New Guidelines for Thromboembolic disease

New guidelines for DVT and PE are appearing in the Feb. Annals Internal Medicine and the Journal of Family Practice and a overview of is found here.

Here are some of the highlights.

1.Low molecular weight heparin (LMWH) is preferable to unfactionated heparin (UFH). UFH is history for that application.
2.It is o.k. to treat DVT as an outpatient.Not everyone , of course, but for those patients who have the wherewith all to do the necessary things, such as take the LMWH injections and travel to where ever to get INRS-(coumadin and LMWH typically started simultaneously), etc. Further, in selected patients maybe you can treat PEs as out patients. This may give older docs a little heartburn and again this is not for all patients.
3.Three to six months is probably long enough for a provoked DVT.
4.For recurrent DVT -more than 12 months is recommended.
5.Use of Prediction Rules ( like the Wells Rule) is encouraged. Caveat-this is for uncomplicated cases, i.e. younger patients without co-morbidities.I have expressed my reservations about decision "rules" before.
6.The D-dimer is ready for prime time and with low pre-test probability ( probably as indicated by a prediction rule) and a negative high sensitivity D-dimer, further testing can be eliminated. Caveat-this may not apply to older patients with co-morbidities.
7.A negative ultra sound does not rule out a calf DVT.Ultra sounds do better for proximal DVTs.
8.Compression stockings are important in an effort to decrease the likelihood of post thrombosis syndrome.Begin use within one week and continue for a year.

Are SSRIs bad for the bones?

In the January 22, 2007 issue of the Archives of Internal Medicine, Dr. J.B. Richards et al have written a paper providing evidence that SSRI use is associated with increased falls, increased number of fractures and decrease in bone density measurements in a group of patients age fifty and over.

This was a prospective, multi- institutional study which selected 5008 adults fifty years of age and older and followed them for five years for incident fractures. They found a hazard ratio of 2.1(C.I. 1.3 to 3.4)for fragility fractures. There was a dose effect noted and there is some animal experimental data which provides some degree of biological plausibility.There are functional serotonin receptors in bone and some data suggesting decrease bone mass in mice administered SSRIs.

I have frequently harped about the growing tendency in medical publications to overemphasive the significance of small increases in relative risks or odds ratios (i.e. less than 2). Here we have a fairly credible number for the OR and some biological plausibility but the authors indicate that previous analyses of this possible relationship failed to show an association. So the case is not proven but it is reasonable to consider SSRI use as a possible risk factor in the context of osteoporosis and falls and to have a quicker trigger finger to do BMD measurements and to emphasize the value of adequate amounts of vitamin D and calcium to older patients who take SSRIs.

Is endurance exercise bad for the right ventricle?

For someone who recently finished his 50 th marathon, (with a - modestly put- incredible comeback from a mysterious orthopedic disability) the last thing I wanted to hear about is this article presenting evidence that all that running may be setting me up for a problem with my heart, specifically my right ventricle.

As a non-cardiologist I struggled to try and make sense ( and to try and deny the implications of) the observations made. Here they are:

1.22 patients, endurance athletes, with rhythm problems were referred to Dr. Hein Heidbuchel, a cardiologist in Belgium.
2.In 6 the diagnostic criteria for arrhythmogenic right ventricular dysplasia (ARVD) were met.

(ARVD diagnostic criteria can be found here It is a rare cardiac condition,a cardiomyopathy with fatty degeneration and fibrous replacement of the right ventricular wall, tendency to ventricular tachycardia and often a positive family history.The EKG may show inverted t waves in right sided leads and the so-called epsilon waves.)While rare in the U.S., Apparently this entity is significantly more common in parts of Europe (according to the Wikipedia article on ARVD).

3.In 82% of the 22 the criteria for the diagnosis of ARVD were not met but there was some abnormality showing up on testing-i.e. either the ekg,echo or morphology.The summary did not detail exactly what the findings were.

4.In the 5 who had right ventricle biopsies, none had light microscopy evidence of ARVD.

The authors postulate that the volume overload put greater stresses on the thin-walled right ventricle and might be causing ARVD. On the other ( and more reasonable hand), it has been recognized that a cause of arrhythmia in athletes is ARVD.Since these were athletes referred for rhythm problem it is not surprising that some had findings suggestive of ARVD since that condition seems to be fairly well known as a cause of rhythm problems in athletes,at least in parts of Europe.

