Derm emergencies

Reviewed in CMAJ. One of the references is to a review of hereditary angioedema.

More mainstream medical dabblings in pseudoscience

This time it’s the University of Minnesota department of CME teaming up with the American Board of Holistic Medicine. Their recent Integrative Holistic Medicine course featured Chi Gong, homeopathy, Native American Medicine, Traditional Chinese Medicine, Ayurvedic Medicine and much more. The course schedule speaks for itself.

More data on the benefits of preoperative statin use

Reported here in the International Journal of Cardiology.

Add one to the list of cardiac channelopathies

First there was long QT syndrome. Then in the late 80s we had Brugada syndrome. Now there’s short QT syndrome (reviewed in CMAJ). This is another must-not-miss electrocardiographic diagnosis. Three mutations have been characterized so far, all of which increase conductance through the potassium channel, thus shortening repolarization. The patients have high risk of sudden cardiac death from ventricular arrhythmias. An interesting and characteristic association is a high incidence of paroxysmal atrial fibrillation in patients or their families. The only treatment at present is device therapy, although investigations are ongoing with drugs that prolong the QT.

Help fund your own alternative medicine research

Take the Randi challenge. If your health claim is implausible in the known biophysical model, provide convincing proof and collect a million bucks. Eligible theories include homeopathy, chiropractic healing (other than bone and joint problems), therapeutic touch, Qi Gong, reflexology and applied kinesiology. The bucket of money started small in 1964 and is growing. No one has collected yet.

Sally Satel on SSRIs and suicide

Psychiatrist and author Sally Satel comments on the American Journal of Psychiatry report refuting the notion that antidepressants cause suicide. She notes “This is a paradigm case for why the FDA needs a flexible risk management strategy that focuses more on helping doctors and patients make nuanced decisions based on evolving science, rather than blanket warnings that can cloud the real issues at stake.” The article is worth the read.

Oxygen transport in critical illness

These two articles in November’s Chest belong in the libraries of hospitalists and critical care specialists. [1] [2] They outline theory, practices and controversies concerning oxygen delivery.

Medical searching secrets

Told by Mohammad Al-Ubaydli in this article from PLOS Medicine. Although Google medical searching has been well covered by the med bloggers I found some new tips here. There’s also good information about some of the other search engines and a caveat: handy as Google is it lacks the precision of Pub Med. Pub Med’s a must if your search has to be comprehensive, or if you need to know exactly how the search was executed. Ovid Medline works similarly but it’s not free.

And speaking of conflicts of interest-----

The country’s most popular alt med guru may have a few of his own. Though receiving far less publicity than mainstream docs and Big Pharma it has been exposed by the Center for Science in the Public Interest and is covered here and here. Thanks to the Health Fraud List for the links.

Medical professionalism and Big Pharma

An article in today’s JAMA received heavy coverage in the media and around the blogosphere. (Via DB’s Medical Rants). The authors, concerned that the pharmaceutical industry corrupts medical ethics, want stringent regulations. My first read was the New York Times coverage which hypes the issue in the opening paragraph: “The free gifts, drugs and classes that pharmaceutical and medical device makers routinely give doctors undermine good medical care, hurt patients and should be banned, a group of influential doctors say in The Journal of the American Medical Association.” (Italics mine). So--- pens, note pads, drug samples and sponsored CME activities hurt patients! The JAMA authors, to their credit, said no such thing. And, as I have blogged previously, there’s not a shred of evidence to support that assertion.

I agree with some of the points in the JAMA article. However the authors are inconsistent on their position concerning conflict of interest. Out of concern for conflict of interest they argue for elimination of small gifts yet acknowledge the token nature of such gifts under existing regulations.

They assert: “Arguably, the most challenging and extensive of these conflicts emanate from relationships between physicians and pharmaceutical companies and medical device manufacturers.” Yet, as Health Care Renewal pointed out today, our profession is faced with many conflicts of interest other than those created by the pharmaceutical industry. Perhaps the most pervasive, at least in primary care, is the perverse financial incentive to spend less time with individual patients due to an ill conceived compensation system, as recently pointed out by DB.

Finally, I think their restrictions on CME support are ill advised. I’m afraid if they have their way we can say good bye to Medscape, emedicine, and CME as we now know it.

