Saturday, October 26, 2013

Living With Cancer: Brains on Chemo -

Over the past few months, a number of headlines in The New York Times have stumped me.
Tomatoes Have Devastated American Indian Families in Oklahoma
U.S. Workers Are Grounded by Deep Cats
Wall Saint Banks Woo Children of Chinese Leaders
Of course, those weren't actually the headlines The Times had written. But why am I staring at the word "Tornadoes" and reading "Tomatoes"? Looking at "Cuts" and reading "Cats"? Interpreting the abbreviation "Wall St." as "Wall Saint"? After three cycles (or 18 sessions) of chemotherapy, I seem to be dealing with a weird sort of dyslexia.
Chemo brain is a phenomenon that patients have described for quite some time as a thick mental fog resulting from chemotherapy. For quite some time, too, physicians discounted chemo brain as a figment of patients' imaginations. Now, however, the American Cancer Society terms it "a mild cognitive impairment" that for most people only lasts a short time.
Doctors were skeptical about chemo brain because many factors can induce mental glitches. Forgetfulness, trouble concentrating, memory blanks, inattention, word loss, retention problems and disorganization can result from aging, sleeplessness, depression, fatigue, anxiety, low blood counts, the onset of menopause and other medications.
Isn't it curious, though, that chemotherapy often accelerates aging, causes sleeplessness and depression, promotes fatigue and anxiety, lowers blood counts, causes the onset of menopause and requires powerful secondary medications to deal with its side effects? We seem to be caught in a dupe — oops, I mean a loop.
P.C.C.I., or post-chemotherapy cognitive impairment, after being attributed to patients' hang-ups, finally became the subject of serious research while I was undergoing treatment. Such investigations therefore could not yield pragmatic solutions quick enough to help me locate my car in the parking lot or my keys maybe inside it.
While I was going through chemotherapy, the phrase "mild cognitive impairment" did not pertain to the stupefaction I experienced at forgetting a close friend's name. I found myself bewildered about what task had led me to my university office and then lost on the way home. I had to enact a convoluted guessing game to get my husband to provide the word "egg." On more than one occasion, it became apparent that one of my daughters was confiding in me, but about what?
From that time on, I got hooked on two aids many people use to survive with a minimum of mortification. First, on my computer and iPhone, I have an elaborate calendar listing not only events that must be attended or tasks that must be accomplished but even menus and their ingredients. I study it hourly so I will remember what needs to be performed, purchased or produced — when, and for or with whom.
Second, I always have a small pad in my purse, another by the side of my bed, another next to my computer, another in the kitchen. Often I scribble suggestions or snippets of conversation so — if they are decipherable — I can mull them over later and learn to remember the information they convey in a new, if more laborious, manner.
Because of the cumulative effect of chemicals, sometimes those aids do not help. A few years ago, I suffered the bane of chemo brain most intensely toward the end of six infusions of Taxol and Carboplatin, when a fuzzy hesitancy spiraled into blank enervation. I could not think to think, stand to stand, or feel to feel. Vacancy morphed me into a zombie or humanoid. I felt somehow exiled from myself, a mishap never mentioned in the cheerful brochures on chemotherapy displayed in oncology waiting rooms.
A friend of mine now on the same drug combination weeps while considering suicide, although she is taking an antidepressant. "It's the chemicals, stupid," she has to keep reminding herself.
Even when Carboplatin alone was later prescribed for me, I had trouble reading. I tried, but when I turned the page I became convinced that either there was a page missing or I had skipped a page. My eyes would roll over a paragraph without being able to snag on a sentence … sort of a hindrance for an English teacher.
These days, while I take a targeted drug, the aftereffect of chemo brain persist in milder forms, making my reading quite stimulating — but for the wrong reasons. As I study a recipe calling for 1 ¼ teaspoons of salt, I wonder how to measure 11 fourths. I am regularly surprised by discussions of kidney stores (instead of kidney stones), dejection tissues (instead of digestion issues), the sex dive (sex drive) and constipations after surgery (rather than complications after surgery).
As a self-identified "chemosabe" in my support group assures me, at least the recognition and naming of chemo brain prove we are not (completely) crazy.

Should Medical School Last Just 3 Years? -

Sandwiched between three mind-numbing years of basic science courses and hospital rotations and the lockdown years of residency training, the fourth year of medical school has long been a welcome respite for future doctors. It is the only time in their medical education when students have few requirements and a plethora of elective course offerings – and the time to go on vacation and spend time with friends and family.

