Senator raises questions about the quality of Quality Improvement Organizations ( QIOs)

Probably most people and likely many physicians have never even heard of QICs. Here is their website where we learn that the QIC program is directed by CMS and consists of 53 QICs who are tasked "to make sure patients get the right care at the right time."

Senator Chuck Grassley is asking for changes in this program because- according to a recent news blurb in the Capital Health Call section in JAMA of "questionable expeditures,potential conflicts of interests and lack of effectiveness." He raises questions about the quality of the program purported to ensure quality of medical care.

The American Health Quality Association, which is described as a QIC trade organization seems to admit that the program need changes-probably they would favor more funding- but blames the problems on poorly written laws.

Purportedly, there was a need for these QICs because physicians left to their own devices would not deliver "quality care", so it would seem reasonable that what we need now is another layer of quardians who can watch over and insure the quality of the organizations that were to insure the quality of care., but ,of course, they will have to be audited.

More on Disease Mongering

Health Care Renewal recently referenced a symposium on Disease Mongering (DM) and the full text essays are now available on the PLOS website.

In recent months,I have written about certain aspects of the promotion of the diagnosis and treatment of two conditions,bipolar disorder and restless legs syndrome (RSL) as having features of the DM phenomenon.

Let me attempt to preempt one line of possible criticism by stipulating that Bipolar Disease is a very serious psychiatric disorder and warrants treatment by qualified physicians and that RLS can be in some patients a very disturbing disorder with definite morbidity relief from which could be very worthwhile.

However, I had questioned the drug company initiative to round up primary care doctors to seek out and take on the often daunting task of managing a bipolar patient,an enterprise in which psychiatrists really earn their fee.(I will admit that in No-trees Texas type locations the PCP may have to take on the job as the region may be bereft of psychiatrists).I also questioned the wisdom of screening for RLS with a drug company sponsored questionnaire with the objective of offering treatment with a dompamine agonist for positive screenees.

The PLOS symposium essay on RLS is worth reading as it takes up several aspects of this matter with much greater development of the issues than my gut feeling sense of it that I posted. Hats off to Doctors Steven Woloshin and Lisa M. Schwartz of Dartmouth Medical School .

Another article questions the evidence or lack of it underpinning the whole issue of diagnosis and treatment of bipolar disorder.

It can be argued that the marketers manipulate the motivations of physicians and various support groups . The physicians are obviously an essential element in the equation. It is their desire to foster the welfare of their patient and do the right thing that is necessary for the DM process to flourish. I believe the "shame of being ignorant" is branded into the limbic cortex of medical students .Hats off to the ever insightful author of the blog PURRY GUD (tomwaitsatemyaby.blogspot.com) who used that phrase recently.

Physicians-many at least-are haunted by the fear that we will harm someone or fail to help someone because of something we do not know (there are certainly other ways we can harm also). This motivation to know what we need to know allows marketers to direct our energies to detection of new illness and to accept wider definitions of disease . Medications are not prescribed because we like the free food or notepads or pens even if we like the free food. Free lunches are not really the problem. The marketers not only manipulate the physcians' hypertrophied sense of duty but the prestige of evidence based medicine as well with all the tricks and traps one can squeeze into a randomized trial to give the veneer of solid science to something that may be no more than a comparison of their drug with one no one would use anyway.

The good news here, if there is any, is that we are catching on. The DM symposium is evidence of that.

We are getting more skeptical about what we read.We are realizing there is more to a RCT than the fact is randomized and blinded. With Google and other search engines it is easier to more quickly confirm or deny material from various promotional efforts. (The bad news is who has time to check and analyze everything that appears in print)

But even as our duty pushes us to strive even harder to figure out what it is we should do to do the right thing we learn of still another tactic to thwart and divert our efforts.

Medical news you really can't use

Medical Journals sometimes publish POEMs-which in this context stands for "Patient Oriented Evidence that Matters". The criteria for a study to be elevated to high level on the epistemological food chain are:

1.addresses a question physician face.
2.has measure(s) of outcome and
3.has the potential to change the way doctors practice.

