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.

Rumors of homocysteine’s death as a cardiovascular risk factor have been greatly exaggerated

I’ve made this point before. A recent editorial in Stroke entitled “Homocysteine: Call Off the Funeral” provides reasons in addition to those I cited. One factor is the increasing importance of vitamin B12 relative to folic acid as a determinant of elevated homocysteine levels. Increased fortification of foods with folic acid has diminished the incidence of folate deficiency and may be masking milder cases of B12 deficiency. Moreover, the shifting demographic toward an older population has increased the importance of B12 deficiency due to food-cobalamin malabsorption syndrome for which the optimal dose of oral vitamin B12 is unclear. Some of the vitamin trials used doses of vitamin B12 which may have been inadequate to overcome this common absorptive defect.

Declining clinical skills

Herbert L. Fred, MD, professor of Medicine at the University of Texas Health Science Center at Houston, calls it hyposkillia and believes it to be one of the more pervasive threats to our profession. In a recent editorial in the Texas Heart Institute Journal he correctly points out that over reliance on diagnostic technology has led to intellectual laziness and a neglect of basic clinical skills. J. Willis Hurst once said that you must master low technology (history, physical examination, electrocardiography) before you can make effective use of high technology (echocardiography and other imaging modalities).

I would argue that there are other factors. Extremes in evidence based medicine have produced some unfortunate consequences. The shunning of experts, for example, threatens the extinction of the master clinician-teacher. Over reliance on resources like Up To Date and slavish adherence to algorithms have become substitutes for thought. The increasing percentage of precious curriculum time spent on pseudoscience (euphemistically termed “complementary and alternative medicine”) undermines education in the basic sciences.

This dumbing down of clinical skill is ironic coming as it does in the midst of the ACGME’s core competencies initiative. Is outcome based medical education failing? A more optimistic view might be that the outcome project is early in implementation and we have yet to see its benefits. But a proposal written a few years ago in BMJ for the medical school of the future was not promising. In this Renaissance School of General Medicine “….gone will be the days of freestanding courses in biochemistry, physiology and anatomy” and “There will be no exams in anatomy, physiology, or biochemistry, and no one will need to learn by rote the entire Krebs cycle or the names of all those little holes in the skull.” This is scary.

Inferior vena cava filters remain controversial

The expanding use of IVC filters has outpaced clinical evidence. Most of the current uses of filters are unsupported by high level evidence. JAMA Medical News and Perspectives has a commentary in the March 1 2006 issue. A concise and rigorous statement on IVC filters from the Thrombosis Interest Group of Canada can be found here.

The use of retrievable filters is appealing although evidence is limited. Of three retrievable filters approved for use in the United States only two remain available; one was removed from the market due to a high rate of complications.

Isabel versus Dxplain in a case of giant cell arteritis with atypical manifestations

A while back I mentioned two web based differential diagnosis resources, Isabel and Dxplain. I have access to Dxplain through Merck Medicus and signed up for a free trial of Isabel, so I decided to plug a challenging case into both programs and compare their performance.

The CPC in the February 9 2006 NEJM featured an uncommon presentation of giant cell arteritis dominated by chest pain and respiratory complaints. Myalgias were also present, mistakenly attributed to statin drugs. The following findings were entered into both programs: chest wall pain; ear pain; shoulder pain; myalgias; hoarseness; exertional dyspnea; fatigue; sore throat. Age (elderly) and gender (female) were entered. Although both programs encourage entry of laboratory results you can enter as much or as little data as you wish, and I decided to see how the programs did with only the initial presenting clinical manifestations. I opted not to enter the patient’s sedimentation rate of 90. That would have made it too easy.

Isabel missed the boat entirely with a long list of diagnoses across multiple specialties, with the only rheumatologic diagnosis offered being relapsing polychondritis. Dxplain fared better by coming up with polymyalgia rheumatica. Neither program diagnosed giant cell arteritis or temporal arteritis. So, Dxplain wins the first round. As time permits before my free Isabel trial expires I’ll try more cases and report back.

Clostridium difficile review

This open access CCJM review of C. diff provides an overview of diagnosis and treatment as well as an update on the new NAP 1 strain. A few tidbits--

Fluoroquinolones appear to be more strongly associated than other antibiotics including clindamycin.

The new NAP 1 strain produces more toxin than old strains and may be responsible for recent trends toward more severe disease.

Antiulcer medications add to the risk for disease.

Recent reports of treatment failures with metronidazole have suggested changed treatment recommendations. This review suggests metronidazole as initial treatment for mild disease with consideration of oral vancomycin as initial treatment for moderate or severe cases.

Clinical progress rather than repeat toxin assays should guide management decisions and surgical consultation is recommended when disease progresses during treatment.

Adjunctive measures such as probiotic therapy, IVIG and agents to bind toxin have garnered interest but are not supported by high level evidence.

Antimotility agents including narcotics should be avoided, as they increase the risk for megacolon.

Clinical vignettes on perioperative beta blockers

From Mayo Clinic Jacksonville. Via Post Graduate Medicine.

Diabetes type 1.5

AKA Flatbush diabetes, atypical diabetes, diabetes type 1B and more recently ketosis prone type 2 diabetes. This increasingly recognized but still under appreciated condition was reviewed in the March 7 2006 issue of Annals of Internal Medicine.

With the emergence of this relatively new profile of diabetes the traditional classification has been challenged. Older concepts, though useful and largely true, must now be nuanced. For the past 20 years the defining characteristic of type 1 DM has been that when deprived of exogenous insulin the patient invariably develops ketoacidosis (DKA) in the basal state. In contrast, while type 2 diabetics may develop ketosis under stress (e.g. with myocardial infarction, sepsis, etc.) they never develop DKA in the basal state.

For classic types 1 and 2 these principles remain valid. They were a welcome replacement to the outmoded notion of “adult versus juvenile onset” types and the more recent (and extant but nevertheless confusing) terms “insulin dependent” and “non-insulin dependent” diabetes.

Enter now the new profile which might be described as the occasional but not invariable development of DKA during exogenous insulin deprivation in the basal state. These are the patients who come in with DKA (often with no apparent precipitating stress) but who, weeks or months later, discontinue insulin and do just fine. At times they behave like DM-1; at other times they look for all the world like DM-2.