"Do it now," a mentor said as I was about to start my last year, "because you may never get the chance again."

I followed that advice wholeheartedly. I spent most of my fourth year away from my medical school, caring for children with hematologic disorders one month, then shadowing cancer surgeons for another, in hopes of figuring out which specialty I liked more. I spent time working in a laboratory, something I'd never done before, learning how to culture and freeze cells, care for mice, and critique studies. I attended national medical meetings, hung out with old friends, and slept and ate to my heart's content at my parents' home.

For me, it was a pivotal, reassuring year.

But not all of my classmates felt the same. One friend interested in a particularly competitive residency spent much of the year in high-stress "audition clerkships," four-week clinical tours at hospitals where she hoped to train; she resented having to pay tuition at our home school while paying travel and living expenses so she could learn at other institutions. Another, older classmate, who had already spent 10 successful years in another profession, was just eager to get on with his training; for him, a fourth year filled with electives and extended vacations was a waste of time and tuition money.

"The fourth year is kind of bogus," one friend recently recalled. "It might have been fun at the time, but I'm not sure it made me a better doctor."

These disparate opinions came to mind recently when I read twoperspective pieces in The New England Journal of Medicine on eliminating the fourth year of medical school.

For several years, medical educators have been engaged in an increasingly heated, and occasionally cantankerous, debate about streamlining medical education and training. Many experts have suggested lopping years off the residency training process, but surprisingly few have argued for such similarly dramatic changes in the medical school curriculum.

Established over a century ago as part of a sweeping change to a chaotic collection of schools, apprenticeships and fly-by-night training programs, the four-year medical school curriculum is the sacred cow of medical education. Like soldiers in lockstep, nearly all medical students over the last 100 years have spent their first two years in lecture halls learning the theory and basic science of medicine and their third and fourth years on the wards learning the practical clinical applications. Apart from a few short-lived experiments during World War II and in the 1970s to shorten the curriculum to three years, not even the most radical of educational reformers have dared stray from the norm, carefully integrating their changes well within the venerated four-year framework.

But now it appears that the perfect storm of physician shortages, rising health care costs and student debt has begun to tip this hallowed heifer. In 2010, responding to the physician workforce shortage, Texas Tech University Health Sciences Center School of Medicine began offering a three-year medical school track for select students interested in primary care. Soon thereafter Mercer University School of Medicine's campus in Savannah, Ga., followed suit; and this fall, New York University School of Medicine welcomed, in addition to its traditional four-year students, its first group of students to pursue a three-year option.

Proponents believe that the three-year programs will help address several pressing issues. By producing doctors faster, three-year M.D. degree programs help to address the critical doctor deficits predicted over the next 15 years. In addition, with almost two-thirds of medical students graduating with $150,000 or more of educational debt and with more students entering medical school at an older age, the three-year option allows students to begin practicing sooner and with as much as 25 percent less debt.

"We can't dissociate medical education from societal and student needs," said Dr. Steven B. Abramson, lead author of the perspective piece in favor of three-year programs and vice dean for education, faculty and academic affairs at N.Y.U. "We can't just sit back in an ivory tower and support a mandatory year of prolonged adolescence and finding oneself, when society needs doctors to get out into the community sooner."

But critics are quick to point out the failures of past attempts to do the same. In the 1970s, for example, with support from the federal government, as many as 33 medical schools began offering a three-year M.D. option to address the impending physician shortages of the time. While the three-year students did as well or better on tests as their four-year counterparts, the vast majority, if offered a choice, would have chosen the traditional four-year route instead. Many who completed their work in three years were exhausted by the pace of accelerated study; and as many as a quarter asked to extend their studies by a year or two anyway.

The most vocal critics were the faculty who, under enormous constraints themselves to compress their lessons, found their students under too much pressure to understand fully all the requisite materials or to make thoughtful career decisions.

The three-year experiments were quickly abandoned.

"You can't pretend to have a great educational experience without spending time on the educational experience," said Dr. Stanley Goldfarb, lead author of the perspective piece against three-year programs and associate dean for curriculum at the Perelman School of Medicine at the University of Pennsylvania.

Dr. Goldfarb and other critics contend that a host of new issues complicate the issue. The amount of material that students must assimilate, for example, has increased dramatically since the 1970s; and regulations now limit the number of hours trainees can work in the hospital. Taking away an entire year of the educational process dramatically whittles away the time young doctors have to interact with patients and gain critical clinical experiences.