There are several "medical news newspapers" typically distributed without charge to physicians, one example of which is the " Internal Medicine Report",which I usually read if for no other reason than for the excellent essays by Dr.Philip R. Alper . This type of publication has no shortage of information that you really can't use,as well as some you can , the trick being to know the difference.

Here are some of the "unPOEMs" from that publication.

They reference an case control study from Urology (2005,67:73-79,which noted that risk for BPH was increased by eating more cereal,bread, eggs and poultry while risk was decreased by eating more soup,legumes, cooked veggies and citrus fruit. Try putting this factoid into your practice. Mr. Jones, with your BPH- I would recommend you eat less bread and more soup.

Another reference was to a paper presented at meeting of the American Stroke Association in which patients who had endovascular closure of patent foramen ovale (PFO) has less migraine headache than a comparison group that was treated medically.This was a retrospective,nonrandomized study and recall bias was an obvious issue. Again try and put this "observation" into practice.

In the same issue we also "learn" that Sulfonyluea therapy for type 2 diabetes linked to cancer" and "moderate coffee consumption may keep Type 2 diabetes "at bay".

Many of these factoid unPOEMs derive from case control studies that are correctly described as hypothesis generating studies that sometimes alert researchers to apparent associations that lead them to push on with more definitive techniques and sometimes are just statistical noise dead ends.

Carotid endarterectomy-AAN guidelines

The updated and long awaited guidelines from the American Academy of Neurology are available on line in full text. Their previous guidelines were published in 1990.

Two large Class I studies provide good data for their recommendations regarding symptomatic carotid stenosis (CS), the NASCET trial and the ECST. Entry into the studies required a TIA or non-disabling stroke within the previous 6 months.

For symptomatic patients with stenosis greater than 70% ( but less than "near total" occlusion) carotid endarterectomy (CE) is recommended if the surgical stroke or death frequency is believed to be less than 6% and the patient has an expected survival of five years or more. The absolute risk reduction is 16% with a NNT of 6.3.

If the stenosis is less than 50%, surgery is not recommended and medical treatment is preferred.

In regard to asymptomatic patients CE should be considered if the stenosis is 60-99 % and the surgical stroke or death risk is less than 3% and the patient has an expected 5 year or greater survival.

Due to the slow accumulation of big time Class I studies we may have gone about as far as we are likely to go any time soon with learning about CE versus medical treatment, but what about carotid stents? The jury is just beginning to hear the evidence and there are advocates with convincing arguments on each side.

Coronary stents have certainly become worthy rivals of CABGs and catheter treatment of cerebral aneurysms -at least in some clinical situations-may be better than surgical clipping. I believe that increasingly we will see more and more endovascular catheters at work and less classical surgery. I wonder how long it will take for enough data with head to head ( or neck to neck) comparisons between CE and stenting to accumulate to determine the role of catheters versus surgery in this setting.

You need more than FEV1 to judge bronchodilator response

Bronchodilator drug trials and often clinical followup have focused on the changes in the forced expiratory volume in one sec (FEV1) to judge therapeutic response. However, it is recognized that exercise intolerance and dyspnea may improve with no significant change in expiratory flow rates.
Improvement in exercise tolerance actually seems to correlate better with indicators of improvement in overinflation,a simple measure of which is the inspiratory capacity (IC).

The IC is the sum of the tidal volume and the inspiratory reserve capacity which is the volume of air inhaled on top of a tidal volume. In COPD the IC is reduced as a result of the hyperinflation ( increased residual volume and functional residual capacity) so that the tidal volume is performed at the upper part of the lung's pressure volume curve which is a region of low compliance and an increased load on the inspiratory muscles.The overinflation present at rest is worsened with increasing airtrapping during exercise with increased respiratory rate and decreased time to exhale and is currently thought to be a major variable that relates to exercise intolerance and the sensation of dyspnea.

In the March 2006 issue of Chest ( subscription required for full text), authors from Holland demonstrated that a long acting bronchodilator (LABA),formoterol plus once a day tioptropium ( a long acting anticholinergic) brought about significant improvement in expiratory flow rates and -probably more importantly from a symptom improvement point of view-a significant increase in the inspiratory capacity.

