October 15, 2018

A Bone to Pick?

Increasingly, research studies published in major medical journals conclude the same way: with a plea for more studies. The writers say they have found evidence leading them to believe that drug X “may be helpful” or drug Y "did not produce a measurable difference in outcomes" and urge additional testing to confirm (or presumably refute) their results. So, it was interesting to note that a recent study of vitamin D and bone health concludes not only that the authors found no evidence that vitamin D is beneficial in preventing or treating falls, fractures, or osteoporosis, but that also that no further study is warranted. The writers confidently assert that this latest study, a meta-analysis that examines all the well-done studies to date, including 45 recent studies that were not included in previous meta-analyses, should be the last word on the subject. Unless you have rickets or osteomalacia, two relatively rare conditions, the authors conclude that you should not bother to take vitamin D supplements.
In the past, the response to negative studies of vitamin D has been a chorus of “but, but, but.” But what about the effect of the dose of vitamin D—maybe 400 International Units is not enough to do anything but 800 is. The current examination looked at this question and failed to detect any difference in outcomes between people taking high dose or lower dose vitamin D. But what about the importance of age—can vitamin D make a difference in the oldest old, people at the highest risk of fracture? The current examination didn’t find any evidence it does. But what about the thickness of the bones at the time that vitamin D is initiated—maybe it’s too late to matter if there has already been a great deal of bone loss, but can be helpful at an earlier stage. The authors of the new report don’t think so.
Two years ago, I addressed the issue of vitamin D in my blog post, “Make No Bones About It.” I concluded that the evidence supporting vitamin D supplements was weak, but because falls and fractures are so devastating for older people and the cost of vitamin D is so low, with almost non-existent side effects, it wouldn’t hurt to take it—and maybe, just maybe, it might help. What do I advocate today? What will I personally do? Well, I still have a large bottle of vitamin D (1000 IU capsules) in my medicine cabinet. I’ll finish the bottle. Then what? Unless someone comes up with a compelling reason to continue, I’ll probably stop. But I will make sure to drink lots of milk, eat cheese, and get plenty of sunshine to ensure that my non-medicinal intake of vitamin D is sufficient.

September 30, 2018

The Nurse Will See You Now

           

          Articles in medical journals tend to pay scant attention to the role of nurses in treating illness—or for that matter, to the role of social workers, physical therapists, and many other clinicians. Hence, when JAMA, one of the major American general medical journals, published an article in 2002 entitled, “Hospital Nurse Staffing and Patient Mortality, Nurse Burnout, and Job Dissatisfaction,” it was a bombshell. The lead author, Linda Aiken, is a nurse researcher at the University of Pennsylvania where she is a Professor of Sociology and the founding director of the Center for Health Outcomes and Policy Research. Looking at survey data from 10,000 nurses and administrative data on nearly 250,000 medical and surgical patients hospitalized in Pennsylvania in 1998-1999, she drew some dramatic conclusions: each additional patient per nurse was associated with a 7 percent increase in the likelihood of dying within 30 days of hospitalization, and each additional patient per nurse was associated with a 23 percent increase in the odds of “burnout” and a 15 percent increase in nursing job dissatisfaction. 

          Aiken's analysis, along with other smaller studies, have led to calls for an increase in the nurse to patient staffing ratios in hospitals. In light of general hospital administrative reluctance to make such increases, many nurses have demanded and some state legislatures have proposed mandatory increases in nurse to patient ratios. Massachusetts voters are being asked to vote this November on a referendum that would establish mandatory staffing ratios. To date, the only state to have instituted such a requirement is California—which passed legislation in 1999, before Aiken’s landmark study. California’s experience offers an unparalleled opportunity to ask whether mandatory ratios result in the desired improvements in quality of care and whether they produce a variety of unintended consequences. In principle, it could also shed light on whether nurse to patient ratios are particularly important for older people.

            California’s law specifies different nurse to patient ratios for intensive care units, surgical units, and medical units. Compliance was at first uneven, but gradually hospitals conformed to the requirements. Several studies have attempted to assess the outcomes. They are limited because California did not conduct a randomized, controlled experiment before passing its legislation—it did not impose mandatory minimum ratios on some hospitals and not on others. Moreover, nursing staff ratios are hardly the only factor affecting outcomes that changed in the early years of the mandate: many other federal quality improvement initiatives were undertaken to encourage hospitals to prevent pressure ulcers, falls, catheter-related infections and other major hazards of hospitalization. Hospitals have also experienced major financial pressures: the cost of hiring nurses was only one of many economic challenges. Determining cause and effect is not easy. Nearly twenty years later, what do we know?

