Saturday, December 24, 2005

Being a patient: hope

The New York Times has an article on hope published today in their ongoing "Being a patient" series. It tries to describe the pitfalls and perils of both "false hopelessness" as well as "false hope." It's journalistic, showing "both sides of the story," and--inevitably--quotes Emily Dickinson. But it does capture pretty well what many of us confront daily.

Dr. Eric Cassell
gives a good quote:
[Patients do not need] false hope that is personified in useless therapy with nontherapeutic effect.

(Typically, NY Times articles are only available--with free online registration--for about a week. Otherwise you need a pay NY Times Select subscription. If you're reading this in January, & really want this article, let me know.)

Saturday, December 24, 2005 by Drew Rosielle MD ·

"Respect for persons entails dialogue, perhaps even confrontation, but only to ensure honesty in each party, in the face of death."

The December Journal of Medical Ethics has an opinion piece questioning the teaching of the "Four Principles" (beneficence, non-maleficence, autonomy, and justice) to medical students.  In fact, it generally savages the 4 principles all around (not so much for the ideas themselves but for the their promotion as bedrocks of ethical medical decision making).  The piece smacks somewhat of a medical ethics in-fight, but the author has some choice things to say.  I appreciated the article for a few reasons: 1) I whole-heartedly agree that the 4 Principles are just not very useful--when was the last time you consulted them to help you think about a difficult case? 2) "autonomy" is often misused by physicians as a way of avoiding making difficult decisions about medical care with their patients (cf. the Hastings Center Report, 3rd article, by R. Burt), & 3) for its contrarian rhetoric & use of the word "palaver."

Some highlights...
[The Four Principles] remain utterly fatuous. Let me take the two neologisms first. What does beneficence mean other than "be nice"? What does non-maleficence mean other than "don't be nasty" (however noble sounding the Hippocratic Oath)? Such heavy-sounding principles are hardly going to enlighten anybody, let alone solve ethical puzzles. After all, every time I give an injection I am harming the patient. Instead, there are perhaps two sets of genuine ethical questions that are needlessly obscured by the bureaucratic verbiage: (i) is this action really harmful, in what sense, according to what criteria, in whose judgment, is the response to the harm appropriate, etc, and (ii) is this harm justified by the quality and likelihood of the subsequent benefit? My point is: if these are the real questions, why not go straight to them, without all the palaver?

Some have claimed that the Four Principles could act as a structural framework for analysis or "a useful 'checklist' approach to bioethics for those new to the field".  I would say that anybody who is morally obtuse enough to need such a checklist would not be capable of interpersonal relationships of any complexity, and certainly should not be practising medicine.

Autonomy is more philosophically robust than the first two, but it is no philosophical achievement to conclude that "X should be done because it respects the patient's autonomy". When a competent patient declares what he wants or does not want, then of course this should be respected where possible: but that's not a high blown Principle of Medical Ethics, that is how we should treat anybody. Again, the real ethical questions are unnecessarily obscured: should the patient be given what he wants when there is a doubt about whether he understands his situation and the options available? Should the patient be given what he wants when it is judged medically futile? Too much emphasis on autonomy leads to a conception of health care as merely another service to be provided to customers on demand. In this I agree with Alastair Campbell, who prefers to speak of respect for persons rather than respect for autonomy: "Respect for persons entails dialogue, perhaps even confrontation, but only to ensure honesty in each party, in the face of death".

And on this note I wish Pallimed's readers Happy Holidays & Safe Travels.

     --Drew.

by Drew Rosielle MD ·

Friday, December 23, 2005

"Palliative care with the knife, needle, poison, & ray-gun."

As the holidays come storming towards me, I haven't been posting as much, & I expect things from my end will be lax until after the new year. Thanks to Christian for picking up the slack. I can't emphasize how interesting the Hastings Center report is, and appreciate Dr. Sinclair's posts.

I wanted to briefly highlight two journal issues which have devoted a series of articles on end of life care:

First, Journal of Clinical Oncology has published 3 pieces on pediatric death & end of life care--one about end of life preferences of kids dying of cancer; one about patient and physician impressions about what constitutes quality terminal care; and the last a survey of bereaved parents regarding stress/coping/etc. What was striking about the first article (which involved interviews with 20 kids aged 10-20 years who were dying) was how similar their end of life preferences, decision making algorithms, etc. were to what I see as adults' preferences & algorithms. Top on the list was both how their disease and decisions affected family members as well as concerns about their symptoms/suffering.

The Journal of the American Osteopathic Association has published a supplement on "Holistic care for cancer pain" (Table of contents here; there's free full-text on all of these articles). There are articles on non-pharmacologic & complementary treatments of cancer pain, pharmacologic therapies, etc., as well as the American Osteopathic Association's statement on end of life care which is very reasonable.

I was greatly disappointed however by the article "Palliative care: optimizing quality of life." With a title like that, I thought it would be a nice, soft, promotional overview of the profession and patient-care model I know as 'palliative care.' Instead, we get an a section on "palliative chemotherapy" (perpetuating the confusion between non-curative but life-prolonging chemo & truly "palliative," symptom-reducing treatments...such as they are**), palliative radiotherapy, palliative surgery, and palliative interventional therapies (celiac plexus blocks and the like). All of this is swell & all of these interventions can be wonderful, but this is a very different conception of palliative care that I, & I suspect most of us, see daily--which involves help with end of life decision making, advanced care planning, grief/bereavement/spiritual support for patient and family, & a whole bunch of medical therapies for pain & symptom management. All of these, I hope, are part of "optimizing" quality of life.

I'll stop my tirade now. Maybe I'm just thrown by the title, which should instead be something like "Palliative care with the knife, needle, poison, & ray-gun."

**See here & here.

Friday, December 23, 2005 by Drew Rosielle MD ·

Dr. Hallenbeck's blog and VA Journal Club

Dr. James Hallenbeck at the VA Palo Alto has made some great online resources available for Palliative Care. He has a blog through Growthhouse, an online Palliative Care Resource center. One of his blogs talks about Palliative Care Journal Club, and he has made a available through the VA Palliative Care website 49 topics with journal references to cover most of the common Palliative Care topics. For those looking at a year-long curriculum resource or just something to read throughout the year, this is already well-developed and well-researched. I am thinking about using it in our fellowship with proper credit to Dr. Hallenbeck and the VA, of course. If you find it useful, make sure to drop him a line and let him know.

by Christian Sinclair ·

Wednesday, December 21, 2005

Intracranial Cerebral hemorrhage Prognosis

The free article from the Journal of Neurology, Neurosurgery and Psychiatry on prognosis of ICH-type strokes provides a good tool for use in the ICU. The development and validation of the Essen ICH Score can be useful to neurologists and palliative medicine physicians dealing with this devastating illness.

Using a functional index of daily activities called the
Barthel Index (0-100, worst to best) to assess independence and functional recovery, the study followed 340 patients from stroke onset to 100 days post stroke. The Essen ICH Score is derived from 3 factors: Age, NIH-Stroke Scale (NIH-SS), and NIH-SS Level of Consciousness. The maximum Essen ICH Score is 10 with >7 indicating likely death, and <3>95 on the Barthel Index). They compared the sensitivity, specificity, Positive and Negative Predictive Value (PPV and NPV) for the Essen ICH Score, physician's prediction and the old standard prognosis scales the ICH Score and the Modified ICH score.