Evidence based mechanical ventilation

For years technological advances in respiratory care have outpaced clinical evidence, resulting in a confusing array of opinions about the best way to deliver and “wean” from mechanical ventilation (MV). But evidence based medicine is here, enabling a systematic approach. This approach is nicely summarized in a review by Neil MacIntyre in the November issue of Chest. The article is worth reading in the original. A few summary points are made below.

The review pertains primarily to acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) but many of the principles are applicable to other forms of respiratory failure. MV itself can injure the lungs, a concept known as ventilator induced lung injury (VILI). There are two well known mechanisms of this injury: volutrauma (over distension of alveoli) and atelectrauma (alveolar shearing caused by repetitive opening and closing of marginal or “recruitable” alveoli). These mechanisms of injury suggest a rationale for the prevention of both forms of VILI by maintaining tidal ventilation between the lower and upper inflection points of the pressure volume curve. Theoretically this means utilization of low tidal volumes combined with high levels of peep designed to recruit alveoli. However, somewhat surprisingly, only one of these strategies—low tidal volumes—is supported by high level clinical evidence. As for the use of peep, the best approach may be that outlined by the ARDS net peep scale.

The current synthesis of evidence also enables a systematic, almost algorhythmic, approach to discontinuation of MV. The process of discontinuation has traditionally been termed “weaning”, a misconception, since it implies that liberation from mechanical ventilation is done gradually. This concept was the basis for the now outmoded approaches of gradual reduction in levels of pressure support or frequency of machine delivered breaths in the SIMV mode. (Patients with poor cardiovascular reserve may occasionally constitute an exception to the rule that true weaning is not necessary. Because resumption of spontaneous breathing is a cardiovascular stress, patients with marginal reserve may experience ischemia and pulmonary edema upon abrupt withdrawal of ventilatory support. That issue is addressed briefly in another review in the same issue of Chest).

The process has two phases, the first of which consists of clinical assessment for readiness, and which should be done daily. The criteria that must be met are 1) evidence of stabilization and/or improvement in the original disease process; 2) blood gas parameters reflecting PO2/FiO2 > 150, peep level of less than 8, FiO2 less than 0.5, and ph greater than 7.25; 3) hemodynamic stability; and 4) ability to make an inspiratory effort. This assessment must also take into account the patient's general condition and neurologic status.

Once those criteria are met the patient may be considered for advancement to the second phase, the spontaneous breathing trial, which can be done with the patient on a T-tube, C-pap, or pressure support. If the patient maintains a frequency/tidal volume ratio under105 over the first several minutes, the trial is continued for 30 minutes to 2 hours. Tolerance of the period of spontaneous breathing without adverse clinical signs generally indicates readiness for withdrawal from MV, tempered by clinical judgment. Patients who fail the trial should have their disease process, nutrition, pain control, fluid balance and overall management reviewed and breathing trials repeated as appropriate.

Hyponatremia, hypokalemia and thiazide diuretics, part 2

Click here for part 1.


“Thiazide diuretic prescription and electrolyte abnormalities in primary care”, published in the January issue of the British Journal of Clinical Pharmacology, has several important lessons on the use of thiazides. Thiazide induced hypokalemia is generally known to be dose related, and the better safety profile with chlorthalidone in ALLHAT compared to MRFIT is believed to reflect the lower doses used in ALLHAT. However, low doses of thiazides were used in the current British study. No patient whose electrolyte disturbance was categorized as severe exceeded the usual starting dose of the thiazide, and 75% of patients with severe disturbances received only half the starting dose. So, while lower doses of thiazides are safer they do not eliminate the problem. Unfortunately the British study does not address mortality, nor does it tell us how many patients were hospitalized as a result of electrolyte disturbances.

Hyponatremia deserves special mention. Unlike hypokalemia, thiazide induced hyponatremia is less predictable. It appears to be an idiosyncratic reaction. This complication of thiazide treatment can have severe clinical consequences: lasting neurologic sequelae and deaths have been documented. This is the subject of a fascinating editorial from last August’s issue of Nephrology Dialysis Transplantation which reviews several unique clinical characteristics and risk factors for the syndrome. The principal mechanism of thiazide induced hyponatremia is probably not mineral depletion. There is evidence to suggest that thiazides promote retention of free water by up regulation of aquaporin channels in the renal collecting ducts.

