A contrarian view of the drug companies

Dr. Jerald Kreisman, associate clinical professor of psychiatry at St. Louis University, in Defending the Drugmakers writes “Over the past several years, the pharmaceutical industry has replaced managed care as the Bad Boys of Health Care. Public opinion, government oversight, and litigation pressures have obliged the industry to adopt a litany of mea culpa declarations.” Indeed “Big Pharma” has become analogous to big oil, big money and everything else that’s big and bad. Alongside that physicians, many of whom interact with drug company representatives, are portrayed as the mindless minions of an industry-led conspiracy to harm patients. Notwithstanding the patent absurdity of this characterization the drum beat is getting louder and louder.

Doctors are not devoid of critical thinking skills. Moreover, there’s no convincing evidence that physician-industry interactions result in net harm to patients’ health. Immediately comes the shrill cry “What about Vioxx?” Yes, the promotion of Vioxx has been linked to harm. What is not known is how this balances against the effects of promotion of clearly beneficial yet underutilized therapies such as DVT prophylaxis and beta blockers and ACE inhibitors for heart failure.

Finally, haven’t we heard about enough of the tired old argument that doctors succumb to drug company deception because of their dependence on free trinkets such as pens and note pads? Where’s the evidence for that argument? (I’ve done without for seven years and couldn’t care less about ‘em). I’m much more concerned that continued industry bashing will lead to an erosion of support for CME and the ultimate end of resources like Medscape and emedicine.

What’s evidence based in ARDS?

A review in Cleveland Clinic Journal of Medicine summarizes the latest findings on several modalities. Low tidal volume ventilation (6 ml/kg ideal body weight) is well established. High “recruitment levels” of positive end expiratory pressure (PEEP) are theoretically appealing but do not improve outcomes. Prone positioning, high frequency ventilation, and nitric oxide have failed to live up to initial promise. Conspicuously absent from this article was the mention of corticosteroids for late phase (greater than 7 days) ARDS, recently studied in the ARDSnet Late Steroid Rescue Study. This study has been completed and, after publication date of the CCJM article, was published in NEJM with the conclusion that late phase corticosteroid therapy for ARDS is not beneficial.

Timing of hip fracture surgery

In this observational study of 129,522 patients admitted with femoral neck fracture, surgery delay of more than one day was associated with increased mortality with an odds ratio of 1.27 (1.23-1.32) after adjustment for comorbidity.

Hospitalists are often called on to optimize medical management of hip fracture patients prior to surgery. Physiologic disturbances and laboratory abnormalities must be addressed as fully as possible, but these and other recent data suggest that the time window is short and that lengthy preparation has diminishing returns.

Something new in COPD

Inhaled corticosteroids decrease mortality, as reported here in Thorax.

ICD-9 coding

I have always rebelled against ICD-9 codes. The terminology is archaic and often clinically irrelevant. As a physician I have more important things to keep track of. Nevertheless ICD-9 is part of the game I’m forced to play.

Fortunately, for those inevitable occasions when you have to sign off on medical equipment and the coder isn’t handy there’s help on line. Kevin once showed us how to Google for ICD-9 codes and pointed us to this resource. Wikipedia has this user friendly index and an overview of the International Classification of Disease. The classification system is horribly out of date. ICD-9, still in use, was published in 1977. ICD-10, conceived in 1983, completed in 1992 and probably already out of date, has not yet been implemented in the U.S.

The new C. diff marches across Canada

It’s not unique to Quebec anymore. It’s turned up in 7 provinces according to this CMAJ report. I previously mentioned it here.

Is rock-and-roll stardom hazardous to your health?

I know of no systematic studies but here’s a collection of anecdotes---dead rock stars. Read and be amazed. The causes of some of the deaths are in dispute. For example, did Karen Carpenter really have anorexia nervosa? The Pathology Guy thinks not. Maybe she had right ventricular cardiomyopathy, Brugada syndrome, LQTS or some such.

Via The Pathology Guy.

Sally Satel on clinical trials

Sally Satel, psychiatrist and scholar at the American Enterprise Institute, gives us a refreshingly balanced and sober perspective on the interpretation of clinical trials in her April 19 article in Medical Progress Today, Patients Adrift in a Sea of Clinical Trials.

