Thursday, November 1, 2007

Many Items, Part 2

Part 2 of my previous post: breast cancer prognosis, emotional well being and cancer survival, dialysis survival, don't tell mother, opioids and respiratory depression, informed assent for DNR orders, fMRIs, The Undertaking, Hinduism, comment email updates.

1)
A couple from Cancer.

First is one on prognosis in breast cancer patients with CNS metastases. It's basically a case series of >400 patients treated at MD Anderson with breast cancer and CNS mets. Major findings: median survival after diagnosis of any metastases was 21 months; median survival after diagnosis of CNS metastases was 7 months. Nothing was significantly correlated with longer survival except younger age and estrogen receptor positivity. They do give this helpful information, however, about long-term survivors:

"Eighty-two patients (19.5%) were alive at least 18 months after diagnosis of CNS metastasis. Of these 82 patients, 25 patients (30%) had HER-2-positive breast cancer. Furthermore, 18 patients (4.2%) were alive at least 60 months after this diagnosis. The median age of these relatively longer surviving patients was 42 years. Most of these patients had tumors of the ductal histologic type, tumors classified as T1 or T2, lymph node status N0 or N1, and a metastatic status of M0 at diagnosis. Approximately 50% of these patients had ER-positive or PR-positive disease, and 73% had grade 3 disease. Forty-six percent of these patients had a single CNS metastasis."

The other is a study on survival and emotional well-being in head and neck cancer patients. The data come from prospectively gathered trial data from a couple head and neck cancer radiation studies in which quality of life and emotional well-being were collected (at baseline and throughout). Basically, emotional well-being had zero effect on survival (whereas things like age, baseline performance status, etc.) did. No power analysis is mentioned at all - one assumes it was done for the trial portion of this study but not this secondary analysis and there's definitely a concern for type-II error. How much concern? Well you can't know without the power analysis so.... The authors rhetorically frame their study as being a counter to the apparently widely held belief that one's emotional state is a predictor of outcome in cancer. I wasn't aware of this belief (other than one that cancer patients themselves have - 'gotta keep positive' - which itself is not an indication of emotional well-being) being seriously endorsed by the medical community but perhaps I'm naive. Comments?

2)
CMAJ recently had an article about prognosis in elderly patients receiving dialysis (free fulltext here). It looks at survival in patients over 65 years old who started dialysis between 1990 and 1999 (using data from a Canadian, nationwide, voluntary database). It found that more 'very-old' patients were initiating dialysis and that survival had, overall, improved a little across the decade. Long-term survival however remains quite poor: for patients 75 or older at the time of dialysis initiation 1, 3, & 5 year survival rates were 69%, 37%, and 20% respectively (life-expectancy for a 75-79 year old initiating dialysis was estimated to be ~3 years).

A quote from the accompanying editorial:

"Optimal provision of renal replacement therapy continues to present formidable challenges to patients, family members, health care professionals and policy makers. To date, most of the large trials including patients with end-stage renal disease have focused on "hard" outcomes like death and cardiovascular disease, and the results have been disappointingly neutral. Patient-perceived quality of life has rarely been used as a primary consideration. This is surprising, especially when one considers the financial costs of renal replacement therapy and the ambivalence felt by many patients who are considering these therapies."