The major improvement with the Essen ICH Score is that it helps to predict functional recovery which the ICH score and modified ICH score never did. The PPV and NPV of the Essen ICH score to predict death is 88.7% and 81.0% and to predict functional recovery is 69.8% and 86.7%. Of note these scores are very similar to the physician's predictions. In fact, the prognosis of the physicians had a better PPV for death (93.3%) and for complete recovery (79.2%).
An interesting last line of the article:

In contrast, the even higher positive predictive value of the physicians´ prediction of death may hint at a self-fulfilling prophecy.
I will have to see what the three articles that were cited have to say on this matter. The self-fulfilling prophecy of prognosis and the classic physician's dilemma is one that has been written about by Christakis in a number of articles and in his book, Death Foretold.

Wednesday, December 21, 2005 by Christian Sinclair ·

Hastings Center: EOL report

The Hastings Center has released a report on the progress made in EOL care in the past decade. It was sponsored by RWJF and published in early November. I just got around to reading most of it. Hope you find some of the topics below interesting. (Note: you do have to register and log on to get the report, but it is free.)

Here are the articles and authors:

  • Preface-Bruce Jennings
  • Death: The Distinguished Thing - Daniel Callahan
  • The End of Autonomy - Robert A. Burt
  • Living Long in Fragile Health: The New Demographics Shape End of Life Care -• Joanne Lynn
  • Conflict and Consensus at the End of Life -• Nancy Neveloff Dubler
  • Hope for the Future: Achieving the Original Intent of Advance Directives -Susan E. Hickman, Bernard J. Hammes, Alvin H. Moss, and Susan W. Tolle
  • Recognizing Death while Affirming Life: Can End of Life Reform Uphold a Disabled Person's Interest in Continued Life? - Adrienne Asch
  • Making Room for Dying: End of Life Care in Nursing Homes - Sandra H. Johnson
  • The Past and Future of Palliative Care - Kathleen M. Foley
  • The Role of Litigation in End of Life Care: A Reappraisal - Alan Meisel
  • The Quest to Reform End of Life Care: Rethinking Assumptions and Setting New Directions - Thomas H. Murray and Bruce Jennings
I don't have the time or space to go into details about some of the great articles and understanding of Palliative Care history that is contained within this report. But the reading is quick and refreshing and covers many different topics. It totals about 60 pages with a great list of references. I highly recommend it.

by Christian Sinclair ·

Friday, December 16, 2005

Symptom burden in radiation oncology clinics

The current Journal of Pain and Symptom Management has the usual assortment of interesting articles.  What struck me most, however, was a very modest article looking at changes in symptoms over time in patients undergoing radiotherapy.  This was a large, single-center study in which ~1100 patients' symptoms were prospectively measured for 5 weeks while undergoing radiotherapy (they were able to gather a full 5 weeks' worth of data on ~400 people).  This was an unselected group of people undergoing a variety of radiation therapies for a variety of different cancers.  Much data is presented in the article, too much to discuss in detail here, but their findings were pretty consistent and depressing:  troubling symptoms are common before radiotherapy and overall worsen throughout the 5 weeks.  Fatigue, drowsiness, &--of course--skin problems worsened the most.  Pain didn't decrease at all in the cohort, although they couldn't select out those receiving radiotherapy for painful bony mets.  Not surpringly, those receiving head and neck radiation seemed to fare the worse. 

These findings are congruent with another piece published in JPSM in August, surveying symptoms in a radiation oncology clinic.  All of this magnifies the need for improved palliative care in the radiation oncology clinic, and improved symptom/palliative education & support for our rad onc colleagues.

(Somewhat along the same line, in this issue there's also an article on the symptom burden of those with HIV receiving palliative care.)

Friday, December 16, 2005 by Drew Rosielle MD ·

Thursday, December 15, 2005

Artificial nutrition and hydration redux

Is it because the Holiday eating season is upon us?  Or because this is how long it takes medical journals to solicit and publish papers in response to a national trauma?  Because there's another article about artificial nutrition and hydration that's just been released, this time in the New England Journal of Medicine .  This one is much more mundane than the last one --really it's just a recap of the basic medical, ethical, & legal framework for why stopping ANH can be appropriate.  Their commentary, however, promoted several agenda items that I enjoyed seeing in the pages of The Journal--including improving physician reimbursement for family conferences & removing laws that limit the ability of surrogates to make decisions about forgoing ANH (they rightly argue that ANH should not be treated differently by the law than other medical decisions).  Also appreciated was this:

[D]ecision making about ANH in nursing homes should be shielded from financial and regulatory pressures. Although the loss of the ability to eat is an expected part of dementia, one third of cognitively impaired nursing-home residents have a feeding tube.   Nursing homes should not be reimbursed at a higher rate for residents who are receiving ANH than for those not receiving ANH, since providing ANH costs less than feeding by hand.  In addition, staff and surveyors should be informed that nursing homes should not be cited when a patient loses weight after a decision to forgo ANH.  Finally, publicly reported data on weight loss, which are available on the Centers for Medicare and Medicaid Services Web site, should exclude data for residents whose weight loss is the result of a choice to forgo ANH.

Thursday, December 15, 2005 by Drew Rosielle MD ·

Wednesday, December 14, 2005

Side effects of rapid opioid titration for cancer pain

The European J of Pain has an intriguing article looking at the side effects of rapid, inpatient opioid titration, from Sebastiano Mercadante's group in Palermo. If you read the abstract there is some implication that the study helps disentangle side effects from cancer vs. those from opioid titration, but this is unfortunately not true. (Some chart reviewer, presumably in his or her own idiosyncratic way, decided which side effects were from opioids and which weren't, and--perhaps an acknowledgment of how unreliable this is--these results were only mentioned qualitatively in the discussion.) Nevertheless it's an interesting study, one of those "let's look quantitatively at something we do everyday," with some findings worthy of comment.
The authors prospectively gathered symptom data from 33 patients who were admitted to a palliative care unity for acute symptom management. These patients all had cancer, but were not in the "terminal" phase (all had Karnofsky's >50 & a life expectancy >1mo). All had rapid opioid escalations (50% a day during the escalation phase) and, on average, achieved a stable opioid dose at 40 hours. They measured a bunch of symptoms at the time of admission, at the time the patient achieved a stable opioid dose, and then 10 and 20 days later. The symptoms that clearly worsed during this were drowsiness and constipation (drowsiness did abate by 20 days but remained a little higher than baseline). Dry mouth was a touch worse at the time patients achieved stability but this abated by day 10. Weakness, confusion, appetite, and mood didn't change much at all.
Most interestingly, however, is that nausea/vomiting didn't change at all during the study. The patients received anti-emetics at the treating doc's discretion (but 9 out of 33 patients received them), so this is heartening news that it appears possible to rapidly uptitrate opioids without this dread side effect.

This article also introduced me to a new word for enema: clyster.

Wednesday, December 14, 2005 by Drew Rosielle MD ·

Tuesday, December 13, 2005

"Artificial" vs "natural" nutrition and hydration...and Terri Schiavo

The current Archives of Internal Medicine has two articles of note.
First is a commentary questioning the distinction between 'natural' and 'artificial' nutrition and hydration .  This is their proposition:

[W]e propose that under certain circumstances surrogates may choose that all forms of hydration and nutrition be forgone, regardless of whether they are administered artificially (by tube) or naturally (by hand-feeding). More specifically, we argue that the justification for withdrawal of feedings does not hinge on whether feeding is administered artificially or naturally; rather, it is based on the fundamental rights to self-determination and bodily integrity that permit patients to refuse any unwanted intervention.
 
