Flexible sigmoidoscopy (flex sig) -Is it being phased out?

Flex sig seems to be going the way of the doctor visit when enough time was available to discuss things in depth with the patient. With flex sig, however, time does not seem to be the issue.Money is part of it (low reimbursement may barely cover costs) as it the popularity of colonoscopy for cancer screening.

The February 17, 2006 issue of Medical Economics reports the following all of which speaks to the decline of sigmoidoscopy:

1.About 25 % of internists provided flex sig versus the 1986 figure of 75%.
2.A recent AAFP survey reported that about only 25 % of FPs preform the procedure.
3.Both ACP and AAFP no longer teach the procedure at their annual meetings.
4.Dr.Patrick Alguire,director of education at ACP,is quoted as saying that flex sig is now offered only as a elective in IM residency programs.

Colonoscopy got a big boost when Medicare added screening colonoscopy to its approved procedure list and GI docs had to be pleased with the publicity of Katie Couric's on air colonoscopy.

I used to tell patients if they wanted to have their colon examined for early cancer or polyps they needed to get their entire colon examined and I believed offering them a flex sig in place of a colonoscopy ran the risk of giving them a sense of false security not to mention the malpractice issue.

Estrogen only arm of WHI:Maybe estrogen does not increase heart risk

The Women's Health Initiative (WHI) has had a major impact on the use of hormone replacement therapy (HCT) for post-menopausal women. The latest and final analysis of the effect of conjugated equine estrogen (CEE) alone on cardiovascular events in women who had a hysterectomy is found in a recent issue of the Archives of Internal Medicine (subscription required for full text).

Overall, no increase in CV risk and in one age subgroup, the suggestion of an apparent benefit was found.

The study began in 1993 and 10,739 women were randomized to placebo or 0.625 conjugated equine estrogen daily.The follow up was 6.8 years. In the group who were 50-59 years of age at entry into the study the hazard ratio for coronary artery disease events was 0.63 ( C.I.-0.36 to 1.08) while the hazard ratio for revascularization was statistically significantly reduced with a hazard ratio of 0.55 ( C.I.- 0.35 to 0,86).

These results differ from the WHI estrogen plus progestin arm in which an increase in cardiovascular events was demonstrated (7 more events per 10,000 patients per year as well as 8 more strokes).

Why the difference? The simple or perhaps simplistic answer is maybe the progestin is the culprit.The study's authors tended to favor that explanation as their statistical analyses seemed to make baseline risk factor differences and differential statin use not likely to account for the difference between CEE alone and CEE plus a progestin.

I doubt we will see large scale recommendations for estrogen to prevent heart disease, but at least women who are post-menopausal and who are taking estrogen may be somewhat less concerned about their HRT increasing their heart attack risk.

Women's Health Initiative Study may demonstrate that vitamin D and calcium work only if you take it

A recent NEJM article will get wide press coverage as it will allegedly be shocking. The Women's Health Study strikes again, this time seemingly crushing the hopes of those women who take vitamin D and calcium with the expectation that they decrease the risk of osteoporosis.

I think the study demonstrated that vitamin D and calcium in the dose intended only decreased the risk of fractures in those women who actually took the medication.

The authors understate this by saying "It is also plausible that there was benefit only among those women who adhered to the study treatment."

In support of this radical theory,they report a statistically significant 29% decrease in hip fracture risk among adherent participants. Only 59 % of participants took the intended dose by the end of the study.

Another significant issue is that the 400 units of vitamin D may not be enough.The authors quote references that support that claim.

Another issue was the reported increase in kidney stones in the treatment group with a hazard ratio of 1.17 in the treatment group. So few participants actually took the medication as intended, and with such a slight increase in risk measurements it is hard to know what this means and the authors did not discuss this finding in any detail.

It has not been a good month of the WHI results-wise. One study showed that reduction of total dietary fat did not decrease risk of heart attack. Cardiologists,for some time now,have not recommended to decrease total fat but rather saturated and transfat. And now a major, expensive,randomized trial seems to show Vitamin D and calcium only decreases fracture risk if you actually take the pills.

It is currently trendy for folks in the medical policy arena to talk about value as defined by the ratio to quality to cost. Ignoring for the moment the monumental problems of measuring quality, if you consider this study enrolled 36,282 participants and the NEJM needed 9 printed lines to list the authors and only arguably demonstrated that medicine only works if you actually take it, you have to wonder about the value of that effort.

How low can a relative risk be and still mean anything?

A death blow or near death blow to the use of Vitamin E in the prevention of whatever it was supposed to prevent was dealt by an article that claimed Vitamin E increased the risk of death. The relative risk reported in that meta-analysis by Miller et al was 1.01.

Should a relative risk (RR) that tiny convince anyone of anything? What value should a RR be to have clout or significant evidentiary value?

That question was posed by the EBM folks at McMaster to a venerable guru of epidemiology, Sir Richard Doll ( see pg. 162 of the book, "Evidence Based Medicine", Sackett, D L et al, , second ed. Churchhill Livingstone Press, 2000). His reply was cautious. He is quoted as saying " It's almost impossible to set a level of risk which is so high that the findings in a well-conducted epidemiological study would necessarily exclude confounding." He continued saying that if the RR were 20 that would be almost sufficient to indicate causality.

Sackett and co workers went on to indicate that a RR of greater than 3 was "convincing".

A relative risk of greater than 2 is being used by courts to reach the threshold of more likely than not which is current level of proof in most tort cases.( I do not know what RR would be needed to reach the level of "clear and convincing evidence".) Weak associations, ie RRs barely above 1, are more likely to be explained by undetected biases.

