or to alert them to the alternative treatments patients are seeking, perhaps? No. This article in SBMJ actually promotes Ayruveda. The article asks “Is scientific medicine the only way?” The author notes “Studying Ayurveda provided me with an alternative system for categorising and describing states of health and disease.”
So much for intellectually sound material.

Heparin induced thrombocytopenia and open heart surgery—news from Chest 2005

The annual meeting of the American College of Chest Physicians recently took place in Montreal. One of the presentations (reported in eMedicine news) concerned the prevalence of heparin-platelet factor 4 (HPF4) antibodies in patients about to undergo open heart surgery. HPF4 antibodies are found in patients with heparin induced thrombocytopenia (HIT) and are instrumental in its pathogenesis. The Milwaukee investigators screened patients before surgery and found antibodies in 5.4%. Antibody positivity was associated with longer ICU stays and a higher incidence of prolonged mechanical ventilation, limb ischemia, renal dialysis and gastrointestinal complications. These findings raise the question of whether all cardiac surgery candidates should be screened.

I’m anxious for some details not available in this sound bite version. What was the mechanism of the bad outcomes associated with antibody positivity? How many of those patients actually met criteria for HIT?

We previously knew that many cardiac surgery patients (up to 50 %!) treated with unfractionated heparin (UFH) test positive for antibodies during their perioperative course but of those only 2% develop HIT. In contrast, fewer orthopedic surgery patients treated with UFH develop antibodies but substantially more antibody positive patients in the orthopedic group develop HIT. Thus the presence of antibodies is more predictive in orthopedic patients than in cardiac surgery patients. [1]

An iceberg model has been proposed for HIT. [2] At the base of the iceberg is a relatively large number of patients who have antibodies. Toward the surface is a smaller number who develop a drop in the platelet count, and at the tip of the iceberg are those who develop thrombosis. The interacting risk factors are complex and the actual number of antibody positive patients who develop HIT seems to vary with the patient population, as the above data suggest.

Tuesday, November 29, 2005

A warning form the Infectious Disease Society of America

The Infectious Disease Society of America (IDSA) has written a white paper about the rising problem of antimicrobial resistance. Compounding the problem is an alarming trend: research and development for antibiotics is waning. After investigating the problem for over a year the IDSA concluded that antibiotic development is not profitable in today’s environment. The executive summary warns “The pipeline of new antibiotics is drying up. Major pharmaceutical companies are losing interest in the antibiotics market because these drugs simply are not as profitable as drugs that treat chronic (long-term) conditions and lifestyle issues. Drug R&D is expensive, risky, and time-consuming. An aggressive R&D program initiated today would likely require 10 or more years and an investment of $800 million to $1.7 billion to bring a new drug to market.”

The report recommends incentives such as patent extensions, liability protection, and relaxation of FDA requirements for clinical studies. It warns of emerging serious infections without effective treatments unless there is prompt action to promote antibiotic development.

Elevated troponin in non-cardiac critical illness---what does it mean?

This is a controversial situation that comes up frequently in the ICU, especially in patients with sepsis. It was the subject of a prospective study published September 28 in Critical Care. Earlier literature has suggested that elevated troponin in the setting of sepsis is associated with left ventricular dysfunction [1] [2] [3] [4] [5] and mortality [2] [6] [3] [4] [5]. These same studies demonstrate elevated troponin in close to half of sepsis patients.

In keeping with previous reports, the Critical Care paper found troponin elevation in almost half of their population of ICU patients. About half of those with elevated troponin were found to meet previously defined criteria for myocardial infarction. The new finding in this study was that among patients with elevated troponin only those meeting criteria for myocardial infarction had a worse outcome. Troponin elevation absent other criteria for MI was not associated with a worse prognosis.

Although the mechanism of elevated troponin is non-cardiac critical illness remains uncertain this study adds significantly to our understanding of the problem.

Monday, November 28, 2005

Another paper challenges metformin’s contraindications

This time it’s specifically in reference to heart failure, which is listed as a contraindication in the product labeling. As I recently blogged, the vast post marketing experience with metformin indicates that it is safe, and that lactic acidosis has been difficult to attribute to it despite widespread contraindicated prescribing.

