I have held for a long time an erroneous idea of the risk of disease transmission aboard airplanes.I envisioned the passenger cabin as some sort of 3-d Petri disk crammed full of various viruses and other pathogens.
An excellent article in the July 2007 issue of Mayo Clinic Proceedings corrected my misconceptions. The editorial " Dealing with threat of Drug-resistant Tuberculosis" written by Dr. Priya Sampathkumar is an excellent review of the basics of drug resistant TB and the quality of air in a plane from a medical point of view and can be found free, full text here.
The recent news stories of a person with XDR-TB (extensively drug resistant TB) traveling repeatedly by air from country to country greatly increases the interest level of this article.
He tells us that the recommended rate of air exchanges in a hospital isolation room for TB is 6-12 exchanges per hour. Modern aircraft have 20-30 exchanges per hour.Further,there are high efficiency particular air filters that remove 99.9% of particles that are between 0.1 and 0.3 micra. Mycobacterium is about 0.5 to 1.0 micra. More reassurance comes from the fact that air enters and leaves the cabin at the same seat row so that there is little flow from the front to the back of the plane. Of course, all of this assumes everything is working as it should and as always anything that can work can break down.
Consistent with this description of how the air is handled in planes is the observation that in all instances of transmission of TB on board a commercial airliner occurred to passengers who were seated within 2 rows of the index case.
The scary factor of the Andrew Speaker case was greatly enhanced by the fact he had XDR-TB. Regular-that is drug sensitive TB-is no longer a scary disease. Treatment with first line drugs for six to nine months results in a cure in 95% of patients.MDR-TB is defined as TB being resistant to both INH and Rifampin and treatment with the less effective,often poorly tolerated second line drugs for 18 to 24 months results in cure anywhere from 50% to 70% of the time.
MDR-TB burst on the scene in the early 1990s mainly in patients who were infected with HIV in whom the mortality rate approached 80% and there were reported instances of transmission to health care workers and prison guards.In 2005 there were 95 cases reported in the U.S but according to the National Jewish website 450,000 cases worldwide.
XDR-TB appeared in 2005 in an outbreak in South Africa and is characterized by resistance to INH,Rifampin,a fluroquinolone, and at least one of the three injectable drugs.From 1993 to 2006 in the United states, 49 cases have been reported with 12 deaths and 12 loss to followup.National Jewish has treated a small number of cases and states that their treatment including resectional surgery may result in a 50% cure rate.Until MDR-TB and XDR-TB came on the scene, surgery for TB was largely a history book chapter, not so now.
Thursday, June 28, 2007
Wednesday, June 27, 2007
Some of the unintended consequences of restrictions on house officer hours
The NEJM (June 28,2007) has two commentaries regarding the fall out and continuing analysis of the effects of the changes in house officer hours and rules governing how much time the trainees can work at the hospital.One of the two is available full text for free and can be found here. There is also an audio file interviewing Dr. Ethan Fried, a residency program director.
There is a tension between the hoped-for reduction in errors by having better rested residents and the fear of increased errors and dropped balls by having frequent hand-offs between teams of residents. Dr. Fried believes there may be more risk of the latter in the first day of admission to a hospital but also believes that the supervision and backup by more senior residents can mitigate that tendency.
In addition to the issue of is-the -new- system -less- error prone, there is the fact that since house officers are working less someone else has to. Accordingly, there is a trend to having non-teaching services maned by hospitalists and NPs and PAs at a cost some institutions are hard pressed to bear.
But, in my view even more important is what the new system might do to the evolving competency and mind set of the residents. This issue is discussed by Dr.Wes with his usual insightful analysis.
He wonders if an error free residency what we really want? Do we not learn in part by making errors in an environment where we are buffered and protected by our mentors and more senior colleagues?How will this cohort of residents fare when they are truly out on their own and there will be no team to hand off to when they have been up most of the night taking care of patients and fielding phone calls? Will they call their office and tell them they won't be in until noon because they need their protected ten hours post call ?.
The ACGME kicked off this major change in post graduate medical education in July 2003 and now four years later we seem to be seeing the fall out of a program that may have been initiated and mandated without sufficient planning regarding what now seems obvious collateral effects.The jury is still out regarding if this restricted duty plan actually improves safety or paradoxically has the opposite effect while increasing costs.
When I am old (OK, older) and sick will I want my medical advocate (wife) to insist on a physician who finished his training before July 2003? I have ranted before about the effects of changes in the IM program brought about by ACGME that in my opinion result in a marked loss of the sense of personal responsibility by the doctor for the patient. Teams and systems and protocols and flow charts are no substitute for a physician who believes she is personally responsible for the medical welfare of her patient even if she may be tired. A shift work mentality may be fine for a factory worker but when I grew up medically it was unthinkable for a physician.
There is a tension between the hoped-for reduction in errors by having better rested residents and the fear of increased errors and dropped balls by having frequent hand-offs between teams of residents. Dr. Fried believes there may be more risk of the latter in the first day of admission to a hospital but also believes that the supervision and backup by more senior residents can mitigate that tendency.
In addition to the issue of is-the -new- system -less- error prone, there is the fact that since house officers are working less someone else has to. Accordingly, there is a trend to having non-teaching services maned by hospitalists and NPs and PAs at a cost some institutions are hard pressed to bear.
But, in my view even more important is what the new system might do to the evolving competency and mind set of the residents. This issue is discussed by Dr.Wes with his usual insightful analysis.
He wonders if an error free residency what we really want? Do we not learn in part by making errors in an environment where we are buffered and protected by our mentors and more senior colleagues?How will this cohort of residents fare when they are truly out on their own and there will be no team to hand off to when they have been up most of the night taking care of patients and fielding phone calls? Will they call their office and tell them they won't be in until noon because they need their protected ten hours post call ?.
The ACGME kicked off this major change in post graduate medical education in July 2003 and now four years later we seem to be seeing the fall out of a program that may have been initiated and mandated without sufficient planning regarding what now seems obvious collateral effects.The jury is still out regarding if this restricted duty plan actually improves safety or paradoxically has the opposite effect while increasing costs.
When I am old (OK, older) and sick will I want my medical advocate (wife) to insist on a physician who finished his training before July 2003? I have ranted before about the effects of changes in the IM program brought about by ACGME that in my opinion result in a marked loss of the sense of personal responsibility by the doctor for the patient. Teams and systems and protocols and flow charts are no substitute for a physician who believes she is personally responsible for the medical welfare of her patient even if she may be tired. A shift work mentality may be fine for a factory worker but when I grew up medically it was unthinkable for a physician.
Tuesday, June 19, 2007
Alternative Medicine-homeopathy allowed in ACCP's journal, Chest
I was thumbing through a older issue of the journal, Chest and by looking at the summary and title of a particular article nothing much seemed unusual or really very interesting. However, the last paragraph of the discussion section gave me a very different view .
The title was "Influence of Potassium Dichomate on Tracheal secretions in Critically Ill Patients". Nothing out of the ordinary there. But go down to the affiliation of the authors and we see that three are from a School of Homeopathy in Austria. (Chest/127/3/March 2005, p. 936).
Here is a link to the article.
Then, in the material and methods section we are told that:
"we used a preparation of C30,which is equivalent to a potentiation of 30 dilutions in which each of the 30 dilutions steps is foll0wed by subsequent succussions.Therefore the [well known toxic effects of chromium if undiluted] were eliminated". Certainly at that dilution (a 30C dilution is dilution by a factor of 100 to the 30th power), the test liquid is very unlikely to have any K dichomate in the liquid at all.It is just water. Apparently, in the homeopathy belief system one can make a solution so dilute as to make it non toxic but somehow allow it to retain-or gain-some therapeutic effect.
But the discussion section is best of all. It ends with the following:
While the mechanism of potentized ( diluted and vigorously shaken )drugs remains subject to research...the effect may be best explained by cybernetics,which means that the information of the homeopathic drugs act consensually on the regulator.Thereby, the body regains its original property to regulate physical parameters
This is not written in the language of science but in the language of woo. It is hard to believe that the editors of the journal of the American College of Chest Physicians,none of whom claim to be homeopathic practitioners,would publish such an article.The final paragraph does not even make sense to a non-homeopathic believer and no effort is made to even try and explain what the heck they are taking about when they refer to a drug acting consensually on the regulator or regaining one's original property.
The Journal does a disservice to its readers when it presents a homeopathic jargon filled discussion as if a scientific discussion is taking place. There was no editorial explaining the reasoning behind publishing such an article.One of the characteristics of science is its coherence.The sciences of pharmacology,physiology and toxicology build upon and are consistent with the laws of chemistry and physics.To talk about diluting a substance to the point where it is undetectable and then explaining how it works to heal flies in the face of the principles of those disciplines.It is too late to write a letter to the editor but I hope someone did.
The title was "Influence of Potassium Dichomate on Tracheal secretions in Critically Ill Patients". Nothing out of the ordinary there. But go down to the affiliation of the authors and we see that three are from a School of Homeopathy in Austria. (Chest/127/3/March 2005, p. 936).
Here is a link to the article.
Then, in the material and methods section we are told that:
"we used a preparation of C30,which is equivalent to a potentiation of 30 dilutions in which each of the 30 dilutions steps is foll0wed by subsequent succussions.Therefore the [well known toxic effects of chromium if undiluted] were eliminated". Certainly at that dilution (a 30C dilution is dilution by a factor of 100 to the 30th power), the test liquid is very unlikely to have any K dichomate in the liquid at all.It is just water. Apparently, in the homeopathy belief system one can make a solution so dilute as to make it non toxic but somehow allow it to retain-or gain-some therapeutic effect.
But the discussion section is best of all. It ends with the following:
While the mechanism of potentized ( diluted and vigorously shaken )drugs remains subject to research...the effect may be best explained by cybernetics,which means that the information of the homeopathic drugs act consensually on the regulator.Thereby, the body regains its original property to regulate physical parameters
This is not written in the language of science but in the language of woo. It is hard to believe that the editors of the journal of the American College of Chest Physicians,none of whom claim to be homeopathic practitioners,would publish such an article.The final paragraph does not even make sense to a non-homeopathic believer and no effort is made to even try and explain what the heck they are taking about when they refer to a drug acting consensually on the regulator or regaining one's original property.
