More on “futility”

A couple of weeks ago Drew blogged on a short essay/case report in Journal of Clinical Oncology that addressed a physician’s struggle in prescribing chemotherapy that he considered to be futile. The same day I got my latest issue of Oncology with an article (with 2 invited responses, here and here) on patient demands for chemotherapy that clinicians feel is futile. I believe this is the inaugural offering in the new feature, “Areas of confusion in oncology.”

The Oncology article is a fairly wide-ranging piece that begins by addressing what is meant by “futile care.” The authors point out that there is no common or consensus definition [I imagine that at least some of this is one of those “I know it when I see it” phenomena]. A recurring theme in this paper is discordance of perceptions and perspectives between patient and physician. Expert panels struggling over guidelines, a physician facing a desperate or resolute patient, children not willing to contemplate “giving up” on Mom, a patient with a religious belief that “everything” must be done, third-party payers—whether private or government, and John Q. Public (i.e., “society”) in the grip of a compelling drama may have varying and conflicting perspectives.

The authors quote a 1993 article in which the reader is advised to distinguish an effect from a benefit. That dovetails nicely with an observation later in the paper that some patients overestimate prognosis because they confuse response with cure.

Not surprisingly, a major cause of the disparate perceptions is assigned to inadequate communication between patient and physician. And not all the blame falls on the physician. When each is waiting for the other to bring up discussions of goals, values, quality of life, prognosis, end-of-life issues, etc., “misalignment of perceptions” can be expected. The physician may even have thought that s/he provided adequate information on prognosis. But if they provide too wide a range of outcomes, don’t periodically come back to the discussion, or don’t check in with the patient to see what was understood, the discrepant perceptions can grow ever wider. “Lack of patient-provider communication regarding prognosis, goals of therapy, and benefits of aggressive symptom management (hospice) all play a role in the delivery of futile chemotherapy.”

There are several interesting tidbits provided that may be helpful to both experienced clinicians and to students or junior clinicians who are trying to get their heads around the issues related to futility dilemmas.

• Over 20% of Medicare patients begin a new chemotherapy regimen within 2 weeks of death
• A recent survey of oncology practices showed a range of 0-34% giving chemotherapy within 2 weeks of death
• At least one study has shown that some patients with previously treated non-small cell lung cancer would accept chemotherapy with a survival benefit of as little as one week, while others would not take it even for a benefit of two years
• Another study showed only a 25% concordance between what patients said their decision-control preferences were and the provider’s perception of the preference.
• Some patients appear to be willing to discuss hospice with a physician other than their oncologist, but not with the oncologist [is it too hard for the patient; does the patient think it will be too hard for or hard on the oncologist?]
• In one study, physicians initiated a hospice discussion 50% of the time, patients or families one-third of the time
• One-quarter of physicians will occasionally administer futile chemotherapy to maintain patient hope.
• The median length of hospice stay is no longer lengthening, but getting shorter (down to 26 days in 2005 vs 29 days in 1995); one-third enroll in the last week of life and 10% on the last day.

An important observation that I have never heard invoked in discussions among clinicians about futility, is that there insufficient information available for patients with advanced disease to access independently. Accurate but vague statements such “current treatments do not cure the cancer” are not helpful for a patient struggling with finding their own process for decision-making. There is very little to be found about the advantages and disadvantages of chemotherapy at this stage, what a patient might reasonably expect, or alternatives such as palliative and hospice care. These points relate to patient questions such as “will I feel better or worse?” (if I take the chemotherapy); “will my cancer shrink [and what does that mean in the short & long term]?;” “how do other people make decisions about these things?”

The authors’ recommendations:

• Don’t go it alone—use trusted colleagues to share concerns, avoid isolation and burnout
• Ask the patient how much they want to know, how they want to make decisions
• Bring up hospice early as a future possibility; emphasize nonabandonment and aggressive symptom management; avoid euphemisms: use “death” and “dying” [while I personally agree with that philosophy, there are cultural overlays and sensitivities than need to be considered.]
• Use family conference as a way to get the same information simultaneously to multiple people who may be family decision-makers; be prepared to share actual studies to bolster your position that there is little or no benefit to further chemotherapy and that there may be significant burden or harm [is “symptom burden” a useful construct for patients who have been focusing on tumor shrinkage? I think it is.]

