The Surviving Sepsis Campaign guidelines: evidence based or not???

An exhaustive review on sepsis in the October 19 issue of the New England Journal of Medicine (NEJM) covers nomenclature, pathophysiology and treatment, including a discussion of the Surviving Sepsis Campaign guidelines. But in what could be viewed as a strange attempt on the part of the Journal to appear “fair and balanced” the same issue’s Perspective piece entitled Surviving Sepsis---Practice Guidelines, Marketing Campaigns, and Eli Lilly dismisses the guidelines as little more than a marketing strategy disguised as evidence based medicine. The authors base their criticism entirely on the role of Eli Lilly in the development and promotion of the guidelines, which endorse its drug Xigris (activated protein C) for restricted indications in patients with severe sepsis. (When I wrote about this controversy 5 months ago I took the more moderate position that the Eli Lilly ties deserved exposure and these guidelines, like any guidelines should be viewed with healthy skepticism. I also took the position that any responsible criticism of the guidelines should appeal to the primary sources of evidence and not be based solely on arguments concerning industry affiliation).

Guidelines, though useful, are imperfect. This can have unintended consequences when they are promulgated by agencies like IHI and JCAHO or become the focus of pay-for-performance initiatives. Even greater harm can result when they are hijacked by the trial lawyers and their hired guns under the rubric of “standard of care.”

Although the authors correctly point this out their criticism of the sepsis guidelines is misdirected and at times defies logic. Proper criticism of the guidelines should be based on the measuring stick of evidence. Portions of the Surviving Sepsis Guidelines indeed depart from high level evidence. The Perspective piece authors, however, don’t seem to care about evidence and disregard the fact that the only examples of the guidelines’ departure from evidence are unrelated to influence by Eli Lilly.

So let’s look at how each recommendation in the guidelines stacks up:

Early goal directed therapy----supported by high level evidence.
Diagnostic studies to ascertain source and microbiology---supported by low level evidence.*
Antibiotic therapy---supported by low level evidence.*
Source control---supported by low level evidence.*
Fluid therapy recommendations---supported by low level evidence.
Vasopressor recommendations---supported by low level evidence.
Inotropic agents---supported by low level evidence (high level evidence if used as part of early goal directed therapy).
Corticosteroids---conflicting evidence; use is controversial.
Activated protein C---supported by high level evidence.
Low tidal volumes for patients requiring mechanical ventilation---supported by high level evidence.
Sedation protocols and avoidance of neuromuscular blocking agents in mechanically ventilated patients---supported by high level evidence.
Intensive glycemic control---not supported.
Renal replacement therapy recommendations---supported by high level evidence.
Non-recommendation of bicarbonate therapy for most cases of hypoxic lactic acidosis---supported.
DVT prophylaxis---supported by high level evidence.
Stress ulcer prophylaxis---supported by high level evidence.

*Although diagnostic studies, antibiotic therapy and source control recommendations are based on “weak” evidence the guideline authors unequivocally recommend these measures. The ethical problems in demanding high level evidence for these modalities are obvious.

From the synopsis above it is readily apparent that any evidence based criticism of the Surviving Sepsis Guidelines would have to question intensive glucose control and the use of corticosteroids. The Perspective authors were conspicuously silent about these, the two weakest recommendations in the document. Why? Because they can’t blame it on the drug companies! Cheap, generic, plain ole insulin and hydrocortisone, the only non-evidence based drugs supported by the guidelines, are of no financial interest to the drug companies.

Gotta ask this question: is this ad hominem attack on the sepsis guidelines anything more than gratuitous bashing of the drug companies?

Harry Potter would be right at home in today’s medical schools

Orac, dangit, you beat me to it.

Homeopathy: Holmes, Hogwarts, and the Prince of Wales. This piece in the FASEB Journal isn’t just about homeopathy. It takes on many forms of pseudoscience currently promoted by NIH, NHS and U.S. medical schools. It concludes: Hogwarts is certainly on the move! If the trend persists, perhaps MIT or Cal Tech will march in step with the medical schools and offer prizes for integrative alchemy or alternative engineering.

More evidence of under-utilization of VTE prophylaxis

Presented at the American Heart Association’s 7th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke.

Via Internal Medicine News and World Report.

A boost for open access

Five major UK research funders now require open access publishing of all their supported research. We can expect more and more studies to be published in open access journals. Read the rest from Biomed Central.

Biphosphonates and osteonecrosis

Two brief items appeared in September’s Internal Medicine World Report.

General update on the problem.
New guidelines with focus on prevention of osteonecrosis

New web resources for hospital medicine

Aggravated DocSurg stopped by the virtual doctor’s lounge and shared a couple of interesting new web sites presented at ACS.

The venous disease resource center.

UCSF perioperative beta blocker and clonidine protocols.

Avoiding ambulance diversion: how does it work in the real world?

Recent blog discussions [1] [2] [3] [4] [5] about ambulance diversion have been generally critical of the Institute of Medicine’s unrealistic mandate for hospitals to avoid diversion and patient “boarding” by improving the efficiency of patient flow.

St. Louis area hospitals, feeling the crunch, offer a picture of what can realistically be achieved by the most aggressive bed management conceivable, as reported in today’s Post Dispatch. It’s an impressive effort---arguably the best hospitals could be expected to make. These folks are organized, and they’re trying everything in the book, from more efficient room cleaning to electronic tracking systems. The results? Although diversion lessened it still occurs at a rate of one to two hours per day in spite of some patient boarding.

When there’s no room there’s no room, and there’s only so much you can do.

More criticism of the Institute of Medicine

A recent commenter on ER crowding and the IOM said----

“The IOM is basically a government agency whose aim seems to be to find fault with and criticize health care professionals without having to find the means to properly fund their mandates. They make headlines and take the public's attention away from the real issues of healthcare economics. Our various professional organizations are afraid to refute their findings because we don't want to sound like we're whining. Yet we had better do so or all we're going to see is continued finger pointing and no real change.” I certainly agree with that. If the professional organizations won’t do it maybe the bloggers will!

