Mastodon 05_12 ~ Pallimed

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.


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: 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.

( 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 ·

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