What’s going on? Since these folks were first noticed in 1987 they tended to be regarded as a fuzzy overlap syndrome, poorly understood. Research in the ensuing years has improved our understanding of the condition and it’s all nicely summarized in the Annals review. Take home points follow.

1) It tends to be seen in African American and Hispanic persons, though not exclusively so. 25% to 50% of African American and Hispanic patients who present with DKA (not to be extrapolated to all African Americans and Hispanics with diabetes) have been reported to exhibit this profile.
2) Unlike classic DM-1, patients tend to be obese at presentation with DKA.
3) It does not appear to be an autoimmune disorder, in contrast to the well documented autoimmune beta cell destruction of classic DM-1. Instead it’s an intermittent reversible beta cell failure.
4) The beta cell failure appears to be, at least in part, an exaggerated form of glucose toxicity. Thus, presentation with DKA may follow a prolonged period of uncontrolled hyperglycemia, with recovery of beta cell function following a period of glycemic control with insulin.
5) More than 80% of patients have a family history of DM-2.
6) This profile of diabetes is to be distinguished from other atypical forms of diabetes including MODY and LADA.

Note---to confuse things, LADA in some writings has been given the designation DM-1.5. One of these days maybe the experts who sit down at meetings and talk about such things will deliver a clarification, written in stone.

Tools to sharpen your baloney detector

The SkepticWiki

Hospitalist consultation for hip fracture surgery

Mayo Clinic Proceedings provided another addition to the growing literature on hospitalist care with this study of hip fracture surgery, comparing hospitalists with traditional primary care physicians for medical consultation. Hospitalist consultation was associated with statistically significant reductions in time to consultation and time to surgery. Cost and length of stay reductions were not statistically significant. Previous literature has suggested that reduced time to surgery is associated with better outcomes.

The discussion section describes practice patterns of hospitalists at the study site (Mayo Clinic Jacksonville) and speculates how hospitalists might improve outcomes for surgical patients.

How good are systematic reviews of alternative medicine?

Only as good as their major reference source, Medline. But Medline is biased toward alternative medicine. I recently pointed out that Medline searches of topics related to Complementary and Alternative Medicine (CAM) were overwhelmingly uncritical. Why? According to this editorial by Wallace Sampson, the process of journal selection for Medline indexing is riddled with conflicts of interest.

He concludes: This situation has resulted in an advocacy-dominated fund of material that biases research reports, systematic reviews, and meta-analyses; alters student research projects and medical school teaching; and biases patient and physician searches.

A physician believed the drug reps, took Vioxx and had a heart attack

Now he’s suing the drug company. “I would never have taken the drug, nor would I have prescribed it to any of my patients, had I known of any of the risks,'' Braun said yesterday in an interview. “You assume that when someone comes in to the office with literature about the drug that what they're telling you is true. You assume this drug is safe.'' Read more.

Paroxetine and recurrent depression in the elderly

From the March 16 NEJM comes this paper reporting a greater than two fold increase in risk of recurrent depression in elderly patients who switch from paroxetine (Paxil, Paxil CR) to placebo after an initial response. The number needed to treat to prevent one recurrence was 4.

New findings on health care disparities

From a large survey reported in the March 16 2006 NEJM:

Over all, “recommended care”, as defined across a spectrum of multiple quality indicators, was delivered just over half the time, a finding consistent with previous studies. Variation among groups was less than the overall quality gap.

There were some surprising findings. Quality scores were higher for women than for men and higher for blacks and Hispanics than for whites.

The authors conclude: “Quality-improvement programs that focus solely on reducing disparities among sociodemographic subgroups may miss larger opportunities to improve care.”

What form of anticoagulation is best for unstable angina and NSTEMI?

The on line edition of NEJM has published, ahead of print, a large study by the OASIS-5 investigators comparing enoxaparin (Lovenox) and fondaparinux (Arixtra) in patients with non-ST segment elevation acute coronary syndromes (unstable angina and NSTEMI). Enoxaparin is a low molecular weight heparin. Fondaparinux is a synthetic pentasaccharide inhibitor of factor Xa. The primary efficacy endpoint was similar in the two groups but bleeding was markedly less in the fondaparinux group. Over all the number needed to treat with fondaparinux instead of enoxaparin to prevent 1 death was 150.

Of particular interest was how these agents were dosed compared to their doses for other indications. Fondaparinux showed non-inferiority despite a relatively low dose in comparison to enoxaparin. The low dose may explain the lower incidence of bleeding. Put another way: both agents are approved for both the prophylaxis and treatment of venous thromboembolism (VTE) with much higher doses for the treatment indication (two or more times the prophylactic dose). However in this study of acute coronary syndrome fondaparinux was administered in its VTE prophylactic dose while enoxaparin was given in its VTE treatment dose.

Both drugs are eliminated by renal excretion. For VTE indications enoxaparin’s labeling allows for dosage adjustment in renal failure whereas fondaparinux carries a contraindication for patients with creatinine clearance less than 30.

An accompanying editorial provides perspective.

Multifocal chorioretinitis in West Nile Virus Infection

A report in Mayo Clinic Proceedings from a West Nile Virus (WNV) outbreak in Tunisia points to a strong association with a characteristic variety of multifocal chorioretinitis. In the survey of patients presenting with a picture of encephalitis or meningoencephalitis, the presence of multifocal chorioretinitis had a 100% positive predictive value for the diagnosis of WNV. The authors suggest that ophthalmologic evaluation be routinely carried out when WNV infection is considered.

Has the homocysteine hypothesis been debunked?

No! But you can bet that’s what the media will say about two studies just released ahead of print by NEJM. One, the NORVIT trial, we already knew about. It was presented at the European Society of Cardiology months ago and I blogged my perspective here. The other, HOPE 2, had findings consistent with NORVIT: non-selective use of folic acid, vitamin B6 and vitamin B12 is ineffective for secondary prevention of vascular events.

Why don’t these results debunk the homocysteine hypothesis? Because the studies didn’t ask that question. These vitamins were tested on patients irrespective of their homocysteine levels. Baseline levels in the study populations were around 12 or 13---hardly what we would consider elevated, and not in the range that has been found to be associated with clear evidence of hypercoagulability in previous studies. What this work does confirm is a) if there is an optimal homocysteine target for cardiovascular health that target is unknown---previous targets of 9-10 were unnecessarily low and b) the popular practice of routine supplementation with B vitamins to prevent vascular events is not warranted. There still may be a role for measurement of homocysteine in selected patients, with consideration for treatment if it’s clearly elevated.

