JCO issue on supportive and palliative cancer care

Journal of Clinical Oncology recently devoted an entire issue to supportive and palliative cancer care (table of contents for the entire issue here). It is mostly a series of review articles about measuring and improving the quality of supportive/palliative & end of life care for cancer patients.

I wanted to highlight one paper in particular, about the use of aggressiveness of care at the end of life as a quality measure. This is an issue we've discussed before on the blog (most recently here). The current paper is written by some of the researchers who helped develop/define the concept in a research sense (i.e. how to measure 'aggressiveness' of care at the end of life - proportion of patients who initiate a new chemotherapy regimen within the last month of life, proportion of patients whose hospice lengths of stay are less than 3 days, those sorts of things) and the paper is a summary of their work and an overview of the field as a whole.

I was most interested in their discussion of the validity of these measures: are they actually reasonable quality measures? This is what they had to say:

To explore the validity of the measures, we sought to relate each of our measures to the outcome of family members’ satisfaction with quality of care near the end of life. We have examined data from a prospective cohort study looking at patient and family needs among women with hormone-refractory metastatic breast cancer treated at two Canadian regional cancer centers, and limited analysis to the patients who died during follow-up. Family members were asked to complete the FAMCARE instrument within 2 weeks of patient death. FAMCARE is a 20-question survey that asks about satisfaction with symptom control, psychosocial care, information provision, and availability of providers. Among 51 consecutive women who died and had a caregiver complete the FAMCARE instrument, there were trends toward less satisfaction with care when chemotherapy was continued within 14 days of death, death occurred in an acute care setting, or there was no or only a short ( 3 day) hospice involvement. These did not reach statistical significance, however, perhaps because of the small sample size. Interestingly, variability in scores appeared to be mostly driven by the "information giving" and "physical care" subscales of the FAMCARE instrument, suggesting that inadequate communication and symptom management may be associated with aggressive anticancer treatment. A larger validation study is underway in the National Cancer Institute–funded Cancer Care Outcomes Research and Surveillance (CanCORS) consortium comparing these measures with patient and family assessments of the overall quality of care patients with lung or colorectal cancer receive before death.

Well, I guess we'll look forward to the CanCORS results then. It of course seems intuitive that increased aggressiveness of care at the end of life for cancer patients is an indicator of 'poor' quality of care, but there are patients/families who would disagree with that, as well as some patients for whom treatment decisions to be 'aggressive' made sense/were appropriate at the time they were made despite the eventual 'poor outcome' and so defining the proportion of patients for whom aggressive care in the last month of life is inappropriate is going to be tough (10% emergency room visits in the last month good, 20% bad?).

Along these lines, death in an acute care setting is often proposed as a quality measure (increased hospital death implying worse care). One of the problems here is that rates of hospice use vary dramatically and at least partially by geography and hospice availability and I'm assuming that access to inpatient hospice facilities/hospice units is distributed unevenly as well. Given that, there are likely a certain number of dying patients for whom dying in the hospital is absolutely the best place to be (to get symptoms managed etc.). Higher rates of hospital deaths then may reflect more of a lack of access to hospice units (so it's a quality failure regarding equity in access to hospice care but not, for instance, a failure on the part of the patient's doctors/caregivers). In a general sense I'm sure higher rates of hospital deaths aren't a good thing, but the problem with quality measures is that once you create them people (e.g. Medicare, other payors, the JC, etc.) start using them (pay for performance etc.) with unintended consequences.

Anyway, it appears I began to ramble, and none of this is to suggest that this shouldn't be carefully investigated, and it's exciting to look at how people have operationalized this concept, and perhaps the CanCORS study will continue to clarify things.

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.

.

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.

.

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.

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 recalled, due to a leakage problem.

This one is a little less clear to me, but it seems all the generic extended release oxycodone products are no longer available. This is because Purdue Pharma won a patent infringement lawsuit. This is apparently not news to the legal crowd or the pharmaceutical industry watchers, but it has caught many clinicians unawares. There are reports of shortages of Oxycontin because of the increase in demand for the branded product. I don’t know whether 3rd party payers who mandate generics have caught up with this.

