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Is the new professionalism and ACP's new ethics really just about following guidelines?

The Charter ( Medical Professionalism in the New Millennium.A Physician's Charter) did not deal with just the important relationship of ...

Friday, December 30, 2005

Is promotion of "excessive sleepiness" the latest example of disease mongering

I previously posted about the notion of "disease mongering" . Ads are recently appearing alerting the public and/or the medical profession to the "common and debilitating" of excessive sleepiness (ES). The Epworth Sleepiness scale is recommended to determine if your level of sleepiness rises to the level of being designated as "excessive".The reader is told that 50 % of work related accidents and 25% of household accidentss are due to ES,it is common in depression (as many as 1 our of 5), 80% of Parkinson pateints have it and, of course, it is common in patients with obstructive sleep apnea (no argument there). I also posted about a new alertness drug,modafinil, which was featured in an NEJM article and was accompanied by a somewhat skeptical editorial.In Jan. 2002 the FDA sent Cephalon (modafinil's manufactuer) a warning letter for "false and misleading material" which promoted its use for sleepiness and lack of energy when at the time it was only approved for narcolepsy. In October 2003,the FDA expanded the approved use to obstructive sleep apnea/ hypopnea related sleepiness and to sleepiness due to shift work sleep disorder.Interestingly, even though the Cephalon ES advertisement mentions Parkinsons disease as a condition in which excessive sleepiness may be a issue, a recent RCT from Baylor Medical School failed to show any benefit from modafinil in Parkinson patients.In 2005 a number of RCTs were published that evaluated modafinil in:ADHD,Obstructive Sleep Apnea,shift work shift disorder,cocaine dependence,shizophrenia,patients with incomplete response to SSRIs and as an analgesic potentiator. There were with mixed results. It may well prove to be of some value in several conditions but my concern is with the advertisement approach in which physicians are encouraged to "screen" for ES as it is "often unreconized and untreated".Physicians are encouraged to include the Epworth Sleepiness Scale into "routine evaluations".I wonder if we be seeing that ES seminars will be part of the medical meeting scene and "thought leaders" will be discussing the latest research involving modafinil in a variety of conditions and patient advocacy groups will enlisted and can direct to consumer advertizing be far behind. In short the whole disease awareness campaign to promote a condition as serious,common,underdiagnosed and treatable might be gearing up.Interestingly,today (12/3o/04) I received in the mail an invitation for a seminar worth 4 hrs. of CME on the topic of excesssive sleepiness.I'm going to pass on this one.

Wednesday, December 28, 2005

More on community acquired pneumonia and guidelines

The Dec. 20, 2005 issue of the Annals of Internal medicine published an article evaluating various implementation strategies for pneumonia guideline implementation.This was a RCT but not a trial to see how effective or safe the Pneumonia Severity Index (PSI) is but to determine the preferred method to implement the guidelines based on the PSI. It did not go unnoticed that one of the authors is Dr. MJ Fine who is credited with the Fine PSI.The authors concluded that a "high intensity" intervention increased the proportion of "low-risk"patients with pneumonia who were treated as outpatients. A key outcome of interest was the number treated as a outpatient.Importantly they listed numerous contraindications to outpatient treatment.These conditions trumped the PSI.Many of the reasons that inpatient treatment was opted for were the reasons that clinicians used to hospitalize patients in the study quoted in a earlier posting.The trump list included:frailty,serious comorbid conditions,extreme abnormalities in vital signs or laboratory values,clinical or psychosocial factors that could compromise the outpatient use of oral antibiotics.Viewed in this light,the PSI is a much more limited tool.It is useful unless any of the above list applies.Most of the items in the list require clinical judgment.How frail is the patient,how seriously abnormal the lab finding, etc.etc.The authors tout the value of the PSI and for them apparently the only issue is how best to implement it.However, the PSI is only a part of the assessment process as they implicitly admit by recognizing the many clinical factors that override its use. I find the importance placed on proportion of patients treated as outpatients somewhat disturbing.
While we do not want to needlessly hospitalize patients the basic doctoring mission is to do the right thing for patients and in that regard to measure success at what we do in terms of how many patients did we send home with pneumonia seem to miss the main point of what physicians do.The AJM article previously blogged about pointed out the importance of clinical judgment, the Annals article seemed narrowly confined to how to minimize hospitalizations by determining the best method of implementing the PSI and seems to ignore the importance of clinical judgment .Dr. Robert E. Siegel from the Mount Sinai School of Medicine in an editorial in the American Journal of Medicine (Amer. J. Med. 118:1311,dec.2005) said of the PSI ,"formulas, points and classes, no matter how helpful are no substitute for experience and judgment."A similar view was expressed by the American Thoracic Society in their 2001 paper on CAP when they spoke of the admission decision as an "art of medicine" decision and said that no rule by itself can determine the need for hospitalization.

Community acquired pneumonia-Pneumonia severity index falls short

One of the operational rules of the medical-quality "thought leaders" is that "variation is bad" and it must be mitigated.(The borg has a similar philosophy and more effective implementation methods).According to an interesting and useful article by Marrie and Huang (American Journal of Medicine:118:1357,2005)marked variation in the admission rate for community acquired pneumonia(CAP) lead to the development by Fine et al of the pneumonia severity of illness(PSI) score as a guide to the admission decision. These AJM authors reviewed 3065 admissions in Edmonton with a diagnosis of CAP over a 2 year period. 586 (19.1%) were classified as "low risk" using the PSI. Was the hospitalization of " low risk" patients a shameless, thoughtless waste of precious medical resources? Apparently not. Almost half ( 48.4%) were sick enough to be in the hospital for more than five days.19% suffered one or more complications and 31% were still unable to ear or drink to maintain hydration by the fifth hospital day. Clearly the admitting physician's clinical judgment appropriately overruled the PSI score. Fine's classification system keys to mortality rate.Those in risk classes I to III have a < 1 % mortality rate.The authors point out that the PSI does not work if the patient has COPD or pulmonary fibrosis or HIV infection or immuno suppression, etc. etc. and there are important prognostic factors not captured by the Fine index including nausea,shortness of breath and diarrhea . Their final sentence is: " It is clear that low-risk patients are a heterogenous group and that a low risk for mortality is not the only factor to be considered in admission decisions".Fortunately for a significant number of patients with CAP, the admitting physicians used what seems to often elude guidelines and algorithms namely clinical judgement.Of course,low risk patients are heterogenous:patients are heterogenous-biological variability is what it is all about. All patients classified as having the same illness are not the same,patients do not all react to the same treatment in the same way.Our ability to figure everything out ahead of the facts as they unfold is very limited.Humans dealing with the human condition are doomed to have to improvise and be inventive and use judgement.Off-the-shelf rules do not and never will adequately cover all the contingencies that we face in medicine or for that matter in most everything else. Credit is due to the authors of the Emonton pneumonia critical pathway which seemed to have emphasized that "physician judgement should take precedence over guidelines" an insight seemingly unable to penetrate into the bean counter mentality.

Friday, December 23, 2005

Have patient monitor own blood pressure-What a thought.

Medscape has a good summary on the current Blood pressure measurement advice. Home mesurements are important and may be a better indicator of the "real" day to day pressure than the occasional office reading.I have told patients that for years and asked them to buy an automatic cuff and to bring in their cuff and check it against the doctor's office mercury BP unit. Dr. George Burch, chief of Medicine at Tulane when I trained, told his patients that and in those days had a family member learn how to take the BP with the arm cuff and stethoscope (automatic units had not yet been invented). Burch also emphasized the importance of proper cuff size. It looks like it took 40 years for the American Heart Association to catch up with my old prof's advice.

Long acting beta-agonist (LABAs) and the dilemma of "coarse grain" data

The FDA has recently issued an advisory saying that LABAs may increase the chance of severe asthma episodes and death when those episodes occur,this warning appearing more than 10 years after salmeterol was first approved for use in the U.S. Formoterol ,another LABA is used less widely in this country but the combination of salmeterol and a steroid sold as Advair is very widely used by allergists, pulmonologists and family practice doctors.The warning does not apply to LABA use in COPD.
As early as 1994 some increase in asthma deaths was attributed to salmeterol. A Lancet article
by Castle et. al which was designed to compare albuterol with salmeterol showed a non significant increase in death by a factor of 3 in the salmeterol group while asthma control seemed better in those treated with salmeterol. Even though the increased number of deaths was not statistically significant, the FDA's concern lead GSK to initiate the SMART trial, the interim analysis of which has lead to further concern and the warning issued by the FDA. In this trial salmeterol was compared to placebo and after 26,000 patients were enrolled, data indicated that asthma related deaths were 4.4 times higher in the treatment group. The reason that I call the data coarse grained is that neither the Lancet paper or SMART have adequate data regarding which patients were also receiving inhaled steroids (ICS) to make a determination regarding whether steroids will mitigate or eliminate any increased risk from salmeterol.This is important as standard therapy consists of adding an ICS for asthma as severe as"mild persistent", so we need to know the risk of adding a LABA to ICS for the more severe degrees of asthma. Two large RCTs do not provide that critical information because there is not enough detail and/or statistical power available to indicate if there were increased deaths occurring in patients receiving ICS plus LABA.A post hoc analysis suggested that the risk was greater in African-Americans.
It has been the experience of pulmonary docs and allergists that for most patients the addition of a LABA to ICS is beneficial yet there may well be the possibility of a rare serious side effect.
LABAs , to a greater degree than short acting beta agonists have been accused of down regulating the beta 2 adrenoreceptor and inducing subtherapeutic response to the rescue inhalers which is a proposed mechanism for the worsening of asthma. It may well be that genetic polymorphism in these receptors may account for a small subset of patients who are at risk of worsening asthma if treated with LABAs.The coarse grain data we currently obtain from epidemiologic methods cannot tell us who they are. Should we change our practice in light of the FDA warning? I continue to believe LABAs are appropriate to add on to the asthma patient's regimen when ICS and rescue inhalers are not enough. Theophylline preparations and leukotriene antagonists may be used instead but the ease of use,the low incidence of acute side effects and the patient acceptance of the LABAs make me think there will be little change in the number of prescriptions written. This belief is strengthened by the MEDSCAPE review of the Harvard study suggesting that many physicians do not pay that much attention to the black Box warnings anyway. The National Jewish website has this page that should reassure their asthma patients and at least gives the impression that they plan no major changes in their treatment approach.This page from the CMA journal give a good overview and some common sense recommendations with which most would agree.These include:LABAs are not to be used as rescue inhalers,be sure the patient is taking an ICS before LABAs are added to the treatment plan, and use the lowest dose when possible and if symptoms worsen contact your physician.

