Saturday, June 22, 2013

After Chemo | The Scientist Magazine

When my mother was treated for inflammatory breast cancer 20 years ago, I watched as she forgot appointments, where she had put her keys, and whether or not she had taken her medications. Once she even put a chicken still in its wrapping into the oven and didn't realize the mistake until the plastic began to smoke. As a psychologist and a pharmacologist, I suspected what many patients complain of to their oncologists: that the chemotherapy was affecting her ability to remember and to reason.

The American Cancer Society estimates that more than 1.65 million new cancer cases will be diagnosed in 2013. For many cancers, the prognosis will be very good. For example, 90 percent of breast cancer patients will survive their cancers for at least 5 years. But while cancer chemotherapy is lifesaving, it also has a number of post-treatment adverse effects. Despite the fact that most chemotherapeutic agents do not enter the brain in significant amounts, recent research has shown they can directly and indirectly produce a number of acute and delayed changes to the central nervous system, such as headaches, vision or hearing loss, and cognitive dysfunction, colloquially called "chemo fog" or "chemo brain." These effects can last for years, then dissipate, or, when they occur in young children, can ripple into adulthood.

In part because of my own experience and in part because my colleague Robert Raffa at Temple University suggested I collaborate with him, I began to research the phenomenon of chemo fog. What I learned at the start was that little preclinical or animal research definitively linked chemotherapy to cognitive effects, and some researchers didn't believe that chemotherapy was really responsible for the observed decline. In recent years, however, more clinical and preclinical researchers have begun to tease out the contribution of chemo, and have created models that are a useful first step in developing interventions that could mitigate the cognitive decline.

From the clinic

It is challenging to pinpoint whether the drugs used to kill cancer cells are really causing cognitive deficits, because there are so many confounding factors that cloud the observations. Patients are often administered multiple cancer chemotherapeutic agents in different phases of treatment, as well as additional drugs to mitigate the accompanying nausea, fatigue, suppressed immune function, and anemia. Aside from this battery of drugs, surgery can also affect cognition.

In addition to factors that can affect the brain directly, chemotherapy has been known to induce menopause in premenopausal women and bring on depression and anxiety, both of which can affect cognition.1,2 What makes it even more difficult to pinpoint the effects specifically caused by chemotherapy is that not all cancer patients will exhibit cognitive deficits—the prevalence ranges from 17 to 75 percent in breast cancer patients, for instance, depending on the drugs used and the cognitive tests employed by the study. And patients can experience the effects years or even a decade after treatment has ended. Thus, controversy remains over the existence, extent, and underlying mechanisms of chemotherapy-induced cognitive dysfunction.

A number of clinical trials and animal studies have tried to address some of the confounding factors and reveal the precise contribution of chemotherapy treatments. Part of the difficulty in identifying cognitive changes in humans can be attributed to how and when baseline measures of cognitive function are taken. Chemotherapy-induced cognitive deficits are best measured with a full battery of neuropsychological tests administered by a psychologist trained in performing such surveys. However, these tests can be expensive and time-consuming, so about half the clinical studies in this area have used simpler, but less-informative, screening measures. In longitudinal studies, the baseline control tests can be administered before diagnosis to rule out the emotional impact of the news on cognition, before surgery to remove tumors, and after surgery but before chemotherapy, which together provide results that aren't easily comparable. These methodological differences add to the variability in the field, and researchers have begun to call for consensus in the timing and quality of testing.

Despite these difficulties, neuroscientists have been making progress in identifying some of the underlying brain structures that chemo may be impacting—information that will be helpful in categorizing the deficits and knowing what to test for in cognitive experiments. Imaging studies have revealed volume decreases in areas of the brain that correlated with poor attention and impaired memory. Functionally, even years after chemo, patients showed lower levels of responsiveness in both the prefrontal cortex—which is involved in executive functions such as decision-making and social behavior—and the parahippocampal gyrus, which feeds into the hippocampus and is involved in memory formation and retrieval. Using magnetic resonance diffusion tensor imaging, which produces a structural picture of the functionality of the neural tracts, researchers have also found decreased structural integrity of white matter in a number of brain regions, including frontal cortex, as well as white-matter microstructure damage in breast cancer survivors.3 

The majority of clinical studies examining chemotherapy-induced cognitive deficits have been performed in women with breast cancer because of how long they tend to survive after treatment and because the chemo regimens are somewhat more standardized than for other cancers. However, the Childhood Cancer Survivor Study has also been following patients treated as children with chemotherapy for acute lymphoblastic leukemia (ALL) and measuring the prevalence of chemotherapy-related cognitive deficits later in life, known as late effects. These effects, which include impairments in attention, working memory, IQ score, and processing speed, manifest in adolescence and young adulthood in 40–70 percent of ALL survivors. Evidence from neuropsychological and physiological testing has indicated involvement of the hippocampus, prefrontal cortex, and white matter, but few imaging studies have been done in children to confirm the areas implicated by cognitive tests.

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Cancer Clinical Trials of Tomorrow | The Scientist Magazine®

We stand on the cusp of significant change in the fundamental structure of cancer clinical trials, as the emphasis begins to shift from large-scale studies of relatively unselected patients to smaller studies testing more narrowly targeted therapies in molecularly characterized populations.

The previous (and still current) generation of trials established the cancer treatment standards used today. Trials that demonstrated the value of combination chemotherapy in the adjuvant treatment of breast cancer are an excellent example. Meticulous development of treatment regimens through Phase 1 and Phase 2 trials, followed by large-scale comparisons of the new regimens to established treatment protocols, have defined the modern practice of oncology for the last 4 decades. Future cancer clinical trials will be very different from those of the past, adopting a more personalized, sometimes called "precision," approach.