This large observational study from Diabetes Care showed that heart failure patients treated with metformin, as monotherapy or in combination with sulfonylureas, had significantly lower rates of mortality and hospitalization than those treated with sulfonylurea monotherapy. The average follow up period was 2.5 years. The mechanism may be the alleviation of hyperinsulinemia.

The authors suggest that the strict labeling of metformin may represent unfounded concerns which have deprived patients of beneficial treatment, and challenge the precautionary principle with this statement: Although "patient safety" studies often seem to focus on finding and reducing the use of previously widely prescribed medications that are of unproven benefit or even harmful, our study should serve as a reminder that there is another side to the patient safety coin—some medications that are currently considered contraindicated may have been defined as such on the basis of little or no evidence beyond pathophysiological rationale. Since this rationale alone is considered insufficient evidence for efficacy, it should also be insufficient to declare harm. We believe that the onus in the patient safety literature should shift to acknowledge that both types of patient safety issues can lead to suboptimal prescribing practices.
Well said.

Hemostatic risk factors for arterial thrombosis

Although venous thrombophilic states have recently been well defined the hemostatic (non-atherosclerotic) risks for arterial clotting have been less clear. The topic is reviewed here in Atherosclerosis, Thrombosis and Vascular Biology. The review points out that homocysteine, fibrinogen, C-reactive protein, lupus anticoagulant and anticardiolipin antibody assays are justifiable tests. Somewhat surprisingly, in those patients with concomitant vascular risk factors, in those <55 years old, and in women, testing for factor V leiden and prothrombin mutation may be justifiable.

Saturday, November 26, 2005

More resources on CA-MRSA

[1] [2]

More evidence regarding panic disorder and heart disease

I recently posted this regarding myocardial perfusion changes during panic attacks. Now this study (Psychosomatic Medicine) suggests an epidemiologic association (almost two fold risk of coronary disease in patients with panic disorder) which is even worse if depression coexists.

Friday, November 25, 2005

The emerging threat of community acquired methicillin resistant Staphylococcus aureus

Methicillin resistant Staphylococcus aureus (MRSA) has been well known for decades as a nosocomial pathogen. More recently MRSA has been increasingly reported in the community. Community acquired MRSA (CA-MRSA) tends to present as a new strain with features which distinguish it from the more familiar nosocomial MRSA. I found this helpful review in September’s Mayo Clinic Proceedings. (The abstract is linked here. Full text open access will be available in March 2006).

Although some community isolates appear to have escaped from hospitals, the new strains (“true” CA-MRSA) arise de novo in the community. Here are some important distinctions pointed out in the review:

1) CA-MRSA has a unique genetic determinant of resistance---the type IV Staphylococcal cassette cartridge (SCC).
2) Unlike the “old” MRSA which has multiple drug resistance, CA-MRSA is typically sensitive to many non beta lactam antibiotics. Sensitivity patterns have regional variation and tend to show a typical pattern in a given region, which may be the clinician’s principal clue that CA-MRSA rather than the older strain is present.
3) CA-MRSA appears to be more virulent than other S. aureus strains, in part due to expression of the Panton-Valentine leukocidin.
4) CA-MRSA appears to have increased transmissibility and infectivity compared to other S. aureus strains.
5) Skin infections, soft tissue infections and necrotizing pneumonia are characteristic compared to other strains, and necrotizing fasciitis has been reported. Bacteremia and endocarditis are less characteristic.

Perhaps the most troubling aspect of CA-MRSA is its emergence as a cause of community acquired pneumonia. The authors state: “It is now prudent to consider CA-MRSA as an etiology of severe CAP in the correct clinical context. Severe necrotizing pneumonia with or without hemoptysis after an influenzalike illness in high-risk patients warrants therapy directed against MRSA.” The antibiotics of choice for pneumonia are vancomycin and linezolid.

Medical journals promote pseudoscience

Recently I picked on medical schools for promoting unscientific health claims [1] [2]. Today a medical journal got my attention and reminded me that the compromise of science by “mainstream” medicine is pervasive, and not confined to medical schools. What’s ironic is that the journal is BMJ, supposedly a champion of evidence based medicine. This week’s issue contains a review of the homeopathy promoting book “Passionate Medicine: Making the Transition from Conventional Medicine to Homeopathy.” Trouble is, the review is favorable to the book, giving it a four star (the highest) rating. Worse, four homeopathy promoting links are posted on the same page as the review.

