Friday, December 23, 2011

Myelodysplastic syndrome versus myeloproliferative disorder

I've seen fuzzy use of these terms and evidently the question came up at Emory morning report, hence a post at The Bottom Line:

Myeloproliferative diseases are characterized by large numbers of abnormal blood cells (red, white or platelets) growing and spreading in bone marrow and blood. On the other hand, myelodysplastic syndrome includes various clonal hemopathies characterized by decreased production of blood cells and are associated with a risk for development of acute leukemia.

Thursday, December 22, 2011

Pancreatic neuroendocrine tumors

From a review in Gastroenterology.

Most are “malignant” with the exception of insulinomas. “Malignant” is quotes because clinical behavior in terms of tumor bulk and metastasis is generally indolent, and the major clinical impact is from the secretory products, though some tumors are nonfunctional.

Prophylaxis against spontaneous bacterial peritonitis in cirrhotic patients---I'm confused

This was a recent topic of an evidence summary posted at The Bottom Line according to which the only universally accepted indication is for cirrhotic patients hospitalized with UGI bleeding while they're in the hospital (and maybe for a few days after). For non-bleeding ascitic patients with other risk factors, while a prior history of SBP seems to be a strong factor in favor of prophylaxis, the recommendations are all over the map, (and I checked Up to Date regarding this) reflecting the less than optimal quality of available evidence.

Wednesday, December 21, 2011

UpToDate versus Harrison's and other traditional text books---it's about apples and oranges

You wouldn't criticize an orange for not being a good apple. In terms of taste, texture and many other attributes an orange isn't supposed to be a good apple. So why in the world would you criticize Harrison's or Cecil's for not being good “look up” treatment references like UpToDate is? They're not supposed to be. They are mainly background references, not point-of-care references. So they have a different role.

An interesting exchange of tweets between Ves, the author of Clinical Cases and Images and Joel, who blogs at Precious Bodily Fluids seems to ignore this point:

@DrVes: UpToDate is likely the most read medical reference tool, at least in the U.S. - how did Harrison's, Cecil's, etc. manage to lose that war?

Thus a false dichotomy is set up between UpToDate and the traditional textbooks. It's both-and, not either-or. The resources should not be in competition. They are complementary. When I'm rounding and need a quick look up of the latest and best information on the treatment of interstitial lung disease complicating systemic sclerosis I go to UpToDate. At home that night I might want to review some background information on the pulmonary complications of systemic sclerosis---pathophysiology, radiographic patterns, disease characteristics, natural history and the like. For that, my best bet is Harrison's or Cecil's.

Don't get me wrong, I love UpToDate. It may even save lives. But UpToDate by itself is not enough. You need additional resources. If your Harrison's is serving primarily as a booster seat for one of your kids at the dinner table you could put it to better use. What do you think? (I'm opening up comments again in hopes the spammers will stay away).

Warfarin versus the new oral anticoagulants

This review belongs in the hospitalist's library. It covers the two new agents approved in the U.S. as well as those in the pipeline. It cites a lot of comparative effectiveness research. (Not that comparative effectiveness research is anything new, but that's what it's trendy to call it when there are two or more active treatment arms).

So is warfarin dead? No. This little appreciated perspective is offered:

Warfarin's long, effective half-life of approximately 40 hours, may work to the providers' advantage in a nonadherent patient, Therefore, a degree of nonadherence may have a negligible effect on anticoagulation levels, compared with an anticoagulant with a short half-life.

The lack of a requirement for monitoring may also deny the physician the opportunity for patient education and the earlier detection of problems. It denies the practitioner the ability to tailor the intensity of anticoagulant therapy for patient-specific factors, such as for patients on single or dual antiplatelet therapy, or for those patients with an increased bleeding risk. Lastly, it may make it difficult to determine if the specific therapy has failed. If a patient develops a thromboembolic event on warfarin, the INR is measured to determine if the event is truly a failure of therapy or whether the patient was subtherapeutic (due to noncompliance or other factors influencing the INR).

And, my suspicion is that the purported safety and ease of use of these new drugs could lead to complacency in heeding renal precautions and other labeling concerns.

Monday, December 19, 2011

The high osmolal gap---toxic alcohol poisoning and other disorders

This topic was reviewed as part of the acid-base teaching series of the American Journal of Kidney Diseases.