It is, of course, not entirely true that past clinical trials did not include efforts to target treatments to the right patients. Where possible, targeted therapies are already being implemented. Using the presence of endocrine receptors to guide endocrine therapy for breast cancer was one of the first forays into molecular selection of patients. Unfortunately, the ability to select subgroups of patients for study has been severely curtailed by a still-limited knowledge of human cancer biology.

This is rapidly changing, however, thanks to advances in genomics and comprehensive cancer biology research over the last decade. Large-scale efforts, such as The Cancer Genome Atlas, are comprehensively defining many of the crucial molecular characteristics of human malignancies by illuminating genetic alterations that are clinically and biologically important, and which, by virtue of their functional roles, are viable targets for cancer treatment. At the same time, the ability to design small-molecule inhibitors of specific cancer targets is rapidly accelerating. In 2011, two new agents exemplified the power of these trends: crizotinib was approved for the treatment of lung cancers that harbor a specific mutation in the ALK gene, and vemurafenib was approved for the treatment of melanomas with a specific BRAF mutation. In both cases, the drugs were approved along with companion diagnostic tests that identify patients with the target mutation, who are therefore likely to benefit from treatment.

Smaller, more precise trials ahead

Clinical trials are being transformed by these trends. It will not happen overnight, as the knowledge of cancer biology and the availability of targeted agents are uneven. Unselected populations of patients will still be studied, but it is inevitable that there will be a rise in the number of trials that incorporate molecular tumor testing prior to treatment, with treatment selection informed by the molecular features of each individual's cancer. Such personalized trials have the potential to yield better outcomes by increasing the probability of response and to employ less toxic therapies by increasingly targeting cancer-specific functions, rather than normal proliferative functions.

To the extent that targeted therapies will prove more effective when given to selected patients, clinical trials should get dramatically smaller. Trial size is largely driven by how effective the treatment is expected to be, so fewer participants are needed when the therapeutic benefit is larger. But the promise of smaller trials will not to be universal; for example, when two targeted agents are compared to one another in the same molecularly selected population, the differences in efficacy may be small and larger trials will be required.

As approaches to cancer treatment advance, there will need to be continual engagement with patients and with cancer survivors.

Furthermore, smaller trials may not necessarily move faster or be easier to complete, as they will require the "right patients," who may be hard to find. Many of the mutations that represent promising targets are present in a minority of tumors. Today, molecular characterization of tumors is often done as part of the screening process for each trial. Many, and sometimes most, of the patients prove ineligible, making this approach frustrating and difficult to carry out. A better avenue of attack would be to make comprehensive molecular characterization of tumors a routine part of establishing a patient's eligibility for a range of therapies. With the plummeting cost of genomic analysis, one can envision a day in the near future when a complete cancer genome (and perhaps other molecular evaluations) becomes a standard component of an initial diagnostic evaluation. Patients will be armed with molecular information about their own tumors, and thus able to make more-informed decisions about standard and investigational therapies that match the mutations driving their cancer.

New challenges

The road to personalized and targeted treatment strategies will offer new challenges. For rare targets that are present in a minority of cases across many different types of cancers, one will have to consider clinical trials that include a number of different cancers. There are many design pitfalls to such trials, chiefly the additional clinical and molecular heterogeneity introduced by the inclusion of more than one cancer type. Despite these challenges, it will inevitably make sense in some settings to select patients who share a particular tumor biology, regardless of the tissue of origin.

Another major challenge is how to combine targeted therapies to improve clinical outcomes. To date, targeted therapies have not been able to cure advanced solid tumors. Clinical benefits, while sometimes quite impressive when compared to marginally effective treatments, still fall far short. It stands to reason that redundant survival and growth pathways enable tumors to overcome therapies that inhibit a single target. The simultaneous inhibition of relevant redundant pathways may yield dramatically better results, but will also dramatically increase the complexity of molecularly personalized clinical trials.

As approaches to cancer treatment advance, there will need to be continual engagement with patients and with cancer survivors. Fewer than 5 percent of adult cancer patients participate in a clinical trial. To carry out meaningful clinical trials in the future, that number must increase. This will be most important for treatments that target relatively rare mutations; a large number of potential volunteers will have to be screened to identify a sufficient number who harbor the relevant target. To succeed, we must partner with a much larger fraction of cancer patients.

Designing and executing future cancer clinical trials will not be easy, but physician-scientists are armed with a fast-growing body of omics-informed knowledge with which to surmount these hurdles. 

Tomasz M. Beer is deputy director of the Knight Cancer Institute and a professor of medicine at Oregon Health & Science University in Portland. He is the coauthor of Cancer Clinical Trials: A Commonsense Guide to Experimental Cancer Therapies and Clinical Trials. Written for people living with cancer, the book is accompanied by a blog ( that seeks to disseminate knowledge about clinical trials.

Friday, June 21, 2013

NeuroTalk Support Groups - Psych Central

A place for people to find support for neurological and brain disorders.

Networking Medicine | The Scientist Magazine

Although fully organized patient-run trials are still few and far between, patients are taking a more active role in clinical research. Now, more than ever before, patients have access to scientific knowledge as it's reported, and advocate communities are flourishing, thanks to the wide-ranging, faster, and more accurate communication provided by the Internet. This increasing patient activism, and an accompanying willingness to share personal stories, has resulted in a veritable deluge of patient data.