Scores of bronchodilator trials focused only ( or at least mainly) on FEV1 measurement. ( I was involved in several as a pulmonary fellow) and as we learn more about the pathophysiology and the clinical correlates of lung function measurements we are better able to develop therapeutic measures to improve the disabling exercise intolerance of COPD patients.

It may have taken the surgical lung volume reduction experience to remind lung doctors that we have been doing pharmcologic lung volume reduction therapy all along when we have been using bronchodilators.

Comments about Deficiency of clinical skills

Dr. RW's post referencing Dr. Herb Fred's editorial in the Texas Heart Journal generated several negative responses in KEVINMD's march 30.2006 blog following his reference to that piece.

Several ad hominem comments accused Dr. Fred of being basically a disgruntled, out of date, grumpy old doc who-in the words of one such writer-never practiced in the real world. Ad hominem arguments are -well -just that and usually do not warrant detailed refutation.

Unlike some of the commenters' suggestions, Dr. Fred seems quite aware of the calling-the-shots nature of managed care and the time restriction brought about by the third party payers' domination. He says that the HMOs force physicians to care for a maximum number of patients, in a minimum number of minutes for the lowest number of dollars.

His rant is about the decline of clinical skills and the factors responsible.He believes that values and priorities are not what they used to be.
When he trained in the mid-1950s ( and also when I trained in the 1960s) :

"... hard work,self pride,devotion to duty, strict accountability and pursuit of excellence were the norms" .

To expand on that-Things were framed in the relationship between the individual doctor and the individual patient.We did not speak about or -except in extreme circumstances-consider the " greater good" or conservation of some abstract and apparently collectively owned "resources".It seems that the core competencies of the ACGME do espouse-at least in part-values other than the one-on-one doctor patient relationship.

The ACGME core competences speak of :

..Responsiveness to the needs of patients and society

...practice cost effective health care and resource allocation

...understand how their patient care and other prorfessional practices affect...the health care organization, and...the larger society.

If I were managing an HMO, those "values" are certainly those that I would have inculcated into the doctors who are allocating my resources.

Not enough time for medical training-A problem in Europe as well?

The restriction of work hours for residents has lead to complaints from several fronts and concerns from both sides of the Atlantic.

Aggravated Docsurg has recently discussed the issue and quotes an interesting article in the American Journal of Surgery. The article reveals that 89% of surgery residents who completed an anonymous survey reported they "cheated" on the 80 hour work restriction rule. That is- they worked longer but did not report the hours correctly. This also occurred in 74% of non-surgery residents.

The authors of the article seemed to be alarmed that surgery residents were placing their allegiance to the concept of individual responsibility for patient care above a team approach and to adhere to the rules. When did individual responsibility stop being a core value of being a physician or -in current jargon- a major element of professionalism ? Recent apparent revisions in the expressed views of ACME seem to point in that direction. I have written about that before. In 2003 the ACME eliminated the statement that is a touchstone of interning training:

"Physicians...Must recognize their obligation to patients is not discharged at any given time or any given day".

Are there competing visions- the individual responsibility physician versus the shift work doctor.?

The new work hour restrictions in Europe have generated concern that there is not enough time to properly train specialists.Summer's Radiology Site references an article in which British gastroenterologists report trainees no longer have time to perform the necessary number of endoscopies to become proficient due to the duty time restrictions. This lead to the following comments by one of the GI docs involved in a training program:

"You can't shoehorn more training and other work into less and less time and expect the same quality of training."


This statement echos the opinion of the training program directors quoted above who said:

"There is simply insufficient time to educate the internal medicine residents in the present regulatory environment."

This transatlantic meeting of the minds is sobering. The folks who make the rules (ACGME in the U.S.) and whoever in Europe ought to listen to the real life experiences of those program directors and the trainees who have to live by their rules before we have a generation of less well trained specialists who will go home at 5 p.m.