BMJ has been taken to task for this sort of thing before and Quackwatch has BMJ on its list of nonrecommended periodicals.

Controversy in treatment of deep vein thrombosis

The treatment of deep vein thrombosis (DVT) has been controversial concerning prevention of the post thrombotic syndrome (PTS). Although systemic thrombolytic therapy is superior to conventional anticoagulation in restoring venous flow and preserving the function of the venous valves, it is associated with greater risk of hemorrhage and its effect on meaningful clinical outcomes has been disputed.

The hemorrhage risk of systemic thrombolysis has spurred interest in local interventional modalities including catheter directed local thrombolysis and catheter extraction techniques. This review from the American Journal of Medicine explores such techniques for the prevention of PTS and discusses the complication of venous gangrene (phlegmasia cerula dolens) which may be amenable to such strategies. It draws upon experience from the National Venous Thrombosis Registry suggesting improved health related quality of life outcomes for patients treated with interventional strategies as opposed to conventional anticoagulation alone.

The take home message is that physicians should be aware that such modalities are available and should familiarize themselves with the capabilities at their individual hospitals. Physicians should be prepared to resort to these strategies in the desperate situation of venous gangrene complicating massive DVT and consider offering the techniques to selected patients with DVT for the prevention of PTS.

The paper unfortunately did not mention that the widely accepted modality for prevention of PTS, compression stockings fitted to 30-40 mm Hg, work pretty well for this purpose.

Tuesday, November 22, 2005

More on the disruptive physician

Medscape General Medicine recently posted a provocative discussion on this topic, which I had blogged about November 5. There appears to be a burgeoning power struggle between hospital administrators (and their lawyers) and some rank and file physicians. It’s an unintended consequence of the Health Care Quality Improvement Act of 1986, which sought to protect hospital peer review. It provides immunities for hospitals in the peer review process, greatly enhancing their power to discipline physicians. Some physician groups are concerned that this has lead to abuses of peer review as hospitals, for a variety of reasons, increasingly seek to control doctors, setting increasingly narrow boundaries for behavior. A related development has been the emerging notion of the “disruptive physician.” Originally conceived with the good intention of addressing the genuine problems of incompetence and abusive physician behavior, the concept has come to be used as a pretext for stifling dissent, eliminating economic competition and abusing the peer review process.

This article and an accompanying editorial discuss the related issues of sham peer review and the abuse of the “disruptive physician” concept.

Monday, November 21, 2005

Hype versus evidence in patient safety

At last----a refreshingly sober assessment of medical errors and patient safety, here in CMAJ.

Don’t forget the thyroid in chronic urticaria

There is a high prevalence of thyroid autoimmunity in patients with chronic urticaria. The patient with urticaria and anti-thyroid antibodies may be euthyroid, hyperthyroid or hypothyroid. The mechanism of the association is poorly understood. The Thyroid and Urticaria is a review of the topic in the October issue of Current Opinion in Allergy and Clinical Immunology.

Some patients may achieve remission with L-thyroxine, which of course is indicated for those who are hypothyroid. Such treatment of euthyroid patients is not supported by high level evidence and is controversial.

Thyroid testing should be considered in patients with chronic urticaria. Knowledge of this association could help a patient and might come in handy some day on internal medicine boards.

Sunday, November 20, 2005

Irresponsible diet hype is being offered by the media

Don’t trust popular media for health information
The lay press lacks nuance and perspective in reporting on medicine and health, with the result that the consumer gets served an endless series of hyped up sound bites. These sound bites are often superficially contradictory, leading readers to wonder if medical science can make up its mind about much of anything. Nowhere is this better illustrated than in the popular coverage of diet trends.

The latest offering is this shocking headline: “Low-Carb Diet: An Alarming, New Danger.” Then, in bold type, the first sentence of the article reads “Low-carbohydrate diets may lead to dramatic weight loss, but dieters pay a big price for their thinner waistlines.” The article goes on to say that the diets lead to reduced myocardial energy storage and impaired cardiac relaxation. This is based on an Oxford University study that was apparently presented at the American Heart Association last week.