While the British study informs us about electrolyte disturbances we desperately need data on the frequency with which such disturbances lead to clinical consequences. Such information is elusive in the case of hypokalemia given the difficulty in knowing the prevailing potassium concentration at the time of sudden cardiac death. The link between severe hyponatremia and neurologic sequelae is more easily established. Although multiple instances have been documented in the literature we don’t know the true frequency because we lack a denominator. Clinical events related to electrolyte disturbances, though they must have occurred, were not reported in ALLHAT.

These observations have implications for clinical practice and research.

1) As DB pointed out, electrolytes should be monitored regularly in patients taking thiazides.
2) Because thiazide induced hyponatremia is idiosyncratic and may occur early, the first electrolyte panel should be obtained within two weeks of the start of treatment.
3) Though normal electrolyte levels would seem a reasonable goal for most patients this recent paper from the Journal of the American College of Cardiology suggests that for patients with underlying heart disease normal is not enough. The authors recommend a potassium target of 4.5.
4) If the data are available the ALLHAT investigators should report the frequency of clinical sequelae and hospitalization related to thiazide induced electrolyte disturbances.

Defending scientific medicine

I have blogged critically about alternative medicine. This post is driven by readers’ comments. They follow several general themes to which I offer this response.

They laughed when researchers claimed a bacterial infection could cause ulcers. Those researchers just won the Nobel Prize.
Several readers made this point after I criticized “research” that was not based on biologic plausibility. This premise, that the mainstream rejected the bacterial theory, is false. A Pub Med search yields a spate of favorable articles within several years of the 1983 Helicobacter paper. There’s a distinction to be made. The notion of a bacterial cause of peptic ulcer was novel but not implausible. Furthermore it had an evidentiary basis. (Those researchers could actually look in the microscope and see the critters inhabiting the stomach lining). Contrast that with homeopathy---the idea that once all molecules are diluted out of solution a force is left behind which imparts clinical effects. I would be the first to urge research funding for homeopathy if there was even a shred of evidence that such a force exists. If it’s powerful enough to cure multiple ailments why hasn’t it been measured in the more than 200 years since Samuel Hahnemann advanced the theory? Wouldn’t it alter the physical properties of water in some way---maybe alter the electrostatic charges or the hydrogen bond configuration? I think the folks at MIT would have demonstrated something by now.

Mainstream medicine ignores the psychosocial dimensions of health and disease.Moof said it well: “I think that the reason the general public is so keen on that sort of thing is because the pseudo-scientific 'medicines' are more in the business of connecting with people on an emotive level than they are on a medical level. To counter this, serious medicine may have to try a bit harder to relate to more than just the physical aspects of illnesses.” Although a scientific underpinning doesn’t preclude an emotional connection doctors, for a variety or reasons, don’t spend enough time with patients. The unfortunate consequence is that alternative practitioners have hijacked the concept of “treating the whole person.”

Mainstream medicine doesn’t have all the answers.Of course not. Tune up your baloney detector and run from any medical system that claims to have all the answers.

Mainstream medicine is just following the money.
That’s partially true, and maybe it’s why the mainstream increasingly embraces quackery. It sells.

If patients think it works, what’s the harm?Patients have the right to choose. They are and should be free to go to the local herbalist or purchase the latest colon cleanse remedy. It’s quite another thing for us in the mainstream to endorse invalid methods. We claim to base our practices on good science and that’s what the public expects of us. If we accommodate unscientific practices through some sort of “integration” we endorse those practices, either explicitly or implicitly. Our science then becomes pretense. That’s pseudoscience. It betrays the public’s expectation and is, in my opinion, unethical.

Arnold Relman versus Andrew Weil

April 9, 1999 marked a defining moment in the alt med controversy. The future of “integrative medicine” was the subject of a debate between Arnold Relman, editor emeritus of the New England Journal of Medicine and Andrew Weil, director of the University of Arizona program in Integrative Medicine. A partial transcript of the debate was published several months later in the Archives of Internal Medicine. Relman took the skeptical side, arguing that pseudoscience and mysticism cannot be meaningfully “integrated” with Western science.