"When you have gigabytes of data, perhaps hundreds of gigabytes, for each patient, that's more data than has existed in all clinical trials combined up until a couple of years ago," says Marty Tenenbaum, who in 2010 founded Cancer Commons, a database that collates real-time patient data and up-to-the-moment basic medical research to inform cancer treatment.

The online networking site PatientsLikeMe, for example, has accumulated more than 175,000 users who are recording information about hundreds of diseases, treatments, and outcomes. Of the 200,000 customers of direct-to-consumer genetics company 23andMe, some 85 percent have contributed their genomic and phenotypic information to research—totaling more than 80 million phenotypic data points for more than 60 conditions. And the Personal Genome Project, launched by Harvard Medical School's George Church in 2006, has accumulated about 200 full genomes and 400 partial sequences, with some 1,500 additional volunteers who have already made trait data available online and are willing to share their whole genomes.

But the availability of such data is only one side of the coin. Without expert analysis, patient-generated data would be useless to the drug development community. Fortunately, initiatives and companies are cropping up left and right to support and take advantage of this movement.

Among the benefits of such stockpiles of data is the ability to sift through the challenging heterogeneity of patients, their diseases, and their case information. "Clinical trials, especially as they've been traditionally constituted—large randomized trials—just are a disaster in cancer, because of the nature of the disease," says Tenenbaum. "Every tumor is unique at some level." Databases that collate genetic data, such as patient genomes or the genomes of their tumors, could facilitate the identification of biomarkers to help differentiate responders and nonresponders, speeding a drug's path to the clinic. "It could literally slash years, if not decades, off the normal process," Tenenbaum says.

Platforms that support patient input can also help researchers develop better benchmarks for assessing disease progression and more accurate measures of patient health, as well as point to novel indications for existing drugs and promising drug combinations. "We're enabling a new partnership between the patients and the physicians," says Jamie Heywood, cofounder and chairman of PatientsLikeMe, "and that new partnership should produce outcomes at lower costs with lower risks and better innovation."

Do-It-Yourself Medicine | The Scientist Magazine

On August 10, 2011, Joan Valor Butler diluted a solution of 5 percent sodium chlorite in 1 gallon of slightly salted water, and slowly injected 1 liter of the mixture into her 42-year-old son's feeding tube, at his request. Sodium chlorite is a chemical commonly used in low concentrations in camping water-purification kits and for municipal water treatment. Many also believed it to be the active ingredient of a promising drug in clinical trials for amyotrophic lateral sclerosis (ALS)—a disease Eric Valor has lived with for the better part of the past decade.

As the disease gradually paralyzed his entire body, Valor became an avid student of ALS, a degenerative disorder commonly known as Lou Gehrig's disease and characterized by a deterioration of motor neurons. He had first learned about the intravenous drug, called NP001, in 2010, when its developer, Neuraltus Pharmaceuticals, announced it would soon be starting a Phase 1 trial and was recruiting ALS patients. Animal toxicology tests had demonstrated the drug's safety, and a small study in an ALS mouse model suggested it may slow disease progression—most likely by reducing macrophage-initiated killing of neurons, a recently proposed mechanism for how ALS wreaks havoc on the body. Valor started a thread on an online ALS patient forum to discuss NP001, and several patients decided to inquire about taking part in the trial. But 7 years removed from diagnosis, Valor's disease was far too advanced for him to qualify as a trial participant.

Though he has outlived the average ALS lifespan of just 2 to 5 years, Valor's muscular paralysis is severe. Within 6 months of his diagnosis, Valor—once an avid surfer and snowboarder—had difficulty walking. He started using a cane, then a walker, then a wheelchair. Eventually the disease confined Valor to his bed, where a ventilator forces air into his lungs 6 to 8 times per minute. By the time NP001 was making a splash in the ALS community, his speech was barely intelligible, and he was unable to move any part of his body except for his eyes and some of the muscles of his face. In his condition, Valor was a risk for any clinical trial testing a treatment expected to slow progression: for the drug to show a noticeable effect, he would actually have to start getting better, rather than simply stop getting worse—something no drug had ever done for ALS patients.

So Valor looked into treating himself at home, scouring the Web through a computer linked to an infrared camera that tracks the movement of his right eye. (See photographs below.) Dozens of other patients who couldn't get into the trial also searched for another way to try the experimental drug. On the basis of a literature search, a Phase 1 trial consent form, and a patent owned by Neuraltus cofounder Michael McGrath, the patients believed NP001 to be a formulation of sodium chlorite. Some purchased NP001's precursor, WF10, which was known to contain just over 50 percent sodium chlorite and could be ordered from Thailand, where it was approved for treating the autoimmune consequences of cancer radiation. But for many, the cost of $12,000 for a year's supply was prohibitive. Sodium chlorite, on the other hand, could be purchased from online suppliers for just $50 per quart—15 years' worth at the dosage outlined in the patients' documented protocol.

There's a new model of medicine in my opinion. You see these DIY programs where patients are deciding, after doing an Internet search, that this is what they want to do; they go get the medicine; they take it; and they log their own output measures.
—­ Richard Bedlack,
Duke University ALS Clinic

Self-dosing patients went to great pains to ensure that what they were doing was safe. Because WF10 was already approved in Thailand, they knew that at least one form of chlorite had completed safety testing to satisfy that country's regulatory authorities. Patients reached out to the drugs' inventors, and spoke to their doctors and each other about the risks and the proper dosing. Even test engineer Tom Poast, who does not have ALS, chimed in on the patient forum with insights on the purity of chlorite solutions available for purchase, dilution and mixing, and the chemical's behavior. More than 1 year and 1,000 forum posts later, some two dozen ALS patients decided ingesting sodium chlorite was worth a shot.