            First and foremost, did the mandatory ratios result in improved quality of care? One of the most carefully performed studies was undertaken by the California Health Care Foundation, part of UCSF, in 2009. This report looked at pressure ulcers, pneumonia deaths, and deaths from sepsis (blood-borne infection) and were unable to find any statistically significant change after the law was implemented in 2004 (following a multi-year study period to design the regulations). Another study that focused exclusively on pressure ulcers and falls used data from CalNOC, a large nursing database for the entire state, to conclude there was no change in fall rates. They did note a paradoxical increase in pressure ulcers in patients admitted to “step-down” units, units between an ICU and a general medical or surgical floor in the acuity of their patients, after the requirement of more nurses per patient was introduced (presumably a reflection of sicker patients). A systematic review of the literature, published in the Annals of Internal Medicine in 2013, failed to find any statistically significant effect on a variety of safety measures. Of note, none of the studies I identified looked at either patient or nursing satisfaction.

            If mandatory nurse to patient ratios did result in more face-time with patients but no demonstrable improvement in overall quality of care, might older patients nonetheless be one subgroup that did benefit?  All we can say is that many of the quality measures that were examined—pressure ulcers and falls, for example—are particularly relevant to older people. 
            What about the feared adverse consequences of imposing rigid nursing staff ratios? An analysis in Health Affairs in 2011 found no evidence that hospitals were substituting less well-qualified staff (who still meet the legal requirements) such as LPNs for registered nurses. The California Health Care Foundation did conclude that hospitals were increasingly relying on “travel nurses,” (nurses from out of state or from other countries, hired for short periods of time) and on “float nurses” to move from floor to floor to compensate for lunch breaks by the regular staff. Such changes may result in less continuity of nursing care for patients. They also showed that hospitals across the state experienced shrinking operating margins beginning in 2002, especially in the hospitals that were initially fiscally strongest. However, they emphasize that many other factors could account for this phenomenon. Hospitals of all types did comply with the law, resulting in more hours of nursing care for each patient every day:
          On balance, regulating nurse to patient staff ratios in isolation is not likely to make much of a difference in patient outcomes, nor is it likely to devastate hospitals' finances. Hospitals are complex institutions with many interrelated parts. Just because hospitals with low nurse to patient staffing ratios tend to have poorer outcomes than other hospitals does not mean that if we "fix" the ratio, care will necessarily improve. Assuring that there are enough nurses to provide good care is essential, but that step alone is unlikely to dramatically improve the hospital experience.
             



            
  





September 24, 2018

Of Mice and Men

For middle-aged mice, these are the best of times. Scientists now understand genetic factors that lead to the development of disease, disability, and death—in mice. Most importantly, researchers have found ways to improve the “healthspan,” the period of disease- and disability-free life before death—in mice. The question is whether the approaches they are developing will be applicable to people, and the ethical implications if they are.
The basic ideas are spelled out in a trio of “viewpoint” articles published in JAMA last week. S. Jay Olshansky, writing from an epidemiologic perspective, observes that over the past century, dramatic gains in life expectancy have been accomplished by reducing in mortality of children and young adults. But once these gains have been made, the only remaining way to lengthen life expectancy is by extending the lives of people at the other end of the age spectrum. Medical science has therefore concentrated on tackling the diseases of old age, one by one. Unfortunately, as Barzilai et al comment in their essay, “efforts focused on preventing individual diseases will have limited net effect on population health because one disease will be exchanged for another.” We’re already seeing this phenomenon: as fewer people die of heart disease, they develop and die of Alzheimer’s instead. Far better would be to tackle the aging process itself. Targeting the underlying driver of all the chronic diseases at once could, in principle, prevent or at least delay those disorders.
So, what do we know about turning off biological aging? We know there’s a gene in mice with the euphonious name rps6kb1 and if it’s “knocked out” (molecular genetics speak for “inactivated”), female mice live longer, healthier lives. We know there’s another gene called Sirt6 (short for Sirtuin 6), which is present in multiple mammalian species including humans, and if it is “overexpressed” (genetics speak for “turned on”) in male mice, they live longer. We also know that all creatures including people have “senescent cells,” cells that, old cells that start releasing all kinds of chemicals. When an individual has more than some threshold number of such cells, it develops chronic diseases, frailty, and is at high risk of dying. When the senescent cells of a mouse are destroyed, the mouse lives longer and without a long period of deterioration before death.
And what progress has been made in identifying drugs that achieve these goals in mice? And what about in people? Reportedly, the Interventions Testing Program, funded by the National Institute on Aging, has examined 26 “candidate drugs” for their effects on mice. They have identified 6, including the anti-inflammatory drug, aspirin, the anti-diabetes drug, acarbose, the immunosuppressive drug, rapamycin, and the estrogen, 17a-estradiol, as effective in some mice. Intervening in mice of an age equivalent to 70 human years has “extended life by more than 20 years and increase[d] health span even more substantially.” Other studies have found that the drug dasatinib (related to the anti-cancer drug, Tarceva) has a powerful effect in destroying senescent cells. In mice that are the equivalent of 80 human years, treatment with dasatinib combined with quercetin (a plant chemical found in green tea, red wine, apples, and other foods) increases survival 36 percent without increasing disability before death.
We don’t know whether any of these chemicals work in humans. And we have no idea at all whether they will produce side effects, though we do know that earlier attempts to interfere with cell lifespan were associated with the development of cancer. This is not entirely surprising, as the essence of cancer is uncontrolled cell proliferation. So even the very upbeat article by Tchkonia and Kirkland, the third of the triad, ends on a cautionary note: “…Patients should be advised not to self-medicate with senolytic agents or other drugs that target fundamental aging processes in the expectation that conditions alleviated in mice will be alleviated in people.”
If, years from now, human studies indicate the drugs or others like them are effective, we will have to deal with the ethical implications of extending the “healthspan.” What will they cost? Will everyone have access to such medications? Will we create greater inequality within society? Between countries? Banning such research on the grounds that a ballooning of the elderly population is unsustainable is almost certainly going to be impossible—the lure of more disease-free life will be irresistible. But we can begin to think about the consequences of our brave new world.