In attempting to dig deeper I was unable to find quality reporting on the study. The AHA will have some of the meeting presentations posted on the web later this month. I did find this from the British Heart Foundation, which sponsored the study. Their web page says that myocardial energy storage was measured by magnetic resonance spectroscopy. There were no clinical endpoints studied.

What’s irresponsible about the reporting is this study is far too preliminary and too low-level to warrant prime time. Specifically, the study period was all of two weeks, and the study population consisted of 19 subjects (the investigators themselves along with some of their friends and family!). Not exactly high level evidence. It’s hypothesis generating at best.

Next I did a Google news search and got this. Sure enough, the usual parade of contradictory sound bites appeared. The first few hits tell me low carb is bad (it reduces energy stores in the heart)---but, the next few headlines say it’s good for the heart (it helps improve the metabolic syndrome). So what’s the deal? Is low carb good for us? Yes and no, if you follow the popular press. Good last week, deadly today. What will it be tomorrow?

All this, of course, is rubbish. Science doesn’t move like the daily news. Its progress is gradual, with each new set of observations integrated cautiously with what was known before. There are no pat answers about low carb diets. They are probably good for some patients and bad for others. Basic research paints an enormously complex picture and suggests that it depends on one’s genetic makeup and associated risk factors.

If I were not such a passionate believer in open sharing and expression of ideas I’d be calling for a media ban at scientific sessions. I guess we shouldn’t blame them for being faithful to the interests of their stockholders. After all, hype sells.

The down and dirty on avian flu

Here’s some information from the infectious disease folks at Vanderbilt (Vanderbilt Reporter, November 4) which cuts through the hype and tells you the essentials.

Saturday, November 19, 2005

Hypertensive headache?

We were traditionally taught that hypertension is a silent killer, and that the notion of hypertensive headache is a myth. This meta-analysis in Circulation reports that antihypertensive treatment prevents headache, NNT=30, without regard to antihypertensive class. Four classes of medication with differing mechanisms of action were studied. Maybe our patients knew what they were talking about all along.

Community acquired methicillin-resistant staphylococcus aureus: what to tell the family

Many young and otherwise healthy patients are now being hospitalized with community acquired methicillin-resistant staphylococcus aureus (CA-MRSA) infections. Family members, taking notice when we place these patients on contact isolation, naturally want to know if they should take similar precautions when the patient goes home. Here’s a little blurb from Patient Care on how to counsel patients and family at discharge.

This is a big deal for a couple of reasons. First, as pointed out in the Patient Care article, CA-MRSA seems to be more transmissible than the “old” and more familiar MRSA. Worse, at least some CA-MRSA strains are hyper-virulent, associated with severe and rapidly progressive infections such as necrotizing pneumonia, due in part to the Panton-Valentine leukocidin. The issue of CA-MRSA pneumonia was reviewed in last April’s Current Opinion in Infectious Disease (subscription required).

Friday, November 18, 2005

Giant cell arteritis

Here’s a review on a must not miss diagnosis, giant cell arteritis (GCA). Of particular interest to me are the following points:

1) GCA can have unexpected late extra-cranial manifestations such as aortic aneurysm.
2) Steroids must be started as soon as the diagnosis is suspected and need not await temporal artery (TA) biopsy. Biopsy results are not affected by several days of steroid treatment. (This comes in handy if the patient presents with signs and symptoms of GCA late on a Friday afternoon).
3) Bilateral TA biopsy is sometimes necessary.
4) Combining the erythrocyte sedimentation rate with the C-reactive protein is superior to either test alone. In a population of patients undergoing TA biopsy, combined abnormal results of both tests was associated with a specificity of 97%. *

Thursday, November 17, 2005

What is the supposed mechanism of homeopathy?

Where better to find out than from its supporters? Here’s a pro-homeopathy alt med blog found via the Health Fraud List. This post from the blog outlines the “mechanism.”
Concerning the dilution of the remedy it says “Once we reach the 12C potency, according to chemical science, there should be no more physical substance left in the dilution……..Potencies above 12C work very effectively as though there was still a material substance present. Even though there is nothing left of the original physical substance, the medicine acts as though there were.” Then how could there be any biological effect? Reading on----“the vital force in the water, which now holds the impression from the original substance, acts upon the vital force of whoever takes the medicine.”

