Saturday, January 1, 2011

Students are the perfect medical guinea pigs – I should know |-

I've done a lot of medical and psychophysiological experiments on both sides – as a subject and as a experimenter. When I first went to Germany as a foreign student, it was without any financial support, so being paid to take part in experiments often formed a large chunk of my income.

I can't say I have taken part in anything quite as interesting as the ketamine experiment mentioned in Comment is free's recent open thread, but some have been hair-raising. I once had to stay on a hospital bed for 10 hours with three IVs in my right arm and two IVs in my left, one of which was used to take regular blood samples. The experiment involved taking a chemical that suppressed some liver functions, and left me showing mild diabetic symptoms for a week afterwards – this annoyed me greatly as I thought the experiment had paid very little for rather a lot of discomfort.

The best and easiest experiments were psychophysiological ones, as I was paid quite a bit for just 90 minutes' attendance. One involved lying on a comfortable recliner chair in a soundproofed room, in which I had to concentrate on not falling asleep. If I did, the researchers would yell through an intercom; they could easily see when a subject was drifting away by the constant EEG recording. That experiment had only one drawback, which was the sounding of single short and very loud noises at random times. The test was about shock reactions and, yes, a nasty and savagely loud noise heard at random can be very shocking indeed.

Once I had got much further in university, myself and others started running experiments ourselves. A friend of mine ran psychological experiments measuring emotional reactions: for the pleasant condition, he used holiday snaps he had taken himself, and for the shock condition, he used a set of slides he had got from the local police – photographs of murder victims and scenes in that city. There is a real immediacy about photos of genuine murder scenes that leaves Hollywood in the shade and is electrifyingly unpleasant.

Murder is sometimes part of the picture, too. Apart from the infamous Tuskegee syphilis study (an observational study of the long-term course of untreated syphilis), there was also the abhorrent experiments run by US doctors in Guatemala in the 1940s, where subjects were deliberately infected with syphilis without consent. In the same vein, novelist John le Carré wrote a thriller, The Constant Gardener, based on rumours of underhand pharmaceutical experimentation in Africa. And of course, everyone also knows about the Nazi and Japanese medical experiments run on prisoners during the second world war period, and the Soviet Union experiments in alleged "psychiatry" run on captive political dissidents. Clinical trial can also unexpectedly develop into lethality: back in 2006 six volunteers for a medical trial in London became life-threateningly ill.

Should such experimentation be carried out on humans? At some stage it must be, because computer and animal models are simply not enough for final testing of drugs designed for humans. We are always experimenting on ourselves: possibly the largest group of self-experimenters are those who are chronically ill or suffer from chronic pain, most of whom are only too willing to try out something new (in private, non-scientific ways) to see if it can alleviate their suffering.

Should volunteers be paid for taking part in such experiments, thereby encouraging what may be seen as vulnerable segments of the population to undertake risk? Not paying volunteers would be the far worse option; it's difficult enough to get volunteers without refusing them recompense for their time, discomfort and risk.

While medical researchers often experiment on themselves too, for true results you need quite large groups of subjects. I believe that university students being the favoured group for such processes is a lot better than using villagers in Africa: the students are western consumers who benefit most from new pharmaceuticals, and it seems fair that they should be the experimental test rabbits – plus the income is often of great help to them. They are also the ones most able to complain loudly and get proper treatment and compensation should anything go wrong. And, well, it gives them something to talk about at parties.

All in all, it's most often a win-win solution – except when things go horribly wrong.

Real Life Among the Old Old -

I ewcently turned 65, just ahead of the millions in the baby boom generation who will begin to cross the same symbolically fraught threshold in the new year to a chorus of well-intended assurances that "age is just a number." But my family album tells a different story. I am descended from a long line of women who lived into their 90s, and their last years suggest that my generation's vision of an ageless old age bears about as much resemblance to real old age as our earlier idealization of painless childbirth without drugs did to real labor.

In the album is a snapshot of my mother and me, smiling in front of the Rockefeller Center Christmas tree when she was 75 and I was 50. She did seem ageless just 15 years ago. But now, as she prepares to turn 90 next week, she knows there will be no more holiday adventures in her future. Her mind is as acute as ever, but her body has failed. Chronic pain from a variety of age-related illnesses has turned the smallest errand into an excruciating effort.

On the next page is a photograph of my maternal grandmother and me, taken on a riverbank in 1998, a few months short of her 100th birthday. For one sunny afternoon, I had spirited her away from the nursing home where she spent the last three years of her life, largely confined to a wheelchair, with a bright mind — like my mother's today — trapped in a body that would no longer do her bidding.

"It's good to be among the living again," Gran said, in a tone conveying not self-pity but her own realistic assessment that she had lived too long to live well.

Yet people my age and younger still pretend that old age will yield to what has long been our generational credo — that we can transform ourselves endlessly, even undo reality, if only we live right. "Age-defying" is a modifier that figures prominently in advertisements for everything from vitamins and beauty products to services for the most frail among the "old old," as demographers classify those over 85. You haven't experienced cognitive dissonance until you receive a brochure encouraging you to spend thousands of dollars a year for long-term care insurance as you prepare to "defy" old age.