As long as we’re picking on the IOM, NEJM recently reported on the IOM’s assessment of pay for performance. As we know, P4P is merely “playing for the test” and has little if any impact on real quality. Not to my surprise I found the IOM recommendations a little naïve. You can listen to the interview here or access a free transcript here.

The interview raises a few questions. They want to expand the P4P concept to reward not just quality, but also efficiency and “patient centered” care. Well, we already have a very powerful negative efficiency incentive----that hidden provider tax known as DRG. We also began a massive experiment in efficiency incentives almost a decade ago known as managed care.

And what is meant by “patient centered care”? It sounds great, but I thought all medical care was basically patient centered. It must mean something extra special----so what is it, exactly? Those folks at the IOM must be mighty smart if they can measure something as nebulous and subjective as patient centeredness. For phase two of their initiative they might consider measuring compassion, honesty, and empathy.

Although those are pretty lofty goals they’re going to start with the basics: reward providers “just for reporting data, at least initially.”

Bloggers respond on ER overcrowding

In response to my post on ER overcrowding DB notes that the Institute of Medicine (IOM) is unrealistic on many issues and points out the relationship of ER overcrowding to under compensation of general ambulatory care. Increasing utilization of the ER as a “clinic” by patients without access to primary physicians overtaxes emergency care. Worse, some ER patients require hospital admission largely due to the shortage of clinic doctors and inordinate wait times which preclude expeditious out patient work ups.

Today Grunt Doc offered a dissenting view and said (referring to DB, Kevin and myself): “The linked commenters in the first paragraph give a 'suck-it-up ED' subtext that rankles. We're doing that.” I guess I pushed the wrong button here, but no such subtext was intended. I was being critical of the IOM, not emergency departments. I have no doubt they’re doing the best they can.

He made this comment over at DB’s blog: “I think there’s a lot of arrogance in absolving the hospital of any responsibility to ease ED overcrowding. Overcrowding isn’t a result of ED inefficiencies, it’s a lack of hospital ownership of the patients admitted to the hospital through their own ED.” Wait a minute---nobody’s blaming the ER here. This isn’t “us against them.” The emergency department is part of the hospital. Their problems are the hospital’s problems, and vice versa. If the ER is overtaxed the entire hospital feels the strain due to extensive overlap and sharing of resources.

What’s Grunt Doc’s solution? Hallway beds. Fine. It seems to work at his institution. I’m not exactly sure what the hallway protocol entails, but I suppose it means that if all regular beds are occupied (hospital “full”) you put the patients where ever there’s physical space, initiate care and hold them there until a regular bed opens up. To me that’s a form of boarding, but you do what you have to do. There’s nothing written in stone in my mind that such boarding has to take place in the ER unless the patient needs cardiac monitoring.

But hallway boarding has its problems too. If the hospital has reached the capacity of its licensed beds (presumably the case if its wards are really full) might those hallway admissions run afoul of the law? In many cases it’s about more than licensed beds and physical space----it’s about staffing. That’s a patient safety issue. There’s plenty of evidence that higher patient to nurse ratios are associated with increased mortality. In this study, for example, 30 day mortality rose 7% for each patient added per nurse.

I’ll say it again. My whole point was directed at the IOM. They say hospitals wouldn’t have to divert or “board” if they’d just be more efficient. That is simplistic. Hospital administrators, physicians and case managers have been working their fannies off to make hospitals more efficient under draconian negative cost incentives (AKA DRGs) that have been in place for 23 years. That is not the answer to ER crowding.

Related criticisms of IOM:

The hyping of medical errors.

The promotion of pseudoscience.

Wish I’d said that

A commenter (Okulus) over at Kevin MD’s link to my post on the Institute of Medicine’s recommendations concerning ER overcrowding wrote:

Now the IOM will become the deserving target of the AHA. Given the abstracted and unrealistic ideas that seem to come with great regularity from the IOM, perhaps it is time government funds were spent elsewhere.
It seems wasteful to fund the production of so-called analysis that produces such wasteful and stupid results.

So right.

Speaking of ER delays and overcrowding---

In view of all that’s been written lately on the hazards of ER delays, this Perspective piece in NEJM is timely. The author, Arthur Kellermann, M.D., M.P.H., reports findings and recommendations from an Institute of Medicine (IOM) committee on emergency care. Due to increased utilization and shrinking resources, according to the article, ER care has reached a point of crisis. It points out that EMTALA, intended to improve ER access has in fact diminished it by giving emergency rooms an unfunded mandate.

As I read the article everything seemed reasonable until I got to the discussion of ambulance diversion and emergency department boarding. Briefly, when no inpatient beds are available for hospital admission the emergency department may commence care of the patients and keep (“board”) them in the department until an inpatient bed becomes available. In extreme situations ambulances are diverted to other area hospitals. These practices have become quite common due to overcrowding. But now the IOM is recommending these practices cease, except in disaster conditions. That’s all well and good, but what’s the hospital to do when there’s no room in the inn? Dr. Kellermann writes that the IOM decrees “Hospitals can achieve this goal by adopting operations-management techniques and related strategies to enhance efficiency and improve patient flow.” Huh? Isn't that what hospitals have been struggling to do for their very survival ever since DRGs were enacted in 1983? This is supposed to solve the problem of ER overcrowding, suddenly? It strikes me as naïve. The full IOM report is here.

If you’re experiencing STEMI-----

Do not pass go, do not collect $200.00 and do not stop in the ER. Go straight to the CCU or cath lab. That’s the message of an observational study published in the October issue of Heart. Patients with ST segment elevation MI who were shipped directly to the CCU or cath lab were admitted earlier (by 48 min) and had a lower mortality than those who were admitted via the ER.

Mortality for ER patients was 8.6% for ER patients and 4.9% for those directly transported to the cath lab or CCU. By my math that means that the benefits of direct transport are RRR 43%, ARR 3.7%, NNT 27. In terms of relative risk, mortality rose by 0.9% per minute of delay, translating into 54% per hour.