The Journal does a disservice to its readers when it presents a homeopathic jargon filled discussion as if a scientific discussion is taking place. There was no editorial explaining the reasoning behind publishing such an article.One of the characteristics of science is its coherence.The sciences of pharmacology,physiology and toxicology build upon and are consistent with the laws of chemistry and physics.To talk about diluting a substance to the point where it is undetectable and then explaining how it works to heal flies in the face of the principles of those disciplines.It is too late to write a letter to the editor but I hope someone did.
Saturday, June 16, 2007
Old wine-new bottles-you have to be a doctor to the whole village?
Dr. David Eddy authored a series of articles in JAMA ( Eddy DM. Rationing resources while improving quality.How to get more for less.JAMA.1994:272,817-824) promising to tell the great unwashed cadre of trench dwelling physicians how they could increase quality and save money at the same time. The trick was the utilitarian imperative-do the greatest good for the greatest number. In his moral calculus it was not only appropriate but it was ethically demanded that, for example, one would not waste money by for example offering yearly mammograms to women between 40 and 50 if a greater bang for the buck could be achieved by offering smoking cessation session to pregnant women. Cost effectiveness analysis was to guide what was offered to the group It was the health of the collective that mattered and that was true even if the collective was a thrown together bunch of strangers whose employers happened to sign up to a given HMO. The traditional fiduciary duty of the doctor to the patient as well as the legal manifestation of that relationship and the aspect of human nature that says I want what is best for my health and my family's health not for some alleged aspect of a fictional collective would have to moved past and we would be on the road to the solution for all that ails American medicine and health care. Doctors should not be hoarding resources for their patients.
Policies create winners and losers , a point that Dr. Eddy did not deny.He spoke of the consequences of "allocating a limited pool of resources to maximize the health of all of the people[in the]pool"even if that meant some would loose out on a benefit. The argument that the "insurance pool" or HMO population or some other organizational collective would gain if the net gains would outweigh the net loses is to endorse a utilitarian ethic but also relies on the cost-benefit assumption that everyone is the same so that costs and benefits can be appropriately aggregated.
In a recent JAMA commentary, the President of the American College of Physicians and the Chief Medical Officer of Aetna ( Dr. Christine K Cassel and Dr. Troyen E.. Brennan) expound on how the ails of American medical care can be remedied. Their exposition seems to me a rehash of Eddy's series although I missed where the authors admitted that there are some who would loose out in the collective cost benefit analysis driven policy decisions.(JAMA ,June 13, 2007, Vol 297, no. 22, p. 2518, "Managing Medical resources.Return to the Commons"
They speak of an abstract hypothetical " medical commons" and how the current emphasis by the physician on the welfare of the individual patient will spoil the commons much as the farmer who selfishly grazes his cattle on public land without regard for depleting the resource will destroy the resource.Physicians are implored to "reconstitute the medical commons" and think in terms of resource conservation and allocation so at the end the greatest medical good can be done for the greatest number of patients.They admit there is not currently such a commons. There never has been so I am unsure how a return is possible.
The medical commons figure of speech seems particularly lame.While a grassy knoll for the villager's sheep can be defined by a specific surveyor description, the "medical commons" is a extremely large amorphous array,the elements of which almost defy enumeration, and every changing, with some elements growing ,others contracting and innovations cropping up constantly.There is no easily defined entity called "medical resources";it is an amorphous abstraction.Further, to speak of allocation means some one or some elite group will be the "allocator in chief ". Decisions will not be made by thousands of individual physician-patient pairs.
Cassel and Brennan assert that a market based or a regulatory approach will allocate resources without the caring and wisdom that clinicians can bring to the endeavor. In their analysis the only choice is a medical commons with physicians and patients moving hand in hand willing to put aside the petty concerns of the individual when necessary for the greatest good of the group.Collectivism has been so successful in the past, why would it not work here?
Does American medicine have many troublesome problems? Yes, it does. I cannot see a rehash of Utilitarian ethics and a very bad analogy and some pie-in-the sky medical collective farm fixing much of anything.
Policies create winners and losers , a point that Dr. Eddy did not deny.He spoke of the consequences of "allocating a limited pool of resources to maximize the health of all of the people[in the]pool"even if that meant some would loose out on a benefit. The argument that the "insurance pool" or HMO population or some other organizational collective would gain if the net gains would outweigh the net loses is to endorse a utilitarian ethic but also relies on the cost-benefit assumption that everyone is the same so that costs and benefits can be appropriately aggregated.
In a recent JAMA commentary, the President of the American College of Physicians and the Chief Medical Officer of Aetna ( Dr. Christine K Cassel and Dr. Troyen E.. Brennan) expound on how the ails of American medical care can be remedied. Their exposition seems to me a rehash of Eddy's series although I missed where the authors admitted that there are some who would loose out in the collective cost benefit analysis driven policy decisions.(JAMA ,June 13, 2007, Vol 297, no. 22, p. 2518, "Managing Medical resources.Return to the Commons"
They speak of an abstract hypothetical " medical commons" and how the current emphasis by the physician on the welfare of the individual patient will spoil the commons much as the farmer who selfishly grazes his cattle on public land without regard for depleting the resource will destroy the resource.Physicians are implored to "reconstitute the medical commons" and think in terms of resource conservation and allocation so at the end the greatest medical good can be done for the greatest number of patients.They admit there is not currently such a commons. There never has been so I am unsure how a return is possible.
The medical commons figure of speech seems particularly lame.While a grassy knoll for the villager's sheep can be defined by a specific surveyor description, the "medical commons" is a extremely large amorphous array,the elements of which almost defy enumeration, and every changing, with some elements growing ,others contracting and innovations cropping up constantly.There is no easily defined entity called "medical resources";it is an amorphous abstraction.Further, to speak of allocation means some one or some elite group will be the "allocator in chief ". Decisions will not be made by thousands of individual physician-patient pairs.
Cassel and Brennan assert that a market based or a regulatory approach will allocate resources without the caring and wisdom that clinicians can bring to the endeavor. In their analysis the only choice is a medical commons with physicians and patients moving hand in hand willing to put aside the petty concerns of the individual when necessary for the greatest good of the group.Collectivism has been so successful in the past, why would it not work here?
Does American medicine have many troublesome problems? Yes, it does. I cannot see a rehash of Utilitarian ethics and a very bad analogy and some pie-in-the sky medical collective farm fixing much of anything.
Friday, June 15, 2007
Oncologists accused of giving chemo.for profit not patient benefit
I do not want to believe that oncologists would give chemotherapy(CMT) to patients who they do not believe would likely benefit simply because they can make a profit on their mark-up on the drugs they administer. I have always had nothing but admiration for oncologists who day by day deal with seriously ill and dying patients and manage to be current and proficient in the variety of cancers they treat and the multiplicity of drug regimens and toxicities and complications.
The ones I have practiced with deserve to be called physicians with all the positive connotations that term can garner.
A recent article in the NYT paints a different picture of some oncologists. Here is some background.For a number of years CMT has been given in oncologists offices. The CMS and third party payers fees exceeded the costs to the docs so there is a make up profit involved. Recently, changes in CMS rules have cut the margin .
The gist of the NYT article is that oncologists are making up for the shortfall with an increase in volume of patients treated with CMT implying that some patients are being given CMT inappropriately.
NYT quotes Dr. Richard Deyo ,a professor at the University of Washington,describing him as a"expert in health care spending" as saying:
There's pretty good evidence at this point that there are plenty of patients for whom there's little hope,who are terminally ill,whom chemotherapy is not going to help, who get chemotherapy
That comment, like most of the NYT article, is heavy on accusations and generalizations and light on supporting data and facts. Dr. Deyo may have analyzed numerous cases and determined that in many instances the CMT was inappropriate but if so I would like to see that analysis. What is the nature of the evidence for his statement? I would be very surprised if Deyo's comments are based on patient level data in which cases are analysed by physicians expert in CMT and wherein inappropriate treatment was found in "plenty of patients". I would not be surprised if that type thing has happened in some cases but I doubt that level of data is what Deyo's statements is based on. Broad brush, coarse grain data is the more likely currency for the type outcomes research that Deyo has been known for (and has gained a well deserved reputation for his work in low back pain treatment outcomes). He may have well done some outcomes research in the CMT area and his comments may have based on that but if there is such data he should have made that fact known to the NYT reporter so the article would appear less like a typical drive-by-media encounter. If he does not have that data, then he may have done disservice to the thousands of patients now receiving CMT who may now wonder if it is avarice and not likelihood of benefit that formed the basis of the decision to treat them.
The ones I have practiced with deserve to be called physicians with all the positive connotations that term can garner.
A recent article in the NYT paints a different picture of some oncologists. Here is some background.For a number of years CMT has been given in oncologists offices. The CMS and third party payers fees exceeded the costs to the docs so there is a make up profit involved. Recently, changes in CMS rules have cut the margin .
The gist of the NYT article is that oncologists are making up for the shortfall with an increase in volume of patients treated with CMT implying that some patients are being given CMT inappropriately.
NYT quotes Dr. Richard Deyo ,a professor at the University of Washington,describing him as a"expert in health care spending" as saying:
There's pretty good evidence at this point that there are plenty of patients for whom there's little hope,who are terminally ill,whom chemotherapy is not going to help, who get chemotherapy
That comment, like most of the NYT article, is heavy on accusations and generalizations and light on supporting data and facts. Dr. Deyo may have analyzed numerous cases and determined that in many instances the CMT was inappropriate but if so I would like to see that analysis. What is the nature of the evidence for his statement? I would be very surprised if Deyo's comments are based on patient level data in which cases are analysed by physicians expert in CMT and wherein inappropriate treatment was found in "plenty of patients". I would not be surprised if that type thing has happened in some cases but I doubt that level of data is what Deyo's statements is based on. Broad brush, coarse grain data is the more likely currency for the type outcomes research that Deyo has been known for (and has gained a well deserved reputation for his work in low back pain treatment outcomes). He may have well done some outcomes research in the CMT area and his comments may have based on that but if there is such data he should have made that fact known to the NYT reporter so the article would appear less like a typical drive-by-media encounter. If he does not have that data, then he may have done disservice to the thousands of patients now receiving CMT who may now wonder if it is avarice and not likelihood of benefit that formed the basis of the decision to treat them.
