Tweet

In brief...

Most of the December 27th issue of JAMA was notable:

1)
On the prognosis front--there's an article looking at trends in stroke mortality. Rates of stroke are decreasing, as is 30-day mortality in men (14%). 30-day mortality in women has remained stable for decades at ~20%.

2)
There's a coda for the recent Perspectives on Care at the Close of Life on frail, elderly adults.

3)
There's also Perspectives piece about end of life care for homeless patients. This, for me, is the most best of the (overall excellent) Perspectives on care at the close of life series--probably because it's an area I know little about, and the case/story presented in the piece is extremely compelling. It involves an older, homeless, heroin-using man with renal cell cancer. He was told when first diagnosed (and when he possibly had curable cancer) that he couldn't get his nephrectomy unless he quit abusing drugs(!). So after his renal cell spreads everywhere and there's nothing to do about it he is cared for by a palliative care team in San Francisco. He continues to use heroin both 'recreationally' (acknowledging there is nothing recreational or fun about heroin addiction) and for analgesia early on while under the care of the pc service. Then, as he gets sicker, and constantly seeking out heroin becomes more difficult, he quits and is maintained--apparently without incident--on prescription, oral opioids. All the legal, social, and financial issues are discussed at length. It made me hope they dedicate an entire piece in the Perspectives series on caring for people actively abusing substances at the end of life.

4)
And finally, there's a series of letters about the recent Clinicians' Corner discussion of patient refusal of care (which involved a debilitated elderly woman in an objectively unsafe home environment who refused to be discharged anywhere other than home). (I was sure I blogged this but I can't find it anywhere which means I in fact didn't blog it. This is unfortunate given that last week I tried blogging an article only to realize half-way through I had already blogged it. I'll publicly state it now: I don't want a feeding tube.) It's a thoughtful, provocative article about patients refusing (what we believe is) clearly beneficial care.

Tweet

1)
Lancet Oncology has a couple of articles to note:

First is a randomized controlled trial of sertraline in advanced cancer patients suggesting it's not good for what ails you. This was a randomized, placebo controlled trial of 189 patients with advanced cancer who weren't feeling great (had some symptoms of depression, fatigue, anxiety, etc.) but who weren't felt to be actually depressed. What was meant by that last phrase - it's a little tricky - the patients had to score 4/10 on scales of self reported depression, anxiety, or fatigue - but who didn't have 'major depression' by the assessment of the 'responsible' clinician. That is, the patients weren't formally assessed for major depression, meaning that probably some of them indeed had major depression given how depression is notoriously under-diagnosed in cancer patients (on the other hand this does replicate 'real life' insofar as these weren't patients the treating clinician would have likely treated anyway). Patients were given 50mg of sertraline or placebo and primary analyses were at 4 & 8 weeks (although it seems patients were followed longer). Numerous assessment scales were employed.

Most patients were over 60 and had ECOG scores of 1. Sertraline did not come out looking good: basically no benefit on any of the many measures they took of depressive symptoms, fatigue, quality of life, etc.; it was discontinued earlier and more often than placebo due to adverse effects; and the study was actually stopped early because it looked like the sertraline patients had higher mortality than placebo (this wasn't significant in the final analysis however and was probably a statistical event and not a clinical one).

Prior to seeing this study I hadn't been aware people had been suggesting SSRI's for advanced cancer patients without a clear indication for them as a "quality of life booster" or a preventive measure against future depression and this study will likely squelch further investigation of this. I wonder though if further investigation is needed and that's to see if sertraline is effective for at all 'true' major depression in advanced cancer patients particularly given than some of these patients certainly had major depression and pretty much all of them had depressive symptoms. This, I think, is the true implication of this study. I would need to do a literature review here, and maybe a reader could help out, but my impression was that there are a handful of quality studies looking at antidepressants in cancer that were generally positive. What I'm unsure of is how many of these studies were of advanced cancer patients as that may make a world of difference.

I'll also briefly mention a trial of radium-223 in hormone-refractory prostate cancer with painful bone mets. Radium-223 is beginning to be studied in humans as a novel radionucleotide (similar to strontium or samarium) and this was a phase II study in which it (or placebo injection) was given to patients undergoing concurrent external beam radiation. It only involved ~60 patients and the main outcomes were tolerability (it was well tolerated) and markers of bone turnover (alkaline phosphatase). Tantalizingly their results suggested an antineoplastic effect of the radium (slowed down PSA rise and the patients who received it lived longer) although the study wasn't really designed or powered to show this. Pain/analgesia and quality of life weren't measured at all. One assumes that these will be looked at in phase III trials and I hope these outcomes don't get lost as people get excited over this as an antineoplastic agent.

2)
JAMA has a couple pieces recently as well.

First is a another installment of JAMA's 'perspectives on care at the close of life' series - this one on palliative care for patients with ALS. Like the rest of the series it is a comprehensive review based around a case and patient/family/clinician interviews. One of the most interesting aspects of the article to me was its discussion of tracheostomy and long term mechanical ventilation and that there's some evidence to suggest that many patients who receive this do so under emergency circumstances and without their explicit consent. Yikes.

Last is a 'coda' to their recent one on management of fatigue at the close of life. I really appreciated these lines. This is July, the time when fresh palliative care fellows are starting their training, and understanding this perspective is key to their education:

"I am deeply humbled by my experience in caring for Mrs D. She taught me much about balancing "cure" and "care" in patients facing chronic and progressive illness. She reminded me that the challenge of providing genuine "patient-centered" care—care is fundamentally grounded in a patient's goals and preferences—especially within the context of great uncertainty.