Thursday, December 22, 2005

DCCT/EDIC : Glycemic control may decrease cardiovascular risk

For a number of years I have told type 2 diabetics that it is important to control the blood sugar to decrease the risk of damage to the eye, kidneys and nerves but that we needed a different approach to decrease their risk of heart disease. Now the follow up part of the landmark DCCT give us evidence that at least in type 1 diabetics that glycemic control decreases the risk of cardiovascular disease. The decrease in cv disease risk is impressive,in part, because the treatment group enjoyed lowered blood sugar values for only 6.5 years. After that, during the followup period (from 1993 until Feb. 2005) there was little difference in glycemic control.Yet apparently that 6.5 years of better control translated into an impressive 57 % decrease in non fatal MI,stroke and cv disease death. We do not know if this benefit will accrue to type2 diabetics when and if they achieve control such as that seen in the treatment group of the DCCT (glycosylated hemoglobin of 7.4 versus 9.1 in the usual treatment group) but my bet is that it would. You have to wonder what results would have been seen if the Hb A1c values were closer to current treatment goals. I like to poke fun at the RCT religious zealots but a well designed and executed RCT-such as the DCCT- is a thing of beauty.

Evidence Based Medicine proponents need to watch out for their friends

Dr. H. Brody et al authored an interesting article in a recent issue of Perspective in Biology and Medicine which point out problems posed by so-called friends of EBM. They speak of those who
exhibit "decerebrate genuflection before the alter of the RCT".These are the folks I spoke of in a earlier blog who denigrate the use of parachutes because their use has not been validated by a RCT.The second group of friends are the commercial sponsors of RCTs who sometimes at least corrupt the process by stacking the deck to mislead the readers.The third group is populated by those "advocates" such as HMOs and insurance companies who also corrupt the process by using RCT's to justify limiting care aka saving money whose mantra seems to be " If there is no RCT we don't need to pay". Much of the Autumn 2005 issue of Perspectives is devoted to thoughtful essays on EBM. Unfortunately there is no open web resource for the entire issue which made me actually go to the Medical society library to read it, a trip I have not made in years. One more quote, this time from the article from Dr. R. Upshur who speaks of a "near religious belief [in which] assertion has replaced argument."

Tuesday, December 20, 2005

The efficacy of parachutes and the nature of evidence based medicine

Dr.RW in his increasing prolific and useful blog recently referenced an article by Dr. Norman Laton, a professor of neurology at Cornell.Laton points out that RCTs are not always needed nor always possible. There is a long list of things doctors do that do not have RCTs supporting their use. A few are: appendectomy for acute appendicitis,inserting a chest tube for tension pneuomothorax,setting a fractured bone,draining an subdural hematoma,taking time to listen to a patient,doing a lumbar puncture with suspected meningitis,getting an ekg on a patient with chest pain. Dr. Laton particularly criticizes EBGs (evidence based guidelines) that consider only RCTs as evidence.
The current EBM gurus as well as those who are credited with the foundational thinking of EBM do not maintain that RCTs and meta-analyses are the only evidence that we can use in determining the value of what we do.They realize that clinical judgment and patient values cannot and should not be cast aside.However,I hear physicians at meetings as well as medical student's comments that indicate they seem to believe that if there is not a RCT to a specific point then the tenets of EBM dictate that that procedure,treatment or whatever cannot be rationally used and to use it anyway will not only waste precious resources but may well be harmful. Here's the thing;There are many things that we do that are correct and which no RCT addresses. Further there are RCTs that are facile and basically empty (such one that compares a new antibiotic or ARB , or ACE or PPI with a barely adequate or inadequate dose of a comparator drug.There are many of these studies that drug companies do to show comparative efficacy with a drug which has proven efficacy).
A similar thought to some of what Dr. Laton said was expressed at a recent CME on hypertension by Dr. Tom Giles, President of the American Society of Hypertension when an audience member questioned some statement Giles made because there was " no evidence based medicine" proving the value of the proposed medical management issue.Paraphrasing Giles's reply.'RCTs can be very useful although some provide little useful new information.And some things may not need a RCT for validation. It would be hard to recruit subjects for a RCT to investigate the efficacy of parachutes to manage gravitational challenge.'

Wednesday, December 14, 2005

Endurance exercise hyponatremia-how does it happen?

One of the gurus of the medical aspects of endurance exercise, Dr. T.D. Noakes, of Cape Town has published a detailed study of 2,135 endurance event participants and gives us slow-marathon and slow- ultramarathon runners some authoritative insight ( Only an abstract seems available so far)into marathoner's hyponatremia. First of all some folks simply drink too much water.These people actually gain weight during an ultra event.Most runners loose weight, which, it turns out, is safer.The second reason is "inadequate suppression of ADH". The third reason he offers is failure to mobilize osmotically inactive sodium from bone. Looking at his data, 19% of the 2,135 runners were hyponatremic in the range of a sodium from 129-135 and another 11% had values less than 129. Weight gain during the race was the tip-off to low serum sodium values but most of those gaining weight (70%) did not have low sodium values. In a separate,earlier publication, Noakes et al studied 6 Iron man participants with a history of hyponatremia and 6 control Iron Men with a water loading experiment and was unable to discern any characteristic pathophysiological features to explain why some do and other do not develop low serum values. Hyponatremia can occur in some elite runners although data from several marathons indicate that the current apparent increase in marathon hyponatremia more typically occurs in slower runners who tend to overhydrate,are inexperienced and tend to be thin and female. The older advice to drink at each hydration station and do not wait for thirst has changed and some race directors are actually recommending fewer aid stations.The official hand book of the New York marathon recommends only 8 oz. every 20 minutes as a maximum. Mild hyponatremia, according Noakes' chapter in "Endurance in Sport" by Shepard and Astrand, is usually mild and self limiting but there are dramatic exceptions including fatal cases.
Hopefully,as inexperienced marathoners are disabused of the notion of excessive water intake during a marathon we will be seeing fewer cases.

Tuesday, December 13, 2005

charges, counter charges,innuendos and more re: Vioxx,NEJM,Merck,Cleveland Clinic

Almost everyone involved in the Vioxx matter is either accusing someone of something and/or is being accused of something.The editors of NEJM are accusing Merck of not being forthcoming with the VIGOR study heart attack data.Merck counters with the statement that they did not supply NEJM with the "extra" heart attacks because they occurred after the cutoff date for data accumulation and that they did report the deaths to the FDA. Eric Topol is outspoken in his criticism of both Merck and the FDA. Topol has been accused of conflict of interest because he was advisor to a hedge fund which is said to have sold Merck short. Topol has been relieved of his position at the Cleveland Clinic Lerman school of Medicine where he had been provost and chief academic officer. Topol has charged that this action resulted from his role in criticism of Merck both in and out the court proceedings. The clinic counters that the job loss was the result of administrative reorganization and was not related to Topol's role in the Vioxx matter.The CEO of the clinic, Dr. Toby Cosgrove, who demoted Topol had been accused of conflict of interest in several other matters as outlined in interesting detail by hcrenewal .Some medical bloggers question the motives and the significance of the NEJM editors publishing their e-editorial describing the missing 3 heart attacks while the third Vioxx trial was still underway in federal court in Houston.
And if all of that is not enough, McDonalds has accused both Topol and Cosgrove of opportunism and demogogery in working to remove McDonalds from the Cleveland Clinic.This,of course is note related to the Vioxx and the Topol demotion issue, but makes me think how easy it is to make accusations and how hard and often expensive it is to prove them. What is even harder is to try and sort it all out from newpaper stories and boggers comments and revelations. My bias and my sympathy lies with Dr.Topol and not with Merck . As to Topol v.Cleveland Clinic administration, I do not know how to begin to sort all of that out. It could be as simple as a power struggle between two very accomplished physicians or one act in a morality play in which big interests and big conflicts of interests are on the stage.