AAHPM Pre-Conference Preview Part 1 (AAHPM Sessions)

Early this year I posted a preview section for the AAHPM/HPNA conference in Salt Lake City. Of course last year when I decided to post it, it was too late for people to people to change their registered pre-conferences, so this year I am going to cover the pre-conferences early enough to give you some thoughts on what might interest you. Today, I highlight the AAHPM pre-cons, later the HPNA pre-cons.

I started doing the preview because one of my favorite things about conferences is talking to other people to see what they are interested in, so feel free to tell us what you are going to and why. If you are giving any of these talks, I encourage you to leave some comments to get more people aware of your talk. There are some good ones!

Wednesday January 30th, 2008
8am-Noon

Hospice Medical Director Course Module B - Regulatory Issues

The AAHPM includes this as part of a series (A,B,C) with the other sessions usually taught at Current Concepts or other times throughout the year. Since I completed a palliative medicine fellowship, I have not seen the need to go to this, although there may be some tips to be picked up here. I have not heard anyone ever rave about the regulatory module (YAWN! (but important if any Medicare officials are reading this blog!)) , but I think that is probably due to the nature of having an important foundation in hospice regulations if you plan on being a hospice medical director. Regulations...you gotta know them, you may not like them, you may think they don't make sense, but they are here to stay. Until they change next year.

Quality Measures for Hospice & Palliative Care
by Dy, Hanson, Asch, Wenger, Walling

To me quality indicators are just a little more exciting then regulatory issues. So my review will be biased a certain direction. (I would be happy to hear form any self-described policy afficianados, who want to comment on the importance of these and advocate for more people going to this session.) A lot of important work went into creating these standards and I hope our field will be better off for applying a structure, but part of the cynic in me worries about creating an administrative framework that has minimal bearing into clinical practice. This session will talk about PEACE, ACOVE, and ASSIST, of which I am familiar with none, and also features speakers who I am not familiar with so this anemic review will end. Now. (Please enlighten if you know more about this session)

Moving Beyond "I Hate These Discussions": Gratifying Tools to Facilitate Patient and Family Decision Making Near the End of Life
by Menkin and Weiner

Ah the dreaded words 'role play' are stuck at the end of this description. But fear not! Role play should never keep you from going to a session. You should jump at the chance to ply your skills in front of people who could give some great feedback. One of my favorite things about role play is that it gives you the opportunity to mess up really bad. And often times if you do the first role play with intentionally making it a horrible horrible situation, you can highlight the obvious things that did not work and refine from there. While I am not familiar with these speakers the idea of giving structure to family decision making is a good topic for all. A theme which resonates in the pre-cons. With a structure guiding you, one is allowed improvise with more confidence as the situation changes, which is one of the most important factors to becoming a skilled clinician.

Opioid Dosing Strategies and Toxicity
by Davis, Lasheen, Walsh, LeGrand

Is it just me, or does that list not seem impressive if you leave out first names. Davis means nothing to me, unless I see Mellar in front of it, same with Walsh without the Declan, and LeGrand is unique enough to stand alone. The good folks at Cleveland Clinic return with a comprehensive opioid talk. A good one for feeling more confident in titration and conversions which is something all good palliative care practitioners should feel comfortable with. While MD based, I think this could be very beneficial for nurses as well since they often are catalysts in titrating opioids and the first line in the home at observing potential toxicities.

Discipline-Specific Leadership Skills Development
(Physician 8-Noon, SW 8a-5p, Nurse 6p-10p)

While the brochure is lacking in faculty lists and has a generic description these sessions look to be a pretty good deal for junior leaders (or soon-to-be leaders) in our field. I'll tell you that being such a new field there will be lots of room and need for leadership in the coming years at national, regional and local levels. Networking and career development sessions such as these and the more in-depth Harvard PCEP are great opportunities that compresses and shares many years of experience in just a few hours. For more info on each one, click on the link for the discipline above. These are sponsored by the College of Palliative Care and have NO FEE!! Thanks CPC!

