From meeting presentation to peer reviewed journal---POISE hits the pages of Lancet
The POISE (Perioperative Ischemic Evaluation) beta blocker study was presented at AHA last November. I blogged about it in a year end wrap up of developments in perioperative medicine. Last Tuesday the study was published in Lancet. The spin regarding this study has been largely negative. Missing from the discussion is the fact that the beta blocker use was associated with benefit for the primary endpoint. From the Lancet:
The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal cardiac arrest……Fewer patients in the metoprolol group than in the placebo group reached the primary endpoint (244 [5·8%] patients in the metoprolol group vs 290 [6·9%] in the placebo group; hazard ratio 0·84, 95% CI 0·70–0·99; p=0·0399). Fewer patients in the metoprolol group than in the placebo group had a myocardial infarction (176 [4·2%] vs 239 [5·7%] patients; 0·73, 0·60–0·89; p=0·0017).
But wait a minute. Secondary endpoints pointed to harm associated with metoprolol:
However, there were more deaths in the metoprolol group than in the placebo group (129 [3·1%] vs 97 [2·3%] patients; 1·33, 1·03–1·74; p=0·0317). More patients in the metoprolol group than in the placebo group had a stroke (41 [1·0%] vs 19 [0·5%] patients; 2·17, 1·26–3·74; p=0·0053).
Clinical trial experts criticize conclusions based on secondary endpoints when such endpoints are positive, as seen in the PROACTIVE controversy.
So, how should we view the POISE results? In the case of POISE the secondary endpoints were those that mattered more. The authors concluded:
Our results highlight the risk in assuming a perioperative β-blocker regimen has benefit without substantial harm, and the importance and need for large randomised trials in the perioperative setting. Patients are unlikely to accept the risks associated with perioperative extended-release metoprolol.
Understated, perhaps, but true. The second sentence was interesting in that it acknowledged the role of patient participation in decision making.
DB blogged about the study Friday as an important lesson for the performance and safety movement:
Second, the performance indicator and safety movement which has a "ready, fire, aim" philosophy, must reevaluate their strategies. One must wonder if our current push towards performance measurement has caused strokes and death in some patients. Finally, 30 years after finishing my residency, I continue to reshape my medical knowledge. As new knowledge appears we must quickly adjust our practice. I am interested in the ability of the performance movement to adjust. Of course, they will shrug off the unintended consequences that they caused here.
It gets you thinking---who makes up these safety and performance measures anyway? What are their credentials other than being effective cheerleaders (“champions” is the trendy term, I believe)?
DB also linked to Medscape’s Heartwire report about the trial. Dr Philip J Devereaux, who originally presented the POISE data at AHA, said in the report:
"If even only 10% of physicians followed these guidelines—which incidentally in the United States are used in quality assessments, where you have people going around ranking hospitals in terms of whether or not they are giving perioperative beta blockers—and if the POISE data are true, then in the past decade 800,000 people would have died prematurely and 500,000 would have had a major stroke perioperatively because we gave beta blockers….”
Where’s the press coverage of all these deaths? While a few reports such as this one hyped the results by and large the media response was modest. They didn’t have Big Pharma to pick on. What if, instead of an old, cheap off-patent medication the drug in question had been a new expensive block buster which had been heavily promoted by one of the big drug companies? I can only imagine.
Juan Carlos Ayus spoke last week at the American College of Physicians annual meeting on hyponatremic encephalopathy, as reported by DB’s Med Rants. Having heard Dr. Ayus speak on this topic before, I wish I could have heard the talk. Ayus has talked and written extensively on the dangers of hyponatremia and believes they are underemphasized, perhaps due to concerns about osmotic myelinolysis which can follow correction of hyponatremia. He co-authored this article from Nature Clinical Practice Nephrology (via Medscape, linked in DB’s post) in which he recommends a much more aggressive approach to the prevention of hyponatremia and the treatment of hyponatremic encephalopathy than is currently popular.
Hyponatremic encephalopathy is a dire emergency and must be treated rapidly. Reluctance to do so may stem from confusion between this condition and the more commonly encountered chronic hyponatremia which carries the greater risk of osmotic myelinolysis.
Of note, from the article:
In contrast with healthy persons who have a normal renal and neuron-humoral milieu, virtually all hospitalized patients are susceptible to hyponatremia. Elevated vasopressin levels can be taken for granted, as they have been associated with most hospital diagnoses.
Unless there is a special situation requiring hypotonic IV fluids, normal saline should be used in all patients requiring IV fluid. Ringers lactate, by the way, often considered isotonic, is actually hypotonic.
