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.