Whither primary care?

An article in Medical Economics discusses the primary care crisis and wonders where it’s heading. It cites all the disturbing trends we’re well aware of including increasing demands of an aging population and fewer doctors choosing primary care careers. As interesting as the article itself are the reader comments. One that really got my attention comes from Mark Flodin M.D. of Tallahassee: “You assert that Internists would be better able to manage the more complex medical issues of the elderly than Family Medicine physicians......that's total nonsense.”

That’s a perfect example of the pervasive misconception that Internal Medicine is not really a specialty in its own right. Professional organizations such as the American College of Physicians have, unfortunately, done little to alter that perception.

Background: Internal Medicine’s identity crisis.

BNP and NT-proBNP testing in heart failure

Here’s an update on natriuretic peptide testing in heart failure patients published in CCJM.

Bartlett on avian flu

John G. Bartlett, MD, John Hopkins University School of Medicine, provides perspective on avian flu in this Annals of Internal Medicine review. We don’t know when or even if an H5N1 pandemic may occur or what its impact will be. Bartlett warns that we should assume worst case scenario, and that at present we are woefully unprepared for a pandemic resembling that which occurred in 1918 and 1919.

It’s an alarming trend

Hospitals are selling out to alt med in increasing numbers according to American Hospital Association data. Via Fox News.

A randomized trial of D-dimer testing in suspected pulmonary embolism

This is the first ever randomized controlled study to determine whether a negative D-dimer test can safely obviate additional diagnostic testing in certain patients with suspected PE. The researchers found that in patients with low clinical (pre-test) probability a negative D-dimer excludes PE as effectively as a strategy of nuclear scanning and lower extremity venous ultrasound. Via Annals of Internal Medicine.

Earn continuing education credit while sharing the cosmic consciousness

From the Vancouver Prophets Conference brochure:

The limited linear view of reality in which we abide does not support the nourishing healing consciousness so needed at this time. But, there are visionaries in science who are able to address this linearity in ways that bring it into a complementary and coherent place. These people are offering evidence that immeasurable distances can be spanned instantaneously by a thought, and that past, present, and future may be bridged even within ourselves. We are then learning of the dimensional fields where materialist and metaphysical views join into a universal consciousness, and from this place we begin the realization process and acceptance of personal and planetary healing. This is the place of miracles, and as our minds bridge and break open to greater receptivity we can rest in this place and become whole.

RNs will earn continuing education units for this. ‘Nuff said.

Clarification of off label prescribing and an update on Dr. Gleason

After the lively exchange triggered by my recent post on off label promotion of pharmaceuticals I thought this follow up might be useful. A commenter was concerned by my statement that off label prescribing was legitimate: “Yet, off label prescribing is, by definition, prescription to treat conditions for which there is NO EVIDENCE that such prescription works.” Thus the question is raised---does “evidence based” equate to “FDA approved”?

Not necessarily. I cited metformin for polycystic ovary syndrome, sildenafil for pulmonary hypertension, anticonvulsants and tricyclic antidepressants for neuropathic pain and caspofungin for invasive candidiasis as examples of evidence based treatments, all of which lack FDA approval for those uses. In other words, current examples of legitimate off label prescribing. Another example is the use of vasopressin in cardiac arrest---fully in accordance with ACLS protocols yet off label. And if memory serves, there are past examples in which evidence based prescribing preceded eventual FDA approval for particular indications. Thus, angiotensin converting enzymes were validated and used for heart failure at a time when they were only approved for hypertension.

The flip side is FDA approved (on label) prescribing which is not evidence based. Doxazosin, for example, (Cardura) is FDA approved as monotherapy for hypertension despite strong evidence from ALLHAT that such use is inappropriate. Old farts like me may remember phenformin (Ciba-Geigy’s DBI, the granddaddy of metformin) which remained on label and FDA approved for years despite clear evidence of harm. How many thousands of patients died of lactic acidosis before the FDA finally took action? So much for the FDA as the guardian of evidence based medicine!