Archives Internal Medicine article-some good news about the third heart sound and practice

The March 27,2006 issue of the Archives of Internal Medicine published an article that happily tended to confirm some of my biases. ( "Relationship between Accurate Auscultation of a Clinically Useful third heart sound and Level of experience." Marcus,G et al. Arch Int Med. vol 166,March 27, 2006 p.617-622)

The authors studied the auscultatory prowess in regard to detection of a third heart sound (S3))of docs at various levels of experience-from intern to cardiac fellow to attending cardiologist) by having them examine 100 patients shortly after cardiac cath and constructed correlations with LV ejection fraction, BNP and echocardiography.

Findings include:

The finding of a S3 by auscultation is very specific for heart failure (HF).In other words a S3 goes a long way to ruling in heart failure but it is not very sensitive- so not great at ruling out HF.

A cardiologist's perception of an S3 is as good as a phonocardiogram.

And here is the one I really like -Cardiologists and cardiology fellows do better than interns and residents in internal medicine. Who would have thought?

Yes Virginia, practice and experience matter and sometimes the physical exam may be of value.

We speak now of third sounds-in an earlier era we talked more about " gallops " and "gallop rhythms". Dr. George Burch in his 1953 text " A Primer of Cardiology" says a " protodiastolic gallop rhythm is present when the gallop sound occurs early in diastole"..It is due to an exaggerated third heart sound and is common in congestive heart failure."

The medical language of the 1950s did not include the words sensitivity and specificity but the cardiologists and internists of the day knew that a gallop usually ruled in heart failure.

Practice and experience do matter and Dr. David L Simel who wrote the editorial discussing the article wondered if the current trend in reduced house staff training time will be counterproductive in creating an environment wherein that practice and repetition can take place. I think the answer is obvious, of course it will- absent some major effort on the part of the training program to remedy that,given the recent history of ACGME to pile more and more new requirements to be carried out in less and less time.

Physicians' " Guild" breakup and the alleged move to free markets

I believe everyone should read HEALTH CARE RENEWAL everyday but a recent post exceeds that blog's high standards. The article is entitled " The consequences of Breaking the Physicians' "Guild" ".

According to Dictionary.com a guild is "An association of persons of the same trade or pursuits, formed to protect mutual interests and maintain standards "

In it, Dr. Poses ( about whom we have to wonder when he sleeps) talks about Alain Enthoven's managed competition and his strategy to break up the physicians guild which- in Enthoven's view- is the main reason why medicine costs so much and is of such poor quality in this country. We also hear about the consequences of this strategy.

You would be wrong if you thought Enthoven's views on prepaid group practice, universal coverage and managed competition went away with the demise of Senator Clinton's health care task force.

In the same piece, Dr. Poses give a chilling rendition of the transformation of the pharmaceutical marketing landscape including comments about the new drug reps aka Drug Ken and Drug Barbie.

I'll admit I must have slept though most of the 1980s and 1990s ignorant of the Jackson Hole group and the "intellectual" verbiage that feed the HMO movement, my hat is off to Poses and the other contributors to HCR. They are doing us all a great service.

NEJM article on who is at greatest risk of poor quality health care

The March 16, 2006 issue of NEJM published an article reporting the results of applying RAND's Quality Indicators ( some 439 of them) for 30 medical conditions based on telephone interviews followed by review of medical records for those participants who gave permission.

The quality indicators were chosen by a nine member multispeciality "expert panel" using the RAND-UCLA modified Delphi method. The degree to which physicians "comply" with these opinions of what is good care is the measure of quality.

One could haggle with how to measure quality in this type study but nevetheless some of results will give ammunition for health policy wonks of almost any persuasion.

Those who believe a single payer (government) system is best will have to gloss over the authors' sentence that says:

" In the United Kingdom,with universal coverage, a study using our methods found that the overall proportion of recommended health care that was received was similar to what we have reported"

and what they report in this article is that the " problems with quality of care are indeed widespread and systemic and require a system wide approach."

You have to wonder what approach they would recommended as they seem to say both the single payer and the current U.S. set up give equally unacceptable results.

Surprisingly they found that :
"..Blacks had higher scores than whites for the quality of heath care".

This differs markedly from what many other studies have shown.

They also found that
"...health insurance status was largely unrelated to the quality of care".

So is all this concern about the large number of uninsured people misdirected?