"The complexity of medicine is greater than it's ever been," Dr. Goldfarb noted. "Compressing what has become more complex than it's ever been seems counterintuitive."

Four more medical schools are nonetheless currently considering adding a three-year M.D. option to their traditional programs. And while all of these shorter programs still remain an option and not the norm, the debate they have incited has brought greater attention to other exciting initiatives, like anovel assessment method that is based on a student's actual skill rather than the number of years completed. This "competency-based" assessment would mean that students would be allowed to graduate when they demonstrated the skills and not just when they fulfilled the four-year requirements of a 100-year-old standard.

"Everything has changed around us," Dr. Abramson said. "Specialties have changed, society has changed and the debt burden has changed. We are never going to be able to adapt of changing needs of society and of our students if we continue to believe that the way we educate medical students is sacred."

Why New Drugs Are So Expensive | MIT Technology Review

In January 2012, the U.S. Food and Drug Administration approved Kalydeco, the first drug to treat the underlying cause of cystic fibrosis, after just three months of review. It was one of the fastest approvals of a new medicine in the agency's history. Vertex Pharmaceuticals, which discovered and developed the drug, priced Kalydeco at $294,000 a year, which made it one of the world's most expensive medicines. The company also pledged to provide it free to any patient in the United States who is uninsured or whose insurance won't cover it. Doctors and patients enthusiastically welcomed the drug because it offers life-saving health benefits and there is no other treatment. Insurers and governments readily paid the cost.

Several months later, Zaltrap was approved to treat colorectal cancer. The drug was discovered by Regeneron, an emerging biopharmaceutical company like Vertex, but sold by the French drug maker Sanofi. Though it worked no better in clinical trials than Roche's cancer drug Avastin, which itself adds only 1.4 months to life expectancy for patients with advanced colorectal cancer, Sanofi priced Zaltrap at $11,000 a month, or twice Avastin's price. Unexpectedly, there was resistance. Doctors at Memorial Sloan-Kettering in New York, one of the world's leading cancer centers, decided Zaltrap wasn't worth prescribing. They announced their decision—the first time prominent physicians anywhere had said "Enough" to the introduction of a high-priced cancer drug—on the op-ed page of the New York Times. Three weeks later Sanofi effectively dropped its price by half through rebates to doctors and hospitals. Even so, British health authorities said they would not pay for the treatment.

The FDA approved 39 new drugs in 2012, the most in a decade and a half—a sign that the pharmaceutical industry may be recovering from its long fallow period. Wall Street applauded the revival, especially because many drug companies are facing patent expiration for their top-selling products and could see dwindling revenues after years of lackluster research productivity. Most of the new drugs either treated rare diseases like cystic fibrosis or were marginal improvements over existing cancer drugs. All carried extremely high price tags.

But a closer look at the rollouts of Kalydeco and Zaltrap reveals startling differences in how companies value a drug and justify its price. It also provides a preview of a likely future in which extremely costly drugs are common.

More ...