Their argument seems to go like this: 
If a competent patient can refuse any intervention and can choose to stop taking food/fluid--or could competently refuse being orally fed food/fluid--then why can't a surrogate make this decision?  What I'm having trouble with is imagining a situation when this would occur and be an "issue." The authors relate this to the Schiavo case, but--her parents' claims notwithstanding--she couldn't take orals (she received aggressive speech therapy early after her arrest to no avail).  My sense is they are proposing a scenerio like the following.  Someone becomes neurologically devastated but retains some swallow reflex and is technically capable of being nutritionally sustained with conscientious hand-feeding.  Their surrogate says they'd never want to be kept alive like this and asks for the hand-feeding to be stopped totally.  Is this ethical?  If it's permissible, let's say, for a competent quadriplegic to refuse needed tube feeds, then why not an incompetent neurologically devastated person refusing hand feeding via a surrogate? 
Technically, I think this is true, although an extremely unlikely/uncommon/unnecessary event.  Issues of potential discomfort due to stopping feeding aside, the major problem I have with this is via thinking about a situation I see commonly.  Particularly, I'm thinking of the situation where an elderly person undergoes a large stroke from which they are unlikely to recover much/any cognitive & motor function (although they may very well live a long time if they were 'artificially' fed); their family/surrogate says they wouldn't want to live in this condition; everyone agrees; the patient is kept comfortable with meticulous symptomatic care; and they usually die in a week or two.  During this, if the patient shows any interest--or at the initiation of the family--they are offered food/drink as a comfort measure (although this is not enough to change/delay their outcome).  During this, there's no sense of obligation towards giving the patient as much oral sustenance as they could possibly take.  And this is what seems to be missing from the article; the authors' take on the ethical injunction to not withhold oral sustenance is interpreted as an injunction to force 'nutritionally adequate' oral sustenance onto anyone who could conceivably 'take it.'  Regarding patients who are dying, most people, I would guess, interpret this ethical standard as meaning we should offer oral food/drink to them to offer comfort etc. but not out of some injunction to give 'adequate' nutrition.  If you take away the idea that it's necessary to 'force feed' people 'adequate nutrition' (I have no clue what adequate nutrition is for a dying person) then the 'need' to deny someone a little food or drink goes away. 

That was a long paragraph that I'll probably decide doesn't make sense in the morning...

Second, there's a brief analysis on public opinion about the Terri Schiavo case.  It looks at polling data on public opinion about whether people thought it was justified to remove her feeding tube, as well as how they thought the courts and politicians 'performed' during the saga.  Not too many shocks--public opinion was divided but on the whole most people thought that it was OK to remove the tube.  Most people would not want to be kept alive in a similar condition, and most thought that politicians had performed pretty poorly during the whole thing.  Not surprisingly, evangelicals and "highly religious" Catholics were more inclined to think that removing the feeding tube was a mistake.  Overall, it is heartening to know that those threatening violence against Ms. Schiavo's hospice, her husband, and Judge Greer (& even Governor Jeb Bush for not sending state troopers in to kidnap and, presumably, forcibly reinsert her feeding tube) represent a minority--albeit, however, a substantial one.  This not-too-welcome news concludes the article:
Efforts are already under way to pass legislation placing limits on who can make choices when a patient is in a vegetative or comatose state for a long period and has left no written directive, as well as regarding what level of proof should be required before such choices can be implemented. This includes a proposal for a partial moratorium on the removal of food and water from people diagnosed as being in a PVS or "minimally conscious state" in the absence of new diagnostic processes or a written directive or power of attorney by the person.  In addition, we predict that these issues are likely to spill over into the selection process for judges at various levels of government as organizations representing these individuals try to get judges appointed who share their views.

Tuesday, December 13, 2005 by Drew Rosielle MD ·

Saturday, December 10, 2005

How to subscribe to Pallimed updates using a newsreader

There's been some interest in how people can get notified when Pallimed is updated so I thought I'd try to highlight that Pallimed is accessible via XML syndication (in this case Atom, which is very much like RSS). For those of you who know what RSS/Atom/Newsreaders/News aggregators are--swell--& I added a link to the XML feed in the links section of Pallimed (it is: http://pallimed.blogspot.com/atom.xml) for convenience.

For those of you how don't know what this is but are really interested in automated update notification I suggest reading this from Wikipedia. Essentially news aggregators gather updates from news websites or blogs, in real time, and display all the updated headlines in a single place for easy access. So you can see all the new headlines/posts from, say, the NY Times, Slate, Wired News, Pallimed, and Gizmodo at once and then click on the ones you want to go to. The problem is that if you're not already using a news aggregator downloading a new program just to subscribe to Pallimed's feed seems a bit excessive. These news aggregators work best for people who frequently read multiple, constantly updated websites. Some programs have news aggregators embedded in them that many of you may already have such as the Yahoo toolbar, Google Desktop, Mozilla Firefox (you can subscribe to RSS feeds and display them in the bookmarks toolbar; in addition there are Firefox add-ons that integrate newsreaders into the browser window), Safari, Gmail--I'm sure there are more.

Yes, all of this seems like a lot of work, however there are no other ways I know of to get automatic updates to Pallimed. We usually try to make at least 3 postings a week so it's updated pretty regularly. If there's sufficient interest I can make up some sort of Pallimed New Post Notification Email List--so let me know (via email) if that's something you'd be interested in.

(Growthhouse.org has a good overview of syndication.)

Saturday, December 10, 2005 by Drew Rosielle MD ·

Transdermal fentanyl vs. SR morphine

Spine has published a randomized trial of transdermal fentanyl vs. SR morphine for chronic low back pain.  I immediately took note because here was a chance to evaluate these two drugs head to head.  The study, unfortunately, is rife with problems, but there are some interesting findings nevertheless.  It is a randomized, but non-blinded, study of transdermal fentanyl vs. SR morphine in "strong-opioid" naive patients with chronic low back pain.  Basically they randomized ~670 patients to either 25mcg/hr of fentanyl or 30mg bid of MS Contin, and gave both groups reasonable, patient-directed titration instructions.  Concern about starting long-acting opioids on opioid-naive patients was not mentioned, & to their credit they didn't have any major adverse events (given the recent excitement about this topic, one would have appreciate more mention of this from the authors, especially about how much "weak" opioid use--were these patients truly opioid naive, etc?)
The authors found that after an average of ~240 days, pain was the same & dosing was roughly equianalgesic between the groups (mean morphine dose of 140mg/day vs. fentanyl dose of 57mcg/hr).  Pain ratings were equal in each groups (mean visual analog scores ~55/100mm) at the end of the study.  I was perplexed that baseline VAS scores weren't mentioned at all; for that matter neither was baseline medication use; nor, while we're at it, were standardized as-needed short-acting analgesics part of the protocol. The abstract annoyingly makes the claims that while the two drugs were equivalent on the VAS, fentanyl was 'significantly' better for pain at rest and pain at night.  All of this was based on a per-protocal analysis and the actual difference in percent of patients reporting pain at rest/night was miniscule (a few percentage points); my point here is that this is a likely meaningless finding that has made its way into probably the most important part of the article--the abstract.  In fact, this was one of those articles where I had to read each paragraph twice to keep track of when they were reporting an intention-to-treat analysis or a per-protocol.  This is all a bad sign.  In addition, in the "Table 1" (which is always patient characteristics) they inexplicably divide the patients' pain into 'neuropathic,' 'nociceptive,' 'neuropathic with psychologic factors,' & 'nociceptive with psychologic factors.'  Huh?  There's no mention as to how these distinctions were made or by whom; nor did they do anything with these distinctions later on.  This too is a bad sign.