Clinical trials often disappoint us. Why? Because we expect too much. We want simple answers when the real truth is complex and nuanced. Too many of us—journalists, opinion leaders and, yes, bloggers—are too lazy to look beyond the abstract or the sound bite, so it’s no wonder we feel deceived and beguiled. For most clinical research papers the devil’s in the details. But now more than ever those details are largely transparent and accessible for those willing to go to the trouble to dig them out.

The bugaboo of industry funding of trials must be addressed by a skepticism that looks beyond the surface and asks hard nosed questions rather than a cynicism that knocks everything down and rejects out of hand all experimental work with industry ties. Industry funded and non-industry funded studies are sure to mislead if simplistically interpreted, but both can yield valuable lessons when examined critically.

These concerns and more are addressed in the article and solutions are offered.

Blogosphere challenges controversial autism paper

Recently I cited a controversial paper on autism and thimerosal containing vaccines. Bloggers like Orac were quick to point out flaws in the paper. Now Joseph at Autism-Natural Variation is pressing for a retraction, citing misleading terminology. The authors of the paper apparently took notice and requested additional data from one of their sources, the California Department of Developmental Services. Joseph suggests this is an implicit admission of error but awaits a more substantive response by the authors and the Journal of American Physicians and Surgeons. He’s not letting go, and this face-off will test the scientific integrity of the Journal and the Association of American Physicians and Surgeons.

An under appreciated consequence of obesity

Non alcoholic fatty liver disease (NAFLD) is an increasingly prevalent form of liver disease characterized by hepatic fatty infiltration associated with obesity and the metabolic syndrome. Non alcoholic steatohepatitis (NASH) is the condition resulting when NAFLD is complicated by hepatocellular inflammation and necrosis. This spectrum of liver disease may have replaced hepatitis C as the most common form of chronic liver disease. Like other forms of liver disease NASH can progress to cirrhosis and hepatocellular carcinoma.

NAFLD and NASH are reviewed in the April 2006 issue of Current Opinion in Endocrinology and Diabetes. Key points:

Sensitivity and specificity tend to be poor with readily available blood and imaging tests.

However, NAFLD is likely in obese patients with the metabolic syndrome.

Magnetic resonance spectroscopy has identified NAFLD in 33% of the general population in the Dallas Heart Study.

The prevalence of NASH in morbid obesity may warrant routine liver biopsy in patients undergoing bariatric surgery.

Weight loss can reverse the histologic changes and is the best treatment.

Thiazoladinediones such as pioglitazone show promise in treatment but definitive recommendations await higher level studies.

Statin drugs, often indicated in the dyslipidemias associated with NAFLD, appear to be safe.

Fluconazole prophylaxis in non-neutropenic critically ill patients

It was beneficial in this Cochrane review. The reviewers conclude “In patients at increased risk of invasive fungal infections, antifungal prophylaxis with fluconazole should be considered.”

Open access stuff

Directory of open access journals
(Via Krafty Librarian)


The Free Medical Journals Site
(Also has links to free medical books)


High Wire Press
(Keeps track of free trials and back issues)

Review of treatment of antiphospholipid syndrome

From the Clinician’s Corner feature, JAMA, March 1, 2006.

Thiazolidinediones and heart failure

Two thiazoladinediones (TZDs) are currently approved for the treatment of type 2 diabetes: pioglitazone (Actos) and rosiglitazone (Avandia). Through unique actions these drugs improve insulin sensitivity, endothelial dysfunction and the dyslipidemia associated with type 2 diabetes, properties which have sparked interest in their potential antiatherogenic effects. The first large study to evaluate vascular outcomes, PROACTIVE, suggested a protective effect of pioglitazone on such outcomes. Controversy regarding that study was reviewed here.

One of the safety issues surrounding TZDs is their ability to exacerbate heart failure, a topic which was reviewed in the April 2006 issue of Cleveland Clinic Journal of Medicine. Current evidence suggests that TZDs are associated with fluid retention in some patients, and that such fluid retention may occasionally be associated with precipitation or exacerbation of heart failure. These effects appear to be due to renal and vascular effects rather than deleterious effects on the myocardium itself. The effects are reversible and may require stopping the drugs. Rather than cause heart failure outright it is more likely that the drugs induce fluid retention thereby unmasking previously asymptomatic cardiac dysfunction.