Friday, December 09, 2005

NEJM editors claim Merck withheld data re: Vioxx study heart attacks

In a turn of events more typical of John Grisham novel than a real trial in a federal court, editors of the NEJM announced in their online journal they had become aware of Merck withholding data from the Vigor trial manuscript which would have made the cardiovascular relative risk even higher.This occurred while the third Vioxx trial is underway in federal court in Houston.Just when you thought revelations about Merck's alleged misdeeds could not get any worse, the editors at NEJM accuse Merck of deleting data so that three additional heart attack deaths did not appear in the data tables.This change did not alter the basic finding of increased risk in the Vioxx treated patients so you wonder why the researchers bothered to make that change.Material,that included internal Merck e-mails- that become public during the trial seemingly lead the editors to take the unusual action of re-assessing data from a several year old article. This raises the lack of credibility to previously unreached levels as regards clinical trials funded by drug companies. Merck has issued a statement in reply to the NEJM editorial statement that in part states the three deaths occurred after the agreed upon cut-off date for the end of the trial and those deaths were reported to the FDA. We have not heard the last of this. We teach medical students that the reasons for an association or lack of one in a clinical study are: chance, causality,bias and confounding. The fifth factor, fraud, was not typically emphasized in that regard, now it maybe it should be.

Thursday, December 08, 2005

More problems with CPOE-this time apparently fatal ones

Dr. Andy comments on a tragic situation at a pediatric ICU resulting from the institution of a computerized physician order entry system(CPOE) that apparently significantly impeded proper care with resultant increase in ICU mortality. This experience is described in an article in Pediatrics.(abstract only for non-subscribers)
Previously I had commented on increased adverse reaction rate reported from a VA hospital after they put CPOE into place, but this is worse. According to the proposed explanations of what went wrong, basically the CPOE disrupted the normal flow of care by skilled nurses and doctors and seriously interfered with the procedures,practices,systems and mechanisms that were designed or evolved in that pediatric unit and while they may have not been perfect they were obviously much better than what replaced them.Treatments and diagnostic tests were apparently delayed and the important team work between bedside nurses and physicians was seriously damaged.The ICU is not a forgiving place for delays in treatment and poor communication.I hope this important and frightening article is widely read and appreciated. Systems that alter critical operations at a hospital should not be implemented without considerable input and advice from the people on the ground (the docs and nurses) and need a shakedown cruise or two before it goes live and should run parallel with the old way until folks can determine if it works.If a given IT "solution" will be useful or harmful is an empirical question and to assume that safety or efficiency or whatever positive thing is claimed will automatically occur just because it is IT is foolish. A recent JAMA article on error rate with a CPOE attracted considerable interest.The following quote from an article commenting on that study gives a good description of what it is that computer systems have to deal with in the medical management of patients."Designers of healthcare information technology must be exquisitely sensitive to the non-linear,context dependent, fast communication- dependent,interruption-filled,uncertain and collaborative nature of hospital clinical practice". Unforeseen circumstances will occur with new systems and ways of doing things.We should not be surprised at that.However, in this era of evidence based medicine it is ironic that physicians permit systems to be implanted without evidence of efficacy or safety of a particular system in a particular setting.

Tuesday, December 06, 2005

The medical profession-have we been divided and conquered?

Thoughts plucked for the insightful editorial ( for which I do not seem able to set up a hyper-link) by Dr. Philip R. Alper (Internal Medical World Report, November 2005) makes me think we have been divided by the power of managed care and the self-interested economic activities of hospitals.Somewhere in the mixture the hospitalist movement may also serve to divide and conquer even if that may be an unintended consequence.
The disruption of the traditional and customary lines of referral occurred early in the managed care era. It became too routine to refer to physicians not because you thought they were the best for your patient but because they were on the patient's insurance plan.Dr. Alper speaks of the growing divide between physician who practice at hospitals and those who are just on the staff. As hospitalists and intensivists grow in number so do the IM and FP docs who do not even go to hospitals except often enough at staff meetings to maintain privileges. He discusses growing tension between those specialists, such as orthopedists, who must be on call at the ER and the docs who-after hours and often during hours-send their patients to the ER and never see them there or later in the hospital.He talks about hospitals who advertise the purported advantages of certain operative procedures by some of its staff surgeons while other surgeons on staff who do not do that particular procedure fume.His theme was in part that all of this and more have lead to a major decrement in the collegiality of physicians. He believes one manifestation of this is the loss of previously almost universal practice of giving professional courtesy. Previously Dr. Alper has written that HCFA and insurance companies have poisoned the relationship between physicians and patients, now he posits that those and other forces seem to be poisoning the relationship between physicians.

Monday, December 05, 2005

Might some good come from the drug-trial book cooking of big pharma?

What good could possibly be derived from publishing misleading medical information in main line journals?
I'll admit this may be carrying the half-full half-empty glass thing a bit too far. But here goes. We-the medical professionals-are now on notice that when we read about a RCT or doze through a meta-analysis that we have to be much more critical and skeptical that ever before. We should now more than ever know better than to say that because there was a RCT showing that drug x did whatever good thing that we now should use that drug and now we have evidence based medicine behind our decision. An RCT may be the best tool we have to assess drug and procedure efficacy and give some data regarding safety but one or even two RCTs are not necessarily sufficient to wrap the banner of EBM about the decision to use that medication.RCT design can be structured to give positive results that are in fact bogus. For example,you can compare your new drug with a lower than maximally effective dose of a old drug and there are many other more subtle tricks of the trade that we can now detect thanks to the growing recognition of the sometimes duplicitous behavior of drug companies. Big Pharma's antics have made us better consumers of medical information and more able to recognize the various forms that pharmaceutical infomercials (I 'm taking about free dinner talks and some of the material in the throwaways) now take. Importantly, medical journal editors are taking steps to make more transparent the mechanics of how clinical trials are put together and analyzed and requiring the authors to make more meaningful statements regarding their role in the publication.Academic centers are beginning to access FDA data and independently re-analyze date regarding drug safety and efficacy.(Kudos to the folks at Cleveland Clinic for leading the way in that regard).Lastly, although hyper-rapacious and overreaching plaintiff attorneys have earned their less than overwhelmingly positive reputations with physicians and the general public, the VIOXX trials may well not only inform us about how drug companies may place short term profits above all else but will serve as a major wake up call to the drug industry that that the jig is up in regard to misleading the medical profession and the public about their products.
We have learned that RCTs are vulnerable to manipulation and- because of that and the fact that typically the subjects chosen for the trials are not always enough like the patients we treat-as important a tool as they can be, they need to be classified as more as a silver standard than a gold standard. Knowing that a given finding resulted from a RCT should not end the discussion, that fact should be the beginning of a consideration of the details of the trial and analysis wherein sometimes the devils lie.Our recognition of some of the ways Big Pharma has manipulated certain aspects of evidence based medicine may have served to alert and inform us about the limitations of EBM.

Saturday, December 03, 2005

Noted Cleveland Clinic Cardiologist blasts Merck in deposition

Eric Topol,chief of cardiology at Cleveland Clinic has little good to say in his deposition about Merck's actions in the Vioxx matter and in the efforts of Merck's executives to silence his criticism.Importantly, for the current trial,Topol's deposition stated that Vioxx could increase risk of heart attacks soon after starting the drug.How soon any increased cv risk might manifest itself is apparently an issue at the trial. Merck is taking the position that Vioxx increases risk only after 18 months of use; the plaintiff in this case used it for only one month. This is the third Vioxx trial. His deposition criticized Merck's alleged efforts to spin trial data to decrease any statistical demonstration of increased risk and what he described as the company's efforts by their executives to influence him to stop his publications regarding Vioxx and CV deaths. He states that a former CEO of Merck contacted the CEO of Cleveland Clinic and a VP visited Topol to attempt to dissuade him from publishing anything reflecting poorly on their drug.
All of this came to light on the heels of Topol et al's JAMA publication regarding CV risk of a dual PPAR agonist, muraglitazar, which Merck had submitted to FDA for approval. Merck's interpretation of their data showed no increased risk while Topol and colleagues did.
The David and Goliath drama playing out between Topol and one of the biggest of Big Pharma is just one aspect of the still growing lack of credibility of drug company clinical trial data by the medical community and the general public.Another David story is told by HCRENEWAL wherein a Sheffield University researcher, Dr. Aubrey Blumsohn, is suspended by the university because of a dispute between Proctor and Gamble and Blumsohn regarding a study involving risedronate. That case seems to exemplify the "golden rule" which states that whoever has the gold make the rules.

Tuesday, November 29, 2005

Studies suggesting prolonged survival in COPD by ICS may have been biased by "immortal time"

In discussing tiotropium (a recent posting)I mentioned that the best we have seen so far with medication in COPD is alleviating symptoms and decreasing exacerbations and hospitalizations and improving the nebulous quality of life.It was pointed out off line to me that ICS had been shown to prolong survival.However, the study that reached that conclusion may have been flawed by something called the "immortal time bias". Something that obscure (although with Google can anything be obscure for long?) and with as interesting a name as that needs to be talked about a bit. An explanation and example regarding COPD treatment with ICS can be found here.
The author explains that this bias refers to a cohart study in which the followup time during which a subject in one group cannot by definition develop the outcome of interest, such that during that time they are "immortal". A rate ratio based on that type division of treated and untreated will be biased.The literature regarding ICS treatment in COPD is interesting. A meta-analysis demonstrated improved pulmonary function but no difference in number of exacerbations while subsequent RCTs demonstrated no changes in pulmonary function but fewer exacerbations with ICS treatment.Once again the highly touted meta-analysis was trumped by RCTs. References to those studies are found in the introduction of the article referenced above.I take some sort of perverse pleasure in pointing to situations in which the two highest rungs on the epistomologic hiearchy of evidence based medicine when they investigate the same issue appear to contradict each other. This is not a rare occurence.