Friday, October 25, 2013

NYTimes: Agency Initiative Will Focus on Advancing Deep Brain Stimulation

Worldwide, 100,000 people have electrical implants in their brains to treat the involuntary movements associated with Parkinson's disease, and scientists are experimenting with the technique for depression and other disorders.
But today's so-called deep brain stimulation only treats — it does not monitor its own effectiveness, partly because complex ailments like depression do not have defined biological signatures.
The federal Defense Advanced Research Projects Agency, known as Darpa, announced Thursday that it intended to spend more than $70 million over five years to jump to the next level of brain implants, either by improving deep brain stimulation or by developing new technology.
Justin Sanchez, Darpa program manager, said that for scientists now, "there is no technology that can acquire signals that can tell them precisely what is going on with the brain."
And so, he said, Darpa is "trying to change the game on how we approach these kinds of problems."
The new program, called Systems-Based Neurotechnology and Understanding for the Treatment of Neuropsychological Illnesses, is part of an Obama administration brain initiative, announced earlier this year, intended to promote innovative basic neuroscience. Participants in the initiative include Darpa, as well as the National Institutes of Health and the National Science Foundation.
The announcement of Darpa's goal is the first indication of how that research agency will participate in the initiative. The money is expected to be divided among different teams, and research proposals are now being sought.
Darpa's project is partly inspired by the needs of combat veterans who suffer from mental and physical conditions, and is the first to invest directly in researching human illness as part of the brain initiative.
The National Institutes of Health, which has not decided on its emphasis, appears to be aiming for basic research, based on the recommendations from a working committee advising the agency.
Dr. Helen Mayberg, a neuroscientist at Emory University School of Medicine who has pioneered work on deep brain stimulation and depression, said, "Darpa's initiative says in no uncertain terms that we want to concentrate on human beings." She said she was particularly pleased with the emphasis on deep brain stimulation: "This adds to a growing recognition that this approach to brain disease is a promising strategy."
Cori Bargmann of Rockefeller University, one of the leaders of the health institutes committee dealing with the direction of that agency's work under the brain initiative, also applauded the direction of the Darpa research.
"It plays to their strength in brain recordings and devices, and it addresses psychiatric issues that are major concerns for the military," she said.
Darpa's goal would require solving several longstanding problems in neuroscience, one of which is to develop a detailed model of how injuries or illnesses like depression manifest themselves in the systems of the brain.
The next step is to create a device that can monitor the signs of illness or injury in real time, treat them appropriately and measure the effects of the treatment. The result would be something like a highly sophisticated pacemaker for a brain disorder.
Darpa is asking for research teams to produce a device ready to be submitted to the Food and Drug Administration for approval within five years.
"Is it overambitious? Of course," said Dr. Mayberg, adding that working with the brain is "a slow process." But she said that it was an impressive first investment and that the clear emphasis on human illness was "stunning."
Whether or not the specified goal is fully achieved, Dr. Sanchez said, "We're going to learn a tremendous amount about how the brain works." And, he added, "we're going to be developing new medical devices."
The testing of any such devices would involve both animals and human subjects, and Dr. Sanchez said Darpa had set up an ethics panel for the new program and other Darpa neuroscience work. A presidential bioethics commission also oversees all aspects of the brain initiative.
The Obama administration is budgeting $100 million for the first year of the brain initiative. A committee of the health institutes produced a draft report in September that indicated the agency would concentrate its $40 million share on systems or networks in the brain, not individual cells and not the whole brain.
Darpa is allocated $50 million this year under President Obama's brain initiative. The agency would not specify precisely how much it would spend in the first year, and all the numbers are dependent on the final federal budget.

Sunday, October 20, 2013

Climb two mountains and call me in the morning - In Practice -

Mark Twain once quipped: "Everyone talks about the weather, but nobody does anything about it." Is the same true of exercise? Despite a growing, multibillion dollar fitness industry, despite an increase in sales of treadmills, weights, and other home exercise equipment, despite public education campaigns like Let's Moveeighty percent of Americans--four out of five of us--do not get the recommended amount of cardiovascular and strength training. 41 million Americans belong to gyms--less than half of those actually go to them regularly.

Doctors know that exercise benefits health in many ways, from relieving depression to preventing heart disease and cancer. And yet, our efforts at counseling patients about exercise range from absent to haphazard. In my own practice, I confess, that though I do ask people about their exercise habits when I first meet them and at their annual physicals, the conversation is often unproductive (and occasionally comical). A couple of recent examples:

Me: Have you been exercising?
Patient: Yes, now that the weather is nice I'm walking outside.
Me: But this Boston. Soon the weather won't be nice. What then?
Patient: I hadn't thought about that.

Me: Have you been exercising?
Patient: Yes! I walk my dog.
Me: Great! What kind of dog do you have?
Patient: A chihuahua.

Why aren't I doing a better job at this? Lack of time, for one thing. it's hard to squeeze a motivational conversation about exercise into a medical visit in which so much else needs to be covered (managing diabetes and high blood pressure, immunizations, flossing...). Also, frankly, doctors get very little training on how to counsel patients about exercise--and we may be no more likely to exercise than our patients! Also, sadly, we operate in a culture in which writing prescriptions is easier and more valued than talking.

So what if exercise counseling came in prescription form? It does.

Several studies, such as the one summarized here, have shown that when a doctor, nurse practitioner hands a patient a specific exercise recommendation--type of exercise, intensity, duration, etc.--the patient is more likely to exercise. Here is a sample of what that looks like:

A new partnership between Massachusetts General Hospital For Children and the Appalachian Mountain Club takes an especially creative approach to exercise prescription. Called Outdoor Rx, the program trained 60 health professionals in the pilot sites, Waltham and Framingham, to write prescriptions giving families special access to information and activities sponsored by the Appalachian Mountain Club.

Doctors know exercise benefits health, and we also know most of our patients aren't exercising--and neither are most of us. Maybe we need to do more than talk about it.

Suzanne Koven is an internal medicine physician and a Boston Globe columnist.  She blogs at In Practice at