Can We Talk?

Roz Chast first published Can't We Talk About Something More Pleasant? in May of 2014. I thought it was one of the most honest, trenchant, and poignant descriptions of the last phase of life I'd seen. It's funny; it's sad; it's insightful. And it has much to teach caregivers. In honor of the imminent release of the paperback version, I had the opportunity to ask the author a few questions, which I'm posting here together with her responses. I'm including half the answers this week and the remainder will be posted next week.

MG: Your parents died in 2007 and 2009, but it looks as though you finished your book in 2014. Were you working on it all that time, creating the cartoons and the accompanying text, in which you capture your mother’s emotions, your father’s emotions, and your emotions, so beautifully—guilt, denial, affection, exasperation—or did you only start working on it years after their deaths? What made you decide to do this book, which is sometimes painfully honest and not the most flattering portrait of an aging couple?

RC: I wanted to remember my parents. I wanted to remember who they were—what they sounded like, the kinds of things they talked about. What they ate, what they argued about, how they looked… I have a kind of horror of forgetting things, and for me, writing and drawing about something is a way of remembering.

MG: In your book, there’s no mention of any doctor ever trying to engage your parents in a discussion of their wishes, not until years later when your father was 95 and hospitalized with a hip fracture and a DNR order was finally written. To the best of your knowledge, in the years between the beginning of the end (2001) and their respective ends (2007 and 2009), did any doctor ever try to bring this up? What do you make of this?

RC: As far as I know, no doctor brought this up. But I didn’t go with them to their doctor appointments until the very end, so I don’t know.

MG: One of my favorite cartoons in the book is the “Wheel of Doom.” The roulette ball could land on “death,” “deafness,” or “blindness then death,” to name a few. And then there are the “cautionary tales from [your] childhood,” truly implausible possibilities such as “killed by a baseball.”

RC: That is a completely true story. It was the son of my parents’ friends. His name, as I recall, was Ricky Laska. The  others were also stories I’d heard growing up: flower pot falling on guy, oboe, sitting on ground. ..Just thought I’d mention that.

MG: You present this as a way of showing that for your parents, all these outcomes are equally bad, a perspective that must have driven you crazy. But what it made me wonder was whether part of the problem with advance care planning as physicians conceive of it is that we tend to get too specific. We talk about “coma” and “persistent vegetative state” and “kidney failure,” which for normal people must sound much like your wheel of doom. Now your mother did say that she wouldn’t want to be a “pulsating piece of protoplasm.” Do you think your parents would have responded if their doctor had said, “So if you are ever a pulsating piece of protoplasm, we would not try to keep you going, but instead would try to keep you comfortable. But there’s a lot between the way you are now and a pulsating piece of protoplasm. If you couldn’t do anything for yourself—you couldn’t dress yourself, or get to the bathroom, or feed yourself—should we also focus mainly on comfort?”

RC: I think it’s so individual, when that border is crossed. And it’s possible that it changes. I.e., I remember when age 60 seemed impossibly old. Now, not so much. ;-)

MG: Speaking of states in between functioning—sort of—and being a pulsating piece of protoplasm, you do a terrific service by dwelling so much on what I call the in-between state, on frailty and decline, not just on death. For much of the time between your first visit to Brooklyn in 2001 and your mother’s death in 2009, she was frail. Your father spent over 5 years in this state of progressive dependence and disability. Do you have other thoughts about what would be useful to adult children when their parents are in that period of gradual decline?

RC: Get an elder lawyer to help your parents sort out stuff, to get a current will, to learn what “power of attorney” and “health care proxy” means, etc. And if you’re the person in charge, keep a notebook where you write down  all of the info you’ll have to keep track of: what drugs your parents are on, the dosages, their doctors, their doctors’ phone numbers, their pension plan information, the super and the super’s number, their neighbors and their numbers, bank info, your parents’ social security numbers… And if you’re in charge of hiring people to help take care of them, you’ll have to keep track of all of that too. Maybe to some people, this stuff is a big nothing. To me, it was very anxiety-producing.

The final part of this interview will be posted next week.

How is this Monoclonal Antibody Different from all Other Monoclonal Antibodies?

A new study published in Nature offers some potentially good news. The researchers report that a monoclonal antibody given intravenously to patients with mild cognitive impairment (referred to as “prodromal Alzheimer’s) or mild Alzheimer’s disease was generally well-tolerated and effective in reducing amyloid plaques in the brain. The drug also seemed to have beneficial clinical effects, although the study was not designed to address clinical outcomes. The results were impressive and the prospect of an effective treatment tantalizing. But the response to the paper was at best guardedly enthusiastic.  Why so tepid—given the hype that usually surrounds promising studies of this and other dread diseases?