If the hyponatremic symptoms are severe (active seizures, respiratory arrest) the article recommends a 100 ml 3% saline bolus over 10 minutes. Elsewhere Ayus recommended this same regimen for marathon runners suffering from severe symptoms of hyponatremic encephalopathy. Milder symptoms of acute hyponatremic encephalopathy (nausea, vomiting, confusion, single resolved seizure) can be treated with the traditional 3% saline slow infusion. I was never taught to bolus patients with 3% saline. I did a quick search of UPtoDate and the new editions of Harrision’s and Cecil Medicine, none of which mentioned the bolus regimen. Though it seems extreme it makes sense in the situations described---the patient is about to herniate.
With respect to the risk of osmotic demyelination the overall rate of correction at 24-48 hours is more important than the hour to hour rate during the first few hours of treatment of hyponatremic encephalopathy. The article describes counter-measures and precautions to help prevent excessively high sodium concentrations at 24-48 hours.
The article mentions the relationships between hyponatremic encephalopathy and respiratory disturbances. These relationships are complex and exist on several levels. Hyponatremic encephalopathy causes two forms of respiratory failure: hypercapnic respiratory failure and non-cardiogenic pulmonary edema. The pulmonary issues associated with hyponatremic encephalopathy are discussed in greater detail in this paper co-authored by Ayus.
The top three reasons for the shortage of geriatricians are: compensation, compensation and compensation. But the president of the American Geriatrics Society, interviewed at Med Page Today, doesn’t seem to get it. He waffles and talks around it, and talks about the “medical home”. Go to Kevin M.D. and watch the video.
---other than Grand Rounds. From morning report to CPCs to Jeopardy sessions, many academic medical centers post the content on the web. Many of the presentations are created by house staff and fellows and are of good quality.
Let’s start the list with the collection of medicine rotation topics covered at Cleveland Clinic, compiled by Clinical Cases and Images blog.
Here are some more (some are a bit dated, others are updated often):
It’s been a good week for the exposure of the fraud, corruption and pervasive conflicts of interest in high places in the world of woo. Just last Tuesday the Medscape Journal of Medicine published an article exposing the bad science and pervasive conflicts of interest behind the National Center for Complementary and Alternative Medicine’s ongoing chelation trial. Today David Colquhoun, blogging at DC’s Improbable Science, wrote about Integrative baloney at Yale in which he exposed, with videos and other examples, some of the wooiest of woo being taught there.
Junkfood Science recently blogged about the program at Yale. Concerning the general problem of medical academic woo she wrote:
Some have questioned if CAM-trained doctors are able to practice as primary care physicians and if we can trust their judgments. The concern that probably most comes to mind is whether these doctors are being taught the scientific process and how to recognize sound evidence from modalities that negate all known laws of science and biological plausibility.
She posted a follow up today. Both bloggers mentioned an astounding statement by Yale professor David L. Katz, MD, MPH, FACPM, FACP, associate professor, adjunct, of Public Health and director of the Prevention Research Center (PRC) at the Yale University School of Medicine. From DC’s post:
Pretty remarble uh? Dr Katz goes through several different trials, all of which come out negative. And what is his conclusion? You guessed.His conclusion is not that the treatments don’t work but that we need a “more fluid concept of evidence”.
That announcement by a prominent medical academic made it official: we are in the era of post-scientific medicine.
DC went on:
It’s equally bizarre to hear Richard Belitsky, Dean of Medical Education at Yale saying he is “very proud” of this betrayal of enlightenment values. If this is what Yale now considers to be education, it might be better to go somewhere else.
DC cited the Flexner report and made a point I wrote about before:
Flexner would have thought it quite inconceivable that in 2007 medical schools would be offering Continuing Medical Education in homeopathy.
He asked why other academics at Yale aren’t up in arms and suggested, earlier in the post, that it’s about money:
Very few university administrators have the intellectual integrity to turn down money, whatever the level of dishonesty that is required by its acceptance. You can buy a lot of silence for $100m…
…citing NCCAM and massive philanthropic funding of academic woo.
By the way, where’s the AAMC in all this? Aren’t they supposed to be guardians of integrity and professionalism in medical education? Are they asleep at the switch or is money silencing them too?
And a final note--- I got the idea for the term “post-scientific medicine” from the Carlat Psychiatry Blog. Dr. Carlat, writing about AAMC’s new proposal to limit the influence of pharmaceutical companies in medical academia, declared that we are now in the era of “post-deception medicine”. I respectfully disagreed.