Now you can watch the debate in its entirety here (scroll to April 9, 1999 and choose Real Player or Windows Media Player format). It was recently posted at the Video Archives of the University of Arizona. (Gotta go with Relman on this).

A verbal spanking from Jacob

My remarks on alternative medicine evidently pushed some buttons. Jacob of Family Medicine Notes commented on yesterday’s post: "You are joking right? These people are doing research. I don't get why you would discount something just because it is not mainstream big-pharma funded. If a well-researched alternative to the traditional treatments turns out to be effective - I would call this SCIENCE .. and your knee-jerk rejection of all things "integrative" to be the pseudo-science. Shame on you!"
Wow. Where to begin. Jacob reminds us that research is being done. I acknowledge and applaud high quality research in CAM. Note the proviso high quality. If, for example, the large NIH sponsored placebo controlled chelation therapy trial demonstrates benefits for patients with coronary artery disease I’ll accept chelation as something that works. Mainstream or not the real distinction is between health claims which have been scientifically proven to work and those which have not.

Other notions proffered for “research” are, in my considered opinion, exercises in pseudoscience---attempts to validate claims that have been debunked and have no biologic plausibility. What’s the point of looking for clinical effects of energy fields undetectable by instruments of physicists and Star Wars forces left behind in water after active ingredients are diluted out?

A strict empiricist might object to my requirement of biologic plausibility, but I maintain a line must be drawn. Otherwise we might as well burn the chemistry and physics books and study every claim that comes along. Why stop with Therapeutic Touch, Homeopathy and Reiki? Let’s go on down the slippery slope and fund studies of astrology, telekinesis and shamanism. And while we’re on the subject of energy medicine why not resurrect Franz Mesmer’s theory of animal magnetism? If only we do enough research his claims will surely be validated. (Discredited in the 18th century, Mesmer would likely be on faculty at a medical school today).

But it’s not so much the research I criticize as the uncritical promotion of baseless methods. Jacob thinks I'm pseudoscientific. Is it pseudoscientific to be skeptical, ask questions or require proof? Having now elaborated on the basis for my objections I hope Jacob and other readers will not regard my opinions as knee-jerk. Finally, I’m afraid I’m missing Jacob’s point about big-pharma funding---it hasn’t entered into my opinions on pseudoscience.

If it seems I’m beating the drum on pseudoscience, I have a distinct purpose: exposure. People who expect institutions of medical education and health care to be based on rigorous science and intellectual integrity need to know what’s going on. Or maybe I’m just full of negative energy.

Pseudoscience promotion by hospitals

Memorial Herman Katy Hospital is hosting a workshop this week on ancient healing methods. Participants will be taught “how to use sound and movement to cleanse and recharge the internal organs of stagnant energy, standing meditation and other postures that drive qi or ‘pure energy’ through the bones, increasing strength and balancing the immune system.”

Exercise and dementia

Here’s the primary source for my recent post on this subject.

Medical school pseudoscience is pervasive

When I first began researching the antiscientific agenda in medical education I thought it was confined to isolated examples popping up here and there. I was wrong. It’s become organized. There’s a consortium of academic medical centers pushing for more pseudoscience in the curriculum. Is your favorite med school on the list?

Hyponatremia, hypokalemia and thiazide diuretics, part 1

DB of DB’s Medical Rants recently posted a discussion of a study highlighting hyponatremia and hypokalemia in patients taking thiazides. The metabolic effects of thiazides have long been controversial and this paper adds to our understanding of the problem. My interest in the topic of thiazide safety was piqued by the controversies in the field of hypertension in the wake of ALLHAT. DB’s post prompted me to review the literature.

Although the true magnitude of the metabolic consequences of thiazide diuretics is not known it is likely to be increasing with heavier use of the drugs following the publication and promotion of ALLHAT. Upon release of the ALLHAT results an aggressive media campaign, which pushed thiazide diuretics, was launched. Less than a year later the boosters of ALLHAT announced plans (Lancet, subscription required) to enlist hundreds of doctors as a sales force and train them in the techniques used by drug companies to market products. The goal was to get out the message that thiazides should be the “first step” drugs for most patients in hypertension treatment. A recent increase in the thiazide market share suggests that the message was effective.