This is one more piece of evidence that ER delays are lethal (see this recent post citing evidence that, across the board wait time is associated with 20% mortality per hour for all patients admitted) and that by some folks’ definition there are lots of emergency department homicides out there.

So how do you know if you’re having a STEMI (as opposed to NSTEMI or non cardiac chest pain)? Well, you don’t, initially. But the paramedics can tell from their pre-hospital ECG.

That raises another point. If you experience chest pain DO NOT come to the ER in a private car. Call an ambulance. Transport by private car was the first mistake in the Illinois heart attack death recently ruled a homicide.

Neuropathic pain management

Tricks of the trade reviewed in CCJM.

Abraham Flexner’s legacy---NEJM authors miss the point

The New England Journal of Medicine (NEJM) launched a series of articles on medical education with this piece on the legacy of Abraham Flexner. The 1910 Flexner Report, a comprehensive and highly critical evaluation of medical schools in the United States and Canada, helped spur a revolution in medical education, setting a blueprint for the twentieth century.

The authors, discussing how medical schools today might measure up in Flexner’s view, cite poor training in procedural skills, compromised teaching due to competing research and economic agendas and a lack of attention to professionalism and ethics. These are valid concerns. But conspicuously absent form the discussion was mention of a major problem plaguing medical training today about which we were warned in the Flexner Report: the rampant teaching and promotion of quackery and pseudoscience in medical school. Almost a year ago I pointed out that medical schools had backslidden from the recommendations of the Flexner Report as evidenced by their promotion of homeopathy, Reiki, Ayurvedic medicine and innumerable other unscientific claims.

As I reviewed the Flexner Report in its entirety this weekend I caught myself wondering whether the NEJM authors even read it at all. Flexner’s concern for the sanctity of science, practically an obsession, is evident throughout. If the authors read the report they must have skipped chapter 10 which warns strongly against what medical educators today call “integrative medicine.” The chapter is titled “The Medical Sects”, in reference to groups of teachers and practitioners who advocated for various non-scientific claims, referred to by Flexner as “dogmas.” Chapter 10 opens questioning the integration of dogma with science thusly: “Is it essential that we should now conclude a treaty of peace, by which the reduced number of medical schools should be pro-rated as to recognize dissenters on an equitable basis? The proposition raises at once as to whether in this era of scientific medicine, sectarian medicine is logically defensible; as to whether, while it exists, separate standards, fixed by the conditions under which it can survive, are justifiable.” Flexner’s emphatic answer, bolstered by eloquent arguments in the succeeding pages, is no.

Medical schools are showing increasing disregard for the principles of science. If the NEJM in its forthcoming series of reviews on medical education ignores this pernicious trend it will have done the profession a great disservice.

Orac exposes the “pharma shill” gambit

It’s a favorite fallacy for the alt-med crowd. It’s been used on me a time or two.

NCCAM study site tour---Part VI

The Wellness and Longevity Center of Louisiana is one of the NCCAM chelation study sites. According to the web page the Center’s vision is “…to prevent and treat chronic disabilitating diseases such as obesity, high blood pressure, Parkinson and Alzheimer’s disease, chronic fatigue, fibromyalgia, heart attack and stroke by integrative medicine which combines standard medical practice with alternative and complementary medicine…” (That’s right, it really says disabilitating).

The chelation therapy information page states “Every single study of the use of Chelation Therapy for Atherosclerosis that has ever been published, without exception, has demonstrated an improvement in blood flow and symptoms.” What journals have these folks been reading? And this: “Adverse editorial comment to the contrary lacks evidence and stems primarily from physicians with a vested interest in catheterization and surgery.” Yeah. I’m reminded of a guy I saw one time on TV promoting his perpetual motion machine, claiming that the fuel industry was suppressing the science behind his invention. Then there’s this claim: “Scientific studies have proven that blood flow increases after Chelation Therapy.” Too bad they left out the citation. I’d like to look that one up.

Aren’t researchers supposed to be unbiased?

Obesity state by state; process and outcome in Arkansas

Report cards are out. They contain no real surprises but there was a curious finding in my state. Although Arkansas, as expected, is one of our more obese states (13th in the nation) it received one of the best report cards----one of only two states to earn a B (no state got an A). Why this gap between process and outcome? Arkansas’s vigorous anti-obesity initiatives (and its good report card) can be attributed largely to the efforts of Gov. Mike Huckabee, who believes the measures will just take time.

But the battle of the bulge in Arkansas may be difficult. Arkansas clearly is in the obesity belt. It’s a culture war. It may not be as bad here in my neck of the woods, the culturally transformed rapidly emerging retail capital of the world, as it is in more rural pockets of the state as suggested in this county by county analysis.

Huckabee’s personal story is noteworthy. A few years ago our morbidly obese governor, barely able to make it to the top of the capitol building stairs, lived in fear that he would be met there, breathless, by media, and be unable to give an interview. When he turned up with type 2 diabetes his doctors said, in effect, “diet or die.” Thereupon the former Baptist minister “got religion” about his health and embarked on a comprehensive program of nutrition and exercise, shedding over 100 pounds. Later he decided to share his success and put his state on a diet.

That may strike some people as ironic. Huckabee’s a Republican. He’s a conservative. But he doesn’t fit the mold of libertarian conservatives who complain about the “fat police.” In the minds of some who think his health initiatives too intrusive Huckabee is chief of the fat police. A Little Rock restaurant owner told the New York Times concerning Huckabee’s weight loss “it’s fine for him….But he ain’t got to make the whole state lose weight.”

According to the New York Times the Arkansas anti-obesity measures, some of which exceed federal requirements, include exercise breaks for state employees, strict guidelines for school lunches, and the reporting of BMI on school report cards. But perhaps more remarkable than all that is the example set by the governor. His speaking engagements and writings (such as Quit Digging Your Grave With A Knife And Fork) recount many testimonials, and he has completed the Little Rock marathon.

It’s nice to see my state get a good grade in something. Will it translate into better health outcomes? I remain to be convinced.

House takes on the antivaccination crowd

And Orac provides the transcript. This is too funny.