For a good perspective on these studies read the accompanying editorial. Don’t bother with the media reports.

Corticosteroids in sepsis

“Megadoses” of glucocorticoids were in vogue for sepsis treatment in the 1970s and early 1980s. The practice was abandoned in the late 1980s when studies suggested lack of benefit and possible harm. More recent evidence has suggested benefits of lower pharmacologic doses of hydrocortisone in patients with septic shock. Consequently, hydrocortisone treatment is included in the surviving sepsis guidelines and the sepsis bundle. Part of the rationale for such treatment is the new concept that patients in septic shock have “relative adrenal insufficiency”, a form of decreased adrenal reserve which differs from classic Addison’s disease. Although evidence in favor of corticosteroid treatment for septic shock is accumulating, controversy persists concerning how relative adrenal insufficiency should be defined and how patients should be selected for treatment. Some of the unanswered questions are now being addressed in the CORTICUS trial. It’s all nicely updated in December’s issue of CCJM.

Practicing medicine----can we self-actualize?

First described by Kurt Goldstein, the notion of self-actualization was popularized by Abraham Maslow in his description of the hierarchy of needs. Simply put, the theory holds that along the path to achievement of one’s potential (self-actualization) is a hierarchical progression of prerequisite needs to be met.

R. Whit Curry, Jr, MD, Professor of Community Health and Family Medicine at the University of Florida, writes in the March 11 issue of Patient Care about the seemingly joyless struggle of practicing medicine. He challenges us to get past the “baggage” of the medical profession and self-actualize by focusing on the uniquely positive aspects: the satisfaction of helping and making a difference, the joy of learning and the privilege of glimpsing a fascinating slice of life.

But the hierarchy of needs is an obstacle course which can be difficult to ascend at times. The baggage of medicine can suck the joy right out of us; it gets in the way of the path to self-actualization. This baggage must be shed in order to achieve professional satisfaction. Maslow’s categories of needs have parallels in medicine: physiological needs (sleep deprivation, overwork); safety (looming threats of litigation and Medicare audits); love/belonging (patient complaints, critical colleagues, family stress, sense of isolation) and esteem (law suits, culture of blame).

These are difficult issues. The joy of practicing medicine (or self-actualization, professional satisfaction, call it what you will) can be elusive. Those who achieve it are of a special breed. Without a major cultural shift they will remain an elite group. (I wonder---can you blog your way to self-actualization?).

Invasive group A strep anecdote

A 44 year old nursing home employee jammed her hand in a wheel chair. Her thumb became red and swollen and she was dead within 3 days, evidently of group A streptococcal necrotizing fasciitis. Read here.

Everything you wanted to know about community acquired MRSA---

can be found in the March 7 2006 issue of Annals of Internal Medicine. A study from Atlanta found that 63% of staphylococcal skin and soft tissue infections were due to CA-MRSA, underscoring the need to direct empiric therapy of such infections toward CA-MRSA. Empiric antibiotic selection in 2/3 of these cases was inadequate. (Kidney Notes cited this paper).

Despite the vast increase in CA-MRSA infections this nation wide survey of colonization rates revealed that in noninstitutionalized persons the prevalence of any Staph aureus nasal colonization was 31.6% but only 0.84% for MRSA. There is no clear explanation for this seemingly discordant finding. Perhaps transmission and invasion of CA-MRSA does not correlate with nasal carriage, reflecting differences in transmissibility and pathogenesis compared to “old” MRSA strains.

An editorial in the same issue offers these pearls about CA-MRSA, some of which I’ve mentioned before:

1) CA-MRSA is a distinct form of MRSA. It is not a spread of the old nosocomial strain to the community---it’s a new bug which is distinguished by its genome, its pathogenicity and its antimicrobial sensitivity pattern. Indeed the distinction between hospital and community is becoming blurred, as the new strain is showing up increasingly in hospitals.

2) Almost all CA-MRSA (and virtually none of the traditional MRSA) produce the Panton-Valentine leukocidin (PVL). This toxin causes tissue necrosis, possibly explaining the association of CA-MRSA with necrotizing fasciitis and severe necrotizing pneumonia. The fact that such severe necrotizing sequelae are seen only in a small minority of CA-MRSA infections suggests the necessity of variable co-factors conspiring with PVL to produce severe infections. The presence of PVL may be responsible for the necrotic center characteristic of the much more common skin infections leading to the frequent mistaken impression of spider bite.

3) CA-MRSA isolates are sensitive to tetracyclines, trimethoprim-sulfamethoxazole and clindamycin. Although the use of such agents is popular the author cautions that they have not been studied in clinical trials. Clindamycin has the added problem of frequent acquired resistance which can be anticipated if the isolate is resistant to erythromycin and predicted in the micro lab with the “D” test. For severe infections vancomycin or linezolid should be used. Daptomycin is acceptable if there is no pulmonary involvement.

Some physicians really are disruptive

The definition of disruptive physician behavior is often in dispute, but sometimes you just know it when you see it. Via MSSPNexus Blog.

Safety regs must take into account Americans’ weight gain

Coast Guard assumptions about the average passenger’s weight were based on 1942 estimates. The trouble is, folks were slimmer back then. This, according to the National Transportation and Safety Board, was one factor in the capsizing of a Baltimore water taxi in 2004, which killed five people. Underestimation of passenger weight has been a factor in other accidents. Read more here.

Orac does his homework on controversial paper about autism and vaccines

About the same time I was blogging about chelation deaths and the related topic of chelation as a treatment for autism a paper was published claiming to demonstrate an association between mercury based vaccine preservatives and neurodevelopmental disorders. I decided to make a preemptive strike and expose the paper to the light of day before someone came along and said “See…….”

I was dubious about the paper. Buried in the somewhat obscure Journal of American Physicians and Surgeons the paper seemed unlikely to undergo the trial by fire of critical commentary normally afforded controversial articles published in major journals. Nevertheless it’s already been given heavy promotion in the media as breaking news of a mercury-autism link. [1] [2] [3] [4] [5] [6] [7] [8] [9] [10]. Not surprisingly, the articles are sensational and largely uncritical. So, I figured it was up to the blogosphere to provide appropriate critical analysis.

Orac at Respectful Insolence did not disappoint. He quickly weighed in with a detailed and insightful analysis which casts doubt on the validity of the paper’s conclusions. He’s done a much better job than I could have, so go and read his rant. He must have burned some midnight oil in preparation of this post. I only hope he didn’t have surgery scheduled the next morning.