What did truly seem to be significantly different between the groups was that constipation occured more frequently with morphine than transdermal fentanyl: 48 vs 31%.  Frustratingly, starting or at least offering stool softeners/stimulant laxatives to the patients wasn't part of the protocol, despite it being a well accepted standard of care (although I'll be the first to admit that that's not data-driven).  Nevertheless, this is the first data I've seen in a head-to-head trial supporting the notion that transdermal fentanyl is less constipating than oral morphine, not that I've ever looked.

Janssen, who has recently put out a press release warning about starting opioid naive patients on Duragesic, funded the study.

by Drew Rosielle MD ·

Friday, December 9, 2005

Many things mentioned briefly

Things are stacking up this week...

Supportive Cancer Care has a review on oxymorphone, highlighting the new oral short & long-acting formulations. It's written by Eric Promer from UCLA, but it's unclear to me whether the oral form of oxymorphone is actually now, or is going to be, available in the US (it's implied that these are now available, but not specified where, and Eric Prommer is from the States, but for the life of me I can't find any oral formulations of oxymorphone available here). Nevertheless--if it does become available--this will be a good reference for us oxymorphone novices, as the article reviews the pharmakokinetics, supporting clinical data, and opioid conversion data for oxymorphone. Leave a comment if you know of the status of oral oxymorphone in the US.

The New England J of Medicine has published a "medical progress" article on renal cell carcinoma. It's full of molecular biology. As I've recently been keeping track of mentions of palliative/supportive care in cancer review articles in major journals, I'll note that this one doesn't mention it at all. Thus, we have sentences like these...
"The poor prognosis of advanced renal-cell carcinoma demands an aggressive search for new therapeutic agents and strategies."
True, to be sure; but this poor prognosis also demands top-notch supportive and palliative care.

Chest has published the American College of Chest Physicians statement on end of life and palliative care for people with advanced cardiopulmonary disease. For professional society statements it is quite excellent--a very thorough overview. I particularly appreciated the mention of the need for better/more education for medical trainees on end of life/palliative care. In addition it has a section on care-giver (that is--nurses/docs/etc.) support/grief. I don't recall seeing this mentioned in any professional society statements before.

And finally, December's J of the American Geriatrics Society has multiple end of life related articles, too many to review...

DNR trends in patients admitted to nursing homes under the medicare benefit (rates vary widely geographically)

Cataract surgery doesn't seem to improve cognitive function (this has nothing to do with palliative care--it's just interesting)

Racial differences in the place of death for hospice patients (African Americans are a little more likely than whites to die in an inpatient hospice)

A descriptive study on the development of DNR policies in Belgium

and...In a cohort of nursing home residents--those who died utilized more medical resources than those who didn't die. Yes, it's true.



Friday, December 9, 2005 by Drew Rosielle MD ·

Tuesday, December 6, 2005

"I don't believe in God. I believe in Schering-Plough."

Lancet Oncology has published an article on quality of life for those with glioblastoma.  Specifically, the authors present data from a previously published randomized controlled trial showing that adding temozolomide to radiation therapy prolonged life by ~2.5 months for those with gliobastomas.  During the same trial the authors gathered health-related quality of life data for ~570 patients receiving either radiation or radiation plus temozolomide.  Essentially, they found that except for a bit more GI and appetite disturbance during the treatment phase, the groups didn't differ much--that is, temozolamide didn't do much harm, & clearly did some good.  All of this is fine.  I was a little curious as to why they published the quality of life data as a separate paper, and a little confused as to whether I thought this was a good thing.  One could argue that publishing the QOL data separately gives special attention to the importance of QOL as an outcome, especially for a uniformly and rapidly mortal disease like glioblastoma.  Conversely, keeping the QOL data from the "major" article--in the New England Journal of Medicine no less--relegates it to a secondary status behind the all-powerful Mortality Outcome.  I really don't know, but am inclined to think that publishing it separately is best, not least because it flashing "quality of life" in the title made me pay particular attention to the piece. 

Both of the studies were, of course, funded by Schering-Plough.

Which brings me to the first mention of morbid palliative care related humor on this blog.  A non-palliative care colleauge of mine was telling me about a patient which she eventually referred to the pall care service at my institution.  She was trying to be a good, thorough physician, and tried to explore spirituality with the patient who was transitioning to the "dying phase" of her cancer.  The patient's response was "I don't believe in God.  I believe in Schering-Plough." 

Tuesday, December 6, 2005 by Drew Rosielle MD ·

Monday, December 5, 2005

Risk of death with conventional vs atypical antipsychotics

Well, the debate evolves. The New England Journal of Medicine has published a study trying to compare the risk of death in elderly patients who take conventional vs atypical antipsychotics. (Check out the Oct. 20 posting for another blog about this.) Everyone has been a little excited recently about the apparent increased risk of death associated with elderly dementia patients on newer antipsychotics, and many have asked the obvious question "Do conventional antipsychotics have this increased risk also?" The NEJM article tries to answer this--it's suggestive--but overall I think it just muddies the water, despite getting a decent amount of media attention. It's a retrospective cohort study from a Pennsylvania prescription database that looks at people 65 years old & older who received either conventional or atypical antipsychotics at any time. 23,000 people were evaluated over a 10 year period; the authors looked at who died within 180 days of receiving an antipsychotic prescription. They found that 18% of people who received typical antipsychotics died within 180 days of the prescription vs 14.6% of those who received newer agents. Not a big difference, but highly significant in this large population. This mortality difference was largest immediately after the index prescription date and tapered off afterwards (that is, there was a wide difference in mortality within 30 days of the index prescription which became less apparent as time passed beyond the intial date of the prescription). The authors then did multiple subgroup analyses controlling for medical comorbidities and still found a higher risk amongst the conventional antipsychotics group.
My interpretation of the data presented, even with the subgroup analyses, is that--compared to atypical antipsychotics--the use of typical ones in this population is a marker of a higher risk of death, & that no grander conclusions can be made. Looking through the characteristics of the conventional vs atypical group it is clear that they are medically distinct groups (those who received conventional antipsychotics were more likely to have "medical" diseases, whereas the atypical group were more likely to have neuro or psychiatric illnesses such as dementia, delirium, mood disorders). The attempt to control for comorbidity (things like CHF or HIV) does not rule out an unmeasured factor being related to mortality and conventional antipsychotic use. The fact that the difference in mortality between conventional & atypical antipsychotics was more pronounced early on may mean nothing more than docs reaching for haloperiodol more often than quetiapine for patients they sense are doing poorly or dying. In addition, the data implicating atypicals comes from recent randomized placebo-controlled trials which unfortunately clearly show a small increase in the risk of death amongst elderly demented people taking atypicals chronically. Not only was this new study not a randomized trial, but there was no way of measuring in the study how much & for how long the patients received the antipsychotics--many of these precriptions could have been for one time orders, etc. My point is that what the authors of this article are catching here is a different population & circumstance than the recent trials involving atypicals.
Of course this does not mean that conventional antipsychotics are any more safer than newer ones! They may very well not be, & if the purported mechanisms of lethality from antipsychotics (anticholinergic effects, QT prolongation, etc) are true then it is likely that conventional agents are as harmful as newer ones. This paper is suggestive at best however and not much more should be taken from it. My guess is is that this will be looked at with increasing scrutiny in the future.

NEJM has also early-released a few articles & an editorial about the outbreak of the new strain of C. difficile in Quebec. Humbling stuff, that could seriously affect our patients lives if it becomes pandemic.

