Metformin as an adjunct for type I diabetes???

From Medscape Ask the Experts.

Among the possible benefits of metformin for DM 1 the article talks a lot about weight control. Which makes me wonder if all the subjects in the clinical studies cited really had DM 1 as opposed to DM 1.5 or DM 2 but requiring insulin for glycemic control.

Observations on the American College of Physicians Ethics Manual

So the sixth edition of the manual has just come out. You can go here to access a link to download the entire manual for free. For the most part the language is pretty standard, similar to other codes of ethics we're familiar with, such as that put out by the AMA. Here I will comment on some new areas of content and other aspects of the document that got my attention.

The readability and clarity of the document, particularly the sections on the ethics of decision making and end of life care, should make this a useful resource for clinicians. I found fault with some portions of the manual and will make note below.

Financial conflicts of interest

The ACP ethics manual considers all forms of conflict including those inherent in one's practice arrangement and of course the ever contentious subject of physician-industry relationships as it pertains to gifts, financial subsidies and the like. Concerning the issue of gifts from drug and device companies the manual affirms the College's long held position that this practice is unethical and that even very small, nominal gifts such as ink pens are problematic. Unfortunately there is a credibility gap here because the College has not practiced what it preaches in this area. If you have ever attended one of their national meetings you know what I'm talking about. In the exhibit hall one finds a lavish array of pharmaceutical company displays. Until recently the exhibit hall was a vast repository of industry freebies. The ink pen giveaway is a non-issue now because that particular type of gift has been banned. Still, support received by the College from industry does offset registration fees. So if you attend the ACP national meeting industry, whether you know it or not, is underwriting a substantial portion of your registration fee. Now I'd say that's a pretty substantial gift! The College has come under fire in the past for this duplicity from organizations such as No Free Lunch, but to my knowledge has done nothing about it.

More pervasive financial conflicts of interest are inherent in the environment in which we work. Very few physicians are free of cost incentives. The vast majority of us are under positive or negative incentives or a mixture of both. This is as true of our health care organizations as it is for us as individuals. The ACP manual says all these conflicts should be disclosed. This can be exceedingly difficult. Consider Gramma, who's been on full life support in the ICU for a month. A family member approaches you and asks “How much longer will Medicare pay for all this?” Shall I tell her the truth? She'd better be sitting down because the full disclosure answer is that Medicare stopped paying for Gramma's hospital charges at least two weeks ago! The public is profoundly ignorant of the negative cost incentives of Medicare's Prospective Payment System (DRGs).

And while we're at it maybe we better disclose all our P4P incentives (now euphemistically known as value based purchasing) including the latest one, HCAHPS. When patients wonder why we're so much nicer all of a sudden should we disclose that it's a script we're being paid to perform? It's a financial incentive, and according to my reading of the manual the ACP is saying we need to disclose all this stuff. It won't do the patient much good but if it raises public annoyance at our misguided policies maybe it'll help promote change. After all the new professionalism is as much about the community as it is the individual patient.

Assisted suicide and euthanasia

The College opposes assisted suicide and euthanasia but does so in a very round about way as if to leave wiggle room for future accommodation of the practices. Why couldn't they make a strong simple statement against the practices like the one they made against participation in the execution of prisoners? This strikes me as duplicitous concerning the College's stand on the sanctity of life.

Blogs and social media

The manual deals only briefly with this topic. But this is a growing issue and I expect to see expanded discussion in future editions of the manual. In addition to the usual cautions about patient privacy the manual urges us to maintain a professional demeanor and relate to others on line just as we would in person. Maybe this means that whether we blog openly or anonymously some of us need to turn down the snark.

Complementary and alternative medicine

This portion of the manual was a disappointment. Here the College missed the elephant in the room concerning the ethics of CAM and integrative medicine, which is our profession's egregious acceptance of the infusion of quackery into mainstream medical treatment and, worse, the incorporation of quackery into the curriculum of our teaching institutions, which I once termed quackademic medicine. To add insult the manual cites the NCCAM as a reliable source of information for patients! This amounts, in my view, to an indirect endorsement of non-evidence based, unethical and sometimes even fraudulent medical practices.

CDC developing seed virus for A(H3N2)v

---as a step toward possible vaccine development, just in case.

Catheter directed thrombolysis to prevent post thrombotic syndrome after DVT---an evolving story

This open-label randomized controlled trial reported a reduction in PTS attributable to local thrombolytic therapy in patients with iliofemoral DVT. The NNT was 7 and there was a downside of bleeding. The authors recommend the treatment, on top of conventional anticoagulant therapy, for patients with upper thigh DVT extending into the iliac, if appropriate expertise is available at the treating institution.

Medscape commentary here.

A(H3N2)v: the next pandemic?

Last fall the CDC reported two cases of infection with this novel influenza strain in children in Indiana and Pennsylvania. By the end of 2011 that number had increased to 12, involving 5 states. So what's up with this?

What is it? It's a hybrid of a swine H3N2 known for several years, containing a genetic segment from the 2009 novel H1N1 strain.

Human to human transmission capability? If so it appears to be inefficient according to the CDC. The possibility exists, because while some of the cases were attributable to direct animal contact some others were not.