Equally valuable as the main article, the reviews provide valuable nuance and perspective. One practical idea is the "differential diagnosis" of a patient request that the oncologist thinks is not in the patient's best interest. What underlies the request--unrealistic expectations? Fear of abandonment? Present hospice as a treatment [reminiscent of Andy Billings' statement that family meeting is one of palliative care's most important procedures]. "A 20-60 minute conversation between an oncologist and a patient . . . is miniscule when weighed against a lifetime of family values, traditions, culturally held beliefs, and deeply entrenched religious beliefs."

Khatcheressian J, Harrington SB, Lyckholm LJ, Smith TJ. 'Futile Care:' What to Do When Your Patient Insists on Chemotherapy That Likely Won’t Help. Oncology 2008;22(8):881-887 (free full text) http://www.cancernetwork.com/cme/article/10165/1168027

Methadone, methadone, methadone

Three recent methadone-related reviews, two by the same group, are well worth the reading. The first two, on conversion ratios and drug-drug interactions, respectively, are the long-awaited published versions of presentations made at the AAHPM/HPNA conference in Salt Lake City in 2007. They are among the most thorough and well-organized reviews on any topic that I have read in recent years. The third is a consensus guideline on parenteral methadone in palliative care.

Methadone conversion ratios:
The authors reviewed clinical trials, retrospective analyses, case reports, and case series published from 1996 to 2006; reviews were excluded. A total of 41 papers (22 studies, 19 case reports; N = 730) were reviewed. None of the studies were deemed to be of high value. Not surprisingly, they identified the heterogeneity of studies as the biggest challenge in their analysis. Not only were different methods and populations used, as well as different descriptive statistics and outcome definitions, but different conversion values and tables for non-methadone opioids were used. While most suggested conversion procedures recommend converting all opioids to morphine equivalents, some use oral equivalents and some use parenteral equivalents. Rather than just throwing up their hands in frustration, the authors recalculated many of the formulas presented, using consistent values.

It should be well known by now that there is not a simple ratio of morphine to methadone that works at all dose levels. Most studies stratified patients according to the pre-rotation morphine-equivalent dose because of the “dynamic inverse potency relationship between methadone and other opioids.” The most common ratios reported were 4:1 and 10:1; the review authors estimate that 30% of all patients were converted using one of these ratios. However, the reported range was 4:1 to 37.5:1.

Using scatter plots, the authors sought to determine the correlation between prerotation morphine dose and the morphine: methadone ratio. They identify a “strong, positive linear relationship between the prerotation morphine dose and the postrotation methadone dose,” but the dose ratio is not constant in relation to the previous morphine dose. When attempting to apply these findings to individual patients, there is confounding due to large interindividual pharmacokinetics with methadone. They emphasize that the “care process” or conversion procedure as well as the calculation of dose ratios varies considerably across studies. “It may be less important to determine an exact opioid ratio . . . than to be sure that the patient is an appropriate candidate for methadone rotation, the switch is carried out over a time period consistent with the therapeutic goals, and that the patient is monitored closely by medical staff throughout the process.” They note that there is no consensus regarding the various published methods of conversion, but that the majority of patients are successfully rotated in all settings regardless of method employed and ratio used.

There is also acknowledgement that conversion ratios are not bidirectional and that there is almost no guidance in the literature for conversion from methadone to another opioid.

Finally, there is a long discussion of the deficits in the research literature and suggestions for the future direction of research.

I’m not sure that anyone already experienced in methadone conversions will change his/her clinical practice because of this paper, but it may well provide rationales for teaching and encouragement for reseach.

Weschules DJ, Bain KT. A Systematic Review of Opioid Conversion Ratios Used with Methadone for the Treatment of Pain. Pain Med. 2008 Jun 18. [Epub ahead of print] DOI:10.1111/j.1526-4637.2006.00289.x


Methadone drug-drug interactions:
This is an advanced primer in the clinical science of managing patients on multiple drugs, especially when one of them is methadone. It should be in everyone’s teaching and reference files. The paper includes:

• Eye-opening dissertation on just how complex methadone metabolism is
• Good description of the cytochrome-P 450 (CYP450) enzyme system in drug metabolism
• Other mechanisms—including some that are pretty esoteric—that can affect how methadone is absorbed, metabolized or eliminated, including the effect of changes in urine pH
• The important effect of the order in which drugs are added—or removed—from a regimen
• Theoretical vs clinically observed interactions
• Class-by-class descriptions of actual or potential interactions
• Limitations of the evidence base
• The fact that pharmacy drug-drug interaction checkers can pick up an interaction when a drug is added but not when it is removed from a regimen