That said, I’m sure there are widespread instances of off label prescribing that are non-evidence based and even harmful. One more point about inappropriate prescribing: off label prescribing is to be distinguished from on label prescribing which ignores warnings and contraindications in product labeling. I have blogged about this unfortunately widespread practice here and here.

On to Dr. Gleason. The commenter seems to have misperceived me as defending Dr. Gleason’s promotional activities and questioned my basis for stating that he did nothing clearly illegal. Having no legal expertise of my own, I merely cited experts quoted in the Times article who made that point. If this is a fuzzy area of the law subject to prosecutorial discretion, or zeal, it could be a dangerous precedent of concern to all who speak at CME events.

A discussion forum concerning Dr. Gleason has been set up here for those who wish to keep abreast or weigh in.

Chronic thromboembolic pulmonary hypertension

Reviewed in CMAJ.

Noteworthy: 3.8% of patients who present with acute PE will develop chronic thrombolic pulmonary hypertension (CTPH) within 2 years. Among patients presenting with CTPH only 50% will have a history of PE or DVT. In suspected cases, the workup should begin with V/Q scanning and echocardiography. The prognosis of untreated CTPH is poor. Pulmonary endarterectomy is the treatment of choice.

Be careful what you say about off label prescribing

Do you speak at continuing medical education conferences on drug therapy? Do you ever mention off label use? Be concerned. You may wind up in handcuffs. That’s what happened to Dr. Peter Gleason, a Maryland psychiatrist whose career has been destroyed in an episode characterized by the New York Times as illustrative of the “murky” relationship between drug companies and physicians who help promote their medications. Dr. Gleason frequently spoke about off label use of the Jazz Pharmaceuticals product Xyrem, a drug approved for narcolepsy. Although the extent of Dr. Gleason’s promotional activities are concerning this may be a case of over zealous prosecution. Dr. Gleason stated that he was arrested and charged only after he refused to cooperate with the prosecutor’s investigation of the company. Moreover, according to independent legal experts interviewed by the Times, Gleason’s activities were not clearly illegal. Rather, prosecutors were concerned merely that Dr. Gleason “went too far.”

Off label use of drugs is legitimate. The mention of off label drug prescribing is commonplace at drug company supported CME events. This prosecution sets a dangerous precedent. There are no clear legal constraints regarding such activities, and this could happen to any speaker at drug company supported educational events.

The myth of the normal coronary angiogram

The most common expression of this myth is the cardiac catheterization report which reads “Conclusion: no significant coronary disease. Plan: cardiac reassurance.” Such reassurance, however, may be false. It is increasingly recognized that patients with angiographically “minimal” coronary disease (usually interpreted as “No significant coronary disease”), or even “normal” coronary arteries, experience coronary events.

In the July 10 issue of Archives of Internal Medicine is a report of pooled data on patients experiencing non-ST segment elevation acute coronary syndromes, 9.1% of which had angiographically “insignificant” or no coronary disease. Long term follow up of such patients revealed a significant rate of recurrent events.

The mechanism of such seemingly discrepant findings is clarified by intravascular ultrasound (IVUS), which has shown that in the initial stages of atherosclerosis the growing plaque presses the adventitia outward rather than the intima inward. Since the lumen is uncompromised the coronary angiogram of such a patient (essentially only a “luminogram”) would appear normal. Nevertheless such a plaque could rupture, producing a coronary event.

A review of advanced coronary imaging, including a nice discussion and images of IVUS, is here.

How safe is warfarin? It depends on the setting

An important paper in Chest reported that levels of anticoagulation are out or range more frequently in community practice than in anticoagulation clinics or clinical trials. This demonstrates once again that drugs are safer in the hands of clinical trialists than in the hands of community physicians. Drug safety is not absolute. It’s all in how they’re used.

The optimal duration of warfarin anticoagulation for venous thromboembolism is controversial, and clinical decisions are often based on the expected annual rate of bleeding. This paper reminds us to be cautious in the interpretation of clinical trial data in estimating this risk.