1-5pm

Essential Grant Writing Skills for Junior Investigators
by Casarett, Ferrell, Tulsky, Kramer, Bakos

Also a NO FEE talk, this talk is a similar theme to pre-cons in the past few years. We got to build our research base people! Hopefully many will get inspired and do some great non-observational research (i.e. RCT's and treatment trials). I found this talk very helpful/inspirational in the past, but the one thing this talk will likely not get you is an infrastructure to do research, so hopefully you already have one in place, because you won't learn how to make you community hospice into a research institute in the next 24 months. Great speakers by the way and always nice to have Alexis Bakos from the NIH to help get us the inside scoop.

Mediating Ethical Dilemmas at the End of Life
by Williams and Arnold

While no class on ethics will ever tell you the answer to every ethical dilemma you have encountered, having a structural framework that is clinically applicable and teachable (as this session promises) is a great tool for our field. I am not sure what a MB ChB is, but Charlotte Williams, MBchB from UAB joins Bob Arnold for what looks to be a new and invigorating addition to the pre-cons.

"Is There Something I Should Know About Your Beliefs that Will Help Me in Your Care?" Talking to Patients About Their Beliefs and Spiritual Concerns
by Pulchalski, Blatt, Lunsford, Baird

FICA is your friend. No really. This is a great tool, and this session will highlight this tool and other strategies and themes. I have not yet had the pleasure to hear Christine Puchalski speak, but I have heard good things about her sessions in the past. This session should be a good one, and if you think you know FICA, they will likely expand your understanding and flexibility in approaching this powerful subject. I just hope the session has a wide audience and attracts more than just the choir (sorry) so that some people become more comfortable about spirituality and medicine.

Alternatives to Oral Opioid Therapy for Refractory Pain Conditions
by Yellig, Fine, Panchal

In under 4 hours, this session will cover some very interesting areas, such as ketamine, and interventional pain techniques. I find these sessions very intellectually stimulating but I shortly after being inspired at the session, I realize all the work I may have to do once I am back in my local environs to ally with the interventionalists or get staff more familiar with ketamine for pain control. I would like to see more appropriate and early access to nerve blocks and the like in our field, but I worry if our field will start to subspecialize even more.

Overheard conversation at AAHPM/HPNA in 2015:

Sue: "Hi! I'm a Spiritual Palliativist."
Tom: "Nice to meet you. I am an Interventional Palliativist. Have you met Joe? He is our new Conversational Palliativist."

Sorry that became more of an editorial. Final verdict: looks like a good session.

I will review the HPNA pre-cons in the next couple of days. And I am by far not the final word on any of these. Pick what interests you and feel free to offer comments about why you are going to any of the above session.

• Interesting Quote of the Month with Palliative Care Influences:

  “Life is not what we experience, it is what we remember and how we remember in order to retell it.” - Gabriel Garcia Marquez, Living to Tell The Tale
  

• Pallimed represent! I (Christian) will be at the Cachexia Conference in Tampa next week. I will have a Pallimed sticker on my badge, so feel free to come say hi if you see me, or post a comment or email me if you are going to be there and want to got to a Tampa Bay Lightning game Thursday night. I plan to report back from the conference to tell all Pallimed readers how to defeat cachexia!
  

• Tom recently posted some info on "disadvantaged dying." Pallimed reader K Jacobs chimed in with this link to the AAIDD position statement on EOL care in the disadvantaged.
  

• Edwin Leap, MD reflects on witnessing the impact of death in the ED, and how it seems like an alternate universe when he comes home to his family. I think this is something that could be echoed loudly by our field. Seeing death on a regular basis in our work makes little things in life much more valuable. It would be great to see some more palliative care oriented blogs to balance out the ED ones. (via Kevin MD)
  

Sativex for neuropathic pain; Research issues; VTE treatment in palliative care; Etc

Happy Thanksgiving to those of you who celebrate it - I won't be posting until after the holiday weekend.