This is not outcome data. We have no idea from this study what effect these alleged non-compliances have on the health outcomes. This is process data collected by a method prone to bias ( telephone interviews),using a huge list of quality indicators some of which are evidence based and some expert based. If the medical record did not document a given medical act it is counted as it it did not occur. Further, we are not told in the article what sort of infractions occured and how serious they may be. It is like being told there were 17,242 crimes in a given state over a given time period and we are left in the dark as what types of crimes were documented and how many in each category.

I'll bet we will see a flurry of letters to the editor attacking various aspects of this article.

New Orleans Charity hospital- Dead? But not forgotten

Having grown up medically in halls and wards of Big Charity, news items and blocs about it attract me immediately.

The March 15,2006 issue of JAMA has a poem by a physician, Dr. Wayne F. Larrabee, Jr. who trained there. The poem states in part:

"Charity Hospital, New Orleans 1735-2005 ...Generations climbed her stone steps, disappeared for years inside gray walls, learned to live thirty-six hour days and then to sleep without dreams...

Our hands remember though how to wield a knife, separate good tissue from bad, preserve vessel and nerve and something more- how to touch a dying patient whisper a wordlessly benediction and receive a blessing in return. "

The Haversion Canal blog, authored by a Tulane med student is keeping us current on a planned rally at Charity to save the hospital which has sat unoccupied since Katrina and it seems the state of Louisiana has determined it cannot be repaired and must close permanently.

The featured speakers include LSU and Tulane faculty. I wish I could be there and I wish there were some hope to salvage the institution. It is impossible to think of LSU Medical School and Tulane Medical School without thinking of Charity. I think the med students and house officers who trained there all received a " blessing in return ".

Caveats regarding carotid sinus massage

The March 12, 2006 issue of the Archives of Internal Medicine has an interesting article on the issue of syncope and carotid sinus hypersensitivity and a useful related editorial.

The editorialist make a good point about the contraindications for carotid sinus massage (CSM) as a diagnostic maneuver. The presence of a bruit has traditionally been considered a contraindication but because of the limited diagnostic value of listening over the neck arteries Dr. Neil Coplan suggests it would make more sense to do a carotid ultrasound first if there is concern about the presence of carotid artery disease. And in an elderly patient with a history of syncope you would almost always have that concern and the suggestion is that the absence of a bruit may not be sufficient reassurance.

The article, itself,showed that among community dwelling older folks in England, carotid sinus hypersensitivity was seen in 35 % of the sample ( n=1,000) who did not have a history of falls, syncope or even dizziness. So the point is that a positive result on CSM does not necessarily mean that the patient with syncope has carotid sinus hypersenstivity as the cause and other causes still need to be ruled out. How do you determine if the hypersensitivity is the causative? Basically you check out the other likely suspects and make a clinical judgment.

Since carotid sinus hypersensitivity may be fairly common in the older population, a comment regarding safe use of stethoscope seems in order. At some point in time, which so far has not been accurately pinpointed by medical historians, a sea change occurred in the way stethoscopes are worn. Older docs may still place the ear pieces around the back of the neck while younger ones drape the instrument around the neck with the ear pieces dangling on one side of the chest and the heads of the instruments on the other. Why or when this important cultural change occurred is unclear and the ergonomic issues need to be discussed but older docs need to shift to the modern method if for no other reason than to avoid syncope. This link shows the safe way to carry your stethoscope when not in use and on this link we see Dr. Kildare with the style of another stethoscope era.. Another reason that it is good to keep current.

Homocysteine- three randomized trials suggest maybe everyone will not benefit from supplementation with b12 and folate

A pre-publication release from the NEJM on line gives us the results of 2 randomized trials (RCTs) which investigated the effects of treating patients with known cardio-vascular disease with folic acid and B12. These trials known as the HOPE 2 trial and the NOVIT trial join the previously published VISP trial.

Overall, there was no benefit in terms of the composite end point of recurrent myocardial infarction,stroke or sudden cardiac death. In HOPE 2, there was a statistically significant reduction in stroke among treated patients versus placebo. In all 3 trials the treatment did reduce the homocysteine levels. The concept of using composite end points is interesting and leaves me a bit puzzled. What is the rational of adding up cases of MI and strokes? Is not each outcome an important concern per se? How do authors decide to lump or split outcomes?