While the ALS community has taken do-it-yourself (DIY) medicine further than most, patients across the board are starting to play a noticeably bigger role in their own care. "There's a new model of medicine in my opinion," says neurologist and clinical researcher Richard Bedlack, director of the Duke University ALS Clinic. "Once upon a time we had a very paternalistic system, where patients would come, and they would have a set of symptoms, and doctors would ask all the questions and give all the answers. And in the past decade things have really shifted almost to the other side, where a lot of medicine is autonomous now. You see these DIY programs where patients are deciding, after doing an Internet search, that this is what they want to do; they go get the medicine; they take it; and they log their own output measures."

And although Bedlack has concerns about the safety and effectiveness of patient-driven trials, he argues that patients' greater involvement is a good thing—both for managing their own health and for deciding the course of drug development. "I don't think anybody has more to gain or lose from all this than patients," he says. "So I think they should be driving the agenda."

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I Have Cancer, But Don’t Call Me Brave - One Eyed Dog

There is a special lexicon reserved for people with cancer: we talk of survivors and journeys. The verbs we use tend to be martial: we "fight" or we "battle" cancer. This vocabulary of struggle is partly a response, cells on the march, its positions firmly entrenched in our organs, its stealth troops quietly setting up distant outposts in our bodies.

As part of this lexicon, cancer patients are almost universally thought of as brave. It is rare to see a headline about someone's death from cancer that doesn't describe the deceased as brave. "Swinton Man Loses Brave Cancer Battle." Since my diagnosis many people have said they have admired my courage — and I thank them for that, as it's certainly better than being regarded a spineless, simpering worm — but it always leaves me thinking: How exactly am I being brave?

People have told me that if it were them, they would be curled up in a ball, locked inside a dark room, not wanting to be around people. They wouldn't be on Facebook, or blogging about cancer, and certainly wouldn't be making jokes. They imagine a kind of mental shutdown, a recoiling of mind and body, where they essentially place themselves in quarantine.

With this notion of how they think they'd respond to having cancer, just living a normal-enough life is seen as being brave: going to work, looking after the kids, climbing mountains, running marathons. But ask any one of those people with cancer if they would regard themselves as brave and most likely they'd tell you, no, absolutely not. The default response to cancer, from the patients I have met in real life and online, is normally one of resilience: a very practical sense of just getting on with it and making the best of things.

Courage is often defined as being afraid of something but carrying on regardless, like jumping out of an airplane, or charging a Taliban position to save your stricken comrades. The key difference is that such displays of courage come with a choice and those choices have consequences. We weigh the consequences, do the calculus, and make the decision. But for most people with cancer, there is little choice. I am sick and I will take the treatment to try to get better. It is no different to any other illness, no more gallant than undergoing surgery for heart disease. My treatment is a life raft extended in a storm and there is nothing remotely brave about clinging on for dear life.

Brave (or perhaps stupid) would be looking my cancer in the face and saying, "I'm confident I can beat this on my own. I'm going to the pub." Or brave might be refusing life-saving surgery and chemotherapy, well aware of the grave consequences, because it is against deeply held moral or religious convictions. Brave would be choosing to meditate my cancer away so confident I would be in the curative power of energy pathways.

People have also said I'm brave for talking so openly about my cancer, but in a world overrun with cancer memoirs, cancer blogs, survivors' forums, I'm not exactly breaking any sacred ground here. It is not 1910 and we are not shunting off cancer patients to windswept sanatoriums to die in a veil of silence. Nor do I have AIDS in early 1980s San Francisco, where prejudice, ignorance, and fear prevented people from talking openly about their conditions. And anyone who knows me knows I am something of an attention whore. I wrote a book about my feelings surrounding my father's death, so I don't exactly need much encouragement to share my inner-most feelings with a bunch of strangers. For me, having cancer and not writing about it would be truly courageous.

There was a piece recently in USA Today about Angelina Jolie's decision to have a double mastectomy and go public about it. It was a sneery, uncharitable piece, written by someone with breast cancer, but it raised the question of courage.

To paraphrase, the author was basically saying that Jolie isn't the brave one, the head-scarfed women battling metastatic breast cancer are the brave ones, fighting their terminal cancer with a dignified silence. That's brave, not Jolie, with her looks, her publicists, and her army of stylists.

I suppose, being charitable to the author, I could see what she was trying to say and I certainly agree with her on the inevitability and laziness with which journalists use the "brave" word, but what was distasteful about the piece was her setting herself up as a judge of other people's courage.

Going for an operation, let alone having a double mastectomy, is a frightening prospect for anyone. (I wept like a baby just before having my anesthetic for my resection. No stiff upper lip here.) Even if your chances are good, just having cancerous cells at large in your body with even the slimmest possibility of recurrence is a scary business. Cancer is not a competition of who suffers the most. I wouldn't necessarily label Jolie as particularly "brave" for taking a sensible decision about her health as I just think that word is inadequate and unhelpful, but I certainly wouldn't want to diminish what she went through by comparing her to others in trickier situations. There is no leader-board for courage.