There is evidence that in the early hours after a marathon or following a full or half Ironman distance triathlon there may occur elevations of troponin in the range seen in myocardial infarctions and there have been reported echocardiographic changes that could be described as cardiac "fatigue". The changes were those of altered relaxation characteristics and a decreased contractility all of which, along with the elevated troponins returned to normal in 48 hours.I am hoping that all of this is just analogous to the sore leg muscles and raised total CK values that remit in a few days and is of as little consequence. On the other hand, here is a paper that uses rather weak and indirect evidence to argue that long term cycling may be harmful to the heart. Also a recent NYT article quotes another study showing increased troponin levels after a marathon and briefly discussed some other tepid voices of concern that have been raised.

In the late 1970s, a pathologist,Dr. Tom Bassler put forth the overblown thesis that running marathons provided virtual immunity to coronary artery disease. The saga of Jim Fixx and the published data of Dr. Tim Noakes proved that wrong. Maybe some of us keep on running distances that are probably too long to make much sense-and much more than makes sense from a protect-the-heart point of view- still carry some of that bogus notion with as we slog along.

Hand off problems or lack of personal responsibility by physician

Here is an interesting and alarming story of what went wrong at teaching hospital allegedly because of problems in the system of "handing off" patients.Handing off or "signing out" has become a hot topic since the increased restrictions on house staff working hours has brought about more time doctors have a shift change and hand off their patients to the next shift.

Here is a much truncated version of what happened.

A 83 year old had a pacemaker inserted without incident and his post procedure chest x ray revealed no pneumothorax.Since he was on a "non-house staff" service" a nurse practioner (NP) apparently was the "doctor" in charge of care of the patient in the recovery unit. Noting increasing dyspnea a floor nurse called the doctor which is now a nurse practioner (NP) but it was after hours and apparently interns cover for the NP. At the floor nurse's suggestion a chest x-ray was ordered but never seen by the intern as before that could occur he signed out on the "night float resident". Ultimately someone recognized the pneumothorax, a chest tube was inserted almost a day after the onset of dyspnea and the patient probably suffered no long term ill effects.

The article's author then described steps taken to improve the system of handoffs which may well be a well designed and worthwhile project but...

Although there are obvious problems that occur with handoffs, my take on this situation is that the story would not have evolved as it did if the procedure doctor took responsibility for the post procedure care of his patient. When we did procedures-bronchoscopies, pleural biopsies, etc we would write on the order sheet, "Call me if there are questions or if problems arise". Just as surgeons- at least in my day- were in charge of the post op care, so were procedural internists in charge of and responsible for the patients after the procedure.

Apparently at this hospital after a procedure the patient goes to recovery where the NP is the "doctor" in charge of care- at least until their shift ends. This seems to be so much the usual way things are done that the author did not even consider why the cardiologist was not called.This is not surprising as the author, a young hospitalist, has likely never known any other way than their current system.

We seem to be replacing personal physician responsiblity with "systems".

What lessons are being implicitly taught to the house staff? The procedure doc seems to have no post procedure responsibility but is content to delegate care to a NP. In that environment how surprised could you be to learn the intern signs out without seeing the chest x-ray. End of shift-end of responsiblity.End of procedure-end of responsibility.

With so much rhetoric about instilling professionaism in medical students and house officers how can individual responsiblity be given such short shrift? In 2003 the ACGME eliminated the following statement from their pronouncements:

Physicians must recognize their obligation is not discharged at any given time or any given day.

No, that is not a typo -they eliminated the fundamental principle of the doctor-patient relationship,that the physician is responsible for his patient.

It is not coincidental that the ACGME 2003 general core competencies statement mentions "systems" or "system" seven times but saw fit not to include the above quoted sentence. To my reading the authors of the competencies seems much more concerned with team play, group dynamics,system blather, and conserving society's resources than inculcating physician responsiblity for their individual patients, which is what I thought it was all about.

Heuristics invaluable but need to be understood and monitored

I was impressed by and wrote about an article by Dr. Croskerry who has studied how physicians think and how they can think better diagnostically when they understand their basic human tendency to think by using ad hoc rules of thumb, cognitive shortcuts or heuristics. DB's MEDICAL RANTS recently (jan. 22, 2007) referenced a great article by Jerome Groopman entitled "What's the Trouble?" which draws upon Coskerry's insights.

A more detailed treatment of these thoughts can be found here in an 2005 article by Croskerry.

I came across another related article entitled "Diagnosing Diagnostic Mistakes" which also talks about diagnostic "errors" and make the interesting and , I think, valid, point that everything called an error might not be.

Dr. Clement J. McDonald authored an excellent article over ten years ago in the Annals of Internal Medicine entitled Medical Heuristics,The silent Adjudicators of Clinical Practice",
It is available in full text on line and well worth reading.

