Thursday, July 27, 2006

Palliative care made law in NY; AAN on coma prognosis

1)
New York State has passed legislation designed to encourage and promote improvements in palliative care and pain management. The Palliative Care Education and Training Act has the following goals:

  • Establish a statewide advisory council on palliative care and pain management;
  • Create undergraduate and graduate palliative care training programs;
  • Establish state Department of Health-designated Centers for Palliative Care Excellence; and
  • Authorize the Department of Health to certify one or more palliative care resource centers to assist physicians in the treatment of patients in pain
What can I say other than wow (that a state legislature is doing this), and great, and that I hope the $4.5 million appropriately annually is well spent.

(Thanks to David Weissman MD for alerting me to this.)

2)
The American Academy of Neurology has published evidence based guidelines for predicting neurologic outcomes for comatose survivors of cardiac arrest in Neurology. For those of you who know the (surprisingly scant) literature on this topic, there are no surprises: the best predictors currently are certain neurologic examination findings in the first few days after the arrest (I won't belabor these here--they're in the abstract). What's interesting, and appreciated, is that the position statement also talks specifically about the role of the neurologist in breaking bad news to the family and helping them make decisions about treatment options, 'comfort care,' etc. Even more interesting, though, is this sentence:

The neurologist can explain that the prognosis is largely based on clinical examination with some help from laboratory tests. In a conversation with the family, the neurologist may further articulate that the chance of error is very small.

There isn't much follow-up given to this sentence, but my interpretation of this sentence is that the position statement is trying to give neurologists permission to make (accurate but) dire & firm prognostic predictions--instead of, say, (technically accurate but) overly general and not-so-dire predictions such "Only God can know what will happen." True enough, but not helpful to a grieving family trying to make decisions. The position paper doesn't say neurologists should be giving firm predictions (ie "the chance of error is very small") but at least it says it's ok that they may.

Thursday, July 27, 2006 by Drew Rosielle MD ·

Friday, July 21, 2006

Nutrition woes

Forgive me as I wallow in a bit of therapeutic nihilism before the weekend with regard to nutrition-related interventions in cancer care...

1)  Per a recent blog topic--interventions for cancer anorexia-cachexia--the most recent Journal of Clinical Oncology presents two randomized, double-blind, placebo controlled trials of interventions for this.  One compared 6 weeks of treatment with a cannabis extract vs THC (marinol) vs placebo and found essentially no differences between groups regarding appetite, quality of life, or adverse effects.  There were lots of drop outs (~240 subjects randomized; 169 completed) and the THC dose was on the lower side ( 2.5mg twice a day) but the results nevertheless were completely underwhelming.  The other trial looked at ~500 patients given eicosapentaenoic acid or placebo for 8 weeks and again found no significant improvements in the treatment arm.  (Eicosapentaenoic acid is a type of purified fish oil extract.)  These were some of the largest studies of their kind for cancer cachexia and these results are disappointing but not, unfortunately, surprising. 

2)
The recent Journal of the National Cancer Institute contains a metaanalysis of trials looking at nutritional interventions and cancer outcomes .  The analysis tries to contain an unwieldy number of trials looking at extremely heterogeneous data (different patient populations such as cancer vs pre-cancerous lesions, different outcome measures, and different nutritional interventions) and is limited by a distinct lack of quality trials.  The authors conclude, rather succinctly, "There is no evidence that dietary modification by cancer patients improves survival and benefits disease prognosis."  A related editorial is included.  I am sure I'm not the only palliative care provider around who constantly tries to answer questions from my cancer patients about "What should I eat?"  In most circumstances I try to encourage my patients to eat whatever they damn well please acknowledging that I have no knowledge of any particular diet benefiting them so they might as well eat what they like.  I am constantly surprised, although I shouldn't be, by how frequently patients find this response dissatisfying, as if there should be some answer, some diet, that will help them to live longer or better.  Part of it may of course be the patient 'picking up' on my own sense of therapeutic nihilism in this area, and I have not yet I guess developed a way of recommending ice cream, pot roast, and cola without sounding... dismissive is the only word I can think of here...even after empathetically acknowledging how frustrating and frightening it can be to see oneself losing one's appetite, weight, and 'battle' against cancer.

Friday, July 21, 2006 by Drew Rosielle MD ·

Thursday, July 20, 2006

Declaration of Venice; NY Times on Katrina charges

2 Quickies:

1)
The IAHPC is soliciting signatures endorsing the Declaration of Venice calling for expanding research into palliative care in developing countries.