Recommendations regarding TZDs and heart failure are summarized. They should be avoided in class III and IV heart failure and used with caution in class I and II heart failure. Given the increased risk for heart failure in all diabetics, careful cardiac assessment initially and at intervals during treatment is wise.

One of the citations in the CCJM review is this excellent overview of the relationship between diabetes and heart failure published in Diabetes Care.

On a related note, macular edema has been associated with TZDs. Given that it tends to occur in those patients who develop peripheral edema it is likely a manifestation of the general tendency for fluid retention. Because the association is based on retrospective reviews and post marketing data the precise incidence is not known and cause and effect relationships are unclear.

TEE “indispensable” in stroke of undetermined etiology

A study in the March 2006 issue of Stroke evaluated the role of transesophageal echocardiography (TEE) in 503 patients with ischemic stroke. Of the 227 patients with no apparent etiology after routine testing (ultrasound, TTE, CT/MR, etc) TEE revealed a “high risk or potential” embolic source appropriate for oral anticoagulation in about one third.

The authors concluded that TEE is “indispensable” when routine testing fails to clarify the etiology.

Surgical options for COPD

What the hospitalist and PCP need to know is when to refer. The principal options are lung volume reduction surgery (LVRS) and transplantation. Although LVRS remains somewhat controversial the National Emphysema Treatment Trial has helped define the best candidates. These include patients with heterogeneous involvement with emphysema, particular upper lobe disease, DLCO > 20% and FEV1 > 20%. These are general principles, and final selection is very nuanced. Patients with more advanced disease might better be considered for transplantation. Although age cutoffs for transplantation are not absolute, patients older than 65 are not usually considered. The topic is reviewed here in Clinical Pulmonary Medicine.

Thyroid disorders and cardiovascular outcomes

Data from the Cardiovascular Health Study published in the March 1 issue of JAMA confirm that subclinical hyperthyroidism is associated with an increased risk of atrial fibrillation, but not with other cardiovascular outcomes. There was no association of any CV outcome with subclinical hypothyroidism or overt hypothyroidism. The number of patients with overt hyperthyroidism was too small for analysis.

OASIS-6: fondaparinux in ST segment elevation MI

OASIS-6 was just reported in JAMA. This is a very complicated and busy paper, the gist of which is that anticoagulation (in this study, with fondaparinux) has a broader role in ST segment elevation MI (STEMI), previously having been restricted primarily to an adjunctive role in patients undergoing thrombolysis. It was studied in a broad range of patients with STEMI and was superior to placebo in patients who were not felt to have an established indication for anticoagulants, and to unfractionated heparin (UFH) in some subgroups of those who were.

I can’t do justice to the detailed data, a good visual representation of which is provided in figure 4 of the paper. Editorial comment can be found here.

Fondaparinux (Arixtra) is emerging as an anticoagulant for acute coronary syndromes. The folks at Glaxo Smith Kline may have something to celebrate. Read here about OASIS-5 (fondaparinux in unstable angina and NSTEMI) and for background info.

Post graduate pseudoscience for nurses

The “Just for the Health of It Prophets Conference” to be held in Boulder Colorado May 19-21 2006 awards 17 credit hours for RNs . According to the course schedule the conference will include instruction in Shamanism and energy healing featuring Adam the dream healer.

A conference and workshops on “The Cutting Edge of Subtle Energies and Energy Medicine” will take place June 23-28 in Boulder and offers nursing education credits. Content includes image therapy, energy medicine, cosmic consciousness and “dynamical systems theory.” One of the workshops entitled “The Five Mystical Stages of Consciousness Experienced through Sound Currents” teaches participants to make “special vocalized sound currents under the direction of a spiritual master” to modulate one’s consciousness and transmit the resulting state to others. A workshop in “energetic psychotherapy” explains the role of the chakras in depression treatment. Other lectures will demonstrate a thermographic record of the hands of a healer and explain how alterations of consciousness can alter our DNA.