Mrs D also taught me much about managing fatigue in elderly persons with progressive illness. Although I seemed to achieve temporary success with treatments like antidepressants, exercise, and appetite stimulants, I truly believe my most important intervention was a willingness and commitment to listen to her frustrations, fears, and hopes around this troubling and refractory symptom. My treatment attempts, regardless of their efficacy, seemed to at least validate her illness experience."

Tweet

Some ramblings on recent papers piling up from JAMA & Journal of Clinical Oncology, following two tenuous threads of 'whopping' and 'modest but measurable.'

JAMA has a brief discussion of allowing terminally ill patients access to experimental drugs (written in the context of the 'Abigail Alliance' ruling see here & multiple posts here). The commentary is not about the Abigail decision(s) per se - about whether patients have the right to obtain experimental drugs - but more a practical discussion of how best to allow patients access - balancing interests, minimizing exploitation, etc.

JAMA also continues its 'perspectives on care at the close of life' series with a review of agitation and delirium at the end of life. Nicely done & good for the teaching file.

Continuing on with JAMA - a randomized trial of deep-brain stimulation vs. best medical therapy for patients with Parkinson's disease has been published. I am in no position to be a good judge of the clinical import of the findings - the major outcome evaluated was time spent in the 'on' state without significant dyskinesias as measured by self-reported patient motor diaries (which seems a somewhat troubling measurement tool particularly given that this was not a blinded study as patients knew whether they had hardware in their brains or not). Patients who received DBS had substantially more 'good motor function' hours a day (4.5 overall) than the best medical therapy patients (which sounds pretty good to me), although at a cost. A whopping 40% had serious adverse events due to the surgery (infections, etc.), and even at 6 months there were some ongoing trade-offs (some increased depression, more falls, mild cognitive decrements) in the DBS patients. I mention the study in large part because interventions like this (up front risky/invasive, costly device therapies/interventions which however may improve either longevity or quality of life in a substantial number of patients - think LVADs) continue to become more common, our patients with highly morbid and/or life-limiting diseases are going to be facing decisions about these interventions more and more (whether to try them, managing complications from them, struggling with considering stopping them), and palliative care folks will be called upon more and more to help patients with those decisions.

JCO recently had a look at the natural history of bisphosphonate associated osteonecrosis of the jaw in multiple myeloma patients. A whopping 26% of patients did not heal over the course of the study (sufficient patients are still enrolled and being followed such that the median follow-up time has not yet been reached: minimum follow-up has been 3.2 years for the cohort).

JCO also has another study looking at the quality of life impact of prophylactic whole brain radiation for patients with extensive stage small cell lung cancer (yes, at least on a time frame of 3 months, it has a modest but measurable impact on health related quality of life for the worse).

Finally, there's a fascinating randomized (routine-care-controlled) study involving giving advanced lung cancer outpatients a quality of life diary (they were asked to fill out a QOL questionnaire once a week and were encouraged to bring concerns to their providers). They found that those who were given the diary had, yes, modest but measurable decrements in their health related quality of life. The diary, if it did anything, seemed to make the patients feel worse. Most diary patients didn't however share their concerns, questionnaire results, etc. with their providers. It's a fascinating study, and if you believe the results a good warning - giving patients these measurement tools without any system for responding to them, any monitoring or routine evaluation of the patients' questionnaire responses, may actually make them feel worse.

It seems we clinicians are stuck in the unfortunate position of having to ask our patients how they are doing.....

Tweet

It is really hard to see a randomized controlled trial conclusion that does not support your previously held view of medical practice or education.*  Yet it's vitally important to pay close attention when this happens, and try to deeply understand what's going on so you can change your practice, if necessary.  So I'm here to pay close attention (and be rather long-winded in the process).

Earlier this month, JAMA published an RCT conducted by Curtis et al. which evaluated the effects of a communication skills intervention for internal medicine and nurse practitioner trainees on patient and family reported outcomes.  The communication intervention, which was developed by the educators at Vital Talk, is popular in the palliative care community.  It's perhaps most commonly known as the intervention used in Oncotalk. At the core of the intervention is high fidelity encounters with a simulated patient or family.  It's an intervention which has been shown to help trainees gain skills related to conveying empathy and talking about serious news/goals of care, etc.  A separate publication documents skill acquisition in the JAMA RCT's intervention group.

But the JAMA RCT took it a step further with an attempt to determine if the educational intervention would positively impact patient-centered outcomes. 

In short: No benefits found in this study.  No increase in patient, family, or other clinician rating of quality of communication surrounding end of life care.  No improvement in mental health outcomes.  In fact, patients exposed to the intervention group's trainees experienced a small but statistically significant increase in depressive symptoms.  Let's take a closer look at the purpose and methods of the study.

What's the purpose of the educational intervention?
The educational intervention is designed to give trainees skills necessary to conduct pivotal conversations- to ensure that patients and their families understand where things stand medically (and where things might be going), empathize and provide support when the news is serious, and to align treatments with patient values and goals.  While I'm not familiar with the specific simulations used in the intervention, from other experiences with this method, the simulations usually feature patients who are at a pivotal point with their health.  A new or relapsed serious illness. Worsening of a condition, indicating that treatments aren't working very well. A transition to the actively dying phase. 