1)
Pain has a randomized, placebo controlled trial of a cannabinoid for neuropathic pain. The study involved using sativex (an oral-mucosal cannabinoid spray which uses THC-standardized botanical material from marijuana plants as its base). It involved ~120 patients (mean age 53 years; all had persistent pain for more than 6 months and most were on multiple other meds; mean pain ~7/10; most had focal neuropathic syndromes like post herpetic neurlagia, radiculopathies, or neuropathic pain involving a single limb) who were randomized to sativex or placebo (after a test dose, patients self-titrated their own sativex dose using a protocol) and followed for 5 weeks. Importantly, only ~20% of patients were prior cannabis users. Both active and placebo sprays were flavored with peppermint to prevent unmasking, and intention to treat analysis was used. It was an industry sponsored study.

Patients receiving sativex had a statistically significant decrease in pain at 5 weeks (and it took well over a week for the pain curves to diverge) - average decrease was 1.5/10 on the 0-10 scale (a 22% reduction) - placebo patients' pain didn't change significantly. They estimated a number needed to treat of ~8 to get a 50% pain reduction. 18% of sativex patients withdrew due to side effects (vs. 3% of placebo patients - damn that peppermint spray!) - the autonomic side effects appeared to be more prominent & disturbing to the patients than the psychiatric ones. Unblinding (patients deducing if they were receiving the active drug or not) was not measured.

My gloss on this is that it's evidence that sativex is a effective analgesic, although most patients get only a mild response (a NNT of 8 for a 50% pain reduction is not great compared to tricyclics or gabapentin which tend to be in the 3-6 range). While side effects were a problem here, it's encouraging that 80% of the patients were ostensibly cannabinoid naive suggesting that it can be effective even in patients not pre-selected to tolerate cannabinoids. Sativex however isn't available in the US, and is pharmacologically distinct from other cannabinoid products (like dronabinol). Any of our Canadian readers using it in their patients for pain?

Image is of cannabidiol (from Wikipedia).

2)
There have been two recent journal issues devoted to research issues surrounding quality of life and symptoms in cancer patients.

Journal of Clinical Oncology has an issue looking at 'patient-reported outcomes' in cancer research. 'Patient reported outcomes' more or less mean symptoms and quality of life as reported by patients/research subjects. The issue contains a dozen summary articles from the National Cancer Institute's Patient Reported Outcomes Assessment in Cancer Trials (PROACT) conference from last fall. Most of the articles read like committee summaries (which they are), and I'm not going to belabor them here except to say it provides a snap-shot of the international research & funding issues about "PROs".

There is a certain sense of the orphan-nature of PROs in cancer research throughout, best put by the summary article:

"Yet, it is fair to say that questions about value added have been raised more frequently about PROs, and HRQOL specifically, than about any of the prominent biomedical outcomes. In part, this reflects the acknowledged importance of survival and disease-free survival as primary objectives of much cancer therapy. But it also reflects recurring concerns among some clinicians, regulators, and even cancer trialists about the meaning, technical quality, interpretability, and decision relevance of the PRO measures themselves. These issues are important because they challenge the validity, or at least the usefulness, of measuring cancer outcomes from the patient's own perspective. However, one of NCI's Strategic Objectives is "to ensure the best outcomes for all, including improving the quality of life for cancer patients, survivors, and their families." Thus, it would seem vitally important to measure the impact of cancer and its treatment on QOL from the perspective of those individuals living with and surviving cancer. For this objective to be realized, we need patient-reported measures of outcome that are valid, reliable, responsive, clearly interpretable, and decision relevant."

The other issue is from the Journal of the National Cancer Institute (Monographs) and is about quality of life and symptom research in cancer trials. These articles come from a symposium in 2005 about QOL measurement & meaning sponsored by the NCI's CCOP. It's more clinically oriented than the JCO issue, focusing more on the clinical relevance and use of QOL measurement in research.