September 17, 2018

An Aspirin a Day...

The headlines this week—aside from the hurricane, the typhoon, and the charge of sexual misconduct in the Supreme Court nominee—are all about aspirin. For older people, unless you live in the Carolinas or Hong Kong, this is definitely the story. A new study (reported as 3 separate studies but really just one study with three different endpoints) threatens to unseat aspirin from its coveted spot as the little-pill-that-could.
A single aspirin a day, many people believed, could stave off heart disease, stroke, cancer, and perhaps dementia. If taken as a “baby aspirin,” a dose of 81 mg a day instead of the 325 mg in a regular aspirin tablet, and with a special “enteric” coating to protect the lining of the stomach, it was touted as effective with virtually no side effects. The truth, unfortunately, seems to be that it is neither effective nor devoid of side effects when taken by healthy older people.
The study, published online in the New England Journal of Medicine, examines three plausible possible benefits of low dose, enteric-coated aspirin. First, they ask whether aspirin has a desirable effect on cardiovascular events such as heart failure requiring hospitalization, stroke, or heart attack. They found no difference in benefit between healthy older people in the US or Australia (where older was defined as over 70 except in blacks and Hispanics, where it was defined as over 65) who took 100 mg of aspirin and those who did not.
Next, they looked at whether aspirin has an effect on how long healthy older people live without developing a disability. Again, they found no statistically significant difference between those who took aspirin and those who didn’t.
Finally, they examined overall mortality in the aspirin-takers and the non-aspirin takers. Once again, the two groups were indistinguishable.
There was, however, one striking difference in outcomes between the 9525 people who were randomized to take aspirin and the 9589 people who were randomized to placebo: the risk of bleeding was significantly higher. And by bleeding, the investigators meant major bleeding such as a gastrointestinal bleed or an intracranial hemorrhage. 
Not only did this randomized controlled study fail to show any benefit from taking aspirin, and not only did it show an increased risk of harm, but even when the results were subjected to subgroup analysis, no group emerged as potential beneficiaries. The authors looked at the composite endpoint (dementia, death, or persistent disability) in several pre-specified subgroups. One was gender: in the past, aspirin has been touted as preventive for healthy men but not women; in this study, neither men nor women benefited. Another was frailty (though I’m not quite sure how 421 of the “healthy” elderly subjects could have met the definition of frailty): in this study, neither the frail nor the non-frail benefited. If anything, there was a trend towards worse outcomes in the frail group, though the numbers were so small that the difference was not statistically significant and might well be due to chance.
No study is perfect and this one is no exception. The median period of observation was 4.7 years, a relatively short period with respect to the time needed to develop dementia or heart disease. The analysis was done on an “intention to treat” basis, which is the way such studies are supposed to be analyzed, but in fact only 2/3 of the people assigned to take aspirin were actually taking it by the end of the study period. The benefit of aspirin might therefore have been under-estimated. The risk of bleeding, however, which was already substantial in the aspirin users, may have also been under-estimated. For some reason, the study used a 100 mg dose even though a standard baby aspirin contains only 81 mg: maybe the results would have been different with an even smaller dose. But the strengths of the study are impressive. It was randomized; follow up was almost complete; data collection seems to have been thorough and careful.
I have a confession to make: for several years, I took a baby aspirin every day. I’m under 70 and I’m female, so my physician did not recommend that I take aspirin. I took it nonetheless because I really don’t want to have a stroke and thought that just maybe taking aspirin was something I could do to help. I took it because years ago, before I went to medical school, I worked in a hematology research lab and spent my days studying platelet aggregation. It turned out that people who had taken a single aspirin tablet within two weeks of my testing their blood showed markedly decreased clumping of platelets, blood cells that are critically involved in the clotting process. About a year ago, I had several episodes of subconjunctival hemorrhage, a benign form of bleeding involving the blood vessels of the eye. I worried the bleeding might be related to aspirin, so I stopped taking it. 
Today, the evidence is compelling that for people without heart disease or dementia or stroke, an aspirin is more likely to cause harm than good. As of now, aspirin has joined the ranks of other failed panaceas such as estrogen and calcium supplements. 