These trials do not provide evidence against the practice of attempting to lower elevated homocysteine levels in patients with CV disease as the trial treated all comers , not just those with elevated levels. What about patients with elevated levels and no history of CV disease?

I cannot leave this topic without noting a meta-analysis quoted by the editorialist in the same NEJM issue as the two articles quoted above. That article "determined" that a 25% reduction in the serum homocysteine levels was associated with an 11 % lower risk of ischemic heart disease. The fact that we now have 3 RCTs that contradict a Meta-analysis should no longer be noteworthy as we see that more than occasionally. My point is that to imply such precision exists in how much benefit will accrue from a given therapeutic manipulation based on a meta-analysis is not warranted and approaches the threshold for silliness. When authors do that it applies a coat of "apparent validity" paint to a structure held together by a complex collection of assumptions.

After I use up my current supply of b12 I guess there is no reason to buy any more.

Physicians deal with individuals not with averages

I blogged previously that a key maxim that medical students should have branded into their brains is "Every one does not react in the same way to treatment".

There is more to it than that. Everyone with the same illnesses does not present in the same way,everyone with same illness does not always have the same results on lab tests or imaging and everyone does not accept a physician's recommendation in the same way.

I came across a memorable quote that captures all of that in an eloquent way and needs to be appended to the hypothetical handout for med students of the very important Milbank Quarterly article by RL Kravitz which is entitled "Evidence-based medicine;heterogeneity of treatment effects and the trouble with averages"

The author is Dr. Leon Eisenberg,the reference "Medicine-Molecular,Monetary, or More than Both", JAMA july 26,1995-vol 272, no. 4 p 331" While I do not agree with all he said the following is dynamite"

"...Medicine deals with phenotypes,not genotypes. Between genotype and phenotype, a lifetime of individual experience has fashioned what began as an envelope of stochastic probabilities into a singular personal embodiment: the patient who faces us.

In clinical practice, it is the particularities and idiosyncrasies of the individual patient that challenge the physician. The same disease never presents in quite the same way in successive patients.

Complaints vary: severity varies, response to treatment varies. Nondisease, that is, nonorganic disease, mimics "real disease" with remarkable fidelity"

In short, there is heterogeniety of almost everything and possibly why Hippocrates noted that experience was treacherous along with judgment being difficult.

Required reading" Aggravated Docsurg's post onThe AMA,Pay for peformance (P4P)

I have written about P4P before and am more concerned than ever about it in light of AMA recent apparent support of it.

Aggravated Docsurg has an excellent post of this topic replete with great links to well written and thoughtful essays pointing out what a bad idea P4P is. I can add nothing to his comments and those he references. The P4P may well work out to be even worse than managed care if that is even possible.

The latest Holly Grail Test for bacterial infection? -Procalcitonin

"Use less antibiotics" has become a common theme. Antibiotics are expensive, pneumonia is a very big ticket item for CMS and hospitals and then there is the often invoked specter of antibiotic resistant in regard to which the conventional wisdom is that overuse of antibiotics is one of the causal elements. Recently, I referenced an article that suggested that effective "education" about overuse of antibiotics might have negative health effects because of underuse.

Procalcitonin, (PCT) as the name implies, is a precursor to the thyroid hormone calcitonin. Normally this substance is found in the thyroid glands but in some conditions,notably bacterial infections-but maybe not viral-blood levels rise.

A recent paper ( reported in the Feb. issue of "Pulmonary Medicine, pg 3, " Procalcitonin can guide antibiotic use in CAP cases) explored its use in community acquired pneumonia, in which the authors claimed that one could use the test to determine duration of antibiotic therapy. For the most part, how long we treat pneumonia is a function of physician preference and reliance on expert opinion.

As a recent journal club discussion of procalcitonin's role in detecting bacterial infections pointed out, already there are a number of "yes,buts" and "howevers". PCT may not always be elevated in bacterial sepsis, and may be elevated in heart failure and cardiogenic shock and I'll bet as time goes by more conditions and medications will be found to effect blood levels.