Playing the quality game

As I recently blogged, the quality and P4P movement is not mature enough for prime time and may be of little more than cosmetic importance. In addition to numerous unintended consequences, some publicly reported “quality” measures (e.g. pneumococcal vaccination) may not even be effective.

Two articles just out in Chest now raise questions about time to first antibiotic dose (TFAD) for pneumonia as a quality indicator. One of these, cited by Kevin and DB, suggests that the incentive could lead to hasty (and inappropriate) antibiotic use. The other paper analyzed records of patients who received antibiotics outside the 4 hour window, thus “failing” the quality screen. The findings suggest that age and comorbidities contributing to an atypical presentation of pneumonia were responsible for the delays. Moreover, these same patient attributes, rather than the delay itself, are causally related to the adverse outcomes associated with delayed administration.

Links between obesity and respiratory disease

Reviewed in CMAJ.

The obvious associations are obstructive sleep apnea and obesity hypoventillation syndrome. Although OSA and OHS overlap there are important distinctions which are reviewed.

Less well appreciated is asthma. Mechanisms for the link may be inflammatory.

Drugs, QT intervals and torsade---the story of methadone

Several years ago a small case series of patients experiencing torsade de pointes (TDP) while taking methadone was published. The doses of methadone were very large (averaging around 400mg) and most of the patients had other risk factors for TDP. Reports such as these prompted in vitro studies confirming methadone’s ability to prolong repolarization by blocking the rapid delayed rectifier potassium current (IKr), the principal mechanism of drug induced TDP.

Despite mounting evidence, the ability of methadone to prolong the QT interval and cause TDP remains under appreciated. Now, a disturbing report in Archives of Internal Medicine places this association decisively in the clinical arena. QTc prolongation was seen in 16.2% of hospitalized patients receiving methadone and none of controls. 3.6% of patients on methadone had TDP. Moreover, QTc prolongation was seen with methadone doses as low as 30mg daily and TDP with doses as low as 40mg. The Center for Education and Research in Therapeutics has now assigned methadone the highest risk rating (category 1).

Thanks to better understanding of molecular mechanisms it is now possible to predict the risk for TDP during the pre-clinical phases of drug development. Drugs with the highest risk of TDP are those which both block IKr and are metabolized by the CYP3A4, 5 and 7 isoforms of cytochrome P-450, as is the case with methadone. These molecular mechanisms and their implications for drug development are reviewed here in Pharmaceutical Discovery and Development. Pre-clinical molecular testing procedures have been codified by an international group of regulatory agencies and experts. Such testing is becoming a standard for mainstream drug development and approval and may reduce the number of post-marketing “arrhythmic surprises.” (In contrast, herbal remedies get a free pass on such molecular testing, another reason not to trust NCCAM funded “research”).

Safety monitoring for risk of TDP has become a daunting task given the ever increasing number of implicated drugs and the difficulty of clinicians in measuring the QT interval. What’s a doctor to do? Linked below are some useful resources.

JAMA review---how to measure the QT, what it means and how to apply it to drug monitoring. Note: although references to specific drugs such as methadone are dated, this is a very helpful general review.

CERT---like the breath mint. It’s the Center for Education and Research in Therapeutics containing a frequently updated list of “QT drugs” and many helpful tools.

Life defining moments with mushrooms

Adventures in neurotheology at Hopkins.

Via Religion News Blog

The American Medical Student Association: consistency after all?

I have occasionally blogged about the inconsistency between AMSA’s Pharmfree campaign (supposedly standing for scientific integrity and evidence based medicine) and their enthusiastic promotion of alternative medicine with its numerous unproven health claims.

One of my posts drew a comment from ba who said “As for integrative medicine, AMSA is not doing enough. The medical schools are still in way too deep with the pharma$ to have credible integrative health programs. So far the integrative medicine programs sound more like mere window dressing and decoys.” That suggests a common thread in the AMSA’s seemingly contradictory positions: the notion that Big Pharma is leading a medical-industrial conspiracy to suppress research in (and the integration of) alternative methods.