We are bombarded by articles that report relative risks between 1 and 2 and some of these , such as the Vitamin E meta-analysis seem to be a tipping point in the discussion about a given medical intervention. Before medical students get too carried away by articles such as the Vit E meta-analysis they should take a moment or two to read the letters to the editor that meta-analysis almost always seem to generate. (When I read these it is not that I understand the often obscure arguments raised but that there is so much disagreement among the experts about how to analyze and interpret the data.) When they see how often and often how vehemently the statistical experts disagree, they will be less influenced by the latest meta-analysis headline of the day.

The two gaps between evidence and clinical practice

Dr. M.R. Tonelli in his 2001 article entitled " The Limits of Evidence Based Medicine" speaks of two gaps or two aspects of one gap between what is referred to by the body of evidence based medicine as "empirical" evidence and the clinical practice of medicine.

The EMB spokesmen acknowledge one gap, the gap requiring considerations of the patient and the professional values.

The second gap exists due to the fact that the evidence is not directly applicable to the individual patient.The data do not "directly answer the primary clinical question of what is best for the patient at hand."

That atorvastatin might in a clinical trial reduce the risk of stroke over a given period of observation by half does not mean Mr.Jones should necessarily take atorvastatin even if his clinical profile as defined by the relatively few parameters which characterized the study group seem to fit fairly closely with his.

The observations from that trial, for example, are only one of several imputs that should be considered in a clinical decision. Tonelli lists the following;

"empirical evidence,experiential evidence, physiologic principles, patient and professional values, and system features. The relative weight given to each of these areas is not predetermined, but varies from case to case "

He does not believe that empirical evidence (which is basically various types of clinical research) should automatically or necessarily supersede clinical experience and physiologic rationale.

Tonelli asserts that EBM has made a conceptual error by grouping knowledge that we derive from clinical experience and pathophysiologic reasoning under the heading of "evidence" and to make matters worse we developed a hierarchy that assigned those forms of knowledge to the bottom tier. Those forms of knowledge differ in kind from empirical data and should be used as complementary to empirical knowledge and are part of the tool set we need to use to bridge the gap.

Since I grew up in a medical era during which pathophysiologic reasoning was emphasized, I am sympathetic to the author's view but I am still processing what he said and my mental jury is still deliberating. The broad definition of EBM is to integrate the best available evidence with clinical expertise and patient values and I think clinical experience and physiologic rational could come to play in the "clinical expertise" category.

However,in the one version of the EBM bible (Evidence -Based Medicine,second edition, by Sackett et al,2000) we find a table of "level of evidence" in which the lowest level is " expert opinion ...based on physiology,bench research or first principles." This quote from scripture tends to support Tonelli's characterization of EBM hierarchy as denigrating physiologic reasoning and not my ad hoc attempt to salvage it under the heading of clinical expertise thus ending my short lived attempt to consider his thoughts as a straw man argument.

Annual "physical exam" as "touchstone for contextualized care"

The Feb. 13,2006 issue of the Archives of Internal Medicine published a letter to the editor which I will reference here to echo the thoughts expressed.

Dr. Christine A. Sinsky writes that she structures her practice around the annual examination. Regarding it she says:

"I structure my entire practice around the annual examination. It is when I address prevention, coach patients on healthy life-styles, and do the annual review of each chronic medical condition. Invariably, patients bring new symptoms for evaluation as well. It is a complex visit, focused on integrated, longitudinal care."

That is also, to a large degree, what I did. Replacing the annual exam with a series of admonitions of what to be screened for is to reduce the patient to an abstraction of eligibilities for various organizations's recommendations for screening rather personally dealing than the individual human being they are with their set of unique feelings,worries, concerns, and questions about their own health and what they should or should not do in regard to some perceived or real health issue.

Of course, one can deconstruct the examination and conclude such things as "listening to the heart is not cost effective" but placing the stethoscope to a person's chest is a "chance to touch" the patient and has value above and beyond the occasional discovery of a significant murmur. It is part of touching and hopefully connecting with a patient.

Her letter was in response to a recent editorial in the Archives that suggested that both patients and physicians support and value the annual examination. Some of the criticism of the annual exam may be from its name. The way Dr. Sinsky ( and I) performed it, it was much more than a exam, the mechanics of which took up a fairly small part of the time for the visit. Most of the time spent was talking.First, on whatever the patient wanted and secondly about what I wanted to impart to the patient regarding her current issue or whatever screening or preventive issues were pertinent to her particular situation. It is a time for assessment of issues, for giving advice, for expressing interest and concern about the patient, it is much more than what happens on a boy scout camp physical.

Was the WHI fat reduction trial asking the wrong question?

The Feb 8,2006 issue of JAMA published the results of a trial that will make headline news and reinforce the beliefs of some folks that the medical profession and research scientists still do not know what to tell people to eat or not eat.

The Women's Health Initiative Randomized Controlled Dietary Modification Trial consisted on over 48 thousand women aged 50-79 who were randomly assigned to a control or intervention group, the later of which was to reduced total fat intake to 20% of calories and increase the veggie-fruit servings to six/day.

The results: The intervention had had no effect on the risk of coronary disease,stroke or total cardiovascular disease.

Let the spinning begin. As the accompanying JAMA editorial asks "Why were there a null finding ?"

Here are some possible reasons:

1)The study did not follow the participants long enough (the follow up was 8.1 years, 2) both groups were fairly healthy and therefore it would be harder to show a difference. 3) there was not really that much difference in the fat intake between the two groups 4) the degree of fat reduction in the treatment arm was not sufficient to expect much of a difference. 5) The intervention was reduction in total fat not necessary in saturated and trans fats.

I believe number 5 is key. The WHI study was basically testing a hypothesis that by the time of publication was clearly outdated. The current party line is reduce saturated fat and trans fat to reduce heart disease risk and monounsaturated fat may actually be good for you.

This is major factor of life in these mega multiyear trials,the hypothesis of several years ago is often not even an issue by the time such a trial is underway less alone completed. Medical knowledge (or theory) grows much faster than we will even keep pace with randomized trials.