Weschules DJ, Bain KT, Richeimer S. Actual and potential drug interactions associated with methadone. Pain Med. 2008 Apr;9(3):315-44. DOI:10.1111/j.1526-4637.2008.00461.x

Parenteral methadone use:
The consensus panel are almost all very well-known pain and/or palliative care clinicians. They review the very limited literature specific to parenteral methadone, then suggest clinical approaches to optimize it’s use. The paper includes a pretty extensive discussion of the implications for QTc interval changes and the risk of torsades de pointes. This paper doesn’t compare in thoroughness to the other two, but it is a useful review and probably unique in its focus specifically on parenteral methadone.


Shaiova L, Berger A, Blinderman CD, Bruera E, Davis MP, Derby S, Inturrisi C, Kalman J, Mehta D, Pappagallo M, Perlov E. Consensus guideline on parenteral methadone use in pain and palliative care. Palliat Support Care. 2008 Jun;6(2):165-76.

Opioid vs Narcotic; ABCs of Medicine; Hyperalgesia; Required Reading

1]
Several times in this blog we have discussed our preference for the term ‘opioid’ rather than ‘narcotic’ when referring to the substances (natural, synthetic, endogenous, exogenous) that occupy the mu receptor. See here and here for a couple of examples. Note the comments, as well. An interesting small, simple, and direct study from the Pittsburgh Veterans Administration Hospital has addressed the important issue of what patients understand when they hear the terms ‘opioid’ and ‘narcotic.’ One of our readers previously commented that using ‘narcotic’ makes sense since that’s the term patients (and other lay people) use and understand. On the basis of this study’s findings, she’s right. The researchers asked 4 (almost) identical questions of 100 people in a clinic waiting room. The “almost” part means that half the patients were asked about the term opioid and half about the term narcotic. The questions: “What is a narcotic/opioid?” “Give an example of a narcotic/opioid.” “Why does someone take a narcotic/opioid?” “What happens when someone takes a narcotic/opioid for a long time?”

The findings are both surprising and not. 83% of the patients in the opioid group did not know what it means; only 10% did not know what narcotic means. Actually both numbers sound high to me. Strikes me as nearly impossible to get well into the adult years without knowing what a narcotic is. I guess its more disappointing than surprising that so many patients don’t recognize the term opioid. Subjects in this study were recruited from outpatient primary care and surgical clinics. There was no breakdown of answers by clinic reported. Of the patients who recognized either term, only half in each group associated it with pain management in their definition and again when asked why someone would take an opioid/narcotic. Again, that is disappointing, but in my somewhat jaded view that may well be higher than the results you’d get polling reporters, DEA agents, politicians, politically-inclined prosecutors, and maybe some strata of the general population.

One of the major concerns expressed by those of us who worry about the negative legal and addiction associations of “narcotic” when applied to pain management was confirmed, but the numbers weren’t too bad, considering. 19 of 50 respondents associated abuse and illegal drugs with the term narcotic. The bad news is that 90% of the people who answered the question on what happens when someone takes an opioid/narcotic for a long time referenced addiction or an adverse outcome and the vast majority of those specified addiction.

The bottom line is that, if these results are generalizable, we have a lot of educating to do, at all levels and via all media.

2]
This must be VA day at Pallimed. Paul Rousseau, a well-known palliative care doc at the Phoenix, AZ VA hospital wrote a short essay for The Left Atrium column in the Canadian Medical Association Journal called ABCs of Medicine. Seemed like the kind of piece you might write after a long day—or week—of tiredly swimming against the continually rising tide of depersonalization that “the System” has become. The trigger is an admission note that begins: “62-year-old male admitted for hospice placement with the diagnoses of HIV, DVT, PTSD, GERD, BPH and PUD.” Digging a bit, he is able to conclude that the patient is a “pleasant and alphabetized man who is dying, no longer smokes, and lives with his wife.” He muses on the various reasons for the “psychosocial silence in this chart.”

3]
One more from the VA: this is a short review of opioid-induced hyperalgesia. It’s not very meaty and it is not a how-to article, but it succinctly lays out the prevailing theories/models of opioid-induced hyperalgesia and the three thus-far-identified interventions: opioid rotation (enough evidence to recommend it as a first line intervention); addition of an NMDA receptor antagonist such as ketamine or dextromethorphan (evidence not very strong and not recommended); addition of an ultra-low dose of an opioid antagonist (again, evidence noy very strong and not recommended). The authors point out that there is an investigational agent (Oxytrex) currently in clinical trials that combines oxycodone and naltrexone for pain management.