Cardiac pacemakers demystified

A review in Clinical Cardiology.

E. coli in perspective

Folks in the popular media don’t seem to know, or care, that the often fatal E. coli (E. coli 0157:H7) causing the current outbreak of hemorrhagic diarrhea, sometimes complicated by hemolytic uremic syndrome, is completely different from the ubiquitous E. coli that inhabits the colon of each of us and commonly causes infection when it winds up someplace is shouldn’t (urinary tract or bloodstream).

If you don’t think this is confusing to people try telling your patient (when 0157:H7 is hot news) with a mild UTI “Oh, it’s just E. coli” and note the reaction. This pathogen should be referred to in media reports as “E. coli 0157:H7”, not “E. coli.”

The ubiquitous form of E. coli is not an intestinal pathogen. Six less common forms do not normally inhabit the human GI tract and are in fact enteric pathogens. These latter forms have little in common except for a propensity to cause intestinal disease, with distinctly different pathogenic mechanisms. Only one of these six forms, enterohemorrhagic E. coli, causes extraintestinal disease (hemolytic uremic syndrome). These are principally of the 0157:H7 variety, the subject of the current news stories.

The only other one of the six forms of enterovirulent E. coli of importance in the developed world is enterotoxigenic E. coli, believed to be the principal etiologic agent of traveler’s diarrhea. The toxin elaborated by this organism increases the production of cyclic AMP and GMP resulting in a secretory (non-inflammatory) diarrhea.

The other forms of enterovirulent E.coli are enteropathogenic E. coli, enteroinvasive E. coli, enteroaggregative E. coli and diffusely adherent E. coli.

Summary and update on the E. coli 0157:H7 outbreak

Today’s issue of Morbidity and Mortality Weekly Report has the latest info as well as links to CDC and FDA updates. This should be a helpful resource.

As an aside, I wish the popular media would bother to distinguish between E. coli 0157:H7 and the common and not so deadly forms of E. coli. Very confusing to the lay public.

Medscape Roundtable Discussion concerning pharmacists on the health care team

For the latest Medscape Roundtable Discussion we were asked “How Can Physicians Stay Current on Prescription Drugs?” Surprisingly the readers’ responses were overwhelmingly “Why didn’t anyone mention the role of pharmacists?” True enough we didn’t mention it. I can only speak for myself here. I regard pharmacists as an important part of the team, and a resource I utilize extensively. But we weren’t asked that. We were asked how we keep up with information in pharmacology, not how we delegate to other team members. Clinical pharmacists perform important tasks, safeguard against inappropriate orders and intercept errors. That doesn’t absolve physicians of the responsibility to expand and update their knowledge, utilizing the most authoritative primary sources available.

On the healthcare team the buck stops with me, the physician. If I’m doing my job I should know the “whole picture” of my patient’s problem better than anyone else including the pharmacist. If the pharmacist makes a recommendation on drug therapy I must understand the rationale. If the pharmacist happens to be wrong I must know how to proceed. The pharmacist has an essential role in patient care. At the same time physicians must independently stay knowledgeable in the field by regularly reviewing authoritative sources of information in prescribing as well as related information in physiology and evidence based medicine.

NCCAM chelation study site tour---Part V

Innovative Medicine in Lafayette, IN is a chelation study site. The clinic offers chelation therapy, hyperbaric oxygen, “advanced thyroid replacement”, chiropractic, acupuncture and “multiple powerful intravenous therapies.” Concerning thyroid treatment, the clinic claims to “easily help people who suspect that they are hypothyroid but have been told their thyroid test is normal.” They also claim that chronic neurologic diseases of any type usually respond to hyperbaric oxygen.

Well, it’s innovative all right. A little too innovative for me, but apparently not for government funded “research.”



Background: part I, part II, part III, part IV

Emergency department homicide???

A patient’s death in a Lake County Illinois emergency room was recently ruled a homicide by a coroner’s jury, finding “gross deviations from the standard of care” which prolonged the patient’s wait time. If a death related to ER wait time is a homicide then how many other undocumented emergency department homicides are occurring on a regular basis? Quite a few, perhaps, according to this study from the Medical Journal of Australia. The death rate went up 20% per hour of wait time in this study, independent of diagnosis or urgency of the patient’s presentation.

Medication safety resource

Institute for Safe Medication Practices.

Features safety alerts, news letters, a message board and more.

The TRIP database

Here’s some good news for EBM enthusiasts. I was a frequent user of this resource until it went paid access a few years ago. Today I’m pleased to learn, via Sumer’s Radiology Site, that TRIP is once again free. It looks as though, in the interim, they’ve made substantial improvements to an already useful site. The search engine is more precise and they’ve added a medical images section. Very nice.

Tygecycline

Reviewed in Baylor University Medical Center Proceedings.

I previously reviewed it here.

Controversies in the treatment of hypothyroidism

Although it ought to be straightforward, several controversies regarding treatment of hypothyroidism have arisen in the past decade. These are covered in a review in the July/August 2006 issue of The Endocrinologist.

What is the optimal TSH target during treatment? 0.4 to 2.5 mIU/L.

Is T4 + T3 replacement superior to T4 replacement alone? No.

Is brand L-thyroxine superior to generic? Not according to the best available evidence.

Should subclinical hypothyroidism be treated? Probably not if the TSH is less than 10 mIU/L.

Geriatric rounding tips

Some rules for geriatric patient safety from Today’s Hospitalist.


Review medications regularly. Watch out for such hospital booby traps as automatic stops, omissions in transfer from ICU to ward, changing renal function requiring dose adjustments, etc. Assess gait, fall risk, functional status and skin problems early and regularly. Get physical therapy involved early.

The tobacco industry helped launch television’s golden age

This week free Camels go to Veterans Hospitals North Little Rock Arkansas and Omaha Nebraska……….

That bit of irony was spoken by Anne Jeffries hawking Camel cigarettes at the close of a 1950s episode of Topper. Video files of this and other cigarette commercials (including John Wayne shilling Camels, and years later urging viewers to fight cancer) are archived at TV Party.