September 09, 2018

Looking Ahead

British researchers recently projected care needs of the very old.  We would do well to pay attention to their analysis—or, if we think Americans are substantially different from their British counterparts, then we should replicate the analysis with our own data. Their study concludes that the number of very old people (over age 85) who will be highly dependent will double by 2035. This despite a marked decline in the anticipated rate of dementia and the growth of the population who remain fully independent. The seeming paradox arises from an increase in the number of comorbidities that the very old will have and the interaction between multimorbidity and dementia. In short, if you do survive to extreme old age and if you are one of the still substantial number of people who develops dementia, you probably will also have several chronic diseases. The combination spells dependence, where the study authors define high dependency as requiring 24-hour care, medium dependency as needing help at regular times daily, low dependency as needing help less than daily, and independence as free from care needs.

A few charts make the points best.

If we look at the proportion of all 85+ year-old men who were highly dependent in 2015, we can see that it was low then and it will have fallen further by 2035. Very old women are somewhat worse off than men today and the discrepancy will increase by 2035. Since the total number of octogenarians will rise considerably over the next 20 years, the total number of dependent, very old men and women will be larger than it is today--in the UK, the numbers will double.


 If, instead, we look at the number of additional years that people who turn 65 can expect to live, we have a more nuanced view. Men who turned 65 in 2015 can anticipate another 18.7 years of life, of which 11.1 years will be spent entirely independent and 1.4 years will be in a state of high dependency. A man who turns 65 in 2035, projections suggest, can expect another 22.2 years of life, during which he will spend 15.2 years independent and only 1.1 years dependent.

Women who turned 65 in 2015 can expect to live another 21 years, during which they will be independent for 10.7 years and very dependent for 2 years. The next generation, which turns 65 in 2035, will have a life expectancy of 24.1 years and will independent for 11.6 of them. Unfortunately, the length of severe dependency will increase to 2.7 years.



The implication of all is that we will need a huge increase in the number of caregivers to accommodate the needs of the very old. Unless we are far more successful in rolling back the rate of chronic disease than we have been to date (cardiovascular disease, diabetes, and stroke are the leading offenders) and can also dramatically cut the risk of dementia, we need to start planning now. We should encourage more people to become nursing aides. This will involve raising the pay and enhancing the status of the job. We will also want to seriously consider increasing immigration to fill the needs of the oldest old. And we should not assume we are better off than our British counterparts: on the contrary, older Americans today experience more sickness and disability than our European counterparts and our health care system devotes less attention to social than medical problems.


August 20, 2018

Hospital at Home?

For years, I’ve been arguing that frail older patients are often better off being treated for acute medical problems at home than in the hospital. I began making this claim during my residency when I wrote about The Ethics of Cardiopulmonary Resuscitation,” claiming that it created cognitive dissonance for physicians in hospitals to go all out for some patients and to withhold selected treatments for others. Better, I suggested, to keep those individuals who didn’t want everything under the sun, and particularly those who didn’t want attempted cardiopulmonary resuscitation, out of the hospital altogether. 

I picked up the theme during my geriatrics fellowship in a paper entitled “Adverse Consequences of Hospitalization in the Elderly," which quantified the frequency with which older patients developed iatrogenic complications, unrelated to the medical problem for which they had been admitted and found it was 40.5 percent in those aged 70 or older, compared to 8.8 percent in those under 70. And instead of suggesting that we build higher siderails—or institute the kinds of interventions that eventually were adopted by Acute Care for the Elderly (ACE) units—we try to avoid hospitalization altogether. 

