Sunday, May 11, 2008


The Checklist
If something so simple can transform intensive care, what else can it do?


by Atul Gawande
11 may 2008--The damage that the human body can survive these days is as awesome as it is horrible: crushing, burning, bombing, a burst blood vessel in the brain, a ruptured colon, a massive heart attack, rampaging infection. These conditions had once been uniformly fatal. Now survival is commonplace, and a large part of the credit goes to the irreplaceable component of medicine known as intensive care.
It’s an opaque term. Specialists in the field prefer to call what they do “critical care,” but that doesn’t exactly clarify matters. The non-medical term “life support” gets us closer. Intensive-care units take artificial control of failing bodies. Typically, this involves a panoply of technology—a mechanical ventilator and perhaps a tracheostomy tube if the lungs have failed, an aortic balloon pump if the heart has given out, a dialysis machine if the kidneys don’t work. When you are unconscious and can’t eat, silicone tubing can be surgically inserted into the stomach or intestines for formula feeding. If the intestines are too damaged, solutions of amino acids, fatty acids, and glucose can be infused directly into the bloodstream.
The difficulties of life support are considerable. Reviving a drowning victim, for example, is rarely as easy as it looks on television, where a few chest compressions and some mouth-to-mouth resuscitation always seem to bring someone with waterlogged lungs and a stilled heart coughing and sputtering back to life. Consider a case report in The Annals of Thoracic Surgery of a three-year-old girl who fell into an icy fishpond in a small Austrian town in the Alps. She was lost beneath the surface for thirty minutes before her parents found her on the pond bottom and pulled her up. Following instructions from an emergency physician on the phone, they began cardiopulmonary resuscitation. A rescue team arrived eight minutes later. The girl had a body temperature of sixty-six degrees, and no pulse. Her pupils were dilated and did not react to light, indicating that her brain was no longer working.
But the emergency technicians continued CPR anyway. A helicopter took her to a nearby hospital, where she was wheeled directly to an operating room. A surgical team put her on a heart-lung bypass machine. Between the transport time and the time it took to plug the inflow and outflow lines into the femoral vessels of her right leg, she had been lifeless for an hour and a half. By the two-hour mark, however, her body temperature had risen almost ten degrees, and her heart began to beat. It was her first organ to come back.
After six hours, her core temperature reached 98.6 degrees. The team tried to put her on a breathing machine, but the pond water had damaged her lungs too severely for oxygen to reach her blood. So they switched her to an artificial-lung system known as ECMO—extracorporeal membrane oxygenation. The surgeons opened her chest down the middle with a power saw and sewed lines to and from the ECMO unit into her aorta and her beating heart. The team moved the girl into intensive care, with her chest still open and covered with plastic foil. A day later, her lungs had recovered sufficiently for the team to switch her from ECMO to a mechanical ventilator and close her chest. Over the next two days, all her organs recovered except her brain. A CT scan showed global brain swelling, which is a sign of diffuse damage, but no actual dead zones. So the team drilled a hole into the girl’s skull, threaded in a probe to monitor her cerebral pressure, and kept that pressure tightly controlled by constantly adjusting her fluids and medications. For more than a week, she lay comatose. Then, slowly, she came back to life.
First, her pupils started to react to light. Next, she began to breathe on her own. And, one day, she simply awoke. Two weeks after her accident, she went home. Her right leg and left arm were partially paralyzed. Her speech was thick and slurry. But by age five, after extensive outpatient therapy, she had recovered her faculties completely. She was like any little girl again.
What makes her recovery astounding isn’t just the idea that someone could come back from two hours in a state that would once have been considered death. It’s also the idea that a group of people in an ordinary hospital could do something so enormously complex. To save this one child, scores of people had to carry out thousands of steps correctly: placing the heart-pump tubing into her without letting in air bubbles; maintaining the sterility of her lines, her open chest, the burr hole in her skull; keeping a temperamental battery of machines up and running. The degree of difficulty in any one of these steps is substantial. Then you must add the difficulties of orchestrating them in the right sequence, with nothing dropped, leaving some room for improvisation, but not too much.
For every drowned and pulseless child rescued by intensive care, there are many more who don’t make it—and not just because their bodies are too far gone. Machines break down; a team can’t get moving fast enough; a simple step is forgotten. Such cases don’t get written up in The Annals of Thoracic Surgery, but they are the norm. Intensive-care medicine has become the art of managing extreme complexity—and a test of whether such complexity can, in fact, be humanly mastered.
On any given day in the United States, some ninety thousand people are in intensive care. Over a year, an estimated five million Americans will be, and over a normal lifetime nearly all of us will come to know the glassed bay of an I.C.U. from the inside. Wide swaths of medicine now depend on the lifesupport systems that I.C.U.s provide: care for premature infants; victims of trauma, strokes, and heart attacks; patients who have had surgery on their brain, heart, lungs, or major blood vessels. Critical care has become an increasingly large portion of what hospitals do. Fifty years ago, I.C.U.s barely existed. Today, in my hospital, a hundred and fifty-five of our almost seven hundred patients are, as I write this, in intensive care. The average stay of an I.C.U. patient is four days, and the survival rate is eighty-six per cent. Going into an I.C.U., being put on a mechanical ventilator, having tubes and wires run into and out of you, is not a sentence of death. But the days will be the most precarious of your life.
A decade ago, Israeli scientists published a study in which engineers observed patient care in I.C.U.s for twenty-four-hour stretches. They found that the average patient required a hundred and seventy-eight individual actions per day, ranging from administering a drug to suctioning the lungs, and every one of them posed risks. Remarkably, the nurses and doctors were observed to make an error in just one per cent of these actions—but that still amounted to an average of two errors a day with every patient. Intensive care succeeds only when we hold the odds of doing harm low enough for the odds of doing good to prevail. This is hard. There are dangers simply in lying unconscious in bed for a few days. Muscles atrophy. Bones lose mass. Pressure ulcers form. Veins begin to clot off. You have to stretch and exercise patients’ flaccid limbs daily to avoid contractures, give subcutaneous injections of blood thinners at least twice a day, turn patients in bed every few hours, bathe them and change their sheets without knocking out a tube or a line, brush their teeth twice a day to avoid pneumonia from bacterial buildup in their mouths. Add a ventilator, dialysis, and open wounds to care for, and the difficulties only accumulate.
The story of one of my patients makes the point. Anthony DeFilippo was a forty-eight-year-old limousine driver from Everett, Massachusetts, who started to hemorrhage at a community hospital during surgery for a hernia and gallstones. The bleeding was finally stopped but his liver was severely damaged, and over the next few days he became too sick for the hospital’s facilities. When he arrived in our I.C.U., at 1:30 A.M. on a Sunday, his ragged black hair was plastered to his sweaty forehead, his body was shaking, and his heart was racing at a hundred and fourteen beats a minute. He was delirious from fever, shock, and low oxygen levels.
“I need to get out!” he cried. “I need to get out!” He clawed at his gown, his oxygen mask, the dressings covering his abdominal wound.
“Tony, it’s all right,” a nurse said to him. “We’re going to help you. You’re in a hospital.”
He shoved her—he was a big man—and tried to swing his legs out of the bed. We turned up his oxygen flow, put his wrists in cloth restraints, and tried to reason with him. He eventually let us draw blood from him and give him antibiotics.
The laboratory results came back showing liver failure, and a wildly elevated white-blood-cell count indicating infection. It soon became evident from his empty urine bag that his kidneys had failed, too. In the next few hours, his blood pressure fell, his breathing worsened, and he drifted from agitation to near-unconsciousness. Each of his organ systems, including his brain, was shutting down.
I called his sister, who was his next of kin, and told her of the situation. “Do everything you can,” she said.
So we did. We gave him a syringeful of anesthetic, and a resident slid a breathing tube into his throat. Another resident “lined him up.” She inserted a thin, two-inch-long needle and catheter through his upturned right wrist and into his radial artery, and then sewed the line to his skin with a silk suture. Next, she put in a central line—a twelve-inch catheter pushed into the jugular vein in his left neck. After she sewed that in place, and an X-ray showed its tip floating just where it was supposed to—inside his vena cava at the entrance to his heart—she put a third, slightly thicker line, for dialysis, through his right upper chest and into the subclavian vein, deep under the collarbone.
We hooked a breathing tube up to a hose from a ventilator and set it to give him fourteen forced breaths of a hundred-per-cent oxygen every minute. We dialled the ventilator pressures and gas flow up and down, like engineers at a control panel, until we got the blood levels of oxygen and carbon dioxide where we wanted them. The arterial line gave us continuous arterial blood-pressure measurements, and we tweaked his medications to get the pressures we liked. We regulated his intravenous fluids according to venous-pressure measurements from his jugular line. We plugged his subclavian line into tubing from a dialysis machine, and every few minutes his entire blood volume washed through this artificial kidney and back into his body; a little adjustment here and there, and we could alter the levels of potassium and bicarbonate and salt in his body as well. He was, we liked to imagine, a simple machine in our hands.
But he wasn’t, of course. It was as if we had gained a steering wheel and a few gauges and controls, but on a runaway eighteen-wheeler hurtling down a mountain. Keeping his blood pressure normal was requiring gallons of intravenous fluid and a pharmacy shelf of drugs. He was on near-maximal ventilator support. His temperature climbed to a hundred and four degrees. Less than five per cent of patients with his degree of organ failure make it home. And a single misstep could easily erase those slender chances.
For ten days, though, all went well. His chief problem had been liver damage from the operation he’d had. The main duct from his liver was severed and was leaking bile, which is caustic—it digests the fat in one’s diet and was essentially eating him alive from the inside. He had become too sick to survive an operation to repair the leak. So we tried a temporary solution—we had radiologists place a plastic drain, using X-ray guidance, through his abdominal wall and into the severed duct in order to draw the leaking bile out of him. They found so much that they had to place three drains—one inside the duct and two around it. But, as the bile drained out, his fevers subsided. His requirements for oxygen and fluids diminished. His blood pressure returned to normal. He was on the mend. Then, on the eleventh day, just as we were getting ready to take him off the mechanical ventilator, he developed high, spiking fevers, his blood pressure sank, and his blood-oxygen levels plummeted again. His skin became clammy. He got shaking chills.
We didn’t understand what had happened. He seemed to have developed an infection, but our X-rays and CT scans failed to turn up a source. Even after we put him on four antibiotics, he continued to spike fevers. During one fever, his heart went into fibrillation. A Code Blue was called. A dozen nurses and doctors raced to his bedside, slapped electric paddles onto his chest, and shocked him. His heart responded, fortunately, and went back into rhythm. It took two more days for us to figure out what had gone wrong. We considered the possibility that one of his lines had become infected, so we put in new lines and sent the old ones to the lab for culturing. Forty-eight hours later, the results returned: all of them were infected. The infection had probably started in one line, perhaps contaminated during insertion, and spread through his bloodstream to the others. Then they all began spilling bacteria into him, producing his fevers and steep decline.
This is the reality of intensive care: at any point, we are as apt to harm as we are to heal. Line infections are so common that they are considered a routine complication. I.C.U.s put five million lines into patients each year, and national statistics show that, after ten days, four per cent of those lines become infected. Line infections occur in eighty thousand people a year in the United States, and are fatal between five and twenty-eight per cent of the time, depending on how sick one is at the start. Those who survive line infections spend on average a week longer in intensive care. And this is just one of many risks. After ten days with a urinary catheter, four per cent of American I.C.U. patients develop a bladder infection. After ten days on a ventilator, six per cent develop bacterial pneumonia, resulting in death forty to fifty-five per cent of the time. All in all, about half of I.C.U. patients end up experiencing a serious complication, and, once a complication occurs, the chances of survival drop sharply.
It was a week before DeFilippo recovered sufficiently from his infections to come off the ventilator, and it was two months before he left the hospital. Weak and debilitated, he lost his limousine business and his home, and he had to move in with his sister. The tube draining bile still dangled from his abdomen; when he was stronger, I was going to have to do surgery to reconstruct the main bile duct from his liver. But he survived. Most people in his situation do not.
Here, then, is the puzzle of I.C.U. care: you have a desperately sick patient, and in order to have a chance of saving him you have to make sure that a hundred and seventy-eight daily tasks are done right—despite some monitor’s alarm going off for God knows what reason, despite the patient in the next bed crashing, despite a nurse poking his head around the curtain to ask whether someone could help “get this lady’s chest open.” So how do you actually manage all this complexity? The solution that the medical profession has favored is specialization.
I tell DeFilippo’s story, for instance, as if I were the one tending to him hour by hour. But that was actually Max Weinmann, an intensivist (as intensive-care specialists like to be called). I want to think that, as a general surgeon, I can handle most clinical situations. But, as the intricacies involved in intensive care have mounted, responsibility has increasingly shifted to super-specialists like him. In the past decade, training programs focussed on critical care have opened in every major American city, and half of I.C.U.s now rely on super-specialists.
Expertise is the mantra of modern medicine. In the early twentieth century, you needed only a high-school diploma and a one-year medical degree to practice medicine. By the century’s end, all doctors had to have a college degree, a four-year medical degree, and an additional three to seven years of residency training in an individual field of practice—pediatrics, surgery, neurology, or the like. Already, though, this level of preparation has seemed inadequate to the new complexity of medicine. After their residencies, most young doctors today are going on to do fellowships, adding one to three further years of training in, say, laparoscopic surgery, or pediatric metabolic disorders, or breast radiology—or critical care. A young doctor is not so young nowadays; you typically don’t start in independent practice until your mid-thirties.
We now live in the era of the super-specialist—of clinicians who have taken the time to practice at one narrow thing until they can do it better than anyone who hasn’t. Super-specialists have two advantages over ordinary specialists: greater knowledge of the details that matter and an ability to handle the complexities of the job. There are degrees of complexity, though, and intensive-care medicine has grown so far beyond ordinary complexity that avoiding daily mistakes is proving impossible even for our super-specialists. The I.C.U., with its spectacular successes and frequent failures, therefore poses a distinctive challenge: what do you do when expertise is not enough?
On October 30, 1935, at Wright Air Field in Dayton, Ohio, the U.S. Army Air Corps held a flight competition for airplane manufacturers vying to build its next-generation long-range bomber. It wasn’t supposed to be much of a competition. In early evaluations, the Boeing Corporation’s gleaming aluminum-alloy Model 299 had trounced the designs of Martin and Douglas. Boeing’s plane could carry five times as many bombs as the Army had requested; it could fly faster than previous bombers, and almost twice as far. A Seattle newspaperman who had glimpsed the plane called it the “flying fortress,” and the name stuck. The flight “competition,” according to the military historian Phillip Meilinger, was regarded as a mere formality. The Army planned to order at least sixty-five of the aircraft.
A small crowd of Army brass and manufacturing executives watched as the Model 299 test plane taxied onto the runway. It was sleek and impressive, with a hundred-and-three-foot wingspan and four engines jutting out from the wings, rather than the usual two. The plane roared down the tarmac, lifted off smoothly, and climbed sharply to three hundred feet. Then it stalled, turned on one wing, and crashed in a fiery explosion. Two of the five crew members died, including the pilot, Major Ployer P. Hill.
An investigation revealed that nothing mechanical had gone wrong. The crash had been due to “pilot error,” the report said. Substantially more complex than previous aircraft, the new plane required the pilot to attend to the four engines, a retractable landing gear, new wing flaps, electric trim tabs that needed adjustment to maintain control at different airspeeds, and constant-speed propellers whose pitch had to be regulated with hydraulic controls, among other features. While doing all this, Hill had forgotten to release a new locking mechanism on the elevator and rudder controls. The Boeing model was deemed, as a newspaper put it, “too much airplane for one man to fly.” The Army Air Corps declared Douglas’s smaller design the winner. Boeing nearly went bankrupt.
Still, the Army purchased a few aircraft from Boeing as test planes, and some insiders remained convinced that the aircraft was flyable. So a group of test pilots got together and considered what to do.
They could have required Model 299 pilots to undergo more training. But it was hard to imagine having more experience and expertise than Major Hill, who had been the U.S. Army Air Corps’ chief of flight testing. Instead, they came up with an ingeniously simple approach: they created a pilot’s checklist, with step-by-step checks for takeoff, flight, landing, and taxiing. Its mere existence indicated how far aeronautics had advanced. In the early years of flight, getting an aircraft into the air might have been nerve-racking, but it was hardly complex. Using a checklist for takeoff would no more have occurred to a pilot than to a driver backing a car out of the garage. But this new plane was too complicated to be left to the memory of any pilot, however expert.
With the checklist in hand, the pilots went on to fly the Model 299 a total of 1.8 million miles without one accident. The Army ultimately ordered almost thirteen thousand of the aircraft, which it dubbed the B-17. And, because flying the behemoth was now possible, the Army gained a decisive air advantage in the Second World War which enabled its devastating bombing campaign across Nazi Germany.
Medicine today has entered its B-17 phase. Substantial parts of what hospitals do—most notably, intensive care—are now too complex for clinicians to carry them out reliably from memory alone. I.C.U. life support has become too much medicine for one person to fly.
Yet it’s far from obvious that something as simple as a checklist could be of much help in medical care. Sick people are phenomenally more various than airplanes. A study of forty-one thousand trauma patients—just trauma patients—found that they had 1,224 different injury-related diagnoses in 32,261 unique combinations for teams to attend to. That’s like having 32,261 kinds of airplane to land. Mapping out the proper steps for each is not possible, and physicians have been skeptical that a piece of paper with a bunch of little boxes would improve matters much.
In 2001, though, a critical-care specialist at Johns Hopkins Hospital named Peter Pronovost decided to give it a try. He didn’t attempt to make the checklist cover everything; he designed it to tackle just one problem, the one that nearly killed Anthony DeFilippo: line infections. On a sheet of plain paper, he plotted out the steps to take in order to avoid infections when putting a line in. Doctors are supposed to (1) wash their hands with soap, (2) clean the patient’s skin with chlorhexidine antiseptic, (3) put sterile drapes over the entire patient, (4) wear a sterile mask, hat, gown, and gloves, and (5) put a sterile dressing over the catheter site once the line is in. Check, check, check, check, check. These steps are no-brainers; they have been known and taught for years. So it seemed silly to make a checklist just for them. Still, Pronovost asked the nurses in his I.C.U. to observe the doctors for a month as they put lines into patients, and record how often they completed each step. In more than a third of patients, they skipped at least one.