McDonald talks about common medical heuristics some of which have been codified into aphorisms, For example Occams razor which advises to choose the simplest hypothesis (or a single disease process)to explain a set of observations.Contrasted to this is the less well know Hickam's Dictum which says a patient can have as many diagnoses as he darn well wants. Another is " treat the patient not the numbers. This adage which was quasi-dogma in my house officer days has been diluted by the development of various lines of evidence that we should in fact treat the numbers, at least when we are considering blood sugar in diabetes and blood pressure values and- at least for secondary prevention of coronary artery disease-the cholesterol level.

A more recent article by Dr. Donald Redelmeier also appears in the Annals, "The Cognitive Psychology of Missed Diagnoses"

He speaks of common heuristics: The availability heuristic-we judge the likelihood of a case by how easily examples spring to mind. The anchoring heuristic-we tend to stick with our initial impression ( this runs counter to the well established scientific principle of checking for evidence that would disprove our working hypothesis).This is also called premature closure.

Humans may well have biologically ancient neurological mechanisms that organize incomplete data into a sensible whole ( our visual system seems to do a great job of that) and gives us an reassuring sense of control and an illusion of a more accurate and more complete understanding of a given situation that we sometimes really have. These and other heuristics have survived perhaps because they do work reasonably well much of time but the missed diagnoses are reminders that much of the time is not all of the time and hopefully awareness of their existence and their potential fallibility will enable us to mentally over ride them when appropriate. This could be a simple as reconsidering the diagnosis as more clinical data becomes available.

Should we consider HIT (heparin induced thrombocytopenia) in cases of DVT and PE?

The answer to the title question is "yes" if the patient is receiving or has recently received unfractionated heparin(UFH) or low molecular weight heparin(LMWH).

This important point is made in an editorial in the Sept 2006 issue of Chest (subscription required) by the guru of HIT, Dr. Theodore Warkentin from Hamilton Ontario.

He quotes an accompanying article by Levine et al who did a meta-analysis that quantitated the risk of HIT in patients in whom VTE (venous thromboembolism) developed while they were taking heparin or shortly there after. ( "How frequently is venous thromboembolism in heparin-treated patients associated with heparin-induced thrombocytopenia" Levin, R L et al Chest 130/3 sept 2006 pg 681). The risk was 12.8% in patients who were receiving UFH and less than 1/100 in those receiving LMWH.

Warkentin raises the important point that a DVT can develop slightly before or at the same time as the platelet count falls ( the drop in platelet count is the clue to diagnose HIT) so therapeutic doses of heparin may be given before one realizes that HIT is present. This refers to the situation in which a patient receiving heparin thromboprophylaxis develops symptomatic VTE. One way to avoid the possibility of giving a patient with heparin induced thrombocytopenia more heparin is to use fondaparinux to treat DVT and PE since it does not cross react with the HIT antibodies. One problem with this is that fondaparinux is not approved in the U.S.for treatment of HIT (only argatroban and lepirudin are).

It has become important to inquire about recent hospitalizations or medical procedures in any patient with VTE.Heparin is widely used in hospitalized patients ( keep-open I.V.'s and heparin flushes being common sources). Prior platelet counts can be critically helpful.

The pathophysiology of HIT is fascinating to internists, who always wax poetic, about the mechanism of disease.It is an immunologic attack in which the antigen is a heparin-platelet factor 4 complex which when linked with an IgG antibody activates and aggregates platelets which form microparticles and induces a thrombin storm of coagulation which must be treated by stopping the heparin and giving antithrombin agents. There is plenty of irony to go around-thrombosis being caused by giving an anticoagulant, thrombocytopenia that is associated with deleterious clotting rather than bleeding and potentially catastrophic venous and arterial thrombosis and gangrene if the old standby coumadin is given to a patient while the HIT process thunders along untreated.

Testing for the antigen-antibody complex,however, is not the basis for diagnosis which is clinical and keys on a decrease in platelets by 50% or a platelet count of less than 100,000.

The"Disruptive Physician" -what is all about ?

A recent blog and a comment by a colleague stimulated my interest in the concept of "disruptive physician". Googling it quickly lead to this example of what really seems to be the peer review process being used to silence a physician who had the courage to point out a serious patient safety issue at her hospital.

The recent action of the Joint Commission regarding a disruptive hospital personnel policy indicates this issue has gone past the point of just talking about it.

