book club

Law 2. Normals teach us rules; Outliers teach us laws

I search for patterns, always have. The logic of symptomatology is Glorious. I suspect this character trait is common in nephrologists. But revelling in the symptoms and signs that lead to a diagnosis and the investigative algorithm that refines the differential into the definite, has meant that I focus on what Siddhartha terms “inliers”. As I seek to make a patient “fit” my pre-conceived pathogenic model, I run the risk of missing a deeper truth. Brahe concentrated on the inliers and modelled the movement of the planets into concentric circles, frustrated that Mars wouldn’t fit this model. Kepler used the movement of the outlier, Mars, to reveal that all the planets orbit the sun in concentric ellipses. By concentrating on the range of normalcy we can only create rules, whereas “outliers” allow access to deeper laws.

Each outlier represents an opportunity to refine our understanding of illness. Asking why one patient in a thousand has responded to a drug, can reveal new disease pathways. David Solit used this approach to investigate why one woman’s advanced bladder cancer had a spectacular response to everolimus, while the drug appeared ineffective for the cohort as a whole. Sequencing that woman’s tumour showed multiple mutations, most interestingly in TSC1 and NF2, suggesting that these genes modulated the response to everolimus. The group went on to sequenced the same genes in the larger cohort and were able to segregate the group into responders and non-responders by the mutation in the TSC1 gene. In doing so they opened up new lines of enquiry and broadened the understanding of everolimus, bladder cancer, tuberous sclerosis and neurofibromatosis.

Through seeking to understand the outlier they opened up a deeper understanding of disease.

Now that case reports have fallen out of fashion, becoming almost impossible to publish and dismissed as anecdote, where are we to find our outliers? One option is to conduct “outlier rounds” as Siddhartha suggests, another is to seek out case report posters at conferences. But a further powerful option is to maintain an open dialogue with colleagues, whether in person or online, to tell our stories and to ask the deeper questions.

Cathy Quinlain

The NephJC Book Club Returns. Vote for your choice.

Last summer we did a book club on Atul Gawande's Being Mortal. The NephJC team blogged its way through every chapter and we did a discussion of the book during one of our Tuesday/Wednesday chats. We think the summer is a great time to slow down from the rapid digestion of medical literature and enjoy a slower paced book. We couldn't decide on a book among ourselves so we are turning to you to pick this Summer's book. Here are the choices:

1. When Breath Becomes Air by Dr. Paul Kalanithi. NYT Review.

2. The Patient will See You Now by Dr. Eric Topol (@erictopol) NYT Review

3. How doctors think by Dr. Jerome Groopman. NYT Review

4. On the Move by Dr. Oliver Sacks. NYT Review

5. The Laws of Medicine: Field Notes from an Uncertain Science by Dr. Siddhartha Mukherjee. Los Angeles Times Review

Being Mortal: Chapter Seven

I did not like the Immortal Life of Henrietta Lacks. I thought the story of the HeLa cells and the story of Ms Lacks and her family was interesting and introduced me to a history of medicine that had previously been invisible. The story was fascinating but the book fell flat because of the way that the author, Rebecca Skloot, inserted herself into the story. Every chapter that was told from Ms. Skloot's point of view came across as having low stakes and was generally uninteresting. I finished the book with the belief that this point-of-view writing was a poor technique for non-fiction.

I was wrong. While it didn't work for the Immortal Life, Dr. Gawande uses it to dramatic effect in Being Mortal. Gawande is a recuring character in the book and the previous chapters we are taken on his journey from a doctor with conventional western medicine understanding about dying o a much deeper and richer understanding. In chapter seven, however, Gawande changes from a researcher to an active participant as his dad suffers a devastating illness and he needs to put his new found knowledge of hospice, assisted living, palliative care and end-of-life decisions to use.