P.S. As I write this Monday PM, Blogspot seems to be having trouble with permalinks, so let me know if you have any trouble with links on the site. Thanks.

Monday, December 5, 2005 by Drew Rosielle MD ·

Thursday, December 1, 2005

Palliative care for Muslims

The J of Supportive Oncology has published a piece overviewing palliative care for Muslim patients (unfortunately there is no abstract & the article is not yet indexed in PubMed; here is the table of contents for the issue; per the website free full-text will be available January 2006; the print version of the journal is available free to anyone in the field in the US).  A Muslim colleague of mine alerted me to the article & vetted it--he thought it was spot on.  It overviews the meaning of suffering in Islam, medical ethics in Islam, and particular issues in Islam at the end of life (modesty, sedating medications, prayer & other rituals).  What my colleague thought was most difficult for many Muslim patients in the West were two things: 1) the importance of Salah, the 5 daily prayers, and the difficulties patients encounter when they are ill--both with physically performing the prayers as well as having their need to pray accomodated by the health care system, & 2) modesty (by Muslim women especially) which results in less eye contact and genial interaction between patient and doctor which is often mistaken for lack of interest or engagement.  Both of these issues are discussed at length in the article.  For those of you who followed the Lancet end-of-life-by-world-religion series, I found this article much more informative that the Lancet one.

Thursday, December 1, 2005 by Drew Rosielle MD ·

Tuesday, November 29, 2005

Respiratory Therapists and Terminal Extubation

As a palliative medicine physician involved in terminal extubations in the intensive care unit, I always encourage a team approach. During my residency I learned very quickly to include the respiratory therapist (RT) in making the plan to terminally extubate someone. I always ask the RT and the bedside nurse before we terminally extubate a patient two questions: Are you OK with this course of action? Do you have any suggestions to improve the care around the extubation? In addition I review the orders and the planned way we will extubate. I also stay with the patient before during and after the extubation to ensure quick access for symptom control measures.

After talking to a RT colleague of mine, I did a lit search on their involvement in the process and ran across this survey of RT attitudes and concerns regarding terminal extubation in the journal of Respiratory Care (free full text here). Since the RT and not the nurse or the physician is the person who actually extubates and enacts the order there may be issues of stress that are not always openly addressed. A one-page questionnaire was given to 183 RT's at 6 facilities in San Diego. Some of the more interesting findings were:

On average, respondents had been involved in terminal extubation on 2.2 occasions (range 0-12) within the last year, and 33 times in their entire career.
The RT's were rarely included in the discussion with family or patient at the time of the decision. The estimates of physician presence averaged 18.6% (range 5.5-66%), and only 29% of RT's felt the attending physician should be present at time of terminal extubation. But they did find a correlation between the RT's perception of need for attending presence and how often the RT's estimated they were present. At the facility with 66% estimate of MD presence, more RT's felt their presence was important. This fact demonstrates how much the difference in ICU cultures can influence EOL care.

There are many more places this survey could go, particularly surveying hospitals with a strong or weak palliative medicine presence.

Tuesday, November 29, 2005 by Christian Sinclair ·

Jaw osteonecrosis with bisphosphonates; new PC-FACS

A couple things:
The current J of Clinical Oncology has a study on the incidence of jaw osteonecrosis in cancer patients receiving bisphosphonates. This is a prospective cohort study of 252 patients with heterogeneous cancers who received long-term bisphosphonates (median of 15 infusions over 20 months). Zoledronic acid & pamidronate were mostly used. Amount of exposure (median of 35 vs 15 treatments in those who did vs did not develop osteonecrosis) and time of exposure (median of 39 vs 19 months in those who did vs did not develop osteonecrosis) were strongly correlated with risk of osteonecrosis. The authors conclude with this:
The American Society of Clinical Oncology guidelines for [multiple myeloma] and breast cancer suggest that bisphosphonates should be administered "until there is evidence of a substantial decline in the patient's general performance status." Taking into consideration the natural history of these diseases, this could result in administration of bisphosphonates to some patients for several years. Nevertheless, the studies on which current guidelines were based usually administered bisphosphonates for a maximum of 2 years. In view of the data reported by us as well as by others, caution is required for use of pamidronate and zoledronic acid beyond 2 years.

This article is part of a larger focus of the issue of cancer treatment complications, including an interesting paper on regression of radiation fibrosis with pe
ntoxifylline.

Also, the latest PC-FACS are out--excellent as always--but it seems the AAHPM is going to restrict them to members only (other than a free trial for non-members) & there are hints they may become subscription only. Perhaps this is part of a larger effort to improve the offerings to AAHPM members & thereby boost membership but there must be better ways. Mostly I'm afraid that this is going to have the inevitable effect of limiting the scope and influence of this valuable resource. Should people sign-up and pay for these? Hell yes. But I've been noticing what has happened at the NY Times ever since it hid its Op-Ed columnists behind a pay-only scheme ("NY Times Select"). Previously, 2-3 of the "top emailed articles" on NYtimes.com were always the latest from Krugman, Friedman, Dowd, and company. Now you rarely see any of them on the list. Sigh. Anyway, maybe there's some master plan that we aren't privvy to.

And finally--I'm trying to be brief--the current New England Journal of Medicine has a piece by GJ Annas about the Supreme Court's California medical marijuana ruling and the commerce clause and what it may all mean for medicine. The upcoming decision on the Oregon physician assisted suicide challenge is mentioned.

by Drew Rosielle MD ·

Monday, November 28, 2005

Epidural methadone for dyspnea

Chest has published an open-label trial of epidural methadone to relieve dyspnea from COPD. The idea behind the study was that the authors had noticed a marked reduction in dyspnea in COPD patients after lung-volume reduction surgery who received epidural analgesia for post-operative pain. The authors enrolled 9 patients with advanced COPD (FEV1 <35% of predicted), placed a T4-5 epidural catheter in each (these were external devices...not implanted pumps), and infused methadone at 6mg/day. They were followed for one month. After a month 3 had dropped out--one for a catheter infection and two due to catheter migration. Essentially, all the findings were positive: at 1 week and 1 month dyspnea & quality of life had improved compared to baseline; the 6 minute walk test (a standard test of exercise capacity in lung disease) had improved; and there was no evidence of CO2 retention (in fact pCO2 decreased a touch in the group). Given that the major putative benefits of epidural vs. systemic opioids are fewer side effects I was disappointed that they appeared to not collect ANY data on the typical & limiting opioid side effects (nausea, somnolence, dysphoria, constipation, etc). In addition, the authors noted that, after completion of the month, most of the remaining patients eventually discontinued the pump due to migration or infection--problems partially due to the use of external pumps. To me, this study has provided "proof of principle" that epidural methadone can palliate dyspnea--that it offers some benefits. What is clearly needed now is a comparison study with systemic opioids to see if the risks & costs involved outweigh those benefits.