"Deny" is the word the hucksters of longevity should be using. Nearly half of the old old — the fastest-growing segment of the over-65 population — will spend some time in a nursing home before they die, as a result of mental or physical disability.

Members of the "forever young" generation — who, unless a social catastrophe intervenes, will live even longer than their parents — prefer to think about aging as a controllable experience. Researchers who were part of a panel discussion titled "90 Is the New 50," presented at the World Science Festival in 2008, spoke to a middle-aged, standing-room-only audience about imminent medical miracles. The one voice of caution about inflated expectations was that of Robert Butler, the pioneering gerontologist who was the first head of the National Institute on Aging in the 1970s and is generally credited with coining the term "ageism."

Earlier this year, a few months before his death from leukemia at age 83, I asked Dr. Butler what he thought of the premise that 90 might become the new 50. "I'm a scientist," he replied, "and a scientist always hopes for the big breakthrough. The trouble with expecting 90 to become the new 50 is it can stop rational discussion — on a societal as well as individual level — about how to make 90 a better 90. This fantasy is a lot like waiting for Prince Charming, in that it doesn't distinguish between hope and reasonable expectation."

The crucial nature of this distinction has become foremost in my thinking about what lies ahead.

My hope is that I will not live as long as my mother and grandmother. We all want to be the exceptions: Elliott Carter, an active composer when he walked onto the stage of Carnegie Hall for his centennial tribute in 2008; Betty White, a bravura comedian who wows audiences at 88; John Paul Stevens, the author of brilliant judicial opinions until the day he retired from the Supreme Court at 90. I, too, hope to go on being productive, writing long after the age when most people retire, in the twilight of the print culture that has nourished my life. Yet it is sobering for me — as it is for Americans in many businesses and professions that once seemed a sure thing — to see younger near contemporaries being downsized out of jobs long before they are emotionally or financially ready for retirement.

Furthermore, I am acutely aware — and this is the difference between hope and expectation — that my plans depend, above all, on whether I am lucky enough to retain a working brain. I haven't mentioned, because I don't like to think about it, that my paternal grandmother, who also lived into her 90s, died of Alzheimer's disease. The risk of dementia, of which Alzheimer's is the leading cause, doubles every five years after 65.

Contrary to what the baby boom generation prefers to believe, there is almost no scientifically reliable evidence that "living right" — whether that means exercising, eating a nutritious diet or continuing to work hard — significantly delays or prevents Alzheimer's. This was the undeniable and undefiable conclusion in April of a major scientific review sponsored by the National Institutes of Health.

Good health habits and strenuous intellectual effort are beneficial in themselves, but they will not protect us from a silent, genetically influenced disaster that might already be unfolding in our brains. I do not have the slightest interest in those new brain scans or spinal fluid tests that can identify early-stage Alzheimer's. What is the point of knowing that you're doomed if there is no effective treatment or cure? As for imminent medical miracles, the most realistic hope is that any breakthrough will benefit the children or grandchildren of my generation, not me.

I would rather share the fate of my maternal forebears — old old age with an intact mind in a ravaged body — than the fate of my other grandmother. But the cosmos is indifferent to my preferences, and it is chilling to think about becoming helpless in a society that affords only the most minimal support for those who can no longer care for themselves. So I must plan, as best I can, for the unthinkable.

I have no children — a much more common phenomenon among boomers than among old people today. The man who was the love of my adult life died several years ago; now I must find someone else I trust to make medical decisions for me if I cannot make them myself. This is a difficult emotional task, and it does not surprise me, for all of the public debate about end-of-life care in recent years, that only 30 percent of Americans have living wills. Even fewer have actually appointed a legal representative, known as a health care proxy, to make life-and-death decisions.

I can see that the "90 is the new 50" crowd might object to my thinking more about worst-case scenarios than best-case ones. But if the best-case scenario emerges and I become one of those exceptional "ageless" old people so lauded by the media, I won't have a problem. I can also take it if fate hands me a passionate late-in-life love affair, a financial bonanza or the energy to write more books in the next 25 years than I have in the past 25.

What I expect, though — if I do live as long as the other women in my family — is nothing less than an unremitting struggle, ideally laced with moments of grace. On that day by the riverbank — the last time we saw each other — Gran cast a lingering glance over the water and said, "It's good to know that the beauty of the world will go on without me."

If I can say that, in full knowledge of my rapidly approaching extinction, I will consider my life a success — even though I will have failed, as everyone ultimately does, to defy old age.

Susan Jacoby is the author, most recently, of the forthcoming "Never Say Die: The Myth and Marketing of the New Old Age."

Friday, December 31, 2010

The Daily Nightly - 'Diagnosing dialysis': An investigative report

Why is the government withholding data on clinics that perform dialysis treatments? NBC News teamed with the investigative group ProPublica. Below are links related to the report.
The Dialysis Facility Tracker (
A site is for dialysis patients and others who want to learn about the quality of care at individual dialysis clinics. Among other things, you can learn how often patients treated at a facility have been hospitalized, report certain types of infections or are placed on the transplant list.
National Kidney Foundation

The Doctor vs. the Computer -

Electronic medical records promise efficiency, safety and productivity in the switch from paper to computer. But there are glitches, as a patient of mine recently brought to light.