Read the brochures and be amazed. Then find out if your state’s nursing board approves post graduate education in shamanism, mysticism and energy healing.

Pneumothorax review

Found in the December 2005 issue of Postgraduate Medicine.

Cutaneous signs of systemic disease: vitiligo

Here’s a review of systemic disease associations.

What does the evidence say about clinical skills?

An editorial lamenting poor clinical skills provided grist for discussion among several blogs last week. The controversial article in question was just an opinion piece. But that opinion may be evidence based according to last week’s Archives of Internal Medicine. With the exception of cardiology attendings and fellows, cardiac physical examination across the career spectrum never improved beyond the junior medical student level in this study. Even teaching faculty proved no better than medical students. To me the most telling finding was that participants could correctly differentiate systolic from diastolic sounds only 66% of the time!

The power of physical examination of the heart was shown in this related article which evaluated the third heart sound (S3) as a test. Although not very sensitive, the S3 showed high specificity in predicting elevated BNP, elevated filling pressure and systolic dysfunction.

Findings such as this motivate me to improve my basic clinical skills. With basic knowledge and skill in clinical medicine come power. I’m preaching to myself here. David L. Simel provides editorial commentary on the two studies.

Isabel and Dxplain tackle two more cases from the New England Journal of Medicine

(See my earlier post on this subject).

I managed to try the programs on two more NEJM cases before my Isabel free trial expired. Isabel outperformed Dxplain on this Clinical Problem Solving case of cholesterol atheroembolism. Presented with the case of a cachectic man with severe hypertension, renal failure, constitutional symptoms and atherosclerosis of the aorta both programs offered a long list of diagnoses but only Isabel included cholesterol atheroembolic disease. The atheroembolic syndrome is a great masquerader. I was a little disappointed in Dxplain. The presentation of an unexplained multisystem illness with renal failure and hypertension in a patient with atherosclerosis should always bring that diagnosis to mind.

The tables turned when I entered the CPC case of Brugada syndrome discussed elsewhere in this blog. Dxplain nailed it while Isabel struggled with numerous cardiovascular diagnoses, failing to mention the correct one. That concerns me. Given a couple of telltale ECG signs in a patient with cardiac arrest it should be a no brainer.

So Dxplain wins the best two out of three series. What can we conclude from this small sample? Perhaps only that both software programs are hit-and-miss. I’m more familiar with Dxplain, having toyed with it since the late 80s. It’s an unpretentious and longstanding work in progress of education and research, making no claims about saving lives. I have decided not to spend my medical group’s money on Isabel. I was a bit put off by its gaudy testimonials and hyped up claims.

Direct to consumer advertising

A lively discussion about DTC advertising took place on NPR’s Science Friday featuring our very own DB of Med Rants. It’s archived here and definitely worth the listen. When I was doing ambulatory medicine a few years ago there was relatively little DTC advertising. I’m sure it would drive me crazy now. One of the greatest harms done by DTC advertising, as pointed out by DB, is that patients tend to come to their appointments requesting unnecessary medications. As a result doctors have so spend 5 minutes or so explaining to the patient why that medication is inappropriate. That takes precious time away from more important matters.

Many of the ads hawk “me too” and lifestyle drugs although that is not always the case. One caller saw ads for Novolog and Lantus---revolutionary advances in the treatment of diabetes---and had to ask her endocrinologist for a prescription.

Conspicuously absent from the discussion was any mention of the effect of the incessant criticism of pharmaceutical marketing to doctors on DTC advertising. I suspect it has led to increased DTC ads.

John Ritter’s family settles malpractice suit

Actor John Ritter died of a dissecting thoracic aortic aneurysm September 11, 2003. His family brought suit against the hospital and doctors approximately one year later. It is reported that the family was seeking more than $25 million in damages, and recently entered into a tentative settlement agreement. Although the amount is undisclosed, this and several other reports state that Ritter’s family members “are potentially receiving a large monetary settlement in this case."

The suit claimed that Ritter underwent “improper and unnecessary procedures”, and “would be alive and well today” if proper procedures had been followed. Is that fair? According to his death certificate he underwent an angiogram and a thoracotomy within a matter of hours. Those are proper procedures for aortic dissection.