Television was dependent on the tobacco industry in the early years. A blockbuster network show typically had only one or two sponsors, and the sponsor was often a tobacco product. As the medium matured it became less dependent, and tobacco commercials were finally banned on January 2 1971.

Clostridium difficile update

This review in Baylor University Medical Center Proceedings focuses on the history of our experience with this pathogen, pathophysiology, diagnosis and treatment. Newly appreciated risk factors are profiled including proton pump inhibitors, chemotherapy and post pyloric tube feeding.

An idiot’s guide to AICDs

Here’s what the non electrophysiologist needs to know.

And speaking of useful medical records---

As implied in the post below, the problem oriented medical record has been hijacked by coders and auditors. In contrast, here’s a report from the field in the Journal of Clinical Outcomes Management about a new concept in medical record keeping for patients with complex chronic problems.

First a disclosure. The author is a local colleague, and I reviewed and commented on an early draft of the manuscript. I’ve also seen this system in use.

Potentially adaptable to both electronic and paper based records, the system expands the traditional problem list into a comprehensive treatment summary. The use of symbols enables the summary to be contained in a single page. The summary itself is meant to be updated with key information in real time, freeing up the traditional progress note to depict clinical concerns in a meaningful narrative form without redundancy. You’ll need to get the full text article (which I can’t link here) to really see how it works.

While this tool will facilitate clinically meaningful charting it may not make the coders happy, which is why the author concludes the abstract with: “Feedback and guidance from Medicare audit will be crucial prior to widespread application of the system.”

Buffing the chart

While I was away Retired Doc linked to this article in the Annals of Internal Medicine, fueling more skepticism about pay for performance (P4P). The results of P4P programs, according to this systematic review, may be more cosmetic than real. Providers seem to be gaming the system and treating the chart rather than the patient.

This isn’t new. We’ve been playing chart games ever since reimbursement was tied to E and M coding, leading to the popularity of template generated progress notes. As a hospitalist who cares for a large number of “unassigned” patients I depend a great deal on outside records. From the vantage point of patient care the template generated notes (of which I’m seeing more and more) are the least helpful. Templates force all the “right” questions to make the coders happy, but produce little meaningful clinical information. P4P will fuel even more cosmetic charting and make the problem worse.

Musings on continuing medical education

I’ve just returned home from a CME course, combined with a little vacation. It was one of those traditional CME activities centering on didactic presentations and workshops, held at a nice relaxing location. It was co-sponsored by a major professional organization and received financial support from several drug and device companies.

In my 28 year obsession with career learning I’ve availed myself of multiple methods---didactic, case based and Internet based to name a few. I’ve also become convinced that individual doctors have differing learning styles. I find that the different learning methods offer multiple dimensions, serving my educational needs in different and uniquely important ways.

Learning at the point of care about a specific clinical question (e.g., foreground reading) often directly impacts clinical decision making and sharpens my focus on diagnosis and treatment. Equally important is background learning, focusing on more general clinical features, treatment principles and pathophysiology. Background learning may employ textbooks, narrative reviews and didactic presentations. Although such learning has little immediate impact on my prescribing behavior it strengthens my conceptual framework for understanding medicine.

These two examples may represent opposite poles of a spectrum of learning styles. Both are essential. Without foreground learning we miss the best and most current evidence applicable to patient care. Without background learning we lose the underpinnings of medicine and resort to formulaic practice based on rote memorization and slavish adherence to algorithms. (See How and why do doctors read?).

For me the traditional didactic meeting offers a unique educational experience. The occasional retreat to a relaxed setting in a remote location, away from the time pressures and constant interruptions of the “point of care” helps me to maintain a receptive and enthusiastic frame of mind. Without these getaways I would miss an important aspect of lifelong learning.

Lately I’ve been troubled. In recent years these meetings have struggled for attendance and sponsorship. They’ve come under attack by naysayers from various camps. Some are unhappy with pharmaceutical company sponsorship. Others, like thought police, believe they know what type of continuing educational activity is best for me.

This salvo comes from a Medscape General Medicine video editorial by Dr. Jordan Cohen, president of the Association of American Medical Colleges. Dr. Cohen, describing “A New Vision for Continuing Medical Education”, wants to overhaul our CME system and thinks the didactic format should be used “only for appropriate issues, such as a basic science breakthrough.” Then there’s this astounding statement: “Research shows that the lecture-based format of CME does not change physician behavior or, more important, change the health outcomes for patients.” What’s the level of evidence for that claim? Moreover, the whole premise is wrong. A litmus test for CME that requires activity A to be measurably associated with behavior B is faulty because it ignores important intangibles. Under such a standard there would be no place for activities that teach pathophysiology, clinical diagnostic skills, general principles of evidence based medicine, or ethics. All are useful educational endeavors to be sure, but would change physician “behavior” mainly in intangible, and not readily measurable, ways.

Then there’s this curious statement (italics mine): “The vast majority of CME should employ self-directed, interactive, and relevant learning experiences that enable physicians to acquire the knowledge and skills necessary to exceed minimum expectations.” Well, that’s some vision. What if some doctors want to strive for excellence? If this is the latest theory on “outcome based” education applied to CME I’m underwhelmed.

As I’m often fond of doing I’ll invoke the memory of one of my favorite medical school mentors, Thomas Brittingham. His letter to third year students embarking on their Medicine clerkship concluded with “….for each one of us the primary teaching responsibility now and for the rest of his life lies within himself.”

Acupuncture, a walk in the woods, a pinch on the butt

And speaking of Dr. Wallace Sampson (see post below), check out this piece in the San Francisco Chronicle, Healthy Doubts in which Sampson takes on acupuncture.

"It is nonspecific," Sampson says. "If it has the effect of, say, releasing endorphins through the application of needles, well, many things release endorphins -- a walk in the woods, a 5-mile run, a pinch on the butt."

Via DB’s Med Rants.