3)
Supportive Care in Cancer presents further observational data that respiratory depression is rare during opioid titration. The current study echoes the previous one I blogged about except that this time the patients were receiving intravenous hydromorphone for dyspnea. It involved 14 advanced cancer patients (mean survival 20 days) admitted to a palliative unit with moderate to severe dyspnea for whom opioid therapy was being started (patients with COPD were, unfortunately, excluded). Findings: at 120 minutes dyspnea improved, respiratory rate decreased (39 to 29/minutes), and O2 sat and pCO2 (transcutaneous measurements were used) didn't significantly change. While this is swell, and supports the observation that opioids palliate dyspnea at non-respiratory depressing doses, it doesn't help answer the more urgent question of what happens with patients at high risk of respiratory complications of opioids (i.e. people with advanced COPD and who retain CO2 at baseline, those using other CNS depressing meds, etc....). The COPD literature on this has also demonstrated the safety and efficacy of opioids for dyspnea in a handful of small trials but have avoided studying the patient population we're most worried about - those who retain CO2. If opioids are shown to be safe - great, and maybe they will be used more appropriately for high risk patients with refractory symptoms - but even if they're shown to actually increase pCO2 in high risk patients that doesn't mean they're inappropriate to use - it just (at least for me) helps to better define the risk.

4)
JCO has an Art of Oncology piece about requests from families not to give bad news to a patient. It's a practical primer on the topic - one which I know gives many clinicians belly pain (I am constantly asked by housestaff what to say when the family stops you in the hall and asks you not to tell the patient what's going on). I particularly appreciated the first words in its section on responding to such requests: Do Not Over-React. Which reminded me of this.

5)
Chest has a point - counterpoint - rebuttal series on 'informed assent' (not consent) for DNR orders in the ICU. The 'point' is a proposal that physicians, when they strongly feel that CPR is not indicated for a critically ill patient, basically ask for assent from families for a DNR order and not ask for consent. The difference being in the first the physician explains the situation, recommends a DNR order, and then asks the family if it's ok with them that she or he makes that decision vs. asking the family what they'd want, or if they'd agree to a DNR order. (The distinction is real, although it can be subtle, and the article would have been greatly strengthened by providing examples of actual language.) The background to this, which the authors frame, is that many family members feel the 'tyranny of autonomy' when they are asked to make what feels like life & death decisions and may be reluctant to actively endorse treatment limitations because it feels like they're endorsing 'letting the patient die' (even if, medically speaking, the patient is dying anyway). So, if the physician offers to take over/take the responsibility for the decision (with the family's assent), it can be emotionally easier on the family. The counterpoint is pretty interesting, but one has the sense from it that the author feels, in fact, that patients/families have a right to receive medical care even if no one else thinks it's indicated.

6)
Continuing to track the fMRI & prolonged states of unconsciousness thread running through the recent scientific and popular literature...a recent New Yorker had an article by Jerome Groopman about this. It's less philosophically minded that the Salon piece I wrote about earlier. My sense is that in the not too distant future this and similar technologies are going to be widely clinically available, we may or may not however know what to do with the data, but it's going to make decision-making that much more complicated for us and grieving families, so we'd best be ready.

7)
After having watched it, I would definitely mention the PBS show about Thomas Lynch, 'The Undertaking.' There's a transcript of an interview of a couple who were featured in the documentary (who's son died of a rare genetic disorder) which is worth a read:

"A lot of our friends or family, even if they weren't uncomfortable, were just inexperienced. So it was hard. We were all fumbling through it, and when you're talking about a child dying, it just seems wrong. So people feel more comfortable remaining hopeful: "Oh, well, he just might get better," or, "Maybe this new medicine will work," or, "Maybe when he turns two," or "There's always this hopeful future." And we would a lot of time have to speak that way with other people and then come home and feel different, feel like that's really what wasn't going on. So in that it felt lonely."

I've mentioned before on the blog my discomfort with hope-talk ("you're either a survivor or nothing") and so I was particularly struck by their mention of the isolating aspects of it. (In the interview a major theme that this couple brought up was that what they really liked about hospice was the simple fact that they could talk with someone about what is actually happening.)

8)
The Journal of Pain has a review on pain and suffering in Hinduism and potential implications for pain management.

9)
Finally, Blogger has added an enhancement to the comments. You can subscribe (via email - Google account required unfortunately) to a post's comments so that you can automatically be updated if someone has commented on a post you're interested in or have yourself commented on. (Click on the 'Email follow-up comments to...' box in the comments page.)

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