4]
Check out this title: “A matter of definition—key elements identified in a discourse analysis of definitions of palliative care.” Sounds terribly dry, but it turns out to be surprisingly readable and so well put together that I will make it required reading of my students next semester. The article is fascinating from an historical, etymological, sociological, and cross-cultural perspective. The authors are all palliative medicine physicians (turns out there is no translation for palliative care other than ‘palliativmedezin’ in Germany) affiliated with German universities. They searched for definitions of ‘palliative care’ and ‘palliative medicine’ in Google and in textbooks, finding a total of 35 definitions in English and 26 in German. They then used discursive practice—“a process by which cultural meanings are produced and understood”—to analyze the definitions.

Key elements identified were target groups, structure, tasks, expertise, theoretical principles, and goals of palliative care.

Among the conclusions:

• The term palliative care is a pleonasm (a new word for me—means redundant) since both palliative and care are concerned with the issue of protection.
• Palliative care/medicine is unlike any other specialty since it doesn’t have a specific object of study nor define itself by the age of its patients
• In fact, it has a hard time defining its population of focus at all. Protection of the patient “means a comprehensive and at the same time diffuse orientation.”
• Only a very few definitions explicitly describe the philosophy of palliative care.
• Having the family and patient as both the unit of care and as members of the care team creates some inherent role difficulties
• There is no consensus on the meaning of the terms multidisciplinary and interdisciplinary
• There is an emphasis on symptom control, but Kearny is quoted as warning against becoming a ‘symptomatologist,’ as symptom management is only the beginning of palliative care therapy.
• In that context, the human being is the focus of care, the goals address suffering and quality of life, and emphasizing wholeness through a respect for autonomy and dignity is a defining value.
• Interestingly, the current American definitions are seen to de-emphasize death and dying as compared to historical and some European definitions.
  

There is much more and I can’t do it justice in this space. This is a great journal club article, and can be grist for both introductory discussion and reflection on practice and meaning for veterans and their teams.

References:
Mangione MP, Crowley-Matoka M. Improving Pain Management Communication: How Patients Understand the Terms "Opioid" and "Narcotic." J Gen Intern Med. 2008 May 31. [Epub ahead of print]

Rousseau P. ABCs of medicine. CMAJ. 2008 Jun 3;178(12):1580-1581.

Leonard R, Kourlas H. Too much of a good thing? Treating the emerging syndrome of opioid-induced hyperalgesia. J. P-harm Pract 2008;21(2):165-168.

Pastrana T, Jünger S, Ostgathe C, Elsner F, Radbruch L. A matter of definition - key elements identified in a discourse analysis of definitions of palliative care. Palliat Med. 2008 Apr;22(3):222-32.

American Pain Society Meeting

I attended the first two days of the American Pain Society Annual Scientific Meeting in Tampa, Florida. It is a big affair, over 1300 people. I was quite impressed by the quality of the speakers--not just the the content of the presentations, but the speakers were, for the most part, good presenters.

The most prevalent recurring theme in the clinically oriented (as opposed to the basic science) presentations was the issue of prescription opioid abuse. It got a bit wearisome after awhile, perhaps because I presented on the same topic at the Nursing SIG session! Kinda reminded me of a recent cautionary comment by Kathy Foley at another meeting that pain management is being eclipsed by risk management. The most controversial session, on the Washington State opioid guidelines (see previous mention), was well managed and avoided descending into a shoving or shouting match. I'm still left unconvinced that the identified problem (an increase in opioid-related deaths in workman's comp patients) will be solved with the institution of the guidelines. They have been identified as a pilot and an educational endeavor, but one person from the audience said that he had been denied insurance payment for a patient on opioid doses greater than 120 mg unless additional justification was provided (perhaps an inevitable and predictable but unintended consequence). The "education" is being provided by the medical director for the department that handles workman's comp. He was obviously well-meaning and very concerned about safety issues, but he is not a pain specialist, and as far as I could tell, had no special training or experience in pain management.

The exhibit hall also had it's share of substance abuse-related products and give-aways. There were several urine toxicology companies there and multiple free "risk-reduction" education pieces, all sponsored by pharmaceutical companies.