The diagnosis of aortic dissection is challenging. Did Ritter have the classic symptoms and risk factors? Although aortic dissection belongs in the differential diagnosis of chest pain it is distinctly uncommon when compared to myocardial infarction and other conditions. The most characteristic feature serving to differentiate chest pain due to dissection from more common causes is that the pain of dissection is sudden and maximal at onset, usually very severe with a tearing quality. Multiple news reports describe Ritter’s condition otherwise, more suggestive of myocardial infarction. Some indicate that the first sign of anything wrong was that Ritter just didn’t feel well and retired to his dressing room. Some reports described the pain as a tightness or pressure, which would not be suggestive of dissection. Nausea and diarrhea are mentioned in some reports, more suggestive of myocardial infarction than aortic dissection.

So, perhaps the symptoms were deceptive. We don’t really know how accurate these reports are. But did he have any telltale risk factors? Marfan syndrome is perhaps the best known. There was apparently no history of that, and his body habitus would not suggest Marfan syndrome. That said it is known, though not well appreciated, that some patients with annuloaortic ectasia resembling that of Marfan syndrome do not have the typical body habitus. In those patients who do not have Marfan syndrome hypertension is an important risk factor. His death certificate lists hyperlipidemia, a risk factor for myocardial infarction, but makes no mention of hypertension.

So, although there’s a lot of room for speculation here I’m going to have to agree with Galen and Rangel in their posts from September 2004. Go and read what they had to say after the suit was announced.

In defense of clinical skills

On March 30 I lamented the decline in clinical skills and linked to an editorial by Herbert L. Fred, MD on the same subject. A lively discussion on several other blogs followed, and Clinical Cases and Images has compiled those links along with some related content.

I was appalled by the personal attacks leveled against Dr. Fred, particularly by some of the commenters at Kevin’s blog. I have to agree with Retired Doc that these ad hominem arguments (which in effect characterize Dr. Fred as an anachronism out of touch with today’s medical climate) shed little light on the issue and fail to address Dr. Fred’s arguments concerning deficiencies in clinical training.

Dr. Fred longs for renewed emphasis on basic clinical skills. If we dismiss his views just because he’s an old timer entrenched in medical academia we must dismiss similar views of other great teachers such as Henry JL Marriott, J Willis Hurst, Proctor Harvey and David Spodick.

Some commenters responded with a defense of high technology, correctly arguing that plaintiff attorneys drive excessive use through defensive medicine and that many of today’s imaging modalities have supplanted outmoded bedside techniques (a neurologist gave the example of bedside ocular plethysmography). These are valid points but seem to miss the core of Dr. Fred’s argument. In my reading of the editorial high technology is good but its effectiveness is limited by poor clinical skill on the part of the user.

I like the analogy of the shotgun and the rifle. A shotgun approach may be appropriate in limited situations. In the critically ill patient with refractory hypotension of unknown cause the clinician is challenged to make an appropriate differential diagnosis containing all life threatening conditions, then address each one in limited time. Such cases may call for a wide spectrum of expensive tests on the front end. Even in those situations basic clinical skill is essential for correct interpretation of results. But more often the rifle approach is called for with selective testing used in a specific and focused manner. We should all strive for expert clinical marksmanship.

For me the challenge of developing and maintaining excellent clinical skills is part of the joy of medicine that keeps me going. I’m reminded of the great teachers I encountered as a student at Vanderbilt Medical School, in particular the late Thomas E. Brittingham who, as the principal teacher of third year students on the medicine rotation, emphasized the foundational importance of bedside clinical examination. He once said “What you learn in becoming a good medical observer will be useful to you always. Contrast this with the ‘facts’ which you learn from your books. It is said that half of what we are taught in medical school will have been shown to be wrong during the first 10 years after we have graduated.” These lines were from a letter he sent to students about to start the rotation. It was an inspiring pep talk which served to remind us of the power of basic clinical observation. I saved the letter and reread it occasionally when day to day practice begins to feel like a chore.

For those wishing to refresh clinical skills or needing a dose of inspiration I highly recommend Sapira’s Art and Science of Bedside Diagnosis.

Update: Clinical Cases and Images points us to a wonderful collection of instructional videos on physical diagnosis.