The scan revealed a tumor growing inside his spinal cord.
That was the moment when we stepped through the looking glass. Nothing about my father’s life and expectations for it would remain the same. Our family was embarking on its own confrontation with the reality of mortality. The test for us as parents and children would be whether we could make the path go any differently for my dad than I, as a doctor, had made it go for my patients. The No. 2 pencils had been handed out. The timer had been started. But we had not even registered that the test had begun.

In 2006, Gawande's father, Dr. Atmaram Gawande, went for an MRI to diagnose a slowly progressive pain in his neck associated with numbness in his left hand. The scan revealed a spinal cord tumor.

The Gawande's then consulted a pair of neurosurgeons, one in Boston and one at the Cleveland Clinic. Gawande explains the bedside manner of both doctors by describing a paper by the medical ethicists Linda and Ezekiel Emmanuel that described the three type of relationships doctors could have with patients:

  1. Paternalistic
  2. Informative
  3. Interpretive

Gawande describes all three types. The first is the doctor we read about from the 50's. The all knowing God-like figure that tells the patients what they should do and does not discuss options that the doctor does not think are optimal. We would like to think that we are past this but in reality it is more common than we care to admit. 

The second type, informative, is the opposite of the paternalistic relationship. The doctor informs the patient of the facts and figures needed to figure out the best option and then lets the patient make the decision. Gawked explains that this works best for for simple issues with clear choices and straightforward trade-offs. The more complex and emotional the issue the more this method breaks down.

The Emmanuels third option, interpretive, is a hybrid of the two earlier models. “Here the doctor’s role is to help patients determine what they want. Interpretive doctors ask, “What is most important to you? What are your worries?” Then, when they know your answers, they tell you about the red pill and the blue pill and which one would most help you achieve your priorities.”

The chapter winds its way through his father's illness and we see Gawande struggle to use the lessons he has learned to help his father. They make some excellent decisions, they make some mistakes, they meet some excellent physicians and some clunkers. The face decisions on hospice, medical decision making and hospice. Despite some missteps, by the end of the chapter his father is in hospice and living a surprisingly full life.

But walking slowly, his feet shuffling, he went the length of a basketball floor and then up a flight of twenty concrete steps to join the families in the stands. I was almost overcome just witnessing it. Here is what a different kind of care—a different kind of medicine—makes possible, I thought to myself. Here is what having a hard conversation can do.

Being Mortal: Chapter Six

Hector Madariaga, NSMC intern and transplant fellow wrote the summary for this chapter.

Chapter Six: Letting Go

Most of this chapter describes the sad case of Sara Thomas Monopoli and her journey from being diagnosed with metastatic lung cancer while 39 weeks pregnant with her first child to her demise a few months later. She was only 34 years old. Sarah failed multiple rounds of chemotherapy and despite continually deteriorating, she, nor her family, came to terms with her impending death and she passed in the ICU without saying goodbye.

Dr Gawande discusses the fact that 25% of all Medicare spending is for the 5% of patients in their final year of life, and most of that money is spent in the final few months. He describes the finances of breast cancer where $28,000 is spent in the first year, primarily on surgery, radiation and chemotherapy. After that the costs fall to $2,000 per year until the final year of fatal cases of where the costs swell to $94,000. (ref)

Our medical system is excellent at trying to stave off death with $12,000-a-month chemotherapy, $4,000-a-day intensive care, $7,000-an-hour surgery. But, ultimately, death comes, and few are good at knowing when to stop.
— Atul Gawande

This intense medicalization of death arguably does more harm than good. A study in 2008 showed that cancer patients who were put on a ventilator, given defibrillation, chest compressions, or admitted to an ICU had a substatnitally worse quality of life in their last week of life. Worse, is that this trauma is passed on to loved ones. Caregivers of these patients had three times the rate of major depression. (JAMA 2008)

He describes how advancements in medicine make death a long process rather than an event that lasts a few hours to days. He describes ars moriendi, literally the art of dying. These were prescribed customs people followed when they died. These procedures were published in popular pamphlets and described seeking forgiveness from God, letting go of worldly possessions, and provided friends and families prayers and guidance for the final hours. Gawande argues that we need a new ars moriendi appropriate for the contemporary reality of the end of life.