Government bias toward pseudoscience

We’ve heard the tired canard: industry sponsored health information is suspect, government sponsored sources are trustworthy. Is that really true? Not according to Dr. Wallace Sampson, Clinical Professor of Medicine (Emeritus), Stanford University. In a Medscape General Medicine video editorial he exposes an alarming and pervasive bias in favor of complementary and alternative medicine by the NIH, the National Library of Medicine and other agencies.

Medication reconciliation may save lives

In a chart review of diabetic patients admitted with MI, patients who did not resume pre-hospital anti-diabetic medications at discharge (13% of the sample) had a 24% increase in mortality at 1 year.

I wish I knew more of what went on here than was contained in this sound bite version (Internal Medicine News) of a poster presentation at the American Diabetes Association annual scientific sessions. When diabetic patients are admitted to the hospital with acute illness their oral anti-diabetic medications are often supplanted by hospital insulin protocols. Although it is usually the intention to resume pre-hospital medications at discharge such instructions may not always be effectively communicated.

New developments in staphylococcal infections

This week’s NEJM reports a study from the S. aureus Endocarditis and Bacteremia Study Group showing non-inferiority of daptomycin (Cubicin) compared with “standard” therapy (vancomycin or an antistaphylococcal penicillin for MRSA or MSSA, respectively, both initially combined with low dose gentamicin) in patients with Staphylococcus aureus bacteremia and right sided endocarditis. Acquired resistance to daptomycin occurred leading to treatment failure, counterbalanced by increased renal toxicity causing treatment interruption in the standard therapy group, also contributing to treatment failure.

In the same issue is a report from Moran and colleagues on the microbiology and clinical characteristics of skin and soft tissue infections (classified as abscess, wound infection or cellulitis) presenting to emergency departments across a wide swath of the U.S. The majority of isolates were MRSA which possessed characteristics unique to community associated MRSA (CA-MRSA) including expression of the Panton-Valentine leukocidin toxin (PVL) and the characteristic sensitivity pattern.

An editorial in the same issue makes these points about the two studies:

1) When oral antibiotic therapy is indicated, trimethoprim-sulfamethoxazole (TMP-SMX) may be a reasonable choice for CA-MRSA but it is not effective against streptococci. Clindamycin is effective against streptococci but CA-MRSA may exhibit inducible clindamycin resistance. (This Mayo Clinic Proceedings review suggests combining TMP-SMX or a tetracycline with a beta lactam such as cephalexin to get around the problem).
2) Abscesses should be incised and drained and, given somewhat variable sensitivity patterns, culture data should guide therapy.
3) Daptomycin is an alternative to older standard therapy for bacteremia. Emergence of resistance during treatment is a problem. Patients who appear to fail treatment should be evaluated for acquired resistance to daptomycin in addition to sequestered foci of infection. (Daptomycin is not recommended for treatment of pneumonia).

DB weighs in with a discussion of how the problem is handled at his institution.

The restructuring of an embattled medical journal

In the wake of the fracas a few months ago over its leadership, the Canadian Medical Association Journal (CMAJ) is reorganizing. Changes include a strengthening of the Joint Oversight Committee responsible for mediating disputes between the editors and the journal owners. It remains to be seen how the changes will play out but contrary to popular speculation, and no doubt to the disappointment of some, the sky hasn’t fallen at CMAJ.

As debate unfolded in the weeks following the dispute at CMAJ “editorial independence” became a tired mantra. Dr. Jerome Kassirer, a member of the CMAJ editorial board and a critic of the publisher during the dispute, is quoted in the August 15 CMAJ article: "You want an editor who is not intimidated by anything. ... It's critical to have an editor who is beholden to nobody." My translation: an editor who is accountable to nobody. Editorial independence is not an absolute value. There must be a healthy tension between independence and accountability, which is what the people screaming about editorial independence don’t seem to get.

Background: previous notes from Dr. RW on this topic here and here.

Cool neurology sites

Educational web sites covering everything from molecular mechanisms to optical illusions are linked and reviewed here. Via Life Sciences Education.

Changing trends in hospital acquired bacteremia

According to this report form Archives of Internal Medicine the pendulum is beginning to swing back toward gram negatives.

NCCAM chelation study site tour—part IV

The Born Preventive Health Care Clinic in Grand Rapids Michigan and its Crossroad Healing Arts branch in Goshen Indiana are NCCAM chelation study sites. The clinics feature craniosacral therapy for autism, chelation, and Nambudripad’s Allergy Elimination Technique. The clinics offer lecithin infusions in combination with chelation which they claim have been shown to reduce plaques that cause various forms of vascular disease.

In explaining the Nambudripad’s Allergy Elimination Technique the web page offers an interesting theory of allergic diseases: “… blocked energy flow is the first step in a chain of events which can develop into an allergic response.” The section on autism and related developmental disorders attributes the increased incidence as to “excessive vaccination in infants.”

How close are we to an influenza pandemic?

This review from Baylor University Medical Center Proceedings discusses the World Health Organization’s statement: we’re at stage 3 of 6 along the progression.

Complementary and alternative medicine viewed from the perspective of medical ethics

Present day promotion and research on complementary and alternative medicine (CAM) is often unethical. Dr. Wallace Sampson, Clinical Professor of Medicine (Emeritus), Stanford University, in a Medscape General Medicine video editorial focuses on two little discussed issues relating to CAM: informed consent and the ethics of clinical research.

Physicians have a duty to inform the patient if a treatment under discussion is not scientifically validated. Dr. Sampson points out: An ethical dilemma occurs when patients have unrealistic expectations for an ineffective remedy. The practitioner who fails to inform realistically, or leads the patient on, compounds the dilemma. Failure to inform realistically is sometimes rationalized as either choosing not to remove hope or as nonjudgmental patient support.
However, uncritical support amounts to abetting ill-informed, counterproductive, and harmful decisions.

Concerning clinical trials Dr. Sampson points out that subjecting research participants to methods of “negligible plausibility” violates the Belmont and Helsinki declarations. By this standard much of current NCCAM sponsored research would be unethical.

Are statins beneficial in heart failure?