There was an entire session (which I did not attend) on new tamper-resistant formulations of opioids.

Other new products and products in clinical trails of interest to this readership: Subcutaneous methylnaltrexone (Relistor) for opioid bowel dysfunction (see previous post); an oral form is just entering phase 2 trials; a pegylated oral form of naloxone is just entering human trials; an oxycodone-morphine combination tablet has just completed its first phase 3 trial; a sustained-release hydrocodone-acetaminophen tablet has completed a phase 3 trial; a cannabinoid is approaching clinical trials. Most of you are probably aware that there are new dosage strengths of OxyContin (15, 30, & 60 mg), and that all of the generic CR oxycodone products are off the market. There are also new dosage strengths of oxymorphone ER (Opana ER; 7.5, 15, & 30 mg).

There was a lot of exciting new basic science regarding pathways, receptors, neurotransmitters, and other cool stuff that was mostly over my head, but by implication provided new therapeutic targets.

One of the most interesting sessions was on rational approaches to multidrug treatment of neuropathic pain. It's all about patient assessment and pharmacokinetics.

On to the nursing (American Society for Pain Management Nursing) pain meeting in the fall!

Evidence and palliative care; hydration reviewed, sort of; opioid antagonists for OBD

1)

Over here at Pallimed we’ve been having an off-line conversation about “evidence” for palliative care-related practices, and decided to bring it to our readers. The impetus for the discussion is the publication of two new Cochrane reviews, one on medical hydration in advanced illness and the other on mu-opioid antagonists for opioid-induced bowel dysfunction.

Regular readers of Pallimed will know that the three of us are strong proponents of increasing and improving the evidence base for palliative care. We are also very much aware of the difficulty of doing so, especially using the stricter definitions and methods of evidence-based medicine (EBM).

I will disclose that I am not a regular devotee of the Cochrane reviews, but “medically assisted hydration” caught my eye. I was disheartened, however to see that only 5 papers made the cut to be reviewed, and that the conclusion was “There are insufficient good quality studies to make any recommendations for practice with regard to the use of medically assisted hydration in palliative care patients.” It reminded me of a conversation a couple of years ago with a well-known pain physician and researcher. He told me that he doesn't even read Cochrane reviews anymore. "They all end with the same conclusion: there is insufficient evidence to make a recommendation about . . . " I don't think that is necessarily a bad thing, but they are super-strict in their criteria for selection. That makes it particularly difficult in palliative care, where doing the type of research one might do for approving a hypertension agent is almost impossible. The issue, of course, is that the assumed “highest” level of evidence is the randomized controlled trial (RCT). Some have argued that RCTs are not only difficult to design and conduct, but may be unethical in interventions for people with advanced disease where comfort, not cure or control, is the therapeutic goal. Others criticize the misuse of EBM, either attempting to apply broadly the results from a trial in a subset if patients, or conversely denying payment for a successful intervention for a specific individual because the RCT “proves” that the intervention doesn’t work. Fragile patients with advanced disease are usually excluded from RCTs, yet that is precisely the population most in need of evidence-based palliative interventions.

The phrase “perfect is the enemy of good” springs to mind. But the RCT is unlikely to ever be the “perfect” tool for symptom management, population-based or public health studies, and other complex beyond-the-physiology questions.

Carr, an early proponent, points out that EBM continues to evolve, has limits, and can easily be misused. Where applicable, the RCT should be used, but with the results interpreted judiciously for specific populations and individuals. Hallenbeck, Carr (specifically for pain medicine), Aoun & Kristjanson, and Devery are among those who have made reasoned criticisms of EBM, and suggested “other ways” of using EBM or of gaining knowledge. These include an “Equity-based evidence framework” (Aoun & Kristjanson), “narrative-based” evidence (Devery), or recognition that “lower” (not necessarily less rigorous) levels of evidence apply quite well to palliative care.

We’d like to hear how our readers use and interpret “evidence” in their practice of palliative care.