The answer is that similar efforts in the past have repeatedly fizzled. The New England Journal of Medicine published back-to-back articles in January, 2014 of two drugs, both monoclonal antibodies, both tested in patients with mild to moderate Alzheimer’s disease. Both drugs flopped. Bapineuzumab failed to improve the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-Cog11) or the Disability Assessment for Dementia (DAD) when given to patients with mild to moderate Alzheimer’s Disease who were positive for the strongly predictive apolipoprotein E4. And it failed to improve the scores of patients without that apolipoprotein E variant. Solanezumab did nothing for patients with mild to moderate Alzheimer’s disease whether the outcome was the ADAS-Cog11, the ADAS-Cog14, or the Alzheimer’s Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL). A different approach to immunotherapy, use of a “vaccine” to stimulate the production of antibodies against amyloid (rather than passive administration of those antibodies, as with Bapineuzumab and Solanezumab) only led to the desired antibodies in 25 percent of patients and it had an intolerably high likelihood of causing meningoencephalitis, a potentially lethal inflammation of the brain.

In light of these earlier disappointments, CNN asks if the new drug, Aducanumab is a game-changer (rather than simply asserting that it is). Fox News says it “shows promise.” The editorial accompanying the scientific report in Nature says that if the early findings are confirmed in larger studies, it “might help to accelerate the evaluation and regulatory approval of promising Alzheimer’s prevention therapies.”

Just what did the researchers, who were from Biogen (Cambridge, MA), Neurimmune (Zurich, Switzerland), Butler Hospital (Providence, RI), and the Institute for Regenerative Medicine (Zurich, Switzerland) do? They took as their starting point what scientists have known for over 100 years: in Alzheimer’s disease, there is an abnormal accumulation of amyloid plaques in the brain; next they acknowledged what scientists have known for 25 years: the abnormal amyloid peptide, Aβ a 42-amino acid fragment cleaved from amyloid precursor protein, is toxic to neurons (unlike, say, the 40-amino acid fragment more commonly formed from amyloid precursor protein). They then generated a human monoclonal antibody that selectively reacts with particular aggregates of Aβ. Previously, they demonstrated that this antibody, which they named Aducanumab, could cross the blood-brain barrier and clear amyloid plaque from transgenic mice. In the current work, they tested 165 patients with the very earliest stages of Alzheimer’s disease and evidence of amyloid plaques on PET scans. These patients received monthly infusions for one year, of either one of 4 different dosage levels of the drug or placebo.

Only 125 patients completed the trial, with 40 dropping out either because of adverse events they attributed to the study (20 patients), or because they no longer gave consent. Of note, “adverse events” were just as likely in the patients receiving placebo as in the patients receiving any of the three lower doses of the drug. Patients receiving the highest dose of the drug, however, were more likely to report an adverse event.

In terms of the primary outcomes of this small trial, the researchers found that active treatment reduced brain Aβ plaques as measured by PET scan in all the groups. The effects were similar in both the prodromal and mild Alzheimer’s patients.

As to the secondary outcomes—the clinical measures that the study was not designed to examine—the researchers found a dose-dependent slowing of the progress of disease on a variety of measures, including performance on the Mini Mental Status Exam, but no effect on a composite neuropsychological battery.

Finally, with respect to actual adverse events, the researchers did detect a dose-dependent risk of “amyloid-related vasogenic abnormalities,” in particular of edema surrounding blood vessels. This effect usually subsided within 4-6 months and it wasn’t associated with any symptoms, but it did occur in as many as 41 percent of those receiving the highest dose of the drug.

Why did the new drug seem to perform better, at least to the extent that even tentative conclusions can be drawn from this very small pilot study, than its predecessors? The scientists clearly learned something from the earlier failures. They opted not to use a vaccine: the vaccine had caused both meningo-encephalitis and accelerated brain atrophy. Instead, they used a monoclonal antibody. But they created an entirely human antibody, rather than the “humanized” mouse monoclonal antibodies that formed Bapineuzumab and Solaneuzumab. And finally, they made an antibody that targeted a different part of the abnormal Aβ peptide, hoping that this would be less toxic than earlier antibodies.

So will it work? An op ed in Scientific American gave the best response: “A new drug trial that some researchers are calling the most promising yet in the fight against Alzheimer’s suggests it may be possible to clear the brain of the amyloid protein that is characteristic of the disease. The study was small and researchers caution that it is far too soon to declare victory against a fatal disease that robs people of their memories and ability to function in daily life. But despite repeated failures of Alzheimer’s drugs in the past, there was room for enthusiasm about the trial…” (Italics added.) Like everyone else, I am cautiously optimistic. Given my usual level of skepticism, that’s actually pretty positive.