Concluding points from the article:

• Increased serum osmolal gap with or without high-anion-gap metabolic acidosis can be an important clue to toxic alcohol intoxications
• The presence and magnitude of serum osmolal gap depends on several factors, including molecular weight of the offending alcohol, baseline serum osmolal gap, and state of metabolism of the parent alcohol
• Patients with toxic alcohol intoxications can present with an increase in serum osmolality alone, increased serum osmolality and high-anion-gap acidosis, or increased-anion-gap acidosis alone. Rare cases in which both serum osmolality and anion gap are within reference ranges also might occur
• Kidney failure, lactic acidosis, and diabetic ketoacidosis also can cause high-anion-gap metabolic acidosis associated with a large serum osmolal gap
• Given the potential severity of all these disorders, they should be excluded in all individuals presenting with serum osmolal gap, serum osmolal gap and high-anion-gap metabolic acidosis, or high-anion-gap metabolic acidosis alone

Also remember this:

Osmolality must be measured by the method of freezing point depression. Other methods may not be reliable. Fortunately, freezing point depression is the method of most hospital labs.

In contrast to the other toxic alcohols, isopropyl alcohol is not metabolized to an acid (it is metabolized to acetone resulting in ketosis but not ketoacidosis because acetone cannot be carboxylated to produce a ketoacid). Thus isopropyl alcohol intoxications produce elevations in the osmolal gap but not the anion gap unless they produce sufficiently severe hypotension to cause lactic acidosis.

The other toxic alcohol ingestions start with only an elevated osmolal gap. As the parent compound is metabolized to acid metabolite(s) the osmolal gap goes down as the anion gap goes up. Late in the course only the anion gap is elevated.

The higher the molecular weight of the offending compound the less it will contribute to the osmolal gap.

An interesting situation exists with DKA. Ketoacids dissociate and the hydrogen ion is buffered. Sodium pairs with ketoacids to maintain electroneutrality. Because sodium figures in the calculated osmolality the ketoacids do not directly contribute to the osmolal gap. They contribute indirectly because acetoacetic acid is irreversibly and non-enzymatically converted to acetone, an osmotically active non ionic compound which is slowly excreted in breath and urine. Glycerol and some amino acids also contribute to the osmolal gap.

High school chemistry question: what's the difference between osmolality and osmolarity? We use the terms interchangeably but there is a difference. No fair googling.

Monday, December 12, 2011

Does thyrotoxic atrial fibrillation carry a higher thromboembolic risk than other forms of atrial fibrillation?

There's a long held belief that this is true. I first heard it from an old sage who said that when the thyrotoxic patient develops atrial fib, “run for the heparin!”

Thyrotoxicosis is not listed as one of the CHADs risks, so fact or myth?

All the evidence is examined in this review in the Texas Heart Institute Journal. It turns out that multiple studies show an alarmingly high rate of thromboembolism in thyrotoxic patients with a fib compared to rates reported in non-thyrotoxic patients. But these studies were small and had methodologic problems. At least one larger study questioned the association. A systematic comparison of thyrotoxic and non-thyrotoxic patients with a fib has not been done.

Guidelines differ. The AHA/ACC guidelines suggest that indeed thyrotoxicosis is a risk factor and is itself a reason for anticoagulation. The authors of this review conclude:

Given the lack of clear evidence, the ACC/AHA classification of thyrotoxicosis as a moderate thromboembolic risk factor seems to be reasonable, and the recommendation to initiate anticoagulation when there are no contraindications appears to be warranted. More evidence-based trials are necessary to clarify this issue.

Thursday, December 08, 2011

Takotsubo cardiomyopathy versus anterior STEMI: is there an electrocardiographic differentiation?

TC can present with anterior ST elevation, in which case it resembles acute anterior STEMI. This paper demonstrates an electrocardiographic differentiation:

ST-segment elevation greater than or equal to 1 mm in greater than or equal to1 of leads V3 to V5 without ST-segment elevation greater than or equal to1 mm in lead V1 identified TC with sensitivity of 74.2% and specificity of 80.6%.

It is amazing to me how the power of electrocardiography continues to be discovered year after year. However, this finding is of limited practical value. At a specificity of 80% for TC you wouldn't want to rely on this pattern to exclude patients from reperfusion.

Tuesday, December 06, 2011

Quick reference on lead aVR

Reports in the last few years highlight the emerging importance of lead aVR, a long neglected electrocardiographic lead. I have written several posts on the important clues available from lead aVR in the detection of left main or multivessel coronary ischemia, the differential diagnosis of narrow complex tachycardias, the differentiation between VT and SVT with aberrancy, and pericarditis. All these and more are summarized in this quick reference guide, from the Paucis Verbis series at Academic Life in Emergency Medicine.

Televancin and HCAP

It has been approved for the indication in Europe based on two phase 3 trials showing non-inferiority to vanc. In the US it is approved only for complicated skin and skin structure infections.

Monday, December 05, 2011

Fluid resuscitation in acute pancreatitis: is less actually more?

Traditional teaching and guidelines held that we should pour the fluids early on in the treatment of acute pancreatitis. Nobody would say just how much, but a lot. The problem was, these recommendations were not driven by high level data. We had expert opinion, animal data, pathophysiologic rationale and low level studies in patients but nothing more.