So while I don't think Jolie is particularly brave, nor do I think it is the best way to describe those women on the cancer ward. I bet they wouldn't think of themselves as brave either and reducing their complex feelings and emotions to that easy catch-all "brave" is the kind of reductivism the author seems to dislike. People with more advanced cancers, with poorer prognoses, are just getting on with it because they have no choice, facing their own expiry date as people have always done, with faith, humor, fear, solace, sadness. They might regard themselves as fucked, unlucky, pissed off, sad … but brave, I'm not so sure.

So "brave," while well meant and certainly not offensive, just doesn't seem quite right to me. Ultimately, it is just semantics. Having cancer and being described as "brave" is just a linguistic tic, where a default terminology becomes so pervasive that we just use it without really thinking.

It is part of a lexicon that likes to give people with cancer almost super-hero-like powers, great warriors doing battle against an evil disease. It isn't a lexicon that allows much humility in front of a rapacious enemy. Whenever I hear those martial verbs, or hear people being described as brave, I feel a little sorry for people with heart disease or Alzheimer's, who, rather than warriors, tend to be portrayed as passive, voiceless victims, who never get to "fight" their illnesses but only ever "succumb."

Wednesday, June 19, 2013

Nearly 7 in 10 Americans Are On Prescription Drugs - Newswise

Nearly 70 percent of Americans are on at least one prescription drug, and more than half take two, Mayo Clinic researchers say. Antibiotics, antidepressants and painkilling opioids are most commonly prescribed, their study found. Twenty percent of patients are on five or more prescription medications, according to the findings, published online in the journal Mayo Clinic Proceedings.

Researchers find the data valuable because it gives insight into prescribing practices. The statistics from the Rochester Epidemiology Project in Olmsted County, Minn. are comparable to those elsewhere in the United States, says study author Jennifer St. Sauver, Ph.D., a member of the Mayo Clinic Population Health Program in the Mayo Clinic Center for the Science of Health Care Delivery.

"Often when people talk about health conditions they're talking about chronic conditions such as heart disease or diabetes," Dr. St. Sauver says. "However, the second most common prescription was for antidepressants -- that suggests mental health is a huge issue and is something we should focus on. And the third most common drugs were opioids, which is a bit concerning considering their addicting nature."
Seventeen percent of those studied were prescribed antibiotics, 13 percent were taking antidepressants and 13 percent were on opioids. Drugs to control high blood pressure came in fourth (11 percent) and vaccines were fifth (11 percent). Drugs were prescribed to both men and women across all age groups, except high blood pressure drugs, which were seldom used before age 30.

Overall, women and older adults receive more prescriptions. Vaccines, antibiotics and anti-asthma drugs are most commonly prescribed in people younger than 19. Antidepressants and opioids are most common among young and middle-aged adults. Cardiovascular drugs are most commonly prescribed in older adults. Women receive more prescriptions than men across several drug groups, especially antidepressants: Nearly 1 in 4 women ages 50-64 are on an antidepressant.

For several drug groups, use increases with advancing age.

"As you get older you tend to get more prescriptions, and women tend to get more prescriptions than men," Dr. St. Sauver says.

Prescription drug use has increased steadily in the U.S. for the past decade. The percentage of people who took at least one prescription drug in the past month increased from 44 percent in 1999-2000 to 48 percent in 2007-08. Spending on prescription drugs reached $250 billion in 2009 the year studied, and accounted for 12 percent of total personal health care expenditures. Drug-related spending is expected to continue to grow in the coming years, the researchers say.

In ‘What Doctors Feel,’ Pain Is Not Just the Realm of Patients -

In her new book, "What Doctors Feel," Dr. Danielle Ofri tells the unforgettable story of a pediatrician she interviewed, a woman she calls Eva.

In taut, vivid prose, Dr. Ofri describes a tragic event that occurred during Eva's residency. She helped deliver a baby doomed to asphyxiation within minutes of birth because of a severe lack of amniotic fluid in the womb.

The traumatized parents knew the outcome in advance, and made it clear they did not want to see the baby. After the delivery, the room leaden with silence, Eva wrapped the baby in a blanket and wondered where to go. The hospital had no room set aside for this. So the young physician, consumed with sadness for a child who would never be held by anyone but her, took the dying newborn into a supply closet.

There, knowing she would be reprimanded for not observing the precise moment at which the umbilical cord ceased pulsing, she gathered the baby in her arms. "In the cramped space Eva rocked back and forth," Dr. Ofri writes. " 'I love you, baby,' she whispered as the heart began its slow, cratering descent."

In the hands of a less agile and intelligent writer, such a scene could easily grow maudlin. Indeed, calling attention to a physician's emotional pain might be seen as distracting and self-indulgent. It is, after all, the physician's role to ease the suffering of others.

Yet as Dr. Ofri points out, how doctors feel matters. And while she does write of joy, pride and gratitude, her emphasis is on negative emotions — which exert the strongest influence on medical care, particularly when a case grows unexpectedly complicated, frustrating or unyielding. "This is where factors other than clinical competency come into play," she writes. An unwell doctor is a bad doctor.

Dr. Ofri is an internist at Bellevue Hospital Center in New York City, which cares for legions of indigent, uninsured patients, as well as a large population of immigrants. The author of three previous books and a frequent contributor to The New York Times, she writes for a lay audience with a practiced hand.

This book's hallmark is her honesty, particularly when it comes to the emotional fallout of her medical mistakes. When she dismisses a patient's litany of vague symptoms as stress-related, only to miss a blood clot in each lung, she is overwhelmed by shame and remorse.