Major changes in AHA guidelines for CPR and ECC

The 2005 guidelines are available.Full text downloads can be found here.The 15:2 compression-ventilation ratio has morphed into a 30:2 ratio. The shock-shock-shock sequence has been revised to single shock ( with the proper voltage) followed by 2 minutes of CPR initiated without checking for a pulse. The paradigm shift is that with the old way (i.e. what we did yesterday) cardiac compressions were too often interrupted and was too often inadequate.
"Push hard, push fast" is the didactic sound bite of this version of resuscitation instruction.
For HCPs ( this includes the professionals formerly known as doctors and nurses) you should give two rescue breaths,perform CPR at the 30:2 pace,shock,restart CPR for 2 minutes. When an advanced airway is in place give 100 compressions per minute and 8-10 breaths per minutes with no pauses.Not too long ago the emphasis was in getting an airway in place and there were instances where too much time was spent in misguided (literally) efforts to insert an endotracheal tube by folks who were not well practiced at that task,then the emphasis was on repeated defibrillation efforts which at times were carried out and assessed while the CPR was stopped and no oxygen was reaching the brain. And now the emphasis in on effective cardiac compressions. This sounds very reasonable and has to be considered the state of the art. Art here is the operative word.The now discarded approaches seemed very reasonable at the time and were considered the state of the art .It is harder to get things right when we do not have the advantage of multiple useful randomized clinical trials which because of the very nature of sudden cardiac arrest we will likely never have. The pannel emphasized that there are data indicating few victims of cardiac arrest received high-quality CPR. I think this is what you would expect when instruction (and limited practice) typically occurs once every one to two years. I do not believe that is enough practice for HCPs to develop and maintain competency in an exercise that is complex and obviously important.In our clinic we had monthly CPC and ECC reviews with practice exercises lasting about 45 minutes.

Monday, November 28, 2005

New trend in drug company CME sessions?FP docs as the experts.

Three times in the last 4 months I have attended the typical drug company sponsored evening CME held at nice restaurants at which the subject matter expert presenting the talk was a family practice physician. One was on Bipolar disease and it was interesting how many bipolar patients this FP doc had apparently treated. The topic of another talk was BPH and 2 FPs shared the stage.One interestingly mentioned that he had not had a chance to "go over" the slides prior to his talk making the skeptical among us wonder who wrote the script.This talk was given around Nov 3, 2005. In March of this year there were reports of IFIS ( intraoperative floppy iris syndrome) occurring in patients treated with tamsulosin, a popular alpha blocker. Much of the discussion at the meeting was about alpha blockers and their side effect profiles.By October,Health Canada was warning opthalmologists of this entity and to inquire specifically if their pre op patients were on alpha blockers. I make this point because neither of the speakers mentioned this even though there was a very detailed presentation of side effects with the apparent emphasis being that the alpha blocker of the sponsoring company seemed most side effect free. The Health Canada site indicated they at that time the drug manufacturer of the implicated medication (tamsulosin) was working on a notification letter to doctors, so one could assume that the drug companies manufacturing this class of drugs were aware of the issue at least by October 2005 and more likely much sooner than that.This lapse in full disclosure will not likely occur in the future as on November 22 The FDA and tamsulosin's manufacturer issued a physician warning about the floppy iris issue.
It is interesting that family docs are now the experts for some of these talks.A urologist is likely to see many more cases of BPH and have much more experience in the vagaries of day to day assessment and treatment than would a FP physician.Further,urologists have only to be current in urology while FP have the Herculean task of keeping up with just about everything and if for no other reason than that less likely to be expert in anything. So why are they chosen to speak about certain topics to a group that typically consists of FPs,NPs and internists? Maybe they believe that if primary care docs listen to another primary care doctor who is apparently very comfortable in managing bipolar patients,they will have fewer qualms in prescribing the latest atypical antipsychotic medication for the next bipolar patient. Is the message crafted to be "we, primary care doctors, do not need to refer bipolar and BPH patients to the psychiatrists and urologists , we will just prescibe drug x and drug y"?

Wednesday, November 23, 2005

Tiotropium benefits COPD patients and is better than ipratropium

The not-very-easy-to-fool Cochrane Review group has published a meta-analysis of nine RCT's of COPD patients treated with the anticholinergic tiotropium (Cochran Database Syst Rev.2005;(2):CD002876). They concluded that tiotropium reduces exacerbations,reduces hospitalizations, and improves quality of life, a benefit profile shared by the inhaled corticosteroids.That is about as good as a drug seems to get in COPD,at least to date. Mitigating or reversing the long term decline in pulmonary function is still elusive and prolonging survival still is only achieved by long term oxygen administration in those patients with decreased p02s. One of the RCTs involved a head to head comparison with the older ipratropium in which "tio" was the clear winner. It costs more but it seems to be better.I hate to admit it but I can remember a time when anticholinergics were contraindicated in COPD because it would "dry up" secretions and impede expectoration.

Tuesday, November 22, 2005

"Let the doctor pass" and the white coat aura

Years, before I would actually become a physician I had my first personal encounter with the promise,prestige,respect,authority, and the awe that people may have for a doctor. I was a college student working for the summer in a charity hosptial in the south as a woefully undertrained lab tech.I covered the blood bank at night and did cross and match work and drew blood and needed to go to the wards for a sample. I was dressed more like an orderly in "One flew over the Cuckoo's Nest" than a doctor but the group of Afro-Americans sitting on the stairs must have mistaken me for one. One elderly man said to the children who were really not in my way, "Let the doctor pass". It reminds me now of a famous scene in "To Kill a Mocking Bird" when the Gregory Peck character was leaving court and the Black audience in the balcony rose to show respect and one elderly man (Rev. Sykes) said to Scout, "stand up-your father's passin." Aticus Finch had earned their respect. That night over 40 years ago I had personally earned none but nevetheless was the recepient of it because my costume had lead to my misidentification as a physician to whom, for those folks, respect was automatically given. Perhaps less so now than then, respect is automatic and assumed.
The Blog Purty Gud recently spoke of the power of the white coat.He is right-it has a lot. I have mixed feelings about the white coat ceremony that a number of medical schools have started for the incoming freshmen.It is probably a good thing. However,I did not get to wear the white coat until I became an intern. At Tulane , in those days, we wore a long tan lab coat with the Tulane emblem sewed on. So, in way when we got the white coat, we had earned it, although we had certaintly not proven at that point we could really be doctors. Now the students get one right away before they have proven themselves in anyway other than gaining admission to the school, even before they begin to work their butts off. Maybe, the ceremony will have limbic valence and impart a sense of the seriousness of the endeavor and the important role they are choosing to play and become an important first step in the transformation from a lay person into a physician and for that and probably other reasons that may be pointed out to me, the ceremony is a good thing, but still some of us old docs might feel it is just too easy to get the magic coat that way.

Monday, November 21, 2005

How is the NIH "intergrating" alternative medicine with allopathic medicine?

As best I can tell from a non-exhaustive survey of their NIH alternative medicine website they are attempting to use the basic scientific methods to investigate certain treatments - typically herbs and the like-using more or less what we generally do to see if a given treatment works.That seems to be basically what their mission statement claims. Much of alternative medicine is simply not the subject matter for scientific investigation. For example, how do you scientifically investigate the statement that one's illness occurs when the person is "out of balance with nature".
Jacob Bronowski in his "The Origins of Knowledge and Imagination" talks about a major difference between eastern holistic thought and western scientific thinking. Speaking of the scientific method he says, "It is, therefore,an essential part of the methodology of science to divide the world for any experiment into what we regard as relevant and what we regard, for purposes of that experiment,as irrelevant. He talks about putting a fence around the law of nature we are trying to tease out. The best we can get out of this is to put together an approximation of what goes on inside the fence and possibly makes some speculations about the world outside this conceptual fence. As we earn more and make conceptual advance we may be able to enlarge the area surrounded by the fence. We cannot determine if herb x will rebalance someone with nature, but we know to go about finding out if herb x lowers blood pressure or cholesterol using among other things the methods of randomized clinical trials. I don't believe we are really integrating anything in this way. We are just finding particular therapies and investigating to see if they work or cause harm. We seem to be trying to find a few very small islands of medical usefulness in a ocean of mumbo-jumbo.Something works or it does not. Arnold Relman had something to say about that in his 1998 essay about Andrew Weil and is republished on quackwatch. Relman says " There are not two kinds of medicine, one conventional and the other unconventional, that can be practiced jointly in a new kind of 'integrative medicine'. Nor, as Andrew Weil and his friends also would have us believe, are there two kinds of thinking, or two ways to find out which treatments work and which do not. In the best kind of medical practice, all proposed treatments must be tested objectively. In the end, there will only be treatments that pass that tests and those that do not, those that are proven worthwhile and those that are not. can there be any reasonable 'alternative'? "