I have been advising patients for years that the issue is not to decrease total fat in an effort to decrease heart attack risk. I can now use this giant trial to illustrate how that ( the total fat reduction approach which no one really believe now anyway) does not seem to work.

Do we know how to give antibiotics?

There are several current and politically correct maxims regarding antibiotic use which include:

1.We must reduce the use of antibiotics for several categories of respiratory tract infections ( e.g. sinusitis and acute bronchitis) which will mitigate the rising tide of resistant organisms
2.It is more cost effective and therefore of course better to use less expensive antibiotics first and save the more expensive ones for more serious infections.
3.It is imperative that we take steps to decrease bacterial antibiotic resistance
and somewhat strangely
4.Resistance does not seem to matter in regard to clinical outcomes. (This perhaps has not risen to maxim level but there is evidence to that point)

In the premiere issue of Chest Physician, the new publication of the American College of Chest Physicians (subscription required) the Pulmonary Perspective section has some interesting thoughts.Let me preface with a caveat, the two authors are employed by Oscient Pharmaceuticals , which fortunately or unfortunately because of recent events may make the reader more skeptical than in the good old days.

The authors quote some interesting data ( Price et al, Respir Med 2004: 9817) from Great Britain regarding efforts there to decrease the use of antibiotics in respiratory infections. The bottom line is there was a 50 % increase in mortality from the beginning to the end of the two times periods studied concomitant with a 30% reduction in antibiotic use. The effect of the incidence of influenza was controlled for statistically. Association does not equal causality and this is a very broad brush analysis wherein lies many ways to reach the wrong conclusion. Still it is thought provoking . Was the unintended consequence of "educating" physicians not to use antibiotics responsible for an increased number of pneumonia death? Were folks considered to have viral bronchitis given the history of green phelgm who really had pneumonia and were not treated.Well, with this type of study we will never know.

The authors comment that simply cutting back on antibiotics may not be the right solution to mitigating microbial resistance. The WHO supports the authors ' suggestion to " hit hard and hit quickly" or more professionally put "use the most pharmacologically potent member of the relevant class of antibiotics for a short period to decrease the chance of developing resistance".

Is the key to managing what does appear to be a growing problem of drug resistance giving less antibiotics or it is giving the appropriate antibiotic in the correct dose? The problem is, of course, we are still working on the issues of what is appropriate and how long should we give antibiotics.

Medical Economics article:the demise of the doctors' lounge

The Feb 03, 2006 issue of Medical Economics has a interesting discussion of why the tradition of the doctors lounge is dying out. This seems to be something else we can blame managed care for.The authors cite managed care and the rise of the hospitalists as causes. I would spin it this way: the hospitalist movement is in no small measure also a indirect result of managed care.

How does that work? With managed care driven reimbursement decrements it economically behooved primary care docs to see more patients in the office as the pay per patient- encounter decreased.The hospitalist-according to Dr. Wackter-sprang up because their presence allowed the primary care docs to see more office patients by not having to round at the hospital.

Dr. Robert Wachter's version of how hospitalists appeared on the scene is found here and it will likely be the historical orthodoxy. Further, the days of the doctors' lounge being the primary site for networking and consulting each other are largely gone as the physicians that other docs refer to is largely determined by what plan the patient has.

This ties in with an earlier blog I wrote that discussed the observation that not only has managed care driven a wedge between doctor and patients but it has also did the same thing between physicians leading to a gradual withering away of the collegiality that in the best of times existed in the medical profession. I think the demise of the doctors lounge is symbolic of all of that.

The local internal medicine society that I have belonged to for over 25 years once had 75 or more in attendance at our monthly meetings,now has maybe 20 on a good night and usually the older and retired docs are in the majority.The younger internists who in part came to the meetings to become known and make important networking links see no need to do so now. It is basically attended by a few academic internists who are in the med center anyway at that time of day and the retired docs who don't have anything else to do. I believe the demise of this professional organization is probably another victim of managed care.

Does running keep your mind young ?Or do the sharp old folks continue to exercise ?

Observational studies have demonstrated that exercise delays (prevents) dementia to at least some degree. We will all run more confidently on the road to dementia free old age when there are randomized clinical trials that show what the observational data suggest. ( In the interest of complete disclosure I am a marathon runner and only a recalcitrant biceps tendonitis ( the biceps in the leg) kept me from running my 29 Houston marathon in a row in January.

A recent issue of the Annals of Internal Medicine has the latest data . A discussion of this and similar articles must include comments about the concept of "reverse causation". We observed those old folks ( now known as seniors) who exercised regularly had a lower attack rate of dementia. There have been similar studies showing that those folks who are more socially engaged, or more active in mental activities (cards, games,cross word puzzles etc) seem less likely to develop dementias.One explanation could be that something about the early phases of dementia may cloud their judgment or confidence or some combination of cognitive impairment may appear so that they withdraw from of all manner of activities including regular exercise.

Still, those of us who are obsessed exercisers like to think our plodding along generates or releases some sort of hormones or cytokines or something that is neuroprotective.

Blood sugar control in the critically ill patient-the plot thickens

The Feb. 2, 2006 of the NEJM features a randomized trial regarding "tight" blood sugar control in intensive care patients.Physicians caring for the critically ill would have been happier with a more definitive answer but clinical reality continues to be messy and typically resists our efforts to understand it.

Belgian physicians randomized 1200 medical ICU patients into an intensive insulin control group (target blood sugar 80-110) and a conventional treatment group (give insulin if blood sugar greater than 215).

Overall, there was no difference in mortality. When data were analyzed based on length of stay in ICU various answers were forthcoming. Using a 3 day dividing line it seemed that those in ICU beyond 3 days enjoyed a mortality benefit ( 52.5 % vrs 43%). Those who stayed less than 3 days actually showed an increase in mortality. Using five days, the longer stay group enjoyed several benefits in terms of a variety of morbidity indicators but those less than 5 days showed no difference. The authors report less kidney damage in the treated group and earlier weaning from respirators.