Thursday, June 14, 2007
JAMA commentary: Medical commons -conflict of interest?
The journal of the American College of Physicians (ACP), the Annals of Internal Medicine, in 2006 featured a five page article in which the former CEO, and then current board member of Aetna, Dr. John W. Rowe, pontificated on the "moral basis for physicians..to participate in...[P4P]." I commented on that article at the time and noted that Aetna's reputation among practicing physicians was such that Dr. Rowe might not have been the most credible witness to present the case for P4P , a movement which the ACP has tended to favor.
More recently, the current President and CEO of the ACP, Dr. Christine K. Cassel, has teamed with another officer of Aetna, Dr. Troyen E. Brennan, to offer further ethical and moral pronouncements regarding the "responsibility" of physicians. This commentary, " Managing Medical Resources-return to the Commons?", can be found in the June 2003,2007 issue of JAMA (vol.297,no.22 pg 2518).
I will leave a more detailed analysis of their apparent proposal for the establishment of "integrated delivery systems" as "accountable care organizations" (sound like big HMO-like entities to me) and the assumption of those groups of responsibility for a population to another time and focus now on what seems to be a major conflict of interest regarding Dr. Brennan.
Early in the article the authors correctly point out that the inclusion of the duty on the part of physicians to "manage medical resources" that is found in the Physician's Charter on Medical Professionalism is controversial as it conflicts with the primary duty of the physician to the patient. They then ask is "this [responsibility] really our duty?
"Our" is used by Dr. Brennan to apparently speak as a member and express commonality with the group of physicians who "live and work in [what he describes] as a medical commons and bear responsibility for it". Dr. Brennan does hold a M.D. degree and has practised medicine but he is currently an officer (A senior vice president) of large insurance company involved in medical insurance and managed care and as such has a fiduciary duty to foster that organization and work to improve its profits.
The authors , later in the commentary, again correctly note that practicing physicians are skeptical about any savings generated by "quality" or P4P programs will find its way to actually improving or expanding medical care. Would not this firmly based skepticism regarding the motives and actions of insurance companies not also target any proposal made by a officer of Aetna?
I cannot understand how officers of ACP and editors of their journal believe that their case for whatever changes they recommended in U.S. health care will be moved forward by having as a partners in that advocacy officers of a insurance company whose business practices ultimately lead to a very large settlement in a class action brought by a number of state medical societies. (Details of that settlement can be found here). When one argues for a given proposal tactical concerns would seem to favor presenting a credible spokesman.
The capitation type system proposed is unlikely to gain traction as long as physicians continue to believe and act as if their primary duty is to the individual patient and not to the collective.This article seems , in part, an effort to disabuse physicians of this ethical imperative which the authors may consider an obstacle to their scheme to "ensure proper allocation of health care resources".
Both Dr. Cassel and Dr. Brennan close their disclosure statement stating that the views expressed are those of the authors and do not necessarily reflect the opinions of either institution. It would be hard to believe that Aetna would allow one of its officers to publish an article in a widely read medical journal without agreeing with its contents.
More recently, the current President and CEO of the ACP, Dr. Christine K. Cassel, has teamed with another officer of Aetna, Dr. Troyen E. Brennan, to offer further ethical and moral pronouncements regarding the "responsibility" of physicians. This commentary, " Managing Medical Resources-return to the Commons?", can be found in the June 2003,2007 issue of JAMA (vol.297,no.22 pg 2518).
I will leave a more detailed analysis of their apparent proposal for the establishment of "integrated delivery systems" as "accountable care organizations" (sound like big HMO-like entities to me) and the assumption of those groups of responsibility for a population to another time and focus now on what seems to be a major conflict of interest regarding Dr. Brennan.
Early in the article the authors correctly point out that the inclusion of the duty on the part of physicians to "manage medical resources" that is found in the Physician's Charter on Medical Professionalism is controversial as it conflicts with the primary duty of the physician to the patient. They then ask is "this [responsibility] really our duty?
"Our" is used by Dr. Brennan to apparently speak as a member and express commonality with the group of physicians who "live and work in [what he describes] as a medical commons and bear responsibility for it". Dr. Brennan does hold a M.D. degree and has practised medicine but he is currently an officer (A senior vice president) of large insurance company involved in medical insurance and managed care and as such has a fiduciary duty to foster that organization and work to improve its profits.
The authors , later in the commentary, again correctly note that practicing physicians are skeptical about any savings generated by "quality" or P4P programs will find its way to actually improving or expanding medical care. Would not this firmly based skepticism regarding the motives and actions of insurance companies not also target any proposal made by a officer of Aetna?
I cannot understand how officers of ACP and editors of their journal believe that their case for whatever changes they recommended in U.S. health care will be moved forward by having as a partners in that advocacy officers of a insurance company whose business practices ultimately lead to a very large settlement in a class action brought by a number of state medical societies. (Details of that settlement can be found here). When one argues for a given proposal tactical concerns would seem to favor presenting a credible spokesman.
The capitation type system proposed is unlikely to gain traction as long as physicians continue to believe and act as if their primary duty is to the individual patient and not to the collective.This article seems , in part, an effort to disabuse physicians of this ethical imperative which the authors may consider an obstacle to their scheme to "ensure proper allocation of health care resources".
Both Dr. Cassel and Dr. Brennan close their disclosure statement stating that the views expressed are those of the authors and do not necessarily reflect the opinions of either institution. It would be hard to believe that Aetna would allow one of its officers to publish an article in a widely read medical journal without agreeing with its contents.
Wednesday, June 13, 2007
Whole new ball game-case in point Avandia
The spin-off as well as the spin seems endless in regard to the Avandia issue.Nissen's NEJM article catalyzed various reactions many of which were predictable at least in direction if not in intensity. Predictable downstream effects included the reactions by GSK,by pro and anti Pharma blogs and Grass root and astro turf patient-interest groups and by plaintiff attorneys. Also expected are thoughtful posts by medical bloggers such as the one entitled "Avandia:two questions" by Dr. RW. and "The Avandia spin cycle" found at Health Care Renewal.
One of the latest developments is a class action suit by stock holders of GSK accusing the directors of withholding information about the cardiac risk of Avandia. The directors are accused of not providing adequate data to stockholders regarding the company's meta-analysis of cardiovascular deaths that was reported to the FDA.
Over thirty years ago another medical publication dealt with a purported increase in cardio vascular deaths from an oral diabetic medication. The University Group Diabetes Program (UGDP) was presented at the June 1970 meeting of the American Diabetes Association. Data presented indicated that tolbutamide increased cardiovascular deaths by over two and a half times.( R.R of 2.61, C.I.-1.29-5.27 It did not take long for the UGDP study to be referred to as the "controversial" UGDP.
The dispute over methodological issues was played out largely out of the public eye and patients and physicians alike had to largely rely on medical journal hard copy publications to follow the events that they unfolded in what would be considered slow motion in today's frenetic internet pace.Today with the Web within minutes the word spreads over the world and quickly bloggers and news sites and lawyers post messages. It is not long before a Senate hearing is held.
The UGDP study in many ways presented more robust evidence that the Nissen article.It was a randomized clinical trial ( Yes Virginia, clinical trials were done before the folks from Canada descended from the mountain with the precepts of EBM carved into stone) and the R.R. was greater than 2, a number less than which many epidemiologists put little weight as small RR's can be pushed around by small biases.Putting too much emphasis on medical analyses which derive RR's less than 2 has been a issue of interest to me for some time and I have ranted on about that before.
In time, the reputation of the class of diabetic drugs to which tolbutamide belonged was salvaged to some degree by proposing that tolbutamide might interfere with a purported pathophysiologic mechanism called "ischemic preconditioning" while others drugs in this family might not. At the end of the day, a PDR sulfonylurea family warning was issued. As new drugs have been developed to treat type 2 diabetes little discussion seems to take place about these drugs while they continue to be used with little alarm about causing heart attacks.
Sometimes controversies just die out without really being settled with apodictic medical certainty.I think that was the case with tolbutamide.Many articles critical and supportive of the UGDP were generated and for the most part probably largely unread and were it not for the internet amplified and magnified Avandia issue few would even currently think about a possible increase in c-v risk from the sulfonylureas which are still widely used in the early treatment phases of type 2 diabetes. The dogs bark and the caravan moves on.Today with the internet the dogs seem to be able to do much more than just bark.
One of the latest developments is a class action suit by stock holders of GSK accusing the directors of withholding information about the cardiac risk of Avandia. The directors are accused of not providing adequate data to stockholders regarding the company's meta-analysis of cardiovascular deaths that was reported to the FDA.
Over thirty years ago another medical publication dealt with a purported increase in cardio vascular deaths from an oral diabetic medication. The University Group Diabetes Program (UGDP) was presented at the June 1970 meeting of the American Diabetes Association. Data presented indicated that tolbutamide increased cardiovascular deaths by over two and a half times.( R.R of 2.61, C.I.-1.29-5.27 It did not take long for the UGDP study to be referred to as the "controversial" UGDP.
The dispute over methodological issues was played out largely out of the public eye and patients and physicians alike had to largely rely on medical journal hard copy publications to follow the events that they unfolded in what would be considered slow motion in today's frenetic internet pace.Today with the Web within minutes the word spreads over the world and quickly bloggers and news sites and lawyers post messages. It is not long before a Senate hearing is held.
The UGDP study in many ways presented more robust evidence that the Nissen article.It was a randomized clinical trial ( Yes Virginia, clinical trials were done before the folks from Canada descended from the mountain with the precepts of EBM carved into stone) and the R.R. was greater than 2, a number less than which many epidemiologists put little weight as small RR's can be pushed around by small biases.Putting too much emphasis on medical analyses which derive RR's less than 2 has been a issue of interest to me for some time and I have ranted on about that before.