Was patient selection appropriate for this study? 
All of the patients included in the study had serious illnesses (25% outpatients and the rest inpatients), and one might anticipate that each patient would need to have conversations about serious news, goals of care, and end of life care at some point along their disease trajectory.  But at every visit?  Likely not.  Some of the skills taught could be applied at any visit, but would the full benefit of these skills be felt if the patient was stable without troubling new issues?  Could patient stability reduce the importance of applying these skills at many of the visits?

So, how many of these patients were actually at a pivotal point in their disease trajectory during the study encounters?  We don't know, exactly.  Here's what we know:

• Patients in hospice care were significantly less likely to return surveys (only 26% of patients in hospice care returned surveys).  We don't know how many patients in each study group were in hospice or on the verge of hospice referral,which represents one of many possible pivots in a patient's health and care.
• When there was documented communication about end of life issues, patients were significantly less likely to return survey (34% estimated return rate)
• Families of the 16% of patients who died during a hospitalization were dramatically and significantly less likely to return the survey (a measly 29% when the patient died vs. 78% for families when the patient survived hospitalization).
• Among respondent patients who rated their health status as "poor", quality of communication scores were higher in the intervention group.

In this study, those are about the best proxies (albeit insufficient) for whether patients were at a pivot point in their disease trajectory when they encountered the study trainees.  Among patients, there was a 44% response rate and a 68% response rate amongst families.  But response rates were even lower in the patients and families where these communication skills might prove most useful.  Table 2 compares the study and control group with respect to many variables, including how many patients died in the family evaluation group, for instance.  The table probably should have included more of these "potentially at a pivot-point" variables. 

We have no idea what the subject of the conversation was during each visit. Perhaps the control group had sufficient communication skills to navigate routine patient visits and achieve scores comparable to the intervention group.  Reviewing the QOC tool, many of the skills on which patients/families were asked to evaluate trainees are basic skills (making eye contact, etc). Maybe there were enough routine visits to drown out the pivotal conversation visits in the study.  There's no way to know. 

Confounders for the measurement of trainee skill
Another variable which was not reported was the timing of when patient/family/clinician evaluators filled out their surveys.  It's entirely possible that by the time the evaluations were filled out, patients and families might have remembered the face of the trainee.  However, as time elapses from the visit, recall bias likely only grows.  Think of the number of factors which could impact the rating- the plethora of other clinicians the patient could have seen during the same hospitalization or in the interim. One inclusion criteria for the study was patients who had palliative care consultation, but it's not known how many of the patients received this.  You could imagine that being a confounder for patient satisfaction! Also, consider the conflicting messages patients and families receive and the illness experience itself as other confounders.

The depression result
First off, it's not clinically significant by the pre-defined minimial clinically significant difference of a 5-point change in the PHQ-8.  Granted, it was statistically significant, with a covariate adjusted 2.2 point increase between the groups. 

What to make of this clinically insignificant increase in depressive symptoms?  We know sadness comes with some of the messages we have to give to patients and their families.  But none of us want to make someone more depressed, if we can help it.   

PHQ-8 was measured at a a single time.  And we don't know when that was, and whether timing varied for some reason between the intervention and control group.  But let's assume measurements occurred at exactly the same time in each group. 

We have empirical evidence to suggest that the elements of grief have "average" trajectories, with depressive symptoms being an expected element of that grief.  Assuming that trainees in the intervention group were having more end of life discussions (a leap, because we don't know for sure), is it possible that the "arc" of the anticipatory grief experience was modulated somehow?  More depression earlier on, with greater acceptance to come when the control group was hitting the peak of their depression? 

This is merely a hypothesis.  But I think simultaneously while we ponder the possibility of harm, alternative hypotheses need to be considered as well.

How might this mesh with another highly regarded communication intervention trial?
Previously, Lautrette (and Curtis) et al. demonstrated the effectiveness of a communication strategy at reducing depression, anxiety, and PTSD symptoms in bereaved family members three months after the loss of a loved on in an intensive care unit.  One of the core interventions was a structured family meeting that involved clinicians using the VALUE mnemonic.  While this particular mnemonic was not central to the educational intervention in the JAMA study, the intervention helps trainees gain the skills necessary to accomplish the goals central to the mnemonic.  Why the difference in outcomes, then?  I hypothesize that it comes back to patient selection.  All of the patients in Lautrette were clearly at a pivotal point in their care when the intervention was applied. 

Anecdotes remain powerful 
A critical care fellow sends an email noting that after an impromptu late night family meeting, the nurse commented on how smoothly the meeting went and the resident told her he hoped he could communicate like that one day.  Another fellow sends a text with a report that in a difficult conversation, he made a statement admiring the care the family gave to the patient, and the emotionally charged family calmed down, becoming more able to focus on the difficult conversation at hand.  You observe one of your fellows find a new way to align herself with a patient asking for treatments that won't be beneficial, and she remarks afterwards about how she wasn't doing that just a few weeks before, and how useful she has recently found the new technique.

All of the above fellows participated in a communication course conducted using the Vital Talk teaching methods studied in the JAMA RCT.  Multiple studies (including the recent JPM study linked with this RCT) have now demonstrated change in behavior from this intervention.  It's possible that the change is not long lasting.  If we were to set aside some of the methodological issues of the JAMA RCT and believe the conclusions (no improvement in patient outcomes), it's possible that the trainees didn't have adequate reinforcement to change their behavior permanently.  It's also possible that some of the anecdotal success comes from viewing this as an iterative process with high level learners who are a different audience than the intervention group of the study.  For more on that and further commentary, here's Drew...