My patient needs prostate surgery. It is my job, as his internist, to estimate the risks this surgery poses, decide whether he can proceed with the surgery and make recommendations for his medical management before and after the operation.

He is an extremely complicated patient. His hypertension requires three concurrent medications. He's taking pills for diabetes, but he really should be giving himself insulin injections. His kidneys are wending their way toward dialysis. A few years ago he had a reaction to a diabetes medication that caused congestive heart failure. His aortic valve is narrowed — not severely, but enough to keep me on edge.

Estimating my patient's surgical risk and planning for his operative care is not a straightforward process. After our physical exam, I sit down to write a detailed evaluation, because I want the surgeons and anesthesiologists to fully understand the complexity of his situation.

As I type away, I feel like I'm doing the right thing, explicating my clinical reasoning rather than just plugging numbers into a formula. I'm midway into a sentence about kidney function when the computer abruptly halts.

I panic for a moment, fearful that the computer has frozen and that I've lost all my work — something that happens all too frequently. But I soon realize that this is not the case. Instead, I've come up against a word limit.

It turns out that in our electronic medical record system there is a 1,000-character maximum in the "assessment" field. While I've been typing, the character number has been counting backward from 1,000, and now I've hit zero. The computer will not permit me to say anything more about my patient.

I go back and remove excess articles: the, a, an. Then I try to gain a few characters by using abbreviations: DM for diabetes mellitus, CRF for chronic renal failure. Still, I am over the limit.

A new trick dawns on me. Maybe if I cut back on my descriptions of the clinical problems I've already assessed, then I can gain enough characters for his cardiac status and operative assessment.

I nip and tuck my descriptions of his diabetes, his hypertension, his aortic valve stenosis, trying to placate the demands of our nit-picky computer system. Nevertheless, I am still unable to fit a complete assessment into the box.

In desperation, I call the help desk and voice my concerns. "Well, we can't have the doctors rambling on forever," the tech replies.

I want to retort with something snarky, like I hope that his next critical illness clocks in at less than 1,000 characters, but I hold my tongue. Instead I focus on eliminating verbs and prepositions, wondering just how skeletal my text can become.

As I do this, I think about the current push for all doctors to convert to electronic medical records. I don't deny that it is much easier finding information online than running around the hospital hunting for a chart stuck in the dermatology clinic.

But there are huge trade-offs. Nobody, for example, leafs through a chart anymore, strolling back in time to see what has happened to the patient over many years. In the computer, all visits look the same from the outside, so it is impossible to tell which were thorough visits with extensive evaluation and which were only brief visits for medication refills. In practice, most doctors end up opening only the last two or three visits; everything before that is effectively consigned to the electronic dust heap.

Most importantly, the electronic medical record affects how we think. The system encourages fragmented documentation, with different aspects of a patient's condition secreted in unconnected fields, so it's much harder to keep a global synthesis of the patient in mind.

Now I've learned that file-size restrictions will limit the extent and depth of analysis. What will happen to the tradition of thorough clinical reasoning?

I've finally condensed my patient's complicated medical conditions to exactly 1,000 characters. I quickly hit "save" before I lose everything. I wish him good luck on his operation, wondering if his surgeons will have to condense the entire operative report to 1,000 characters as well. What happens if there are complications?

For my next medical evaluation, I think I will use haiku.

Thursday, December 30, 2010

BBC News - Nearly one in five UK citizens 'to survive beyond 100'

The Department for Work and Pensions (DWP) said its figures suggested 10 million people - 17% of the population - would become centenarians.

These are based on Office for National Statistics population projections and life expectancy estimates.

Pensions Minister Steve Webb said the "staggering" figures brought home the need for pension reforms.

"Many millions of us will be spending around a third of our lives or more in retirement in the future," he said, adding that the government was determined to reform the pensions system to make it "sustainable for the long term".

The DWP estimates there will be at least 507,000 people aged 100 or over by 2066, including 7,700 people aged 110 or over - so-called super-centenarians.

Currently 11,800 people in the UK are aged 100 or over and fewer than 100 are over 110.

'New phase'
The government figures suggest that of the more than 10m who will go on to reach 100, 3m are currently aged under 16, 5.5m are aged between 16 and 50, and 1.3m are aged between 51 and 65.

About 875,000 are already aged over 65, it says.

The fear is that longer life spans will put an intolerable pressure on the pensions system and the NHS.

Dr Ros Altman, director general of the Saga Group, said pensions were not the only aspect of older life that needed to considered.

"Saving more and having a good pension is one thing - but there are also opportunities, and should be, for us to keep working longer, but not necessarily full time," she said.

"There is, in my view, a whole new phase of life which has been out there for grabs which still is available to us where we're not working full time. You're not suddenly stopping when you're in your 60s just because you've reached a particular chronological age.

"But you're thinking 'OK, what's my next career going to be?' - which is going to be part-time, let's say three days a week, four or five days a week off. But still earning some money, because at the end of the day, the state pension is not going to give you a decent lifestyle."

Wednesday, December 29, 2010

The Radiation Boom — Stereotactic Radiosurgery Overdoses Harm Patients -

The initial accident report offered few details, except to say that an unidentified hospital had administered radiation overdoses to three patients during identical medical procedures.