The next month, he and his team persuaded the hospital administration to authorize nurses to stop doctors if they saw them skipping a step on the checklist; nurses were also to ask them each day whether any lines ought to be removed, so as not to leave them in longer than necessary. This was revolutionary. Nurses have always had their ways of nudging a doctor into doing the right thing, ranging from the gentle reminder (“Um, did you forget to put on your mask, doctor?”) to more forceful methods (I’ve had a nurse bodycheck me when she thought I hadn’t put enough drapes on a patient). But many nurses aren’t sure whether this is their place, or whether a given step is worth a confrontation. (Does it really matter whether a patient’s legs are draped for a line going into the chest?) The new rule made it clear: if doctors didn’t follow every step on the checklist, the nurses would have backup from the administration to intervene.
Pronovost and his colleagues monitored what happened for a year afterward. The results were so dramatic that they weren’t sure whether to believe them: the ten-day line-infection rate went from eleven per cent to zero. So they followed patients for fifteen more months. Only two line infections occurred during the entire period. They calculated that, in this one hospital, the checklist had prevented forty-three infections and eight deaths, and saved two million dollars in costs.
Pronovost recruited some more colleagues, and they made some more checklists. One aimed to insure that nurses observe patients for pain at least once every four hours and provide timely pain medication. This reduced the likelihood of a patient’s experiencing untreated pain from forty-one per cent to three per cent. They tested a checklist for patients on mechanical ventilation, making sure that, for instance, the head of each patient’s bed was propped up at least thirty degrees so that oral secretions couldn’t go into the windpipe, and antacid medication was given to prevent stomach ulcers. The proportion of patients who didn’t receive the recommended care dropped from seventy per cent to four per cent; the occurrence of pneumonias fell by a quarter; and twenty-one fewer patients died than in the previous year. The researchers found that simply having the doctors and nurses in the I.C.U. make their own checklists for what they thought should be done each day improved the consistency of care to the point that, within a few weeks, the average length of patient stay in intensive care dropped by half.
The checklists provided two main benefits, Pronovost observed. First, they helped with memory recall, especially with mundane matters that are easily overlooked in patients undergoing more drastic events. (When you’re worrying about what treatment to give a woman who won’t stop seizing, it’s hard to remember to make sure that the head of her bed is in the right position.) A second effect was to make explicit the minimum, expected steps in complex processes. Pronovost was surprised to discover how often even experienced personnel failed to grasp the importance of certain precautions. In a survey of I.C.U. staff taken before introducing the ventilator checklists, he found that half hadn’t realized that there was evidence strongly supporting giving ventilated patients antacid medication. Checklists established a higher standard of baseline performance.
These are, of course, ridiculously primitive insights. Pronovost is routinely described by colleagues as “brilliant,” “inspiring,” a “genius.” He has an M.D. and a Ph.D. in public health from Johns Hopkins, and is trained in emergency medicine, anesthesiology, and critical-care medicine. But, really, does it take all that to figure out what house movers, wedding planners, and tax accountants figured out ages ago?
Pronovost is hardly the first person in medicine to use a checklist. But he is among the first to recognize its power to save lives and take advantage of the breadth of its possibilities. Forty-two years old, with cropped light-brown hair, tenth-grader looks, and a fluttering, finchlike energy, he is an odd mixture of the nerdy and the messianic. He grew up in Waterbury, Connecticut, the son of an elementary-school teacher and a math professor, went to nearby Fairfield University, and, like many good students, decided that he would go into medicine. Unlike many students, though, he found that he actually liked caring for sick people. He hated the laboratory—with all those micropipettes and cell cultures, and no patients around—but he had that scientific “How can I solve this unsolved problem?” turn of mind. So after his residency in anesthesiology and his fellowship in critical care, he studied clinical-research methods.
For his doctoral thesis, he examined intensive-care units in Maryland, and he discovered that putting an intensivist on staff reduced death rates by a third. It was the first time that someone had demonstrated the public-health value of using intensivists. He wasn’t satisfied with having proved his case, though; he wanted hospitals to change accordingly. After his study was published, in 1999, he met with a coalition of large employers known as the Leapfrog Group. It included companies like General Motors and Verizon, which were seeking to improve the standards of hospitals where their employees obtain care. Within weeks, the coalition announced that its members expected the hospitals they contracted with to staff their I.C.U.s with intensivists. These employers pay for health care for thirty-seven million employees, retirees, and dependents nationwide. So although hospitals protested that there weren’t enough intensivists to go around, and that the cost could be prohibitive, Pronovost’s idea effectively became an instant national standard.
The scientist in him has always made room for the campaigner. People say he is the kind of guy who, even as a trainee, could make you feel you’d saved the world every time you washed your hands properly. “I’ve never seen anybody inspire as he does,” Marty Makary, a Johns Hopkins surgeon, told me. “Partly, he has this contagious, excitable nature. He has a smile that’s tough to match. But he also has a way of making people feel heard. People will come to him with the dumbest ideas, and he’ll endorse them anyway. ‘Oh, I like that, I like that, I like that!’ he’ll say. I’ve watched him, and I still have no idea how deliberate this is. Maybe he really does like every idea. But wait, and you realize: he only acts on the ones he truly believes in.”
After the checklist results, the idea Pronovost truly believed in was that checklists could save enormous numbers of lives. He took his findings on the road, showing his checklists to doctors, nurses, insurers, employers—anyone who would listen. He spoke in an average of seven cities a month while continuing to work full time in Johns Hopkins’s I.C.U.s. But this time he found few takers.
There were various reasons. Some physicians were offended by the suggestion that they needed checklists. Others had legitimate doubts about Pronovost’s evidence. So far, he’d shown only that checklists worked in one hospital, Johns Hopkins, where the I.C.U.s have money, plenty of staff, and Peter Pronovost walking the hallways to make sure that the checklists are being used properly. How about in the real world—where I.C.U. nurses and doctors are in short supply, pressed for time, overwhelmed with patients, and hardly receptive to the idea of filling out yet another piece of paper?
In 2003, however, the Michigan Health and Hospital Association asked Pronovost to try out three of his checklists in Michigan’s I.C.U.s. It would be a huge undertaking. Not only would he have to get the state’s hospitals to use the checklists; he would also have to measure whether doing so made a genuine difference. But at last Pronovost had a chance to establish whether his checklist idea really worked.
This past summer, I visited Sinai-Grace Hospital, in inner-city Detroit, and saw what Pronovost was up against. Occupying a campus of red brick buildings amid abandoned houses, check-cashing stores, and wig shops on the city’s West Side, just south of 8 Mile Road, Sinai-Grace is a classic urban hospital. It has eight hundred physicians, seven hundred nurses, and two thousand other medical personnel to care for a population with the lowest median income of any city in the country. More than a quarter of a million residents are uninsured; three hundred thousand are on state assistance. That has meant chronic financial problems. Sinai-Grace is not the most cash-strapped hospital in the city—that would be Detroit Receiving Hospital, where a fifth of the patients have no means of payment. But between 2000 and 2003 Sinai-Grace and eight other Detroit hospitals were forced to cut a third of their staff, and the state had to come forward with a fifty-million-dollar bailout to avert their bankruptcy.
Sinai-Grace has five I.C.U.s for adult patients and one for infants. Hassan Makki, the director of intensive care, told me what it was like there in 2004, when Pronovost and the hospital association started a series of mailings and conference calls with hospitals to introduce checklists for central lines and ventilator patients. “Morale was low,” he said. “We had lost lots of staff, and the nurses who remained weren’t sure if they were staying.” Many doctors were thinking about leaving, too. Meanwhile, the teams faced an even heavier workload because of new rules limiting how long the residents could work at a stretch. Now Pronovost was telling them to find the time to fill out some daily checklists?
Tom Piskorowski, one of the I.C.U. physicians, told me his reaction: “Forget the paperwork. Take care of the patient.”
I accompanied a team on 7 A.M. rounds through one of the surgical I.C.U.s. It had eleven patients. Four had gunshot wounds (one had been shot in the chest; one had been shot through the bowel, kidney, and liver; two had been shot through the neck, and left quadriplegic). Five patients had cerebral hemorrhaging (three were seventy-nine years and older and had been injured falling down stairs; one was a middle-aged man whose skull and left temporal lobe had been damaged by an assault with a blunt weapon; and one was a worker who had become paralyzed from the neck down after falling twenty-five feet off a ladder onto his head). There was a cancer patient recovering from surgery to remove part of his lung, and a patient who had had surgery to repair a cerebral aneurysm.
The doctors and nurses on rounds tried to proceed methodically from one room to the next but were constantly interrupted: a patient they thought they’d stabilized began hemorrhaging again; another who had been taken off the ventilator developed trouble breathing and had to be put back on the machine. It was hard to imagine that they could get their heads far enough above the daily tide of disasters to worry about the minutiae on some checklist.
Yet there they were, I discovered, filling out those pages. Mostly, it was the nurses who kept things in order. Each morning, a senior nurse walked through the unit, clipboard in hand, making sure that every patient on a ventilator had the bed propped at the right angle, and had been given the right medicines and the right tests. Whenever doctors put in a central line, a nurse made sure that the central-line checklist had been filled out and placed in the patient’s chart. Looking back through their files, I found that they had been doing this faithfully for more than three years.
Pronovost had been canny when he started. In his first conversations with hospital administrators, he didn’t order them to use the checklists. Instead, he asked them simply to gather data on their own infection rates. In early 2004, they found, the infection rates for I.C.U. patients in Michigan hospitals were higher than the national average, and in some hospitals dramatically so. Sinai-Grace experienced more line infections than seventy-five per cent of American hospitals. Meanwhile, Blue Cross Blue Shield of Michigan agreed to give hospitals small bonus payments for participating in Pronovost’s program. A checklist suddenly seemed an easy and logical thing to try.
In what became known as the Keystone Initiative, each hospital assigned a project manager to roll out the checklists and participate in a twice-monthly conference call with Pronovost for trouble-shooting. Pronovost also insisted that each participating hospital assign to each unit a senior hospital executive, who would visit the unit at least once a month, hear people’s complaints, and help them solve problems.
The executives were reluctant. They normally lived in meetings worrying about strategy and budgets. They weren’t used to venturing into patient territory and didn’t feel that they belonged there. In some places, they encountered hostility. But their involvement proved crucial. In the first month, according to Christine Goeschel, at the time the Keystone Initiative’s director, the executives discovered that the chlorhexidine soap, shown to reduce line infections, was available in fewer than a third of the I.C.U.s. This was a problem only an executive could solve. Within weeks, every I.C.U. in Michigan had a supply of the soap. Teams also complained to the hospital officials that the checklist required that patients be fully covered with a sterile drape when lines were being put in, but full-size barrier drapes were often unavailable. So the officials made sure that the drapes were stocked. Then they persuaded Arrow International, one of the largest manufacturers of central lines, to produce a new central-line kit that had both the drape and chlorhexidine in it.
In December, 2006, the Keystone Initiative published its findings in a landmark article in The New England Journal of Medicine. Within the first three months of the project, the infection rate in Michigan’s I.C.U.s decreased by sixty-six per cent. The typical I.C.U.—including the ones at Sinai-Grace Hospital—cut its quarterly infection rate to zero. Michigan’s infection rates fell so low that its average I.C.U. outperformed ninety per cent of I.C.U.s nationwide. In the Keystone Initiative’s first eighteen months, the hospitals saved an estimated hundred and seventy-five million dollars in costs and more than fifteen hundred lives. The successes have been sustained for almost four years—all because of a stupid little checklist.
Pronovost’s results have not been ignored. He has since had requests to help Rhode Island, New Jersey, and the country of Spain do what Michigan did. Back in the Wolverine State, he and the Keystone Initiative have begun testing half a dozen additional checklists to improve care for I.C.U. patients. He has also been asked to develop a program for surgery patients. It has all become more than he and his small group of researchers can keep up with.
But consider: there are hundreds, perhaps thousands, of things doctors do that are at least as dangerous and prone to human failure as putting central lines into I.C.U. patients. It’s true of cardiac care, stroke treatment, H.I.V. treatment, and surgery of all kinds. It’s also true of diagnosis, whether one is trying to identify cancer or infection or a heart attack. All have steps that are worth putting on a checklist and testing in routine care. The question—still unanswered—is whether medical culture will embrace the opportunity.
Tom Wolfe’s “The Right Stuff” tells the story of our first astronauts, and charts the demise of the maverick, Chuck Yeager test-pilot culture of the nineteen-fifties. It was a culture defined by how unbelievably dangerous the job was. Test pilots strapped themselves into machines of barely controlled power and complexity, and a quarter of them were killed on the job. The pilots had to have focus, daring, wits, and an ability to improvise—the right stuff. But as knowledge of how to control the risks of flying accumulated—as checklists and flight simulators became more prevalent and sophisticated—the danger diminished, values of safety and conscientiousness prevailed, and the rock-star status of the test pilots was gone.
Something like this is going on in medicine. We have the means to make some of the most complex and dangerous work we do—in surgery, emergency care, and I.C.U. medicine—more effective than we ever thought possible. But the prospect pushes against the traditional culture of medicine, with its central belief that in situations of high risk and complexity what you want is a kind of expert audacity—the right stuff, again. Checklists and standard operating procedures feel like exactly the opposite, and that’s what rankles many people.
It’s ludicrous, though, to suppose that checklists are going to do away with the need for courage, wits, and improvisation. The body is too intricate and individual for that: good medicine will not be able to dispense with expert audacity. Yet it should also be ready to accept the virtues of regimentation.
The still limited response to Pronovost’s work may be easy to explain, but it is hard to justify. If someone found a new drug that could wipe out infections with anything remotely like the effectiveness of Pronovost’s lists, there would be television ads with Robert Jarvik extolling its virtues, detail men offering free lunches to get doctors to make it part of their practice, government programs to research it, and competitors jumping in to make a newer, better version. That’s what happened when manufacturers marketed central-line catheters coated with silver or other antimicrobials; they cost a third more, and reduced infections only slightly—and hospitals have spent tens of millions of dollars on them. But, with the checklist, what we have is Peter Pronovost trying to see if maybe, in the next year or two, hospitals in Rhode Island and New Jersey will give his idea a try.
Pronovost remains, in a way, an odd bird in medical research. He does not have the multimillion-dollar grants that his colleagues in bench science have. He has no swarm of doctoral students and lab animals. He’s focussed on work that is not normally considered a significant contribution in academic medicine. As a result, few other researchers are venturing to extend his achievements. Yet his work has already saved more lives than that of any laboratory scientist in the past decade.
I called Pronovost recently at Johns Hopkins, where he was on duty in an I.C.U. I asked him how long it would be before the average doctor or nurse is as apt to have a checklist in hand as a stethoscope (which, unlike checklists, has never been proved to make a difference to patient care).
“At the current rate, it will never happen,” he said, as monitors beeped in the background. “The fundamental problem with the quality of American medicine is that we’ve failed to view delivery of health care as a science. The tasks of medical science fall into three buckets. One is understanding disease biology. One is finding effective therapies. And one is insuring those therapies are delivered effectively. That third bucket has been almost totally ignored by research funders, government, and academia. It’s viewed as the art of medicine. That’s a mistake, a huge mistake. And from a taxpayer’s perspective it’s outrageous.” We have a thirty-billion-dollar-a-year National Institutes of Health, he pointed out, which has been a remarkable powerhouse of discovery. But we have no billion-dollar National Institute of Health Care Delivery studying how best to incorporate those discoveries into daily practice.
I asked him how much it would cost for him to do for the whole country what he did for Michigan. About two million dollars, he said, maybe three, mostly for the technical work of signing up hospitals to participate state by state and coördinating a database to track the results. He’s already devised a plan to do it in all of Spain for less.
“We could get I.C.U. checklists in use throughout the United States within two years, if the country wanted it,” he said.
So far, it seems, we don’t. The United States could have been the first to adopt medical checklists nationwide, but, instead, Spain will beat us. “I at least hope we’re not the last,” Pronovost said.
Recently, I spoke to Markus Thalmann, the cardiac surgeon on the team that saved the little Austrian girl who had drowned, and learned that a checklist had been crucial to her survival. Thalmann had worked for six years at the city hospital in Klagenfurt, the small provincial capital in south Austria where the girl was resuscitated. She was not the first person whom he and his colleagues had tried to revive from cardiac arrest after hypothermia and suffocation. They received between three and five such patients a year, he estimated, mostly avalanche victims (Klagenfurt is surrounded by the Alps), some of them drowning victims, and a few of them people attempting suicide by taking a drug overdose and then wandering out into the snowy forests to fall unconscious.
For a long time, he said, no matter how hard the medical team tried, it had no survivors. Most of the victims had gone without a pulse and oxygen for too long by the time they were found. But some, he felt, still had a flicker of viability in them, and each time the team failed to sustain it.
Speed was the chief difficulty. Success required having an array of equipment and people at the ready—helicopter-rescue personnel, trauma surgeons, an experienced cardiac anesthesiologist and surgeon, bioengineering support staff, operating and critical-care nurses, intensivists. Too often, someone or something was missing. So he and a couple of colleagues made and distributed a checklist. In cases like these, the checklist said, rescue teams were to tell the hospital to prepare for possible cardiac bypass and rewarming. They were to call, when possible, even before they arrived on the scene, as the preparation time could be significant. The hospital would then work down a list of people to be notified. They would have an operating room set up and standing by.
The team had its first success with the checklist in place—the rescue of the three-year-old girl. Not long afterward, Thalmann left to take a job at a hospital in Vienna. The team, however, was able to make at least two other such rescues, he said. In one case, a man was found frozen and pulseless after a suicide attempt. In another, a mother and her sixteen-year-old daughter were in an accident that sent them and their car through a guardrail, over a cliff, and into a mountain river. The mother died on impact; the daughter was trapped as the car rapidly filled with icy water. She had been in cardiac and respiratory arrest for a prolonged period of time when the rescue team arrived.
From that point onward, though, the system went like clockwork. By the time the rescue team got to her and began CPR, the hospital had been notified. The transport team got her there in minutes. The surgical team took her straight to the operating room and crashed her onto heart-lung bypass. One step went right after another. And, because of the speed with which they did, she had a chance.
As the girl’s body slowly rewarmed, her heart came back. In the I.C.U., a mechanical ventilator, fluids, and intravenous drugs kept her going while the rest of her body recovered. The next day, the doctors were able to remove her lines and tubes. The day after that, she was sitting up in bed, ready to go home.
What Makes a Good Clinical Teacher in Medicine? A Review of the Literature.