Without the teeth of the Hospital Review committees, talk about the disruptive physician would mean little. However, abuse of the peer review system has been written about for a number of years. Here is a good review of the anatomy and physiology of the legal structure of the peer review world, a world that seems far remote from the usual notions of due process and innocent until proven guilty and meaningful appellate mechanisms. A key point is that federal law gives peer review committees immunity and you do not want to be on the bad side of a group of people who are not restrained by the threat of tort action.

The peer review sword can be used to remove a physician whose actions are in fact placing patients at risk but can be wielded to restrict competitors or to silence or threaten an physician whose comments are "disruptive" to a hospital administration's plan to do what it wants without bothersome input by physicians.

Observational data is important but how do we analyze the data.

Here is a summary of a recent JAMA article that should make it clear that the statistical techniques on which a study result may turn are definitely not your father's t test, p-values and simple regression equations any more.

Here is a summary of the JAMA article by Stukel et.al.

My simplistic "understanding" of all of this follows.

Randomized clinical trials (RCTs) are the best way to measure treatment effects because they reduce or ideally eliminate selection bias making the treatment and control group equal in regard to all features. If done properly the study should be protected from known and unknown confounders eliminating the need for statistical manipulations.

There is an important difference between the outcome of a RCT wherein the patient self selects to be randomized and there are often many criteria which exclude subjects such as age, sex, other medical conditions present, etc. and the outcome that occurs when the treatment is applied to patients in the more real ,non-RCT world of medical practice. This is often called the "effficacy (RCT results) -effectiveness (real world results) gap. Observational studies relate to the second.

Observational studies- though plagued by selection bias-can be valuable:they provide data when there are no relevant RCTs and they are capable of finding deleterious treatment effects in the longer run with more patients.RCTs are not the end-all in regard to side effects with recent examples being cardiac outcomes of selective NSAIDs and the long term occlusion of drug eluting stents.

So we need observational data but statisticians have to deal with selection bias.
Stukel and co-workers compared various statistical methods to address these selection biases using Medicare data on the use and outcomes of cardiac catheterizations following myocardial infarctions.

They compared something called "propensity score methods" with "instrumental variable methods". As explained in an accompanying editorial by Drs. D'Agostino, Stukel's group maintained that the instrumental methods were better because they produces an answer closer to RCTs and they eliminated bias due to unobserved variables.

The editorialists seem to cast doubt on that conclusion with statistical arguments that quickly escalate from my level of understanding but they did share my concern with the authors's comment " instrumental variable analyses...are more suited to answer policy questions than to provide insight into a specific clinical question for a specific patient." The D'Agostinos say "treatment effects should deal with effects relevant to patients." Of course, what else could it be all about? How can policy decisions not affect patient management decisions?

If you juxtapose the article with editorial you quickly see that experts in the field of statistics differ in major ways about the the best way(s) to analyze observational data to mitigate the potentially misleading effect of selection bias but both groups agree that the choice of analytic method can have major effects regarding the conclusion as to what the data are thought demonstrate. So it is important how you analyze the data but statisticians differ as to how to do it. The devil seems to be in the details of analysis but the intricacies and understanding of these details seem increasingly to be beyond the reach of many practicing physicians.

I seem to stumble across more and more studies whose conclusions seem to vary by the choice of statistical technique and the discussions regarding the choice of techniques seem to get more and more obtuse.

Combining CABG with carotid endarterectomy-good or bad idea?

A recent article in Neurology suggests that the combination of coronary artery bypass surgery with carotid endarterectomy may not be a good idea.

Dr. Wes takes this article on in his blog and provides a very insightful analysis of the issue and delves into the problems that are involved with this type of retrospective analysis of administrative data. This is the type study that I like to call a "coarse grain" study, a satellite view of the forest providing no essential data about the individual trees.

Dr. Wes says it well when he speaks of the study as:

"... a retrospective chart review of computer-code data set....in an attempt to glean a flicker of data with which to draw a glimmer of a trend-NOT a conclusion."

In regard to the authors's disclaimer regarding "the limitations to the use of administrative data sets" his translation nails it:

"we know the data are poor and we fixed them a bit to clean them up and erased some data, but don't worry about that."

When the odds ratio is corrected for the various things that epidemiologists like to think they can correct for it shrinks from a value of 2.25 to an unimpressive 1.38. The uncorrected odds ratio is the one that will get the emphasis in the lay press and will serve to worry and frustrate patients and their physicians particularly since this study seems to not support the current position of the American College of Cardiology and American Heart Association. One retrospective, administrative coding analysis should not have the evidentiary weight to effectively contradict the ACCP/AHA position. Calls for a randomized clinical trial to "settle" this issue appeared quickly.