Over time, increasing evidence has accumulated that many people can be cared for at home and that this approach not only decreases the chance of adverse events (including unwanted treatment), but also results in comparable outcomes. A new study in JAMA Internal Medicine  suggests a way to pay for “hospital at home” model--by paying a single fee for acute care plus 30 days of post-acute care.
The Hospital at Home model (which, unlike the study authors, I won’t abbreviate as HaH since that makes it seem like a joke) used in this study offers hospital-style care for any of 19 common medical conditions (including pneumonia, urinary tract infection, flare of heart failure, and cellulitis) in clinically stable, interested adults who have adequate home supports. Their outcomes were compared to those of contemporaneously hospitalized adults who were eligible but either declined to participate in the study or couldn’t participate because services could not be set up for them at the particular time (night time) or day (weekends) when they showed up in the emergency department.
The results were overwhelmingly positive. Patients cared for at home, when compared to controls, were much less likely to be (re)hospitalized for any reason in the month after discharge (8.6 percent vs 15.6 percent); they were less likely to go to a skilled nursing facility after treatment of the acute episode (1.7 percent vs 10.4 percent); and they were far more likely to rate the quality of their care as excellent (68 percent vs 45 percent). While 12.2 percent of the Hospital at Home patients did end up in the hospital for treatment of the acute illness, there were no differences in mortality. There were also no differences in complications such as falls or infections, but the number of either of these adverse events was too small to draw any definitive conclusions.
On the other hand, as the authors of the accompanying commentary indicate, the study was a case control study, not a randomized trial, and the “controls” were significantly different from the cases: they were younger (a lot younger—an average of 71.5 compared to 76.0), less well educated, and better functioning (55.5 percent had at least one area of difficulty in daily activities, compared to 71.5 percent in the Hospital at Home patients). However, finding that the home care patients fared at least as well and, in many instances, better than their hospitalized counterparts, even though they were older and frailer suggests that they may have more to gain by staying out of the institution.
It's heartwarming to see evidence that treating many medical problems at home is achievable without sacrificing any important benefits and to discover there are plausible ways of paying for such care. My concern is that the “hospital at home” model, while an improvement over the hospital environment precisely because it takes place in a familiar location, may bring too much hospital technology with it. I would like to have a better understanding of just what hospital at home includes. I’m reminded of the final days of Pope John Paul II, dying of Parkinson’s disease and its complications. The Pope was cared for at home—but with a feeding tube, a ventilator, and physician care. He was, for all intents and purposes, receiving ICU care at home. So, by all means, let’s make medical care available to older people at home; let’s keep them out of the hospital if possible. But that should not mean bringing the hospital in entirety to them.

August 12, 2018

Ove-Lite

Think “A Man Called Ove,” Fredrik Backman’s bittersweet novel about a lonely man who tries repeatedly and unsuccessfully to commit suicide but ultimately finds meaning in life by helping others. Water down Ove-- take away his rage against injustice and dilute his frustration with modern technology. Make him 85 instead of 59-going-on-80. Preserve the pet cat, the needy neighbor, and the enduring love for his deceased wife. What you get is the protagonist of Elizabeth Berg’s new novel, “The Story of Arthur Truluv.” The book is a sentimental portrait of another octogenarian, Arthur Moses, nicknamed “Truluv” by the lost teenager he befriends because of his devotion to his wife, whose grave he visits daily. 


It’s high time we had more fictional treatments of older people, so I’m happy we have another contribution to the genre. And Truluv is an endearing old fellow with a big heart—albeit one apparently affected by heart failure. He, unlike Ove, is a glass-half-full sort of a fellow, whereas Ove, at least until the end of his story, is a glass-with-a-hole-in-it sort of a guy. While I appreciate that Berg does not completely sugar coat old age, giving both Arthur and his neighbor Lucille an assortment of maladies and expeditiously killing off Lucille’s elderly boyfriend with a massive heart attack, Arthur is so nice that he’s a bit hard to take. His teenaged friend Maddy, pregnant and estranged from her father, needs both a job and a place to stay? No problem, Arthur lets her move in and serve as his housekeeper. The irksome woman across the street, whose main virtue is her baking skill, decides she’d like to move in, too? Fine, she can do the cooking. Maddy hasn’t seen her father in months and secretly would like to reconcile with him before she gives birth? Arthur intuits what’s going on and invites him for Thanksgiving dinner. 

I’m a pushover for over-the-top amazing octogenarians, so I confess I enjoyed reading this book. It’s short—222 small pages, peppered with dialogue—so I only had to devote a few hours of my life to this endeavor. Maybe I would have liked it more if I hadn’t recently read “A Man Called Ove,” a tragicomic masterpiece with a protagonist who seems old even if he isn’t, a NY Times bestseller that has been translated into 43 languages. But maybe Elizabeth Berg will next turn her talents to writing about an octogenarian who is frail but who nonetheless finds meaning in life. Now that would be a major contribution to the literature on aging.