Clinical Education Academic Medicine. 83(5):452-466, May 2008.Sutkin, Gary MD; Wagner, Elizabeth; Harris, Ilene PhD; Schiffer, Randolph MD
Abstract: Purpose: The authors perform a review of the literature pertinent to the question, "What makes a good clinical teacher in medicine?"
Method: After framing the question, based on discussions of their own experiences with clinical teachers, the authors performed a search of the literature pertinent to the question, "What are the qualities of a good clinical teacher in medicine?" Between July and December, 2006, they reviewed titles from Index Medicus (1909-1966), PubMed (1966 to the present), PubMed Related Articles, and referenced articles. The initial selections were chosen by scanning pre-1966 Index Medicus title lists and post-1966 abstracts. Chosen articles were then read in their entirety, and those which described specific characteristics of clinical teachers were selected for inclusion. Qualitative analysis was used to identify themes.
Results: From 4,914 titles, 68 articles were selected for analysis-26 published before 1966, and 42 published after 1966. Four hundred eighty descriptors were identified and grouped into 49 themes, which were clustered into three main categories: physician, teacher, and human characteristics. Echoing the authors' intuitive descriptions, noncognitive characteristics dominated the descriptions and themes.
Conclusions: Excellent clinical teaching, although multifactorial, transcends ordinary teaching and is characterized by inspiring, supporting, actively involving, and communicating with students. Faculty development programs and future research should focus on development of the noncognitive attributes of clinical teachers, as well as the knowledge and skills associated with effective teaching.
Can You Catch Up on Lost Sleep?