The results here are complicated and we are inundated with data and with so much data and with medical ICU patients being so heterogeneous in presentation and in the other treatments received simple answers elude the researchers .Controlling one variable in an experiment with so many other variables influencing the outcomes may well lead to a bottom line more ambiguous than certain. Various sub-group analysis which may give hints as to what is going on may also give false positives due the multiple comparison phenomenon and false negative due to low power statistical power with the small numbers in each group. Which of the multiple outcomes analyzed should be determinative for the clinical physician caring for ICU patients? The trial that seemed to be the tipping point for more aggressive glucose control was done in a surgical ICU units with less seriously ill patients whose medical conditions were less multifaceted and complex.

Dr.Atul Malhotra, in his editorial tries to give the reader some suggestions. He looks at the bright side choosing to emphasize the reported improvement in some aspects of morbidity rather than ambiguity in mortality outcome. He suggests target blood sugar of less than 150 for the first 3 days and then use the 80-100 target used in this trial recognizing the possibility of harm being done to the patients in the short stay in ICC. Certaintly, hypoglycemia is not a good thing and there were more episodes in the treatment group. There is another trial in the wings (the NICE-SUGAR trial).Ignoring the overtly cute name of this trial, hopefully we can look forward to more clear cut answers when that is published.

Dr. Malhotra's suggestions seem reasonable based on the analysis of the Belgian data;it makes sense to be less vigorous in the first few days with insulin therapy and then tightening more on glucose control afterward. However the 3 day value may be more an artifact of the post-hoc analysis of the data than a magic number that may or may not hold up when further trials become available.

More things I did not become an internist to do

The Jan-Feb issue of the ACP Observer in its "the Business of Medicine" section has a number of suggestions to improve the bottom line for internists who are being squeezed by decreasing reimbursements.

Recently, I wrote about a piece by an internist who talked about things he did not become an internist to do. This article makes the list longer, at least for me.The author suggests group weight loss session and group smoking sessions clinics as well as group stress reduction clinics.Group therapy for whatever was somehow left out of my training program in internal medicine-we seemed to be hung up on mainly learning how to take care of sick patients with complicated medical problems- and even with the new program I somehow doubt internists are particularly trained so that they would consider the skills and knowledge base for those activities part of their "core competencies".

 In my opinion the list gets worse.They mention pulmonary function testing and "breathing treatments". Spirometry makes sense-it is a great tool.Breathing treatments for what? In my years of practicing with 4 other pulmonary docs, we seemed to have no indications for bring folks in for breathing treatments.Another was "dermatological procedures".Again, when did internists begin to think that have any business doing skin biopsies and skin tag removals.At an ACP meeting not too long ago, they offered a mini-course in how to do skin biopsies.The trick there is not so much the technical expertise but the clinical judgment of what lesions to biopsy.That is why we have dermatologists.

Let me end with one more of their suggestions made that will certainly thrill the aunt Suzys and grandmother Marys as they wait in your office. Their suggestion of doing court order drug screening will certainly bring some interesting folks into your waiting Nothing like dealing with unhappy people who are ordered to be tested and who suddenly develop shy bladder.The ACP at its meetings and in its publications seems to insist on trying to make internists more like family docs and in this article more like dermatologists,and psychologists and occupational docs. We will probably hear more of this until and unless major changes occur in how primary care doctors are reimbursed.

Is CMS administrator threatening doctors to report on quality measures?

American Medical News (subscription required) quotes Dr. Mark McCleland as saying " there is a strong congressional interest in not doing more than one year payments adjustment without seeing more visible progress in quality reporting and quality improvement programs". According to American Medical News, Dr. McCleland declined to say exactly which legislators were saying that.He might not just be threatening physicians as you could argue the real losers in further cuts in medicare payments are the elderly who are bumping up against more internists and FPs opting out of Medicare and by cutting fees, often practices respond by cutting time spent with patients.Some physicians and some Medicare recipients might wonder how CMS can talk about docs improving quality on the heels of a somewhat less than stellar kickoff of Medicare Part D following promotion of the program which including a major underestimate of the cost when the program was spun to Congress. This week in Houston hundreds of volunteers are gathering to try and help explain the program to those eligible.25 states are having to pay for meds for folks who otherwise might go without meds due to glitches in the program. Similar programs are sprouting up over the country as citizens voluntarily do what they can do to fix a typical government snafu.Physicians,whose practices are admonished to improve their quality, are taking time in their busy office practices to try and explain the program to their patients.

reports of serious liver toxicity with Ketek

FDA's Medwatch reported 3 serious cases of liver toxicity with Ketek (telithromycin).The patients were not on other medication and said to be in good health.Some alcohol use may have involved in some case(s). This drug has been heavily promoted not only by usual advertising but also I have been to several "CME" events which seemed to emphasize the theoretical advantage of less resistance developing with this drug as have discussions in journal supplements gently leading the reader to the conclusion that the problem of increasing drug resistance might be mitigated by using telithromycin. It makes sense to not be among the first physicians who prescibe a new drug particularly in situations where there are multiple alternatives whose track records are long and the side effects are better known.

Does Legionella not cause pneumonia any longer?