August 07, 2018

The Truth About Hospice

Hospice is widely touted as the best form of care near the end of life. As a result, the proportion of people who are enrolled in hospice at the time of death has been steadily increasing. Nearly half of all Medicare patients are receiving hospice care at the time of death. But a new report suggests that the quality of care they receive may not be what it should be. Moreover, a chunk of the $16.7 billion that Medicare spends on hospice (that was in 2016; it's more today) goes towards care that is unnecessary or not provided at all. What exactly is the problem? How widespread is it and how can patients and families identify hospices that provide high quality care?
While substandard care and fraudulent billing are distributed throughout the country, these practices occur disproportionately in the 64 percent of hospices that are for-profit. The bad behavior predominantly involves two specific variants of hospice care: general inpatient hospice care and hospice services that are provided within institutions, whether skilled nursing facilities or assisted living facilities. General inpatient care is an intensive form of care offered when symptom control cannot be achieved elsewhere (ie at home], so the patient is transferred to a hospital or skilled nursing facility. For this type of care, Medicare pays a per diem rate of $720, compared to $187 for home hospice (actually this is the rate for days 1-60, after that, the rate drops to $147 per day). The kinds of abuses that have been reported are indeed disturbing: the report gives several examples.
However,  General Inpatient Care accounts for only 1.5 percent of all the days that patients were enrolled in hospice. 
Other cases of allegedly inappropriate billing take place in Skilled Nursing Facilities (SNF) or in Assisted Living Facilities (ALF). Some instances were unequivocally fraudulent, as when hospices paid facilities to enroll patients in hospice, sometimes without the knowledge of patients or their families.  But again, it’s important to keep this in perspective.  A minority of hospice patients are cared for in these environments: 25 percent of hospice beneficiaries during the period the study examined (2006-2016) lived in a SNF and only 13 percent in an ALF.
Several of the criticisms leveled by the report are of questionable significance. The study says that many hospices fail to develop the mandatory “comprehensive care plan,” a document that spells out what services the patient needs and how they will be provided. This failing was especially egregious in the inpatient setting, where in 85 percent of cases, no such plan was documented. But the absence of a written plan doesn’t mean there was no plan or that inadequate care was provided. It means just what it says—the hospice did not create the requisite piece of paper. Maybe, just maybe, they thought it was a waste of time, a meaningless bureaucratic requirement.
Hospice care is also criticized for failing to provide physician visits. Actually, hospice does provide one physician visit. A face to face visit with a physician at the time of admission to hospice has been mandatory since 2011, so hospice patients do see a physician at least once during their hospice stay, which in many cases is short: over half of all hospice patients are enrolled for less than 30 days, and over one-fourth are enrolled for a week or less. Many hospice patients and their families would like more involvement of the medical profession, particularly their primary care physician or the relevant specialist, but that’s different from suggesting that the quality of care was poor because there were no medical visits at all.
Skilled nursing facilities are accused of double dipping, of billing Medicare for services that they already routinely provide as part of their usual care. This has been a worry since Medicare agreed to cover hospice care in a SNF. Care by nurses and nurses’ aides are a normal component of nursing home care. But that doesn’t mean that the services offered by hospice are redundant; on the contrary, the reason that hospice can be beneficial in the SNF environment is precisely because the usual nurses may not be skilled in pain management and the amount of aide time may be totally inadequate for a dying patient.
Lastly, the report argues that the payment system incentivizes hospices to minimize services and to cherry pick patients, selecting low-need, long-stay patients, such as those with advanced dementia, rather than high-need, short-stay patients, such as those imminently dying of cancer. We’ve known about this phenomenon for some time. In fact, CMS responded by modifying its payment system to pay more for the first few days of care and for the last few days of care and less for the in-between days. The practice of complementing high-cost patients with low-cost patients is only a problem if the low-cost patients don’t deserve to be enrolled in hospice at all. If they do, and there’s every reason to think they do, then it’s simply a good business strategy. Hospitals do the same thing when they add services for which they are generally reimbursed well to compensate for the services for which they are poorly reimbursed. The alternative would be to abandon the per diem payment system and go to fee-for-service. But that’s the model that is gradually fading away from the rest of the medical system because it promotes the use of volume rather than quality.
What should we conclude about hospice care in America? How should prospective patients respond to this report and how should Medicare respond? 
Patients and their families would do well to consult Hospice Compare, the CMS website, for basic information about quality. This tool relies principally on patient and family satisfaction surveys rather than objective measures, but it’s very revealing. Rather than add more measures, which is what the authors of the report propose,  I think the tool should be publicized: I was familiar with Hospital Compare and Nursing Home Compare, but I confess I did not know about Hospice Compare until recently--and the site was launched in August, 2017. 
If families have a choice between a not-for-profit hospice and a for-profit hospice, they may find it prudent to select the not-for-profit option.  On average, not-for-profit facilities are associated with higher quality care. 
As to steps that Medicare should take, increased across the board regulation, which is what the report advocates, seems unduly burdensome. Far wiser would be to target enhanced supervision and regulation to those areas that need it most, namely skilled nursing facilities and assisted living facilities. Stiffer penalties for malfeasance would also be wise. As with banking fraud, it’s not enough to slap the owner or executive director on the wrist. Jail time is a much more powerful disincentive to bad behavior. And the bad behavior we’re talking about here is neglecting people who are dying and in pain.


July 29, 2018

Treatment for Alzheimer's or False Alarm?

The most promising treatment of Alzheimer’s disease to date uses monoclonal antibodies to rid the brain of amyloid plaques. These plaques are widely thought to be crucial in the development of Alzheimer’s disease, the form of dementia that afflicts over 5 million Americans—and, unless we find a way to cure or prevent it, will afflict millions more in the coming years. Researchers hope that these drugs will prove to be “disease-modifying,” that they will disrupt the cascade of events that produces the symptoms of the disease. 