By Molly Webster
11 may 2008--Let's do some sleep math. You lost two hours of sleep every night last week because of a big project due on Friday. On Saturday and Sunday, you slept in, getting four extra hours. Come Monday morning, you were feeling so bright-eyed, you only had one cup of coffee, instead of your usual two. But don't be duped by your apparent vim and vigor: You're still carrying around a heavy load of sleepiness, or what experts call "sleep debt"—in this case something like six hours, almost a full nights' sleep.Sleep debt is the difference between the amount of sleep you should be getting and the amount you actually get. It's a deficit that grows every time we skim some extra minutes off our nightly slumber. "People accumulate sleep debt surreptitiously," says psychiatrist William C. Dement, founder of the Stanford University Sleep Clinic. Studies show that such short-term sleep deprivation leads to a foggy brain, worsened vision, impaired driving, and trouble remembering. Long-term effects include obesity, insulin resistance, and heart disease. And most Americans suffer from chronic deprivation. A 2005 survey by the National Sleep Foundation reports that, on average, Americans sleep 6.9 hours per night—6.8 hours during the week and 7.4 hours on the weekends. Generally, experts recommend eight hours of sleep per night, although some people may require only six hours of sleep while others need ten. That means on average, we’re losing one hour of sleep each night—more than two full weeks of slumber every year.The good news is that, like all debt, with some work, sleep debt can be repaid—though it won't happen in one extended snooze marathon. Tacking on an extra hour or two of sleep a night is the way to catch up. For the chronically sleep deprived, take it easy for a few months to get back into a natural sleep pattern, says Lawrence J. Epstein, medical director of the Harvard-affiliated Sleep HealthCenters.Go to bed when you are tired, and allow your body to wake you in the morning (no alarm clock allowed). You may find yourself catatonic in the beginning of the recovery cycle: Expect to bank upward of ten hours shut-eye per night. As the days pass, however, the amount of time sleeping will gradually decrease.For recovery sleep, both the hours slept and the intensity of the sleep are important. Some of your most refreshing sleep occurs during deep sleep. Although such sleep's true effects are still being studied, it is generally considered a restorative period for the brain. And when you sleep more hours, you allow your brain to spend more time in this rejuvenating period.As you erase sleep debt, your body will come to rest at a sleep pattern that is specifically right for you. Sleep researchers believe that genes—although the precise ones have yet to be discovered—determine our individual sleeping patterns. That more than likely means you can't train yourself to be a "short sleeper"—and you're fooling yourself if you think you've done it. A 2003 study in the journal Sleep found that the more tired we get, the less tired we feel.So earn back that lost sleep—and follow the dictates of your innate sleep needs. You’ll feel better. "When you put away sleep debt, you become superhuman," says Stanford's Dement, talking about the improved mental and physical capabilities that come with being well rested. Finally, a scientific reason to sleep in on Saturday.
Adopting Moderate Alcohol Consumption in Middle Age: Subsequent Cardiovascular Events