Could these positions be part of a broad political agenda? Go to the AMSA’s main page and search such hot button issues as reproductive rights, universal health care and, last but not least, malpractice. Extensive material is posted concerning these issues. After perusing their articles on malpractice I gather they are not in favor of damage caps, think the liability crisis is exaggerated and seek other solutions to rising premiums such as reforming the insurance industry, reducing medical errors and disciplining bad doctors.

Medical students and faculty should be aware that while AMSA purports to be concerned with medical professionalism it is very much a political activist group. At 60,000 members it is the largest medical student organization. Medical students are being groomed to transform the culture of the profession, and in a way that should concern us.

I agree with commenter ba on one point. The integrative medicine programs in most medical schools are not credible. The remedy for this credibility gap is not to decrease reliance on “pharma$”. Instead medical schools need to dispense with magical thinking and be appropriately critical of pseudoscience.

Cephalosporins in penicillin allergic patients

Stay away from first generation cephalosporins, but second and third generation agents appear safer than commonly believed. In a systematic review of PCN allergic patients receiving cephalosporins (originally published in J Fam Pract and abstracted as POEM in CCJM) rash occurred in 2% but anaphylaxis was rare (0.1%-0.0001%). Patients with a history of type I hypersensitivity to PCN should avoid first generation cephalosporins but may be able to safely take second or third generation cephalosporins.

Background: Coombs and Gell classification of hypersensitivity.

Internal Medicine’s identity crisis

An introduction to the specialty of Internal Medicine from the University of Maryland School of Medicine website linked in my June 15 post on the subject has this description: (italics mine) “But the internist always remains the physician (or the diagnostician as internists were called in former times) whose special competence is solving difficult diagnostic problems and personally applying, or obtaining from a colleague, the best treatment available.” It also contains this statement: “Internists have always required special training to acquire their knowledge and skills and have continuously shown a particular interest in the scientific basis of clinical work.”

DB expanded on this view when he described what attracted him to Internal Medicine: (italics mine) “I am driven by both the intellectual challenge and the interpersonal relationships in medicine. I enjoy puzzle solving and relating to individual patients.” Also this: “Internal medicine deals with the most complex patients and most complex situations. Internists handle complex comprehensive care.”

Internal Medicine is thus distinguished by a unique emphasis on scientific underpinnings of medicine and the handling of complex problems. What is the popular notion of Internal Medicine? In search of something “official” I checked the American College of Physicians webpage and was disappointed. They characterize internists merely as "doctors for adults" and elaborate by listing what internists don’t do, such as deliver babies and treat kids. That’s it. For a description of a specialty this definition contains nothing special! The American College of Physicians has thus succeeded in defining Internal Medicine as nothing more than a subdivision of Family Practice, further contributing to Internal Medicine’s identity crisis.

More evidence in favor of inhaled steroids for COPD

This meta-analysis published in the Annals of Family Medicine showed improved outcomes attributable to inhaled steroids, particularly a reduction in frequency of exacerbations. There was a trend toward reduced mortality which failed to reach statistical significance.

Background: I previously posted on this subject here.

Effects of obesity on natriuretic peptides: implications for the evaluation of heart failure

We’ve known for some time that natriuretic peptide levels (BNP and, to a lesser extent, pro-BNP), correlate inversely with body mass index. Obese patients may have deceptively low levels, decreasing the sensitivity for the diagnosis of heart failure.

In this paper from the American Heart Journal (via Medscape) the Breathing Not Properly Multinational Study investigators analyzed BNP levels in various categories of body mass index in order to quantitate the effect of obesity on the test characteristics of BNP in heart failure. The authors conclude that “B-type natriuretic peptide cut-points to maintain 90% sensitivity for a HF diagnosis were 170 pg/mL for lean subjects, 110 pg/mL for overweight/obese subjects, and 54 pg/mL in severely/morbidly obese patients.”

Bugs outpacing drugs

There is an impending shortage of antibiotics to combat emerging resistant infections. The antibiotic pipeline has been regulated to death, so says a commentary from last May in the Washington Times.