On the AAMC’s proposal concerning Pharma gifts, I’ve changed my tune---somewhat
A commenter on my recent post about the AAMC proposal took me to task for not reading the report in the original. Although her reasons for suspecting me were wrong (I twice referred to the AAMC as AAMS, typo’s I’ve since fixed) it turns out she was correct that I hadn’t read the report in the original. I had read some blog reactions and the New York Times article, none of which contained a link to the report.
So I did what I should have done in the first place. I went and read the report. Turns out the proposal isn’t so bad. Not as bad as I thought, anyway. I disagree with the scope and the extent of the restrictions proposed and find it odd, even hypocritical, given all their talk about professionalism and integrity in medical education, that they turn their back on the shameful and pervasive problem of woo. Nevertheless, my characterization of the proposal as “simplistic and extreme” was too strong.
I think it was the NYT article that was simplistic. It implied a total ban on free food. Wrong. According to the AAMC proposal, industry-supplied food is permissible if served at an activity carried out according to ACCME standards and accredited for CME. Some academic medical center Grand Rounds, though perhaps not all, are accredited. So, this proposal will not banish free food from the academic environment. Many activities won’t be affected at all. What it may do is encourage more programs to get their Grand Rounds accredited. That would be a good thing.
Moreover, the report doesn’t ban drug reps from medical campuses. It merely sets standards for drug company presentations and requires oversight by faculty. In other words, drug reps can’t just wander in and, like self appointed faculty, proceed to “teach” students free of any administrative supervision!
My big mistake was that I dropped my guard and violated the cardinal RW rule: always, when possible, go to the primary source! That’s what I get for trusting the New York Times.
One more thing. I had to chuckle at Carlat Psychiatry Blog’s declaration following the announcement of the AAMC proposal: The era of post-deception medicine is finally here. No way. We can’t enter an era of post-deception medicine until we leave the era of post-scientific medicine. Selective outrage?
They have increased cardiovascular mortality and approximately double the risk of metabolic syndrome as compared to other positions. Via the American Journal of Cardiology.
You don’t have to be a subscriber to the American Journal of Cardiology to read J. Willis Hurst’s editorial on cognitive errors in medicine---the full text is free. I highly recommend it.
The popular approach to limiting cognitive error was recently articulated in Jerome Groopman’s marvelous book How Doctors Think. I call it the negative approach to cognitive error because it emphasizes pitfalls to avoid. Hurst’s essay suggests a more positive approach. It outlines things to do in the systematic collection and processing of clinical data. These approaches are complementary and both ultimately address the same types of error.
Hurst’s approach centers around the medical record as a tool for teaching and learning (thus addressing gaps in the clinician’s knowledge), defining data that need to be collected, analyzing the data and applying the information to the patient’s problems. He advocates the problem oriented medical record (AKA the Weed system) of which he has been a champion for manyyears.
Most of us would say we use the problem oriented medical record as the ever present SOAP notes and problem lists attest. But a careful reading of Hurst’s essay suggests it’s merely a pretense. The problem oriented record as originally conceived is systematic and rigorous. While it seems cumbersome, Hurst notes that it can be utilized quickly and efficiently once proper habits are developed.
The problem list must designate each item at the level of resolution achieved, from symptoms and laboratory abnormalities at the low end to definitive diagnoses at the highest level. Moreover, diagnoses must reflect the most up to date disease classification and terminology.
That raises an important question. Is it possible to generate and maintain a true problem oriented medical record in today’s environment where the record is hijacked by coders, core measure police and others with competing agendas? Just one example of this problem is the basing of diagnostic terminology on the decades obsolete (created in 1977 and replaced in 1992) ICD-9 classification. In paper based records if you use precise and up to date terminology your patient’s chart is likely to “bounce back” from the coding department and ultimately find itself on the delinquent list. In the electronic world where all diagnoses are inseparably linked to ICD-9 codes the best terms may not be available.
An effective medical record is more than an accurate problem list. Hurst writes (italics mine):
The medical record should reveal the thoughts and actions of the physician in charge. The challenge for the physician is to make the record simultaneously brief and complete. The record should be easily understood by another physician. Each page of the record should be uncluttered, and important information should be displayed prominently so that it can be retrieved easily.
I wonder what Hurst thinks of today’s template generated charting.