A new wrinkle in the controversy on autism and vaccines

The claim behind chelation therapy for autism is that the condition is related to mercury poisoning. Remove the mercury, cure the autism. In a recent post on chelation related deaths I cited a lack of evidence for the claim.

Now in the interest of being fair and balanced I must acknowledge this paper which was just published in the Journal of American Physicians and Surgeons. Looking at trends in the diagnosis of autism and related disorders before and after thimerosal was removed from vaccines in the U.S. the study purports to show a decline in neurodevelopmental disorders which parallels the withdrawl of thimerosal. Thimerosal (AKA merthiolate) is a mercury containing preservative.

A press release accompanied the publication of this paper, which will probably receive heavy media coverage. A discussion at the Health Fraud List is critical of the study and cites this blog concerning the credibility of the authors.

Although I’m skeptical of this paper I lack expertise in the field and would welcome critical analysis from readers.

Chelation therapy deaths: wrong drug or wrong indication?

I recently linked to an article in MMWR, a CDC sponsored periodical, about three chelation therapy deaths. Although other bloggers covered the issue thoroughly some months ago it resurfaced with the March 3 MMWR piece and the spate of media reports that followed. Reporting on the issue of chelation deaths was distorted from the beginning and the distortion persists in this latest barrage. A piece from the Pittsburg Post-Gazette characterized the death of 5 year old Abubakar Tariq Nadama as an example of medication error. CDC’s Dr. Mary Jean Brown is quoted "It's a case of look-alike/sound-alike medications." But this misses the larger point: chelation therapy was given to the child for the unproven and unapproved “indication” of autism.

The case has been well covered by other bloggers. Orac has blogged about it since August. I just found this insightful post by Dr. Kimball Atwood at Health Care Renewal who points out that Dr. Brown misses the real tragedy. It is not a simple case of medical error.

The January 18 Post-Gazette article quotes Dr. Brown as making the misleading statement “that it was medical error, and not the therapy itself” that caused the death. Worse, the article reports “Dr. Mary Jean Brown, chief of the Lead Poisoning Prevention Branch of the Atlanta-based Centers for Disease Control and Prevention, said yesterday that Abubakar Tariq Nadama died Aug. 23 in his Butler County doctor's office because he was given the wrong chelation agent.” Now I’m confused. That statement implies the existence of a “right” chelation agent. But can there be a right agent for a wrong indication? Although chelation therapy has seen an exponential rise in popularity as a treatment for autism there’s no scientific evidence that it works. According to this Quackwatch article, “The use of chelation therapy to treat autistic children is completely bogus.”

Maintaining that calcium EDTA is safer than disodium EDTA (used in the treatment of Abubakar Tariq Nadama) Brown “quoted from a 1985 CDC statement: Only Calcium Disodium EDTA should be used. Disodium EDTA should never be used ... because it may induce fatal hypocalcemia, low calcium and tetany."

That’s interesting, because as I pointed out (so did Atwood in the Health Care Renewal Blog) disodium EDTA, this dangerous drug which the CDC expert says should never be used, is exactly what is being used in the NCCAM sponsored Trial to Assess Chelation Therapy (TACT). Maybe the NCCAM should have checked with the CDC before launching the study. As I understand it TACT is to be the definitive study to determine whether chelation therapy is ready for prime time in the treatment of cardiovascular disease. But aren’t there safety standards that must be followed in such trials? One of the purposes of phase 1 and 2 studies in mainstream drug development, as I understand it, is to help establish conditions for optimal drug safety in phase 3 studies and beyond. Well, this isn’t mainstream drug development.

But I digress. Another chelation related death mentioned in the MMWR article involved a 53 year old woman being treated in a naturopathic practitioner’s office. In my previous post I didn’t comment on the appropriateness of the treatment because the indication wasn’t given. However, I subsequently found this report which states the treatment was given for “clogged arteries.” The type of chelation solution she received is apparently not known. The media seem most interested in finding out what type of preparation was used, downplaying the more important issue of pseudoscience.

The CDC and its media accomplices have wrongly spun these cases as examples of medication mix ups. In fact only one of the three deaths profiled in the MMWR report, the case of a child being chelated for lead poisoning, was attributable to medication error. The best information we have indicates that the other two patients were being treated for purported indications not scientifically validated. In the absence of any scientific indication for the modality in question there’s little point in talking about the right versus the wrong drug. There’s no right drug for a wrong indication.

Cochrane review on gabapentin for neuropathic pain

This Cochrane review is abstracted in the February 1 issue of American Family Physician. Gabapentin is effective with a number needed to treat (NNT) of 4. Adverse effects including dizziness, somnolence and headache occur with a number needed to harm (NNH) of 4. This is a significant trade off which must be gauged by patient preference. Tricyclics and carbamazepine have lower NNTs and are less expensive.

The CDC is investigating chelation related deaths

The CDC’s Morbidity and Mortality Weekly Report describes three cases in its March 3 edition. The common thread appears to be severe hypocalcemia, a complication associated with Na2EDTA as opposed to CaEDTA and other chelating agents. The first case was for the appropriate indication of lead intoxication in a 2 year old girl. Treatment was properly begun with the safer CaEDTA. For reasons unclear the second infusion consisted of Na2EDTA, followed by severe hypocalcemia and fatal cardiac arrest.

The second case was that of a 5 year old boy with autism who died during the infusion of Na2EDTA. The report doesn’t say the treatment was being given for the indication of autism although proponents have advocated chelation for autism treatment in spite of a lack of supporting evidence.

The third case involved a 53 year old woman who died 10-15 minutes after the start of an infusion being administered by a naturopathic practitioner. Although her calcium level during the resuscitation attempt was low, neither the indication for chelation nor the type of chelation solution was specified in the report.

When chelation is used for the unproven indication of atherosclerosis, the more dangerous Na2EDTA preparation has traditionally been used and is the preparation currently used in the NCCAM Trial for the Assessment of Chelation Therapy, according to the TACT study protocol.

Under appreciated vascular complications of giant cell arteritis

Thoracic and abdominal aortic aneurysm, aortic dissection and limb artery stenosis are not uncommon. Such complications can present during the active treatment phase or years later. According to this review (Current Opinion in Rheumatology) 1 in 5 patients with GCA will develop an aortic aneurysm and 1 in 16 will dissect. A strategy for screening and surveillance is presented.