2)
Contrary to my predictions a couple of days ago, the NY Times today published a very reasonable article on the Katrina physician/nurse murder charges. The article involves interviews with bioethicists and does a good job of discussing the issues. Thanks to Dr. Lynn Bunch for alerting me to this. (NY Times pieces are usually available free online for about a week.)

Thursday, July 20, 2006 by Drew Rosielle MD ·

Wednesday, July 19, 2006

Hurricane Katrina physician murder charges

Well it's happened. A physician and 2 nurses have been charged with the murder of 4 people at Memorial Hospital in New Orleans during the Hurricane Katrina catastrophe. Probably more indictments will be forthcoming. I cannot of course pass judgment on what happened--either to defend it or outright condemn it--the legal process has to play out, and all I can hope for is justice for all involved. Euthanasia (if that is what this is, which it probably actually isn't...) is morally objectionable to most of us practicing medicine in the US, including palliative medicine, but at this point it's too early to get any clear sense of what actually happened, let alone judge or defend what happened one way or the other, particularly given the extreme circumstances these individuals were acting in.

That said, I'm quite concerned the media coverage of the charges and the public discussion of what happened is going to spill over onto 'regular' end of life care and be full of misrepresentations, half-truths, and gloriously inaccurate and damaging portrayals of end of life symptom management, comfort care, etc. being life- shortening care, and somehow dangerous and ethically suspect.

Example one, from the breaking story yesterday on cnn.com:
According to the court document, the morphine was paired with midazolam hydrochloride, known by its brand name Versed. Both drugs are central nervous system depressants. Taken together, Foti said, they become "a lethal cocktail that guarantees that you die."

(Mr. Foti is the district attorney bringing the murder charges.) One had better inform (the majority?) of ICU survivors in the US that were intubated that they received at some point during their hospital stay a 'lethal cocktail' which should have guaranteed their death.

This same CNN piece at one point seems to differentiate between euthanasia (usually conceived of as a physician deliberately ending a patient's life early at the request of the patient in order to end suffering in the setting of a life-limiting disease) and run-of-the-mill homicide and then later conflates the two. It's going to be a mess.

I invite submissions of aggregious misrepresentations of end-of-life medical care, medical ethics, etc. that come up during this case--email me or leave a comment here.

Wednesday, July 19, 2006 by Drew Rosielle MD ·

Tuesday, July 18, 2006

Withdrawing care in Japan; ketamine; diabetes management; anorexia-cachexia

As a new father I find myself coming home in the evening and realizing all I want is baby-time and not bloggy-time so I apologize for the sparseness of posts of late. Here are a few publications from my backlog....

1)
The most recent Lancet has a disturbing article about physicians in Japan being criminally prosecuted for withdrawing life-prolonging treatments (ventilators). These cases, per the article, appear to cases where ventilator withdrawal was clinically appropriate as well as had the approval/assent of the families. There seems to be an extreme amount of confusion in Japan in the public, media, and law-enforcement communities about euthanasia vs 'mercy killing' vs withdrawal of life-sustaining treatment etc. (extreme meaning more even than North America). Chilling.

2)
A recent BMJ has an editorial (seemingly out of the blue, ie--not related to a concomitantly published article) arguing for (cautiously) expanding the use of ketamine as an analgesic. There's a lot of UK-regulatory stuff in here but it's interesting to see this discussion seemingly thrown haphazardly into the middle of a BMJ. The same issue also has a brief first-person account of caring for a child dying of cancer in the UK, particularly regarding the frustrations of accessing good palliative care in the community.

3)
The Journal of Clinical Oncology's latest issue is on imaging in cancer and includes this primer on imaging techniques in cancer. It's a nice review for those of us who take care of a lot of cancer patients.

4)
Home Healthcare Nursing has a case-based review on glycemic management at the end of life. It would make good educational material for trainees.

5)
Supportive Care in Cancer has an intriguing basic-science article on the role of the ubiquitin-proteosome pathway on the cancer anorexia-cachexia syndrome. It is really more of a review of the pathophysiology of anorexia-cachexia highlighting the role of ubiquitins and proposing that a treatment for the syndrome may involve ubiquitin modulation. All of this is good but it seems that the physiology research is far outpacing the clinical-therapeutic research and that insofar as no therapy has clearly & consistently shown quality of life or mortality benefit--glucocortioids, androgens, progesterones, cannabinoids, hyperalimentation, omega-3 fatty acids, etc.--I'm not holding my breath.

Tuesday, July 18, 2006 by Drew Rosielle MD ·

Thursday, July 13, 2006

'Noninferiority' trials review; sham acupuncture

1)
Yes we just received a large bolus of comment-spam--too much for me to tidy up at once so sorry about that.

