Family Practice may be joining Internal Medicine in identity crisis

This recent commentary in a family practice journal speaks of a major attitudinal change in family practice . Recently trained Family doctors seem to abandoning their "roots".According to the author the rigors, and risks of doing ob is something that only a shrinking number of FP docs choose to do. Other recently minted FP docs seem to be opting to doing fellowships in such areas as geriatrics, sports medicine, OB, and hospital and critical care seemingly abandoning their traditions of generalism just as some one us believe that internists may be abandoning their tradition of the care of complex and critically ill patients for the regular hours of an office practice,doing mainly primary care and punting to the hospitalists (who ironically now may as likely as not be a family practice doc) when someone gets sick.

The forces of increased medical school debt and decreasing payments for physicians-particularly those in primary care- seem to be at work in fostering the turmoil in both FP physicians and IM physicians. As IM and FP docs seem to be spending much of their time doing the same things the other does-at least in an office setting-there seem to be the same trend for both FP and IM docs as they end their residency to further specialize gaining higher pay,shorter hours and probably more prestige.

The author, Dr. James Glazer, argues for the value of maintaining the core values of the FP generalism which he believes is the heritage of the Family Practitioner. We are seeing internists morphing into primary care docs and the classical primary care doc-the family practice physician-morphing into a "generalist specialist".

As best I can tell, neurosurgeons at least, still know who they are .

Tight blood sugar control for ICU patients-stay tuned again

Randomized clinical trials work best for discrete outcomes in well defined groups of patients. In studies involving more complicated, heterogeneous groups of patients with multiple variables, results tend to be less clear cut as biases, confounding factors, the play of chance and the problems of squeezing subset analysis to make some sense of it all conspire to often make the conclusions less than satisfying or useful for real life clinical medicine.

A case in point is the recent prematurely stopped trial of tight glycemic control in ICU patients reported here. No advantage in terms of 28 day mortality rate or duration of stay in the ICU was seen in the tighter control group although other trials have suggested that mortality is lowered with stricter glucose control.Two studies from Belgium had been hailed by some as landmark studies ( at least the 2001 surgical ICU study was) and largely on the basis of the 2001 study both the ADA and the AACE issued recommendations regarding tighter control of blood sugar, the former organization targeting glucose values less than 180 and as close as possible to 110. A new standard of care emerged. Here is a thoughtful analysis of the 2001 NEJM paper and a partial review of other data tending to dampen enthusiasm for tight sugar control.

The 2006 medical ICU Belgium study, which I have commented on before, gave intensivists ( a group of physicians who treat very sick patients and used to be called internists) pause for concern in their enthusiasm to "treat to goal" (a recent mantra that makes me wonder what about the old saw about treat the patient not the numbers) as the data had to be tweaked to show a mortality advantage to the tight control group.(One analysis seemed to indicate increased mortality for the first 3 days and then a mortality advantage for the tighter group). There did seem to be less need for dialysis and there was earl er weaning from ventilators in the tight control arm of the study.

The recently reported study (European Glucontrol trial) found no mortality difference for the 536 patients treated to a blood glucose of 80-110 as compared to a group of 546 who glucose was maintained in the 140-180 range.One of the investigators, Dr. Presier from Belgium, is quoted as saying that there is no reason to recommend the use of 110 mg as a target and that 140 or 150 would be wise.

I think we have learned that elevated blood sugars should not be ignored in the critically ill patient but that we can go the way of "too much of a good thing" in attempting to impose a blood glucose of 80-110 particularly in light of recent evidence of lack of clear cut benefit and the very real increased risk of hypoglycemia about which I am just old-fashioned enough to believe it is not a good thing. In the Glucontrol trial of those with a serious hypoglycemic the mortality was 18% versus 11.6 % in those without such a reaction. For those of us still optimistic enough to believe a bigger better randomized trial will show the way, we can wait for the results of the Nice-Sugar trial.

Medical Knowledge Self Assesment Program (MKSAP) -one more time at least

MKSAP 14 has been available for over a year and I finally could resist it no longer and ordered a hard copy of it.I have enjoyed/suffered through all of the previous editions.Even though I am no longer in practice I felt compelled to spend the hours reading the texts and taking the tests-perhaps it gives me a bit of a illusion of still doing what I used to do.