Cerebral palsy verdict could close hospital

“Tyrone Hospital said in a court petition filed Monday that it will declare bankruptcy or close its doors if a Blair County judge does not reduce a $4 million verdict awarded by a jury two weeks ago.” Read the rest here.

The propagation of the absurd in mainstream medicine

Wallace Sampson and Kimball Atwood put aside political correctness and pull no punches in their criticism of mainstream medicine’s widespread uncritical acceptance of unproven and implausible alternative claims. Their uncompromising viewpoint on complementary and alternative medicine (CAM) appears in the December issue of the Medical Journal of Australia (MJA). I’ve been hammering away in the pages of this blog trying to issue a plea for scientific integrity in medical education and in our healthcare institutions for some months now. I haven’t succeeded nearly as well as these authors have. A few of their points will be mentioned here.

The authors blame postmodernism for much of the uncritical acceptance of CAM, noting that postmodernism tolerates multiple and contradictory ways of thinking, “without need for resolution through reason and experiment, resulting in a medical pluralism.” I made a similar point about postmodernism driving alternative medicine in a previous post.

Detractors are fond of saying “but medical students need to know about these things” or “they’re doing research”. Trouble is, much of this so called “education and research” amounts to little more than uncritical promotion of quackery. I’ve given examples before, and the authors of the MJA piece make the case effectively. They cite data, for example, that of the 175 medical school CAM courses in existence only 4 take a critical approach. This means that the vast majority of curricula promote unproven and implausible methods, implicitly if not directly. Moreover, Medline abstracts overwhelmingly promote, and few if any critique CAM. They also note that the NIH web pages link only to promotional CAM sites as opposed to objective critical sites like Quackwatch.

Finally the authors address the problems inherent in researching biologically implausible claims by urging a Bayesian approach in which research findings are interpreted in light of prior knowledge and plausibility.

Read the article in the original and bookmark it as a powerful expose of pseudoscience.

Targeted statin therapy versus usual care: The ALLIANCE trial

Recently published in the American Journal of Medicine, the study compared a formal strategy of treating to new aggressive LDL targets (<80 mg/dl) with “usual care.” The formal strategy used atorvastatin in doses up to 80 mg daily and was associated with improved cardiovascular outcomes. It is not clear how many of the usual care patients received statin drugs, but apparently a substantial number. 66% of all patients were on lipid lowering medications at study entry. The usual care group achieved an average post treatment LDLC level of 111 mg/dl as opposed to 95 mg/dl in the formal treatment group. Treatment adjustments in the usual care group were at the discretion of the primary physician, to simulate “real world” conditions.

Usual care in this study, achieving an average LDLC of 111 mg/dl, was surprisingly good. Nevertheless the formal targeted strategy was better. To me this finding speaks strongly for the use of dedicated lipid clinics. I know of no better way to apply these results to community practice. Finally, these results are in marked contrast to the lipid arm of ALLHAT which found pravastatin 40 mg daily to be no better than usual care.

Differential diagnosis resources

Although I trashed last week’s controversial New York Times article about misdiagnosis the article was not totally devoid of substance. It pointed me to Isabel, a web based differential diagnosis reminder system. It’s named after Isabel Maude, the girl with chicken pox and a delayed diagnosis of necrotizing fasciitis who was profiled in the New York Times story. When Isabel was on the mend at the tertiary care center, staff there began hinting that the case had been mishandled. The parents were angry and friends urged them to sue. Instead, Jason Maude decided to direct his energies more constructively. He founded a software company to develop a program to help physicians improve diagnostic accuracy.

How does it work? Typing in the patient’s presenting signs and symptoms yields an extensive list of possible diagnoses, with the idea that the physician will be reminded of rare diseases or uncommon presentations of more common diseases which might otherwise be overlooked. Isabel started out as a pediatric resource but has since been expanded to include adult medicine.

Other differential diagnosis resources are out there. I’ve had some experience with Dxplain, a program from Mass General. Although Dxplain is primarily licensed to institutions, a free portal is available for individual subscribers to Merck Medicus. I occasionally use Dxplain and have signed up for a free trial of Isabel. I’ll plug a few cases into both programs for comparison and report back soon.

Meanwhile the web version of the New York Times article links to an audio interview of Jason Maude. (Check the left sidebar). He discusses his daughter’s case and the history of development of the Isabel program. It gets a little self promoting at the end. Jason suggests patients ask their doctor “Have you tried Isabel?” There’s talk of developing a consumer version. Now that could get interesting. Imagine your patient with gastroenteritis telling you “I did an Isabel search and it told me vomiting can be due to a cerebellar tumor or hemorrhage. I want an MRI.”

Canada’s struggle for health care quality

The Institute of Medicine’s Quality Chasm report stresses that health care must be timely and patient centered. How’s Canada doing? They’re trying, but non-emergency health care there is anything but timely. Newly announced federal wait time benchmarks, hailed as a major improvement, are deemed inadequate by Canadian physician specialty groups according to this report in CMAJ. They include cancer irradiation within 4 weeks, hip fracture repair within 48 hours, hip and knee replacement within 6 months, cataract surgery within 4 months for high risk patients, and coronary artery bypass surgery in 2 to 6 weeks in high risk patients. And that’s considered improvement.

Worse, there’s a wait time for the improvements. Canada’s provinces were given 2 years to set implementation targets.

Resolution of pulmonary emboli

This study in Chest questions the conventional wisdom. We assume pulmonary emboli resolve, and those few whose emboli do not are the ones destined to get chronic thromboembolic pulmonary hypertension. But this systematic review indicates residual thrombi present in 87% of patients at 8 days following diagnosis and 52% at 11 months. The authors suggest re-imaging after treatment to establish a baseline. I’m not sure how it applies to the real world. The study has its flaws---only 4 of 29 papers of widely varying methods were included in the analysis.

Why do newspapers so often get it wrong?

There’s been some fallout from the New York Times article this week on misdiagnosis. Evidently the NYT got wind of their error of describing a case of necrotizing fasciitis as a flesh eating virus. Although they published no acknowledgement of the error, at least that I can find, they’ve changed the wording of the web version to read “flesh eating infection.” They were so sneaky about it that I began to doubt the accuracy of my own reporting. Had it really said virus? I tried Google’s cache and the Wayback Machine to no avail.