A recent article in the Archives of Internal Medicine by Dr. D. Shefet et al who performed a systematic review and an editorial review of that article with comments in Courtlandt Forum might make you think there is no Legionairre's disease and therefore no need to empirically include antibiotic coverage for that possibility in patients hospitalized with community acquired pneumonia (CAP).The Archives article and the comments in Courtlandt are similar to a meta-analysis published in the BMJ in 2005 by Mills et. al. from New Zealand and comments in the Cleveland Clinic Journal that I wrote about last year.That MA focused on less than severely ill patients and found beta-lactams did as well as antibiotics that are effective against the atypicals except in the subgroup with Legionella infection.The authors concluded that beta-lactam should remain (that is or was the standard recommendation in UK) the antibiotics of choice in mild or moderately severe cases of CAP which is contrary to the guidelines of both the Infectious Disease Society of America (IDSA) and the American Thoracic Society.My reading of the Shefet article is that they did show an advantage to appropriate coverage in cases of Legionella although the conclusion does not give that impression nor does the review in Courtlandt. Further, the regimens which were compared were a beta-lactam and either a fluroquinolone or a macrolide given as single drugs.While the IDSA guidelines include the option of a fluroquinolone alone the alternative recommendation and one that is commonly used is the combination of a macrolide plus either of two specific cephalosporins ( ceftriaxone or cefotaxime).The Archives systematic review had no data on that issue. The results section said "these regimens[those with coverage for atypical pathogens] showed a significant advantage in clinical success for Legionella pneumophilia." The summary said " "no benefit of survival or clinical efficacy".
The section in the Courtlandt Review is called "evidence-based medicine"and purports to highlight "important new studies applicable to primary care".The section editor,Dr. Daniel Tobin, concluded that even though the systematic review may be underpowered to show a difference that "there does not appear to be a benefit to survival or clinical efficacy" to atypical coverage not quoting the results section comments regarding the clinical success advantage. He stops short of recommending not to give atypical coverage but this seems to be implied by his approach or at least could easily be interpreted in that way unless the original article is studied and the issue considered in light of "all of the evidence".
I consider this analysis typical of what I believe is an increasingly common "application" of what passes for EBM, namely emphasizing a meta-analysis as if it should be determinative and ignoring the context of the totality of evidence and other concerns regarding a particular issue.In this regard here is some of the other evidence that is necessary to consider in antibiotic management of CAP: 1)L.pneuomophilia is a recognized cause of serious and at times fatal cases of CAP 2)fluroquinolones and macrolides are effective treatment for L.pneumophilia infection.3)there is no test nor set of clinical findings that can exclude with reasonable certainty that L.pneumophilia is present at the time of clinical presentation of CAP.4)In seriously ill CAP patients antibiotics need to be given promptly and be correct (ie cover the usual suspects). From this set of evidentiary material the conclusion to cover atypicals (basically to cover L.pneumophilia as mycoplasma and chamydia are generally less potentially serious) follows. That- in part- is the evidence likely considered by the panels responsible for the current U.S. guidelines. In addition, macrolides and fluroquinolones are not particularly toxic or difficult to use medications and the practice of giving broader coverage initially and then focused therapy if and when a specific organism is identified continues to be sound practice.A systematic review for which the statistical power is suspect is not the type of trump card evidence that should overturn current practice.
Evidence based medicine should be based on the totality of the evidence and then blended with clinical judgment and in those regards there is more to factor in than simply randomized trials and systematic reviews of coarse grained outcome data.Systematic reviews should not be dismissed out of hand but neither should their results be determinative. They should be considered and given appropriate weight in the analytic process,

More on alternative medicine and falsifiability,Karl Popper and Andrew Weil

Two medical bloggers have recently disagreed a bit regarding integrative medicine or alternative medicine. We speak of the art and the science of medicine. The philosopher of science, Karl Popper, was very interested in the question of what separated science from pseudo-science . His well read essay on this issue can be found here.

It should be part of any handouts given in a medical school course in evidence based medicine.This is particularly important now given the prevalence of pseudo-scientific alternative medical disciplines given inappropriate implicit validation by various medical schools. Popper's formulation is that science as opposed to pseudoscience is stated in such a way that the proposals can be tested and thereby falsified.This is way Popper put it:
"Every good scientific theory is a prohibition:it forbids certain things to hapen.The more a theory forbids,the better it is....A theory which is not refutable by any conceivable event is non-scientific.Irrefutability is not a virtue of a theory but a vice....Every genuine test of a theory is an attempt to falsify it, or to refute it.testability is falsifiability...One can sum up all this by saying the criterion of the scientific status of a theory is it falsifiability, or refutability,or testability."There are elements of what passes for alternative medicine that can be tested. We can even do a randomized trial for some as we could to see if this or that proposed ancient medication did what its advocates claim it does.
Now, lets see if we can think of a way to test, for example, the Qijong proposition of sound and posture being able to cleanse and recharge the internal organs of stagnant energy.Perhaps we could devise experiments of delivering sounds to patients and then measuring the stagnant energy of organs.Wait, how can we measure stagnant energy when no one know what that even means ?Well, you get the point.
So why did the title mention Dr. Andrew Weil? (let me give a plug to Arnold Relman's essay about Weil.) He is being featured at a meeting sponsored by AMA on medical communication.The AMA can invite whomever they want to a conference but I question the appropriateness of inviting folks who advocate non-scientific alternative medicine.Does that not give Weil an implicit endorsement? I will , of course, have to admit Weil has been very successful at communicating whatever it is he is selling and it is a conference on communication but could they have not found someone who is skilled at selling science and scientific thinking?

The big three cure for all that ails medicine.

Singly or in combination it seems that whatever problem is identified,worried about or exaggerated, the proposed cure will be 1)IT-that is, some form of information technology, 2) a single payer system and/or 3) evidence based medicine. Those who have irrational exuberance for these panaceas might look carefully at how well the Medicare Part D has worked so far as it relates to items one and two mentioned above. At least we can't blame EBM for this fiasco. So far, it looks like the states have had to jump in to help seniors who otherwise would leave the pharmacy without their meds and the federal government is proposing legislation to repay them. All of this on the heels of numerous reports of the profound difficulty many seniors had in trying to figure out what the program was and how to sign up.Naturally a congressional investigation will be formed to try and determine why a government program did not work as advertised. Can you imagine such a thing?