So, let’s see. The original active ingredient, though diluted so many times that no molecules remain in the water, leaves an “impression.” That impression is held in the vital force of the water, which in turn acts upon some vital force in the patient. Got it? Aren’t you glad this is supported by your tax dollars?

Wednesday, November 16, 2005

Statin use in elderly patients

Here’s a review in Clinical Cardiology with some useful perspectives on statin use. It makes a case for the safety and effectiveness of aggressive lipid lowering across the spectrum of age and risk. Keep in mind one caveat: be cautious regarding choice and dose of statin in patients on clopidogrel to prevent stent thrombosis. (I previously blogged about that here).

Tuesday, November 15, 2005

How did pseudoscience get admitted to medical school?

My recent post (scroll down) entitled “What is happening to our medical schools” took medical education to task for promoting pseudoscience. A commenter (Retired Doc) asked how this was allowed to happen and suggested in his own insightful post that it may be a form of political correctness.

Several trends over the past 15 years are at play. In his book review of the Institute of Medicine Report on Complementary and Alternative Medicine Stephen Barrett points to a subsidiary of the NIH which has poured large sums of money into the promotion of bogus claims. This funding was paralleled by an explosion of consumer interest in Complementary and Alternative Medicine (CAM) driven by the Internet. These two forces created a substantial financial incentive for medical institutions to become involved in CAM.

And although to a large extent it’s about money, it’s not entirely about money. There is also an important philosophical shift towards postmodernism, in which political correctness plays an important part. The postmodern view has influenced not only art, literature and politics, but also science. It places the individual’s internal reality above any external truth. To the postmodernist it’s not THE truth but rather MY truth and YOUR truth. It asks “Who is to say one version of truth is more valid than any other.” One can begin to see how this might lead to an eclectic view of medicine.

The movement’s influence is described in this important paper in Lancet entitled Postmodern Medicine. Author JA Muir Gray notes in the introduction that “Postmodernism is characterised by relativism, namely that there are no such things as objective facts…..” Good news there for the alt med folks. It goes on to say “Postmodernism also challenges the objectivity that science has claimed is its defining characteristic as spurious and unsupportable, and although many different theories are encompassed by the term ‘postmodernism’, a suspicion of science lies at the core of such theories.” Gray points out that postmodern medicine is driven in part by increasing regard for patient values and preferences, the rise of consumerism over paternalism and increasing concern for the unintended adverse consequences of science. These are beneficial trends to be sure, but in his defense of postmodernism Gray doesn’t seem overly concerned about its disregard for science. Citing a striking parallel to my previous commentary on the mixing of science and pseudoscience in medical schools Gray notes “The relativism of the postmodern world can be seen in Blackwells, Oxford's most famous bookshop, where evidence-based texts on gastroenterology are sold alongside a book on colonic irrigation.”

I am reminded of a conversation with an acquaintance extolling the benefits of her favorite alternative modality. As I pressed for a scientific defense she finally relented and said “well, OK, I can’t explain how it works, but I just know it works for me.” On a larger scale such thinking is behind the fallacious attempt to justify pseudoscience by citing its rising popularity among consumers. Perception equals reality in postmodern thinking, no matter the science. Postmodernism is a dangerous trend in medicine and is a driving force behind the explosion of CAM.

Saturday, November 12, 2005

What is happening to our medical schools?

Abraham Flexner is turning over in his grave.Almost a century ago Abraham Flexner, a secondary school educator, was commissioned by the Carnage Foundation to study medical education in the United States and Canada. The conclusion of the Flexner Report was scathing. Medical education was a sorry state of affairs. (Download the original report here ---large pdf file).

As a result of the report medical schools closed, others merged, and those that survived instituted major reforms. Medical education for the twentieth century and beyond was to have scientific underpinnings. The Flexner Report has since been celebrated as a pivotal document in medical education.