Finally I found a paste of the original version on the UCSF Emergency Medicine List where there is a lively thread. Indeed the original NYT version described the flesh eating infection as a virus. Several doctors on the UCSF list object to the article’s comparison of health care to the airline industry. One writer, Bob Solomon, said “Airplanes are machines. Patients and their families are people. Comparisons are absurd.”

What Isabel Maude, the girl with the flesh eating infection, actually had was chicken pox complicated by Group A Streptococcal necrotizing fasciitis and toxic shock syndrome. DB weighed in and one of his commenters made a good point about necrotizing fasciitis. He said “I can’t believe that the NYT could not come up with a better example of ‘misdiagnosis’ than that. The kid DID have chicken pox, complicated by necrotizing fascitis (a bacteria Ms. New York Times reporter, not a virus). This was an example of incomplete diagnosis, not misdiagnosis. Also, necrotizing fascitis can move incredibly fast, so who is to say that it was present at a detectable stage when the patient first presented.”

Finally, a commenter at Kevin MD questioned the accuracy of autopsy data in assessing diagnostic error: “Finally, because the rate of post-mortem exams is now so low, only cases with some uncertainty are subject to this final check. The application of the post-mortem exam is not a randomly assigned process, but is selected by the presence of strong clinical uncertainty on the part of physicians and/or family.” Well said.

The nuts and bolts of troponin measurement

Troponin is a reliable marker for cardiac injury but questions often arise. What non cardiac conditions are associated with elevations? What is the significance of elevated troponin levels in renal failure? After PCI, ablation procedures or cardioversion? Here in CMAJ is one of the better troponin reviews this blogger has seen.

Why are smart people so stupid about health claims?

Maybe it’s a failure of our educational system, suggests this writer. There’s too much effort to teach us what to think rather than how to think. Even college education seems to have a minimal impact on people’s beliefs in ESP, astrology and alternative medicine according to one survey.

New York Times on misdiagnosis: a follow up

My post about the NYT article on misdiagnosis sparked discussion by commenters and other bloggers. I wrote that pay for performance (P4P) has not been demonstrated to improve quality. An anonymous commenter said “Uh, the study DID show improved screening rates for cervical cancer (at least according to the abstract).” To elaborate: three measures, cervical cancer screening, mammography, and hemoglobin A1C measurement were analyzed. After implementation of P4P there was no difference in improvement for two of the three measures. Cervical cancer screening showed a modest difference in improvement (3.6%). Moreover most of the bonus money went to providers already above the quality thresholds at baseline, who demonstrated little improvement. I stand corrected for not having nuanced my statement about the study findings, although these data do not make a convincing case that P4P improves quality. Perhaps we can agree, at the risk of being trite, that more study is needed.

Kevin linked to my post. One of his commenters, Dr. Hebert, pointed out the absurdity of rewarding or penalizing doctors for outcomes. He said “If doctors are paid by outcome, patients that have diseases with poor prognoses, like liver cancer or spinal injuries, will find themselves unable to find a doctor.”

Hippocrates at health voices weighed in with “Fighting the public's perception that there is room for improvement in health care quality is a losing proposition, both politically and economically. Skyrocketing health care costs make demands for accountability inevitable.” Hippocrates may have missed my point. I would never argue against room for quality improvement. I was merely taking the New York Times to task for distorting the facts. Talking about incentivizing quality, the Times piece says “For a politician looking to make the often-bloodless debate over health care come alive, this is a huge opportunity.” Is the author looking for a political football or a blood bath? That’s the problem I have with this piece. Can’t we keep the health care debate sober and factual?

Hippocrates also said “Pay-for-performance is an easy concept for the public to grasp and ignoring this is an indefensible position.” Ignoring it is one thing; asking for proof is another. What’s missing from this discussion is consideration of the cost of widespread adoption of P4P with incentives that are meaningful. Once the public grasps the true cost how will they perceive it?

Alternative medicine is not harmless

An outbreak of cutaneous Mycobacterium abscessus infection was traced to an acupuncture clinic, as reported in BMC Infectious Diseases.

The open access movement

There is a burgeoning drive for more free access to on line scientific publication. Here’s a blog devoted to the issue, which has links to open access resources.

Newspaper hype versus clinical reality

A February 22 New York Times article entitled “Why Doctors So Often Get It Wrong” (registration required) deals with the problem of medical diagnostic error. Claiming that medicine suffers from a “misdiagnosis crisis” the article asks “How can this be happening? And how is it not a source of national outrage?”

We are told the story of a little girl who suffered consequences of delayed diagnosis. The New York Times piece states that the girl, diagnosed as chickenpox, actually turned out to have a flesh eating virus which her doctors failed to diagnose until her organs started shutting down. Hmmm----what’s a flesh eating virus anyway? Chickenpox is a virus. Did the doctors diagnose the wrong virus? A more accurate BBC report indicates that the girl actually had chickenpox complicated by necrotizing fasciitis, a bacterial infection.

With that little trifle out of the way let’s consider the article’s major premise about misdiagnosis. The article mentions autopsy data showing a 20% misdiagnosis rate, with JAMA as the source. Although the Times gives no citation, the JAMA article in question is probably this systematic review of autopsy-detected diagnostic errors. What the Times neglected to point out is that although the JAMA analysis found a 23.5% error rate, the rate of errors likely to have affected outcome was only 9%. Moreover, while the Times article claims that the error rate has not improved since the 1930’s the JAMA study found a continuous decline in the error rate between 1966 and 2002.

Although the Times article suggests that pay for performance and penalties for errors might solve the “crisis” the data suggest otherwise. Studies on Pay for Performance to date have failed to demonstrate improved quality. A spate of articles analyzing medical error indicates that promotion of a culture of blame by penalizing doctors for honest mistakes is counter productive.

The JAMA perspective is more nuanced: “However, it remains unclear to what extent clinically missed diagnoses represent errors per se, rather than acceptable limits of antemortem diagnosis in the face of atypical clinical presentations. In fact, because the vast majority of autopsy studies come from teaching hospitals, published autopsy series may be enriched for atypical cases.”

Trends in massage therapy

Massage therapy has some useful applications. It is not inherently pseudoscientific. But like medicine, education and practice in the field have seen considerable contamination by pseudoscience and fraud. The American Medical Massage Association (AMMA) is concerned and has taken a stand against such practices.