One of the major additions in recent versions of MKSAP is a very large booklet entitled "General Internal Medicine". This section seems to me in part to be the manifestation of the doctrine "Why can't an internist be more like a family doctor?"

There are sections on contraception and abnormal uterine bleeding. When I trained and when I was in practice women who wanted advice about contraception and who had abnormal uterine bleeding were referred to their gynecologist.Very few of the women I saw as patients did not have a gynecologist.

Does the American College of Physicians (ACP) believe and encourage that internists should be adequately expert and trained to go through the vagaries of abnormal uterine bleeding complete with ordering ultrasound and doing a endometrial biopsy? Some of the questions seem to imply just that. Are IM residents trained in this now? At best we internists might be sort-of well read novices in this area and should we not as a matter of professional ethics refer our patients to the specialists who are best able and most expert? Some of the questions in this section seem to assume internists should be able to manage these maters.

I have recently encountered some younger internists who have carved a pseudo-niche in "women's health".These, in my limited experience are mainly female internists, who among other things do the annual paps and help their patients "manage menopause" and offer contraceptive advice. As I have commented on before this is not why I became an internist.Expanding the services I offer perhaps to compete with family doctors and NPs was not something I choose to do.

Internists seemingly are also expected to be able to diagnose and treat various skin disorders including the papulosquamous problems as well as lice and scabies. A section on corneal abrasions implies internists need fluorescein strips and Wood's lights in their office as the expectation is that not only will such patients be evaluated by the internist but treated and the internists will have the patients come back for follow up observation to see if a referral to an opthalmologist is needed.This sounds like the days of gate keeping when every referral needed approval by the insurance clerk.

In spite of the apparent theme that internists need/should/might do many of the things dermatologists and gynecologists do the, MKSAP is a great exercise in reviewing the ever increasing panorama that internal medicine has become. Plus it is probably the only time you will "see" or at least answer a question about a case that turns out to be Whipple's Disease.

The efficacy-effectiveness phenomenon stirkes again-this time with drug eluting stents

Our old friend,the efficacy-effectiveness phenomenon (EEP) can be found in the drug eluting stent (DES) controversy.The NEJM electronic issue hit the ether on 2/14/07 presenting 4 meta-analyses, two editorials and the well publicized Swedish registry study which alarmed cardiologists and patients. Subscribers also could listen to an audio segment in which Dr. Steve Nissen of Cleveland Clinic debated Dr. Donald Baim of Boston Scientific. Nissen recommended that a RCT be done to compare DES with bare metal stents while Dr. Baim announced that a trial was already underway to compare DES with coronary artery bypass surgery (CABG).The DES which seemed to have solved the problem of early stent restenosis stand accused of leading to late stent thrombosis and increased coronary events-trading short term gain for long term harm. Data and conflicting interpretations and opinions fly back and forth.

The term EEP refers to the often striking differences in outcomes that occur when an intervention shown to be very efficacious and safe in a RCT is applied to a broader group of patients as the intervention moves from the very controlled world of a trial to the more chaotic settings of real clinical practice.

Some of the difference is due to the fact that the intervention is now being used to treat patients who may vary in many important-and outcome determining-ways from the treatment group in the trial. A recent article in the Archive of Internal Medicine suggest that a more subtle mechanism may be at work as well.Results may also be less impressive when the intervention is applied to patients with the identical characteristics as the treatment group in the trial an effect speculated by the Archives article authors to be due at least in part to general greater care in their treatment and more uniform and consistent application of other generally accepted and recommended aspects of care. Further. there may well be differences in trial subjects related to the fact that they agree to be in a trial.

Safety issues are more likely to become evident in the observational data that accumulate as the intervention becomes widely used. RCTs are relatively small and generally recognized not to be the method of choice to determine if less common side effects occur. Observational data as they accumulate develop much more statistical power for short term effects and because observation can continue much longer the longer term outcomes become evident.So we clearly need to rely on observational data but the rub occurs in interpretation of the data. The groups that are compared in observational data are not randomized and while various statistical techniques are applied to try and compensate for the biases that plaque non-randomized comparisons there is a thick messy residue of doubt and controversy. The techniques seem an attempt to make observational data more like controlled trials which of course they aren't.