Although the body of evidence is small it suggests numerous beneficial effects and no harm, according to a review in American Heart Journal.

Type 1.5 diabetes---a clinical vignette

In the summer 2006 edition of Clinical Diabetes is a case study of atypical diabetes along with a brief topic review. I previously posted on type 1.5 diabetes here.

What test for suspected aortic dissection?

Transesophageal echocardiography, computerized tomography and magnetic resonance imaging performed equally well in the evaluation of patients with suspected aortic dissection in this meta-analysis published in Archives of Internal Medicine.

Pulling old antibiotics off the shelf

Gram negative infections in hospitalized patients are re-emerging, along with multiple antibiotic resistance. Options for dealing with such infections are limited because, with the exception of tygecycline the antibiotic pipeline is running dry. Tygecycline is a welcome addition to the formulary and may be an option for some, but certainly not all multiply resistant gram negative infections.

The June issue of Clinical Medicine and Research contains a review of the use of polymyxins for such multiply resistant gram negative infections. Polymyxins are polypeptide cationic antibiotics. The commercially available parenteral polymyxins, colistin (polymyxin E) and polymyxin B, were used extensively for a number of years before falling out of favor in the 1960s due to concerns about toxicity and the emergence of newer agents. The toxicity is primarily renal and neuromuscular (similar to aminoglycosides) and, the article cites more recent literature to suggest that this toxicity is less severe, or more manageable than reported decades ago.

We’ve been there before with polymyxins. This paper provides a memory jog back to my days as a Vanderbilt medical student. When I was doing my senior elective in infectious disease the VA hospital was in the throes of a severe epidemic of Serratia marcescens resistant to all commercially available antibiotics. It was 1974. Our big guns for gram negative infections were gentamicin and carbenicillin. The ID folks were able to get amikacin for some patients but it was investigational (then known as BBK8) and difficult to obtain. The polymyxins, which had already fallen into disuse by that time, were not effective against Serratia. Synergy against Serratia, however, was known to occur between the polymyxins and sulfamethoxazole/trimethoprim. The combination of sulfamethoxazole, trimethoprim and polymyxin E (STP) proved clinically effective against the infection. The Serratia epidemic and the use of STP were reported here in Antimicrob. Agents and Chemother. in 1976.

NCCAM chelation study site tour part III

This is the third in a series of posts in which I will examine some of the study sites for the National Center for Complementary and Alternative Medicine (NCCAM) sponsored Trail to Assess Chelation Therapy (TACT). The purpose is to address questions about the quality of the research based on conditions at the study sites. The vast majority of sites are private clinics at remote locations across the U.S., raising questions about supervision, and many are alternative or holistic medicine clinics, raising questions about scientific qualifications and investigator bias.

The next study site we will examine on our tour is Wellness Works in Brandon Florida. The mission of Wellness Works is, in part, “to offer our patients an evaluation, treatment, and education based on the holistic model of body-mind-spirit.” Services offered include the assessment of hormone status via saliva testing, intravenous vitamin therapy to treat neurologic dysfunction and immune deficiency, and chelation therapy for atherosclerosis.

The chelation page of the Wellness Works web site describes chelation thusly: “Chelation therapy is also thought by many doctors to be effective in reducing plaque in the arteries. By softening ‘hardening’ of the arteries, this process makes them capable of carrying much more oxygen and nutrients to all the organs of the body.”

Because this seems to be a recurring misconception among TACT investigators, a comment on the pathophysiology of atherosclerosis is in order here. Although reducing the lipid content of atherosclerotic plaques would be expected to reduce the risk of coronary events, reduction of plaque size to enable more blood flow would not. In fact, highly stenotic plaques appear to be an uncommon cause of acute coronary syndrome compared to plaques producing milder degrees of stenosis. Moreover, softening of plaques is not beneficial, as softer plaques are more prone to rupture and cause acute coronary syndrome (Ayala TH-Cardiol. Clin.-1-Feb-2006;24(1):19-35).


Background: Part I; Part II.

Medscape Roundtable

The first installment of Roundtable Discussion is posted at Medscape. The topic is physician obesity. Be sure to stop by the discussion page and “weigh in” with your opinion!

The fox is guarding the henhouse of science and public trust

And the National Council for Complementary and Alternative Medicine (NCCAM) doesn’t seem to mind. In researching for my posts on the NCCAM chelation study sites (Trial for the Assessment of Chelation Therapy, TACT) I’m becoming convinced that the NCCAM is entrusting chelation research to promoters of unscientific health claims who have a vested interest in the results. This is particularly concerning because the blinding of the investigators is faulty. According to the study protocol the chelation solution must be mixed at the individual study sites. Patients randomized to the EDTA arm have ascorbic acid injected into the chelation solution at the local study site. Those assigned to placebo have placebo ascorbic acid injected into the mixture. The problem is, the ascorbic acid solution is yellow, while the placebo ascorbic acid is colorless. The work around for this problem is to wrap the ascorbic acid and placebo syringes in tinted translucent tape. It is claimed that the ascorbic acid does not cause a yellow puff when injected into the infusion bag. It would seem easy enough, though, to waste and inspect a few drops of solution before or after injecting the infusion bag.

For insightful and humorous commentary on chelation and the NCCAM check out this week’s Friday dose of woo by Orac.

NCCAM chelation study site tour part II

The Trial to Assess Chelation Therapy (TACT) is a National Center for Complementary and Alternative Medicine (NCCAM) sponsored study to evaluate chelation therapy for patients with coronary artery disease. The study is conducted at multiple sites across the U.S., almost 100 of which are private clinics, with only 12 academic medical centers participating. Although this selection of study sites facilitates enrollment of large numbers of patients and has the purported advantage of simulating “real world” conditions, the approach has problems. Some authorities have expressed the view that investigation of chelation therapy should be restricted to academic centers. Supervision and credentialing of investigators at multiple non-academic sites is compromised and leaves research vulnerable to fraud, fabrication and faulty methodology, as illustrated recently by the Aventis sponsored Ketek trial.