Monday, November 28, 2005 by Drew Rosielle MD ·

Monday, November 21, 2005

Fatigue after breast cancer treatment & a review of treatment for cancer-related anorexia in JCO

The current J of Clinical Oncology has several articles of note.
First, a longitudinal look at factors related to fatigue in woman undergoing standard vs. high-dose chemotherapy for breast cancer. This was a prospective study looking at levels of fatigue, mental health, musculoskeletal pain, and hemoglobin/anemia in women receiving standard vs. high-dose chemo for high risk breast cancer. They were followed for 3 years. Fatigue occurred in ~20% of patients, did not change over time, and was not different between the treatment groups. There was a minor relationship between anemia and fatigue, a moderate one between musculoskeletal pain and fatigue, and a strong one between "mental health" and fatigue. This mental health score was derived from the Short Form 36 quality of life assessment & can't directly be used as an index of depression or anxiety or any specific mental health diagnosis. No conclusions can be drawn as to a causative relationship between mental health<-->fatigue<-->pain in any direction; however the relationship between mental health and fatigue was evident at the time of randomization suggesting that it is not a treatment effect.
Also, there's a systematic review of treatment for cancer-related anorexia and weight loss. It is not a metaanalysis due, presumably, to the heterogeneity between the trials; only randomized controlled trials were considered & each was systematically rated for quality however. I won't belabor this: the authors found evidence only for progestins (megestrol and medroxyprogesterone acetate) and corticosteroids for improving appetite or weight gain (which were their major outcome measures). They did mention if quality of life was measured/affected during the trials & it overall appears to be a wash--maybe for methylprednisolone & maybe for MPA. How much, and in what ways, treatment improved QOL was not included in this study. The authors note: "treatment of anorexia alone is unlikely to have a major impact on the course of disease, because tumor biology and the proinflammatory response by the host will not be altered by appetite stimulants." Overall one is left with a sense of therapeutic nihilism about the current state of the art. Anorexia and weight loss are poor prognostic markers, as well as often disturbing to patients and families. A couple treatments for this symptom (progestins and steroids) work, as far as subjectively improving anorexia and curbing weight loss, but evidence of further benefits is small.
And...
Happy Thanksgiving to all of Pallimed's readers. My posts this week will probably be sparse as I celebrate the holiday.

Monday, November 21, 2005 by Drew Rosielle MD ·

Saturday, November 19, 2005

Meta-analysis of sedatives for insomnia in the elderly

BMJ has just published a metaanalysis evaluating the risks-benefits of sedatives for treating insomnia in the elderly.  Sedatives here means benzodiazepines and benzo receptor agonists (zolpidem/Ambien, zaleplon/Sonata, etc).  It aggregates data from 24 (total n=2400) randomized trials of sedative agents in people >60 years old.  Most of the studies were for 2 weeks or less, although a couple were longer.  They found that the number-needed-to-treat for any measurable sleep "improvement" (which was measured heterogeneously across the studies) was 13, & the number-needed-to-harm was 6 (this number catches any measurable side effect...from benign--GI upset--to severe--falls, etc).  The average increase in sleep length was 25 minutes vs. placebo.  The head-to-head studies of benzo's vs benzodiazepine receptor agonists essentially found no difference in effectiveness or adverse effects, including cognitive ones.  Morning or daytime fatigue was significantly worse with active treatment vs. placebo, with quite a strong odds ratio (3.8, 1.88 to 7.8, p<.001).  They did not mention that they were able to compare benzos to non-benzos specifically for this outcome. 
All of this has me asking why do I prescribe these drugs at all and why do patients like them so much?  What's the point if you feel worse the next day?  This is naive of course, and insomnia is an unpleasant symptom that may have nothing to do with actual sleep/daytime energy/etc. for many patients, and these agents are effective (somewhat) for this symptom.  What disappoints me is how relatively high the NNT is:  13 is great when you're saving lives through cardiovascular drugs but not to treat an unpleasant symptom.  In addition, the NNH is not helpful in deciding, for a given patient, if the benefits outweigh the risks.  GI upset or headache are qualitatively different from falls/severe psychomotor side effects and aggregating a global NNH is clinically meaningless.

And, I must add that in the middle of the article sits this sentence:
A significant improvement in sleep quality improved significantly[.]   It actually makes sense in context but there must be a better way to say this...

Saturday, November 19, 2005 by Drew Rosielle MD ·

Friday, November 18, 2005

New and Lingering Controversies in Pediatric EOL Care

My wife is a pediatric emergency physician (done with fellowship in 2006!) and so I get the pleasure of perusing her Pediatrics journal when it is delivered to our mailbox monthly. Well the October 2005 Issue was particularly exciting because my wife was the lead author on the first paper. (Not a palliative med article)

But since anyone reading this blog is unlikely to be primarily concerned about the correlation between HSV and the signs of pediatric abuse, I will get to the 2 palliative medicine minded articles that were in this issue. I will focus here on one of them.

The first article highlighted 6 controversies in Pediatric EOL care and the knowledge of these issues from residents, attendings and nurses. Now in reading this I thought these are just as relevant in adult EOL care and I thought there could probably be more pediatric oriented EOL care issues than these. Here are the 6 issues.

1. Withholding versus withdrawing life support.
An assessment, from the child's perspective, of the burdens and benefits of offering or continuing treatment is what should count ethically, not whether a treatment has begun or not.

2. Medically supplied food and fluids.
Medically supplied nutrition and
hydration are not ethically and legally required in all circumstances. They can be stopped or foregone, like all other medical interventions, when their burdens outweigh their benefits.

3. Use of opioids.
However, recent research suggests that, if the dosage has been titrated properly, then respiratory depression is rare even when opioids are used at very high levels.

4. Use of paralytic agents.
Their use should never be initiated during the withdrawal of life-sustaining treatments.

5. Brain death.
In all 50 states, death can be defined on the basis
of neurologic criteria (complete cessation of brain function) as well as cardiac criteria, and permission of the family is not necessary for withdrawal of ventilatory support when either type of criteria is met.

6. The dead-donor rule.
Permanently unconscious patients are not allowed, by current ethical standards, to serve as organ donors.
I would think a more pediatric oriented EOL dilemma is the issue of autonomy and surrogate decision-making in the pediatric patient; especially for the tween to teenager ages.

They took these 6 issues and asked nurses, attendings and residents about them and found that many had concerns of conscience. Statements such as:


At times, I have acted against my conscience in
providing treatment to children in my care.

“Sometimes I feel we are saving children who should
not be saved.”


demonstrated that pediatric Hem/Onc attendings felt this less than critical care attendings (p=.0051). And over 50% of house officers and nurses agreed with these statements. But attendings agreed with these statements around 30% of the time. There are some more nuggets in this article, and it is a good read for contrasting what people say they know, and what they show they know.

Friday, November 18, 2005 by Christian Sinclair ·

Wednesday, November 16, 2005

Myers-Briggs & ICU end of life decisions

Anaesthesia has an interesting and somewhat unusual article about end of life decision making in the ICU and Myers-Briggs personality typing. It looks at several years of a single ICU's practice of limiting/withdrawing life sustaining care prior to death, and analyzes the frequency of those decisions by attending physician, and by the attending physician's Myers-Briggs personality type (yes, I am embracing Christian's use of Wikipedia). The study is unfortunately limited by a whole series of assumptions that the authors made to determine, given how often the attendings worked, what percent of the treatment limiting decisions they should have each made (assuming there was no variation between attendings). Much of what they found is not surprising: ~80% of ICU deaths were made after a decision to limit life-sustaining care in some way & there was a wide variation amongst physicians regarding the frequency of being involved with treatment limiting decisions. What they then did was to administer the MB to the docs & they found that those who were disproportionately involved with treatment limiting decisions clustered towards the 'judging' end of the judging/perceiving domain.

Wikipedia on judging types:
J[udging]-types tend to prefer a step-by-step (left brain: parts to whole) approach to life, relying on external rules and procedures, and prefering quick closure...

& the authors of the article:
These individuals prefer a clear idea of what is expected, communication that is clear and concise, and decisions to be made quickely, clearly and finally.