2)

Getting back to the Cochrane reviews:
Hydration: there was only one “high quality” study (2 RCTs) but over a very short duration (2 days) and very underpowered. Overall, results of the 5 studies reviewed were somewhat contradictory, but showed suggestions of improvement in sedation and myoclonus. Negative effects cited were fluid retention leading to peripheral edema, ascites, and pleural effusion. In their conclusion, the authors acknowledge the difficulty of conducting clinical research in the palliative care population. They also comment “the issue of medically assisted hydration in palliative care patients causes such divergent views, yet there are so few studies to guide clinical practice properly. As well as looking at further RCTs in this area, the evidence base will be improved with at least more prospective controlled trials.” It should be noted that the "best" study had quite a few patients with reasonably good performance status, especially in the intervention group. It was not really helpful, therefore, in answering the question: "is medically assisted hydration a helpful intervention in patients in the last days of life?" One of the included studies, a prospective controlled trial, attempted to mimic real world decision-making by allowing physician preference in allocating to the intervention arm. This introduces bias,of course, but downgrading the score on the study design because of it may make some clinicians grind their teeth. The whole point in reading a study is to find help in making real world decisions, isn't it? That raises questions for a future conversation.

Opioid antagonists for opioid-induced bowel dysfunction (OBD):
Naloxone, nalbuphine, methylnaltrexone, and alvimopan were reviewed. There was only one study of nalbuphine. All studies were placebo-controlled RCTs (which makes sense in this case; active-controlled studies would also be welcome). Some studies of the newer agents (methylnaltrexone & alvimopan) were in healthy volunteers. The authors report that their task was made more difficult by use of various opioids in trials, and by inconsistent definitions of postoperative ileus. In general, though, they found (in a limited number of studies with small numbers) that methylnaltrexone and alvimopan were sufficiently safe and effective (increased transit time/decreased constipation) to be labeled “promising.” It should be noted that methylnaltrexone was administered parenterally in these trials, and that oral methylnaltrexone has yet to be reviewed. Alvimopan trials were interrupted because of excess cardiac events. The current target indication for alvimopan (not yet approved) is postoperative ileus.

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Just as an aside, the last author on this review is Dan Carr, cited above in the EBM discussion.

There is another recent review here.

A just-published RCT was not part of either review. Subcutaneous methylnaltrexone (Relistor) was approved by the FDA last week for patients in late-stage advanced illness and should be available next month.

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So, who among our readers is waiting impatiently for methylnaltrexone to become available? Given the route, cost, and limited research, are you eager to give it a try? In general, are we adequately treating opioid-induced constipation, but need this for backup? How will you determine which patients receive it? How many other interventions do you need to go through before you determine that constipation is refractory to more conventional treatment? Oh, and do any of you actually use the newly minted term 'opioid bowel dysfunction' (OBD)? The Comments link awaits you.

Pain Crisis; cure & heal; The Dreaded “D” Word.

1]
In JAMA’s ongoing series “Perspectives on Care at the Close of Life,” the Memorial Sloan-Kettering team tackles the management of acute cancer pain crisis.

This is definitely one for the Teaching File. As always in this series, a fairly graphic or complicated case is presented with definitions, descriptions, prescriptions, strategy, and philosophy interspersed. I’ll list the salient points:

• Pain crisis is “an event in which the patient reports pain that is severe, uncontrolled, and causing distress for the patient, family members, or both.” Pain crisis can occur anywhere in the disease trajectory. Pain crisis is a medical emergency that requires aggressive assessment and intervention.
• Management strategy focuses on

1. making a pain diagnosis, differentiating reversible from intractable causes of pain and making decisions about further workup,
2. selecting the opioid and monitoring and treating adverse opioid effects,
3. titrating and rotating opioids and coanalgesics,
4. consulting experts to treat a pain crisis as quickly as possible to prevent unnecessary suffering, and
5. identifying and co-opting the available institutional resources. [this is my favorite]

• There are no epidemiologic data on the incidence of pain crisis. Approximately 20-25% of all palliative care referrals at MSKCC are for pain crisis [which strikes me as high—what’s your experience, readers?]
• Rapid response is crucial
• Intervention is guided by goals of care. “Reestablishing goals of care” and planning interventions “congruent with goals of care” are emphasized over & over. When possible, the patient “leads the discussion” on goals of care.
• Provide continuous support for patient & family
• Continuously reassess response to interventions

There are several boxes and tables that summarize and expand on information in the narrative. NOTE: there is an error in Table 4 which displays an incorrect hydromorphone-methadone ratio when the 24-hr dose of hydromorphone is less than 330 mg. The listed value is 16:1; there is a decimal point missing: it should read 1.6:1. I was hoping they had corrected it by now in the online version, but as of Monday morning it is still unchanged. The conversion values for hydromorphone and methadone are tenuous at best, anyway. Personally, I think it makes sense to convert all opioids to morphine equivalents—either IV or PO, depending on the circumstances—so that there is a familiar and consistent constant.