After perusal of the TACT web site I became concerned that many of the study sites are clinics which are engaged in the practice and promotion of unscientific methods. Disclaimer: The profiles of NCCAM study sites in this and subsequent posts are not intended as criticisms of the clinics in question or their staffs. Although I disagree with the health claims to be discussed here I do not question the sincerity of the providers and respect their right to compete in the marketplace of ideas. The observations made are with the sole intention of raising questions about the quality of the research.

The first stop on our tour is Tequesta Family Practice, Tequesta Florida. Among the alternative practices featured there are heavy metal analysis for chronic fatigue, intravenous infusion of vitamins and minerals for chronic fatigue, evaluation and treatment of “dysbiosis”, evaluation of colonic “ecology” by various culturing techniques, intravenous colchicine infusion for spinal disk herniation and, of course, chelation therapy.

The clinic’s uncritical promotion of chelation raises questions about the objectivity and scientific qualification of the investigators. Chelation therapy is touted by the clinic as “one of the premier anti-aging therapies” and as useful for scleroderma, Alzheimer’s disease, rheumatoid arthritis, multiple sclerosis and porphyria.

Worse, the comments about how chelation therapy “works” reflect a misunderstanding of the pathophysiology of coronary heart disease: “…..to literally strip calcium out of the artery plaques that cause the clogging of the blood vessels that cause heart attacks and strokes. It can ‘soften’ the ‘hardening’ of the arteries caused by atherosclerosis, reversing the disease process.” I won’t go into a detailed explanation of the mechanisms of coronary atherosclerosis---look it up in any standard text or review---just suffice it to say that “soft” coronary plaques are much more rupture prone than “hard” plaques, and that a treatment to “soften” atherosclerotic plaques would be the wrong treatment. From the promotional comments about chelation therapy it is clear that the investigator(s) there believe that its effectiveness has already been proven.

In summary, consider these questions: Are the site investigators biased in favor of the treatment? Could such bias compromise the scientific integrity of the study, particularly given that the blinding of the investigators is faulty? Do the site investigators understand the pathophysiology of coronary heart disease and is such an understanding important for research on a treatment modality?

Background:
Part I
General criticisms of NCCAM here, here, and here.

A magical mystery tour of NCCAM chelation study sites---part 1

On first learning of the National Center for Complementary and Alternative Medicine’s Trial to Assess Chelation Therapy (TACT) I was optimistic that it would settle the chelation controversy once and for all. But examination of the TACT web pages raises concerns about the quality of the study. The scientific integrity of many of the research sites is questionable. Only 12 of the 110 study sites are located in academic medical centers. Worse, a substantial number appear to be engaged in dubious practices, making pseudoscientific and even fraudulent health claims. This is the first in a series of posts in which I will profile some of the questionable NCCAM study sites involved in TACT.

What is important about a study site? The investigators must be knowledgeable in the scientific underpinnings of the question being studied. Skills in the methodology of clinical research are important. The investigators must be honest, and conflicts of interest must be addressed. As you read my descriptions of the study sites in the posts that follow, keep these points in mind.

Can the overall study quality be any better than that of the individual sites? An argument could be made that because the study is double blinded, it would be shielded from bias that may exist at individual sites. A close reading of the TACT protocol, however, reveals that the blinding is not secure. First of all, the chelation mixture is not stable and therefore must be mixed at the local site. The ascorbic acid which must be injected into the mixture is yellow in color and highly viscous. The work around for this problem is to cover ascorbic acid, chelation mixture and placebo syringes and bags with tinted translucent tape and to add concentrated dextrose solution to the placebo syringe to make it as viscous as the ascorbic acid.

At the very least, the study conditions which I will point out raise serious questions about the validity of the trial.

Good housekeeping and mortality in mechanically ventilated patients

Six simple interventions have been demonstrated to improve outcomes in mechanical ventilation: daily interruptions in sedation, stress ulcer prophylaxis, DVT prophylaxis, elevation of the head of the bed, aggressive glycemic control and spontaneous breathing trials. The first four of these comprise the ventilator bundle. But as basic as they seem their rate of implementation is variable across clinical settings and low overall.

In this report from the American Journal of Medical Quality cases involving mechanical ventilation were reviewed from 38 academic medical centers. Compliance with the six practices was determined and a logistic regression model was used to estimate the effect of each measure on mortality. Compliance rates varied among institutions and were poor in general. Of the six measures, sedation interruption and glycemic control were associated with reductions in mortality.

This is all about the elusive goal of putting evidence into practice. The authors discuss barriers and potential solutions.

Whither primary care?

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

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

Background: Internal Medicine’s identity crisis.

BNP and NT-proBNP testing in heart failure

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

Bartlett on avian flu

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

It’s an alarming trend

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

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

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

Earn continuing education credit while sharing the cosmic consciousness

From the Vancouver Prophets Conference brochure:

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

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

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

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

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

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

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

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

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

Chronic thromboembolic pulmonary hypertension

Reviewed in CMAJ.

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

Be careful what you say about off label prescribing

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

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

The myth of the normal coronary angiogram

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

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

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

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

How safe is warfarin? It depends on the setting

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

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

Playing the quality game

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

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

Links between obesity and respiratory disease

Reviewed in CMAJ.

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

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

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

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

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

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

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

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

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

Life defining moments with mushrooms

Adventures in neurotheology at Hopkins.

Via Religion News Blog

The American Medical Student Association: consistency after all?

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

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

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

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

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

Cephalosporins in penicillin allergic patients

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

Background: Coombs and Gell classification of hypersensitivity.

Internal Medicine’s identity crisis

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

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

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

More evidence in favor of inhaled steroids for COPD

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

Background: I previously posted on this subject here.

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

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

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

Bugs outpacing drugs

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

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

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

Exposing absurdity

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

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

FDA supports easier standard for CAM research

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

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

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

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

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

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

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

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

Evidently, according to the San Francisco Chronicle.

Via the Healthfraud list

Background: About the UCSF Center for Integrative Medicine.

Biphosphonates and jaw osteonecrosis

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

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

The July phenomenon

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

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