Like Lyle, I have been trained in and use the techniques used by the Oncotalk/Vitaltalk crowd, and, via first-hand experience, strongly believe they are effective in improving the quality of communication. I watch communication skill acquisition happen rapidly, in a way that is nearly giddying (as an educator) to watch. In my own fellows, I perceive that these improvements have a lasting effect on the level/quality of my fellows' communication skills. So, for me, it was disheartening to see such a well-designed study of these techniques be so 'negative.' Admittedly, my first-hand experience with this is has been so positive that I find it nearly impossible to believe that the techniques aren't effective.

That said, as I have thought about this investigation, one of my conclusions is that perhaps the reason I perceive the techniques to be so effective is that I have been using them, myself, to train palliative care fellows (not medical interns). My fellows 1) are physicians who are very, very motivated towards excellence in physician-patient/family communication, and 2) after the Vitaltalk-style workshop they continue to have close supervision and feedback from me and my faculty on their communication. Effective, empathetic, patient-centered communication is a huge, explicit part of their curriculum, as opposed to ineffective, aloof, and pathology-centered communication being a huge part of the "hidden curriculum" as it is for too many other medical trainees. I think it's possible that those phenomena may, in part, explain the disconnect between the apparent ineffectiveness of the Curtis trial vs my own experience with these training methods.

I'll also note that I don't necessarily believe patients are the best judge of physician communication quality. Certainly, patient satisfaction with physician communication cannot be the sole measure of quality (note: I'm not suggesting that the Curtis trial judged the quality of communication uni-dimensionally). I am reminded of the CanCORS study, which showed patients with metastatic lung or colon cancer who did not understand that their chemotherapy was not going to cure them, were more satisfied with their oncologists' communication than patients who were better informed. Sobering stuff.

Conclusion
While the results of this trial are disappointing, the negative results may reflect how challenging it is to study patient centered outcomes of educational interventions.  This study also gives us an opportunity to reflect on how to define the patients who benefit most from communication training interventions, when the benefit is most likely to occur, and which trainees/practitioners might be in the best position to receive the intervention.  No doubt, there are other interventions which may improve clinician communication in pivotal conversations, and we should also reflect on ways to improve the studied intervention.  As a palliative care community, we should be interested in a multi-faceted approach that involves changing both practitioner behaviors and early patient/family preparation for pivotal moments near the end of life.  Evidence supports the notion that we can help trainees grow their communication skills.  Fortunately, we don't need FDA approval to disseminate medical education interventions which help trainees develop skills that most would agree are valuable.  This intervention remains an integral part of the equation.

For other perspectives on this study, see the JAMA editorial by Chi and Verghese, Vital Talk's commentary, and Geripal's commentary. 


*Disclosure: Lyle currently receives funding from an IU Health Values Grant to use these teaching methods with various fellowships at IU School of Medicine.  All opinions expressed in this post are solely those of the authors. 

Tweet

JAMA has published two Perspectives on Care at the Close of Life pieces in the last few weeks.

1)
The first is a review on palliative care for Latinos. With all due respect to the consistently excellent PCCL series I have to say this has been my favorite, perhaps for the simple reason that my own content-knowledge in this area is lower relative to the other ones. (This is despite doing my medicine training in Denver - I did not however learn about aspects of care particularly relevant to death and dying). Perhaps also because it is contains such well-written prose:

A young pregnant woman develops a fatal cancer and dies before her daughter reaches her first birthday. Her partner cannot bear the thought of her dying. The suffering experienced by this patient, her partner, and the health care team suffuses all of the care providers' descriptions of this case. The deep sadness here is universal. What is also clear is the profound influence of culture and immigration on this young woman's experience at the end of her life and on that of her partner.

The paper discusses important cultural norms/narratives such as familismo, fatalismo; barriers to care from language/interpretation (this is one of the best, short, practical discussions of using medical interpreters I've seen anywhere), and issues regarding religion and immigration status. This is now at the top of my teaching pile for cultural issues.

2)
The second is about self-care for physicians caring for dying patients. It focuses on burn-out and compassion fatigue, but also devotes a large amount of space for positive coping/responses to workplace stress, grief, and loss, and on the 'best-practices' of clinicians who thrive/endure in stressful environments full of loss.

The physician who formed the case for the piece made a comment which I really appreciated:

'The stuff that burns me out has nothing to do with loss. . . . It's fighting insurance companies . . .'

I think many who don't do palliative care assume the major stressor is the death/loss - for me and most that I've spoken with about this issue this is not the case (it's there of course, and there can be individual cases which are devastating, although routinely caring for dying patients and their families is invigorating and a source of great satisfaction). It's the grind of documentation, patient-load overload, administrative-academic-clinical duties pulling at you at once, etc. etc.

Along these lines, they discuss the enriching aspects of caring for the dying:

Posttraumatic growth is characterized by positive changes in interpersonal relationships, sense of self, and philosophy of life subsequent to direct experience of a traumatic event that shakes the foundation of an individual's worldview. Posttraumatic growth is not uncommon and may occur concurrently with negative sequelae of trauma. The term vicarious posttraumatic growth describes the phenomenon of clinician growth that results from witnessing positive sequelae of other people's experiences of trauma. This may include the clinician's feelings that his or her own life has been enriched, deepened, or empowered by witnessing the patient's or family's posttraumatic growth. When patients experience meaning and peacefulness in relation to their approaching death, this enriches the lives of the clinicians involved. This phenomenon appears similar to the "healing connections" identified by Mount and colleagues.