A new study, representing the best evidence we have to date, challenges that teaching:

A total of 247 patients were analyzed. Administration of greater than 4.1 l during the initial 24 h was significantly and independently associated with persistent OF, acute collections, respiratory insufficiency, and renal insufficiency. Administration of less than 3.1 l during the initial 24 h was not associated with OF, local complications, or mortality. Patients who received between 3.1 and 4.1 l during the initial 24 h had an excellent outcome.

In our study, administration of a small amount of fluid during the initial 24 h was not associated with a poor outcome.

I don't have access to the full text of the paper to know how severity adjustment was done. The authors, when interviewed by Medscape, spoke strongly against the practice of massive fluid resuscitation for all patients with pancreatitis.

How might this study change practice? To me it challenges the dogma that patients with acute pancreatitis should undergo massive initial fluid resuscitation just because they have acute pancreatitis. The game changer may be that we'll have to adopt a more individualized approach to fluid management based on volume assessment. For patients who seem well perfused at presentation, a strategy like that suggested by the authors, aiming for 3-4 liters or so over the first 24 hours, may be reasonable with the caveat that frequent clinical and laboratory assessment over that time may be necessary to identify those patients who need to be switched to a more aggressive volume loading strategy. We'll need further study of this question to refine the approach.

A new challenge to Obamacare---the Interstate Health Care Compact

Interstate compacts are older than the Constitution itself although this effort just got going a few months ago. A few states have signed up with many more standing in line. These folks seem very determined and at a minimum they'll open a new front in the battle over health care.

Friday, December 02, 2011

GPs in the British National Health Service

Bob Wachter, on sabbatical in England, has been blogging about the National Health Service. In his latest post, noting Donald Berwick's romanticism about the NHS and the political consequences he reaped, Bob is not so romantic. While acknowledging many of the negatives of the NHS he finds a few things to like. Let's look at some of those and decide how likeable they really are.

A GP can make more than a surgeon, and brings home about 20% more than a subspecialist. (We aren't told how much that is and how it compares to primary care in the US). This is largely due to a big P4P incentive implemented by the NHS in 2004. The incentive, as Bob portrays it, is like our own system on steroids:

In 2004, the NHS negotiated a new contract with GPs, which included a “Quality and Outcomes Framework” (QOF), an unprecedentedly far-reaching pay-for-performance system in which GP practices could earn substantial sums based on performance on over 100 quality measures...

But the most prominent wall decoration is a large white board, located in the practice’s main thoroughfare, its grids filled with data on the group’s performance on the QOF measures. All the doctors, nurses and staff track these numbers daily because their livelihood, literally, depends on them. In addition to tracking process and outcome data via the white board, the practice’s sophisticated computer system allows caregivers to track their adherence to evidence-based quality measures and to see how the practice is doing against benchmarks and bonus thresholds.

Well, you can just imagine the distraction this creates away from real quality and clinical skill along with other unintended consequences. I have blogged many times before (and cited evidence) on the fallacy of performance as a surrogate for quality. (In the above quote I wish Bob had put the word quality in quotation marks). Beyond that, recent evidence suggests that even the effect on performance of P4P incentives is modest at best. The same was found to be true for the NHS incentive in particular in this NEJM study. More than that, under the British QOF incentives there was deterioration in adherence to uncompensated measures.

And there was this tidbit:

Moreover, the NHS limited GP practice hours to 8 am-6:30 pm, weekdays only, creating alternative ways (mostly through a series of urgent care clinics and, of course, through emergency rooms) for patients to receive after-hours care.

GPs in the NHS apparently like this, but can you imagine the US government setting your practice hours?

Finally this, speaking of the GP group Bob toured there:

..they review every case in which a patient goes to the ED, is admitted to the hospital, and is referred to a subspecialist.

Yes, the decision to refer even a single patient to a cardiologist or nephrologist needs to be defended. As far as I could tell, this is not because the costs of subspecialty consultation come out of the practice’s resources (although this may soon change, as the Cameron government’s plans to turn over most of the healthcare budget to GPs, called “commissioning,” are rolled out over the next few years). Rather, it seemed to me to be an issue of professional pride.

Can you imagine a US primary care practice reviewing every one of its subspecialty consults? They wouldn’t have any time left over to see any patients.

These reviews flow from the UK’s overall care model, which requires that all patients go through their GP in order to access subspecialty care and most sophisticated tests (one vivid example: a GP cannot order a CT scan or MRI—they need to be ordered by subspecialists). They don’t call this “gatekeeping” here, but that’s precisely what we would call it in the US.

Yes, gatekeeping. Remember the days of heavy managed care? Again, on steroids.