Dana E. King
11 may 2008--Moderate alcohol use is part of a healthy lifestyle, yet current guidelines caution nondrinkers against starting to drink alcohol in middle age. The purpose of this study was to evaluate whether adopting moderate alcohol consumption in middle age would result in subsequent lower cardiovascular risk.
Methods
This study examined a cohort of adults aged 45-64 years participating in the Atherosclerosis Risk in Communities study over a 10-year period. The primary outcome was fatal or nonfatal cardiovascular events.
Results
Of 7697 participants who had no history of cardiovascular disease and were nondrinkers at baseline, within a 6-year follow-up period, 6.0% began moderate alcohol consumption (2 drinks per day or fewer for men, 1 drink per day or fewer for women) and 0.4% began heavier drinking. After 4 years of follow-up, new moderate drinkers had a 38% lower chance of developing cardiovascular disease than did their persistently nondrinking counterparts. This difference persisted after adjustment for demographic and cardiovascular risk factors (odds ratio 0.62, 95% confidence interval, 0.40-0.95). There was no difference in all-cause mortality between the new drinkers and persistent nondrinkers (odds ratio 0.71, 95% confidence interval, 0.31-1.64).
Conclusion
People who newly begin consuming alcohol in middle age rarely do so beyond recommended amounts. Those who begin drinking moderately experience a relatively prompt benefit of lower rates of cardiovascular disease morbidity with no change in mortality rates after 4 years.
Arthritis as a Potential Barrier to Physical Activity Among Adults with Diabetes --- United States, 2005 and 2007