We sometimes forget that adjuvants and coanalgesics have a role to play in pain crisis. Several options are listed. I used to use a lot of ketorolac. Acute pain very often (almost always?) has an inflammatory component. Unless otherwise indicated, it is a great analgesic booster while trying to titrate to the effective opioid dose.

There is a brief, but good, discussion of methadone and the implications/relative risk of QTc prolongation.

Please note that there is nothing in the article about PCA. Far too often clinicians think that PCA is the answer to uncontrolled pain. It isn't. PCA is for maintaining control once reached. It would have been nice if they had made that explicit. Otherwise as thorough & worthwhile as you can find on this topic in a general medical journal.

2]
Some of you may have seen the patient-directed periodicals cure, and heal. I’ll bet they’re in your treatment center’s waiting room or in your patient support center. They come from the same publisher. heal’s target audience is cancer survivors, and the target demographic for both magazines appears to be the well-educated, information-mining patient. On the whole, these are good, informative magazines. There is a particularly good article on palliative care in the Spring issue of cure (unfortunately, that issue is not yet available online). The only complaint I had is the use of the term “palliative medicine,” as in Betty Ferrell is “a national leader in training nurses in palliative medicine.” But that’s just a little late night whining. A good one for the patient Teaching File.

3]
The Left Atrium is a regular column in Canadian Medical Association Journal (CMAJ). It’s sort of a non-cancer version of JCO’s “When the Tumor is Not the Topic” column. This week’s essay is by a medical student recounting an experience in her surgical rotation (I think the student is a “she.” If I have it wrong, I apologize for my cultural ignorance). The student is paged to see a patient after the surgical team has gone home for the night. The patient has decided to forego the scheduled surgery and go home to see his children—and to die. The essay is short, well-written, and open access. I recommend it. There’s an engaging image, too. The important kernel of insight: “I realized that I had come in at the tail end of what must have been a long, introspective process for Mr. Lee and his family.” By the way, this author, Pari Basharat, has honed her writing skills previously in CMAJ with both poetry and narrative. Good stuff.

Pallimed 2008 Annual Survey Results

Thanks to all the readers who took our survey at the end of January. As promised we wanted to share some of the results with you as 'payment' for taking the survey.

We had a pretty good response for a voluntary survey. Of the 600+ readers at the time of the survey we received 87 surveys for a 15% return rate. So next year we are aiming for 25%! Thanks to all of you who participated, we appreciate your input.

88% of responders were in the medical field and 75% of those worked in hospice and palliative care primarily. Figure 1 is the distribution of disciplines. I am pretty surprised we did not have more fellows answer, since I would expect them to be technologically hip to RSS and looking for good articles for journal club. We even got a response from a hospice librarian. I did not know such people existed, but that is great!

Over half of the respondents have been reading Palllimed for over 6 months and most of you accessed Pallimed via the web site directly or email subscriptions (see 2nd Figure). If you don't know what RSS is you can see our First-Time Visitor Page for a good explanation.

Most people preferred the current format of 2-3 posts per week, and multiple subjects in each post. Interestingly this is not the usual blog format, which is one subject for each post, and multiple small posts per day or a few large posts each week. We appreciate the individual feedback about the format and will be taking some of these into consideration in tweaking upcoming posts.

As far as the future of Pallimed many people responded positively to the ideas we floated including calendar function for conferences, PowerPoints, handouts, audio/video podcasts, guest posts by readers/senior faculty, polls, and interviews. Now obviously we cannot do all of those things at once, but since CME and CE did not get a large positive response, we will likely be crossing those off the list for now given the amount of work those take. Drew, Tom and I are trying to keep the core content of high enough quality and figure out how to slowly implement some of these additions. We also don't want to duplicate content that you can get at other sites. If you would be interested in contributing to any of these new prospects, please feel free to email Drew at his gmail dot com address (drosielle).

One function we are interested about is the use of comments. The ability to comment is one of great things about blogs. It allows for near real-time conversations about the topics that we post on. You can even use it as a forum to have a public conversation on something off-topic.

Only 24% of respondents had placed comments on Pallimed. All the blue shades in Figure 3 are the "never commented" responses and the reasons for the response. The other category was filled with answers that could be placed in multiple of the other no categories. A high number of responders (21%) did not realize we had a comments section. Many people felt they had nothing to add. Drew, Tom and I do not profess to be the experts on all the topics we write about. There is a lot of opinion here, which means there is room for debate.