When DES were approved by the FDA the striking fact impacting the minds of interventional cardiologist was that the restenosis rate ( the main problem with bare stents) was about 20% and that seen in the DES trials for the coated stents was about 10%. Of course, cardiologists were anxious to apply that technology to their coronary artery patients and very quickly DES took over and by a year after approval about 80% of the percutaneous interventions involved use of DES. Not only were they applied to patients who were exactly like those in the trials ( basically short lesions and large arteries in a non acute setting) but also to patients with more complicated lesions and those in the middle of an acute coronary syndrome.

From a mechanistic point of view, it seems that the addition of drugs to the stents worked to prevent the over-exuberant growth of intimal cells onto the stents causing early restenosis ( in the six month time frame) but also may have overdone it in some patients leading to inadequate neointimal coverage of the DES and late thrombosis of the stent. Some cardiologists have suggested that the late thrombosis event coincided with stopping Plavix and have suggested continued use of Plavix for three or more years rather than the one year now commonly recommended.

The FDA's position seems to be that for the on label indications for DES, there appears to be no real issue with late thrombosis and that there is an increased risk of late thrombosis in patients with more complicated lesions and those with renal disease and diabetes. . How long to take anti-platelet drugs is an unsettled question as is the use of DES in patients whose coronary artery disease features do not confrom with the current on-label indications.

When a RCT is published and publicized and the results appear to be really great the best advice may be -as Bob Dylan said- "don't speak too soon, the wheel's still in spin"

addendum: 3/23/07.I have revised the next to last paragraph as somehow the original published version was garbled .

A patient as "a fellow creature in pain"

A reprint of a  no longer recent " A Piece of My Mind" section of JAMA should be handed out to all medical students. The title- "The importance of the Right Heart" by Dr. Lawrence J. Hergott. (reference-JAMA Feb.,7,2007 vol. 297, no 5 p 447)

He speaks about making judgments "beyond the medical judgment". Much is being written about the diseases that are "self inflicted " and the blame that physicians may place on those patients which may well be manifest as "an attitude that would be difficult to conceal from such people they treat."Obesity, diseases closely associated with cigarette use and excess alcohol and "unsafe" sex come to mind. We have all seen that attitude manifest as comments about patients who are obese or who abuse themselves with drugs and alcohol and I remember hearing and making those comments from the time I was a medical student and intern. Who has not tended to treat with " greater feeling" the blameless patients, perhaps a young mother ravaged by cancer than the street bum reeking of alcohol and dirt dumped in your hospital while you are on call.

Dr. Hergott's current essay is only available by subscription but an earlier JAMA submission is full text available here and is more than worth the reading time.Here he speaks of the difference between reputation and character.Another essay entitled "Playing the Moonlight Sonata from Memory" is found in a 2002 issue of JAMA and in it he writes eloquently about the anguish a physician experiences when a patient dies because of what the physician did and the extremely long half life that anguish possess. All of his essays would be valuable to medical students and all resonate with physicians who have been there and done that for a while.

Near the end of his current manuscript he quotes part of the Oath of Maimonides:

May I never see in the patients anything but a fellow creature in pain.

Not as someone who deserves his dyspnea because of cigarette use defying years of advice to quit, not as someone whose ascites is his just due from profligate use of alcohol, not as someone who should not be in this country at all, not as someone who would not be having the myocardial infarction at all if he had done what his doctors told him to do and not as someone who is taking "scarce medical resources" from someone who deserves them more or for whom the treatment could be more cost effective but as a fellow human whose is in need of what physicians spent so many years of their lives preparing themselves to be able to offer.

The oath should remind us that being face to face with a fellow human in need

..makes judgment beyond the biomedical not only unnecessary but inappropriate.

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.

The Limits of Risk Factor Epidemiology

First a great quote, from Michale Thun, VP of Epidemiology and Surveillance Research at the American Cancer society:

With epidemiology you can tell a little thing from a big thing.What's very hard to do is to tell a little thing from nothing at all.

Gary Taubes in his widely cited article,"Epidemiology Faces Its Limits",Science, Vol 269,p. 164,July 1995, followed that quote with this comment:

...journals today are full of studies suggesting that a little risk is not nothing at all.