Appropriate restraint in the enthusiasm for thinking that PCT will always paint a bright line between bacterial and viral infections is expressed in this review by two investigators who have done some of the often quoted research in this area. PCT testing may well evolve into common use as one of the diagnostic elements to consider in evaluating a patient with possible infection.

Annals Internal Medicine article-you can't rely on RCTs alone to determine drug safety

In the Feb.21,2006 issue of the Annals of Internal Medicine, Ioannidis et al have an excellent article on adverse efffects (AEs).(Ioannidis,et al "Adverse effects;The more you search, the more you find", Ann Int Med 144 (4) Feb 21, 2006)

"It is almost always inappropriate to make statments about no difference in adverse rates between groups of non-significant p values....rates of adverse events that are derived from single, modest-sized trials that are not statistically significant typically do not exclude with certainty the possibility of major,clinical important differences in harm between groups"

Randomized trials are often small and designed to test efficacy in patients in which the dosing is well controlled and often patients with co-morbidities are excluded. Only after many more patients are treated do side effects become apparent.

The latest two in what could be a very long list of medications for which serious safety issued arose after RCTs were done and FDA approval issued are Tegrin (gatifloxacin) and Ketex.

The issue with gatifloxacin drug is diabetes and now it seems to be contraindicated in patients with diabetes. Serious liver problems have been noted with Ketex.

Interestingly, gatifloxacin has been associated both with hypoglycemic reactions in diabetics on treatment and hyperglycemia in patients previously not known to be diabetic.One cannot but wonder what the mechanism(s)is/are.

A recent review of gatifloxacin-hyperglycemia cases found most were associated with decreased renal function. That the blood sugar effects are not limited to just gatifloxacin is suggested by another recent review that showed approximately equal numbers of "dysglycemias" with gatifloxacin and levofloxacin.Still another review study demonstrated a greater risk of blood sugar alterations with gatifloxacin.

Even though the RCT rests on the top perch in the party-line version of the heirarchy of the evidence used in evidence based medicine, we have to fall back on the lowly case report and observational studies to alert us to serious drug side effects. We have to realize RCTs may be best to determine efficacy not the risk of adverse effects.

ACP'S " Advanced Medical Home" will that dog hunt?

If you live in Texas, sooner or later you have to say something about "dogs and hunting" and I apologize in advance for seeming to treat a very serious,and I presume thoughtful, set of suggestions from the American College of Physicians in what seems to be a flip manner.

The ACP rightfully claims that primary care medicine is in a crisis mode. I agree. Their proposal called "Advanced Medical Home" (AMH) call for widespread changes in reimbursement, practice mechanics and systems and even medical education.

The proposal recommends:

"Voluntary certification and recognition of primary care and specialty medical practices that provide patient-centered care based on the principles of the chronic care model; use evidence based guidelines, apply appropriate health information technology, and demonstrate the use of best practices to consistently and reliably meet the needs of patients while being accountable for the quality and value of the care provided".



The ACP calls for:

public policy and third party financing changes and changes in medical education and national pilot testing of their proposal.

Reading though the 20 plus pages (plus appendices) I am somewhat discouraged by finding every current buzz word and platitude that are usually used in policy wonk type discussions of health care ( patient centered, value, best practices,etc,etc) but it is clear that primary care is in trouble and the ACP is at least aware of some of the issues. They seem to rely on the hope that evidence based medicine and information technology and the team approach will save the day for primary care and that somehow or other the folks with the check books (CMS,insurance companies) will cooperate with their suggestions.

The model that they proposed is supposed to improve quality and reduce cost and physicians can share in this "system wide" savings. We all know how physicians shared in the cost savings that Managed Care was to bring about. In this era of evidence based medicine where is the evidence of efficacy or safety for what they propose? Where is the evidence that this approach will save money.

Will what they propose matter? Will anyone ( CMS and third party payers)
listen? Does it all make any sense? I would be very interested in what the real doctors out there think about this.