Tweet

JAMA continues the wonderful series "Perspectives of Care at the Close of Life" with an article from Dr. Harrington and Dr. Smith from VCU about the timing of chemotherapy in patients with advanced cancer who may be dying (sub req'd). This is particularly relevant because of the recent Dartmouth Atlas report on geographic variability in aggressiveness and costs in the last two years of life despite no large differences in outcomes.

A common opinion is that health care spending is higher then it should be in the last two years/year/6 months of life. Taking this position is clearly a sign of superior skills in prognostication or it demonstrates the ability to use a 'retrospectoscope.' Reading the case presented of a gentleman with metastatic non-small cell lung cancer as he progresses through three lines of chemotherapy will sound familiar to many palliativists. But it is not necessarily obvious when he become 'terminal.' Thus the dilemma of when to shift from curative to palliative care as a primary goal.

The two interviewed physicians in the case do well to show respect for the other, but you still get a sense of the tension that can exist between oncologists and palliative doctors. After being consulted the palliative care doctor called the oncologist and clarified the issues at hand, but they did not explicitly share prognosis as this quote from the palliative care doctor shows:

"They were shocked about the prognosis that I offered . . . of days to weeks. They were still expecting more chemotherapy. Here I was, walking into the room and basically saying, “Okay, folks, it’s time for hospice.”

Curiously as much as prognosis plays a role in these decisions it is somewhat glossed over in the article. This quote from the authors somewhat baffled me:

"When the prognosis is predictable, as with Mr L, why do most oncologists not directly address it?"

The answer to the question is that the prognosis is not always so predictable. We need more prospective studies to demonstrate prognostic skill that so greatly influences decision making. The article quotes many studies showing use of new chemotherapy regimens within a few weeks of someone dying. What is not always clear is was it appropriate to be on the chemotherapy. It is easy to imagine the patient with an ECOG of 4 or PPS of 30 as one of those patients who died within a few weeks after the new chemotherapy started. But what if their ECOG was 2 and the PPS 60 or 70% and they still died. Would you consider that use of palliative chemotherapy appropriate?

These prospective studies of clinician and patient prognostication and the impact on clinical decision making is what medicine needs to better determine if we are making the 'right' decisions at the right time. Looking retrospectively only generally informs us of a existing challenge. It does not provide the answer.

The article is a good read with some great references and an excellent one for the teaching file for oncology and palliative medicine. The focus is not really on prognosis as I have made it here, and what it does cover the authors do an exemplary job. The tables are also particularly notable:

• What Patients Know About Their Advanced Cancer and Its Prognosis
• Palliative Chemotherapy for Metastatic Disease for 4 Common Solid Tumors
• Helpful Questions to Consider Asking About Palliative Chemotherapy
• Things to Do or Say (and Not to Do or Say) About Chemotherapy for Advanced Cancer
• Studies of Concurrent Palliative Care With Oncology Care

The lead author of the article was also one of the selected speakers for the Annual Case Conference for Professionals-in-Training in 2006 at the AAHPM. Way to go Sarah! COngrats on the JAMA publication.

The article was highlighted in USA Today this week, and here are a few of the interesting comments from the website article:

Sorry for the long comment, but I have seen people refuse treatment and die because they were afraid of chemo or something as silly as losing their hair. Chemo is not that bad and has the possibility of extending a life significantly.

As a physician, we don't have crystal balls. To say, you have 5 weeks or 5 months is extremely difficult. We can say based on a certain type of cancer or terminal disease, MOST PEOPLE with this disease typically survive "X" amount of time....but to narrow it down to the individual patient is not feasible. There are many variables.

Palliative care is the wave of the future. These highly trained doctors and nurses do outstanding work with patients and the medical team assigned to those patients. Many times, my sister (the nurse practioner) has had to counsel doctors, interns and other nurses on how to talk to the patient and what to say. She herself has worked with scores of terminally ill patients and their families walking them through the journey, talking directly but gently, and helping them to see the full picture. Hopefully as this unique practice grows, most, if not all, hospitals will have palliative units to help everyone with these difficult issues.

Harrington, S.E., Smith, T.J. (2008). The Role of Chemotherapy at the End of Life: "When Is Enough, Enough?". JAMA: The Journal of the American Medical Association, 299(22), 2667-2678. DOI: 10.1001/jama.299.22.2667

Tweet

Many items....

1)
From JAMA:

First is one in their ongoing series 'perspectives on care at the close of life' on palliative care for patients with head & neck cancer. Besides being a solid review of the topic, as are most of the 'perspectives' pieces, this one stood out for two reasons. It's the most 'supportive care-y' one in this piece, and really reflects a broad perspective of palliative care as not just for the dying (despite the name of the series). The other is this wonderful (and rarely seen in the medical literature) discussion of self-image and blame:

Although some patients may blame themselves and feel they caused their own illness, patients may also feel guilt about the toll that the illness takes on their family and caregivers. Eating is a major social, cultural, and religious ritual in society, and patients with head and neck cancer often cannot participate in this activity. Even going out to dinner can become an impossible task, and patients may often be concerned about the impact this has on their family. Likewise, facial disfigurement—even if only temporary—may make it emotionally difficult for patients to leave the house, which can change the dynamic between patients and their loved ones. Feelings of guilt and self-blame in patients with head and neck cancer are therefore not only related to their own role in their illness but also to the belief that they are to blame for the impact the illness has on the quality of life of their loved ones. Physicians can assist patients with these feelings by encouraging them to talk about them with their loved ones, and even facilitating these conversations. For example, if a patient is accompanied to an office visit with a caregiver, the clinician can ask both of them, "What role has the illness taken on your relationship?" or even more directly, "Are you finding it difficult to eat out in public? How are you handling the changes imposed by the cancer on your social life or religious practices?"