Marketing considerations and regulatory costs have exacerbated the antibiotics drought. Until about a decade ago, all major pharmaceutical makers had antibacterial research programs, but they have dramatically trimmed or eliminated these efforts, focusing instead on more lucrative drugs that treat chronic ailments and lifestyle issues. Read the rest.

I previously cited the Infectious Disease Society of America’s warning here.

Exposing absurdity

Retired Doc discusses the corruption of medicine by pseudoscience and links to an article from the Medical Journal of Australia on the absurdity of it all.

Unscientific healing methods may compete in the marketplace of ideas, but does mainstream medicine have to embrace them uncritically? The absurdity lies in the attempt to “integrate” science with quackery and ethical practice with fraud.

FDA supports easier standard for CAM research

In the same San Francisco Chronicle article I linked concerning UCSF’s promotion of herbal tea to boost the immune system is another tidbit concerning lax FDA standards for research on herbal products. Apparently the FDA thinks it’s OK to study unrefined plants without even knowing the active ingredient. The article reports the FDA position thusly:

“The agency is even allowing researchers to experiment with plant materials in clinical drug trials without first identifying their active ingredients. ‘There's a need to adjust our approach if we want to encourage study of these complex mixtures,’ said Shaw Chen, botanical team leader with the FDA's Center for Drug Evaluation and Research. “ Translated: let’s adopt a double standard.

It's all bass akwards in contrast to legitimate drug development which starts with the search for, discovery and characterization of compounds based on anticipated effects on molecular targets. Then come animal studies followed by preliminary safety and dose finding studies on humans, leading, ultimately and tediously to phase III clinical trials.

And the consequences? If an herbal product fails a clinical study the boosters can just say “Since we don’t know the active ingredient how do we know we studied the right component of the plant, or the right species? Were the climate and soil optimal? What about the dose?” Endless questions and more excuses to pour tax dollars into CAM “research.” It’s all quite convenient for the NCCAM which continues to ride the gravy train despite the fact that no significant medical advances have been made in all its years of existence. No breakthroughs. No debunkings.

A recent example is the story of echinacea. NCCAM’s response to disappointing results of one of its own studies was, in effect, let’s try again; maybe we should focus on the roots; or maybe the flowers, or the seeds; maybe we used the wrong echinacea species---and on it goes.

The double standard for research is becoming pervasive. The NCCAM has adopted it for some time. Now the FDA is on board. It’s going to get worse. As I recently posted, a generation of medical students is being indoctrinated.

Background:
Forget the Echinacea (DB’s Med Rants)
NCCAM should be defunded (Quackwatch)

Is UCSF promoting herbal tea and massage to “boost the immune system?”

Evidently, according to the San Francisco Chronicle.

Via the Healthfraud list

Background: About the UCSF Center for Integrative Medicine.

Biphosphonates and jaw osteonecrosis

My post about biphosphonates and osteonecrosis of the jaw (ONJ) drew an interesting comment from Liz, author of a blog devoted to the problem. Concerning my reference to a linked study showing that the major incidence of ONJ is with parenteral biphosphonates in patients with myeloma or metastatic bone disease she states: “That simply isn't true. Oral surgeons and dentists have been seeing patient after patient with jaw necrosis from Fosamax and other bisphosphonate drugs.” Wait a minute. Not so simply, please. According to the systematic review the oncology patients on parenteral therapy represent 94% of published cases despite much heavier use of oral biphosphonates such as Fosamax.

Yes, there are are many “real world” anecdotes about Fosamax, but in order to be convincing Liz should give us a denominator, which I suspect would be huge! Then and only then will we have any idea of the absolute risk for ONJ form oral biphosphonates.

The July phenomenon

As the first day of the new academic year for residency programs draws to a close it’s appropriate to reflect on the July phenomenon. There’s an urban legend that patients check into academic medical center hospitals during the month of July only at their peril. That’s when a new crop of interns, green and fresh out of med school, takes over. But is the notion evidence based? Not according to this paper in SGIM (via Medscape).

Maybe there was something to the idea decades ago. Nowadays house staff are better supervised.