11 may 2008--The American Diabetes Association and the American College of Sports Medicine agree that increasing physical activity among persons with diabetes is an important public health goal to 1) reduce blood glucose and risk factors for complications (e.g., obesity and hypertension) in persons with diabetes and 2) improve cardiovascular disease outcomes (1,2). Among adults with diabetes, co-occurring arthritis might present an underrecognized barrier to increasing physical activity, but to date this has not been directly studied. To estimate the prevalence of 1) diagnosed arthritis among adults with diabetes and 2) physical inactivity among adults with diabetes by arthritis status, CDC analyzed combined 2005 and 2007 data from the Behavioral Risk Factor Surveillance System (BRFSS). This report describes the results of that analysis, which indicated that 1) arthritis prevalence was 52.0% among adults with diagnosed diabetes and 2) the prevalence of physical inactivity was higher among adults with diabetes and arthritis (29.8%) compared with adults with diabetes alone (21.0%), an association that was independent of age, sex, or body mass index (BMI). The higher prevalence of physical inactivity among adults who have both diabetes and arthritis suggests that arthritis might be an additional barrier to increasing physical activity. Health-care providers and public health agencies should consider addressing this barrier with arthritis-specific or general evidence-based self-management and exercise programs.
The BRFSS survey is a state-based, random-digit--dialed telephone survey of the civilian, noninstitutionalized U.S. adult population aged >18 years and is conducted in all 50 states, the District of Columbia (DC), Guam, Puerto Rico, and the U.S. Virgin Islands. Diabetes was defined as a "yes" response to the question, "Have you ever been told by a doctor that you have diabetes?" Doctor-diagnosed arthritis was defined as a "yes" response to the question, "Have you ever been told by a doctor or other health professional that you have some form of arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia?" This question is included in the BRFSS core questionnaire in odd-numbered years only. Physical activity level of respondents was determined from six questions* that asked about frequency and duration of participation in nonoccupational activities (i.e., lifestyle activities) of moderate and vigorous intensity; those reporting no participation in such activities were classified as inactive (i.e., engaged in no nonoccupational physical activity), and all others as active. BMI was calculated from self-reported height and weight.
To obtain adequate sample sizes for greater statistical power, CDC combined data for the 50 states and DC from 2005 and 2007, calculated estimates, and applied an annual average weighting; 95% confidence intervals (CIs) were calculated using sample design factors to account for the multistage probability sample. To assess factors potentially confounding an association between doctor-diagnosed arthritis and physical inactivity among those with diabetes, data were combined across states/areas in unadjusted and adjusted (by age, sex, and BMI) logistic regression models. Age groups were 18--44 years, 45--64 years, and >65 years. BMI groups were underweight/normal weight (BMI <25.0),>30). Statistical significance was determined by nonoverlapping CIs. State-level estimates then were calculated for the 50 states and DC (reported medians were based on these areas) and for Guam, Puerto Rico, and the U.S. Virgin Islands. Council of American Survey Organizations (CASRO) response rates among the 50 states, DC, and the three territories for 2005 ranged from 34.6% (New Jersey) to 67.4% (Alaska) (median: 51.1%), and cooperation rates ranged from 58.7% (California) to 85.3% (Minnesota) (median: 75.1%).† CASRO response rates for 2007 ranged from 26.9% (New Jersey) to 65.4% (Nebraska) (median: 50.6%), and cooperation rates ranged from 49.6% (New Jersey) to 84.6% (Minnesota) (median: 72.1%).§
During 2005 and 2007, the prevalence of arthritis among adults with diabetes was 52.0% (CI = 51.3%--52.7%), compared with 26.9% (CI = 26.7%--27.1%) for all adults aged >18 years. The prevalence of arthritis among persons with diabetes was higher than in the general population for both sexes: males (45.9% [CI = 44.8%--47.1%] versus 22.6 [CI = 22.3%--22.9%]); females (58.0% [CI = 57.1%--59.0%] versus 30.9% [CI = 30.7%--31.2%]), respectively. In addition, arthritis prevalence among persons with diabetes was higher than in the general population for all age groups (i.e., 18--44 years, 45--64 years, and >65 years): 27.6% (CI = 25.7%--29.7%) versus 11.0% (CI = 10.8%--11.2%), 51.8% (CI = 50.8%--52.9%) versus 36.4% (CI = 36.1%--36.8%), and 62.4% (CI = 61.3%--63.5%) versus 56.2% (CI = 55.8%--56.6%), respectively. Prevalence of physical inactivity was lowest among adults without arthritis or diabetes (10.9% [CI = 10.7%--11.1%]), higher among adults with arthritis alone (17.3% [CI = 17.0%--17.6%]) and diabetes alone (21.0% [CI = 20.0%--22.1%]), and highest among adults with both conditions (29.8% [CI = 29.0%--30.7%]) (Figure). In logistic regression analyses, the unadjusted odds ratio (OR) for the association between doctor-diagnosed arthritis and physical inactivity among adults with doctor-diagnosed diabetes was 1.6 (CI = 1.3--1.7); adjusted for age and sex, the OR was 1.4 (CI = 1.3--1.5); and adjusted for age, sex, and BMI, the OR was 1.3 (CI = 1.2--1.4). In state-specific analyses, the state median prevalence estimate of physical inactivity among adults with diabetes and arthritis was 28.9% (range: 20.2% in California to 46.4% in Tennessee). The state median prevalence estimate of physical inactivity among adults who had diabetes and no arthritis was 19.5% (range: 9.0% in Alaska to 30.2% in West Virginia) (Table).
Reported by: J Bolen, PhD, J Hootman, PhD, CG Helmick, MD, L Murphy, PhD, G Langmaid, Div of Adult and Community Health, CJ Caspersen, PhD, Div of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, CDC.
Editorial Note:
In the United States, approximately 20.6 million adults were reported to have diabetes in 2005 (3), with nearly seven in 10 having diabetes diagnosed by a health professional. In addition, during 2003--2005, approximately 46.4 million adults had arthritis (4). Because physical activity is a recommended self-management strategy for both conditions, examining the effect of co-existing arthritis and diabetes on physical activity levels is warranted.
The results of this analysis indicated that, during 2005 and 2007, doctor-diagnosed arthritis affected approximately half of adults with doctor-diagnosed diabetes. The prevalence of self-reported physical inactivity was significantly higher among those with arthritis and diabetes than among those with diabetes alone. This association remained significant after adjustment for age, sex, and BMI, factors that might have otherwise explained the association. State-specific estimates were consistent with the overall findings, with state-to-state differences likely attributable to differences in the distribution of factors associated with both arthritis and physical inactivity in the state population. Because BRFSS data are cross-sectional, they can only demonstrate an association; the temporal sequence of condition onset is unknown.
The associations between arthritis and physical inactivity among adults with diabetes found in this analysis suggest that arthritis might be a barrier to being physically active in this population. Being more physically active (e.g., through aerobic exercise or strength training) can benefit persons with either arthritis or diabetes and those with both conditions (1). Persons with diabetes who are inactive and become more active benefit from improved physical function and glucose tolerance (5), but they face the same common barriers to being more physically active as most adults, such as lack of time, competing responsibilities, lack of motivation, and difficulty finding an enjoyable activity (6). Those who also have arthritis face additional disease-specific barriers, such as concerns about aggravating arthritis pain (6) and causing further joint damage, and they might be unsure about which types and amounts of activity are safe for their joints. Health-care providers interested in improving diabetes management might want to especially consider arthritis-related barriers among persons with diabetes who are physically inactive.
Specially tailored self-management education interventions, such as the Chronic Disease Self Management Program (7) and the arthritis-specific Arthritis Foundation Self-Help Program, help adults learn to manage arthritis pain and discuss how to safely increase physical activity (8). In addition, several exercise programs, including EnhanceFitness (2), the Arthritis Foundation Exercise Program, and the Arthritis Foundation Aquatics Program (8), are available in many communities and are appropriate for adults with diabetes and arthritis. Self-directed physical activities, including joint-friendly activities such as walking, swimming, and biking, also are appropriate for adults with both conditions.¶
The findings in this report are subject to at least five limitations. First, doctor-diagnosed arthritis, doctor-diagnosed diabetes, and activity level are self-reported in BRFSS and have not been confirmed by a health-care provider or objective monitoring; however, such self-reports have been shown to be valid for surveillance purposes (9,10). Second, BRFSS is a telephone survey and does not include persons without landline telephones, persons in the military, or those residing in institutions. Third, comparisons of tabular data between states should be made with caution because the prevalence estimates are not adjusted for population characteristics (e.g., age) that might explain differences. Unadjusted data are presented in this report to provide actual estimates for state-level program planning. Fourth, BRFSS response rates were low for both survey years. BRFSS weighting procedures partially correct for nonresponse. The effect of low response rates is uncertain. Finally, the findings in this report do not account for persons with undiagnosed diabetes.
In 2007, CDC released a reference guide for planning physical activity interventions for older adults, including those with diabetes (2). This guide suggests different programs sensitive to the medical needs of persons with diabetes and those with chronic disease complications or physical limitations, and promotes active aging among persons not yet limited by complications or limitations of diabetes or arthritis. Because arthritis appears to be an additional barrier to increasing physical activity, state-level diabetes programs whose aim is to increase physical activity among adults with diabetes might meet their own goals more readily by integrating their efforts with arthritis programs.