2) Annals of Internal Medicine has recently published two articles of note.
First is an analysis and discussion of 'noninferiority' trials. These tend to be randomized, controlled trials which instead of a placebo control use an active, 'standard-of-care' control in situations where it is considered unethical to offer placebo and not an active treatment. A trial comparing a novel chemotherapy to an established regimen would be one example; a trial comparing a novel analgesic compound, formulation, or route to, say, oral morphine would be another example pertinent to palliative care. The outcome in these trials then is to show that the novel therapy is as good as, noninferior to, some standard treatment. These trials are relatively common in palliative care, particularly pain trials, and are fraught with methodologic problems which are what this review discusses. It discusses these in a detailed, statistical manner; but for those of us who are interested in these things this is a paper worth reading.

Next is a randomized controlled trial of acupuncture vs. sham acupuncture vs. 'standard care' for knee osteoarthritis pain. Sham acupuncture here was using needling at defined distances away from standard acupunture points; both acupuncture groups received 10 visits total over 6 weeks. The standard care group received 10 clinic visits and diclofenac or rofecoxib (our old friend Vioxx). The acupuncture groups were blinded as to whether they received sham or 'therapeutic' acupuncture; the standard group of course was not blinded. ~1000 subjects were studied. Pain and function improved in all groups (this is not surprising); it improved more in the acupuncture groups vs. the so-called standard care group (this is also not surprising). What is of note is that the sham acupuncture group did just as well as the 'therapeutic' acupuncture group suggesting acupuncture's effect is from placebo or from needling itself (irrespective of where the needles are placed). This is contrary to two other studies which found therapeutic acupuncture superior over sham in the treatment of knee OA pain and disability. This study was larger than these, but there are significant methodologic differences between them all to really make any sense of this. To me, acupuncture is very much still a therapy in search of a (medical) indication.

Thursday, July 13, 2006 by Drew Rosielle MD ·

Monday, July 10, 2006

Missed opportunities in ICU conferences

A couple from my backlog...

1) Clinical Medicine recently devoted an issue to palliative care (well, at least a CME section of an issue). It has several general review articles about pain management, nausea & vomiting, psychological issues in palliative care, and cancer cachexia and fatigue. The articles are all well written & reasonable, but quite basic, and one doesn't know whether to be happy that CM is devoting an entire issue to palliative care or depressed that this basic level of information is what the general medical reader is in need of. Could make good teaching materials for medical students, basic pall care talks, etc., though.

2) The American Journal of Respiratory and Critical Care Medicine published a piece about missed opportunities during family conferences about end of life issues in the ICU (free full-text here--it was actually published last year but only recently was indexed as a palliative care article by Medline which is why I read it only recently). It involves analyses of audiotapes of ~50 ICU family conferences involving breaking bad news or discussions about life-prolonging treatment limitations (these 50 conferences were about half of those that were screened for the study--the remainder were excluded because the family declined participation, etc.). The authors analyzed the tapes for 'missed opportunities' in the conferences. A couple things about this. One, they found that ~30% of conferences had a missed opportunity of one sort or the other ( e.g. physician not responding to family member emotion; not answering a question, etc.). This strikes me as a low number and either the ICU docs studied are very thorough or the authors are missing some, um, missed opportunities. Which bring me to point two, which is that by their methods they seemed to not have decided upon strict criteria to define a 'missed opportunity.' Instead it appears that they first flagged the missed opportunities, after deciding to look for them, and then analyzed them to determine what were their character (ie, how many involved not sharing asked for information). My point here is that this methodology is adequte for helping the authors define and characterize missed opportunities (which was their major goal), but not identify their frequency. This is all fine, and I hope they continue to develop this concept as in my experience they are exceedingly and flagrantly common in family meetings and similar communications in & out of the ICU and an interesting thing to study.

This group appears to have been developing a conceptual framework for studying ICU goal setting and breaking bad news conferences (this article describes their overall project and methods).

Monday, July 10, 2006 by Drew Rosielle MD ·

Tuesday, July 4, 2006

Hepatotoxicity with acetaminophen

JAMA has published a perplexing article about hepatotoxicity observed with supposedly non-toxic doses of acetaminophen (APAP).
Perplexing for two reasons.

1)  The data presented were from a study being performed to evaluate a novel hydrocodone-acetaminophen combination analgesic; however no data presented involved anyone taking hydrocodone.  I just thought this was weird. 