The message recommended a stepped care approach to hypertension similar to one popularized decades ago, which was used for the intervention group in the Multiple Risk Factor Intervention Trial (MRFIT). That study, published in 1982, was important because it first raised awareness of the metabolic hazzards of thiazides. In a subset of the MRFIT cohort (patients with electrocardiographic abnormalities) thiazide use was associated with sudden cardiac death. It was believed to be due to hypokalemia and perhaps activation of the renin angiotensin system.

Starting in 1982 the rate of thiazide prescribing began to decline. Although this finding has been spun to reflect on industry promotion of newer more expensive brands of antihypertensives, the new safety concerns raised by MRFIT undoubtedly had a negative impact on thiazide use. (In 1982 the only angiotensin converting enzyme inhibitor available was captopril. Although three calcium channel blockers were being marketed at the time for angina and arrhythmias, none were yet approved for hypertension).

Subsequent studies such as the SHEP trial suggested a better safety profile for thiazides as did ALLHAT. But the latest article cited by DB suggests the pendulum once again swinging towards heightened safety concerns. The paper appeared in the January issue of the British Journal of Clinical Pharmacology, and an open access full text version is available here.

In part two I will review this paper in some detail and discuss practical clinical implications of the metabolic hazards of thiazide diuretics.

Hygienic measures to avert dementia

Gardening, walking and modest alcohol intake according to this Australian study.

And, just today emedicine reports a soundbite version of a study due out in tomorrow’s Annals of Internal Medicine with similar implications.

Evidence based medicine--- old ideas recycled

It’s widely believed that evidence based medicine is a new idea. I’m not so sure. Although the general view is that the concept originated with Gordon Guyatt in 1992 I found something interesting in the almost century old Flexner Report (large pdf download).

The promoters of EBM say we need to replace dogma with evidence, tradition with science and physiologic assumptions with empiric observations. They tell us that old practice patterns need continual re-evaluation in the light of new evidence.

Great new ideas, right? Well, page 156 of the Flexner Report says-- “The modern point of view may be restated as follows: medicine is a discipline, in which the effort is made to use knowledge procured in various ways in order to effect certain practical ends. With abstract general propositions it has nothing to do. It harbors no preconceptions as to diseases or their cure. Instead of starting with a finished and supposedly adequate dogma or principle, it has progressively become less cocksure and more modest. It distrusts general propositions, a priori explanations, grandiose and comforting generalizations.” So this, Flexner’s view of the scientific basis of medicine, reads like a defense of EBM today.

A few sentences later Flexner issues a plea for evidence in medicine stating “It wants not dogma, but facts.” And, sounding again like an EBM apologist he says this concerning bias and conflict of interest in research: “The sectarian, on the other hand, begins with his mind made up. He possesses in advance a general formula, which the particular instance is going to illustrate, verify, reaffirm, even though he may not know just how. One may be sure that facts so read will make good what is expected of them; that only that will be seen which will sustain its expected function; that every aspect noted will be dutifully loyal to the revelation in whose favor the observer is predisposed: the human mind is so constituted.”
Another supposedly new tenet of EBM is the destruction of medical myths. But Flexner long ago recognized the hazard of medical myth: “Scientific medicine therefore brushes aside all historic dogma.” Finally, we all know how EMB decries reliance on experts. Flexner anticipated the problem, declaring “No man is asked in whose name he comes—whether that of Hahnemann, Rush, or of some more recent prophet. But all are required to undergo rigorous cross-examination.”
In these prescient words of Abraham Flexner we read the principles of EBM articulated some 95 years ago. (The full Flexner report is an interesting read, but long. A more easily accessible html page containing the section of the report referenced above can be found in this article from HomeoWatch).

Is it OK to give cardioselective beta blockers to patients with COPD?

This Cochrane review, which looked at studies using single doses or longer durations of administration, says yes. The beta blockers did not affect the patients’ symptoms, spirometry measurements or their response to bronchodilators.

Examples of cardioselective beta blockers include atenolol, metoprolol, esmolol, bisoprolol and acebutolol. Propranolol, timolol, carvedilol, labetalol and sotolol are non-selective beta blockers.