But what would Abraham Flexner think of medical education at the dawn of the twenty first century? Have medical schools backslidden? Sadly, medical education has forgotten some of Flexner’s warnings, as evidenced over the past decade by the increasing uncritical acceptance of unscientific teaching in the medical curriculum. This conclusion is supported both by systematic research and examples such as this uncritical homeopathy promotion by the University of Maryland Medical Center. (Thanks to the Health Fraud List for this link).

I do not oppose the right to teach or practice alternative medicine, or patients’ rights to choose it. The problem is that much of alternative medicine is a separate realm, outside the biological model. Thus it can not “complement” science based practice nor can it be “integrated” with it. Yes, it’s a free market place of ideas. The homeopath, the colonic irrigator and the herbalist have every right to compete in this market and patients have a right to choose. I would submit, however, that their practices cannot be integrated with mine. And, although medical students need to be made aware that such practices exist, medical schools should not be promoting them.

Flexner asserts precisely this notion. Let’s examine a portion of the Flexner Report concerning science based medicine. (The portion of the Flexner Report discussed here has been reproduced on this page from Homeowatch). Referring to homeopathy and other unscientific methods as “dogma” the report notes “The ebbing vitality of homeopathic schools is a striking demonstration of the incompatibility of science and dogma. One may begin with science and work through the entire medical curriculum consistently, exposing everything to the same sort of test; or one may begin with a dogmatic assertion and resolutely refuse to entertain anything at variance with it. But one cannot do both. One cannot simultaneously assert science and dogma;”. So, from this passage in Chapter X of the report comes a strong message: institutions of medical education must decide what they’re all about. Choose science or choose another path. One or the other please, not both. Clearly Flexner’s mandate left no room for “complementary” or “integrative” solutions.

Another offering from the University of Maryland School of Medicine Center for Integrative Medicine is Reiki. The course description for Reiki level II says the student will learn to “send distant healing to others as well as to past or future events.” Maybe Harry Potter should apply. In the Advanced Reiki training course the student will “learn how to use crystals and stones with Reiki and create a Reiki grid that will continue to send Reiki to yourself and others after it is charged.”

This sort of thing is going on to an increasing degree at numerous medical schools. Here’s a sampling from the University of New Mexico Health Science Center. Or, just Google up any medical school and combine a search term for your favorite alternative modality.

I hope our medical schools don’t devolve into institutes for the eclectic healing arts. In 1910 Abraham Flexner cleaned house in American medical education. By 2010 we may need him back.

Medication discrepancies at the transitions of health care

Quality improvement efforts in medication safety have traditionally focused on errors during hospitalization. In contrast, medication errors at the transitions between hospital and home have received little attention. I pointed this out before. A recent issue of Archives of Internal Medicine contains this study which found medication discrepancies between home and hospital medication lists in about 14% of patients. Risk factors for discrepancies were the number of medications taken and the diagnosis of heart failure. Discrepancies were associated with an increased risk of readmission. The Joint Commission on Accreditation of Healthcare Organizations is now focusing on this problem. Attention to this aspect of quality and safety is long overdue.

Thursday, November 10, 2005

The Thrombosis Interest Group of Canada

This is an excellent open-access resource on clinical issues in thrombosis. It contains a series of evidence based topic reviews, a summary of the ACCP conference guidelines on antithrombotic therapy and more.

Tuesday, November 08, 2005

Guillain-Barré Syndrome

I think I’ll put this article from Archives of Neurology on the must read list for hospital medicine. This nuts-and-bolts review focuses on the supportive aspects of care (if you want the latest on IVIG or plasmapharesis you’ll want to look elsewhere). In the treatment of patients with Guillain-Barré Syndrome the devil’s in the details of such things as DVT prophylaxis, pain management, respiratory care, skin care and rehab. This review, while acknowledging a lack of high level evidence, covers them all nicely. I’ve linked to the abstract but the full text is worth having. It definitely belongs in your library if you’re a hospitalist or a critical care doc.