American Medical News article on "relationships" leaves retired doc confused

The Jan 16, 2005 issue of American Medical News (subscription required) features a frontpage article on what they describe as the new buzzword in medical care "relationship". A special supplemental issue of the Journal of General Internal Medicine is devoted to that topic.The references to what this movement is about in the AMNews article left me uneasy. I could not get my mind around what was being said.One quote:" At its core, relationship-centered care calls on physicians and patients to have longstanding compassion relationships with each other." So, we or someone is to call on patients to have compassion for the doctor? Our job is to take of the patient, to place the patient first, to have a fiduciary relationship with the patient. Physicians may well have compassion for their patient, we typically do empathize with patients. What would generate compassion for the physician? Typically we are well paid,enjoy a generally prestigious status in the human food chain, are in a position of knowledge superiority in the patient's medical condition .The fact we work hard and often really seem to care-and often do care-make well cause the patient to feel a variety of emotions toward the doctor: gratitude, resentment (the doctor is is not sick),faith in her ability, relief of being told nothing serious is wrong, hope that the physician's reassurance is correct, and many others but compassion does not seem one of them. Quite frankly , I have trouble deciphering what is meant or hoped to be accomplished by comments like "moving away from the customer comes first and into something more focused on producing a fruitful, robust relationship." I would like to know what that "something" is and what will be the focus and I always though the "customer" formerly known as patient did come first. The editor of the special issue of the general medicine journal is quoted as saying " this is not just sitting around and holding hands and singing 'Kumbaya"...
But,knowing only what is in the AMNEWS report and observing doctors and patients for 40 years and while realizing that a good relationship is important, until I can learn more specifics about what it is they are advocating it does seem like hand holding and singing.Hopefully one of the handful of readers of this blog who have a better handle on this movement can help me understand it and it may well be that the news article did not do justice to what these folks are advocating.

inguinal hernia-JAMA article:some you can just watch

An article in the Jan 18,2005 issue of JAMA reports on a randomized trial of watchful waiting versus surgical repair of "minimally symptomatic" inguinal hernias and conclude for some watchful waiting is appropriate.The accompanying editorial by Dr. David R. Flynn is interesting as it discusses in some detail some basic issues in the analysis of trials. Should one look at intention-to-treat (ITT) or make the comparison on the basis of the treatment actually received? This becomes an issue as it did in this instance when there is considerable cross over in a trial. Nearly 25% of those assigned to the watch and see group opted to have surgical repair by two years and about 1/3 had done so by the end of the trial (4 years).Further 17% of those assigned to surgery decided not have the procedure. At first thought one wonders what sense it makes to look at results in which nearly 4/10 patients did not actually receive the treatments assigned to them.The argument is that the alternative is worse because here selection bias may enter into the picture since randomization no longer controls who receives which management option.The important point made by the editorial is that what was compared here was not so much treatments per se but management advice, i.e. what you tell the patient and in this regard the two approaches were about the same.As always in RCTs before they are construed too broadly, one has to look at the exclusion criteria for the patients in the trials.Only men were in the trial and only those who were at most minimally symptomatic.

Central versus brachial blood pressure, it that a key to differences in efficacy of medications

The ASCOT trial which demonstrated that amlodipine plus perindopril was superior to a combination of atenolol and a thiazide in terms of reduction in cardiovascular and renal outcomes and overall mortality had an interesting substudy known as CAFE. The Conduit Artery Function Evaluation study investigated the role of central versus peripheral blood pressure in cardiovascular outcomes.The amlodipine-perindopril group had lower central pressures while brachial pressures differed little. Could the greater reduction in central pressure be the reason for the apparent better outcomes of the amlodipine-perindopril regimen? There are data that indicate that calcium channel blockers and ACE inhibitors lower central pressure while atenolol does not.These two data sets were not obtained with catheters in the aorta but rather estimated central aortic pressure with something called "radial applanation tonometry". There are data indicating that this is a reproducibbe technique and provides a good estimate of central aortic pressure.Arterial stiffness as quantitated by several parameters derived from this pulse wave study seem to correlate with coronary artery disease and may be considered a type of end organ damage to which various outcome data correlate. Internists have a tradition of being enamored with pathophysiology and having grown up medically with the imperative of striving to "reason in terms of pathophysiology", I continue to find it intellectually gratifying to find instances where the data seem to be "explained" by underlying pathophysiological observations and theories.Having said that, I realize the theories are provisional and subject to refutation as we continue to try and discern how things work. Still, the mantra of the ALLHAT devotees of "diuretics and beta-blockers are best" is becoming less and less convincing.See also DB"s Medical Rants for an important perspective on diuretics.

New dyspepsia guidelines from American College of Gastroenterology

Upated guidelines for management of patients with dyspepsia have been published by the American College of Gastroenterology (AGA). The AGA publishes its guidelines on line free for everybody. The panel defines dyspepsia as "chronic or recurrent pain or discomfort centered in the upper abdomen" and discomfort as a" subjective negative feeling that is nonpainful". Dyspepsia is distinguished from GERD by the symptoms of heartburn and acid regurgitation.For patients with dyspepsia greater than age 55 or those with alarm symptoms
(GI bleeding,jaundice,odynophagia,palpable mass or enlarged lymph nodes,progressive dysphagia,unexplained iron deficiency anemia or unintended weight loss) early endoscopy is recommended. For those younger patients several approaches are acceptable. These include a trial of proton pump inhibitors (PPIs), testing for H. pylori (with the stool antigen or urea breath test) and then treating if positive with triple therapy and several variations of those themes.They do not recommend h, pylori treatment without a positive test.The entire paper is worth reading as it offers the latest party line thinking and specific treatment details for a very common complaint.The issue of non-gerd dyspepsia continues to be vexing for patients and physicians and in this regard they talk about "fundic dysaccomodation" and visceral hypersensitivity for neither of which is there clear cut advice.
The panel presents data that indicate that only a minority of patients with dyspepsia are shown to have reflux esophagitis (though they may have reflux symptoms),peptic ulcer or gastric cancer. Further although h. pylori may be diagnosed and treated the presenting symptoms may remain. Even so the treatment algorithm for dyspepsia relies on PPI trials and treatment for h.pylori. Those tools work well for those two specific conditions but many patients' symptoms are not due to those conditions. We are left with many patients labeled as functional dyspepsia and for them we have nothing as effective as PPIs are for acid reflux symptoms.