Dopamine agonists (?particularly pramipexole) and compulsive gambling

When I first learned of a putative association between a particular medication ( pramipexole (Requip)) I was reminded of a defense in a bank holdup in which the attorney for the defendant argued that Halcion made the person rob the bank.

I am less skeptical after reading the report from Mayo clinic and the series of letters to the editor that followed. Dodd et al reported 11 patients with pathological gambling who were taking pramipexole for Parkinson Disease (PD). Other dopamine agonists and levodopa have also been implicated. Also other compulsive behaviors have been described.

The authors postulated that the apparent greater prevalence with this particular agonist may be due to its greater effect on the D3 dopamine receptors in the limbic cortex. However, one letter challenged the excess dopamine theory by relating one case of compulsive gambling in a PD patient who was treated with deep brain stimulation of the subthalamic nucleus.

The theory is that with increased dopaminergic stimulation there is increasing loss of impulse control. Supporting this association between dopamine agonist and gambling is the reported reversal of the condition by discontinuing the medication.

A pathologist with PD from Texas has filed a law suit against the manufacturer of the medication.

Does all of this raise philosophical questions about free will ? Can a medication really make some one carry out the complicated acts such as are required to take part in repeated gambling? I would be interested in hearing some thoughts about that.

NPR reports on investigation of possible mercy killing in New Orleans hospital after Katrina

NPR reported on the ongoing investigation of possible euthanasia at Memorial Hospital in New Orleans.

The report describes 4 eyewitnesses that testify about activites that suggest but do not prove patients on the 7th floor ( operated by the Lifecare Hospital) were given lethal doses of drugs after it was decided that the "critical" patients either could not or would not be evacuated. The 7th floor housed a long term facility not operated by the corporation who owned Memorial Hospital.

According to NPR, witnesses described hearing that the decision had been made that the DNR patients on 7 would not be evacuated or left alive after the other patients were evacuated.

Apparently there are no witness testifying that they saw anyone administer the medications.

The New Orleans coroner is quoted as saying the bodies were too decomposed to allow a definitive diagnosis of cause of death.

To date no charges have been filed.

Regardless of the final outcome of the investigation and legal actions that may be taken and what really happened , this is one more sad aspect of the tragic events of Katrina.

Knee osteoarthritis- glucosamine and chondroitin- we still don't know

Seldom are the results of a randomized controlled trial (RCT) so definitive that the issue is settled and and more questions are not raised. The GAIT trial is no exception.

Published in the February 23, 2006 issue of the NEJM this multi-center,placebo and celecoxib controlled trial found that glucosamine hydrocholride and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group..but the combo "may be effective" in the subgroup with moderate to severe knee pain.

"Hydrocholride" is in bold print because as the editorialist suggests, perhaps the"wrong" type of glucosamine was used. While one recent meta-analysis of 8 RCTs showed no difference from placebo when glucosamine hydrochloride was used, another meta-analysis of 7 RCTs which used a particular brand (Rotterpharm brand) of glucosamine sulfate showed significant symptom improvement and functional improvement versus placebo. On the face it appears to be another example of dueling meta-analysis but not if we consider different types of glucosamine. It is possible that the sulfate works better than the hydrocholride. Further, there are two trials that purport to show slowed radiographic progression from the sulfate preparation.

RCTs almost always are paired with an editorial that is replete with many "howevers", "Yes, buts" and "on the other hands" and typically a plea for more data collection. Yet, when the desired data is published there is usually another round of "howevers". There is a reason for that;RCTs often do not settle the issue.

Often , the best we can squeeze out of a RCT is a tentative general "Game plan", subject to future modification or even refutation. Here as the editorial suggested it may be:

If the patient wants to try a nutrional supplement, he should go with glucosamine sulfate plus chondroitin sulfate for about 3 months and if no better discontinue them.

Clinical trials are not rocket science. At its best rocket science deals with deterministic, differential equations that tell us with impressive precision where the rocket will hit absent the ambiguity, uncertainty, seemingly uncontrollable biological variability and the problems that arise from placing too much confidence in our statistical techniques to control for or "quantitate" the uncertainty that are intrinsic to clinical trials.

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.