It's mostly about health-related QOL, and avoids the perplexing philosophical questions about what QOL really means, but gives a few nods to 'global' QOL (excerpt is from this article):

"There is evidence that overall QOL is a distinct concept from the other components of the model of Wilson and Cleary, providing different information than symptoms, functioning, and perceived health status. In a study of 493 older patients, Covinsky etal. demonstrated a lack of concordance between patient ratings of health and their global QOL. They found that 43% of those with the worst physical functioning rated their global QOL as good or better. Conversely, of those with the best physical functioning, 15% thought their QOL was only fair or poor. They also found a lack of concordance for psychologic health and QOL. Of those with the fewest psychologic symptoms, 21% rated their QOL as only fair or poor. In addition, patients consider different aspects of life when rating QOL than when rating health status. Based on a meta-analysis of 12 studies in chronic disease, Smith et al. developed path models that demonstrated that patient ratings of their health and global QOL were influenced by different things. Perceived health status was most affected by physical functioning and to a lesser extent by emotional well being. On the other hand, global QOL was affected to the greatest extent by emotional well-being and less by physical functioning. A logical extension of these findings is that conclusions may differ depending on whether outcomes are measured in terms of health status or global QOL, particularly if there is lack of agreement between them. This provides an argument for the inclusion of overall QOL, in addition to measures of symptoms, functioning, and health status."

Together, the paper mentioned above, and this one here, make a good introduction to the measurement and meaning of QOL assessment in cancer research and would make good articles for the teaching file (particularly for fellows - I wouldn't necessarily throw these at medical students).

3)
Postgraduate Medical Journal has a review of managing thromboembolic disease in the 'palliative' setting. It's a general review of the topic, and makes some eyebrow raising statements. Notably it cites research to suggest that 25% of British oncologists were unaware of the elevated risk of thrombotic disease in cancer patients (looking at the study it cites about that it seems it was mostly about the increased thrombotic risk associated with tamoxifen and similar hormonal therapies). It also makes this statement:

"In the case series reported, most patients continued anticoagulation until they entered the last few days of life. These data, while shedding light on how long we should continue anticoagulation, also suggest that the majority of palliative care patients are appropriate for investigation and treatment of suspected VTE. Sometimes the biggest danger faced by the palliative care patient is not a complication of the disease process but rather the paternalistic nihilism inflicted on them by the attending clinician."

To be clear: there was a case series (lead-authored by the author of this review) which showed that one palliative service used anticoagulation until the final days of life - these descriptive data have now apparently morphed into normative data on what we should be doing, and, indeed, if we're not doing this, we are inflicting paternalistic nihilism on our patients.

What really gets me about this is that the sum of data we have on anticoagulating dying patients is a few RCT trials showing low molecular weight heparin is probably better than coumadin for VTE disease in advanced cancer patients; some descriptive data on what some centers are doing; and some tolerability data about LMWH shots (patients don't seem to mind them). What we don't have is any controlled data on actually anticoagulating patients with very short prognoses (less than a few months), and while one can reasonably argue that of course we should be anticoagulating these patients one could also reasonably argue that we don't know the risks of this and the benefits may not be great. We don't know - things that seem to make sense often don't turn out to be true in medicine - and because of that it seems like intimating patient abuse ('inflicting nihilism') is a bit premature.

It is not yet time for mud-slinging. That said, I'm looking forward to the die when I don't have to argue with hospice agencies about low molecular weight heparin.

4)
A couple e-pubs from Journal of the American Geriatrics Society.... One is a review of hypodermoclysis to treat dehydration. It's a straight-forward narrative review, mostly geared towards nursing home patients, but provides a good single source for the research base underlying the practice's safety and efficacy.

The second is about using cardiorespiratory fitness to predict mortality in the elderly long term. It shows that yes, long-term mortality (over a decade) is closely associated with CRF (in this case as measured on a treadmill test), but doesn't tell the average clinician much more, unless you're a prognosis junkie, as is one of the Pallimed contributors.

Many Items, Part 1

This is the first of a couple posts of 'many items in brief' as my inbox is overflowing with articles and I'm resigning myself to covering none of them in depth.

1)
There have been a couple recently published articles about treating 'behaviors' in patients with advanced dementia. First was a randomized, blinded comparison of citalopram with risperidone in the American Journal of Geriatric Psychiatry. It involved ~100 patients who were started on therapy during a hospitalization and followed for 12 weeks. Basically no differences were found between groups. The problem here of course is that antipsychotics aren't particularly efficacious for behaviors in dementia in the first place so the real question is not whether citalopram is 'as good as' risperidone but if it's any better than no drug treatment at all. The other was one in the NEJM looking at donepezil vs. placebo for 'agitation' in dementia. This too was a 12 week randomized trial involving ~270 patients and found no benefit. We've occasionally tracked silly or Orwellian drug/trial-group names on Pallimed and the NEJM study provided a fresh example: the trial-group is called "CALM-AD."