Sunday, November 06, 2005

Learning evidence based medicine by doing

I’ve commented before on the gap between the theory and practice of evidence based medicine. New York-Presbyterian Hospital/Columbia University has developed a unique method of teaching EBM to emergency medicine residents which may help bridge the gap. A series of two hour EBM exercises has been incorporated into the curriculum. The sessions, entitled “Evidence Detectives”, consist of a case presentation followed by a supervised exercise in all the steps of EBM, including question formulation (using the PICO format), “live” on line searching, critical appraisal and article selection, and finally discussion of applicability to the case at hand.

This project, in the early stages of development, impresses me as a wonderful way to teach the essential skills of EBM. I would like to see CME workshops of this type for practicing physicians.

In order to carve out time for the sessions some of the more traditional aspects of the curriculum were cut, with elimination of the traditional journal club and less time for didactics. (The elimination of the journal club concerns me. I’ve already blogged on the importance of “background reading”).

The project was reported in a recent issue of Academic Emergency Medicine.

Saturday, November 05, 2005

Are you a disruptive physician?

The phrase “disruptive physician” has been bandied about at medical staff meetings lately. Apparently, most hospital medical staffs have provisions in their bylaws for sanctioning physicians deemed to be disruptive irrespective of their clinical competence. I’ve always been a bit uneasy about this, since any behavior or opinion someone else (such as a nurse or an administrator) finds objectionable could be categorized as disruptive.

Of course there are occasional examples of physician behavior clearly detrimental to patient care such as intoxication, sexual impropriety and threatening or intimidating behavior so severe as to preclude an effective working relationship among staff. Such episodes require an organized, explicit institutional response. The notion of a disruptive physician policy to deal with these situations is sound. But how do you define disruptive behavior? Greg Piche in his Health Care Law Blog recently remarked “The definition of what constitutes disruptive behavior in most of these policies is left so inordinately broad and so diaphanously vague as to render them effective tools for silencing responsible criticism….” His examples of behaviors that could be considered disruptive are concerning; having a disagreeable personality or willingness to speak out against the administration could perhaps result in a disciplinary proceeding.

So this concerns me. Although the original notion of a disruptive physician policy may be valid it could have the unintended consequences of stifling original thought and dissent. This editorial from the Journal of American Physicians and Surgeons warns about abuse of the concept. Please read the whole article, particularly the little ditty at the end.

Disclosure: I have occasionally bumped heads by playing the medical staff curmudgeon role.

Friday, November 04, 2005

The list of drugs that prolong the QT interval and cause torsades de pointes

is growing so rapidly that clinicians need help in keeping up. Here’s a useful resource: The Center for Education and Research on Therapeutics at the University of Arizona Health Sciences Center, spearheaded by Raymond L. Woosley, MD, PhD Vice President for Health Sciences there. Dr. Woosley has an extensive background on the clinical pharmacology of antiarrhythmic drugs. The site is a frequently updated listing of drugs that cause or increase the risk of TDP. The lists are categorized according to degree of risk and strength of recommendation.

Thursday, November 03, 2005

Under diagnosis of alpha 1 antitrypsin deficiency

A survey in the September issue of Chest reminds us that we are under diagnosing alpha 1antitrypsin deficiency (AATD). The study of 1020 patients with AATD revealed an average of 8.3 years from symptom onset to diagnosis. 20% of patients went through four or more physicians before being diagnosed. Timeliness of diagnosis did not improve between 1968 and 2003.

AATD is easy to diagnose, so why are we doing so poorly? Clinicians under appreciate the fact that AATD can be present in any patient with COPD. It is not, as popularly believed, confined to the rare non-smoker with emphysema or to those patients with primarily lower lobe disease. Moreover, it may not be widely known that current guidelines cast a broad net for screening patients for AATD. In reviewing this topic I was surprised to learn that the World Health Organization, the American Thoracic Society and the European Respiratory Society recommend that ALL patients with COPD be tested for AATD.

The joint statement of the American Thoracic Society/European Respiratory Society was published in the American Journal of Respiratory and Critical Care Medicine in 2003. Here is a partial list of patients for whom screening was definitely recommended (type A recommendation):

1) Symptomatic patients with a diagnosis of emphysema or COPD
2) Patients with asthma whose pulmonary function does not completely normalize after aggressive treatment
3) Individuals with unexplained liver disease
4) Asymptomatic patients with persistent obstruction on pulmonary function tests with known risk factors
5) Adults with necrotizing panniculitis

Wednesday, November 02, 2005

Panic attacks---not so benign

They may be bad for your heart (American Journal of Cardiology).