As I posted previously there is considerable overlap between COPD and cardiovascular disease so that many patients with COPD could obtain cardiovascular benefits from beta blockers. This review suggests that we should not consider them contraindicated in patients who need them for cardiovascular disease. I would caution that cardioselectivity is not absolute, and cardiovascular benefit is often obtained at higher dose ranges in which selectivity is lost. These conclusions should not be applied to patients with asthma.

Grand Rounds (the traditional kind)

You can view the web casts of many of them. Here are the video archives of the NIH Clinical Center and here are the ones from the University Of Arizona Department Of Medicine. The December 14 session at Arizona is about Avian flu.

Another useful avian flu resource

A concise review in CMAJ provides more useful information on avian flu. It briefly sketches the history of the infection since the 1997 outbreak in Hong Kong. Unique clinical features are primary viral pneumonia (as opposed to secondary bacterial pneumonia more characteristic of ordinary flu) and the occurrence of severe infections in young healthy hosts. Unique features of influenza promote genetic shift: 1) the lack of a proofreading mechanism during replication, thus allowing easier mutation and 2) organization of its RNA in the form of 8 separate strands which enables swapping of genetic material between strains when co infection occurs.

Is there evidence that we are actually moving toward a pandemic? The article cites evidence from observations of animal infections that the virus may be changing. The significance of these observations concerning the risk of a pandemic is far from clear. Links to WHO guidelines for infection control and treatment of avian flu cases are provided.

Hepatitis C—a multisystem disease

The extrahepatic manifestations of hepatitis C were reviewed in the November issue of Cleveland Clinic Journal of Medicine. The review points out that cryoglobulinemia is the most strongly associated manifestation. Most cases of what was formerly called essential mixed cryoglobulinemia are in fact due to hepatitis C. Most patients with circulating cryoglobulins are asymptomatic, with about 10% manifesting the typical features of purpura, arthralgia, renal disease and neuropathy, according to the review.

Other disease associations mentioned were Sjogren syndrome (an autoimmune exocrinitis differing from classic Sjogren syndrome in the lack of antibodies to SSA/Ro and SSB/La), lymphoproliferative disorders, prophyria cutanea tarda and membranoproliferative glomerulonephritis (which can occur with or without cryoglobulinemia).

Antiviral treatment for the underlying hepatitis C seems to be the most effective treatment for cryoglobulinemia and some of the other manifestations.

American Medical Massage Association takes firm stand against fringe massage therapy

Pseudoscience is rampant in the field, and AMMA has had enough.
Their position is outlined here. Fringe methods are rampant in the massage community and take up between 20% and 65% of the curriculum in message schools. According to the document “Some subjects taught in massage schools and practices of the general massage community are so extreme in nature as to constitute health care fraud.” Among the methods condemned by AMMA are metaphysical practices such as Reiki, Polarity Therapy and Therapeutic Touch. Others mentioned are those that have no rationale in known physiology such Myofacial Release.

Now why don’t the American Medical Association, the American College of Physicians and the Association of American Medical Colleges have the courage to take a similar stand?

Which CT protocol for appendicitis?

A systematic review in the American Journal of Surgery compared various combinations of oral, rectal and IV contrast for CT scanning to evaluate patients for appendicitis. All protocols performed well including imaging without oral, rectal or IV contrast. The authors believe a prospective comparative trial is needed.

A related commentary in Internal Medicine News mentions some caveats, suggesting that increased experience in interpretation may be necessary for non contrast exams, that non contrast imaging is particularly challenging in lean individuals and that non contrast exams sacrifice some ability to detect other pathology that may cause pain.

This information could prove useful for those patients with possible appendicitis in whom contrast administration is contraindicated.

Goodpasture syndrome and Spanish Flu

There is an under appreciated historical connection between Goodpasture syndrome and the 1918 pandemic (Spanish) flu. We are traditionally taught that Goodpasture syndrome is a pulmonary-renal syndrome characterized by pulmonary hemorrhage and rapidly progressive glomerulonephritis due to antiglomerular basement membrane (anti-GBM) antibodies. But “Goodpasture syndrome” is a misnomer. The patient with pulmonary and renal disease described by Ernest Goodpasture in 1919 (Goodpasture EW. The significance of certain pulmonary lesions in relation to the etiology of influenza. Am J Med Sci 1919;158:863-70) was presented as a case of influenza and probably did not have anti-GBM disease. Yet the myth of Goodpasture syndrome persists. It was a particularly unfortunate misattribution because it diverted attention from Goodpasture’s most monumental work at Vanderbilt in 1931, the development of a chick embryo technique for viral culture. Although this ground breaking work spurred a revolution in virology and brought fame to the Pathology department at Vanderbilt, [1] over time it tended to be forgotten, being overshadowed by the eponymic association with anti-GBM disease.