Saturday, May 10, 2008


Medical know-how raises suicide risk for doctors

By LINDSEY TANNER
10 may 2008--There's a grim, rarely talked-about twist to all that medical know-how doctors learn to save lives: It makes them especially good at ending their own. An estimated 300 to 400 U.S. doctors kill themselves each year — a suicide rate thought to be higher than in the general population, although exact figures are hard to come by.
Some doctors believe the stigma of mental illness is magnified in a profession that prides itself on stoicism and bravado. Many fear admitting psychiatric problems could be fatal to their careers, so they suffer in silence.
And when the pain is too much, doctors have easy access to prescription drugs and a precise knowledge of both how the body works and the amount of a drug needed for an overdose to stop breathing and halt the heart.
"All physicians have access to neat, clean ways to commit suicide," said Dr. Robert Lehmberg, a Little Rock, Ark., surgeon who has battled depression and long considered suicide "an exit strategy if absolutely necessary."
The American Medical Association has called physician suicide "an endemic catastrophe," and pledged two years ago to work to prevent the problem.
But the suicides have persisted. So the American Foundation for Suicide Prevention has launched an educational campaign in hopes of making troubled doctors more willing to seek help.
The foundation, the American College of Psychiatrists and Wyeth Pharmaceuticals, a maker of antidepressant pills, paid for the program. It includes a documentary titled "Struggling in Silence" that begins airing on public television stations this week.
"It really has been swept under the carpet," said Dr. Paula Clayton, the suicide foundation's medical director.
The foundation says 300 to 400 doctors commit suicide each year, based on estimates from research, but that more studies are needed to get a more precise count.
Another estimate of 250 yearly comes from an online article by Dr. Louise Andrew and in American Medical News, an AMA publication. But a spokesman said the AMA doesn't track doctor suicides because accurate numbers aren't available.
Suicide figures in broader society are not completely reliable because suicide is often not given as the cause of death.
The overall U.S. suicide rate among men is four times higher than in women — about 23 per 100,000 versus about 6 per 100,000 in women, according to the most recent government data.
But among doctors, suicide rates are about equal for men and women.
A 28-state study from 1984-95 found women doctors were more than twice as likely as women in the general population to kill themselves. Men were more than 70 percent more likely inside the medical profession than overall to commit suicide.
One explanation is that most suicide attempts in the broader population are unsuccessful, while doctors know how to successfully commit suicide, said Dr. Erika Frank, who specializes in research on physician health.
Depression is often the problem.
Depressed doctors frequently decide to self-medicate but don't seek psychotherapy that could help them deal with underlying issues, said Dr. Glenn Siegel, who runs a suburban Chicago program that treats doctors with drug abuse, depression and other psychiatric problems.
"It's not a safe topic to be as open about in that profession because you're responsible for the well-being of others," Siegel said. "If you're admitting something like that, you're saying maybe you're not fit to do your job."
Adds Lehmberg, the Arkansas surgeon, who is featured in the documentary: "You just would rather take a risk with your health than your career. It's not like you get a second chance with it."
A psychiatrist in the New York area who asked to remain unidentified said he had suicidal thoughts every day for several years. But in medical school in the 1980s, he said he was so embarrassed about seeking help for depression that he went to a pay phone instead of his dorm to call a therapist.
Since then, some schools have begun teaching medical students about depression among doctors, but, he said in an interview, "so much more needs to be done."
Because the stigma persists, he said he didn't want his name used to avoid hurting his family and relationships with colleagues and patients.
Some studies have suggested depression is more common among doctors, especially women physicians, and that the high demands of a job dealing with life-and-death issues makes them prone.
But Frank questions that and said she worries that singling out physicians risks "pathologizing" a profession whose members generally "have it awfully good."
"I think the situation gets portrayed as far more grave than it really is for physicians compared to anyone else in the world," Frank said.
There could be reasons why the stigma would be worse for doctors, "but you can come up with just as many reasons why physicians would be better equipped to acknowledge" mental illness, she said.
"We've all done psychiatric training. We all know bad mental health outcomes happen to good people," she said.
A study in Denmark, published last year, found more suicides in doctors than among more than 20 other professions, including nurses, factory workers, elementary school teachers, corporate managers and architects.
But there are few comprehensive studies on suicides among U.S. doctors.
Some have been based on newspaper obituaries, which are "flawed at best" because suicide often isn't listed as a cause of death, said Dr. Morton Silverman, a University of Chicago suicide expert.
New Jersey physician Ron Brown suffered from depression and killed himself in 2002. His widow, Mumtaz Bari-Brown, said she believes the stigma kept her husband from getting help in time to save his life.
As a boy, Brown had been told his father died of a heart attack, not the real cause of suicide, the widow said.
"We have to stop the hiding and the ignorance and recognize it as a disease like high blood pressure or diabetes," said Bari-Brown, who also is featured in the new documentary.
Dr. G. Richard Smith, Lehmberg's doctor and director of the University of Arkansas for Medical Sciences' psychiatric research institute, said doctors need assurance they won't risk their jobs if they seek psychiatric help.
Smith succeeded in getting changes to questions on medical license applications in Arkansas that he believes will help. The old application asked doctors if they were being treated for mental illness or ever had been. A "yes" answer required a psychiatrist's note declaring they were fit to practice medicine. Now, they need only disclose mental health treatment that was advised or required by medical authorities.
The previous form didn't keep doctors with psychiatric problems from practicing, Smith said. But it did keep "doctors who needed treatment from getting the treatment that they needed."
Acrylamide Raises Kidney Cancer Risk