In time, the reputation of the class of diabetic drugs to which tolbutamide belonged was salvaged to some degree by proposing that tolbutamide might interfere with a purported pathophysiologic mechanism called "ischemic preconditioning" while others drugs in this family might not. At the end of the day, a PDR sulfonylurea family warning was issued. As new drugs have been developed to treat type 2 diabetes little discussion seems to take place about these drugs while they continue to be used with little alarm about causing heart attacks.
Sometimes controversies just die out without really being settled with apodictic medical certainty.I think that was the case with tolbutamide.Many articles critical and supportive of the UGDP were generated and for the most part probably largely unread and were it not for the internet amplified and magnified Avandia issue few would even currently think about a possible increase in c-v risk from the sulfonylureas which are still widely used in the early treatment phases of type 2 diabetes. The dogs bark and the caravan moves on.Today with the internet the dogs seem to be able to do much more than just bark.
Monday, June 04, 2007
Seafood, x-ray contrast material allergies and Iodine
A long standing dogma is that seafood allergies and radiologic contrast material (RCM) allergies are both due to an iodine allergy and therefore a history of seafood allergy places a person at high risk of an allergy reaction to RCM.
Dr. Andrew D.Berry gave a talk at a recent meeting of the American Academy of Allergy,Asthma and Immunology (reported in the may 11,2007 edition of www.internalmedicinenews.com) that should disabuse doctors of what seems to be a medical myth.
According to the article-seafood allergy is due to a IgE mediated antibody to certain proteins in the seafood and the severe RCM reactions are not mediated by IgE at all.
Dr. Berry reported on a survey in which many radiologists and cardiologists would recommend pretreatment with antihistamines and/or steroid for a patient with a history of seafood allergy before injecting a RCM.
Dr. Andrew D.Berry gave a talk at a recent meeting of the American Academy of Allergy,Asthma and Immunology (reported in the may 11,2007 edition of www.internalmedicinenews.com) that should disabuse doctors of what seems to be a medical myth.
According to the article-seafood allergy is due to a IgE mediated antibody to certain proteins in the seafood and the severe RCM reactions are not mediated by IgE at all.
Dr. Berry reported on a survey in which many radiologists and cardiologists would recommend pretreatment with antihistamines and/or steroid for a patient with a history of seafood allergy before injecting a RCM.
Sunday, June 03, 2007
Pneumonia guidelines-Europe versus U.S.
The American Thoracic Society (ATS) and the Infectious Disease Society of America (IDSA) agree that the empiric therapy of mild community acquired pneumonia (CAP) should include coverage for the atypical pathogens.These are Mycoplasma,Chlamydia and Legionella.
In Europe, although ID physicians agree that about 40% of CAP is due to the atypicals,that beta-lactam antibiotics alone should be used anyway even though they have no activity against the atypicals. They argue that these pathogens (except for Legionella)usually cause mild, self-limiting illnesses and that adding broader coverage medications will exacerbate the public health problem of increasing antibiotics resistance.In the U.S, typically, a macrolide would be included in the treatment of CAP.
ID docs in the U.S. argue that the illnesses are shortened by broader coverage and there is also data showing a decreased mortality in hospitalized patients with CAP.One could argue that if hospitalization is needed that the CAP is more than mild.
The European approach seems to place a theoretical concern above individual patient concerns.Further a chest x ray is apparently not required to diagnose pneumonia so it can be argued they over treat viral bronchitis and add to the growing resistance problem. It is hard to argue against the view that more antibiotic use may lead to more pathogen resistance but you have to wonder how much effect under treating CAP would have to mitigate that trend.
In Europe, although ID physicians agree that about 40% of CAP is due to the atypicals,that beta-lactam antibiotics alone should be used anyway even though they have no activity against the atypicals. They argue that these pathogens (except for Legionella)usually cause mild, self-limiting illnesses and that adding broader coverage medications will exacerbate the public health problem of increasing antibiotics resistance.In the U.S, typically, a macrolide would be included in the treatment of CAP.
ID docs in the U.S. argue that the illnesses are shortened by broader coverage and there is also data showing a decreased mortality in hospitalized patients with CAP.One could argue that if hospitalization is needed that the CAP is more than mild.
The European approach seems to place a theoretical concern above individual patient concerns.Further a chest x ray is apparently not required to diagnose pneumonia so it can be argued they over treat viral bronchitis and add to the growing resistance problem. It is hard to argue against the view that more antibiotic use may lead to more pathogen resistance but you have to wonder how much effect under treating CAP would have to mitigate that trend.
Monday, May 28, 2007
Recognition of adverse effects-no quick and dirty way
The recent flurry of scientific comment, speculation, 6 o'clock news type hype, accusations about everyone concerned-except perhaps patients- and thoughtful commentary about the possibility that Avandia increases the risk of ischemic events makes me sit back and think about how did we get to where we are.
The randomized clinical trial is unrivaled in its ability-when properly done-to defy the confounders and the biases and point to a treatment that is efficacious and provides some information about adverse effects and can compare fairly the treated and untreated groups. It deserves its place as king of the hill in the realm of evidence and evidence based medicine because of its ability to eliminate selection bias and ideally chase away the known and unknown confounders that seem to lurk everywhere.
However, in regard to adverse effects (AE) detection RCTS are imperfect and not the most powerful tool in the shed. RCTs are typically short lived and even the larger ones often are too small to have adequate power to detect low frequency AEs. Further,RCTs are designed to demonstrate efficacy-or in some cases the much weaker standard of proof- non-inferiority. The patients in the trial often are less diverse and complicated that a typical subset of patients from real clinical life that will likely be taking the medication.This commentary by Ioannidis,Goodman and Mulrow in the Annals of Internal Medicine speaks more authoritatively that I can in regard to this point emphasizing the limitations of randomized trials in this regard. Further, they make suggestion to make postmarketing surveillance more "routine and efficient".
"Routine and efficient" certainly seems lacking as lately alarm about AEs associated with two blockbuster drugs was sounded by cardiologists and statisticians at Cleveland Clinic rather than the drug manufacturers or the FDA. Regardless of how correct or misleading their analysis may ultimately turn out to be (if there is ever an "ultimately"), I doubt we can always rely or a Dr. Nissen or whoever to oversee the vast drug related adverse effect data set.
It falls on the shoulders of case reports and observational data and meta-analyses to fill in the gaps regarding those less common AEs and those that only develop after the patient has been on the medication for a longer period of time.Sometimes these AEs burst on the headline news with alarming findings as with drug eluting stents,Vioxx, Ketek, and now,it seems, Avandia. They certainly can be alarming but they should not be surprising.
With more patients, and more time, more AEs will become apparent but the AEs have to be plucked out of a data which is plagued by potential confounders, the management of which has generated various statistical techniques which ,in my opinion,exceeds the level of statistical expertise possessed by most physicians and medical journal editors. I have written before about the difficulty in choosing between competing techniques proposed to tame the observational data.
So the RCT may just be the beginning of the data accumulation. The RCT is also the beginning of the onslaught of information,dis-information, useful educational material, misleading spin and well thought out marketing efforts of the drug manufacturer,educational efforts by patient organizations, guidelines from various groups and delicious "educational company"sponsored dinners punctuated by "thought leader" physicians showing slides typically prepared by the company.
Hopefully, postmarketing trials will come more efficient and routine and timely (Nissen's Avandia meta-analysis appeared about 8 years after FDA approval), but this will require a greater or more forceful role for the FDA-an agency which currently enjoys a reputation only slightly less tarnished than big Pharma. Something positive may come out of congressional hearings into various activities of the FDA and then perhaps remedial legislation but is not the current FDA the product of earlier congressional efforts to mitigate what was considered at the time by some a dangerously slow medication approval process?
Meanwhile, until a new day appears, we need to not be overly reassured by "negative findings" regarding side effects derived from RCTs. Ioannidis and co-authors included this quote in the above referenced commentary:
"It is almost always inappropriate to make statements about "no difference"in adverse event rates between groups on the basis of nonsignificant P values. Rates of adverse events that are derived from single,modest sized trials that are not statistically different typically do not exclude with certainty the possibility of major, clinically important differences in harms between groups."
The randomized clinical trial is unrivaled in its ability-when properly done-to defy the confounders and the biases and point to a treatment that is efficacious and provides some information about adverse effects and can compare fairly the treated and untreated groups. It deserves its place as king of the hill in the realm of evidence and evidence based medicine because of its ability to eliminate selection bias and ideally chase away the known and unknown confounders that seem to lurk everywhere.
However, in regard to adverse effects (AE) detection RCTS are imperfect and not the most powerful tool in the shed. RCTs are typically short lived and even the larger ones often are too small to have adequate power to detect low frequency AEs. Further,RCTs are designed to demonstrate efficacy-or in some cases the much weaker standard of proof- non-inferiority. The patients in the trial often are less diverse and complicated that a typical subset of patients from real clinical life that will likely be taking the medication.This commentary by Ioannidis,Goodman and Mulrow in the Annals of Internal Medicine speaks more authoritatively that I can in regard to this point emphasizing the limitations of randomized trials in this regard. Further, they make suggestion to make postmarketing surveillance more "routine and efficient".
"Routine and efficient" certainly seems lacking as lately alarm about AEs associated with two blockbuster drugs was sounded by cardiologists and statisticians at Cleveland Clinic rather than the drug manufacturers or the FDA. Regardless of how correct or misleading their analysis may ultimately turn out to be (if there is ever an "ultimately"), I doubt we can always rely or a Dr. Nissen or whoever to oversee the vast drug related adverse effect data set.
It falls on the shoulders of case reports and observational data and meta-analyses to fill in the gaps regarding those less common AEs and those that only develop after the patient has been on the medication for a longer period of time.Sometimes these AEs burst on the headline news with alarming findings as with drug eluting stents,Vioxx, Ketek, and now,it seems, Avandia. They certainly can be alarming but they should not be surprising.
With more patients, and more time, more AEs will become apparent but the AEs have to be plucked out of a data which is plagued by potential confounders, the management of which has generated various statistical techniques which ,in my opinion,exceeds the level of statistical expertise possessed by most physicians and medical journal editors. I have written before about the difficulty in choosing between competing techniques proposed to tame the observational data.