So far, the studies of monoclonal antibodies in this setting have been very disappointing: Bapinezumab: 3 failed trials. Solanezumab: 3 failed trials. Crenezumab: 1 failed trial. In the past year, three major pharmaceutical companies, Eli Lilly, AstraZeneca, and Merck, all stopped development of the monoclonal antibodies they were testing against Alzheimer’s disease. Another company, Pfizer, closed its neurodegenerative disease research section entirely. Now we learn that a Phase II trial of the as yet unnamed agent “BAN2401” actually “looks promising.” How promising?

Like its cousins, BAN2401 is a “humanized monoclonal antibody.” That means an antibody that was developed in mice and modified so it wouldn’t be rejected as alien by the human immune system. Now mice don’t normally get Alzheimer’s disease but certain strains have been genetically engineered so that they do. Using the genetically engineered mouse model, a monoclonal antibody was created that binds to amyloid. Today, this chemical is called BAN2401; when it enters the next stage of assessment, it will presumably acquire a name that ends in “zumab” to indicate it is just such a humanized monoclonal antibody. So, what do we know about this nameless entity?

We know that BAN2401 made it through a Phase I trial that tested its safety, tolerability, and pharmacokinetics in 80 people with mild to moderate dementia. We know it then entered Phase II of testing in people aged 50-90 with evidence of amyloid on their PET scans and either mild Alzheimer’s disease or mild cognitive impairment (a condition that is not dementia but often evolves into dementia). Five different dose regimens were administered intravenously and compared to placebo in terms of their effects on cognition and on brain amyloid deposits on PET scan. We know that when the preliminary results were announced last December, no cognitive benefit was reported. But now, after 18 months of study, the final results are in. They were presented at the Alzheimer’s Association International Conference in Chicago this past week.

What we don’t know is how this study will fare when subjected to peer review. We don’t know what the final paper will look like. But here’s what I can glean from the press release by Eisai, the company that collaborated with Biogen to develop and test the drug, and the reports by the news media:

--The amount of amyloid in the brain (as measured by PET scan) decreased with all the doses tested. The more drug, the greater the change. The findings were statistically significant. 

--There was no discernible effect on cognitive function except in the 161 people who were treated with the highest dose of BAN2401. In those 161 people, cognitive function deteriorated over time, just as it did in all the other groups, but it deteriorated less.

--Cognitive function was measured in a way that differs from the way it has been measured in other studies of treatments for Alzheimer’s disease. The researchers used a composite measure made up of several scales, each of which has been individually validated as a way to assess mental status, but only one of which is regularly used to report the outcome of clinical trials of Alzheimer’s drugs. 

--The patients tested included a mix of people with mild dementia and people with mild cognitive impairment (who don’t actually have dementia but aren’t entirely normal either) and the study had no way to determine whether the effectiveness of BAN2401 was any different in the two subgroups.

What does all this mean? The PET scan changes indicate that the monoclonal antibodies were successful in destroying amyloid deposits in the brain. That doesn’t prove that whatever effect the drug had was due to its amyloid-busting, but it’s suggestive. It also indicates that to the extent that the drug was a failure, it wasn’t a failure because it didn’t destroy amyloid. 

How should we interpret the cognitive changes? It’s hard to know, given that the researchers used a non-standard means of measuring clinical decline (a test they called ADCOMS). We cannot, for example, say that BAN2401 is better than one of the other monoclonal antibodies that was deemed a failure since nobody looked at the effect of the other drug on the “ADCOMS.” What we can say is that a 30 percent change in the rate of decline may be statistically significant but clinically, it’s a lot less impressive. Everyone  deteriorated, including those given the highest dose regimen; they just deteriorated a little less. How much of a difference actually occurred depends on the absolute decline: suppose the score went from 100 at baseline to 80 at the end of the study in the controls (I don’t know what the actual numbers are, so this is hypothetical). A 30 percent difference in the rate of decline means that the score in the treated group dropped from 100 to 86.  Is that clinically meaningful? Probably not.

So, no, BAN2401 is not likely to likely to dramatically change the course of Alzheimer’s disease. I hope the FDA does not allow the drug’s manufacturers catapult it into a clinical trial prematurely, before it goes through Phase 3 testing. But it has taught us a few valuable lessons. 

We now know that monoclonal antibodies can be designed that destroy amyloid plaques in the brain. We know that only the highest tolerated dose of the drug has any chance of being clinically useful. We should also realize the importance of studying patients with early dementia and those with MCI separately—it’s possible that using monoclonal antibodies once dementia has set in is too late, and I suppose that it’s also possible that using them before dementia has developed is too early. Finally, the study reminds us of the importance of a uniform methodology in conducting this kind of work. If the test that was previously regarded as the gold standard, the ADAS-Cog, is not the right test to use, then researchers need to agree on that and decide collectively what test to use instead. 

ABC News reported the drug as “giving patients hope” and showing “big promise.” Fortune magazine asserted that “world leaders want to end Alzheimer’s by 2025; a new drug breakthrough means we just might.” Investors are closer to the mark: Eisai’s stock price fell 10 percent after the data were reported.