Severity of the illness? In the very limited experience so far it seems to be no worse than ordinary seasonal flu.

Is this year's vaccine effective? Probably not.

Will Tamiflu and Relenza work? Probably according to the CDC.

Above and beyond the ordinary flu swab which patients should have PCR testing specifically for A(H3N2)v? For now, according to CDC: 1) those who've been near pigs and 2) young children with acute respiratory illness in states where it has been reported.

That's the status today.  It will change.

Medscape updates here and here.

A look back at 2011---was there any practice changing evidence for hospitalists?

I've been looking back over my posts for the year 2011. There was a lot of published research over the past year that should be of interest to hospitalists but I found little that was revolutionary, what I would call game changing. There were some articles with practice changing potential, either because of new information or reminders of under-appreciated clinical points, which I have linked below.

GI bleeding prophylaxis (PPIs and H2 blockers) is over-utilized in hospitalized patients. This is driven by performance incentives and, probably, the EMR.

CT angiography is not the diagnostic modality of choice for PE. Not new but certainly under-appreciated.

New guidelines clarify glycemic control in hospitalized patients. The long and the short: intensive glycemic control is not recommended for hospitalized patients with the exception of post surgical patients in the ICU. This is based on the best evidence we currently have. Not new, but contrary to the prevailing dogma.

First ever guidelines for CPAP and BiPAP in critical illness.

Nasojejunal feeding better than TPN in severe pancreatitis.

Long term PPI use and hypomagnesemia. Hypomagnesemia may have consequences for hospitalized patients. If your patient has been taking a PPI it may be worth checking a magnesium.

Hyperammonemia---not just in cirrhotics anymore. Nonhepatic hyperammonemia is an emerging entity which has several causes. Consider ordering a blood ammonia in patients with altered mental status even in the absence of liver disease.

Surgical risk in patients with liver disease. Not new, but under-emphasized. Although patients with heart disease do not generally need to be cleared for elective surgery patients with liver disease often do. Know the contraindications.

New guidelines for fever and neutropenia.

First ever MRSA guidelines.

Don't bother with the AED. It may be great at the mall or the airport but is associated with worse outcomes when patients arrest in the hospital according to a study this year.

Nesiritide---neither beneficial nor harmful in terms of important outcomes. Debate settled. The only remaining question is what is its niche if it even has one.

Outpatient management of low risk PE patients. Not considered standard of care but safe according to a Lancet study this year.

ABCD 2 score for patients with TIA---too good to be true. The sensitivity and specificity depend on what cut off you use for the score. In order to make it sensitive enough you lose specificity and end up admitting just about everyone. The easy-to-use clinical tool, very popular among emergency medicine types, is likely to be abandoned in the wake of the new study linked above.

What's new in ACLS? The most important changes in the 2010 ACLS guidelines impacted the hospital as an institution more than the individual provider. These included the post-resuscitation bundle and the organization of stroke care. So it's your hospital administrators as much as the doctors who need training in ACLS now! Concerning the individual provider the guidelines did make some changes which reflect an increased emphasis on effective compressions. Unfortunately these changes did not go far enough and remain years behind best evidence. In the post linked above I contrasted ACLS 2010 recommendations with current best evidence.

LP not always necessary after CT to rule out subarachnoid hemorrhage.

STEMI versus NSTEMI---a dubious distinction. Does the distinction between STEMI and NSTEMI go beyond the obvious fact that some MI patients have ST elevation and others do not? Ever since door to balloon time for STEMI became a performance measure certain unintended consequences of inappropriate treatment have come to light. Aside from the obvious ones---patients with benign early repolarization or pericarditis getting rushed to the cath lab (yes, it happens)---there are the increasingly reported examples of patients with acute coronary occlusions who are denied timely reperfusion because they lack diagnostic ST segment elevation. Many patients with acute coronary occlusions have “NSTEMI.” Although their need for reperfusion is just as urgent as those with STEMI the performance metric for MI does not recognize them and they may wind up under treated.

That's why the large review of subtypes of MI published in 2010, cited in the post linked above, was so timely. It showed that while patients with NSTEMI tended to be older and have infarctions which were subsequent there was no difference between STEMI and NSTEMI in terms of pathology or outcome.

This is not to say that ST segment elevation is unimportant. It is the most obvious electrocardiographic sign of acute MI and, more than ST depression, helps localize the infarction.

Fluid resuscitation in acute pancreatitis---less may be more. Fluid resuscitation in acute pancreatitis should be guided by perfusion and volume assessment. While many patients will require large volume fluid therapy on the front end, according to a study published last year that strategy may not be appropriate for all patients as is conventionally taught.

New oral anticoagulants. Well, maybe this one is a game changer. Although these agents don't require monitoring of coagulation tests they do require vigilance of a different type, and there's a lot of new stuff hospitalists need to know.

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.

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.

Via The Bottom Line.

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.

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).

Related post: How and why should we read?

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.

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.

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.

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.

Sofia course gallery

Here.

Hospital Medicine Virtual Journal Club

From the Wash U Hospital Medicine section.

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.

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:

RESULTS:

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.

CONCLUSIONS:

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.