What all this means is entirely unclear. However, it is refreshing to consider that the wide inter-personal variability amongst physicians regarding a willingness to broach the withdrawing of life-sustaining care in dying patients has a measure of predictability. On the other hand it's very possible that this clustering on the MB is catching a completely different phenomena not measured by the authors (place of origin, social class, type of medical training [pulmonary vs. anesthesia], age/experience, religiousity, who knows...). I'm just glad the authors asked.

Wednesday, November 16, 2005 by Drew Rosielle MD ·

Pallimed - Now on Wikipedia!

Pallimed: A Palliative Medicine Blog has now been linked to the Wikipedia.

(Pallimed, Blog, and Wikipedia: What are 3 words that my grandparents might confuse for curse words? What are three words I never would have said 12 months ago?)

For those of you not familiar with the editable by anyone internet sensation, Wikipedia, you should check it out. For those already familiar with the Wikipedia, you may have found the Pallimed blog by clicking on the link on the bottom of the palliative care page.

by Christian Sinclair ·

Tuesday, November 15, 2005

Terri Schiavo: A look back

I had the pleasure of hearing Mary Labyak, MSSW, LCSW of The Hospice of the Florida Suncoast speak at the Missouri Hospice and Palliative Care Association meeting this week. She spoke about her experiences as President of the hospice agency that was charged with caring for Mrs. Schiavo. Ms. Labyak's talk fit very well with a recent article in the Annals of Internal Medicine reviewing Mrs. Schiavo's case from three different perspectives. A firm knowledge of the legal, ethical, and medical perspectives of this case from fellow professionals and not the media is essential for anyone willing to call themselves a palliative medicine professional.

Regardless of your discipline in end-of-life care, the issues surrounding the case of Mrs. Schiavo are frequently recalled by patients, families and health care staff. One of my main functions is to overcome misconceptions about end-of-life care that are pervasive. By having a clear handle on the facts of this important case, we do a better service.

A quick review of the American Academy of Neurology’s requirements for persistent vegetative state is followed by a few important facts that discount the likelihood of improved functional status of a prolonged vegetative state:

Of the patients in the persistent vegetative state for more than 3 months after nontraumatic injuries, the probability of moderate disability or good recovery was 1% (99% CI, 0% to 4%), but for patients still in the persistent vegetative state at 6 months, this probability was 0%. No patient, even those with traumatic brain injury, has been reported to recover after a full year of being in the persistent vegetative state.
The authors are a lawyer, an ethicist, and a neurologist from Nashville. (Which reminds me of a good joke...) They do a concise and competent job reviewing this case for the health care professionals interested in end-of-life, palliative medicine and ethics.

Tuesday, November 15, 2005 by Christian Sinclair ·

It's Me - The New Contributor

Thank you for the kind introduction Drew.

I am glad to be a contributor to the Palllimed Blog. Together, Drew and I may be able to cover more area to help you, the Pallimed Blog reader, become more informed about the advances in Palliative Medicine. We appreciate any comments on our posts and any feedback about the site. I look forward to collaborating with Drew and the Pallimed readers!

Christian Sinclair

by Christian Sinclair ·

New contributor!

I'm very excited to announce that Dr. Christian Sinclair of the Kansas City Hospice is joining Pallimed.  I'll let him introduce himself to the blog's readers as he sees fit.  I'll be tweaking the blog's look over the next week to accomodate the change.

by Drew Rosielle MD ·

Sunday, November 13, 2005

Bisphosphonates for bone mets in prostate cancer

The current J of Clinical Oncology is devoted to prostate cancer, & along those lines has a review on bisphosphonates for the prevention and treatment of bone metastases in prostate cancer.  It opens with a succinct summary of the pathophysiology of bony mets in prostate cancer, as well as the pharmacodynamics of bisphosphonates.  Next, it critically summarizes the data for bisphosphonates in prostate cancer, which is not much:  the only drug/situation that has demonstrated benefit is zoledronic acid for the treatment of asymptomatic mets in androgen-independent prostate cancer.  It showed a modest reduction in skeletal events (pathologic fracture, spinal cord compression, surgery or radiation therapy to bone, or change in antineoplastic treatment to treat bone pain) with a number needed to treat of ~10 to prevent one complication for 15 months of treatment.  I'm not suggesting a NNT of 10 is high, especially given the potentially devastating complications--cord compression, etc.--it's just that I was surprised by how little evidence there was. 
The other article I'll note from this issue is a review of therapy for advanced & refractory prostate cancer.  I'll give kudos to the authors for noting that palliation, pain, and supportive therapy are of primary importance in this setting & talking about that first thing in the article, before talking about chemo, etc.  It seems usually in review articles of this sort, supportive care is relegated to a paragraph at the end, if it all.  Newer chemotherapeutic agents and other treatments are briefly reviewed in the rest of the article.

Changes:  I am excited to announce that in the next week or so I'll be joined by a co-blogger on Pallimed!  More info to come....

Sunday, November 13, 2005 by Drew Rosielle MD ·

Friday, November 11, 2005

Attitudes of surgeons towards palliation in cancer

September's Archives of Surgery has a paper examining surgeon's training experiences in palliative care and attitudes towards what they describe as "palliation in cancer."  The study was based on a survey of a heterogeneous group of surgeons in the Sacramento area.  Like most of the rest of the world, the surgeons evaluated had zero to little palliative care training (almost none in residency and fellowship--altho most had been practicing for over a decade--and about half had had a few hours of palliative care CME).  What an opportunity....

Friday, November 11, 2005 by Drew Rosielle MD ·

FDA approves new warnings for celecoxib

Medscape is reporting that the FDA has approved new warnings about celecoxib today (article here--requires free Medscape membership--I can't currently find this news story anywhere else which is weird). This seems to be the meat of it:
"The FDA also warned that chronic use of celecoxib may be linked to an increased risk for serious and potentially fatal cardiovascular thrombotic events, MI, and stroke. As with other NSAIDs, these risks may increase in the presence of existing cardiovascular disease and/or related risk factors. The warning was based on results of the Prevention of Sporadic Colorectal Adenomas with Celecoxib trial in 1,356 patients, showing that use of 400 mg of celecoxib twice daily was linked to a 3.4-fold increase in the composite risk of cardiovascular death, MI, or stroke, relative to placebo (95% confidence interval [CI], 1.4 - 8.5). In patients receiving 200 mg of celecoxib twice daily, the relative risk was 2.4 (95% CI, 1.0 - 6.4)."

Update Nov 13, 2005: well the reason I couldn't find any other news stories on this is because the warnings came out in July, which I completely missed, and for some reason Medscape decided to write a news story about it on the 9th. I'm laughing at myself.

by Drew Rosielle MD ·

Wednesday, November 9, 2005

"Each experiment was started at 2:00pm"

Pain has a couple of very interesting piece amidst the murine model papers I've never been able to appreciate.  First, an editorial about current research that buprenorphine not only has analgesic effects but also anti-hyperalgesic effects (as in opioid-induced hyperalgesia), via kappa-opioid receptor antagonism.  The editorial of course refers to an actual article in Pain, but for the average reader (like me) I'd suggest sticking with the editorial.  "Today, opioids cannot only be considered for their potency to reduce nociceptive symptoms but also for their ability to oppose active processes leading to pain hypersensitivity. This might be a new and beneficial approach for preemptive analgesia and improving the treatment of some forms of chronic pain dominated by central sensitization."
And then, the article which explains several life-long habits of mine:  chewing gum relieves pain.  I'm not going to bother to critique this one--it's actually really interesting with a lengthy discussion about serotonin in nociception, speculation about the the necessity of rhythmic chewing to achieve the nociception, and a brief review of the chewing & analgesia literature. I do want to highlight my appreciation of the authors' quietly funny prose however:
"The NFR recording and stimulating electrodes were attached to the subject. All recording and stimulation electrode sites were cleaned and gently abraded. The reflex was induced by transcutaneous electrical stimulation of the sural nerve at the right ankle while the subject reclined in a comfortable armchair with the lower legs bent to an angle of less than 150 degrees so as to achieve a state of muscular relaxation."

