Jamie Oliver talking at TED2010 on childhood obesity.

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Newsweek ran a cover a few weeks ago bringing forward old, but hardly well publicized, research on antidepressants versus placebo to the public.

In just over half of the published and unpublished studies, he and colleagues reported in 2002, the drug alleviated depression no better than a placebo. “And the extra benefit of antidepressants was even less than we saw when we analyzed only published studies,” Kirsch recalls. About 82 percent of the response to antidepressants—not the 75 percent he had calculated from examining only published studies—had also been achieved by a dummy pill.

Here’s the 2002 paper Sharon Begley is referencing in her piece in Newsweek.

“Many have long been unimpressed by the magnitude of the differences observed between treatments and controls,” psychology researcher Steven Hollon of Vanderbilt University and colleagues wrote—”what some of our colleagues refer to as ‘the dirty little secret.’ “

Essentially except for those with severe depression, the vast vast majority of benefit seen with antidepressants can be attributed to a placebo effect.

The magnitude of benefit of antidepressant medication compared with placebo increases with severity of depression symptoms and may be minimal or nonexistent, on average, in patients with mild or moderate symptoms. For patients with very severe depression, the benefit of medications over placebo is substantial.

That’s the reality that is hardly well penetrated into primary care and the non-psychiatric medical community.

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It’s been more than a hundred and ten years since Marie Currie and her colleagues discovered radium and coined the term radioactive. Currie’s groundbreaking work on ionizing radiation would cost her her life. Since then and great realizations have been made about the therapeutic and disastrous effects ionizing radiation promises.

We’ve gotten smarter, more sophisticated, more skilled at manipulating radiation to do the most benefit in medicine and minimize harm. Ionizing radiation has spurned two whole medical specialties. Doctors now describe themselves as radiologists or radiation oncologists. Whole technology has arisen to more precisely diagnose diseases with radiation and to treat them. Radiosurgery, the use of linacs like the Gamme Knife or Cyberknife to more precisely target pathological areas and spare the normal, has been a huge development.

Of course the more technically complicated medicine gets, the more places things can go wrong. Nowhere is medicine as technically savvy or complicated than in in some of the ways we deliver radiation to patients. And, while admittingly slightly alarmist, the New York Times had a recent expose reminding us of that.

At a VA treatment facility in Virginia,

56 patients were treated incorrectly for cancer of the prostate, head and neck, lung, breast and two other malignancies. Thirty-six had been overradiated and 20 more subjected to “errors in technique,” the hospital said.

The Radiological Physics Center sponsored by the National Cancer Institute,

reported in 2008 that among hospitals seeking admission into clinical trials, nearly 30 percent failed to accurately irradiate an object, called a phantom, that mimicked the human head and neck. The hospitals were all using I.M.R.T., which shapes and varies the intensity of radiation beams to more accurately attack the tumor, while sparing healthy tissue.

“This is a sobering statistic, especially considering that this is a sample of those institutions that felt confident enough in their I.M.R.T. planning and delivery process to apply for credentialing and presumably expected to pass,” said a task group investigating I.M.R.T. guidelines for the American Association of Physicists in Medicine.

Not to quote a comic book or a Sam Rami film but with great power comes great responsibility. To err is human, but we shouldn’t accept it. Every error in medicine is something precious lost to someone, something that should be unacceptable. And when we push the boundaries of technology the odds of mistakes only tick up. Like so much in medicine and life, but to the margins, radiation is a boon and a bust; technology promises to potentially deliver it in more effective and safer ways but only if healthcare knows how to use such technology, only if healthcare respects the power of what it’s dosing out and works to prevent errors.

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A joint British and Belgian group has published new findings with fMRI evaluating consciousness in patient’s previously meeting clinical classification for persistent wakeful unconscious states.

We used functional magnetic resonance imaging (MRI) to assess each patient’s ability to generate willful, neuroanatomically specific, blood-oxygenation-level–dependent responses during two established mental-imagery tasks. A technique was then developed to determine whether such tasks could be used to communicate yes-or-no answers to simple questions.

Of the 54 patients enrolled in the study, 5 were able to willfully modulate their brain activity. In three of these patients, additional bedside testing revealed some sign of awareness, but in the other two patients, no voluntary behavior could be detected by means of clinical assessment. One patient was able to use our technique to answer yes or no to questions during functional MRI; however, it remained impossible to establish any form of communication at the bedside.

The emphasis is my own because it is those findings which made the news as the NEJM published the study ahead of print online. While hyperbolic, the results have elicited titles in the media such as ‘I’m alive! ‘Vegetative’ patient speaks to scientists using his brainwaves‘ and responses from pro-life advocates such as ‘‘Stop dehydration deaths,’ says Terri Schiavo’s brother in response to new brain scan‘.

Functional MRI has been front and center in the news the past several years with claims of scans that can predict people’s responses and actions before they make them and decipher people’s motives or tell us when they’re lying or telling the truth.

And it’s true studies such as those by Monti, et al raise important and serious questions about the right to life and the right to die. In an editorial to accompany NEJM’s publication Dr. Allan Ropper says,

Even in a preselected population, brain activation was infrequent, but it occurred often enough that it will now be difficult for physicians to tell families confidently that their unresponsive loved ones are not “in there somewhere.”

Indeed, the MRC and Belgian group’s efforts are game changers certainly. It, and future studies along the same lines, have made and will make the main stream news and will no doubt be commonly quoteb by anyone faced with a loved one who is awake but seemingly not there by any measure short of fMRI. And they should be. For all the reassurance the medical community gives family and friends the misdiagnosis of persistent vegetative states is a problem. Now further uncertainty is thrown on it.