The Real Advance Planning

Michael Kinsley’s Old Age: A Beginner’s Guide isn’t exactly a guidebook to “life’s last chapter,” as the author promises. The book does talk quite a bit about Parkinson’s disease, even though Kinsley assures us that it isn’t really about Parkinson’s disease, because that’s been Kinsley’s diagnosis for the last 23 years. And his comments about going through “deep brain stimulation,” a surgical technique that can be very helpful to people with Parkinson’s, as well as his discussion of accepting limitations—giving up driving, realizing you’re not going to be promoted—are illuminating. His suggestion that the baby boomers redeem themselves for posterity by erasing the national debt is whacky. But he does deal with something tremendously important, and that is coming up with an immortality project.

I first learned about immortality projects when I read Ernest Becker’s The Denial of Death, which was published in 1973. It had such a profound effect on me that I called my book about aging The Denial of Aging in homage to his. Becker’s point, at least as I remember it, was that it is the awareness of our mortality, more than anything else, that distinguishes us from other mammals. 

Now I don’t know if it’s really true that apes are totally oblivious to the prospect of death. But regardless of whether we are unique in this respect, I do think it’s fair to say that our recognition of our finitude profoundly shapes our existence. Some moral philosophers have even suggested that the prospect of further life extension is bad for us as it would induce a kind of ethical laziness—we would keep on putting off doing good because we figured we’d have plenty of time later. That may be a bit of an exaggeration, but I think there’s truth to the claim that mortality is a great motivator. I don’t think it’s necessary to invoke heaven and hell, some kind of post-mortem day of judgment, to induce people to lead a good life. It’s sufficient to realize that our time on earth is limited: if we want to make something of our lives, we better go ahead and do so. And built into the fabric of our being is a desire to live on after our death, to be remembered, and in that way, to triumph over our mortality. Which is where immortality projects come in.

What Kinsley’s book is about is finding an immortality project. He recommends that the baby boomers undertake a joint project with all the other baby boomers (eradicating the debt), which is more daunting and, in my view, less likely to succeed than embarking on an individual project. But Kinsley’s point is that being diagnosed with a chronic, progressive (and I would add, ultimately fatal) disease brought home to him the recognition that he had better get started. It made him think about what was really important to him—was it material possessions? Was it fame? Or was it something more durable?

Kinsley is telling us is that we need to get cracking. We better define our immortality project, our legacy, and start working on it. For Kinsley, it was the diagnosis of a serious disease that helped him figure out that he ought to have such a project. But for most people, that’s a little late. The real message of his book is not to wait. Don’t wait until you already know what disease is going to kill you. Don’t wait until you have dementia or widely metastatic cancer or advanced heart disease. We’re human: we are mortal and we know it. We should all be working on our legacy for much of our lives, where “legacy” may simply mean being the best person we possibly can be.

In the PACE Space

One of the most disturbing articles I read this past week--from a geriatric perspective-- was a piece in the NY Times about a new development within PACE, the Program of All Inclusive Care for the Elderly. Private equity firms are setting up PACE (Program of All Inclusive Care for the Elderly) programs.

I am a great fan of PACE programs. They do all the right things for the frailest, most vulnerable older people, individuals who are enrolled both in Medicare and Medicaid and who are disabled enough to qualify for nursing home care: PACE keeps them out of nursing homes, prevents hospitalizations, and focuses on quality of life. It does this by engaging patients and families in advance care planning, by talking with them about what really matters to them, and by providing services ranging from podiatry to physical therapy to physician care at home or in the adult day health centers where many of them spend their days. The program receives a substantial sum from Medicare and Medicaid in exchange for their providing all the patient’s medical services. And until recently, PACE programs have always been not-for-profit. But apparently the government changed the rules a year ago and a number of for-profit companies have entered the “PACE space,” hoping to make a substantial profit.

Now I realize that PACE in its traditional form has had a problem—it hasn’t caught on. As of January, 2016, there were reportedly a mere 40,000 people enrolled in one of 100 PACE programs found in 32 states. But are private equity firms the way to go?