It was not until many months later that the full import of what had happened in the hospital last year began to surface in urgent nationwide warnings, which advised doctors to be extra vigilant when using a particular device that delivers high-intensity, pinpoint radiation to vulnerable parts of the body.

Marci Faber was one of the three patients. She had gone to Evanston Hospital in Illinois seeking treatment for pain emanating from a nerve deep inside her head. Today, she is in a nursing home, nearly comatose, unable to speak, eat or walk, leaving her husband to care for their three young daughters.

Two other patients were overdosed before the hospital realized that the device, a linear accelerator, had inexplicably allowed radiation to spill outside a heavy metal cone attachment that was supposed to channel the beam to a specific spot in the brain. One month later, the same accident happened at another hospital.

The treatment Ms. Faber received, stereotactic radiosurgery, or SRS, is one of the fastest-growing radiation therapies, a technological innovation designed to target tiny tumors and other anomalies affecting the brain or spinal cord, while minimizing damage to surrounding tissue.

Because the radiation is so concentrated and intense, accuracy is especially important. Yet, according to records and interviews, the SRS unit at Evanston lacked certain safety features, including those that might have prevented radiation from leaking outside the cone.

The mistakes in Evanston involve linear accelerators — commonly used for standard radiation therapy — that were redesigned by the manufacturer, Varian Medical Systems, so they could also perform SRS. As the devices became more versatile and complex, problems arose when vital electronic components could not communicate with one another.

In the last five years, SRS systems made by Varian and its frequent German partner, Brainlab, have figured in scores of errors and overdoses, The New York Times has found. Some mistakes were caused by operator error. In Missouri, for example, 76 patients were overradiated because a medical physicist did not realize that the smaller radiation beam used in radiosurgery had to be calibrated differently than the larger beam used for more traditional radiation therapy.

Medical physicists say there is nothing inherently wrong with linear accelerators that deliver general radiation therapy, as well as SRS. And, they say, the overdoses might have been caught had users followed a more rigorous system of checks and double-checks.

"Tens of thousands of patients have been treated with protocols properly followed and no mistakes were made," said Dr. Frank J. Bova, a medical physicist in Gainesville, Fla., and a pioneer in developing and enhancing the accuracy of SRS. "It has changed many difficult procedures, ones with high surgical risk, into one-day outpatient procedures."

But radiation safety experts say the retrofitted devices made up of different companies' products present a special challenge.

More ...

Better health care at the click of a mouse - The Globe and Mail

For Canada's economy to remain competitive, we need a health care system that takes good care of our aging population without creating a crushing financial burden for individuals and corporations.

To help achieve this, Canada's doctors need to adopt the slogan once used by Home Depot: "You can do it, we can help." When it comes to looking after our health, we must learn to rely less on our doctors and more on our own resources, otherwise we're going to bankrupt the system. Soon.

A recent Commonwealth Fund report ranked Canada dead last in the prevention and management of chronic disease. So it is no surprise that in the past 10 years health care spending in Canada has more than doubled, to $192-billion from $95-billion. Virtually all this increase is due to the treatment of Canadians living with chronic, but often preventable illnesses such as cardiovascular disease, diabetes, depression and arthritis.

Despite the advancements of modern medicine, our basic approach to health care has remained unchanged for centuries. It assumes that physicians are smart and patients aren't. Doctors wait in their office or hospital for sick people to come to them, then tell them what to do. Traditionally, patients have been passive and ill-informed, playing little or no role in deciding their own treatment. As one physician puts it: "Today's health care institutions are like the old media: centralized, one-way, immutable and controlled by the people who created and delivered it. Patients are passive recipients."

Now, courtesy of the Internet, there are tools that allow us to take more responsibility for our own health. All of us, including newborns, should have our own online Personal Health Page. Just as Facebook keeps you updated on your friends' activities, your Health Page would keep you up to date on issues affecting your health. You could have links to organizations such as Weight Watchers or a local diabetes support group. You could create a community or join medical "causes." And low-cost or free applications could help you measure your own health, prediagnose a sick child or test for possible drug interactions.

By moving the heart of our health care system online, and making each of us more informed and involved in our health, we would get a lot more bang for our health care buck. Knowing what's happening in your body motivates you to change your behaviour. If you weigh yourself daily, for instance, you'll be more successful at shedding pounds and keeping them off than if you weigh in weekly.

When we are better informed about our health, we make fewer trips to the emergency department, we don't make unnecessary doctors' appointments and we require fewer costly home-nurse visits.

Some early examples of this kind of thinking can already be seen online. Users of, a popular online health community, are able to track more than 1,500 symptoms and treatments on a daily basis using iPhone apps that cover both general health conditions, such as weight loss and allergies, and very specific disorders, such as infertility and diabetes. If they want, patients can share this information on a continuing basis with their doctors or caregivers.

Dr. Michael Evans of Toronto's St. Michaels Hospital says doctors should do more to encourage patients to take advantage of the resources available in online health care communities. Dr. Evans cites, a vibrant health care community whose members – 60,000 and growing – suffer from debilitating chronic conditions such as ALS, Parkinson's and bipolar disorder. Members use the site to track the evolution and management of their diseases. But rather than keep all their data private, many members share it with the patient community and the medical research community.