So the RCT may just be the beginning of the data accumulation. The RCT is also the beginning of the onslaught of information,dis-information, useful educational material, misleading spin and well thought out marketing efforts of the drug manufacturer,educational efforts by patient organizations, guidelines from various groups and delicious "educational company"sponsored dinners punctuated by "thought leader" physicians showing slides typically prepared by the company.
Hopefully, postmarketing trials will come more efficient and routine and timely (Nissen's Avandia meta-analysis appeared about 8 years after FDA approval), but this will require a greater or more forceful role for the FDA-an agency which currently enjoys a reputation only slightly less tarnished than big Pharma. Something positive may come out of congressional hearings into various activities of the FDA and then perhaps remedial legislation but is not the current FDA the product of earlier congressional efforts to mitigate what was considered at the time by some a dangerously slow medication approval process?
Meanwhile, until a new day appears, we need to not be overly reassured by "negative findings" regarding side effects derived from RCTs. Ioannidis and co-authors included this quote in the above referenced commentary:
"It is almost always inappropriate to make statements about "no difference"in adverse event rates between groups on the basis of nonsignificant P values. Rates of adverse events that are derived from single,modest sized trials that are not statistically different typically do not exclude with certainty the possibility of major, clinically important differences in harms between groups."
Wednesday, May 23, 2007
Avandia manufacturer issues reply to NEJM article
On their website GSK presents some arguments and evidence to counter the headline-producing NEJM article by Dr. Nissen,who is getting the reputation of the Drugslayer. The NEJM meta-analysis implicated rosiglitazone with causing an increase in cardiovascular events. Denials of heart attack risk by GSK and the complexity and obscure fine points of analysing meta-analysis and ongoing monitoring projects notwithstanding,the drug is in trouble and it is more bad news for the rapidly diminishing reputation of the FDA.
A recent (May 22,2007) entry by Dr. Roy Poses gives us some useful context for the Nissen article and related events and is well worth reading.
Patients who are currently taking Avandia are referred to their physician for advice and counseling. What the doctor ought to say to his patient is not all that clear. This post by Dr. Charles links to an article that tells us what Dr. Psaty says he would tell patients. Psaty was a co-author of the editorial discussing the meta-analysis.
After you read the NEJM article and the related editorial and the reply by GSK you may well reach the conclusion that there seems to be an increased risk of ischemic events with rosiglitazone) and so far probably not with Actos ( pioglitazone) as some data suggest risk may be a little lower with Actos.Or you may conclude the data are not sufficient to change anything. Does an action item flow from that tentative conclusion that there is an increased risk? Should you stop Avandia?
GSK tells us that they have data which does not support Dr. Niessen's findings. I would like someone with more meta-analytical skills than I have to explain why it is fair to exclude those trials in which there were no deaths, which is what Nessin did.I expect we will hear a lot more statistical jabs back and forth before we hear the end of this issue.
Should you switch to Actos? Maybe your patient is taking Avandia becuase that is the only glitizone that his insurance plan will allow.Should you tell the patient lets just wait and see ? Will the FDA act and do something to take the physician off the hook? Will a meta-analysis be forthcoming that suggests metformin increases cardiovascular events?
A recent (May 22,2007) entry by Dr. Roy Poses gives us some useful context for the Nissen article and related events and is well worth reading.
Patients who are currently taking Avandia are referred to their physician for advice and counseling. What the doctor ought to say to his patient is not all that clear. This post by Dr. Charles links to an article that tells us what Dr. Psaty says he would tell patients. Psaty was a co-author of the editorial discussing the meta-analysis.
After you read the NEJM article and the related editorial and the reply by GSK you may well reach the conclusion that there seems to be an increased risk of ischemic events with rosiglitazone) and so far probably not with Actos ( pioglitazone) as some data suggest risk may be a little lower with Actos.Or you may conclude the data are not sufficient to change anything. Does an action item flow from that tentative conclusion that there is an increased risk? Should you stop Avandia?
GSK tells us that they have data which does not support Dr. Niessen's findings. I would like someone with more meta-analytical skills than I have to explain why it is fair to exclude those trials in which there were no deaths, which is what Nessin did.I expect we will hear a lot more statistical jabs back and forth before we hear the end of this issue.
Should you switch to Actos? Maybe your patient is taking Avandia becuase that is the only glitizone that his insurance plan will allow.Should you tell the patient lets just wait and see ? Will the FDA act and do something to take the physician off the hook? Will a meta-analysis be forthcoming that suggests metformin increases cardiovascular events?
Friday, May 18, 2007
SIADH or SIAD-where did the "h" go and does it matter?
Fifty years ago the syndrome of inappropriate secretion of anti-diuretic hormone was described in a lung cancer patient and the term SIADH (Syndrome of inappropriate anti-diuretic hormone secretion) entered the medical vocabulary. The anti-diuretic hormone was later identified as arginine vasopressin (AVP). I have thought for some time that things would have been simpler and easier to think about if instead of anti-diuretic hormone this water retaining hormone would have actually been called "water retaining hormone" but its too late now.
A recent article in NEJM informs the readers that only about one-third of cases of SIADH have non-suppressed levels of arginine vasopressin so that the term "Syndrome of Inappropriate Antidiuresis " is more correct or appropriate.
I thought this was something new rather than some subtlety I have just missed but a perfunctory Google search leads to more than one not- very- recent article than used that term in the sense of SIADH being a subset of SIAD. So the term has been around for more than a year or two.
So what is the pathophysiology in those cases without levels of ADH that are too high for the situation? In some the "osmostat" is reset.This means that ADH release is suppressed only at a lower level of serum osmolality than normal. In other cases, the vasopressin renal receptor is somehow able to concentrate urine even in the absence of arginine vasopressin.These variation in the aquaporin receptor-recently reported in the NEJM bring about a Nephrogenic syndrome of inappropriate antidiuresis.
The authors of the Clinical Practice Review in the May 17.2007 NEJM (Ellison DH and Berl T, MEJM 356;20 p 2064) state that:
"Measurement of the serum level of arginine vasopressin is not recommended routinely, because urinary osmolality above 100 mOsm per kilogram of water is usually sufficient to indicate excess circulating arginine vasopressin."
I am confused by this. I had considered an osmolality above 100 an important criterion for the diagnosis. Yet we are told that only about 1/3 of cases ( that meet the criteria that include the urine osmolality criterion) a have elevated arginine vasopressin.So the urine osmolality criterion does not mean elevated AVP is about 2/3 of cases. In fact, had the authors of the article that described the aquaporin mutations made that assumption the syndrome might still await description and a entire new avenue of water balance physiology would not have been opened.
In any event, apparently the presence or absence of the "h" seems to make no difference in the recommended therapy which as the authors clearly indicate is fraught with disagreement about the specifics.
Treatment has always seemed to involve avoiding hard places and rocks. One risk is that the cerebral edema induced by the hypo-osmolality is clearly a bad thing and should not be allowed to persist and worsen and on the other hand there is the somewhat mysterious spectre of osmotic demyelination which is typically referred to by one of it forms namely central pontine myelinolysis. Here is an excellent 1997 reference which includes a description of the impressive deductive abilities of the ancient ( circa 1940s and 1950s) neurologists who seemed to be able to see into the brain without benefit of MRIs and described the pontine loss of myelin.
The myelinolysis seems to be caused by too rapid correction of the hyponatremia, at least that is the consensus theory while some authors still blame the severe hyponatremia per se.But how rapid is too rapid?It is thought to be more likely to occur with correction in chronic cases ( the brain cells seems to adapt to hyponatremia by loosing osmotically active molecules and thereby limiting the degree of cerebral edema.)
If most-according to the recent NEJM review) cases do not actually have elevated ADH levels ,what does that mean for the efficacy or safety of the "vaptan" group of drugs. There are at least four vasopressin-receptor antagonists with one intravenous drug (conivaptan-trade name Vaprisol) approved already and oral prparations in the drug pipeline. I wonder if the ADH level is not high what good (harm?) would happen if they are used and the ADH level is not the culprit?
A recent article in NEJM informs the readers that only about one-third of cases of SIADH have non-suppressed levels of arginine vasopressin so that the term "Syndrome of Inappropriate Antidiuresis " is more correct or appropriate.
I thought this was something new rather than some subtlety I have just missed but a perfunctory Google search leads to more than one not- very- recent article than used that term in the sense of SIADH being a subset of SIAD. So the term has been around for more than a year or two.
So what is the pathophysiology in those cases without levels of ADH that are too high for the situation? In some the "osmostat" is reset.This means that ADH release is suppressed only at a lower level of serum osmolality than normal. In other cases, the vasopressin renal receptor is somehow able to concentrate urine even in the absence of arginine vasopressin.These variation in the aquaporin receptor-recently reported in the NEJM bring about a Nephrogenic syndrome of inappropriate antidiuresis.
The authors of the Clinical Practice Review in the May 17.2007 NEJM (Ellison DH and Berl T, MEJM 356;20 p 2064) state that:
"Measurement of the serum level of arginine vasopressin is not recommended routinely, because urinary osmolality above 100 mOsm per kilogram of water is usually sufficient to indicate excess circulating arginine vasopressin."
I am confused by this. I had considered an osmolality above 100 an important criterion for the diagnosis. Yet we are told that only about 1/3 of cases ( that meet the criteria that include the urine osmolality criterion) a have elevated arginine vasopressin.So the urine osmolality criterion does not mean elevated AVP is about 2/3 of cases. In fact, had the authors of the article that described the aquaporin mutations made that assumption the syndrome might still await description and a entire new avenue of water balance physiology would not have been opened.
In any event, apparently the presence or absence of the "h" seems to make no difference in the recommended therapy which as the authors clearly indicate is fraught with disagreement about the specifics.
Treatment has always seemed to involve avoiding hard places and rocks. One risk is that the cerebral edema induced by the hypo-osmolality is clearly a bad thing and should not be allowed to persist and worsen and on the other hand there is the somewhat mysterious spectre of osmotic demyelination which is typically referred to by one of it forms namely central pontine myelinolysis. Here is an excellent 1997 reference which includes a description of the impressive deductive abilities of the ancient ( circa 1940s and 1950s) neurologists who seemed to be able to see into the brain without benefit of MRIs and described the pontine loss of myelin.