In the Ritter case, the jury agreed with the defendant physicians and exonerated them of any liability. They were lucky. How lucky? They were able to spend four years with attorneys worrying about their future, including the potential that they would be ordered to pay tens of millions of dollars and be left penniless. So, they didn't really win. They just lost less.
Medscape article blows the lid off of NCCAM’s chelation study
A Medscape article on the National Center for Complementary and Alternative Medicine (NCCAM) sponsored Trial to Asses Chelation Therapy (TACT) declares:
We conclude that the TACT is unethical, dangerous, pointless, and wasteful. It should be abandoned.
Orac has already written a wonderful post this morning in which he opines:
As I go to my office and lab this morning, to try to do high quality scientific research based on good science designed to improve our understanding of cancer and hopefully lead to more effective therapies, it galls me to no end to see the equivalent of 15-20 R01 grants going to fund this woo. Worse, it's TACT is not the only example of an unethical and scientifically worthless trial being funded not because the science is compelling but because powerful lobbies and legislators who are true believers in woo applied pressure to the NIH to do them.
I’ll take this opportunity to put in my two cents---not that I really have anything to add other than to say “I told you so” not only about this study but also about the under appreciated conflicts of interest in government funded research. When I first read about this study a couple of years ago I smelled a rat and have since written a number of posts, several of which Orac linked to this morning. The Medscape article reinforces some of the points I made in those posts, particularly regarding the dubious credentials and obvious conflicts of interest of many of the study site investigators. Just look at this jaw dropping paragraph from the article:
The TACT includes nearly 100 "chelation site" co-investigators who, in our opinion, are unsuitable to care for human subjects or to report trial data. Most espouse implausible health claims while denigrating proven methods; several have been disciplined, for substandard practices, by state medical boards; several have been involved in insurance fraud; at least 3 are convicted felons. Several were members of the ACAM or GLACM IRBs mentioned above. Few appear to have real expertise, required by TACT literature, in treating patients with CAD or in conducting clinical trials. Most continue to promote chelation while the TACT is in progress, contrary to good science, to human studies ethics, and to US Federal Code. The TACT consent form gives no hint of these points.
WOW!! Worse than even I imagined! This stuff belongs in the health pages of the New York Times. (I won’t hold my breath, though. They’re probably too busy exposing the pharmaceutical companies to notice. I hope I’m wrong!). If those ethical issues aren’t egregious enough consider that the study isn’t even securely blinded from the investigators, a concern I raised here and in other posts. The Medscape article describes the problem:
The experimental solutions must be mixed on-site. The 2003 TACT protocol describes a method to preserve blinding and reports that this "has been piloted successfully," presumably in a supervised, academic setting.[5] Nevertheless, the mixing procedure presents simple opportunities for distinguishing between the chelation and placebo solutions. For example, the site coordinator must inject 14 mL of concentrated ascorbate or sham solution into a 500-mL IV bag. The plan calls for the 14-mL solutions to have similar viscosity and to appear similar in color, but a tiny drop applied to the tongue during transfer would instantly identify the ascorbate by its sour taste. Ascorbate goes exclusively with the Na2EDTA solution.
Not only was the protocol itself scientifically implausible, a mix of disodium EDTA and a bunch of supplements, as well as procaine and heparin added for unclear reasons. it is placebo-controlled, but the protocol stipulates that the chelation solution must be mixed on site, allowing ample opportunity for investigators to break blinding, either purposely or even inadvertently.
That may just be the tip of the iceberg concerning TACTs’ design problems. The authors note that the NCCAM was not entirely forthcoming with information in response to their FOIA requests:
Through FOIA requests, we obtained "redacted" copies of the original (2001) and 2003 TACT protocols,[4,5] the roster of the committee that approved the grant application,[39] and the June 2003 consent form.[6] Because the trial had already begun and because our initial FOIA requests were frustrated by delays and incomplete responses, we did not seek further revisions of the protocol or consent form, or other documents that are not available on the NCCAM Web site.
I knew from the get-go this trial was questionable. I didn’t know how bad it really was until I read the Medscape piece. This tops any example you can trot out about the corrupting influence of Big Pharma. What I didn’t cover in my posts was the extent of the pseudoscientific agenda and conflicts of interest that prevailed throughout the planning and implementation of the study. If you think government funding is the answer to Pharma involvement in research this article will give you pause.
---is only part of the DRG revamp rolled out by CMS last year. There’s also the new list of MS-DRGs which replace the old DRGs. And while it may seem like a lot of BS we’ll have to live with it, so we may as well attempt to learn it. An article in ACP Hospitalist offers some tips. Too complicated for me.