This openness ultimately benefits everyone. Patients can learn what's working and, in consultation with their doctors, adjust their own treatment plans. Drug companies can use anonymous patient data to evaluate new treatments and thus bring them to market more quickly. "People think we are a social networking site," says PatientsLikeMe co-founder Ben Heywood. "But we're an open medical framework. This is a large-scale research project."

Of course, without the buy-in of the biggest players – namely provincial governments and doctors – we won't be able to maximize these opportunities and more people will get needlessly sick. Harness these new capabilities, on the other hand, and the medical establishment can join with patients and other stakeholders in making the health care system work for everyone.

Tuesday, December 28, 2010

Prescription Drug Use in Children and Teens -

Gage Martindale, who is 8 years old, has been taking a blood-pressure drug since he was a toddler. "I want to be healthy, and I don't want things in my heart to go wrong," he says.

And, of course, his mom is always there to check Gage's blood pressure regularly with a home monitor, and to make sure the second-grader doesn't skip a dose of his once-a-day enalapril.

These days, the medicine cabinet is truly a family affair. More than a quarter of U.S. kids and teens are taking a medication on a chronic basis, according to Medco Health Solutions Inc., the biggest U.S. pharmacy-benefit manager with around 65 million members. Nearly 7% are on two or more such drugs, based on the company's database figures for 2009.

Doctors and parents warn that prescribing medications to children can be problematic. There is limited research available about many drugs' effects in kids. And health-care providers and families need to be vigilant to assess the medicines' impact, both intended and not. Although the effects of some medications, like cholesterol-lowering statins, have been extensively researched in adults, the consequences of using such drugs for the bulk of a patient's lifespan are little understood.

Many medications kids take on a regular basis are well known, including treatments for asthma and attention-deficit hyperactivity disorder.

But children and teens are also taking a wide variety of other medications once considered only to be for adults, from statins to diabetes pills and sleep drugs, according to figures provided to The Wall Street Journal by IMS Health, a research firm. Prescriptions for antihypertensives in people age 19 and younger could hit 5.5 million this year if the trend though September continues, according to IMS. That would be up 17% from 2007, the earliest year available.

Researchers attribute the wide usage in part to doctors and parents becoming more aware of drugs as an option for kids. Unhealthy diets and lack of exercise among children, which lead to too much weight gain and obesity, also fuel the use of some treatments, such as those for hypertension. And some conditions are likely caught and treated earlier as screening and diagnosis efforts improve.

Gage, who isn't overweight, has been on hypertension drugs since he had surgery to fix a heart defect as a toddler, says his mother, Stefanie Martindale, a Conway, Ark., marketing-company manager.

Most medications that could be prescribed to children on a chronic basis haven't been tested specifically in kids, says Danny Benjamin, a Duke University pediatrics professor. And older drugs rarely get examined, since pharmaceutical firms have little incentive to test medicines once they are no longer under patent protection.

Still, a growing number of studies have been done under a Food and Drug Administration program that rewards drug companies for testing medications in children. In more than a third of these studies, there have been surprising side effects, or results that suggested a smaller or larger dose was needed than had been expected, Dr. Benjamin says. Those findings underscore that children's reactions to medicines can be very different than those of adults. Long-term effects of drugs in kids are almost never known, since pediatric studies, like those in adults, tend to be relatively short.

More ...

Seeking the Connectome, a Mental Map, Slice by Slice -

Dr. Lichtman and his team of researchers at Harvard have built some unusual contraptions that carve off slivers of mouse brains as part of a quest to understand how the mind works. Their goal is to run slice after minuscule slice under a powerful electron microscope, develop detailed pictures of the brain's complex wiring and then stitch the images back together. In short, they want to build a full map of the mind.

The field, at a very nascent stage, is called connectomics, and the neuroscientists pursuing it compare their work to early efforts in genetics. What they are doing, these scientists say, is akin to trying to crack the human genome — only this time around, they want to find how memories, personality traits and skills are stored.

They want to find a connectome, or the mental makeup of a person.

"You are born with your genes, and they don't change afterward," said H. Sebastian Seung, a professor of computational neuroscience at the Massachusetts Institute of Technology who is working on the computer side of connectomics. "The connectome is a product of your genes and your experiences. It's where nature meets nurture."

The task is arduous and years from fruition, and even the biggest zealots acknowledge that their work may not pay off. But connectomics has gotten some meaningful financing: In September, theNational Institutes of Health handed out $40 million in grants to researchers at Harvard, Washington University in St. Louis, the University of Minnesota and the University of California, Los Angeles, to pursue connectomics. Together, their research efforts comprise the Human Connectome Project.

Since the 1970s, researchers have only had one connectome to play with — that of a worm with a measly 300 neurons. Now they are trying a mouse brain, with its 100 million neurons. So far the notion of creating a human-scale connectome — which would illuminate all of the connections among more than 100 billion neurons and unravel the millions of miles of wires in the brain — has proved too daunting.

The task at hand is somewhat similar to trying to untangle a bowl of spaghetti. Each individual spaghetti strand may touch tens of other strands as it weaves in a contorted fashion through the bowl. In this case, the researchers want to do the equivalent of seeing where all the strands connect at the atom level.