Wednesday, November 16, 2005

Another consequence of loss of big pharma credibility- more independent analysis of data submitted to FDA

The Nov. 9,2005 issue of JAMA has a free full text article by researchers at Cleveland Clinic who re-analyzed the data submitted by Bristol Myers Squibb and Merck for approval of muraglitazar.The "glitazar" are characterized as dual alpha/gamma PPAR activators which seem capable of lowering the blood sugar and lowering the triglyceride level and elevating HDL values.
A FDA committee has issued an approvable letter but the JAMA article analysis give a different conclusion than do the statistics submitted by the companies. There either is or is not an increase in cardiovascular mortality in the muraglitazar treated group depending on which analysis you believe.There is also a full text free editorial available that describes what has happened here and give a very interesting list of ways that drug companies( or any one) could manipulate the study and the data in a way to minimize any possible harm that the drug in question might cause. The other side of the coin is that the same could probably be done to maximize the likelihood of demonstrating possible harm. The two analyses differ mainly in how the disease categories are either lumped or split out. You do it one way and an increase in CV events seems significant while another classification leads to the opposite conclusion. Even so, the small number of CV events lead to rather wide confidence limits and neither conclusion could be said to be very robust.
So who is right? There may be no right or wrong here simply different valid ways of looking at the data.But, if approving drugs only after good safety data is submitted is what you desire then you would go with the Cleveland Clinic analysis. In light of the Vioxx situation, you would think the FDA might lean more toward that approach. The editorial says in part "Risk benefit assessment is a dynamic process with few absolutes." The data alone are often not enough but have to be considered in the context of the disease at hand. The disease prognosis and what if any other treatments are available and how effective and safe they are have to be thrown into the decision making process.Should the FDA require more pre marketing trials of sufficient power to more definitively answer the question of increased cv disease risk as suggested by the JAMA article authors or should the FDA accept the suggestion of the sponsors to do post marketing surveillance ? It is not easy to be in charge of approving drugs.
He said-he said clinical epidemiology disputes are not new.What seems new is the widening distrust of drug company data regard medication safety and efficacy to the point where academic researchers have taken it on themselves to "double check" the data.It also speaks to some degree of distrust of the FDA's ability.The era of trusting drugs because the government says they are safe is gone, if it was really ever here.Not only is there some double checking , it is having an impact.This particular drug was leading the pack of glitazars in the path of FDA approval-now its future is uncertain.

Tuesday, November 15, 2005

Is political correctness one of the reasons med schools are teaching " complementary Medicine"?

I suspected that complementary and integrative medicine was making inroads into traditional medical schools but the recent blog by Dr. RW is shocking.Go to the University Of New Mexico Medical School site and see the degree to which this is happening. You will learn about the "manala of health" .There is a clinical service associated with the UNM program where the web site informs us prescriptions are not written and tests not ordered and the role of the primary care doctors is not assumed but at least one practitioner will provide a "comprehensive assessment using the principles of integrative medicine".
A similar clinical program can be found at the University of Arizona Medical School. Again no medications are prescribed or tests ordered. The $300 initial consultation fee is payable at the time of the clinic visit. University of Arizona's program is part of the Consortium of Academic Health Centers for Integrative Medicine as are 26 other centers. One of the driving forces in this movement seems to be the Bravewell collaborative which is described as a philantrophic foundation whose mission is to further integrative medicine. For a scholarly assessment of some of the medical school teaching programs this reference is illuminating, thanks to Dr.RW for the citation.
Clearly medical students need to be made aware of various "alternative" practice claims and importantly learn to analyze and assess those claims and practices and theories. However, it seems that although these programs at medical schools purport to critically analyze other therapies and theories that imperative seems to be mixed in with some material that uncritically promotes those ideas. Here's the thing. Medicine is certainly more than science but some aspects of these programs appear to be ignoring the scientific principles in favor of warm fuzzy politically correct nonsense. It is ironic that in this era of evidence based medicine we also have a strange regression to promote the unscientific and unproven even giving some credence to homeopathy.There is some foundation money involved and the NIH also sponsors research into complimentary medicine but I wonder if the current wave of political correctness in universities might not be inhibiting the resistance to this- at times- patent nonsense that we would otherwise expect from scientists. There is almost a prohibition to pointing out for example that some cultures may be better in certain aspects that are others. Scientists on university faculties may be afraid to say things like "western medicine is better than Chinese medicine". There may be the occasional herb or root of true medicinal value but you do not seek out an oriental herbalist if you have a leaking cerebral aneurysm or testicular cancer or childhood leukemia in regard to each of which the western medical track record is a bit better than the best alternative found in homeopathy,chiropractic or relaxation techniques.Medical students need to be taught about various trendy alternative medicine that are out there, but they need to be aware that as to the efficacy or safety of those methods, the scientific methods of inquiry need to be used. And for those that are basically unscientific nonsense, they need to be told so not offered a rotation in alternative clinics recommending education in the manala of health.
I realize that at least some of these programs have as part of their mission ( as judged by their mission statement) the integration of evidence based practices from complementary and alternative medicine into the mainstream.However, what seems to be left out of the mission statements ( which seem well crafted to hurt no one's feelings) is that they will expose other practices as bunk if that is where the evidence and rational analysis points. Yes, there may be some good stuff interwoven ( I recognize that there may be evidence that various forms of meditation and yoga have some beneficial effects) with the mindless junk but these programs seem adverse to pointing out the nakedness of some if not most of these emperors or even if that possiblity exits .The med school sites I sampled for integrative medicine seemed frighteningly similar to some of the less reputable snake oil sale sites for alternative medicine with more hype than evidence displayed. I imagine that alumni of some of the schools with these programs may be a bit annoyed if not angered. Dr. Roy M Poses of Health Care renewal blog called our attention to a partnering of the University of Pennsylvania Med.School with the Tai Sophia Institute which had to have given some alumni of that prestigious school ( here I mean Penn. not the acupuncture school) some heartburn.

Thursday, November 10, 2005

Screening for depression-has the time come for this idea?

Seemingly so. Aetna will now begin to pay primary care doctors for screening for depression.The NYT article referred to above gives some of the particulars and some interesting background.The IOM has recently published a paper of the issue.SSRI manufacturers have to be pleased with the efforts.I read about this and have mixed feelings.Depression is clearly a bad thing and can be devastating to patients and family members.I cannot help but wonder why a big insurer initiates a program that will at least in the short run cost more money.Comments are made that it will save money in the long run but that is an expectation not a proven cost effectiveness fact.There are so many conditions for which primary care doctors could screen and we are urged to do so for many such conditions such as domestic violence, early COPD in smokers with office spirometry,lower urinary tract symptoms in men to name only a few.
In 2002 the USPSTF gave depression screening in adults a grade B recommendation ("fair" evidence). I claim no special expertise in understanding insurance company reasoning underlying decisions but the "follow the money" rule works most of the time. My guess is that large companies who are Aetna's real clients perceive that they are loosing money (decreased productivity) from employees with depression. They apparently also believe that early detection and treatment of depression will in the long run save them money. This notion is so intuitively appealing that it does not take much of an argument to convince executives. This may be true but I doubt there is much hard evidence to that effect. So I am guessing the coporate clients have pressured the insurance companies to provide this service and likely the cost gets pushed back to the corporate clients.Generally, treating depression is a good thing and maybe screening for it is a good thing as well.However, to expect that someday it will be shown that a given company's productivity increases because of this is very unlikely.The causative chain from screening to improved worker behavior and less time off is long and vulnerable to many potential pertubations.

Monday, November 07, 2005

JAMA commentary: Doctors and Lawyers-can't we just get along?

The October 26,2005 issue of JAMA published a commentary by a physician and an attorney who give their opinions on improving relations between physicians and attorneys. While admitting that malpractice concerns is a major driver in the antipathy between the two professions, they also argue that core values are actually similar but that we differ in approaches to conflict resolutions. They quote a 1987 publication by D.M.Fox ("Physicians versus lawyers:a conflict of cultures, in Dalton H. Burris,S. Ed. AIDS and the Law. New Haven,Conn.Yale University Press: 1987:367-376) in which the author says that are disagreements about five issues:the nature of authority,how to resolve conflicts,the relative importance of substance and procedure, the nature of risk and the legitimacy of politics as a method of solving problems. Fox may have adduced convincing evidence that these factors underlie differences between the two professions, but when is the last time you argued with a lawyer at a cocktail party about the fine points of the relative importance of substance and procedure? They suggest to avoid further "ruptures" in doc-lawyer relations,we should "dialogue" and emphasize shared values and "concerns for patient safety" Now, who could be against patient safety (or quality, or Mom or apple pie) ?
However, I doubt if patient safety is the driver for this article. I believe we find what this article is all about in the final section entitled "next steps". Here we learn that we should dialogue with lawyers in part to learn how to "set limits on resource use".
This limit setting , of course, will be done " in a manner that accommodates both individual autonomy and society wide conceptions of fairness ". Both of the JAMA article's authors are affiliated with Public Health and/or health policy departments, which are typically the sources of discussions regarding limits on resource utilization,which translates into limits of services patients receive. Why is it that clinicians seems to be concerned with what they can do for patients and so often health policy wonks initiate discussions about how we can limit what patient receive? To talk of the need for resource use limits is to assume too much is being used which translates to too much being done for patients which translates further to a third party deciding that the individual decisions of doctors and patients about clinical managment issues have lead to a undefineable "overuse" of resources.Obviously,many in the health policy business believe that patient treatment is too important to leave to the myopic lens of doctor and patient.
The major reason for antagonism to attorneys by physicians is the malpractice issue. Talking about abstract core values the two professions allegedly share and initiating dialogues about how "we" can limit resource use will not change this.My jaded view is this a bait and switch article, the discussion begins with how to improve doctor lawyer relations and ends with a call to to work out way to limit resource use.