The same issue also has a 'coda' for a previous perspectives piece about nausea and vomiting from last year.

And on the general cancer front JAMA also recently published the results of a randomized, controlled non-blinded trial comparing chemoembolization with radiofrequency ablation with both in patients with hepatocellular carcinoma. The study involved ~290 patients with unresectable (but not metastatic) hepatocellular carcinoma, at least one lesion greater than 3cm (as well as certain other tumor-specific entry criteria) & they were randomized to one of the 3 arms. I'm mentioning the trial for a couple reasons. First, there aren't too many therapies out there which have been shown to significantly improve survival in these patients and second, the study provides some general prognostic information for outcomes in this population: median survival was 24 months in the chemoembolization group, 22 months in the RFA group, and 37 months in the combined treatment group; 1, 3, and 5 year survivals were 75%, 32%, 13% in the chemoembolization group (very similar to the RFA group) and 83%, 55%, and 31% in the combined therapy group.

I'm curious how many other palliative clinicians are seeing these patients - my group sees a good number of them (usually referred by interventional radiology) as they near the end of their treatment course (or earlier if they're having a lot of symptoms) - and some relatively solid prognostic data are helpful.

2)
Archives of Internal Medicine has a research letter furthering the Vitamin D For Everything consensus that seems to be gathering in the last several years (falls, frailty/muscle weakness, cancer prevention, cancer therapy, and chronic generalized pain are just a few topics off the top of my head that vitamin D has been shown/purported to impact). This is about vitamin D for neuropathic pain; the letter presents uncontrolled observational data from giving 50 patients with painful diabetic neuropathies (and low serum D levels) ~2000 IU of vitamin D for a few months. The pain got quite a bit better. This is swell, and hypothesis generating to be sure - clearly controlled research is needed.

3)
Two from Journal of the American Geriatrics Society:

First is one looking at 6 month mortality after hospitalization for a COPD exacerbation. This was a single institution (Italian) prospective cohort study of ~240 elderly inpatients (mean age 82 years) with COPD exacerabations who were followed for 6 month mortality. For some reason patients with a previous history of 'chronic hypoxia' were excluded (???). Of note, the study cohort had 'nonacidemic' exacerbations which they defined as an arterial blood pH of greater than 7.34 (they don't clarify if they also excluded chronically hypercapneic patients who had high pCO2 but weren't actually acidemic). 2% died during the hospitalization (seems a touch low to me, given the age of the cohort) and 20% died by 6 months. They found a lot of the usual suspects were associated with a higher chance of death at 6 months (low BMI, poorer performance status, greater severity of COPD exacerbation) in univariate analysis. (None of the data were robust enough or presented in a way to affect clinical decision making, however.)

The one particularly interesting finding was that the functional status (measured via the Barthel Index) at the time of discharge (not at baseline) was predictive of 6 month mortality in the multivariate analysis - the authors comment on this too as it suggests (maybe) that the 'functional hit' one takes during the exacerbation is of particular prognostic importance. This makes sense but it's the first time I've seen it show up and I hope the authors/others look into this.

The other one is really for the prognosis completists out there: it looks at long term survival and functional outcomes for elderly patients who have already survived 1 year after 'planned or unplanned surgery or medical intensive care unit treatment.' Why one would want to study this exact population (both unplanned surgery or MICU stay? already survived one year?) remains unclear to me. Most people were doing fine, but of course they were since they'd already lived a year....

4)
Journal of Trauma has a paper looking at outcomes in elderly patients who suffer cervical spine fractures. This is a retrospective review of a single trauma center's experience with these patients. I have encountered only a very few elderly patients with cervical spine fractures (at least high C-spine ones) who have done well so this paper caught my eye. Acute mortality was ~25%, higher for high C-spine injuries and for those presenting with neurologic deficits (40-50% range). They also looked at the role of having an advance directive (they don't specify at all what they meant by this - POA forms, living wills, treatment limitations or not, etc.) and found that overall hospital length of stay was about 6 days shorter for these patients (despite having worse injury severity scores). They speculate that it may be because these patients' care goals were more palliative focused and so didn't linger in the hospital too long (although their ICU length of stays were identical to patients without ADs). Perhaps, but having an advance directive may also be a marker of increased family/social support, or preexisting nursing home residence, or other factors which could shorten a hospital stay....

5)
Resuscitation has a letter about the (what sounds like informal) development in one Canadian institution of "Do not MET" orders (MET being medical emergency team which sounds like what are frequently called rapid response teams in the US - essentially teams called in to rapidly assess/stabilize/transfer 'crashing' hospitalized patients prior to the patient needing a full 'code' called). It sounds like the MET team is still called even if a patient has a DNR order and so for appropriate patients people at their institution are writing, essentially, 'Do Not MET' orders as well.