The myelinolysis seems to be caused by too rapid correction of the hyponatremia, at least that is the consensus theory while some authors still blame the severe hyponatremia per se.But how rapid is too rapid?It is thought to be more likely to occur with correction in chronic cases ( the brain cells seems to adapt to hyponatremia by loosing osmotically active molecules and thereby limiting the degree of cerebral edema.)
If most-according to the recent NEJM review) cases do not actually have elevated ADH levels ,what does that mean for the efficacy or safety of the "vaptan" group of drugs. There are at least four vasopressin-receptor antagonists with one intravenous drug (conivaptan-trade name Vaprisol) approved already and oral prparations in the drug pipeline. I wonder if the ADH level is not high what good (harm?) would happen if they are used and the ADH level is not the culprit?
Thursday, May 17, 2007
Screening for abdominal aortic aneurysm-looks like a good idea
The May 15,2007 issue of the Annals of Internal Medicine features several articles and an editorial strongly supporting screening for AAAs -at least in men 64 to 74 years of age ,if they ever smoked ( I guess when you get to 75 you are too old to worry about).The USPSTF recommends one time screening for men aged 64 to 75 who have ever smoked but not for the never-smokers. The Annals editorial makes a reasonable argument that non-smokers should be included as well.
One of the articles, done in Great Britain, indicated than the screening is even cost effective.
There is a systematic review (Lederle et al)of treatment of unruptured abdominal aortic aneurysms which found for those aneurysms less than 5.5. cm in diameter no benefit was demonstrated either in all cause or in AAA related mortality.
However,for larger aneurysms and rapidly enlarging aneurysms repair is indicated. I say "repair" because now there is an alternative to the major AAA surgery in the form of a endovascular repair, about which the jury is out regarding the long term results. Certaintly the post procedure recovery time is much more pleasant with the endo aproach.
According to the MKSAP 14,( pg. 72 of the Cardiovascular Medicine booklet) surgery is indicated for AAA greater then 5.5cm in men and for those greater than 4.5. to 5.0 in women. A ruptured AAA is said to have an approximately 80% mortality. One of my former partners collapsed in the hospital while rounding and was very quickly attended by an excellent vascular surgeon who quickly diagnosed the problem and in spite of a rush to the O.R. and a very expeditious effort at surgery, he died on the table.
Ever alert as I am to gratuitous comments promoting P4P particularly from the American College of Physicians, I could not help but chaff a bit at one comment slipped into the editorial.
"AAA screening should be considered ...in pay-for-performance and other large- scale quality initiatives"
I can remember a time-not that long ago really-when a recommendation was made because it was the right thing to do for the patient not because of P4P (aka being bribed to do the right thing) and not because some insurance entity was going to check to see if we had done it according to their version of what should be done.
One of the articles, done in Great Britain, indicated than the screening is even cost effective.
There is a systematic review (Lederle et al)of treatment of unruptured abdominal aortic aneurysms which found for those aneurysms less than 5.5. cm in diameter no benefit was demonstrated either in all cause or in AAA related mortality.
However,for larger aneurysms and rapidly enlarging aneurysms repair is indicated. I say "repair" because now there is an alternative to the major AAA surgery in the form of a endovascular repair, about which the jury is out regarding the long term results. Certaintly the post procedure recovery time is much more pleasant with the endo aproach.
According to the MKSAP 14,( pg. 72 of the Cardiovascular Medicine booklet) surgery is indicated for AAA greater then 5.5cm in men and for those greater than 4.5. to 5.0 in women. A ruptured AAA is said to have an approximately 80% mortality. One of my former partners collapsed in the hospital while rounding and was very quickly attended by an excellent vascular surgeon who quickly diagnosed the problem and in spite of a rush to the O.R. and a very expeditious effort at surgery, he died on the table.
Ever alert as I am to gratuitous comments promoting P4P particularly from the American College of Physicians, I could not help but chaff a bit at one comment slipped into the editorial.
"AAA screening should be considered ...in pay-for-performance and other large- scale quality initiatives"
I can remember a time-not that long ago really-when a recommendation was made because it was the right thing to do for the patient not because of P4P (aka being bribed to do the right thing) and not because some insurance entity was going to check to see if we had done it according to their version of what should be done.
Wednesday, May 16, 2007
Patient-Centered Care-what does it mean?
If you ask patients or other physicians what " patient centered care" (PCC) means I believe you would hear comments like these:
"care in which the doctor places the patient and his/her interests first",
"the physician treats the patients with respect and dignity"
"it's putting the patient first,caring about the patient,treating the patient like you would like to be treated, respecting the patient's values"
These are actual quotes or paraphrases of answers I have heard for doctors and patients and friends.
The Institute of Medicine's definition captures some of this in the following;
"Providing care that is respectful of and responsive to individual patient preferences,needs and values and ensuring that patient values guide all clinical decisions."
Who could argue with that and would not that be a sufficient imperative and worthy objective?
Apparently that is not enough in the eyes of some medical policy wonks.
Authors from the "Quality Improvement Program of the Commonwealth Fund" have declared their " 7 attributes for primary care practices " are something that patients " will value highly".
Their article in the Archives of Internal Medicine describes the results of a survey which inquired about the degree to which their stipulated definition of PCC was incorporated into a set of primary practices that they sent survey questions..
Their comments section emphasize the poor showing in regard to two areas in particular which apparently have risen to issues of major importance: the development of patient registries and patient feedback surveys. We learn that, for example that the American Board of Internal Medicine now requires in their competency maintenance scheme that physicians show competence in patient registries development and survey feedback.
They conclude stating "physicians should be well positioned (once they get the right tools) to provide the services and care that patients want and have the right to expect"
"The right to expect patient surveys" ??
We have come quite a ways from the simple admonition in 1927 by Francis W. Peabody that; "the secret of the care of the patient is caring for the patient." No easy survey audit of that is available.
I think that is what this is all about.People who are making a career at least in part by being quality gurus and who strive to be the judges of quality care need to have "quality indicators" that are easily measurable.They thrive on the search for rules in a world of exceptions and quick and dirty ways to determine if someone else is practicing their version of quality care.
Patient surveys have suggested patients want their doctors to be through,caring, respectful,and I suggest patients could not care less if they are given a survey or are aware that there is a patient registry or if their physician uses a computer based decision making program.
Using electronic means to have real time updated information about your patient and about current medical knowledge and consensus recommendations is important and offers great promise as are workable, efficient office management techniques (appointment access , facilitating consultations and referrals and lab test followup etc.) but..
Measuring how good you are as a physician by asking if you do surveys and have a patient registry is specious. It is form over substance. It is also using words that have a general common sense meaning -patient centered- to mean a list of requirements made up by one or more groups of self appointed experts in quality that may or may not have any direct relationship to level of care or the level of patient satisfaction.
The ACGME and ABIM have "determined" that a key competency of internists involves during patient surveys. Where is the evidence that surveys about services received a)reflects what the recipient really wants or values b)has been linked to any meaningful changes in medical practice with associated outcome changes?
Some data may exist but it seems to be that ABIM and ACGME have adopted this feel-good position even without the solid evidence base of the evidence based medicine to which everyone is obligated to pledge allegiance in every medical publication. Interestingly, in this Archives article, the authors offer no evidence to the efficacy or safety of their proposal and simply quote "authorities" including themselves.
Physicians practiced patient centered medicine-in the sense of what people generally think such a term would mean-before there were computers, patient surveys and patient data bases and will continue to be practiced as long as the physician does in fact place the patient first and takes seriously his fiduciary duty to the individual patient. That duty will be harder and harder to fulfill the more guidelines,rules,P4P imperatives,quality newspeak and CMS directives impinge upon and exert a demoralizing control over medical practice.
"care in which the doctor places the patient and his/her interests first",
"the physician treats the patients with respect and dignity"
"it's putting the patient first,caring about the patient,treating the patient like you would like to be treated, respecting the patient's values"
These are actual quotes or paraphrases of answers I have heard for doctors and patients and friends.
The Institute of Medicine's definition captures some of this in the following;
"Providing care that is respectful of and responsive to individual patient preferences,needs and values and ensuring that patient values guide all clinical decisions."
Who could argue with that and would not that be a sufficient imperative and worthy objective?
Apparently that is not enough in the eyes of some medical policy wonks.
Authors from the "Quality Improvement Program of the Commonwealth Fund" have declared their " 7 attributes for primary care practices " are something that patients " will value highly".
Their article in the Archives of Internal Medicine describes the results of a survey which inquired about the degree to which their stipulated definition of PCC was incorporated into a set of primary practices that they sent survey questions..
Their comments section emphasize the poor showing in regard to two areas in particular which apparently have risen to issues of major importance: the development of patient registries and patient feedback surveys. We learn that, for example that the American Board of Internal Medicine now requires in their competency maintenance scheme that physicians show competence in patient registries development and survey feedback.
They conclude stating "physicians should be well positioned (once they get the right tools) to provide the services and care that patients want and have the right to expect"
"The right to expect patient surveys" ??
We have come quite a ways from the simple admonition in 1927 by Francis W. Peabody that; "the secret of the care of the patient is caring for the patient." No easy survey audit of that is available.
I think that is what this is all about.People who are making a career at least in part by being quality gurus and who strive to be the judges of quality care need to have "quality indicators" that are easily measurable.They thrive on the search for rules in a world of exceptions and quick and dirty ways to determine if someone else is practicing their version of quality care.
Patient surveys have suggested patients want their doctors to be through,caring, respectful,and I suggest patients could not care less if they are given a survey or are aware that there is a patient registry or if their physician uses a computer based decision making program.
Using electronic means to have real time updated information about your patient and about current medical knowledge and consensus recommendations is important and offers great promise as are workable, efficient office management techniques (appointment access , facilitating consultations and referrals and lab test followup etc.) but..