Friday, November 04, 2005

Is even MKSAP(13) vulnerable to drug company influence?

Recently, I received the MKSAP 13 update cd.In the section of migraine, the update contained a review of a RCT on the use of topiramate in migraine prophylaxis.OK, fair enough. A corresponding question regarding management of a patient with two or more migraine attacks per week had as the "correct" answer, topiramate. My concern is not that it may well be a reasonable approach, but that it is the correct approach and no mention was made, for example on the use of propanolol or other often used medications for that application.I wonder if the drug companies have made some docs-including the junior academics who often do the heavy lifting in such ACP educational endeavors-reason at some level that RCT equals evidence based medicine (let us all bow towards Canada) and results from a RCT ( in fairness, there are more than one for topiramate) gives us the correct answer without considering the context of prior evidence-what drugs worked for migraine prophylaxis in the past. It just seemed like short shift was given to reasonable alternatives.I may be making more of this that it deserves but given the insight of the fact of major influence of big pharma on physician thinking and education I seem to see it everywhere.(As an aside the MKSAP CD did not agree with my pentium D ,widows XP machine as soon after I loaded the software, my computer gave me a gosh awful error screen and screeched to halt and the fix-it software recommened de-installing any recent add ons.I did and now I afraid to try it again) So if some details of the above reproach are not quite factually correct,I did this from memory.Let me also say I have gone through all of the MKSAPs over the years and find them a great educational took, warts and all but now that the activities of drug companies in spinning medical research and research reports is common knowledge it is hard to read anything with the naive trust I had before.

Monday, October 31, 2005

To decrease anxiety mongering ,close down epidemiology departments?

Medical journalist, James Le Fanu, quoted in a 2002 BMJ article made the above -presumably tongue-in-cheek-comment in the context of increasingly common mass media medical news articles claiming increasing or decreasing risk of some disease only to find contradictory data soon after.Data dredging refers to statistically analyzing large numbers of variables and number of outcomes, a method well recognized to produce false positives particularly using the p<0.05 level.
Data dredging is not new nor are the attendant problems.A letter to the editor quoted James Lee's "grand equation of truth". All observations are subject to error. What we observe is equal to the truth plus or minus the errors associated with chance,bias and confounding. With increase in the number of possible associations as in data dredging,the play of change looms larger. Our techniques for "controlling" bias and confounding in case control studies ( a major source of data dredging exercises) leaves a lot to be desired.(Of course you can dredge around in RCTs as well looking a various subsets and this also can be the source of epistomologic mischief). None of this is new . What seems new to me are three things: 1)the reporting of scientific studies in the mass media without the appropriate context and in a simplified and simplistic form,2)increasing numbers of dredge reports.(My cynical explanation for part of this increase is the large number of academic MDs in various departments who need to write papers.Having said that I recognize there are many excellent clinician-researchers who turn our worthwhile research without resorting to the quick and dirty case-control multi-comparison expediency) and 3) the ease with which dredging can now be done with modern computer power and software usuable by folks who is the past would have been at the mercy of the few wizards of the mainframes.
Closing down the epi departments may be a bit drastic. Physicians can always fall back on the basics, i.e. look the latest breakthough through the lenses of context and biological plausibility and warn your patients when asked about the latest finding accordingly.

Thursday, October 27, 2005

Are Canadian physicians really going back?

With the introduction of the Canadian single-payer health care system, large numbers of physicians moved south in search of a different practice setting. A news item this week in the AMA News ( American Medical News,October 23/31/2005,)-now requiring a subscription-hints that now the pattern is being reversed. It is probably too early to conclude that but there are some data suggesting that Canadian docs are going back home after finishing training in the U.S. The AMA article is not all that convincing and is lacking in much hard data. Here are the facts they present: For the first time in the last 30 years more docs are leaving the U.S.for Canada than are coming in (202 out, 162 in),there is a growing shortage of physicians in Canada and the government is said to be attempting to upgrade facilities and in some provinces offer higher reimbursements and some other recruitment incentives. I suspect there is no great exodus in the making but the "M and M's" of medical practice discontent ( e.g. malpractice premiums and managed care) are making more than a few docs to leave practice and at least the malpractice premiums seem lower up north and perhaps the paperwork less onerous. DB's Medical Rants recently posted a typical sad situation of a not very old OB leaving practice because of the first "M" even though she had no history of law suits. Her story is not unique.

Tuesday, October 25, 2005

'Why I did not become an internist"

Through the incredible-almost most endless- amount of material that reverberates through the internet I came across a now 10 year old letter to the Annals of Internal Medicine. It is short and expresses much of what I have thought over the last 10 years. Twenty plus years ago, the author did not become an internist to A) be a family doctor, B) to lead the way in informatics C) to master systems and lead quality programs. He learned to take care of sick patients, sometimes very sick patients and quarterback the details of complex, multisystem clinical situations and to try and unravel difficult clinical problems.The author, Dr. Michael Pauszek, receiving his four years of post medical school education in the late 70s, was trained, as was I , to take care of sick patients and have the breath and depth of medical knowledge to diagnose difficult cases. General internists are still needed to do such things but the economic and structural landscape of medicine has changed even more since his 1995 letter that now more than then internists may well not be able to make a living doing what they do best and more and more are relegated to being more like family doctors and would-be office gynecologists and amateur dermatologists in the office while fighting underfunded turf battles with hospitalists and intensivists (words that were not coined when he and I trained) in the hospital (the long ago domain of the internist.) We read of more straw grasping for internists. For example, recently a IM newspaper touted the virtues of an internists developing a niche in sports medicine to supplement income.I recently injured my knee while running. The first thought I had was not "Let me try a find a good internist who dabbles in sports medicine". Another was for internists to consider becoming expert in ob cases with complicated medical problems providing - in my opinion-a unique opportunity to combine physician stress, the same relatively low internist compensation rates plus probably malpractice premiums closer to those of the high risk ob warriors than the procedureless general internist.Of the two suggestions at least the second involved what internists do best, taking care of complicated sick patients, not pretending to be something else.

Monday, October 24, 2005

Yet another problem with guidelines

Guidelines are great; guidelines are terrible. Internists are of two minds-at least two- regarding guidelines. We resist the harness of being told what to do (although the authors of the guides always include a declaimer that they are not telling what to do and clinically judgment and patient preferences must be given weight) but welcome the relief of finding an easy answer to a given clinical issue. We resist even more vigorously the threat and the reality of being graded-and with P4P being paid- according to this or that guideline. Should I get a pap test this year, doctor? Well the ACOG or the ACS says..... Kevin MD calls our blogish attention to a recent article casting a cloud over the process by which at least some guidelines are prepared. The issue here is the putative influence of the drug manufacturers on the process and the ties the guideline writers have to Big Parma. HCRENEWAl and others have done a great job in directing our attention to various ways in which seemingly reputable medical journals are and have been greatly influenced in ways that may put the volume of sales of certain medications about the priority of scientific inquiry and good faith reporting of data. (If we believe the comments of some journal editors,they were as duped as we were). Well, should anyone be surprised if the same entities have considerable influence on the particulars of various panel's recommendations regarding the indications for various drug and procedures and if the default position is to use more medication(s) for more indications? If we accept RCTs as the top of the line evidence and we have good reason to be at least skeptical about the influence of Big Pharma on those trials it follows that guidelines based to a large degree on those studies will be smeared with the same mud.

Monday, October 17, 2005

Internal Medicine academics discuss why fewer student choose IM as career

In the October 2005 issue of the American Journal of Medicine. Dr. Karen Hauer and a group of other academic internists tackle the issue of declining medical student interest in the field of IM particularly general internal medicine. The online version of the journal which is the official publication of the Association of Professors of Medicine offers some full text journals for free but not this one. It is entitled (Educational responses to declining student interest in internal medicine careers) and the reference is Hauer,K et al , 118, no. 10,1164, Oct 2005).