COPD and cardiovascular disease

Two recent offerings from the medical literature suggest an association between COPD and cardiovascular disease that may be under-appreciated. In this study from Chest patients with COPD had twice the rate of hospitalization for a composite of cardiovascular outcomes, adjusted for pre-study cardiovascular risk factors. The follow up period was just under three years.

This paper from the European Heart Journal reports unrecognized heart failure in 20% of patients with stable COPD. Approximately half the heart failure cases had systolic left ventricular dysfunction and half had primarily diastolic dysfunction. Surprisingly, none had right sided heart failure. The authors suggest that right sided failure is characteristic of more advanced COPD than was represented in this study. The reasons for the association may be both physiologic (e.g. ventricular interdependence) and epidemiologic (overlapping risk factors, particularly smoking).

Monday, October 31, 2005

The pioglitazone controversy continues

Pioglitazone (Actose) and rosiglitazone (Avandia) are members of the thiazoladinedione (TZD) class of oral medications for type 2 diabetes. These agents have been surrounded by controversy because their predecessor in the TZD class, troglitazone (Rezulin), was withdrawn from the market because of liver toxicity. Although their beneficial effects on metabolic risk factors for macrovascular disease have long been known, outcome based data regarding protection against such events have been lacking until very recently and the Public Citizen Health Research Group has placed TZD drugs on its “do not use” list.

Recently the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events) demonstrated the efficacy of pioglitazone in preventing macrovascular events. I blogged it here following presentation of the results but shortly after the announcement and before final publication a BMJ opinion piece was harshly critical of the study. My response to the BMJ commentary is here.

Now PROactive has been published in Lancet October 8 along with a commentary by Hannele Yki-Järvinen. Unlike the BMJ editorial the Lancet commentary acknowledges the clinical benefit of pioglitazone in decreasing macrovascular events. The major controversy about the PROactive results concerned the lack of statistical significance for the primary outcome and reliance on the secondary outcome. But Yki-Järvinen points out that inclusion of procedure related endpoints in the primary outcome could have biased the results against pioglitazone and implies (as I said before) that the primary outcome would have reached statistical significance with a longer follow up period, as the curves were diverging at study’s end. The commentary poses questions about the clinical significance of the increase in heart failure and how it might counterbalance the improvement in vascular outcomes.

So is it time for Public Citizen to change its “do not use” recommendation? They defend the recommendation on the basis that the TZDs “may be less effective than other drugs for diabetes and cause liver damage, weight gain, anemia and heart failure.” PROactive and other evidence suggests that this statement may be unfounded. How can the question of effectiveness of TZDs compared to other agents be answered? Because different classes of medication for diabetes have mechanisms of action which are complementary to one another it may be simplistic to ask whether one class of agents is as effective as another. It now appears that pioglitazone can join metformin as another agent capable of improving macrovascular outcomes. As for liver damage, none was found in PROactive. Weight gain (4 kg more than placebo) was seen, but the clinical significance is unknown and anemia was not mentioned. The problem of heart failure remains troubling although no new heart failure concerns were raised by the study.

Friday, October 28, 2005

Why is Alzheimer’s disease getting all the attention?

This study published in Radiology, evaluating structural changes and cerebral blood flow in elderly demented patients compared with age-matched cognitively intact individuals, found reduced cerebral blood flow in the demented patients suggesting that vascular disease is an important factor in dementia in the elderly. We’ve gone through phases in our understanding of dementia. In the nineteenth century dementia was synonymous with general paresis of the insane, later understood to be caused by syphilis. A half century ago dementia was widely believed to be primarily a vascular disease, leading to a proliferation of vasodilators such as ergoloid mesylates, cyclandelate, and papaverine, none of which worked. More recently we’ve better appreciated Alzheimer’s disease. Does the article in Radiology bring us full circle with regard to “vascular dementia?” No, but it suggests that perhaps our emphasis on Alzheimer’s disease has lead to an under appreciation of vascular mechanisms. Here’s info on multi-infarct dementia and Binswanger’s dementia.