If you found the 'METuscitate' in the title unbearable I'll point out that it's from the title of the the letter and I didn't make it up. It got me thinking, however, what does one actually call such a word? Is it a portmanteau? If so, how does one account for the acronym?

Tweet

It looks like JAMA has closed their series 'Perspectives on Care at the Close of Life,' which we covered extensively the last year, and started a new one 'Care of the Aging Patient.' There have already been two so far, but in addition this week's issue has a 'Clinician's Corner' piece about a patient with cardiac cachexia and hospice care. Thus, a JAMA update today.

1)
First, the Clinician's Corner piece. The case begins succinctly: Mrs H is an 86-year-old retired health care professional and grandmother with severe cardiac cachexia. She is considering the best way to have her life end. The case goes on to describe a patient with advanced heart failure, slowly progressive functional decline, and multiple comorbidities, who considers her current quality of life marginal (ok now, but very worried it will be intolerable if things get any worse), and is making statements about wanting her life to end (although is not overtly suicidal). With the brief case discussion, which includes quotes from the patient herself, you really get to know and feel for this patient:

I’m still doing things and I still enjoy life, but I’m taking so many medicines, and each year I’m a little worse. I’m very afraid that I’m going to be incapable of doing anything—I had a grandfather who used to say, "Why doesn't God take me?" Well, my feeling is "Why doesn't my heart stop beating because it's in such bad shape?" I used to think when I got depressed that I could go and throw myself off the top of the building. Now I couldn't even get there.

I talked with my doctor about the fact that I was interested in the end of life and that I was thinking about discontinuing all my food and liquids and all my medicines, including my insulin. She told me that if I stopped taking insulin I might have a very high blood glucose. My experience with high blood glucose was that I got very, very thirsty. And when I thought about it, I thought, "Well, that means I would die of thirst." I realized that didn't appeal to me.

Her physician recommends a hospice referral. The following wide-ranging discussion is about US end of life demographics and hospice utilization, prognostication in CHF, causes and epidemiology of requests for hastened death, and how palliative care consultation and hospice care could potentially help this patient. Voluntary cessation of eating and drinking is also discussed. Overall it's a balanced, realistic look at the issues, including a description of how hospice and palliative care services can help patients like this, and the article would make a good one for the teaching file, particularly for med students and residents.

2)
The first 'Aging Patient' piece is a look at care in the last years of life, and presents an approach to care for aging patients with potentially years to live - health maintenance, prevention, care coordination, etc. The 2nd 'Aging Patient' review is about falls, a problem very relevant for our field. Good reviews both: for those of us who didn't do geriatrics training, a nice refresher.

4)
And finally, a recent issue had an editorial about advance care planning, 'death panels,' and why ACP just is not finding widespread acceptance by the public. Good editorial, but what really made my night was its citation of a 1999 editorial about a SUPPORT study analysis which discusses in terms which are equally valid now as then as to why this is so difficult. I'm showing my age (youth) here by never having read this before, but it's worth reading, and probably should go into the must-read file for fellows. Most of the editorial unpacks the ideas in this paragraph:

For most patients, 2 fundamental facts ensure that the transition to death will remain difficult. First is the widespread and deeply held desire not to be dead. This is not only existential angst, or the dread of ultimate insignificance, it is also the struggle to avoid annihilation. Second is medicine's inability to predict the future, and to give patients a precise, reliable prognosis about when death will come. When death is the alternative, many patients who have only a small amount of hope will pay a high price to continue the struggle. Several other factors, such as certain societal values or family dynamics, also may make it difficult for a patient to make the transition to dying.

Tweet

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.

Tweet

1)
JAMA continues its Perspectives on Care at the Close of Life series with one on referring patients to high quality palliative care at the end of life. It focuses on the referral process, clinician interaction with palliative consultants, and discusses recent efforts to better define and measure quality of care delivered by palliative care and hospice programs. Like all the PCCL articles it is a relatively chatty discussion and literature review: what I appreciated about this one is that it is a realistic and understandable discussion about the similarities & differences between hospital-based palliative care and hospice programs and would make a useful & safe reference/teaching/marketing tool for those with colleagues who, umm..., still don't seem to get the differences ('we can't get palliative care involved - she still wants treatment').

Minor point/unveiling of my ignorance: the table mentions that mean length of stay in hospice in the US is 2 months with median of 21 days. I had it stuck in my head that the mean was in the 2-3 week range. There is no citation for that figure - please leave a comment if you know where the latest figures are.

2)
Stroke has a paper which gives some general prognostic data on intracerebral hemorrhage. The data come from a prospectively gathered, regional (Italy) stroke registry, and involves following 588 patients with ICH (mean age 74 years). Gross mortality was 35% at 7 days, 50% at 30 days, and 59% at 1 year. This paper offers confirmatory evidence that posterior fossa hemorrhages portend a significantly worse prognosis (hazard ratio for death at 30 days was 1.7; gross rate of mortality was not given). I had not seen hard numbers like this before, and the authors caution that these mortality rates are higher than what has been previously reported, perhaps due to the older age of this cohort.

3)
Clinical Therapeutics and Pharmacology has a paper discussing rational prescribing for patients with limited life-expectancy (free full-text available). It's a mostly theoretical discussion, arguing for a consistent approach which balances benefits, risks, goals, life-expectancy, and time to expected benefits. A good introduction to the topic - teaching file sort of stuff. The image is available is an actually readable size in the original paper.

(From Dr. Lyle Fettig's delicious link-pile.)