Recent data on massage therapy practice patterns published in BMC Complementary and Alternative Medicine would seem to validate the concerns of the AMMA. Surveys conducted in Connecticut and Washington reveal the following respective percentages of massage therapists using questionable methods:

Applied kinesiology 2%, 5.8%

Craniosacral therapy 15.3%, 15.1%

Energy work 24.9%, 17.2%

Oriental bodywork 16.6%, 8.6%

Reflexology 15.0%, 15.4%


This paper provides us with new and confirmatory evidence to support Stephen Barrett’s previous assertion that quackery is pervasive in the field.

Here’s an account of one massage student’s experience.

Cryoglobulinemic vasculitis

Cryoglobulinemic vasculitis is due to hepatitis C in the majority of cases. This review (Current Opinion in Rheumatology) covers many of the points I referenced here.

Best practices in hip fracture care

Hospitalists are often involved in the co management of patients with hip fracture. Published in the November issue of the Journal of General Internal Medicine, (linked via Medscape) this systematic review looked at multiple practices in the perioperative care of hip fracture patients. Specialty mattresses to prevent pressure ulcers, regional anesthesia, DVT prophylaxis, antibiotic prophylaxis, replacing continuous urinary catheters with intermittent catheterization, and epidural analgesia are supported by high level studies. Performance of surgery within 24 hours is also associated with better outcomes although there are no level 1 studies.

Somewhat surprisingly, several popular interventions are not supported by evidence. These include traction, postoperative drains and the use of multidisciplinary teams.

Did UCLA accept money from Herbalife?

Apparently so. The Mark Hughes Cellular and Molecular Nutrition Laboratory, a division of the Center for Human Nutrition, UCLA David Geffin School of Medicine, is named for Herbalife’s founder. UCLA professor of medicine and public health David Heber, M.D. PhD, F.A.C.P., F.A.C.N lent his good name to the company by assuming the chair of Herbalife’s Scientific Advisory Board at about the same time Herbalife donated $3 million to the UCLA center according to this report from Forbes.com. It also seemed to dovetail with the promotion of Herber’s book The L.A. Shape Diet which, according to the Forbes piece, recommends one of Herbalife’s signature products. A win-win situation.

The UCLA center’s nutrition syllabus appears to be a mix of good and bad information. Examples of dubious claims include: a “suggestion” that vitamin E be supplemented in doses of up to 400 IU/day (despite lack of evidence of benefit as assessed in multiple studies and a suggestion of increased risk for heart failure in the HOPE trial); the claim that vitamin C lowers cardiovascular risk; statements that vitamins B12 and B6 and folic acid lower homocysteine levels in patients with cardiovascular disease (they may in certain patients, but the statement is deceptive in that recent evidence contraindicates routine supplementation in patients with cardiovascular disease); and the nebulous claim that echinacea boosts the immune system.

Here’s a critical expose on Herbalife from MLMwatch. This Wikipedia article profiles the history of Herbalife and its multilevel marketing practices.

Candida in the respiratory tract

We knew that Candida recovered from the respiratory tract generally meant colonization and not infection. Now there’s evidence that Candida respiratory tract colonization is a marker of risk for bacterial pneumonia in patients on mechanical ventilation. The strongest association is with Pseudomonas. The study was reported in Chest January 2006.

The granddaddy of Atrovent and Spiriva

The nineteenth and early twentieth century predecessor of these inhaled drugs for COPD was Dr. Schiffmann’s Asthmador. It worked because of its anticholinergic properties residing in the active ingredient belladonna. Like Atrovent and Spiriva it blocked muscarinic receptors in the bronchial tree, resulting in bronchodilation.

It’s certainly more “natural” than Atrovent and Spiriva. I suspect the NCCAM would be subjecting it to the rigors of evidence based medicine were it not for a particular disadvantage---the product had to be smoked in a pipe or as a cigarette---a bit of a problem for folks who use supplemental oxygen.

Cost effective treatment of heparin induced thrombocytopenia

HIT is an important issue in hospital medicine. As I’ve blogged before, when there’s sufficient clinical suspicion early treatment with a direct thrombin inhibitor (without waiting for laboratory confirmation via antibody testing) is indicated to avert severe clinical consequences. Now we also have evidence (via Cardiology in Review) that it’s cost effective. Some good clinical points and references about HIT are found in the article.

Cardiac encephalopathy

I’d like to know more about this.

Setting the record straight about Creighton University alt med links

Two commenters cautioned me about my post originally entitled “Creighton University School of Medicine promotes unscientific methods.” Anonymous said “Be careful with your title there ... it clearly states at the bottom of the page that the views on those pages are not those of Creighton University, but of the author.” EoR said “I think the ‘Scientific Information’ link (http://altmed.creighton.edu/crystal/feedback.htm) says it all. Takes you to a page that starts ‘There is no actual scientific evidence’. Exactly.”

Indeed these and other disclaimers are found within the Creighton University alt med links. I took a closer look at the links. Some are appropriately critical, some are neutral, and others are implicitly or explicitly promotional.

The main links page says “The opinions expressed in these articles are those of the authors alone” and “This page is for informational purposes only and the practices described herein are not endorsed by Creighton University.”

The web site is maintained by a professor who teaches the senior medical student alt med elective. Many of the articles appear to be written by the students.

It was not my intent to imply that the promotional material reflects the position of the university as a whole. I regret the misunderstanding and have edited the title of that particular post. Having established that the university does not officially endorse these claims I have to ask why the school of medicine allows such content on its web pages. I will examine more of this content in future posts.

National Center for Complementary and Alternative Medicine admits they’ve been doing it wrong

The director and deputy director of the Office of Clinical and Regulatory Affairs of the National Center for Complementary and Alternative Medicine (NCCAM) wrote this editorial in the Medical Journal of Australia entitled “Complementary and alternative medicine in 2006: optimising the dose of the intervention.” In its research of various herbal and “natural” remedies NCCAM study protocols have selected doses and preparations already in popular use. Apparently they’ve now figured out that’s not the way to go about it, finally realizing that they should have been doing dose finding studies the way mainstream drug research does in phase I and II trials.

Here’s a statement from the introduction of the editorial: “…..one initial approach taken by NCCAM was to sponsor large trials of supplements using doses representative of those commonly used. The rationale included the concern that if the common dose is unsafe, it would be important to alert the public. Moreover, these doses were often used in smaller, less well-controlled studies. However, NCCAM found that this is not an optimal research strategy. As NCCAM defines its priorities and strategies for the next few years, we recognise that reinvestigation and optimisation of customary procedures, especially dose, is needed if NCCAM is to make informed statements.”