They do a good job pointing out numerous factors influencing students. A few of them are: perceived vastness of the IM knowledge base perceived to be difficult or impossible to master,heavy administrative burden,work hassle,income ,less control over lifestyle, unhappy IM residents' influence on students as they rotate on service, economic pressures that promote short patient encounters and leave no time for reflection and pathophysiologic considerations traditionally said to be core values of IM. The panel realizes that, while changes in the medicine clerkship may at least make some directional change in students views of IM that most of the factors are out of the control of clerkship directors. The usual suspects of unmanageable administrative burdens (Let us call it correctly insurance plan hassles), low compensation and time demands and tanking prestige are the real culprits. The medical schools cannot change them. The authors said that " practicing clinicians and their national organizations must address flaws in the current practice environment" I have not given up completely on meaningful change taking place but it sounds like Will Roger's "boil the oceans" [ to eliminate German U-boats]. When I was a medical student or house officer, we did not discuss "lifestyle" specialties and-believe it or not-income differentials were not a pivotal factor in the decisions many of us made. The 21st century medical student is much more savvy regarding what happens in the life post training. I believe the major blow to general internists was and is managed care. I seriously doubt that that juggernaut will be stopped or meaningfully altered by practicing doctors or their largely ineffective and sometimes misdirected national organizations. But I can still hope.

Sunday, October 16, 2005

Pertussis is back giving adults persistent cough,but help is on the way

Pertussis-whooping cough-was something we saw at Big Charity hospital on our pediatrics rotation.After that I rarely even thought of it. In the last several years docs are suggesting it as a cause for their own or their patient's lingering coughs. Adults usually don't get the whooping part . There are now two new vaccines that contain with Tetanus and diphtheria antigens an acellular pertussis antigen which in one form or another has been put into practice in Europe and Canada and efforts are underway to use DTap in place of Td in the U.S. The current issue of NEJM features an article documenting the efficacy of this acellular pertussis vaccine in adolescents and adults. I believe that the reason pertussis was eliminated for the "tetanus" shot for adults was the reaction rate with the old cellular pertussis. Apparently this is not a problem with the new formulations.

Saturday, October 15, 2005

AMA offer programs on lesions we should learn from Nazi doctors.

Beginning in 2004,Tte AMA's Institute for Ethics and the U.S. Holocaust Memorial Museum in Washington, D.C. have offered a lecture series that examines Nazi Medicine and offers perspective on what can be learned from this dark (darkest?) chapter in medical history. A recent AMA newspaper editorial reports that the program has been presented to 12 med schools so far. All of the schools should sign up for this. I did not learn of the incredible behavior of many German doctors until long after I graduated from medical school and I heard nothing about it in college or high school. Here is the link for the AMA web site.CME credit may be obtained. The book " The Nazi Doctors" by Robert Jay Lifton give details of the behavior of individuals who were physicians in name only that is so chilling that I have no words to express the magnitude of the horror. The terrible things that have been done in the name of the "greater good " and the sacrifice of the individual to the collective and when individual responsibility is removed know no bounds.

Friday, October 14, 2005

A blood test to diagnose mesothelioma? Osteopontin

Blood tests for cancer(s) have been widely sought after. It could be so easy. Order a test, voila a diagnosis. So far, only one blood test is widely use to screen for cancer, the PSA and it is not without detractors and critics and the issue of screening is contentious.Generally blood tests for cancer have looked pretty good early on only to disappoint as more data is accumulated. But hope springs eternal.
There is recent data that at least suggests a blood test may be useful in the diagnosis of mesothelioma. Ostopontin, a glycoproten that mediates cell matrix interactions and is overexpressed in mesothelioma, may be of value to distinguish patients with asbestos exposure who do and who do not have mesothelioma. The October 13, issue of NEJM features an article by H. I .Pass et al who studied 76 patients with pleural mesothelioma as well as 69 patients with nonmalignant asbestos disease and 45 subjects with no history of asbestos exposure.Tumor tissue was examined for osteopontin and serum levels were measured. Levels were not increased from asbestos exposure alone and patients with pleural plaques and no pulmonary fibrosis did not demonstrate an increased blood level but mesothelioma patients did. 36/38 cases of mesothelioma studied demonstrated osteopontin staining of tumor cells.
Osteopontin, however, cannot be cannot be called MSA ( mesothelioma specific antibody) because colon cancer cases have also shown overexpression of osteopontin correlated with progression. The colon cancer study linked above did not do serum levels.
The typical mesothelioma case has a median survival of at most one year. There are cases of five year survivals in patients with early disease whose tumor were resected. Certaintly a means of detecting early disease would be welcome. The latency of mesothelioma is very longer, sometimes 30 or 40 years. OSHA has a mandated asbestos surveillance program but that program ends when the workers leave employment. In my experience consulting with a number of petrochemical companies over the past 25 years, most of the mesothelioma cases in refinery and chemical plant workers have occurred in retirees and most companies do not offer an exam program for retirees. The population to monitor and screen for early mesothelioma is the retiree group. On the other hand, pleural plaques in active employee exposed to asbestos in the years before the current OSHA standards were in place are not uncommon. The following issue will likely arise-should employees with pleural plaques be screened with serum osteopontin tests? Pleural plaques are not premalignant per se, that is a plaque is not transformed into a tumor. However, an asbestos exposed person whose exposure is signaled by a plaque is at risk of a mesothelioma. It may be that serial changes in the osteopontin level may be used in a similar manner to the PSA. The so-called PSA velocity may signal prostate cancer and perhaps serial increases in the osteopontin value may indicate early mesothelioma. Perhaps the utility of the test-if further data provides more validation-would be in periodic measurements in retirees with pleural plaques.

Thursday, October 13, 2005

Interview with physician who was in Charity Hospital during Katrina aftermath

Dr. Ruth Berggren,who is on the staff at Charity and faculty at Tulane, give an audio sketch of her days in Big charity In New Orleans as everything fell to pieces after Katrina hit.An audio presentation is available-I think only to subscribers-at the NEJM site. It is worth listening to. Her first hand account points to the pivotal role of gun fire and snipers in aborting the effort to get patients - and everyone else- out in a timely manner. I have written before about the heroics of the medical personal at Charity at this time. She gives her voice to what took place. There was no power, little food and water, a diarrhea outbreak among patients with no working plumbing, heat, darkness, needing to practice medicine in the dark bereft of laboratory assistance and- incredibly- fear of men with guns. The hospital personnel and patients were abandoned on a hellish island. City and state governmental officials-either powerless or ignorant of their plight- were not to their immediate aid. Were there no plans in place to evacuate the critical patients in the event of a catastrophe? Finally on 9/3/05 staff and patients were evacuated. For decades the poor and uninsured in Louisiana relied on Charity Hospital for medical care. We now learn that Charity has been declared past the point of salvage and recovery and can only be torn down. The state of Louisiana talks of plans to build a new hospital. It now looks like many more patients than the ones in hospital on the day the levees broke may be abandoned at least for now.

Monday, October 10, 2005

"Cultural Competency" is not a competency to be checked off like a thoracentesis

Articles on cultural competency seem to be found in almost every journal lately. Certain aspects of this movement have not felt right to me. Linda M. Hunt, an Associate Prof at Michigan State , does an excellent job of explicating some of these aspects. Her article is worth reading;here are some of the highlights:
"Cultural competency (CC-my abbreviation) remains a vaguely defined goal with no explicit criteria established for its accomplishment or assessment. This lack may in part be due to the elusive nature of its central construct:culture". Nevetheless, there are increasing requirements for physicians to receive training in area for which no or few valid criteria for assessment exist.Various residency program include it as do medical schools. The influential IOM recommended training CC for medical students and in New Jersey has passed a law mandating physicians receive training.
She says further, " It is not possible to predict the beliefs and behaviors of individuals based on their race, ethnicity, or national origin."...Paradoxically..what originated in a desire to promote respect for individual differences may instead promote stereotyping and essentializaing...It may reinforce the belief that culture can be diagnosed and treated."
Much of what she said is encapsulated in a comments made by a letter writers to DB's Medical Rants. Letters no 3 and 4 seem on target . Physicians treat individuals not members of some arbitrary sociological construct. Treat patients with respect. Don't worry that a given patient might have some attitude or belief based on their alleged membership in some cultural classification subgroup.
She continues ;"..it [the cultural competency movement] has too often represented culture as a decontextualized set of traits providing a template for the perceptions and behaviors of of group members"..."specific ethnic cultures are represented as a codified body of characteristics that can be identified and then either modified or manipulated to facilitate clinical goals."
Does she offer an alternative? ( my alternative would be do drop the programs, but I don't see that happening for a while). She recommends two things. First be respectful of the unique perspective each patient brings . Respect is certaintly a core value. The second is a bit harder to put into real life clinical experience. Hunt recommends what she calls "cultural humility" by which she means to explore through conversations with the patient similarities and differences between his own and each patient's goals, capacities and priorities. That is quite an assignment even with limitless time but not likely to be achieved in a 10-15 clinical encounter let alone a 7 minute one.
Allegedly, somehow the clinical competency movement is supposed to further the goal of reducing or elliminating the gap between the medical care haves and the medical care havenots.
How programs with poorly defined goals, a flawed conceptual foundation and an intellectual regression to treating folks as members of groups will achieve that remains unclear. Even the much more restricted goal of improving doctor patient communication is not likely to be greatly improved by putting old wine (racial streotypes) into a new bottle. A recent Johns Hopkins study is said to have demonstrated that CC training improved some aspect(s) of patient satisfaction and physician understanding but - not surprisingly-no data are found demonstrating improved health care.
Hunt's closing paragraph says in part " ... being appropriately cognizant of and more responsive to cultural issues shoudl not be thought of a reaching a 'competency' " but she says an ongoing process in which there is a "respectful recognition" of the unique set of charateristics and attitudes and concerns of individual patients.