There is no basic law of science or statistics or epidemiology or metaphysics which will define how large a relative risk or a odds ratio has to be before physicians and patients need be concerned. Here we are talking about the interpretation or weighing of the evidence that accrues in the quest for evidence on which to base medicine.

Committees that author guidelines typically outline for the reader what their evidentiary hierarchy will be, usually randomized clinical trials at the top etc. But what are the rules for judging individual studies particularly the observational ones, e.g. case control studies and cohort studies.How big should a RR (or ORs for case-control studies) be before they consider that study worthy of adding to the pile of evidence worth of consideration ?

To get a sense of what the professionals do in that regard we could survey experts and see rules of thumb they use in knowing when to consider an observational study worthy of worrying about or suitable for publication. What we learn is that it may not be just the size of the RR but the overall context.

Robert Temple of the FDA is quoted by Taubes as saying:

My basic rule is if the relative risk isn't at least 3 or 4, forget it.

However, Dr. John Bailar,from McGill,believes there is no magic dividing line.

If it's a 1.5 relative risk and it's only one study and even a very good one, you scratch your chin and say maybe.

It is not size of the RR alone ( but we have to agree at some point low is too low say 1.03 relative risk) but the results of other studies addressing the same issue and concerns about scientific in general and in specific biological plausibility have to be factored in. Even though the size of the RR or OR ( odds ratio) is not necessarily determinative it is easy to cite a number of experts in the field who favor the notion that RR less than 2 should be- if not dismissed- at least looked at with a very skeptical eye.

While size of the relative risk is not the end of the analysis, it is the case that small RRs are more likely to be generated by undetected systematic error(s) than are large one. A RR of 1.2 should be much more suspect than a RR of 3.2

The observational studies can be considered coarse-grained instruments with bias and confounding being the basis for the coarseness,the hidden variables that can lead to an association that is not real. While calculating a confidence interval takes random variation in the data into account , bias and confounding lie outside its reach.

Sophisticated (and to many medical readers-mysterious) statistical methods such as various types of mathematical modeling may serve to eliminate or minimize some of the systematic errors but in the final analysis the reader or researcher still does not know to what extent biases are not controlled. I have yet to read the discussion section of an observational study in which the authors did not believe that they had "controlled" for sources of bias and confounding even when that study contradicted an earlier one whose authors also believed their methods likely excluded bias.

I believe that the best an ordinary medical reader -one whose wall is not decorated with an advanced degree in epidemiology or statistics-can do is:

1.Be very skeptical of Relative Risks less than 2 and particularly less than 1.5
2.Look in the articles' discussion sections for citation of confirming or contradictory studies.
3.Consider whether the findings fit some concept of reasonable biological plausibility.

Proton pump inhibitors, hip fracture and small relative risks

A JAMA article has generated considerable media attention citing a case control study that linked PPIs (proton pump inhibitors) to an increased risk of hip fracture.

The overall adjusted odds ratio was 1.44 with a confidence interval of 1.3-1.59. There was a dose response relationship demonstrated with duration of therapy.

Observational studies, such as this case-control study, are generally accepted to be so-called "hypothesis generating" studies rather than studies that more suggest a causative relationship (o.k. I'll stipulate causation is a deep, complicated philosophical issue and I use the word here just to indicate that case-control studies are just the beginning of efforts to demonstrate likely causal relationships).

A dramatic example of how observational trials can be misleading can be found in the juxtaposition of two studies in the New England Journal of Medicine dealing with relationship between hormone replacement therapy and coronary artery disease. One study demonstrated a two fold increase in coronary disease risk while the companion article showed a coronary artery risk reduction of 50% in those who used HRT.

There has been a number of conflicting case control studies regarding the relationship between statin use and colon cancer risk which again points our the problems involved when you take the results of one such study too seriously.

Let's quickly apply Bradford Hill's criteria to the PPI-hip fracture issue. The temporal relationship is there. There is a dose response relationship is a reasonable biological plausibility- low stomach acid conditions can interfere with absorption of some forms of calcium.
However, the association (1.44. OR) is not very large and there is not a strong consistency of results in other observational studies. (The JAMA article quote another study with similar results and one that did not demonstrate the association). At the end of the mini-analysis we still don't know if the reported relationship is valid or really know if we should somehow change our practice in regard to PPIs.