If you didn’t read DB’s rants carefully you might get the idea he was somehow against practice guidelines. That wouldn’t be accurate. There’s a difference between skepticism and cynicism. A Grand Rounds presentation he delivered on the topic at UC Davis puts his rants into perspective. Here are some of my take home messages from the talk:
Guideline developers have conflicts of interest. This is not unique to those supported by drug companies. Virtually all organizations and individuals involved in guideline development---governments, professional societies and individuals interested in their academic careers---have a stake.
Guidelines are not immutable rules and are no substitute for clinical judgment.
You can’t apply all guideline recommendations to patients with multiple complex problems---you must prioritize treatments.
Guidelines can provide impetus for ill conceived performance measures.
There’s much more. Follow the link above and watch the video. It’ll make you think.
My recentcriticism of electronic medical records (EMRs) has focused on documentation templates. Now that I’m on a roll with EMR posts I may as well cover the other side of EMRs---computerized physician order entry (CPOE). The push for universal adoption of CPOE is on. Leaders in the patient safety movement tell us it’s a good thing. So what’s so good about it?
For starters let’s look at the description in AHRQ’s glossary:
Physicians (or other providers) directly enter orders into a computer system that can have varying levels of sophistication. Basic CPOE ensures standardized, legible, complete orders, and thus primarily reduces errors due to poor handwriting and ambiguous abbreviations.
It goes on to point out that many systems have decision support built in: suggested doses, allergy alerts and order sets which conform to evidence based practices. More sophisticated systems may integrate patient data such as weight and creatinine clearance.
No one would dispute that these are good ideas. The real rub is how CPOE does in the real world. Do the benefits outweigh the unintended consequences? Bob Wachter, who has written a couple of recent posts on health care technology, seems to think they do. In last Friday’s post he referred readers to AHRQ’s patient safety network where a search on CPOE yields 174 citations. But the top hit is an article on unintended consequences and contains a link to the fabled Pittsburg study showing an increased mortality following the implementation of CPOE. Then there’s this study showing that CPOE actually creates errors. Clearly there’s a trade off between errors intercepted by CPOE (which may or may not have been intercepted “downstream” in traditional paper based systems) and new and unanticipated types of errors introduced by CPOE.
What is the net result in terms of patient safety? To answer that question we need outcome based data. Such data are sparse, but the Pittsburg study is concerning. To be fair, the negative results of that study may reflect learning curve issues more than inherent risks of CPOE itself. On the positive side, Wachter cites this study. But it’s from Brigham and Women's Hospital, raising questions about real world generalizability. Moreover, the significance of the error reduction attributable to CPOE in the study is unclear from the paper. This very recent systematic review demonstrated CPOE’s ability to intercept many errors but failed to show improvement in patient outcomes.
What’s my bottom line as of May 13, 2008? CPOE is a great idea. CPOE has potential. But the boosters of CPOE have a burden of proof which they have yet to satisfy. It has not been proven to help patients. Why is there such a disconnect between theory and real world results? The downside in terms of creating new errors is well documented.
But their’s a less tangible downside. For clinicians, CPOE is a distraction. What do I mean by that? It adds a new burden to our work flow: order processing. Doctors are trained to focus on clinical issues. We need to know what drug to give, when and how much, and what tests to order. We are not trained in how to search the computer for the appropriate orders, how to customize our therapy when the computer’s options are limited, how to be sure that our order entry is properly routed, or how to devise workarounds that are inevitably necessary in such systems. Those issues, formerly in the domain of clerical employees, are now foisted on doctors. They are time consuming and they take away from our clinical focus. The challenge for CPOE development is to create systems that allow doctors to concentrate on the clinical problem at hand, free of questions such as “Where can I find the basal/bolus insulin protocol?” or “Am I sure I entered this right?”
Wachter’s other post puts CPOE in the helpful perspective of the “Technology hype cycle”. New technologies are initially met with unwarranted enthusiasm. Then there follows a back lash when they don’t meet their initial expectations. Finally, gradually, the level of acceptance finds a middle ground in which users appreciate the benefits but realize that the technology isn’t nearly as good as originally hyped. It’s a useful model to keep in mind because it gives us a road map, a kind of sense of where we’ve been and where we hope to end up.
A hospitalist in Northwest Arkansas opining on clinical topics, the interface between medicine and politics and whatever else grabs my attention. This content does not constitute medical advice (consult your physician) nor is it authoritative (check primary sources).
Contact: bkdonnell at cox dot net.