July 23, 2018

The Right Way to Treat Cancer

Kudos to Judith Graham of Kaiser Health News for yet again identifying a new development that has the potential to enormously affect the medical care of older people. Her article, Geriatric Assessments Could Fine Tune Cancer Care for Older Adults,” pointed me to the American Society of Clinical Oncology's (ASCO) new guidelines for the management of patients over age 65 with cancer. The headline (and I know that journalists don’t generally write the headlines for their articles) is the only part of the article that’s misleading: the changes suggested would not merely “fine tune” oncologic care for older people, they would radically transform it.

Here’s the situation: 70 percent of cancer patients are over age 65 and that number will rise in the next 20 years. Looked at differently, the risk of developing cancer at some point if you are a man over age 70 is one in three, and the risk for women is one in four. Despite the predominance of older cancer patients, most clinical trials of chemotherapy drugs include few if any older people: they have too many other problems to meet the eligibility criteria for participating in the study. But those same people, with all their other medical problems and functional impairments, are regularly given chemotherapy, based on the results of studies that didn’t involve anyone like them. That’s a problem. 

What we do know is that 50 percent of older patients with advanced cancer experience severe toxicity from chemotherapy in the first three months of treatment. We also know that the Institute of Medicine’s recent study, “Delivering High Quality Cancer Care,found that the current delivery system is “ill-equipped to address the needs of older patients.” Oncologists agree with this assessment, stating that “the care of older adults with cancer needs to be improved” and putting the responsibility on themselves. Specifically, only one quarter or less of oncologists felt confident in their ability to recognize dementia, identify a fall risk, or assess functional status. And we know from a recent study that patients shift their priorities from sheer survival to quality of life as functional status declines. In light of these observations, what does ASCO recommend?

The new guideline, “Practical Assessment and Management of Vulnerability in Older Patients Receiving Chemotherapy,” makes a series of evidence-based suggestions. From the perspective of patients and their families, what’s important to know is that oncologists who are contemplating administering chemotherapy to people over age 65 should provide a geriatric assessment to identify problems they might not otherwise recognize. Specifically, they should take simple steps to look for falls, to determine how well patients can function day to day, to identify all other medical diagnoses besides the cancer that might impact treatment, to screen for depression, to evaluate cognition and nutrition, and to assess the social support system. Because the guideline is meant to be practical, it suggests specific tools that oncologists can use to achieve these ends. The guideline also advocates determining the approximate life expectancy, both the cancer life expectancy and the non-cancer life expectancy. 



What is the point of all this? How might it help older patients with cancer? The main objective is to avoid both over-treatment and under-treatment, where “too much” and “too little” must be assessed in light of the best available data about what treatment could achieve and knowledge of the patient’s preferences. How the oncologist presents the options should reflect the facts about what the consequences of treatment are likely to be. How much misery a person is willing to endure might well be affected by how much he or she has to gain in the best-case scenario and how much there is to lose in the worst-case, given the nature of the cancer and the patient’s other medical conditions. In short, the information from a geriatric assessment should guide the process of shared decision-making involving the physician, the patient, and the patient’s family, leading to an “integrated, individualized plan of care.”

But there’s another potential outcome, one that perhaps paradoxically undermines the accuracy of the predictive tools on which the recommendations rely. There is the possibility that performing a geriatric assessment will lead to implementing the recommendations of that assessment with resultant improved capacity to withstand the rigors of chemotherapy. The authors of the guideline recognize this possibility. They say, “While there are not yet completed RCTs [randomized controlled trials] that demonstrate that GA-guided care, or ‘GA with management,’ definitely improves outcomes of older patients with cancer, this care model has been shown to improve outcomes in older noncancer populations.”  Randomized controlled trials are reportedly ongoing to evaluate the ability of “GA-guided care” to actually improve outcomes in older cancer patients—not merely to modify their willingness to undergo chemotherapy in the first place, but also their longevity and quality of life if they do accept chemotherapy.

The first step is for patients and caregivers to request and oncologists to perform geriatric assessment. The second step is to act on the findings of the assessment. That doesn’t just mean using the information to guide decision-making about cancer treatment; it means, first and foremost, making some changes that will optimize the patient’s overall condition. These changes might include physical therapy, modification of the non-cancer medical regimen, or providing more social support. 
It might be necessary to delay instituting chemotherapy, and delay talking about whether to start chemo until certain basic interventions have taken place. 

One analogy that may be helpful is rehab. When a patient and family are struggling to decide if it’s going to be possible to return home after a debilitating hospitalization, it’s often helpful to begin with a stay at a rehab facility. The goal is to optimize the patient’s condition before making important decisions about where to live. A second analogy is depression. Depression may color a patient’s decisions about preferences for care. In general, whenever feasible, it’s desirable to treat depression before accepting a patient’s views about, say, limiting care for some other medical condition, as representing his or her true wishes. 

So, by all means, let’s do geriatric assessments on older patients with cancer. How, exactly, that will shape care remains to be determined.