More important caveats re: generalizing from Randomized trials

In the Jan. 9, 2007 issue of the Archives of Internal Medicine, there is an interesting article regarding the external validity of randomized clinical trials. External validity refers to the ability of results of a trial or experiment to generalize to the real world population.

There has been much written about how often the elderly (usually 65 and over) and women are excluded from trials. Clinician have been frequently admonished to be careful about extrapolating results of trials to their patients who differ from the those eligible to have participated in the particular trial. This article raises interesting questions suggesting that those patients who apparently did not differ and were eligible but did not participate in the trial had a higher baseline risk and worse results. Of course, those who were not eligible had a even higher baseline risk and outcome.

Dr.Steg and a group of international investigators divided patients in the GRACE registry (which forms a large multi-national cohort,) into three groups,RCT participants, eligible patients not enrolled in a trial, and ineligible patients. Not only was there a gradient of baseline risk with those participating in RCTs having the lowest, those eligible but not participatng the next lowest and those not eligible the highest but an important observation was that the RCT participants had half the hospital mortality of the eligible, nonparticipating group. (3.6% versus 7.1%)

The authors offered several possible interpretations.The one that strikes my eye is that the better results of the trial patients is due to the "closer medical attention" possibly provided in the trial,e.g perhaps more regular use of the other treatment modalities-aspirin, beta-blockers, reperfusion therapies). Apparently, they had some evidence that this was a factor.In addition, as always, the specter of "unknown confounders" is raised which in statistic-speak means "it could be something else but we don't know what".

What are the implications of this? One is that the treatment groups outcomes would be better irrespective of the benefit derived from the particular therapy at issue.The results of thrombolysis in S-T segment elevated M.I.,for example, may be less impressive even in those patients who characteristics closely resemble those of the patients treated in the trial.

The authors seem to provide evidence for still another reason for the effectiveness-efficacy gap. Even if the direction of the results of a RCT may be correct, we should not expect the results to be as impressive when the therapies are applied to patients even if their clinical characteristics closely mirror those who participated in the trial.

Federal Trade Commission and physician group negotiation

It seems- at least from this account of recent FTC action-the likelihood of groups of physicians banding together to successfully negotiate with third party payers, is either very low or non existent. This is because the FTC considers such action on the part of docs as violating the antitrust laws.

Here is the FTC news release outlining the complaint against a number of groups that represent a large number of physicians in the Chicago area. Appeal of the FTC ruling seems to be an often futile exercise in paying large fees to attorneys with little likelihood of success and very real legal risk. A listing of the large number of physicians who have felt the impact of FTC actions can be found at this site, which also describes the continuing legal battle of one group, North Texas specialty Physicians,whose case is to be heard by the Fifth Circuit Court. Physicians alarmed by the stance of the FTC will not be surprised that both unions and hospitals are apparently exempt from antitrust laws. For a discussion of how the FTC manages instances of alleged "horizontal price fixing" by physician groups from a libertarian, Austrian Economic School point of view go here.

As long as the "negotiation" between third party payers and individual doctors is of the type "here is our offer (based on CMS Medicare numbers),take it or leave it" we have de-facto price controls. Price controls tend to have four consequences: increased demand, decreased supply, poorer quality,and the emergence of a black market. It seems to me that in the medical world of the U.S. we are seeing all but the fourth. See Scalpel for some cogent comments about quality and price controls in medicine.

As long as insurers set the prices for medical services and the FTC prohibits physician groups from negotiating for fees, efforts by physicians to support and take part in P4P programs in the hope that the downward spiral of fees for primary care will be halted will be less effective than rearranging deck chairs on a sinking ship.

Great review of major Hospital Medicine issues-Go Web 2

Dr. R.W. has posted a useful series of essays highlighting his version of the top issues for 2006 in the field of hospital medicine. Anyone who is interested in hospital based care will find these entries valuable sources of information and analysis. I found his most recent posting fascinating as it touches on the issue of how a "feel good" project can develop a mind all of its own even while seemingly forsaking basic principles of evidence based thinking in an effort to claim success in achieving its stated goals. I am referring to the widely hyped Institute for Health Care improvement (IHI) Save 100,000 Lives initiative and their claim for success even though the evidence supporting that claim is not only weak but there are good reasons to believe that some of their efforts may be counterproductive. Details can be found in his posts and more late breaking news regarding heart failure performance measures and their lack of correlation with outcomes can be found here.

I continue to be impressed with how rich and valuable the new or virtual doctor's lounge(i.e.the medical blogosphere) can be. The blogs are only part of the so-called WEB-2 which I believe is really changing the way physicians can obtain medical information.