"Each experiment was started at 2:00pm.
A subject was asked to chew gum voluntarily and rhythmically for 20 min at a comfortable speed (task experiment). To ensure the intensity and rhythm of mastication, we monitored EMG of masseter muscle throughout gum chewing. The composition of gum (Xylish sugarless, Meiji Co., Tokyo, Japan) was gumbase, maltitol, xylitol and so on. The flavor was mint. The quantity of gum was up to the subject. The mean quantity was 4.3±1.4 g."

Finally, there's a review on neuropathic pain from the non-surgical treatment of breast cancer (chemo and radiation therapy).

 

Wednesday, November 9, 2005 by Drew Rosielle MD ·

Tuesday, November 8, 2005

The academic hospice

Annals of Internal Medicine has an article from the San Diego Hospice about " The Academic Hospice."  It is a brief introduction of the relatively new (& according to the authors, exclusive field as there are only 6 in the US) phenomenon.  It is written with the confidence of a specialty/field which is about to come into its own in the mainstream of US medicine.  What, however, is most interesting about the piece are its several opening paragraphs weaving together the history of hospice with the history of medicine.  A sample:

The link between medicine and religion was inextricable until the Renaissance. Religious societies ran the earliest institutions called hospices that cared for the ill, primarily people who became ill while traveling. People either recovered and continued traveling, or died. The words hospitality, hotel, hospice, hostel, and hospital are all derived from the same Latin root word hospes, meaning "guest". Hospitals as identifiable institutions evolved from these early efforts. For example, St. Bartholomew's Hospital in London was founded in 1123. At the time, there was no practical difference between the meaning of hospital and hospice. Hospitals as institutions for teaching evolved from the observation that the care and study of patients are more convenient for physicians if the patients are assembled in one place. The need for hospitals to "market" themselves also evolved. Records from 1544 from St. Bartholomew's Hospital indicate that patients were not to be admitted if they had incurable diseases or conditions. The hospital apparently wanted a reputation for caring for people who could be cured. Subsequently, the term hospice was reserved for dedicated places for the care of patients who were incurably ill (and poor). These hospices were mostly administered and staffed by Christian religious orders in France, Ireland, Scotland, and England. In the United States, early examples of hospice care were the Dominican Sisters of Hawthorne and Calvary Hospital, both located in New York City.

Tuesday, November 8, 2005 by Drew Rosielle MD ·

Monday, November 7, 2005

Schiavo & tube feeding articles in Mayo Clinical Proceedings

November's Mayo Clinical Proceedings has several important articles ( table of contents for the entire issue). 
First, is a lengthy summary and discussion of the, as they put it, Terri Schiavo "saga," that grew out of a grand rounds at Mayo.  It is quite thorough and a good read, and one hopes--probably unrealistically--that certain public officials and prominent opinion makers will read this with an open mind.  It ends with several pages of addressing the specific ethical questions the case raised, as well as asking "Is there a better way?"  Which brings up something I meant to blog a while back:  I attended a speech given by Michael Schiavo (at an end of life ethics conference) & he said a few interesting things.  First, given that it is often mentioned as an unclear point in the Schiavo history (including this article), Michael Schiavo stated that it was, indeed a conflict over money/the settlement that caused the rift between him and the Schindlers.  The second, and much more interesting point, is that Mr. Schiavo said it's his belief that there's nothing doctors/the medical community could have done to prevent the conflict, that it was a family/personal conflict, & not a failure of Terri Schiavo's docs or anyone else.  As a doc, that sounds reassuring to me, and on reviewing the case in this article, it seems like he's right.  Despite being touchstones for all of us, cases like Schiavo's going to the courts are rare; and while getting the courts involved is generally undesirable her case seems like a reasonable one for the courts (to establish what her wishes would be given there was intractable conflict within the family & no written evidence of her wishes).  What went tragically wrong with the case was not this but the extra-judicial involvement, the political intervention--"Terri's Law," Jeb Bush, Bill Frist's speech, Tom Delay's intimations of violence against "activist judges," President Bush flying back from Crawford, Judge Greer getting death threats and booted out of his church, etc.  That's the problem & promoting advanced directives isn't going to fix that....
I've already blogged too long tonight, but there's also a review of the medical and ethical aspects of long-term enteral tube feeding.  Thorough, and despite being written by a bunch of MD's, seems to have a distinct speech-pathologist flavor to it.  It presents much of the same material as the JAMA 2004 review of tube feeding, with more stuff on post-stroke & cancer patients. 
And finally, there's a review of adult acute lymphoblastic leukemia for those of you interested.

Monday, November 7, 2005 by Drew Rosielle MD ·

Wednesday, November 2, 2005

Acetaminophen fails as a panacea for dementia...

The current J of the American Geriatrics Society has a couple of articles of note.  First is a randomized, double-blind, placebo-controlled cross-over trial of acetaminophen (1000mg tid, scheduled, for an entire month) vs placebo to evaluate its effects on the behavior of those with advanced dementia.  To their credit, the investigators used prospectively gathered data on behaviors (things like "direct social involvement,"unattended distress," etc.).  20-some behaviors were measured, and, despite a few of them being significantly but minimally improved (media-time, independent self-care, direct social involvement) for the most part it was a wash & I'm not convinced the few significantly different measures were anything other than noise.  Agitation or psychotropic med use weren't changed either.  It's too bad...chronic, moderate dose APAP use is generally so benign that even moderate improvements would have a good risk-benefit profile.
There's also a lengthy look at breast cancer in alzheimer's disease patients , using data from a national registry.  It confirms what most would have guessed: it's diagnosed at later stages, and demented patients receive less cancer-directed treatment (less chemo, radiation, and mastectomy--but interestingly more breast-conserving surgery).  What they don't report on however is hormonal treatment use (due to the nature of the database used) which is too bad since, compared to chemo/xrt/scalpel, hormonal therapy is much more benign & would presumably be acceptable to many patients/families to whom the other therapies wouldn't. 
Finally, there's a survey suggesting that bereaved families' perceptions of quality of end of life care is lower in areas with a higher intensity of medical services (more ICU's etc.), but it seems to me that this difference cannot be blamed on ICU's per se, as suggested in the paper's title.

Wednesday, November 2, 2005 by Drew Rosielle MD ·

Tuesday, November 1, 2005

NEJM reviews depression

The current NEJM has a review on the medical management of depression.  It's solid.  One sentence of it caught my attention however, in the section about discontinuing treatment:  " The discontinuation syndrome is sometimes called the withdrawal syndrome, erroneously implying drug dependence."  Am I wrong in thinking this is a weird and misleading statement, especially from a psychiatrist?  I have been taught that (physical) drug dependence is in fact defined by the occurance of a withdrawal syndrome if the drug is discontinued (which usually prominently includes somatic symptoms and not necessarily "cravings").  I'm not sure if the author meant to write "erroneoulsy implying drug addiction" or if there's some custom of only using the term "dependence" in relation to drugs of (potential) abuse/addiction.  If so, that seems wrong to me, and not based in physiology.  Correct me, however, if there's something I'm missing.

Tuesday, November 1, 2005 by Drew Rosielle MD ·

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