The authors also state: “In addition, the literature is unlikely to be conclusive because the manner in which an intervention is commonly used is unlikely to optimise the many factors that together could make an intervention successful.”

Admitting that NCCAM’s assumptions were wrong the authors imply that we should disregard negative results in studies of CAM---if only we discover the right dose or the right conditions we will eventually prove efficacy. They write “In addition, the literature is unlikely to be conclusive because the manner in which an intervention is commonly used is unlikely to optimise the many factors that together could make an intervention successful.” And “Early ‘negative’ results present a particular challenge for CAM, given that some people are very sceptical of the field in general, and will seize upon early results of such trials as demonstrating that a CAM treatment is ineffective entirely.”

Such is the sorry state of “research” in alternative medicine.

Allergic reactions to corticosteroids

I find it hard to believe a patient can be allergic to corticosteroids but it happens, possibly with an incidence of 0.3% according to this report in the Journal of General Internal Medicine. It’s more commonly seen in patients with aspirin allergy and should be considered in the differential diagnosis for patients whose asthma attacks fail to respond or worsen after glucocorticoid therapy.

The National Center for Complementary and Alternative Medicine just won’t give up on echinacea

I thought the NEJM report on the NCCAM supported study of echinacea would be the last word on the use of this herbal product for the prevention and treatment of the common cold. DB apparently thought so too. The study, which tested several different extracts of the plant found no benefit in treatment or prevention. Moreover, there was no observed effect on virus titers or on inflammatory markers in nasal secretions. Despite the longstanding popularity of echinacea the NEJM paper points out that systematic reviews of previous studies had failed to demonstrate effectiveness.

So isn’t that enough? With no plausible mechanism of action, no effect on surrogate markers of the disease and no clinical evidence of efficacy in high level studies what could possibly drive further study? NCCAM’s answer is consumer demand to do something about the common cold, coupled with echinacea’s popularity. They apparently intend to throw more of your tax dollars into echinacea. The fall/winter edition of their newsletter article on echinacea concludes with “NCCAM will continue to support research on echinacea. A number of smaller studies are currently under way. This research is being done both because of the public health burden of the common cold and the public's widespread use of echinacea. A recent survey of CAM use by U.S. adults found echinacea is the most commonly used natural product.”

Maybe this is one more example in support of Dr. Wallace Sampson’s position that the NCCAM should be defunded.

Assessing surrogate endpoints with the MCID

In the era of evidence based medicine we insist on meaningful clinical outcomes from research studies as a basis for making decisions. We’re interested in whether patients live longer, have a better quality of life or experience fewer hospitalizations as a result of treatment. More immediate physiologic variables which change as a result of treatment (such as blood pressure or LDL cholesterol) sometimes substitute for clinical assessment and are therefore known as surrogate endpoints. Although useful because they are more rapidly obtainable, they are not always reliable. Some surrogate endpoints such as short term suppression of ventricular arrhythmias by class I-C antiarrhythmics and hemodynamic improvement with inotropic agents do not correlate with clinical benefit at all and may even be harmful. Many surrogate variables are believed to correlate with clinical benefit but the magnitude of change necessary for meaningful outcomes is not always clear. What is the significance of a 2mm reduction in systolic blood pressure as opposed to 10mm? How do these differences translate into the incidence of stroke of myocardial infarction?

Increasingly investigators are trying to address this issue with the concept of Minimal Clinically Important Difference (MCID). For example, using one of a variety of methods researchers might attempt to estimate the minimum blood pressure change needed to translate into some meaningful outcome such as reduction of MI or stroke. One recent example comes from post publication analysis of the National Emphysema Treatment Trial (NETT) which evaluated lung volume reduction surgery [1] [2]. This analysis was discussed at the American Thoracic Society 2005 International Conference by Dr. Neil MacIntyre, linked here via Medscape. NETT helped define subsets of patients who are likely to benefit from volume reduction surgery. Among the lessons learned from the post publication analysis was the delineation of MCIDs for physiologic variable changes in emphysema. Empiric data correlations in NETT suggested that an increase in 6 minute walk distance of 121 feet, an increase in PO2 of 5 mm Hg, an increase in FEV1 of .12 L, and a 5-W increase in maximal exercise capacity were MCIDs for meaningful outcomes in emphysema.

Google enhancement for dermatology

Since discovering Google image search I have seldom used dermatology books. But a weakness of the search engine is that selection of a term requires a diagnosis or list of possible diagnoses. The map of dermatology tool, a significant enhancement to image search, helps solve that problem. Clicking on a body region or sub region generates a list of descriptive terms which in turn are selected, resulting in a differential diagnosis list. Diagnoses on the list can then be selected for entry into the image search.

Whistle blower or disruptive physician?

Buried in most medical staff bylaws is a “disruptive physician” clause. Often vaguely defined, such clauses can be a pretext for retaliatory action against whistle blowing physicians who point out breaches in the quality of hospital care. I have blogged about this issue before, and it is profiled in a recent issue of Medical Economics.

Consequences of methamphetamine abuse

Reviewed in Mayo Clinic Proceedings.

Sleep hygiene study disappointing

An aggressive, multimodal, non pharmacologic program to help nursing home patients sleep failed in this controlled clinical trial. Multiple sleep hygienic measures (probably more elaborate than would be practical in the real world) were applied day and night by research experts, with no benefit. Back to the drawing board (and the sleeping pills).

How deadly is avian flu, really?

This report from Vietnam, published in Archives of Internal Medicine, suggests it may be much milder than popularly believed. The survey of cases of flu like illness linked to close contact with dead or diseased birds in a confirmed poultry outbreak suggests that the usual infection is mild. This is in marked contrast to high case fatality rates reported previously, on the order of 50%. The authors speculate that the high reported mortality rates reflect a bias toward sicker patients, since the data are based on patients referred to hospitals in metropolitan areas. There is likely a larger burden of mild disease in rural areas which goes unreported.

The principal weakness of this paper is the lack of serologic confirmation, which the authors imply is forthcoming. Although the identity of the disease is unproven the authors marshal strong epidemiologic evidence that it’s avian influenza.

Michael Fumento comments and reminds us that he told us so.