2)  The findings themselves were befuddling.  Again, this was a study to evaluate some sort of novel Vicodin-type analgesic which involved 145 healthy, relatively young people given placebo or 4 grams a day of APAP plus various opioids.  These people were all confined to a pharmaceutical research lab, eating the same diet, getting their pills handed to them by research techs, etc. for the duration of the study.  They were supposed to be monitored for 14 days but the study was stopped after 8 days because of the high rates of liver enzyme elevations.  Of note, while no one receiving placebo had ALT elevations over 3 times normal, ~40% of the people receiving acetaminophen did!!  Wait, let me repeat that with more exclamation points--about 40% of those receiving APAP had major elevations of their liver enzymes!!!!  Not surprisingly, but thankfully, those patients receiving APAP alone (that is--they weren't receiving concomitant opioids) had the same ALT elevations that those receiving concomitant opioids (that is--APAP was the culprit here, not the opioids).  Alpha-GST was elevated also, meaning that the ALT elevations truly were liver injury.  The authors conclude, with justification, that 4 gm of APAP in these young, healthy people caused a high rate of liver enzyme elevations; there's no other good explanation here other than some freak event or a mass conspiracy or fraud, all of which seem much less likely than it was the APAP.  (The authors actually gave the manufacturer's lot numbers of the APAP pills given as if to acknowledge that there may be people who suggest that this was a bad batch.) 

So what is going on here?  4 gm daily of APAP, in otherwise healthy people, is considered safe, and has been for a long time, and in my opiophobic VA medicine clinic residency days it was drilled into me to start my patients off with 4gm of acetaminophen before trying anything else.  The authors themselves seemed surprised this happened and their brief literature review in the discussion section of the article more or less confirms the accepted wisdom that 4gm a day is safe.  They dangle out a couple more tantalizing bits of information:  A) that the serum APAP levels were not different between those with evidence of toxicity and those without, and B) there was a large number of Hispanic subjects in this trial, relative to many clinical trials in the US (a little over 50%), and rates of hepatotoxicity trended higher in these subjects than in the non-Hispanic ones. 

I'm blogging this because I'm hoping that someone with a more sophisticated understanding of this will comment and help me out here, as well as to note that until more light is shed on this I'm going to think twice about prescribing 4000mg of APAP, in whatever form, without a hard look at the risk-benefits (or follow-up monitoring). 

(NPR had an interesting story about this today.)

Happy July 4th, & take ibuprofen and not Tylenol for your hangover headache tomorrow AM.

Tuesday, July 4, 2006 by Drew Rosielle MD ·

Monday, July 3, 2006

Sometimes 3 nephrons are all you need

I'm emerging from my new-father cocoon and, well, there are so many things to blog I don't know where to begin. Here are a few blurbs for now & hopefully in the next week or so I'll begin blogging again in earnest.

1)
Oxymorphone extended release oral tabs have been approved in the US. A nice review of oxymorphone is here (& blogged about previously here).

2)
An update on Art Buchwald: he's still alive, and--per this NPR report--is planning on leaving his hospice to go to his summer home on Martha's Vineyard. Sometimes three nephrons are all you need.

3)
June PC-FACS are out.

4)
The Journal of the Canadian Dental Association has a review of oral problems for the palliative care patient. (I was able to access free full-text of this article here.) It is a general and well-written review (mucositis, thrush, xerostomia, etc.), and it's nice to see a topic like this mentioned in a non-palliative care journal.

5)
The European Journal of Cancer has an interesting article looking at clinical trials of so-called palliative chemotherapy for colon cancer, attending to whether or not the authors' interests in the trial outcomes are really palliative or life-prolonging. Part of this has to do with the ongoing confusion about 'palliative chemotherapy'--is it chemo given with the sole intention of improving quality of life or is it 'non-curative' chemotherapy given with the intention of prolonging life? The authors analyze multiple trials of chemo for advanced colon cancer, and essentially conclude that prolongation of life is generally the primary outcome priority of these trials, even if they are of 'palliative' chemotherapy. To be honest, I thought the article was somewhat contrived--using a 'straw man' rhetorical technique of a supposed mis-use of 'palliative' to describe chemotherapy even if the authors didn't actually do that. And, frankly, while quality of life outcomes should be standard for all trials involving advanced, non-curable cancers, what's wrong with evaluating primarily life-prolongation? Most patients would agree. Nevertheless I thought it was notable that someone was actually trying to formally look at the intentions and outcomes of chemotherapy for advanced cancers in this way.

An interesting secondary finding of their analysis is that, for the articles they evaluated, the presence of toxicity from chemotherapy didn't seem to have much impact on whether or not the chemotherapy had a positive quality of life impact.

6)
I'm so damn proud of this baby:

Monday, July 3, 2006 by Drew Rosielle MD ·

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