And because the brain's wiring is so densely packed, building a connectome stands as one of the most formidable data collection efforts ever concocted. About one petabyte of computer memory will be needed to store the images needed to form a picture of a one-millimeter cube of mouse brain, the scientists say. By comparison, it takes Facebook about one petabyte of data storage space to hold 40 billion photos.

"The world is not yet ready for the million-petabyte data set the human brain would be," Dr. Lichtman said. "But it will be."

Neuroscientists say that a connectome could give them myriad insights about the brain's function and prove particularly useful in the exploration of mental illness. For the first time, researchers and doctors might be able to determine how someone was wired — quite literally — and compare that picture with "regular" brains. Surgeons armed with a connectome might also be able to make more calculated cuts in the brain.

"The connectome project is going to show where all the white matter — all the connecting fibers — are," said Stanley Klein, a professor of optometry and vision science at the University of California, Berkeley. "The whole goal in something like a surgery for epilepsy is to delicately slice out some of the white matter without removing any cortex."

Dr. Klein says he has "zero question" that this type of surgery could benefit from developing a connectome.

Other scientists doubt that the results will match the effort. The comparisons to the genome prove haunting, and critics suggest that the connectome fans are wasting valuable research dollars and setting themselves up for a huge letdown.

"There are people that argue we still just don't know enough about the brain to know where to look for insights," said Bradley Voytek, a researcher at the Helen Wills Neuroscience Institute at the University of California, Berkeley. "They also contend that there is no possible way you can build a full connectome in any realistic time frame."

What's more, even if the researchers succeed, they will only produce a static picture of a brain frozen in time, rather than something that shows how a brain responds to different types of stimuli.

Scientists around the world, including Stephen J. Smith, a neuroscience professor at Stanford, and Gerald M. Rubin, a researcher with the Howard Hughes Medical Institute, have pushed past the naysayers and developed varying techniques for mapping the brains and nervous systems of human as well as other creatures.

"There are some people who say, 'Maybe you don't need this information, and given the expense of it, maybe you should put it off,' " said Dr. Lichtman, a professor of molecular and cellular biology at Harvard. "It's a fair controversy."

More ...

The Decline Effect and the Scientific Method : The New Yorker

On September 18, 2007, a few dozen neuroscientists, psychiatrists, and drug-company executives gathered in a hotel conference room in Brussels to hear some startling news. It had to do with a class of drugs known as atypical or second-generation antipsychotics, which came on the market in the early nineties. The drugs, sold under brand names such as Abilify, Seroquel, and Zyprexa, had been tested on schizophrenics in several large clinical trials, all of which had demonstrated a dramatic decrease in the subjects' psychiatric symptoms. As a result, second-generation antipsychotics had become one of the fastest-growing and most profitable pharmaceutical classes. By 2001, Eli Lilly's Zyprexa was generating more revenue than Prozac. It remains the company's top-selling drug.

But the data presented at the Brussels meeting made it clear that something strange was happening: the therapeutic power of the drugs appeared to be steadily waning. A recent study showed an effect that was less than half of that documented in the first trials, in the early nineteen-nineties. Many researchers began to argue that the expensive pharmaceuticals weren't any better than first-generation antipsychotics, which have been in use since the fifties. "In fact, sometimes they now look even worse," John Davis, a professor of psychiatry at the University of Illinois at Chicago, told me.

Before the effectiveness of a drug can be confirmed, it must be tested and tested again. Different scientists in different labs need to repeat the protocols and publish their results. The test of replicability, as it's known, is the foundation of modern research. Replicability is how the community enforces itself. It's a safeguard for the creep of subjectivity. Most of the time, scientists know what results they want, and that can influence the results they get. The premise of replicability is that the scientific community can correct for these flaws.

But now all sorts of well-established, multiply confirmed findings have started to look increasingly uncertain. It's as if our facts were losing their truth: claims that have been enshrined in textbooks are suddenly unprovable. This phenomenon doesn't yet have an official name, but it's occurring across a wide range of fields, from psychology to ecology. In the field of medicine, the phenomenon seems extremely widespread, affecting not only antipsychotics but also therapies ranging from cardiac stents to Vitamin E and antidepressants: Davis has a forthcoming analysis demonstrating that the efficacy of antidepressants has gone down as much as threefold in recent decades.

For many scientists, the effect is especially troubling because of what it exposes about the scientific process. If replication is what separates the rigor of science from the squishiness of pseudoscience, where do we put all these rigorously validated findings that can no longer be proved? Which results should we believe? Francis Bacon, the early-modern philosopher and pioneer of the scientific method, once declared that experiments were essential, because they allowed us to "put nature to the question." But it appears that nature often gives us different answers.

More ...

Monday, December 27, 2010

Prominent Toronto doctor lauds provincial narcotics strategy -

Rick Glazier has seen the toll that narcotics abuse takes on two fronts – in his medical practice and in his own family.

His 18-year-old son Daniel, who struggled with depression and anxiety, died from an accidental overdose of the highly addictive painkiller OxyContin last year.

In the face of stigma and shame associated with addictions, the prominent Toronto doctor is making his family's story public in hopes it will help see new provincial plans aimed at combatting narcotic abuse through to fruition.