She is also frank about her prejudices, particularly toward the worried well. Early in her career, during a summer job at a tony practice on Long Island, Dr. Ofri refused a woman's request for weight-loss pills. "After three years of round-the-clock AIDScancercongestive heart failure and cirrhosis, it was hard to get worked up over a couple of middle-aged pounds," she writes.

But later she rethinks her reaction. "I wasn't able to step past my own issues," she writes. "Maybe underneath the seemingly superficial concerns were serious issues that were crying out for attention."

Then there is the constant thrum of death: Eva and the dying newborn; a young patient under Dr. Ofri's care with heart disease whose stormy course appears to end with a successful heart transplant, only to be followed by a fatal stroke.

It does make one wonder how doctors cope. A study of oncologists cited by Dr. Ofri found that these specialists learned to compartmentalize their grief. Yet the most striking finding of the study was how poorly that strategy worked. Grief spilled into the physicians' daily lives and sapped them of their inner strength.

After the newborn's death, Eva walled herself off from all emotions, only to have them return many months later with full-blown post-traumatic stress disorder.

Bitterness is here, too. Dr. Ofri devotes much of one chapter to malpractice lawsuits. She describes her own harrowing experiences of being sued — in one instance, by the family of a woman she had not just grown close to, but gone well out of her way to care for. "Dealing with a lawsuit is often likened to having a death in the family," she writes. "Doctors end up (often unconsciously) grieving for the doctors they used to be."

Counterintuitively, perhaps, Dr. Ofri is at her most compelling when telling other physicians' stories. It's almost as if she still needs to keep a slight cool distance from her own experiences. But this is not necessarily a sign of weak writing. It is an indication of just how raw the inner life of a doctor can be.

A.M.A. Recognizes Obesity as a Disease -

The American Medical Association has officially recognized obesity as a disease, a move that could induce physicians to pay more attention to the condition and spur more insurers to pay for treatments.

In making the decision, delegates at the association's annual meeting in Chicago overrode a recommendation against doing so by a committee that had studied the matter.

"Recognizing obesity as a disease will help change the way the medical community tackles this complex issue that affects approximately one in three Americans," Dr. Patrice Harris, a member of the association's board, said in a statement. She suggested the new definition would help in the fight against Type 2 diabetes and heart disease, which are linked to obesity.

To some extent, the question of whether obesity is a disease or not is a semantic one, since there is not even a universally agreed upon definition of what constitutes a disease. And the A.M.A.'s decision has no legal authority.

Still, some doctors and obesity advocates said that having the nation's largest physician group make the declaration would focus more attention on obesity. And it could help improve reimbursement for obesity drugs, surgery and counseling.

"I think you will probably see from this physicians taking obesity more seriously, counseling their patients about it," said Morgan Downey, an advocate for obese people and publisher of the online Downey Obesity Report. "Companies marketing the products will be able to take this to physicians and point to it and say, 'Look, the mother ship has now recognized obesity as a disease.' "

Two new obesity drugs — Qsymia from Vivus, and Belviq from Arena Pharmaceuticals and Eisai — have entered the market in the last year.

Qsymia has not sold well for a variety of reasons, including poor reimbursement and distribution restrictions imposed because of concerns that the drug can cause birth defects. Those restrictions are now being relaxed. Belviq went on sale only about a week ago, so it is too early to tell how it is doing.

Whether obesity should be called a disease has long been debated. The Obesity Society officially issued its support for classifying obesity as a disease in 2008, with Mr. Downey as one of the authors of the paper.

The Internal Revenue Service has said that obesity treatments can qualify for tax deductions. In 2004, Medicare removed language from its coverage manual saying obesity was not a disease.

Still, Medicare Part D, the prescription drug benefit, includes weight loss drugs among those it will not pay for, along with drugs for hair growth and erectile dysfunction.

The vote of the A.M.A. House of Delegates went against the conclusions of the association's Council on Science and Public Health, which had studied the issue over the last year. The council said that obesity should not be considered a disease mainly because the measure usually used to define obesity, the body mass index, is simplistic and flawed.

Some people with a B.M.I. above the level that usually defines obesity are perfectly healthy while others below it can have dangerous levels of body fat and metabolic problems associated with obesity.

"Given the existing limitations of B.M.I. to diagnose obesity in clinical practice, it is unclear that recognizing obesity as a disease, as opposed to a 'condition' or 'disorder,' will result in improved health outcomes," the council wrote.

The council summarized the arguments for and against calling obesity a disease.

One reason in favor, it said, was that it would reduce the stigma of obesity that stems from the widespread perception that it is simply the result of eating too much or exercising too little. Some doctors say that people do not have full control over their weight.

Supporters of the disease classification also say it fits some medical criteria of a disease, such as impairing body function.

Those arguing against it say that there are no specific symptoms associated with it and that it is more a risk factor for other conditions than a disease in its own right.

They also say that "medicalizing" obesity by declaring it a disease would define one-third of Americans as being ill and could lead to more reliance on costly drugs and surgery rather than lifestyle changes. Some people might be overtreated because their B.M.I. was above a line designating them as having a disease, even though they were healthy.

The delegates rejected the conclusion of the council and voted instead in favor of a resolution pushed by the American Association of Clinical Endocrinologists, the American College of Cardiology and some other organizations.

This resolution argued that obesity was a "multimetabolic and hormonal disease state" that leads to unfavorable outcomes like Type 2 diabetes and cardiovascular disease.