2)
Diabetes Care had a fascinating study about perceived burdens of diabetes care vs. its complications. It is based on interviews with ~700 adults with diabetes and involved questions about the perceived benefits/burdens of various scenarios (intensive glucose monitoring/control, diabetic complications such as retinopathy, etc.). To be clear - this involved asking real diabetics to speculate on the effects on their lives of hypothetical treatment/health status scenarios - it was not measuring the actual effects of these scenarios on patients' quality of life. They found that the subjects rated intensive medical therapy as bad as (having as much of an impact on quality of life as) all but the worst medical complications of diabetes. That's certainly interesting, but it's hard to make a big deal about it given all the hypothetical modeling going on. More interesting to me is just the fact that this research is going on - people are asking these questions - & I hope more to see more of this in the future.

3)
Journal of Clinical Oncology has a metaanalysis (pooled analysis) about the use of ultra-short screening tools for psychological problems in cancer patients (such as a single-item 0-10 'distress' thermometer). Basically the pooled analysis showed that these tools are, in fact, good screening tools: sensitivity 78% and negative predictive value 93% for depression. However they are poor diagnostic tools and the accompanying editorial stresses that they should be used for screening only.

Another issue looks at psychological distress/burden of spouses of cancer patients in Israel: there is a lot of distress.

4)
Pain is publishing revised evidence-based guidelines on the pharmacologic treatment of neuropathic pain. It's a reasonable and rather practical look at the evidence and divides agents into first line (e.g. TCA's, SNRI's, gabapentin/pregabalin), second-line, and third-line classes. Great one for the teaching file.

There's an accompanying editorial by Nathan Cherny, subtitled 'From Hubris to Humility' which is worth a read. It addresses the guidelines demotion of opioids from 1st to 2nd line agents as well as the reality that neuropathic pain isn't too easy to treat (well). A quote:

"The second change relates to the tone of the document. A new humility has been introduced into these guidelines. The 2007 guidelines are much more circumspect about what can be expected from the outcomes of pharmacotherapy for neuropathic pain. The new document describes the potential efficacy of the recommended agents whilst maintaining a realistic outlook on the actual likelihood of achieving a good outcome for the individual patient. In their conclusion, the authors remind us that despite the best of care and sequential trials of therapy, pain will remain unrelieved or inadequately relieved for 40–60% of patients suffering from neuropathic pain. The hubris is gone and the limits of what can be routinely expected from the best of care are candidly discussed. This somber assessment challenges us on many levels. How can we help the patient with persistent inadequate relief despite sequential trials of individual and combination therapies? How do we, as caring physicians, deal with the limits of our current therapeutic repertoire and with the sub-optimal outcomes our patients must endure? This question has particular poignancy in the context of the asserted right to relief of pain that we ourselves have espoused."

5)
There's a new Cochrane review about methadone for cancer pain. Conclusions are as-expected: it's efficacious, no evidence it's better than morphine, be careful with using it. This is certainly one topic for which there are more reviews than there are actual trials....

6)
A couple media items:

PBS's Frontline is showing a documentary about Thomas Lynch on October 30. He is the undertaker who writes/speaks very eloquently (and idiosyncratically) about death and dead bodies (see my prior post on him here).

The NY Times health blog The Well posted a provocative piece about 'When Doctors Steal Hope' about doctors giving inaccurate and pessimistic prognostic information. Read the comments which are just as interesting as the piece itself. Missing from this context of course is the well-researched reality that most of the time doctors give overly optimistic information (we both tend to overestimate outcomes to ourselves and then deliberately overestimate prognosis - at least longevity - to our patients - see Lamont & Christakis' work on this).

(Thanks to Christian who alerted me to this but was too lazy himself to post about it - c'mon man you've only posted 3 times in the last week!)

7)
The FDA is putting out new warnings about modafinil - Stevens-Johnson Syndrome & other hypersensitivity reactions are being reported.