You can find the comments link at the bottom of every post.
To address some of the individual responses to the questions we surveyed:

No. Absolutely not.
Are you serious?
I thought that was pretty funny too.
I never thought of Drew that way before.

Seriously though, some of you enjoy our attempts at wit, others desire a more serious tone. We try to strike somewhere in between to make it informative and accessible/personal. Whatever you think, thanks for reading Pallimed. We have grown from 4 subscribers last January to around 700 in just over one year. Thanks for helping us in our amazing growth. We appreciate the positive and critical feedback, and hope to see more of you in the comments section. (Feel free to practice commenting on this post!)

Thanks!
Drew, Christian & Tom

GAO Report on end-of-Life Care; Oxycodone review; problems with Duragesic and Oxycontin

1)
End-of-Life Care: Key Components Provided by Programs in Four States is a report commission by Sen. Ron Wyden. Using descriptions from last decade’s IOM Report and a 2004 AHRQ study, as well as interviews with NHPCO and NAHC, and interviews with 10 EOL researchers, GAO identified 6 “key components” of end-of-life care.

• Care management to coordinate and facilitate service delivery
• Supportive services for individuals residing in noninstitutional setting
• Pain and symptom management
• Family & caregiver support
• Communication among individuals, families, and program staff
• Assistance with advance care planning

They then visited 4 states (Arizona, Florida, Oregon & Wisconsin) to determine how these key components are addressed in practice. They interviewed practitioners and administrators in PACE programs (state-administered care programs for elders supported by Medicare); similar but state-specific programs in Wisconsin & Arizona; and 12 palliative care programs of varying designs (at least 2 in each state).

Examples of the key components in practice:

• Care management: case managers; interdisciplinary teams
• Supportive services for patients: adult care programs; meal delivery; housekeeping services; transportation for medical care
• Pain and symptom management: either integral part of the care model, or established referral patterns with low threshold for referral
• Family & caregiver support: respite care; bereavement support; assistance with decision-making; in-home support
• Communication: team meetings; integrated electronic medical records; early and/or continuous conversations with patients to ensure their wishes for care and advance planning are current; use of standard tools to assess patient condition
• Advance care planning: an integral part of each program, usually beginning early in the relationship with patient; includes family; assist patients with completing advance directive documentation; Physician Orders for Life-Sustaining Treatment (POLST)

The two barriers (“challenges”) to delivering the services described that are highlighted in the report are trying to deliver any services in rural areas, and physician training and practices. The rural issues range from distance and poor roads to lack of pharmacies and other collaborating services, as well as lack of qualified nursing and other personnel. “Physician training and practices” will have a familiar ring: lack of training in pain & symptom management & communication skills, especially those related to EOL discussions & decisions; lack of training regarding EOL services such as hospice and palliative care [here they cite the NEJM article that Christian blogged on last year].

This is not like reading a study in a medical or nursing journal. It is intended for a lay audience (specifically, Sen. Wyden & his office), does not belabor demographics or other statistics, has no tables or charts, is quite repetitious, and is simply descriptive with no attempt at analysis or recommendations. Nonetheless, the services and issues described across these diverse states and programs are quite comparable. This makes it useful information for policy makers and legislators (as was its intent), as well as folks like newspaper editorialists, health columnists, and teachers in public health and clinical programs, especially at the undergraduate level. For those looking for something a little more meaty, the IOM and AHRQ reports cited by the GAO may be helpful. While looking for the AHRQ report, I found a more recent one by the same authors. I'm also reminded of a more recent IOM report on palliative care for cancer, and the very recent report on psychosocial care for cancer patients.

2)
There is an extensive review of oxycodone in Current Medical Research & Opinion . This is not a meta-analysis, but a pretty thorough literature review. At first I was concerned that the authors were not taking a particularly critical look at the studies they looked at, but they do indicate weaknesses in individual studies and as well as the general lack of head to head studies with other opioids. After the umpteenth clinical trial of oxycodone in one form or another (including parenteral in Europe) vs placebo, I begin to wonder why there isn’t more solid research basis for what is obviously a very effective analgesic. The article mostly focused on clinical uses; I would have liked a bit more pharmacology. Maybe not one for the teaching file, but it probably has a place in the oxycodone folder because of its very long reference list.

3)
Problems with fentanyl patches and Oxycontin

All Duragesic 25 mcg patches have been