Where is HIPAA when you really need it?

Civil libertarians-and even folks who are not that libertarian-are alarmed at the actions of public health officials in New York. According to news report,hemoglobin A1c levels are being reported from the labs who perform the test without the consent of the patients or the physician involved.Carrying nanny- state activities to new levels may be an understatement. Cynics might say that HIPAA never was really about protecting patient confidentiality but rather making sure that everyone use the same set of insurance billing codes with the result being very large savings for the insurance industry and the confidentiality trappings were appended by the Clinton policy wonks later.It was never designed to protect patient privacy from the government.In a way, it is not surprising for a public health department to dive into diabetes or other chronic illnesses as the introductory statements of many medical articles begin with an almost obligatory comment characterizing the condition being discussed as a "public health problem" by which the authors probably really mean it is common and important and not that the public health agencies should get involved..To put some real teeth into a program like this might require reporting from grocery stores to the public health folks to see who is buying pecan pie and twinkies.

Still another algorithm for diagnosis of pulmonary embolism

The Jan. 11, 2006 issue of JAMA has an article (The Chistopher Study,vol..295,no.2,172-179) with a proposed system or algorithm for diagnosing pulmonary emboli (PE) using the Wells decision rule, the d-dimer blood test and the CT scan. It works like this: if the Well's score is less than 4 then a negative dimer sufficiently excludes PE so that no further tests are done. If the Wells number is 4 or more then a CT is needed even if the dimer is negative.Less than 4 is said to make PE Unlikely and 4 or more is Likely.
This was a large (3306 consecutive patients) study from 12 centers in Holland. The absence of PE was not determined by pulmonary angiography but the study relied on a nearly complete 3 month followup. An important issue is which d-dimer test was used. This study used a very sensitive immunosorbent assay (Vidas d-dimer).The immunosorbent and immunoturbidimetric tests are very sensitive-said to be greater than 95%- while the latex agglutination assays are less so. Excluding PE on the basis of a "unlikely"Wells score plus a negative d-dimer will only work well if a very sensitive assay is used.
I wonder if the "dichotomized"version of the Wells decision rule is too simple.All patients in the "unlikely" category are not equally unlikely to have PE. I have a problem with reducing a physician's assessment of how likely the diagnosis may be to a mechanistic rule and apparently excluding any and all other elements that a physician may call upon to decide the likelihood of a diagnosis. for example a decreased o2 saturation. A clinician's "global assessment"( i.e. considering the overall clinical picture not just the check list from Wells) should trump the decision rule.If you believe PE or DVT is a reasonable diagnosis to pursue,testing should be done even if the Wells rule suggests low risk or unlikely and the d-dimer is negative.(show me a blood test that can't be wrong)
An editorial in the same issue is written by a well respected DVT/PE expert ,Dr. R.D.Hull from Calgary who is enthusiastic about the Christopher study authors' proposed algorithm. He says in part " ... firm recommendations can now be made concerning practical and fairly simple diagnostic algorithms for evaluating patients with suspected PE or deep vein thrombosis". D-dimer testing and the increasingly technically impressive CT imaging techniques are giving us better tools for the often elusive and vexing problems associated with venous thromboembolism but I have concerns that reliance on decision rules make things seem more simple than they really are and there is much more to clinical judgment than is captured in a simple checklist decision rule.

Should we do PSA screening,Case control studies will not settle this issue

Randomized clinical trials enjoy the view from the top of the hierarchy of "truth seeking epidemiologic mechanisms". Medical students are taught that the randomization process serves to immunize the study against the dreaded selection biases. Clinicians generally feel more intellectually confident in reading about a RCT.
Case control studies are another matter.The vagaries of analyzing potential confounders in case control studies elude many physicians and our distrust of case control studies is intensified by the number of dueling or contradictory non -randomized studies over which we have puzzeled.I never get tired of mentioning the juxtaposed, non-randomized, 1985 NEJM articles in which we were told by one group of prestigious researchers that post-menopausal hormone replacement therapy decreased the risk of coronary heart disease (by about one half) and another group of researchers, from an equally prestigious department, told us that the risk increased by a factor of two.These were not rookie epidemiologists or young aspirating medical authors with freshly minted MPH degrees data dredging to bolster their CVs. We are talking about Harvard and the Framingham study.A well respected epidemiologist, Dr. John C. Bailar, has commented that either study taken alone would have been convincing. An editorial by him in that issue seemed to conclude that both articles seemed to be sound in their methodology and that a reason(s) for the discrepancy was not apparent.Bailar suggests that observational studies are subject to a great deal more variation than is usually captured by the statistical tests that are used and that differences such as these may well be due to confounders that are either unrecognized or have larger effects that anyone recognized.
So it is with no surprise that an editorial in the Jan.9,2005 issue of the archives of Internal Medicine ( The PSA Conundrum, Arch. Intern Med/vol 166,Jan 9,2006 pg 7-8)struggles to explain why one case control study concluded PSA screening is efficacious and another concludes it is not. I certainly do not feel competent to assess the relative merits of varying methodological approaches in conflicting case-control studies and I doubt if most physicians do either let alone have the time or energy to attempt to do so. Dr. Michael J. Barry , the editorialist tells us 78% of male primary care physicians and 95% of male urologists reported having a PSA on themselves suggesting physicians seem to believe that on balance PSA screening is a good thing. I am not sure if it is or not but I am sure that another case control study purporting to show either positive or negative results is not going to convince many physicians to change their minds.Two large randomized trials are underway.There is the PLCO screening trial in the U.S. and the ERSPC trial in Europe addressing the issue of PSA screening.Results from both are due in 2009.Let us hope that the two trials point in the same direction.