Measuring how good you are as a physician by asking if you do surveys and have a patient registry is specious. It is form over substance. It is also using words that have a general common sense meaning -patient centered- to mean a list of requirements made up by one or more groups of self appointed experts in quality that may or may not have any direct relationship to level of care or the level of patient satisfaction.
The ACGME and ABIM have "determined" that a key competency of internists involves during patient surveys. Where is the evidence that surveys about services received a)reflects what the recipient really wants or values b)has been linked to any meaningful changes in medical practice with associated outcome changes?
Some data may exist but it seems to be that ABIM and ACGME have adopted this feel-good position even without the solid evidence base of the evidence based medicine to which everyone is obligated to pledge allegiance in every medical publication. Interestingly, in this Archives article, the authors offer no evidence to the efficacy or safety of their proposal and simply quote "authorities" including themselves.
Physicians practiced patient centered medicine-in the sense of what people generally think such a term would mean-before there were computers, patient surveys and patient data bases and will continue to be practiced as long as the physician does in fact place the patient first and takes seriously his fiduciary duty to the individual patient. That duty will be harder and harder to fulfill the more guidelines,rules,P4P imperatives,quality newspeak and CMS directives impinge upon and exert a demoralizing control over medical practice.
A flurry of new guidelines and rules regarding erythropoiesis stimulating agents
CMS has issued draft guidelines regarding the use of erythropoiesis stimulating agents (ESAs) that are certain to cause worry among patients, oncologists and kidney doctors.The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative has revised its guidelines saying in part that ESA therapy should not go above 13 grams/dl. The Foundation may still be wondering what hit it after a recent article and very critical editorial in JAMA.
CMS has very detailed rules about who can and who cannot received ESA, for how long and how much can be given. The oncologists and hematologists will not be able to use ESA for myelodysplasia or myeloid cancers.
ASCO reacted quickly sending email to its members. ASCO stated that some of the CMS proposals lacked scientific basis and at times contradicted scientific evidence and were in conflict with expert opinion as well as current practice. They expressed concern that this would set a dangerous precedent. Well, the dangerous precedent ship left the dock a long time ago. I remember in the 1970s my concern and disbelief that Medicare disallowed payment for oxygen therapy for COPD patients unless their O2 saturation was less than 88%.
It is no great feat of imagination to envision cancer and kidney docs doing what they thought was the right thing-i.e. going by national guidelines- now facing patients who are reading that their physicians were not doing the right things even perhaps harming them and now Medicare will no longer pay for certain treatments . Talk about a trust issue. Talk about how a single payer will solve American medicine's problems.
When medical decisions are taken out of the hands of the individual physician and the individual patients-and they are now with Medicare-this is exactly what you get. Doctors await the latest pronouncement about what they can and cannot do. What the government told you yesterday to do may not be what they tell you to do today and you may well get blamed for what you did yesterday. It is no longer "what should I do for my patient", it is what will the government let me do or make me do for my patient. Remember when Medicare was passed, the statute itself said that the government would not interfere with the practice of medicine. Talk about a trust issue.
CMS has very detailed rules about who can and who cannot received ESA, for how long and how much can be given. The oncologists and hematologists will not be able to use ESA for myelodysplasia or myeloid cancers.
ASCO reacted quickly sending email to its members. ASCO stated that some of the CMS proposals lacked scientific basis and at times contradicted scientific evidence and were in conflict with expert opinion as well as current practice. They expressed concern that this would set a dangerous precedent. Well, the dangerous precedent ship left the dock a long time ago. I remember in the 1970s my concern and disbelief that Medicare disallowed payment for oxygen therapy for COPD patients unless their O2 saturation was less than 88%.
It is no great feat of imagination to envision cancer and kidney docs doing what they thought was the right thing-i.e. going by national guidelines- now facing patients who are reading that their physicians were not doing the right things even perhaps harming them and now Medicare will no longer pay for certain treatments . Talk about a trust issue. Talk about how a single payer will solve American medicine's problems.
When medical decisions are taken out of the hands of the individual physician and the individual patients-and they are now with Medicare-this is exactly what you get. Doctors await the latest pronouncement about what they can and cannot do. What the government told you yesterday to do may not be what they tell you to do today and you may well get blamed for what you did yesterday. It is no longer "what should I do for my patient", it is what will the government let me do or make me do for my patient. Remember when Medicare was passed, the statute itself said that the government would not interfere with the practice of medicine. Talk about a trust issue.
Tuesday, May 15, 2007
Coenzyme Q Parkinsons trial -negative results-what about statin myopathy?
A recent randomized clinical trial with 300 mg.0f CoQ 10 per day for three months failed to show any benefit.
Hope for a neuroprotective effect of CoQ 10 was based in part on animal experiments in which mice with MPTP induced Parkinsonian symptoms were shown to have reduced loss of dopaminergic axons when treated with Coenzyme Q.
CoQ 10 has mainly been a star in the world of alternative medicine but also appears from time in efforts to gain acceptance in the more respected world of conventional medicine. In Europe, it seems to have claimed some role in treatment of heart failure and for time to time I have seen cardiologists adding it on to patients with severe HF. At least one Meta-analysis of clinical trials from Europe concluded it had some role in HF treatment.
Some Co Q 10 believers have latched onto the notion that CoQ10 is essential to prevent a putative loss of that enzyme brought about by statin therapy. In their view statin therapy has largely been responsible for what they characterize as a pan-epidemic of heart failure. In their argument they point triumphantly to the fact that Merck did patent a combination of a statin and CoQ 10. I had written about CoQ10 two years ago and mentioned that some physicians were tentatively using it in patients taking a statin who complained of muscle pain but had normal CK levels. That approach may have some validity.
Dr. Robert L. Wortmann, from the University of Oklahoma Medical School, provides some anecdotal evidence for its value in statin associated myalgia/myopathy syndrome. Anecdotal evidence , of course, does not enjoy the top dog role in the evidence hierarchy but in some cases the greater experience of a subject matter expert might have to suffice until the randomized trial data comes along if it ever does. Dr. Worthman and his group were able to accumulate a number of cases and in their opinion a trial of Co Q 10 sometimes seemed to work. They found that a number of patients were heterozygotes for one of several inborn errors of muscle metabolism such as McArdle disease but were asymptomatic before taking one of the statins.
CoQ10 seems fairly side effect free ( it might interfere with coumadin) but it is not cheap and drug insurance plans won't cover it so most docs may well try a different statin and then punt over to Zetia.
Hope for a neuroprotective effect of CoQ 10 was based in part on animal experiments in which mice with MPTP induced Parkinsonian symptoms were shown to have reduced loss of dopaminergic axons when treated with Coenzyme Q.
CoQ 10 has mainly been a star in the world of alternative medicine but also appears from time in efforts to gain acceptance in the more respected world of conventional medicine. In Europe, it seems to have claimed some role in treatment of heart failure and for time to time I have seen cardiologists adding it on to patients with severe HF. At least one Meta-analysis of clinical trials from Europe concluded it had some role in HF treatment.
Some Co Q 10 believers have latched onto the notion that CoQ10 is essential to prevent a putative loss of that enzyme brought about by statin therapy. In their view statin therapy has largely been responsible for what they characterize as a pan-epidemic of heart failure. In their argument they point triumphantly to the fact that Merck did patent a combination of a statin and CoQ 10. I had written about CoQ10 two years ago and mentioned that some physicians were tentatively using it in patients taking a statin who complained of muscle pain but had normal CK levels. That approach may have some validity.
Dr. Robert L. Wortmann, from the University of Oklahoma Medical School, provides some anecdotal evidence for its value in statin associated myalgia/myopathy syndrome. Anecdotal evidence , of course, does not enjoy the top dog role in the evidence hierarchy but in some cases the greater experience of a subject matter expert might have to suffice until the randomized trial data comes along if it ever does. Dr. Worthman and his group were able to accumulate a number of cases and in their opinion a trial of Co Q 10 sometimes seemed to work. They found that a number of patients were heterozygotes for one of several inborn errors of muscle metabolism such as McArdle disease but were asymptomatic before taking one of the statins.
CoQ10 seems fairly side effect free ( it might interfere with coumadin) but it is not cheap and drug insurance plans won't cover it so most docs may well try a different statin and then punt over to Zetia.
Friday, May 11, 2007
Sarcoid like clinical picture reported in 911 rescue workers
A recent publication, referenced here, reports twenty eight 911 rescue workers with a sarcoid type clinical picture. The article, Published in the May 2007 issue of Chest is available in abstract form here.
Patient were described with hilar nodes and parenchymal changes as well as extra-pulmonary findings.
There is some precedent for the relationship between occupational/environmental exposures and granulomatous type pulmonary reaction. For example,exposure to zirconium has been reported to cause pulmonary granulomatous reactions. Much less obscure has been the well established relationship between exposure to beryllium oxide-used in the manufacture of fluorescent light bulbs-and a clinical picture at times indistinguishable from sarcoid. Unique among pneumoconioses a blood test (beryllium specific lymphocyte proliferation test) is available for specific diagnosis.
Sarcoid is generally considered a hypersensitivity reaction to something (or somethings) but a common etiology for all cases has eluded detection.
It is not surprising that the mixture of respirable particles to which 911 rescuers were exposed would cause lung disease of some sort. Harder to understand is the authors of the Chest article observation that NYFD members demonstrated a higher than expected rate of sarcoid preceding the 911 catastrophe. On the other hand, clusters of cases have appeared from time to time in various places and among various occupational groups (e.g nurses) but over time no confirming data developed that indicated a real pattern.
Patient were described with hilar nodes and parenchymal changes as well as extra-pulmonary findings.
There is some precedent for the relationship between occupational/environmental exposures and granulomatous type pulmonary reaction. For example,exposure to zirconium has been reported to cause pulmonary granulomatous reactions. Much less obscure has been the well established relationship between exposure to beryllium oxide-used in the manufacture of fluorescent light bulbs-and a clinical picture at times indistinguishable from sarcoid. Unique among pneumoconioses a blood test (beryllium specific lymphocyte proliferation test) is available for specific diagnosis.
Sarcoid is generally considered a hypersensitivity reaction to something (or somethings) but a common etiology for all cases has eluded detection.