"The suggestion that obesity is not a disease but rather a consequence of a chosen lifestyle exemplified by overeating and/or inactivity is equivalent to suggesting that lung cancer is not a disease because it was brought about by individual choice to smoke cigarettes," the resolution said.

Monday, June 17, 2013

Death Be Not Decaffeinated: Over Cup, Groups Face Taboo -

Socrates did not fear death; he calmly drank the hemlock. Kierkegaard was obsessed with death, which made him a bit gloomy. As for Lorraine Tosiello, a 58-year-old internist in Bradley Beach, N.J., it is the process of dying that seems endlessly puzzling.

"I'm more interested, philosophically, in what is death? What is that transition?" Dr. Tosiello said at a recent meeting in a Manhattan coffee shop, where eight people had shown up on a Wednesday night to discuss questions that philosophers have grappled with for ages.

The group, which meets monthly, is called a Death Cafe, one of many such gatherings that have sprung up in nearly 40 cities around the country in the last year. Offshoots of the "café mortel" movement that emerged in Switzerland and France about 10 years ago, these are not grief support groups or end-of-life planning sessions, but rather casual forums for people who want to bat around philosophical thoughts. What is death like? Why do we fear it? How do our views of death inform the way we live?

"Death and grief are topics avoided at all costs in our society," said Audrey Pellicano, 60, who hosts the New York Death Cafe, which will hold its fifth meeting on Wednesday. "If we talk about them, maybe we won't fear them as much."

Part dorm room chat session, part group therapy, Death Cafes are styled as intellectual salons, but in practice they tend to wind up being something slightly different — call it cafe society in the age of the meetup. Each is led by a volunteer facilitator, often someone who has a professional tie to the topic (Ms. Pellicano, for instance, is a grief counselor). The participants include people of all ages, working and retired, who are drawn by Facebook announcements, storefront fliers, local calendar listings or word of mouth. Women usually outnumber men.

"In Europe, there's a tradition of meeting in informal ways to discuss ideas — the café philosophique, the café scientifique," said Jon Underwood, 40, a Web designer in London who said he held the first Death Cafe in his basement in 2011 and has propagated the concept through a Web site he maintains.

Mr. Underwood adapted the idea from a Swiss sociologist, Bernard Crettaz, who had organized "café mortels" to try to foster more open discussions of death. "There's a growing recognition that the way we've outsourced death to the medical profession and to funeral directors hasn't done us any favors," Mr. Underwood said. He envisioned Death Cafe as "a space where people can discuss death and find meaning and reflect on what's important and ask profound questions."

In practice, people's motives for attending vary, as does the depth of the conversation. Dr. Tosiello, who said she had never lost a close family member, was there for intellectual enjoyment. Others went to ponder the questions and feelings that the death of a loved one had raised.

For instance, at a Death Cafe meeting this month in St. Joseph, Mo., the host, Megan Mooney, a 29-year-old social worker, asked each of the 19 participants to supply a single word that he or she associated with death. "Freedom," someone said. "Grief." "Transition." "Relief." "Finality." And then, "Graduation."

The last came from Kelly Vanderpool, a 25-year-old mother, who was a high school freshman when a friend with a new driver's license died in an auto accident. "Ever since, I've wanted to know where he was," she said in an interview. "Is it true that life continues? Is Joe around still?"

Jeneva Stoffels, who is 69 and drove 70 miles from Auburn, Neb., to attend the meeting, told Ms. Vanderpool that she did not have an answer. But she did know that her late mother once spoke to her in a dream. "A younger version, glowing and happy, an 'I'm in a good place so you can let go' kind of thing," Ms. Stoffels said in an interview. "Regardless of where it came from, it was reassuring."

Ms. Mooney, the host, asked a series of conversation-starting questions: What is your biggest fear about death? What do you want your legacy to be? She had brought markers and blank boards on which people could finish the sentence "Before I Die I Want to … ." The responses included "See Egypt," "Win the lottery," "Write a book of poems" and "See my daughter grow up."

Over all, Ms. Mooney said, "There are some somber moments, but people laugh. They have fun."

The meetings tend to be more mundane than macabre, and more likely to produce small epiphanies than profound realizations. "It's not like psychotherapy," Ms. Stoffels said. "There's not going to be a big breakthrough. It just widens the door a crack."

Doctors and scholars who study attitudes toward death say that for most people, such conversations are healthy; talking about death can ease people's fears and the notion that death is taboo. "A major part of American society is very averse to thinking about dying," said David Barnard, a professor of ethics at the Oregon Health and Science University who has written extensively about the end of life.

In the United States, Death Cafes have spread quickly. The first one met last summer in a Panera Bread outside Columbus, Ohio, where guests were served tombstone-shaped cookies. Since then, more than 100 meetings have been held in cities and towns across the country, including Atlanta, Baltimore, Cleveland, Los Angeles and Seattle.

"At one cafe, I had someone who believed in reincarnation sitting across from three atheists, telling them about her past lives," said Lizzy Miles, a hospice social worker who organized that first meeting in Columbus and has led the group there ever since. Discussion topics have included euthanasia, grief, the best-selling book "Proof of Heaven" and do-not-resuscitate orders.

Ms. Miles logged 112 participants in her first nine events and determined that a quarter were under 35 and 22 percent were over 65, with most ages 45 to 64 and women predominating. About half of the people who filled out a survey after a meeting agreed with the statement that "I feel more comfortable talking about death and dying now."

The Death Cafe movement has a few ground rules. Meetings are confidential and not for profit. People must respect one another's disparate beliefs and avoid proselytizing. And tea and cake play an important role.