Quality in Medicine-is it a low defect rate?

A dictionary definition of quality is "a measure of excellence".I believe that when most people use the term outside of a technical sense this is about what they mean. A quality product or service is who that is really good and about which the user or consumer has little to complain. The Total Quality Movement (TQM) or " six sigma" body of thought, which was popularized by Motorola, frames quality in terms of "defect rate" and the reduction of process output variability. The six sigma quality goal is to reduce process output variability to no more than 3.4 defects per million opportunities. If you producing computer chips or pencil erasers that type of imperative makes sense.In dealing with inanimate materials, mechanical parts and a process of human design performance measured in terms of defects per makes sense and apparently the TQM movement has been successful in operations of that type. In a manufacturing process variation is undesirable and efforts to eliminate outliers and execeptions makes sense.
In medicine variation is the rule.All patients do not react the same way to a given medication and we do not know ahead of time who will benefit and who will suffer a side effect or fail to enjoy improvement.Some patient get well without treatment.Manufacturing process that turn out bad parts do not spontaneously fix themselves.A well organized and TQM manufacturing process may well achieve a 6 sigma goal of no more than 3.4 defects per million opportunities. Consider the best we may do in a highly selected group of patients with for example coronary artery disease, we may reduce the risk of a coronary event by say 22% (so far it has not been 100%). So that many patients that we treat with all of the currently recommended medications will still have a heart attack. The prestigous-and apparently rarely challenged-Institute of Medicine (IOM) had defined quality in medicine as " the degree to which health services for individuals and groups increase the likelihood of desired outcomes and are consistent with current medical knowledge". So treating the coronary artery patient with all of the currently recommended meds would be quality care as the likelihood of the desired outcome would be increased and the program is compliant with current professional knowledge. This begs the questions of what evidence is required to justify a claim of increased likelihood and who is to determine what is accepted medical knowledge.A low defect rate has nothing to do with it and the manufacturing paradigm is just not applicable.Accordingly if we wanted to measure quality in a clinic or doc's practice we could look at the treatment offered to a patient with coronary artery disease.That would be the quick and dirty way.That would be the way to do it if clinical judgment and patient values did not matter.The question arises, who will do this measurement and for what reason(s). Insurance companies and HMOs do this and their claim is they do it to improve quality and concerning that we discern another apparent definition of quality,doing things as cheaply as we can get away with it.

HCAP as a new pneumonia category

A basic fact about pneumonia is that physicians recommend treatment without knowing the specific pathogen.This is because we have no reliable tests that will identify the culprit bug quickly and accurately.We have to decide on treatment based on what are believed to be the likely etiological agents in a given clinical situation. A scheme that has worked out fairly well is to consider where the infection began,namely in or out of the hospital because different sets of infectious agents are likely to be involved based on that simple dichotomy. So that we talk about community acquired pneumonia (CAP) and nosocomial or hospital acquired pneumonia(NP) and base empirical treatment accordingly.It is also useful to split out those patients who acquire pneumonia while receiving mechanical ventilation (VAP) or ventilator acquired pneumonia because certain bacteria are likely to be involved.
A large data base review by Kollef et al in the December 2005 issue of Chest argues for also splitting off from CAP those patients designated as having "health care associated pneumonia" (HCAP).This designation applies to patients who have been in contact with the health care environment or have been recently hospitalized. It includes therapy in a dialysis center,a nursing home or extended care facility, patients receiving home infusion therapy or home wound care. Kollef's data indicate that patients in these categories are likely to be infected with bacteria that would not be typically covered by the usual antibiotic regimens chosen for empirical treatment of CAP. The data indicate that HCAP is more like NP that it is CAP.
The recent guidelines from the American Thoracic Society and the Infectious disease Society of America for the treatment of NP include patients with HCAP in their nosocomial pneumonia recommendations. Basically this mean that HCAP patients be treated for potential multidrug resistant pathogens including MRSA (methicillin resistant staph. aureus) and resistant gram negative bacteria. It has been my experience that generally physicians are treating nursing home patients with pneumonia with coverage for those two possibilities already but the HCAP category will likely be useful to alert doctors to other non-hospitalized patients who need an antibiotic combo different from the usual garden variety CAP.

Wernicke's syndrome not just for malnourished alcoholics any more

Ataxia, confusion and opthalmoplegia, the classic triad of Wernicke's, that all the IM residents at Charity Hospital were aware of and had the IV thiamin at the ready is said to only occur in about 20% of the cases. Our index of suspicion was aimed at the malnourished alcoholic but now it sometimes can be a disease of medical progress-to the extent that gastric bypass for obesity is considered progress. Medscape presents a CME case of a young woman some few months post op from gastric by-pass whose astute physicians were able to diagnose and treat it. Apparently the MRI has some fairly typical findings.Recovery is variable and the ocular palsy resolves first but ataxia may persist as may the memory problems.How commonly it is associated with by pass association is unclear.A recent report from Brazil documents 4 cases.Vomiting may be the trigger as it seemed to be in two cases reported from Spain.Another case reported from South America described a man with no vomiting but with rather marked voluntary reduction in food intake which lead to this thiamin deficiency syndrome. It is clearly something to be aware in a gastric-bypass patient with vomiting as early treatment can reverse much of the abnormal neurological picture but not always all of it.What about prevention?

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.

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.

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.

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."

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.'

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.

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.

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.

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.

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.

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.

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.