So I sat with her sisters in the ICU’s family room to talk about whether we should proceed with the amputation and the tracheostomy.
“Is she dying?” one of the sisters asked me.
I didn’t know how to answer the question. I wasn’t even sure what the word “dying” meant anymore. In the past few decades, medical science has rendered obsolete centuries of experience, tradition, and language about our mortality and created a new difficulty for mankind: how to die.
— Atul Gawande

e also describes his rounding with Sarah Creed, a nurse practitioner on the hospice service. He interviews the patients and explores their decision to go into hospice care.  One
thing that I learned is that hospice care is not about “letting nature take its course” or to prolong life (that’s the goal of medicine), but to focus on patients' priorities. Their first patient had end-stage heart failure with pulmonary fibrosis. Sarah helped her get medication refills which had been sitting at the pharmacy.

He also explores the rational of terminal patients when they are given a poor prognosis and why they continue to pursue therapy with the hope of extending their lives, when in fact, they only have months to live. Sarah explains that 99% of her patients understand they are dying but they all still hope that they are not. Only about quarter of them have accepted their fate.

The next patient is Dave Galloway, a former firefighter with pancreatic cancer. He is in terrible pain and Sarah has to convince him to use the PCA pump more often. Gawande goes in to detail about a "comfort pack" which is a bundle of useful medications for everything from dyspnea to delirium. Dave's wife knows how to use the medications and is provided with a 24-hour phone line she can call for advice of what medications to use in which situations. The comfort pack provides her an ability to provide care to her husband through his final days and keep him at home comfortably.

Gawande talks a bit about how difficult a problem this is to solve, since solutions often sound like rationing. He then goes on to discuss the story of Nelene Fox, the women who sued Health Net when they refused to pay for her bone marrow transplant for breast cancer. The insurance company did not pay for the experimental procedure. A jury awarded $89 million to her family. Legislators in 10 states then enacted laws requiring insurance companies to pay for bone marrow transplants. The procedure has since been shown to be ineffective for breast cancer. [Note: Intererested readers should check out The Emperor of All Maladies, a great book that digs into the science behind bone marrow transplant for breast cancer and the scientific fraud that perpetuated this practice.]

A landmark study from MGH is also mentioned, in which they randomized 151 patients with stage IV lung cancer. Half received usual oncology care and the other half oncology care plus visits with a palliative care specialist. The results were fascinating. Those in the second group, stopped chemotherapy sooner, opted for Hospice care earlier and lived 25% longer. A similar study is also mentioned in where they too found that palliative care extends survival. As stated in the text:
“You live longer only when you stop trying to live longer.” 

If end-of-life discussions were an experimental drug, the FDA would approve it.

The author also explained the end-of-life discussion in the community of La Crosse, Wisconsin in which their is a systematic and widespread effort to get people to discuss end-of-life wishes prior to the, you know, end-of-life. When ever someone in La Crosse is admitted to a hospital, nursing home or assisted living facility they complete a four question form:

  1. Do you want to be resuscitated if your heart stops?

  2. Do you want aggressive treatments such as intubation and mechanical ventilation?

  3. Do you want antibiotics?

  4. Do you want tube or intravenous feeding if you can’t eat on your own?

They increased advance directives from 15% to 85% in 5 years. The ICU doctor Gawande talked with explained that the benefit is not the answer per se but that people have discussed the issues long before they are admitted to the ICU. End-of-life costs in La Crosse are half the national average.

How to approach the end-of-life discussions? Every case has to be individualized; some general rules are: sit down, take your time to talk to family and patients, learn what’s most important for the patient under any circumstance and finally, listening. As Mrs Block, a Palliative care specialist says: “if you are talking more than half of the time, you’re talking too much.”