But as much as the preservation of life and function is an important goal, arguably secondary only to primum non nocere, I still think caution is in order when using information as Monti et al have provided. Dr. Ropper likely says it better than I can,

First, in this study, brain activation was detected in very few patients. Second, activation was found only in some patients with traumatic brain injury, not in patients with global ischemia and anoxia. Third, cortical activation does not provide evidence of an internal “stream of thought” (William James’s term), memory, self-awareness, reflection, synthesis of experience, symbolic representations, or — just as important — anxiety, despair, or awareness of one’s predicament. Without judging the quality of any person’s inner life, we cannot be certain whether we are interacting with a sentient, much less a competent, person. Moreover, persons who look to this study to justify continued and unqualified life support in all unresponsive patients are missing the focus of the findings.

The presence of some rudimentary preserved cognition that is indicated by means of functional MRI will no longer be in question, but its meaning will continue to be subject to interpretation.

Be gentle in how we use these new resources to define consciousness; how we use these new resources to define who is still is with us.

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New Scientist profiles the Wellcome Collection’s Exquisite Bodies exhibit looking at the portrayal of human anatomy in the Victorian era. I can almost guarantee that the next time I’m in London I will be at the Wellcome Collection; looks very interesting.

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I once had a pharm professor, during my first two years of medical school, predict that we’d see the death of antibiotics during my practice career. The idea being that the antibiotics in the pipeline, the drive for new therapies against pathogenic bacteria was limited compared to the speed at which resistance was growing. Well Kary Mullis has some ideas about that and about the future of the battle against infection.

I know Mullins is a controversial figure and a strange bird at that. He is one of the most unique, choosing that adjective over others, Noble laureates I can remember. In spite of all that the talk, as most TED talks are, is very interesting.

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Lexington, a pseudonymous columnist for my favorite magazine The Economist, had the following to say about efforts to reform American health care,

We are all going to die. And the demand for interventions that might postpone that day far outstrips the supply. No politician would be caught dead admitting this, of course: most promise that all will receive whatever is medically necessary. But what does that mean? Should doctors seek to save the largest number of lives, or the largest number of years of life? Even in America, resources are finite. No one doubts that $1,000 to save the life of a child is money well spent. But what about $1m to prolong a terminally ill patient’s painful life by a week? Also, who should pay?

I couldn’t agree more. I’ve long been a proponent of the idea that expectations of healthcare in the United States are something else, more demanding as compared to the rest of the world. We try everything here in America for a patient, cost not prohibiting, before the plug is pulled. This trend is especially prominent in acute care situations. Situations of immediacy, of life and death.

Consider I’m at a major trauma center for training right now. I know I’m not seeing unique scenarios and I, with some frequency, am witness to scenarios like the following. An 80 year old man comes in following a motor vehicle crash. He was the restrained driver. There was a death at the scene.

He had a prolonged extracation from the vehicle

On the scene he had a Glasgow Coma Scale of 9 and was combative and was intubated for such. En route to the emergency room his hemodynamics become a little marginal and he starts with progressive fluid requirements. On arrival to the emergency room a FAST scan is inconclusive and his pressures, while marginal, are stable enough for him to make a quick run through the scanner. His injuries are documented by imaging as bilateral femurs, open pelvis with active extravisation, splenic and liver injuries with active extravisation, a subdural hematoma on the right with marginal shift and bifrontal contusions.

Coming out of the scanner his pressures collapse as he’s being rolled emergently to the operating room. At this point his TRISS score predicts a mortality approaching 95%.

Intraoperatively he loses close to 20 liters and requires massive resuscitation. Resuscitation includes more than 50 units of packed red blood cells and corresponding fresh frozen plasma and cryo and platelets. He is transported to the SICU status post a splenectomy with an open packed abdomen. He requires continued resuscitation with another 10 of pRBCs and 10 of FFP. He requires ACLS overnight although a pulse is returned. He is not stable enough to make a trip back to the operating room as planned through the whole of the next week. At one point he has a reexploration of his abdominal wound at bedside under sterile conditions because he is too unstable to be transported to the OR.

He continues like this for a week despite the clear non-survivability of his injuries, until finally made comfort care and allowed to peacefully expire.

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…a laugh. I’ll leave the debunking to Orac and others but I thought this video of Irish stand up comedian Dan O’Briain was pretty damn funny.

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I love lacrosse. It’s my favorite sport on the field; my favorite to play. My favorite stick is still sitting next to my bed despite the fact I haven’t stepped competitively on a field in four years.

But it is a surprisingly violent sport and has some unique things about it which make players on the field slightly more prone to blunt cardiac injuries than in other sports. Here’s the study in Pediatrics (subscription).

Although the overall mortality rate of lacrosse was similar to other major sports, the rate of sudden death attributed to commotio cordis (0.63 per 100,000 person-years) was significantly higher for lacrosse than baseball (0.24, P=0.017), football (0.043, P<0.0001), and other sports, except for hockey (0.53, P=0.73).

Don’t freak out too much. Despite that increase in blunt cardiac injuries with lacrosse, the incidence of sudden death amongst lacrosse players as compared to players of other major sports is essentially the same. Sudden death in young athletes gets a lot of attention, as it should, but it is exceedingly rare. Amongst sudden deaths in athletes, the most common etiology is not commotio cordis (or other blunt trauma) but congenital cardiac abnormalities.

I gained a lot more from lacrosse than any risk of commotio cordis I took when stepping out on the field.

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GlaxoKlineSmith has teamed up with a non-profit for work on one of their AIDs vaccines.
The first AIDs vaccine will appear in the next decade. It’s effectiveness may be in question, however.

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