The story of Ernest Goodpasture, pandemic influenza and anti-GBM disease is controversial and seems to vary with every telling. Perhaps the most reliable account can be found in the biography by Robert D. Collins, “Ernest William Goodpasture—Scientist, Scholar, Gentleman.” On pp. 64-67 we find Goodpasture in the Navy Medical Corps in 1918-19, stationed at the Chelsea Naval Hospital near Boston. There he was responsible for performing autopsies of victims of the influenza pandemic. Because many patients with the disease developed secondary bacterial pneumonia it was widely believed that influenza had a bacterial etiology. But Goodpasture postulated a viral etiology and believed that the primary etiologic agent could cause pneumonia. Therefore he was interested in finding cases of influenza pneumonia with negative bacterial cultures. Two such cases formed the basis of his 1919 paper. One of the two was described as unusual in that while the pulmonary pathologic findings were consistent with influenza the pulmonary hemorrhage was profuse and glomerular inflammation was found. It is unclear what underlying disease other than influenza this patient may have had. Attempts to retrieve the slides from Chelsea years later for further study were unsuccessful. According to Collins, Goodpasture did not approve of the association of his name with this syndrome. He writes “In this case, good intentions---recognizing Dr. Goodpasture---paved the road to inaccuracy and inappropriateness.”

And so, with apologies to Paul Harvey: Now you know the rest of the story.

AMSA and PharmFree

A commenter gently cautioned me against the ad hominem fallacy in my recent blog post on this topic. He wrote: “I just wanted to state the point of view that although AMSA may not be the best practitioner of its message that should not take away from the validity of the message.” Regular readers of this blog know my view of the message, which is about the relationship between physicians and the pharmaceutical industry. While I agree partially with their concerns I think the position of PharmFree and organizations like No Free Lunch is extreme. I have expressed a more moderate view in the pages of this blog, filed under the Medicine and Public Debate category.

Although the commenter correctly points out that PharmFree should be judged on its own merits, he may have missed my larger point. The AMSA seems to be claiming the moral high ground in matters of ethics, evidence and doing what’s best for patients. But the claim is baseless when they actively promote bogus (and in my opinion fraudulent) health claims. Moreover, they accuse the profession of engaging in conflicts of interest when they themselves accept money in return for distributing promotional material from an organization which advocates shamanism, ritual healing and New Age fluff. So, it kind of ruffles my feathers when they point the accusing finger and besmirch the ethics of the medical profession. This inconsistency also begs the question of motivation: what is the real agenda of PharmFree?

Is it any wonder so many consumers flock to alternative medicine?

It seems folks will believe anything if it has the trappings of science. Here’s a study of credulity in action.

Should residency programs accept support from pharmaceutical companies?

A point-counterpoint appeared in Skin and Allergy News. Dr. Raymond Comelison Jr., chief of dermatology at the University of Oklahoma and past president of the American Academy of Dermatology says yes, in some circumstances. Dr. Jeffrey Meffert, staff dermatologist at Wilford Hall Air force Medical Center says “just say no”, regardless of the circumstance.

I agree with Dr. Comelison. It is unfair to paint all industry supported activities with the same brush. There is extreme variation in quality. At one end of the spectrum are events amounting to little more than infomercials for a single product. These drug company dinners and junkets of low educational value are easy to spot. Both discussants agree that such activities are not of value. But drug companies also provide support for academic programs to send house staff to high quality CME offerings at national specialty organizations. Here the discussants disagree, and Dr. Comelison points out that if pharmaceutical support disappeared far fewer residents would be able to attend such meetings.

Most would agree with the need for caution in accepting industry support. Dr. Comelison applies the maxim “everything in moderation.” While increasing numbers of people subscribe to Dr. Meffert’s position, it is simplistic and extreme.