Tweet

1)
JAMA has another Perspectives on Care at the Close of Life piece about fatigue in the dying.  It's a nice review; comprehensive, accurate, based in a nice case, etc.  I sort of had this weird feeling while reading it though like I was missing something, or that its structure was disjointed--something was wrong.  That's when I realized the article kept on veering its discussion from fatigue to depression to pain to weight loss back to fatigue, etc.  I then realized that the article, itself, embodied the slug-like epistemological goo surrounding fatigue in the dying/the advanced cancer patient.  Is it a discreet disease (or syndrome) with risk factors, treatments, etc.?  Or is it just a symptom of other diseases/syndromes (cancer, depression, COPD, etc.) whose treatment is the same as the underlying condition's?  Or is it an inevitable, normal part of the human condition, as one's body begins the cascade of dysfunctions which will lead to death--a normal, expected part of dying?  The article sort of acknowledges this, but then just jumps around from one version of fatigue to another without warning and it makes for some off-kilter reading. 

There is a very welcome section at the end about 'managing expectations' about fatigue which has this quote from the doctor interviewed in the piece:

"I have a number of patients who suffer from fatigue who I think mostly just want...someone to listen to them tell them their story." 

This is absolutely the most important sentence in this article.  Insofar as our treatments for this thing called fatigue generally suck, and insofar as it is often a inexorable part of the transformation of a patient's life from healthy to sick to dying to dead (and is therefore unfixable), fatigue is frequently not something to be diagnosed and fixed.  Instead it is an aspect of suffering, a stigmata of that transformation, and our (clinicians') role is to...well...everyone has their own words they like to use here and I always struggle with the right ones...bear witness to it, offer a presence, listen, and acknowlege the mystery and pain of dying.

2)
There's also a coda for the recent Perspectives on palliative care for homeless patients.  The patient is still alive, still homeless/transient, and still receiving palliative care.

3)
And super-briefly--Archives of Internal Medicine has a prospective cohort study further validating the association with SSRI use and osteoporotic fractures in the elderly.  Although the study wasn't really designed to look at this fully, the authors postulate that the mechanism of this is not necessarily increased falls (as with tricyclic antidepressants) but via bone density & health.  The same issue has an article linking psychologic factors with cardiovascular disease:  apparently " cynical distrust" will raise your levels of inflammatory markers.  Does this mean all bloggers are destined to die young? 

Tweet

1)
The Journal of General Internal Medicine has a trial of changing a DNR order policy at a hospital in New York. For those of you not familiar with the NY situation--there is legislation there that most hospitals have interpreted to mean that a patient (or their proxy) has to sign a consent form in order for a physician to write a DNR order. These forms are notoriously long and complicated. (In contrast, at my hospital, while there is a special DNR physician order form, patients don't have to sign anything, and there is a policy in place allowing physicians to write a DNR order against a patient's wishes if resuscitation is felt not to be medically indicated.) In this article the hospital developed a new DNR order form and policy which greatly simplified the process, allowed for verbal 'consent**' only, and prompted physicians to consider multiple categories of treatment limitations as well as palliative priorities (pain, psychosocial & spiritual concerns, etc.). The authors compared what happened at their hospital with a similar 'control' institution which did not change their DNR policy. In short they found that the policy was well received and improved some markers of quality of care, as well as rates of DNR orders. Intriguingly, they looked at surrogate (patient family members, etc.) stress regarding DNR orders and found it decreased after the policy change. This is modest empiric evidence for a long-standing clinical observation--that particularly regarding what are viewed as 'life or death' decisions (such as DNR orders, terminal extubations, etc.) family members generally want physicians to make and be responsible for these decisions (so that the family member doesn't feel like s/he is responsible for someone's death--acknowledging of course that they almost certainly aren't responsible for the death, but they don't want to feel like they are being asked to 'choose'). That sentence was too long, I apologize.

**"Consenting" to a DNR order is somewhat of a weird concept. Consent, in medicine, usually refers to a patient understanding and agreeing to a medical intervention. In this case, however, it is about not using a medical intervention which is unlikely to benefit a patient in any material way. Surgeons 'consent' patients to operate; when surgeons choose not to operate because the risks outweigh the benefits of surgery they don't consent the patient to not operate--it's just considered good medical care.

2)
JAMA has a couple of articles this week. First is a ' coda' for the recent Clinician's Corner piece about spirituality & dying. Then there's a new Clinician's Corner/Perspectives on Care at the Close of Life piece about palliative care for frail elderly adults. It's discussion of hospice care for those with a functional decline but no 'clear' 'terminal' diagnosis is good, and good to see in a general journal.

3)
I stumbled across this press release touting antioxidants as analgesics (some researchers gave some mice a whole bunch of antioxidants and then injected formalin subcutaneously and found that the mice exhibited fewer pain behaviors). It's an interesting bit of research but will likely end up on the trash heap of novel human analgesics, although I hope not. The press release is peppered with a lot of "opioids=addictive=bad" language.

4)
On Monday I took the ABHPM's final board exam before it dissolves and is replaced by the new ABMS hospice & palliative medicine board. It's the end of palliative care's infancy (in the U.S.) which is exciting, but sad to see the ABHPM undergo its planned dissolution. It does mean--assuming I pass--that I can proudly tell my palliative medicine fellows ~30 years from now (some of whom may not be born yet) that I am so old that I was boarded by the ABHPM (I'll reassure them that was long before we discovered antioxidants were fantastic analgesics).