Glazier sat in the public gallery at Queen's Park on Wednesday as Health Minister Deb Matthews introduced new legislation to create a registry to track the prescribing of narcotics and controlled substances in Ontario.

"What Dr. Glazier has experienced first-hand is happening to families province-wide. The facts are staggering," Matthews said, noting that since 2004 the number of oxycodone-related deaths in the province has nearly doubled, as have narcotic-abuse related admissions to treatment and addiction services

Daniel was 14 when Glazier and his wife learned the teen was struggling with mental health problems and taking drugs like marijuana and ecstasy to self-medicate. Within a year, the teen's drug use became more indiscriminate and he was taking anything he could in an effort to feel normal.

Glazier's medical credentials are many, but even he couldn't find local treatment resources for his son. The doctor is a senior scientist at the Institute for Clinical Evaluative Sciences, core scientist at the Centre for Research on Inner City Health at St. Michael's Hospital, a family physician and a professor of family medicine at the University of Toronto.

Because of a severe shortage of treatment beds for young people struggling with both mental health problems and addictions, Glazier sent Daniel to a residential treatment facility in Utah. The teen stayed there for two years, finally returning home clean in 2008. He enrolled in George Brown College and appeared to have turned over a new leaf.

But on July 24, 2009, about a year after Daniel's return, Glazier and his wife were eating lunch at a roadside chip wagon during a drip up north to Algonquin Park when his pager went off. It was the police, calling to say Daniel had been found unresponsive that morning at the Toronto youth residential facility where he had been staying.

It was later learned Daniel had relapsed two weeks earlier and was buying OxyContin and Percocet off the streets. Toxicology tests found he had died from oxycodone toxicity. He had seen his psychiatrist and therapist the day before and showed no signs of being suicidal.

Like many addicts, Daniel hid his symptoms well. And like many young people, he felt invulnerable to the dangers of drugs.

"You couldn't have any idea of how much guilt and how much angst has been involved," Glazier said, his voice choking with emotion.

In the time since Daniel's death, Glazier heard that a panel of experts had been commissioned by the province to make recommendations on a narcotics strategy. He got in touch and asked if he could help. He was in turn asked if he'd be willing to have Daniel's story made public to raise awareness of the issue.

He sat down with his wife and two daughters and they made a decision collectively: "The main purpose (of the strategy) is to prevent these kinds of deaths and this kind of suffering and we felt we had to do what we could to support it, even if it meant being in an emotional and difficult place."

The legislation, if implemented, would lead to the creation of a registry that would issue an alert when someone tries to get the same drugs from different doctors or fills multiple prescriptions at different pharmacies. It would also identify doctors and pharmacists who are prescribing or dispensing too many drugs, ultimately making fewer drugs available on the streets.

The new narcotics strategy is also aimed at educating the health-care sector about appropriate prescribing and dispensing, and there are plans to increase addiction treatment resources.

Glazier's insights into the issue are also informed by his work. Addicts often walk into his Sherbourne St. practice asking for painkillers. He and his colleagues have a policy of not prescribing such drugs during a patient's first visit to discourage the practice of doctor-shopping.

Some say the province's strategy is long overdue. Ontario has the highest rate of narcotics use in Canada, but five other provinces have done more to monitor usage. As well, 41 American states have already enacted legislation to monitor prescription drugs.

Back in 2000, Richmond Hill mother Penny Long lobbied the province to create such a monitoring registry a year after her daughter died of an accidental overdose. Karly, 29, had bipolar disorder and in the week before she died went to emergency departments, walk-in clinics and doctors' offices and managed to obtain hundreds of drugs, including painkillers.

"She was double-doctoring and stockpiling because she was terrified she would run out. She was addicted and no one was helping her . . . ," Long said.

Long said she is pleased the province is finally creating a registry, but wonders how many lives could have been saved had it been done earlier.

"It's a wonderful step forward, but why did it have to take 10 years?"

Sunday, December 26, 2010

Bioethics Discussion Blog - Dr. Maurice Bernstein

What have you been reading, hearing or TV viewing that has provoked some feelings of comfort or concern about what is happening in the world of medicine, medical care, treatment or science? Ethics is all about doing the right thing. Are you aware of any issues in medicine or biologic science which are being done right, could be improved or in fact represent totally unethical behavior? Write about them here.. and I will too!

Those readers of Knol may recognize me as the moderator of the Bioethics Discussion Blog which is now starting its 5th year. On the blog, I set the topics and await for my visitors to write their comments on the ethical issues described. Since I don't want to bias or direct my visitor's responses, I usually do not regularly express my own views on the topic. I thought it would be worthwhile using the format of Knol to let the readers set the topic and if I find that I have enough experience or knowledge to contribute to the topic, I would try. My experience is that of 50 years of medical practice and over 20 years of teaching first and second year medical students and participating in hospital clinical ethics committees.

My MRI Experience - Jerry DeNuccio - Open Salon

Yesterday morning I had an MRI, an experience that, were I a Calvinist, would have convinced me of that faith's two fundamental propositions: that I had, in some way unknown to me but blindingly apparent to omniscient Providence, sinned grievously; and that no affliction is unaccompanied by the catalyzing grace needed to overcome it.