"There's a superstition that if you talk about death, you invite it closer," said Mr. Underwood, the organizer in London. "But the consumption of food is a life-sustaining process. Cake normalizes things."

Cheating Ourselves of Sleep -

Think you do just fine on five or six hours of shut-eye? Chances are, you are among the many millions who unwittingly shortchange themselves on sleep.
Research shows that most people require seven or eight hours of sleep to function optimally. Failing to get enough sleep night after night can compromise your health and may even shorten your life. From infancy to old age, the effects of inadequate sleep can profoundly affect memory, learning, creativity, productivity and emotional stability, as well as your physical health.
According to sleep specialists at the University of Pittsburgh School of Medicine and Western Psychiatric Institute and Clinic, among others, a number of bodily systems are negatively affected by inadequate sleep: the heart, lungs and kidneys; appetite, metabolism and weight control; immune function and disease resistance; sensitivity to pain; reaction time; mood; and brain function.
Poor sleep is also a risk factor for depression and substance abuse, especially among people with post-traumatic stress disorder, according to Anne Germain, associate professor of psychiatry at the University of Pittsburgh. People with PTSD tend to relive their trauma when they try to sleep, which keeps their brains in a heightened state of alertness.
Dr. Germain is studying what happens in the brains of sleeping veterans with PTSD in hopes of developing more effective treatments for them and for people with lesser degrees of stress that interfere with a good night's sleep.
The elderly are especially vulnerable. Timothy H. Monk, who directs the Human Chronobiology Research Program at Western Psychiatric, heads a five-year federally funded study of circadian rhythms, sleep strength, stress reactivity, brain function and genetics among the elderly. "The circadian signal isn't as strong as people get older," he said.
He is finding that many are helped by standard behavioral treatments for insomnia, like maintaining a regular sleep schedule, avoiding late-in-day naps and caffeine, and reducing distractions from light, noise and pets.
It should come as no surprise that myriad bodily systems can be harmed by chronically shortened nights. "Sleep affects almost every tissue in our bodies," said Dr. Michael J. Twery, a sleep specialist at the National Institutes of Health.
Several studies have linked insufficient sleep to weight gain. Not only do night owls with shortchanged sleep have more time to eat, drink and snack, but levels of the hormone leptin, which tells the brain enough food has been consumed, are lower in the sleep-deprived while levels of ghrelin, which stimulates appetite, are higher.
In addition, metabolism slows when one's circadian rhythm and sleep are disrupted; if not counteracted by increased exercise or reduced caloric intake, this slowdown could add up to 10 extra pounds in a year.
The body's ability to process glucose is also adversely affected, which may ultimately result in Type 2 diabetes. In one study, healthy young men prevented from sleeping more than four hours a night for six nights in a row ended up with insulin and blood sugar levels like those of people deemed prediabetic. The risks of cardiovascular diseases and stroke are higher in people who sleep less than six hours a night. Even a single night of inadequate sleep can cause daylong elevations in blood pressure in people with hypertension. Inadequate sleep is also associated with calcification of coronary arteries and raised levels of inflammatory factors linked to heart disease. (In terms of cardiovascular disease, sleeping too much may also be risky. Higher rates of heart disease have been found among women who sleep more than nine hours nightly.)
The risk of cancer may also be elevated in people who fail to get enough sleep. A Japanese study of nearly 24,000 women ages 40 to 79 found that those who slept less than six hours a night were more likely to develop breast cancer than women who slept longer. The increased risk may result from diminished secretion of the sleep hormone melatonin. Among participants in the Nurses Health Study, Eva S. Schernhammer of Harvard Medical School found a link between low melatonin levels and an increased risk of breast cancer.
A study of 1,240 people by researchers at Case Western Reserve University in Cleveland found an increased risk of potentially cancerous colorectal polyps in those who slept fewer than six hours nightly.
Children can also experience hormonal disruptions from inadequate sleep. Growth hormone is released during deep sleep; it not only stimulates growth in children, but also boosts muscle mass and repairs damaged cells and tissues in both children and adults.
Dr. Vatsal G. Thakkar, a psychiatrist affiliated with New York University, recently described evidence associating inadequate sleep with an erroneous diagnosis of attention deficit hyperactivity disorder in children. In one study, 28 percent of children with sleep problems had symptoms of the disorder, but not the disorder.
During sleep, the body produces cytokines, cellular hormones that help fight infections. Thus, short sleepers may be more susceptible to everyday infections like colds and flu. In a study of 153 healthy men and women, Sheldon Cohen and colleagues at Carnegie Mellon University found that those who slept less than seven hours a night were three times as likely to develop cold symptomswhen exposed to a cold-causing virus than were people who slept eight or more hours.
Some of the most insidious effects of too little sleep involve mental processes like learning, memory, judgment and problem-solving. During sleep, new learning and memory pathways become encoded in the brain, and adequate sleep is necessary for those pathways to work optimally. People who are well rested are better able to learn a task and more likely to remember what they learned. The cognitive decline that so often accompanies aging may in part result from chronically poor sleep.
With insufficient sleep, thinking slows, it is harder to focus and pay attention, and people are more likely to make poor decisions and take undue risks. As you might guess, these effects can be disastrous when operating a motor vehicle or dangerous machine.
In driving tests, sleep-deprived people perform as if drunk, and no amount of caffeine or cold air can negate the ill effects.
At your next health checkup, tell your doctor how long and how well you sleep. Be honest: Sleep duration and quality can be as important to your health as your blood pressure and cholesterol level.