As part of the book that I’m writing on the journey through the health care ecoculture, I looked into the role of private equity firms in both the hospital and the nursing home sectors. What private equity companies do is to buy distressed facilities and turn them around so they can sell them for a profit. The jury is still out on what happens to patients in the process—but the data so far are concerning. According to a NY Times investigation of all nursing homes bought up by private equity firms between 2000 and 2006, the result was a dramatic decrease in the number of nurses caring for patients and a concomitant drop in the quality of care. Another report, this one by the Sacramento Bee about nursing home chains in California, found that after one company, Brius LLC, bought up skilled nursing facilities in the state, a slew of complaints ensued. Moreover, the company embarked on a complicated strategy of instituting a convoluted management structure to hide assets as a shield against civil and criminal liability. Nonetheless, the 81 nursing homes in the chain have attracted the attention of the California Attorney General, the California Department of Health Care Services, and even the FBI because of alleged negligence and abuse. To be sure, there is another perspective: of the 81 nursing homes in question, 59 were insolvent and on the verge of closing or else faced decertification due to poor care at the time they were acquired. The chain claims it improved care by investing in these troubled facilities. But it seems unlikely that borderline institutions would provide better care after Brius instituted a worse nurse to patient ratio, as happened across the board.

So when NY Times reporter Sarah Varney published a long piece on the foray by private equity into PACE, I worried. She describes how InnovAge, a Denver-based company, gained a $196 million investment from the firm Walsh, Carson, Anderson and Stowe, a multibillion dollar private equity company, to provide PACE services. The InnovAge model is to do what PACE programs usually do—but more cheaply, by substituting video calls for on site doctoring and other as yet undetermined strategies. The revenue for the new PACE enrollees will come from Medicare and Medicaid, as it always has. Maybe for profit PACE won't cut corners. Maybe rounded corners are desirable. But CMS needs to be extremely vigilant and have a low threshold for pulling the plug.

A Success Story

In a research letter published this week in JAMA, geriatrician Susan Mitchell presents some startling—and encouraging—data. She reports that between 2000 and 2014, the rate of feeding tube insertion in US nursing home residents with advanced dementia fell from 11.7 percent to 5.7 percent.

It’s an achievement to be proud of—and even though the rate of feeding tube use remains high in blacks, the extent of the drop over the last 15 years is if anything more dramatic in the black population: for whites in nursing homes who developed advanced dementia and feeding difficulty, the rate went from 8.6 percent to 3.1 percent; for blacks in went from 37.5 percent to 17.5 percent. How and why did this dramatic change occur? 

Much of the credit goes to the work of Dr. Mitchell herself, who has tirelessly studied the use of feeding tubes in this population since the ate 1990s. Her initial foray into this field was a study with the somewhat inauspicious title, "The Risk Factors and Impact on Survival of Feeding Tube Placement in Nursing Home Residents with severe Cognitive Impairment." Published in what back in 1997 was called the Archives of Internal Medicine, it provided the first compelling evidence that, contrary to common sense expectations, performing a surgical procedure to provide ongoing artificial nutrition to nursing home residents who, in the course of developing advanced cognitive impairment, had stopped eating, did not prolong life. It wasn't a randomized controlled trial and it was confined to nursing home residents in the state of Washington, but it was a carefully conducted analysis of a reliable data base.

When the findings were confirmed in subsequent studies, Dr. Mitchell went on to examine the nursing home factors associated with tube feeding (on-site speech therapy, low aide to patient ratios, and evidence of poor quality care) and the clinical and organizational factors associated with tube feeding (for profit status, large size, and urban location). She looked at the financial incentives for feeding tube use (Medicare pays more) and the cultural factors associated with feeding tubes (facilities with a home like environment, a focus on food, specially trained aides, and an emphasis on advance care planning were much less likely to use them).  And she established that the development of difficulty chewing and swallowing is par for the course as dementia becomes very advanced. Many other investigators contributed to the subject as well: a search on Google Scholar using the phrases “artificial nutrition” and “advanced dementia” today produced 1340 hits.

But evidence does not always change practice, especially in an area as emotionally charged as the use of food and drink. During the same period that tube feeding use was falling in advanced dementia, we witnessed the spectacle of Terri Schiavo, a young woman in a persistent vegetative state, whose feeding tube was repeatedly inserted and withdrawn for seven years as her husband (her official surrogate) and her parents battled in the courts. What else accounts for the change in behavior and what can we learn from this experience about how to influence health care policy?

I suspect three factors played a role in moving the medical profession, hospitals, and the public towards a growing acceptance of palliative care--and away from technological interventions such as feeding tubes-- for individuals with advanced dementia.