How big should the relative risk (RR) or odds ratio (OR) be for us to be concerned with the results? This is the very question asked by Dr. David Sackett in his book " Evidence-Based Medicine. How to practice and Teach EBM", Churchill Livingtone. Second edition,pg 162).For an answer to this the pioneers in EBM turn to argument by authority as opposed to an evidence based reason.

In regard to a case control study he said

We might not want to label an odds ratio from a case-control study as impressive unless it is greater than 4 for minor adverse events and set this value progressively lower [for more serious events].

Further, he says in regard to a cohort study, where there is less potential bias , that a relative risk of greater than 3 might be convincing for a more serious adverse event.I have posted before on the issue of RR in the 1-2 range.

John Ioannidis stirred up the medical community a bit in his article "Why Most Published Research Findings are False" and in regard to small relative risk determinations he is quoted as saying:

The smaller the effect sizes in a scientific field, the less likely the research findings are to be true...more likely true in scientific fields with ...relative risks [ in the 3- 20 range] ...than in scientific fields where the postulated effects are small [in the 1.1-1.5 range]

Could this study, and so many more with RRs less than 2 hit that hit the headline news, not really be worth much concern at all since the reported increased risk is so small ?

Dr. Marcia Angell, NEJM editor, has been quoted as saying that generally they only accept papers if the relative risk is 3 or more, particularly if it is biologically implausible or if it's a brand new finding. In the PPI case, there is some biological plausibility and occurs in the context of at least one study with findings pointing in the same direction.

In some legal venues, a relative risk of 2 or more is required to meet the legal standard of "more likely than not".

The PPI study authors suggest we should recommend that calcium supplements be taken with meals and I would add recommend adequate amounts of vitamin D ( thought to be about 800-1000 units per day now) and to perhaps have a looser trigger finger on the indications for measurement of bone density in those patients who are on long term PPI therapy and/or higher dose. However, I do not think patients whose GERD symptoms have been controlled by PPIs-and sometimes this change has been dramatic-should throw away their pills.

Is being a hospitalist the only way to still be a old time internist?

Dr. Laurence Wellikson seems to believe that the only way -at least a way-to recapture the core of what internist used to do (care for the patient with the complex problem(s))is to become a hospitalist.

Here is a point-counterpoint presentation by Dr. Willikson,CEO of the Society of Hospital Medicine,and Dr. Robert Centor,President of the Society of General Internal Medicine on the topic of "What is an Internist?"

Willikson seems right on target when he speaks about "internists [having] devolved into gatekepers and primary care physicians" ...[and] competing with Family Practitioners and Nurse Practitioners to be the traffic cop for resource use and burgeoning specialization."

He then inserts some of the current- in- vogue- jargon of the business consultants and speaks about the importance of preparing a "value proposition" and then makes what I consider to be a "boil the oceans" type suggestion namely to "reset the reimbursement system".

Given the current power relationship between third party payers and physicians it hard to conceive of what doctors could do to change the system. Hospitalists are either employees of the hospitals in which they practice or are contractors. The only tool either group has to bring about change is the strike, an action that physicians have rarely participated in. Changing the current medical care-reimbursement system is going to take more than hospitalists or internists writing a value statement, which I understand to be a statement made by a business explaining what they do and why the targeted customer should by it. (It occurs to me what if other specialists were exhorted to author a value statement.Perhaps neurosurgeons would propose "We take out brain tumors better than anybody."

Hospitalists do seem to spend most of their work day doing what many of us wanted to do when we decided to become internists and I hate to think the only avenue for the Oslerian type internist to travel is that of the hospitalist but that may be the reality though we have not quite arrived at that point yet. I hate to think that because an important part of what I used to do was not only caring for the complicated case in the hospital but also as an outpatient. This was a common occurence with COPD patients with exacerbations requiring hospital and often ICU type care. Internists should be the ones caring for patients with complex medical problems in and out of a hospital setting. There are still internists who care for the complex cases as in and out patients but clearly it is getting harder to do that. Dr. Wellikson seems to think internists should care for complex cases outside the hospital as well but leaves me wondering how he thinks that will happen.