My appointment was scheduled for 6:45 a.m. Now, an MRI before breakfast, before, even, I've managed to shake off the burrs of sleep and insert the day's coffee IV, strikes me as a squalid defilement of all that is human. Why so early? I live in a rural community and the nearest hospital is located in the county seat some 15 miles up the road. The county hospital does not have an MRI scanner, but a truck bearing one comes every other Tuesday, and on this particular Tuesday it was beginning its rounds at my county's hospital. I arrived at 6:30, knowing that when I reported to the reception desk I'd be spending approximately 15 minutes answering the same questions I've answered on previous visits, filling out the same forms I've filled out on previous visits, and signing various documents confirming that I've been told this or shown that—all of which I've done on previous visits. I then took a seat in the waiting room and picked up a stray copy of Midwest Living, just to scan, for I expected to be MRIed at any moment.

At 7:15, the hospital's lab technician asked me to follow him to the lab so he could draw some blood to test for something or other. "Wait a minute," I said, "I've been to my doctor's office twice in the past week and both times she drew blood. And one hour after the last visit, I got a phone call from her nurse telling me they hadn't drawn enough. So, I had more drawn just yesterday at the local clinic. I'm getting a little tired of being poked, penetrated, and tapped. I feel like a toothpicked cocktail frank in a medical buffet." Truth be told, I'm no High Nooned Gary Cooper when it comes to needles. Perhaps I suffer from aichmophobia, the fear of sharp, pointed objects. No doubt, I am an exuberant sulker; as Voltaire observed, I take "pleasure in complaining" and "delight in viewing only evil." But, he checked his records and, sure enough, he had the blood the test required. Next, he began reading a series of questions, all of which, I quickly saw, had to do with surgeries that would have implanted some ferric object inside me—screws, stents, pumps, and the like. After the 5thquestion, I said, "Look, let's save ourselves some time. Other than a tonsillectomy when I was 3 years old, I have never had surgery of any kind." He was, however, a man indentured to the fierce banality of a process for which he was merely a carrier, not the creator. He continued asking, dutifully checking the "no" boxes, and had me sign a form saying I'd been asked the questions. Then back to the waiting room and Midwest Living, which I now began to read.

In the middle of an article about a corporate executive who had fled his Manhattan suite for small town Iowa living and designer bird-house building, I was called for my MRI. It was 8:05. "You know," I told the two attendants who walked me to the truck, "I was told my appointment was at 6:45, and I'm not a little pissed off that I've had to wait an hour and twenty minutes. Now, I know these things happen, and it's probably not your fault, but, damn, an hour and twenty minutes!" "Oh, I'm sorry," one of the attendants said; "it seems a miscommunication occurred between your doctor's office and the MRI scheduler." A "miscommunication occurred." Such a convenient use of the passive voice; how cleverly it obscures assigning anyone fault, how sly its practiced use in hemming the ragged edge of a patient's anger. Well, I was having none of it. I'm not an English teacher for nothing. "That may well be the case," I said, "but, you know, I'm not in the mood to be Strother Martined." They looked perplexed. "You know, the actor who played the warden in Cool Hand Luke? His tag line is, `What we got he-ah is a failure to communicate." They hadn't seen the movie.

The MRI itself, believe it or not, was a warm Pacific slipstream in the thin, cold current of my wintery discontent. Stretched comfortably on the table, covered in two blankets, head padded in place, the on-call bulb firmly grasped in my right hand, I was gingerly slid into the center of the machine—birth in reverse, a return to the womb. Sure, instead of the soothing beat of the maternal heart, I heard only the cacophonous clang of jackhammer staccato and the stiletto chir of dial-tone buzz, but I tried to imagine it as the atonal music of a John Cage or Arnold Shoenberg. Imagination, however, deals with the essence behind reality, and when that ear-assaulting clangor proved impossible to get behind, I resorted to a strategy I have used intermittently in the past in similar situations: a recurrent fantasy involving Salma Hayek and cellophane—a fantasy so potent that, with five minutes to go in the procedure, it got me through being slid out for yet another poking and penetrating, this one with some strange brew to "provide contrast." Fantasy does not genuflect to the imperial demands of reality. Fantasy is dissociation from reality. I've always been good at dissociating.

And then, finally, I am released from the magnetic womb, rebirthed, released into a world where breakfast and a Mr. Coffee machine await. "Good job, Jerry," one of the attendants said, "we've got clear images." This, of course, was the verbal equivalent of a lollipop, my "good job" being only my capacious talent for lying still. Little did they know the role Salma played in that stillness. I did worry briefly that the images I had conjured might, somehow, leave a residue, a resonance, in those magnetically-generated images of my brain, and that, if they did, they had the potential for being WikiLeaked. That could prove embarrassing. Is the mind in the brain? Detached immaterially from it? Well, that's a cirque du soleil of debates, best left to the experts. I shrugged it off as a kind of wrestling beneath my weight class.

It is reported that French novelist Honore de Balzac carried a cane upon which was written, "I smash all obstacles." Upon hearing that, Franz Kafka declared his cane should read, "All obstacles smash me." Were it not for Salma, the efflorescent Salma, the luminescent Salma, the Salma who redeemed my MRI experience with the magnetic resonance of fantasy, I would have exited that MRI scanner truck, halt and hobbled, leaning heavily on Kafka's cane.