AMSA claims to take moral high ground

The American Medical Student Association’s PharmFree campaign was featured in USA Today. The campaign encourages doctors and medical students to distance themselves from the pharmaceutical industry by refusing to accept gifts or support from drug companies. They say it’s all about ethics, evidence and doing what’s best for patients. But, as I have recently demonstrated, [1] [2] this grandstanding belies an agenda which promotes pseudoscience and bogus health claims.

It’s also supposedly about conflicts of interest. Says the USA Today article: “Behind the modest rebellion is the belief that taking gifts from drug companies creates a conflict of interest for doctors. The argument: To accept handouts is to feel indebted, and doctors indebted to drug firms may not be prescribing medicines based solely on what's best for their patients.” If that’s the argument, why does the AMSA accept support from the anti-science based American Holistic Medical Association? The AMSA document “Successful Ways Past Retreats Found Moola” (which can be downloaded from the AMSA web site’s section on Humanistic Medicine) says the American Holistic Medical Association gives out grants for humanistic medicine “retreats.” Moreover, according to the document, in return for the grant “You have to contact the student rep and agree to give out AHMA (American Holistic Medical Association) materials at the retreat….”

So the AMSA, champions of ethics and professional integrity apparently have no problem accepting money in return for distributing “holistic” propaganda. The USA Today piece goes on to say that student representatives plan to visit 40,000 practicing physicians this year hoping to “pique the consciences of future colleagues.” I hope they pay me a visit. I have some questions to ask.

The link to the USA Today story was via Kevin MD.

Top 10 issues in hospital medicine for 2005------issue 1

State of the hospitalist movement

The hospitalist movement is growing. It is estimated that there were 15,000 hospitalists in North America in 2005. That number is projected to double in 5 years. There are multiple forces driving this growth, but this year there was the somewhat surprising multi-center study which failed to show that hospitalists had better clinical or economic outcomes than their non-hospitalist peers. This made the rounds in the blogosphere and I commented about it here.

Meanwhile there are signs that hospital medicine is moving toward establishment as a formal subspecialty. Robert Wachter, one of the founders and boosters of the movement, has been appointed to the board of directors of the American Board of Internal Medicine. A subspecialty textbook of hospital medicine is now in its second edition. Finally, there’s even a Wikipedia article about hospital medicine!

Top 10 issues in hospital medicine for 2005------issue 2

The Natrecor controversy

Nesiritide (Natrecor) was approved in 2001 for intravenous treatment of acutely decompensated heart failure. Short term results in the VMAC study showed superiority over nitroglycerine, mainly in terms of wedge pressure reduction, with more modest improvement in clinical endpoints. The drug appeared promising for rapid reversal of acute severe decompensation of heart failure and had a better safety profile than dobutamine.

Controversy was sparked, however, with the publication of this pooled analysis in JAMA last April which suggested a trend toward increased 30 day mortality with the use of Nesiritide. Opinion writers and bloggers reacted with harsh criticism of the makers of Natrecor for their promotions, and many called for a ban of its use.

How can we put the findings of the pooled analysis in perspective? First of all it must be noted that of 12 randomized controlled trials of Neseritide only 3 were chosen for inclusion in the analysis and the results were driven mainly by one study (PROACTION) which looked only at the use of Nesiritide in emergency department observation units. Moreover, the trend toward increased mortality was not statistically significant. Nesiritide’s effects on mortality deserve systematic study, and pending the results of such studies it should be used with caution. Nitroglycerine may be a safer alternative. In considering adjunctive infusion treatments alongside intravenous diuretics for acutely decompensated heart failure Nesiritide might occupy a position on the hierarchy between nitroglycerine and inotropes. The swift and contentious reactions to the paper were surprising and, in my view, irresponsible. For over a decade it was known that dobutamine was associated with increased mortality, yet clinicians continued to use it. Where was the outrage?

A reasoned and balanced recommendation on Natrecor is contained in this document from an expert panel chaired by Eugene Braunwald. Any clinician with an interest in treating acute heart failure should be thoroughly familiar with this report.

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.”

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.

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.

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.

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.

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.

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].

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.

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.

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.

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.

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).

This 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.

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.

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.

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.

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.

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.

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.

Podcast at Soundpractice.net

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

Review of diagnosis and management of pleural effusion

here in the October issue of CCJM.

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 cbc.ca 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.

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.

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.