It is not surprising that the mixture of respirable particles to which 911 rescuers were exposed would cause lung disease of some sort. Harder to understand is the authors of the Chest article observation that NYFD members demonstrated a higher than expected rate of sarcoid preceding the 911 catastrophe. On the other hand, clusters of cases have appeared from time to time in various places and among various occupational groups (e.g nurses) but over time no confirming data developed that indicated a real pattern.
Thursday, May 10, 2007
Medical news- the trivial and the amazing
First the trivial:
A recently reported research paper should be reassuring to those folks who have been concerned about the resilency and general toughness of humans. Researchers have determined that all children exposed to some "trauma" do not develop Post Traumatic Stress Syndrome (PTSS).
Another surprising finding-at least to someone who has never watched the six o'clock news or read the newspaper- was that exposure to traumatic events was common. So it seems that traumatic events are widespread and most people get over them.
And the Amazing.
You may remember the physician who incurred the wrath of the politically correct by calling an obese patient "fat". Here is a link to a site that quotes the letter from him nominating himself to be Dean of Harvard Medical School.If I were on the selection committee I would want to interview him; I 'll bet he won't get the call.
A recently reported research paper should be reassuring to those folks who have been concerned about the resilency and general toughness of humans. Researchers have determined that all children exposed to some "trauma" do not develop Post Traumatic Stress Syndrome (PTSS).
Another surprising finding-at least to someone who has never watched the six o'clock news or read the newspaper- was that exposure to traumatic events was common. So it seems that traumatic events are widespread and most people get over them.
And the Amazing.
You may remember the physician who incurred the wrath of the politically correct by calling an obese patient "fat". Here is a link to a site that quotes the letter from him nominating himself to be Dean of Harvard Medical School.If I were on the selection committee I would want to interview him; I 'll bet he won't get the call.
Wednesday, May 09, 2007
More bad news for the physician trust issue-Rebates for EPO ?
A recent issue of the the New York Times reveals that some physician groups have been receiving rebates from drug manufacturers for parenteral recombinant erythropoetin. While volume related rebates to purchasers of various products has been routine and legal the implication is that some physician groups ( nephrologists and oncologists) who may profit from these arrangements are overusing the medications such overuse possibly risking harm to their patients.
Profit to dialysis centers from EPO use as well the possibility of profit enhancement by rebates was mentioned in a recent JAMA editorial which was critical of current guidelines which I discussed recently.
It is hard-if not impossible-to find news of any current trend that would improve what may well be a declining trust in physicians on the part of patients. A recent commentary by the president of the AMA maintains that trust in doctors is quite high ( better that say what politicians enjoy) but everything I read points in the direction of falling trust.
The time and money crunch basically brought about by managed care is a major driver in dwindling trust. Less time with the patient can only be bad. Missed or incorrect diagnoses for the individual patient impacted by it has to be one of the biggest trust busters possible. A hurried encounter with your doc leads only to the impression that he does not really care. A letter from your insurance company telling you your physician is delisted because he doesn't meet the quality requirements may completely destroy trust even though the criteria used may be entirely bogus and born of cost control and not a tool to make your care better.
The renal doctors I have known professionally are not the sort of people who would knowingly overuse a medication ( i.e give too much EPO) to make a profit.I have no personal knowledge of large dialysis companies that would enable me to have the same sense of reassurance. The JAMA editorial lays some possible blame at the feet of the writers of the guidelines which may have recommended doses of EPO or targets for hemoglobin that lead to more harm than good and predictably there was at least the implication of increasingly talked-about conflict of interest on the part of the members of the guideline writing panel.
I don't know if trust in physicians is lower now than before but I do know that my trust titer has tanked and I am many times more skeptical and critical in regard to medical articles that in the not too distant past I would have read without a nagging doubt about the motives of the authors.
Profit to dialysis centers from EPO use as well the possibility of profit enhancement by rebates was mentioned in a recent JAMA editorial which was critical of current guidelines which I discussed recently.
It is hard-if not impossible-to find news of any current trend that would improve what may well be a declining trust in physicians on the part of patients. A recent commentary by the president of the AMA maintains that trust in doctors is quite high ( better that say what politicians enjoy) but everything I read points in the direction of falling trust.
The time and money crunch basically brought about by managed care is a major driver in dwindling trust. Less time with the patient can only be bad. Missed or incorrect diagnoses for the individual patient impacted by it has to be one of the biggest trust busters possible. A hurried encounter with your doc leads only to the impression that he does not really care. A letter from your insurance company telling you your physician is delisted because he doesn't meet the quality requirements may completely destroy trust even though the criteria used may be entirely bogus and born of cost control and not a tool to make your care better.
The renal doctors I have known professionally are not the sort of people who would knowingly overuse a medication ( i.e give too much EPO) to make a profit.I have no personal knowledge of large dialysis companies that would enable me to have the same sense of reassurance. The JAMA editorial lays some possible blame at the feet of the writers of the guidelines which may have recommended doses of EPO or targets for hemoglobin that lead to more harm than good and predictably there was at least the implication of increasingly talked-about conflict of interest on the part of the members of the guideline writing panel.
I don't know if trust in physicians is lower now than before but I do know that my trust titer has tanked and I am many times more skeptical and critical in regard to medical articles that in the not too distant past I would have read without a nagging doubt about the motives of the authors.
Thursday, May 03, 2007
Still more good things from statins?
I had wondered before about whether there was anything that statins did not help.The latest breaking observational study suggest that the risk of sepsis in dialysis patients is markedly lowered by statins.
It obligatory to mention whenever an observational study is cited or discussed to say since this was not a randomized trial we cannot infer causality and this should be considered an"hypothesis generating study".
Even so,it is another block in the argument building to emphasize the non-LDL lowering effect of statins,aka "pleotrophic effect".
The makers of the several statin drugs hope to build on the pleotrophic effect foundation to counter the appeal of Zetia which when teamed with a statin ( Vytorin is Zetia plus Zocor) brings about an impressive decrease in LDL cholesterol. The lower-is -better mantra on the part of the National Cholesterol Panel and its ever decreasing LDL target is just what one would want to encourage sales of Zetia and Vytorin. One counterargument from the statin camp is that " yes Zetia plus statin really lowers the LDL but the statin does more than lower the LDL.It has pleotrophic effects" i.e it decreases inflammation or tendency to clot,pacifies platelets or something beside lowering the LDL to decrease the likelihood of an acute coronary syndrome.
Of course, statins have effects other than LDL lowering. How many drugs do just one thing? Even though we emphasize one aspect and even classify a drug on the basis of that one action, e.g. beta-blockers,calcium channel blockers etc,these drugs all have effects other that the one for which they were named.
Crestor ran into a bit of bad sailing what with Vytorin blazing onto the scene and then Sidney Wolfe ( of Public Citizen ) requesting that the FDA remove Crestor from the market arguing that Crestor had a greater risk of myopathy and possibly renal disease. Here is the FDA letter replying to his request and denying it.
If recent thought- leader dinner talks are any indication Crestor is fighting back arguing the shrinkage of plaque that occured with the ASTEROID trial with Crestor -an effect I believe that has not been seen with the rival statins and promoting the idea that the best indicator of risk and of decreasing risk is the level and then the improvement in the LDL/HDL level, a parameter in which Crestor seems to do rather well.
It may well be that the "best" number to treat to is one that uses the LDL/HDL ratio but so far ( at least with ATP 111) the cholesterol mavens encourage docs to use LDL targets and their desire to go with the ATP playbook is one of the reasons that Vytorin is doing so well and Crestor is on the evening dinner circuit to persuade/convince docs that we need to dance with those that brought us, ie the statins which have shown mortality benefit and that as yet has not been demonstrated with Zetia. Stay tuned, I believe a long term study of the effect of Zetia on coronary event rate is being done.
It obligatory to mention whenever an observational study is cited or discussed to say since this was not a randomized trial we cannot infer causality and this should be considered an"hypothesis generating study".
Even so,it is another block in the argument building to emphasize the non-LDL lowering effect of statins,aka "pleotrophic effect".
The makers of the several statin drugs hope to build on the pleotrophic effect foundation to counter the appeal of Zetia which when teamed with a statin ( Vytorin is Zetia plus Zocor) brings about an impressive decrease in LDL cholesterol. The lower-is -better mantra on the part of the National Cholesterol Panel and its ever decreasing LDL target is just what one would want to encourage sales of Zetia and Vytorin. One counterargument from the statin camp is that " yes Zetia plus statin really lowers the LDL but the statin does more than lower the LDL.It has pleotrophic effects" i.e it decreases inflammation or tendency to clot,pacifies platelets or something beside lowering the LDL to decrease the likelihood of an acute coronary syndrome.
Of course, statins have effects other than LDL lowering. How many drugs do just one thing? Even though we emphasize one aspect and even classify a drug on the basis of that one action, e.g. beta-blockers,calcium channel blockers etc,these drugs all have effects other that the one for which they were named.
Crestor ran into a bit of bad sailing what with Vytorin blazing onto the scene and then Sidney Wolfe ( of Public Citizen ) requesting that the FDA remove Crestor from the market arguing that Crestor had a greater risk of myopathy and possibly renal disease. Here is the FDA letter replying to his request and denying it.
If recent thought- leader dinner talks are any indication Crestor is fighting back arguing the shrinkage of plaque that occured with the ASTEROID trial with Crestor -an effect I believe that has not been seen with the rival statins and promoting the idea that the best indicator of risk and of decreasing risk is the level and then the improvement in the LDL/HDL level, a parameter in which Crestor seems to do rather well.
It may well be that the "best" number to treat to is one that uses the LDL/HDL ratio but so far ( at least with ATP 111) the cholesterol mavens encourage docs to use LDL targets and their desire to go with the ATP playbook is one of the reasons that Vytorin is doing so well and Crestor is on the evening dinner circuit to persuade/convince docs that we need to dance with those that brought us, ie the statins which have shown mortality benefit and that as yet has not been demonstrated with Zetia. Stay tuned, I believe a long term study of the effect of Zetia on coronary event rate is being done.
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