First, physicians who cared for individuals with dementia were increasingly disturbed by the suffering that they saw inflicted on their patients from the growing acceptance of technological interventions. It wasn’t just feeding tubes; it was dialysis and ventilators and ICU care. Just as CPR had spread from use in otherwise healthy individuals who suffered an acute myocardial infarction, complicated by a ventricular arrhythmia, to all dying patients, so too did other invasive technologies proliferate due to “indications creep.” But it was bad enough to do something unpleasant to a dying patient who understood the intention behind the procedure or test; it was worse to do something painful or frightening to a dying patient who was by definition unable to understand its purpose (or intended purpose). As patient involvement in decision-making became more common and competent patients had the option of choosing or rejecting Hail Mary treatment, the plight of the demented patient became more poignant. Several of us wrote articles arguing that from an ethical perspective, there was no requirement to provide patients in the final phase of life with artificial nutrition and hydration. In fact, it was arguably this growing malaise on the part of physicians with the widespread use of burdensome technology in patients with advanced dementia that led to the burgeoning research on its effects.

Second, the field of palliative care has taken off during the last fifteen years. While much of palliative care focuses on cancer patients and on patients who are imminently dying, the discipline is in principle concerned will all serious, life-threatening illness. The growing acceptability of palliative care—as evidenced, for example, by Medicare choosing to pay doctors and nurses for advance care planning meetings—has brought a recognition that what we customarily do to and for patients near the end of life is not always what they want or what is most beneficial to them. Responding to eating difficulties in a patient with advanced dementia by inserting a tube rather than by limited hand feeding is just another example of the tendencies that palliative care challenges.

Finally, forgoing a technological solution to a medical problem is attractive because it saves money. A gastrostomy tube in the setting of advanced dementia is an example of an intervention that manages to simultaneously be useless, burdensome, and costly. We need to find more examples of widely used treatments that meet all three criteria, such as renal dialysis in frail older people. Feeding tubes for people who are dying of dementia is just the beginning. 

Are there Truly No Atheists in Foxholes?

A nagging concern about advance care planning is the possibility that patients may change their minds when faced with imminent death. That’s not a problem if the person is still able to make decisions and really can change his mind. But for the majority of older people whose thinking is impaired at precisely the time that a potentially life or death decision about their medical care must be made, it is very much a problem. By etching their wishes in stone, is an advance directive too inflexible? Does it make it hard for surrogate decision-makers to change their minds on the patient's behalf?

We know that patients do change their minds over time as they adjust to their new (and presumably more  limited) level of functioning. The most extreme case that’s been described comes from younger patients:  individuals with quadriplegia after an accident are initially despondent; after they adapt to their situation, they still aren’t happy with their status, they would still much rather not have quadriplegia, but many if not most of them come to recognize that they are still human beings with emotions, feelings, and abilities. Whatever suicidal tendencies they had at the onset of their disability have typically abated. 

Older people also change their minds over time about what they are willing to live with, but a substantial proportion shift from wanting their medical care to focus on prolonging life at any cost to wanting their medical care to focus on maintaining their level of functioning. And older patients who were recently hospitalized for a serious illness such as heart failure or a flare of COPD, when asked about what matters most to them, reportedly say they would not want life-prolonging treatment if it left them with severe cognitive impairment. But what about the very moment that they are in the hospital, acutely ill, and confronting their own mortality? Do they also say they would rather die than be left with dementia or profound disability? A research letter in JAMA Internal Medicine finds that many of them do.

It’s a small study (only 180 patients) conducted at a single academic medical center (in Philadelphia). They were all, by definition, able to engage in a discussion (actually a structured interview) about their preferences. They were all seriously ill, suffering from advanced cancer, severe heart failure or advanced lung disease. They were asked about 10 different possible forms of functional debility: bowel and bladder incontinence, relying on a breathing machine, unable to get out of bed, constant confusion, dependence on a feeding tube, needing constant care, living in a nursing home, being homebound, in constant, moderate pain, or confined to a wheelchair. While they differed in their ratings of various health states compared to death, large numbers rated each of the possible conditions as worse than death, and the first six were viewed as the same or worse than death by over half of all patients.

Now these patients were not actually confused and many of them weren’t incontinent, on a breathing machine, unable to get out of bed, etc., even temporarily. If they were, they might, like the young person with quadriplegia, adapt. But they were in the hospital with a serious enough illness that they could die. Presumably they knew that (though this is not clear from the article). And what is striking is that none of them had any limitations on life-sustaining treatment documented in their medical record. It’s unlikely anybody had spoken to them about which of the treatments they were getting or they might get could in fact leave them with exactly the condition they indicated in the interview they wanted most to avoid.

The possibility that there really are no atheists in foxholes has to be taken seriously. Maybe most people will change their minds about what treatments are tolerable to them if they are sufficiently close to death. The best we can do is to ask people about preferences who do understand something both about the state they may find themselves in and the nature of the treatment being proposed. That means we should do the asking when people already are old, sick, and debilitated, not when they are young and healthy.