Tuesday, October 04, 2005

Grand Rounds is up again

First-year Tulane medical student, Niels Olson, offers a very well done Grand Rounds, found here. Hurricane Katrina has given new meaning to the nickname "Green Wave". Tulane Medical School restarted its year in Houston hosted by Baylor Med just last week. It will take more than two hurricanes to keep those folks from going to med school. (Rita delayed the opening of Tulane West a few days before)

Monday, October 03, 2005

Provocative PLOS article claims "Most published research findings are False"

John P.A Ioannidis, writing in the August 2005 issue of PLOS, entitled his essay "Why most published research findings are false". If that claim is true, how solid are the foundations of the recently venerablized Evidence Based Medicine"(EBM)? Obviously, not solid at all. He states " It can be proven that most claimed research findings are false" After one rather dense paragraph, he says " ... a research finding is more likely true than false if (1-beta)R >0.05, where 1-beta is the power of the study and R is the ratio of true relationship to no relationships and 0.05 is the typically used alpha( type I error) value. It seems to me that if we knew the ratio of true to no relationships we would have to have had some aprior knowledge of what was true, which we do not. A letter to the editor by Jonathan Wren of the University of Oklahoma goes down this same counter-argument road when he says that yes, the probability that a research findings is true depends in part on the prior probability of it being true but we do not know that probability, we merely makes guesses or estimates about it.
Ioannidis's thesis cannot be verified ( or falsified) unless we had some independent method of determining if study results were true. An individual study can be falsified-if robust contradictory evidence is adduced- or it can become stronger when attempts at falsification fail but the generalization that most studies are false seems to not be the type of statement readily falsified on empirical grounds, since you cannot ever really prove a given study true. You can sometimes prove one is false but to prove most is a Herculean task particularly given the current increasing pace of new studies being published. Wren evokes a type of Russell Paradox argument saying that if most studies are wrong, what about the studies that Ioanndis marshaled to support his thesis and what does that say about Ioannidis's published study.
My eyes glaze over a more than a little bit when I dive into Ioannidis's theoretical argument but his so called " corollaries " seem to ring true and have been widely discussed in the medical literature. These include various factors that tend to make studies less reliable. For example,
smaller studies are less likely to be true as are studies that target small effects ( eg. RR of 1.05) .
Further, the greater the number and the lesser the selection of tested relationship in a scientific field, the less likely the research findings are to be true.
Ioannidis's paper will not derail medical or scientific research-after all science marched on even after David Hume's critique of induction-but I do welcome efforts that might medical students develop a healthy skepticism about research findings. However, even in that light the letter to the editor by Stephen Paulker also worth reading. For a researcher the issue may well be is the finding more likely than not or even a higher standard of evidence but for the clinical doctor the question is- given the circumstances of the patient- what is the best thing to do. Even if we are not sure of a given therapy's efficacy and even if the probability of it being efficacious is less than .5, offering that treatment may be the best thing to do. I think he is saying that even though there may be many good reasons to be skeptical using the best (realizing it is not perfect or guaranteed) evidence we have is really the best we can do. Often-maybe most of the time- we have to go with the evidence we have- not the evidence we want to have.

Friday, September 30, 2005

JAMA article reports dramatic reduction in hip fracture in stroke patients with b12 and folate

A recent article from Japan by Sato et al reported an impressive 80% reduction in hip fractures in a two year trial with B 12 and folic acid in patients with poststroke hemiplegia.Interestingly there were no fewer falls in the treatment group and no change in measured bone density. A reviewer ( Dr. Steven R. Cummings) in ACP Journal Club commented "The huge reduction in risk defies explanation by current paradigms of pathogenesis and prevention of fractures." Actually, we can always make up some pathophysiology to "explain" the facts. Certainty on the face of it, one has to ask why fewer fractures if no fewer falls and no change in bone density. It may well be that the treatment somehow (maybe collagen cross-linkage improvement) may strengthen bone without a measurable difference in bone density. It is well recognized that the bone density measurement does not tell the whole story about likelihood of fracture given a fall, it is just the typically used clinical measure. So should we give B12 and folate try in stroke patients with hemiplegia? It seems safe and after all a RCT resides on top of the EBM epistomologic hierarchy so why not?

Wednesday, September 28, 2005

retired doc back after phone cable cut and Rita

For the past week, I have been off line thanks to a cable cut incident with SBC and then Rita storming into east Texas. There is a lot to catch up with and please stay tuned.

Tuesday, September 20, 2005

American Heart Association and ADA disagree on significance of metabolic syndrome

Recently the ADA issued a position statement challenging the validity of the concept of metabolic syndrome. Their statement can be found here. The ADA authors said that the syndrome lacks a precise definition, is of dubious value and its underlying pathophysiology is in question.
The AHA/NHLBI panel on the other hand said that they "found the ATP criteria for clinical diagnosis of the metabolic syndrome to be a robust and clinically useful tool." and " in the absence of compelling scientific reasons for change, the AHA and NHLBI affirm the overall utility and validity of the ATP III criteria..." The executive summary can be found here. The timing of the two publications is such that it is unlikely that the AHA could have prepared a rebuttal to the ADA paper as they were published within several weeks of each other
The clinical management recommended by the two groups is very similar- more so that their seemingly disparate characterizations of the constellation of findings designated as comprising the metabolic syndrome. Everyone seems to agree that you should treat the various risk factors per se and that there is no specific treatment for metabolic syndrome, i.e. no single pharmaceutical magic bullet to fix or mitigate the underlying pathophysiology if there is one. ADA's statement indicates they are much more skeptical that there is a unifying pathophysiology than is AHA.

Monday, September 19, 2005

American Journal Medicine article paints alarming picture of current Internal medicine residency

The September 2005 of AJM features an article (Internal medicine residency training in the 21st century: Aligning requirements with professional needs, Charap MH et al. Amer J med. 118, number 9, pg 1042, sept 2005) in their APM Perspectives section that characterizes current IM residency training as an almost mission- impossible type situation. The authors from New York University Department of Medicine describe in detail changes made by the ACGME and Residency Review committees (RRCs) since 1980. In 1980, IM training was 3 years as it is now, although at some earlier date (when I trained in the 60s) training was an internship and then three years of IM residency so that total post med school education was 4 years. There was more time then and clearly less to learn . Now the total time in training is less and the amount of time "allowed" during that time frame (i.e. "duty hours") has been mandated to be less.
The entire article is worth reading if you are involved in teaching residents or interested in post graduate education.(I am sent the journal but am unable to download the articles on line so I didn't give the URL).
I found the article very troubling. Most disconcerting to me was that the following statement is no longer included in the current RRC documentation."Physicians must have a keen sense of personal responsibility for continuing patient care and must recognize that their obligation to patients is not discharged at any given hour or any particular day of the week. In no case should the resident go off-duty until the proper care and welfare of the patient is ensured." Previously the RRC-IM was careful to include this caveat that the authors consider it the " touchstone " of the internist's world. This admonition apparently went south when , in 2003, resident duty hours were further restricted by the ACGME. The RRC-Im Program requirements documents for IM residency is now 21 pages having been a single page in 1980. In the last year, training for 6 "core competencies" was mandated including training is "system-based" practice and " practice-based learning" and scholarly activity is also required. The authors make the following alarming statement : "the reality is that residency programs simply cannot satisfy these ever-increasing requirements other than as paper achievements responding to paper audits."
They make several recommendations which include : Restoration of the above quoted "touchstone" statement, not adding more requirements unless they are linked to equivalent reductions, convening a blue ribbon panel ( not affiliated with ACGME) to review all of the RRC-IM requirements, allowing more flexibility in the program to meet the diverse career interests of current day residents.The authors definitely believe that changes must be made because " there is simply insufficient time to educate internal medicine residents in the present regulatory environment"

Thursday, September 15, 2005

If you thought medical school was hard before (katrina)...

A section in the Tulane Medical student web site for comments for the now Katrina displaced(to be largely relocated in Houston) students has the title "'If you thought Medical school was hard before". A sense of humor doesn't hurt. The exploits of Dr. Tyler Curiel-head of heme-oncology at Tulane- could be called " If you thought doing medical research was hard before...". His lab, like so many other labs at both Tulane and LSU, continue to be without power and much research material has either been ruined or will soon be. Some his work was preserved by using liquid nitrogen to freeze valuable samples before the power went out. The nitrogen induced freezing is finite ( maybe two weeks) and his efforts to return to New Orleans and refreeze valuable material are explained here. The logistics of returning to the Tulane Medical center and applying liquid nitrogen to storage chests in a building without power is daunting but apparently Curiel will ( or perhaps at this writing already had) pull it off. He acquired the aid of Phazar Aerocorp who has donated jets and employees to aid in the mission. It will involve carrying 400 lb. tanks of nitrogen up various flights of stairs to the various labs and working in the heat and dark. He and his wife, Dr. Ruth Berggren, spent endless days and nights caring for patients in the Tulane University Hospital and Charity Hospital before being evacuated to Fort Worth. The exemplary behavior of many of Tulane's faculty in that time of unprecedented crisis focused attention of some prime time role models for the Tulane Med students who no doubt have some major challenges to overcome this year to continue with their medical education.(The above referenced newspaper article is now several days old, if any readers have learned more recent information, please let me know).