By Kathleen Doheny
10 may 2008-- Consuming large amounts of acrylamide, a chemical commonly found in French fries, cakes, snacks and even coffee, appears to raise the risk of kidney cancer, especially in smokers, Dutch researchers report.
"Ours is the first report of a positive association between dietary acrylamide intake and renal cell [kidney] cancer," said study author Janneke Hogervorst, a researcher at Maastricht University in the Netherlands.
The report is published in the May issue of the American Journal of Clinical Nutrition.
Studies of the chemical have been ongoing since 1994, when the International Agency for Research on Cancer classified the chemical as a probable human carcinogen. Experts thought the main exposure was environmental, through cigarette smoke and, to a lesser extent, cosmetics.
But in 2002, Swedish scientists reported the presence of the chemical in carbohydrate-rich foods produced at high temperatures, including French fries and potato chips.
Studies of the chemical's link to various cancers have yielded mixed results.
The Dutch research team took data from the Netherlands Cohort Study on diet and cancer, which includes more than 120,000 men and women, aged 55 to 69. They followed them for more than 13 years, looking at all the cases of kidney, bladder and prostate cancers. They took a random sample of 5,000 people to look at their dietary habits.
The average intake of acrylamide from the diet was 21.8 micrograms -- a little less than what is included in a 2.5-ounce serving of French fries. Those who took in the most -- averaging 40.8 micrograms a day -- had a 59 percent higher risk of kidney cancer (but not the other cancers) than those consuming the least.
For most people, coffee was the major source of the chemical. However, a popular snack, Dutch spiced cake, was the main source of the chemical for those consuming the most. The relationship was found to be stronger for smokers.
For each additional 10 micrograms ingested of the chemical, kidney cancer risk increased by 10 percent, the researchers found.
In another study published in the same issue of the journal, researchers found no association between dietary fat intake and prostate cancer risk.
One expert praised the acrylamide study but added that more research is needed. It is also difficult to know how much impact smoking has on the cancer risk, said Marji McCullough, a nutritional epidemiologist for the American Cancer Society.
"Smoking is a [known] risk factor for this [kidney] cancer," she said.
Exactly how the acrylamide boosts cancer risk isn't known, she added, "but the hypothesis is that metabolites [breakdown products] of the acrylamide cause DNA damage."
Limiting the consumption of foods containing the chemical is wise, Hogervorst said. "Also, in preparing food at home, fry potatoes at temperatures below 175 degrees Celsius and fry them to gold-yellow, not dark brown [the more brown, the more acrylamide]. The same goes for making toast and cookies."
McCullough added: "It's best not to smoke and to maintain an ideal body weight. One way to maintain a healthy body weight is a healthy diet."
And that, of course, means limiting the French fries and other snacks.
More information
To learn more about kidney cancer, visit the American Cancer Society.
Prostate cancer deaths fall after screening program

10 may 2008--Prostate cancer deaths fell substantially in the decade after one Austrian state began free PSA screening tests for all men ages 45 to 75, according to a new study.
Researchers found that after the state of Tyrol began a program of free PSA screening and prostate cancer treatment in 1993, the expected death rate from prostate cancer dropped by 54 percent. That compared with a decline of 29 percent in the rest of Austria, where free screening was not available.
The findings, reported in the journal BJU International, suggest that routine PSA testing can save men's lives -- something that has long been an open question.
PSA tests measure the amount of a protein called prostate-specific antigen in a man's blood. Because prostate tumors cause PSA levels to rise, routine PSA testing can catch the cancer early.
But PSA screening is controversial because it is not clear that the benefits outweigh the risks. Prostate cancer is often very slow-growing, and PSA screening may lead to treatment of tumors that would never have become life-threatening; treatment can carry side effects, like incontinence and erectile dysfunction.
In addition, PSA concentrations can increase for a reason other than prostate cancer and confirmation of prostate cancer requires a biopsy of the prostate gland, which itself can have side effects, such as infection or bleeding.
However, in the current study, early detection through widespread PSA screening is likely the driving force behind the greater drop in death rates seen in Tyrol, according to the researchers.
Between 1993 and 2005, nearly 87 percent of men ages 45 to 75 in Tyrol had at least one PSA screening test, the study found. That was up from 11 percent before the free program began.
And while prostate cancer death rates declined throughout Austria during the same period, they fell faster in Tyrol.
"Before the program was introduced, prostate cancer death rates in the Tyrol were similar to the rest of the country," lead researcher Dr. Georg Bartsch, of the University of Innsbruck, said in a statement.
"But after the program was launched the death rate in the Tyrol started falling by an average of 7.3 percent a year, more than twice the 3.2 percent observed in the rest of Austria."
The researchers acknowledge, however, that routine PSA screening remains controversial, and questions such as which men stand to benefit most from screening are still unresolved.
In general, experts recommend that men speak with their doctors about the potential benefits and risks of PSA screening for them personally. The American Cancer Society recommends that doctors offer most men PSA testing and a digital rectal exam yearly, starting at age 50.
SOURCE: BJU International, April 2008.
Carotid Bruit May Predict Cardiovascular Risk

By Charles Bankhead
WASHINGTON, 10 may 2008 -- Checking for carotid bruit can identify patients at high cardiovascular risk, a meta-analysis here suggested.Carotid bruit doubled the risk of myocardial infarction and almost tripled the risk of cardiovascular death, Christopher Pickett, M.D., of Walter Reed Army Medical Center, and colleagues reported in the May 10 issue of The Lancet.When the analysis was limited to studies that permitted direct comparison of patients with and without bruit, the risk of MI and cardiovascular death remained twice as high in those with bruit.
"Our findings accord with the notion that these atherosclerotic changes [that lead to bruit] might be indicative of system-wide vascular pathological change to include the coronary bed," the authors concluded. "Clinicians auscultating a carotid bruit should be concerned that atherosclerosis might not just reside solely in the carotid artery."
They added, "Since auscultation of the carotid is a swift and inexpensive test, it should be used in every patient who might be at risk for coronary heart disease to aid the clinician in assessment of cardiac risk."
The prognostic implications of carotid bruit have focused primarily on cerebrovascular events. However, carotid bruit has only weak predictive accuracy for cerebrovascular events in patients who are otherwise symptomatic, the authors noted.
As a result of the prognostic uncertainty of carotid bruit, screening recommendations vary. For example, the U.S. Preventive Services Task Force and the Canadian Task Force recommend against routine auscultation for carotid bruit, the authors continued. On the other hand, the American Academy of Family Physicians and other groups recommend screening auscultation in select patients.
"Carotid bruits are probably a better indicator of generalized atherosclerotic disease than of stroke risk, and several studies have suggested that patients with carotid artery disease are more likely to die from cardiovascular than from cerebrovascular disease," the authors said.
To examine bruits' predictive accuracy for cardiovascular death and MI, Dr. Pickett and colleagues analyzed data from 22 studies involving a total of 17,295 patients with 62,413.5 patient-years of follow-up. Median duration of follow-up was four years.
The analysis showed that patients with bruits had an MI rate of 3.69 per 100 patient-years versus 1.86 per 100 patient-years in those without bruits. The yearly rate of cardiovascular death was 2.85 versus 1.11 per 100 patient-years, respectively, for patients with and without bruits.
The design of four trials allowed direct comparisons of patients with and without bruits. In that analysis, patients with bruits had a two-fold greater risk of MI (OR 2.15, 95% CI 1.67 to 2.78) and cardiovascular death (OR 2.27, 95% CI 1.49 to 3.49).
In a commentary accompanying the article, Victor Aboyans, M.D., and Philippe Lacroix, M.D. of Dupuyten Hospital in Limoges, France, cited several limitations of the study and findings.
About a third of the study participants had existing cardiovascular disease. Bruit's influence on secondary prevention is unclear.
Bruit's prognostic value was not compared with cardiovascular risk scores, making the incremental value unknown.
Patients without bruit have other clinical signs that could have similar prognostic significance.
Despite those limitations, the editorialists suggested that evaluation of patients for bruit could be added to other simple tests for a simple office-based assessment capable of identifying high-risk patients.
"Prospective studies on asymptomatic patients are needed to study the prognostic value of a combination of simple clinical signs such as neck and groin auscultation and pulse palpation," said Drs. Aboyans and Lacroix. "Heart rate, pulse pressure, or blood-pressure difference between arms could also be considered."
They added, "These studies could narrow the indications of cardiovascular imaging techniques and make them more cost effective in developed countries. In developing countries, the same data could help make the best use of very limited resources dedicated to prevention of cardiovascular disease."
The authors and the editorialists declared no conflicts of interest.
Primary source: The LancetSource reference:Pickett CA, et al "Carotid bruits as a prognostic indicator of cardiovascular death and myocardial infarction: A meta-analysis" Lancet 2008.

Friday, May 09, 2008

AGS: Protocol Shortens Time on Ventilator

By Peggy Peck
WASHINGTON, 10 may 2008 -- ICU patients put on a coordinated, combination weaning protocol spent three fewer days on a ventilator than those for whom traditional methods were used, researchers here reported.The intervention, called the "wake up and breathe" protocol, combines tests of spontaneous breathing along with a reduction in sedative use to trigger awakening, Timothy Girard, M.D., of Vanderbilt University in Nashville, Tenn., told attendees at the American Geriatrics Society meeting. The protocol has demonstrated efficacy in younger adults, but had not previously been tested in older patients, Dr. Girard said. Presenting results of a prespecified subgroup analysis from the Awakening and Breathing Controlled (ABC) Trial, Dr. Girard said that longer ventilator use was associated with worse outcomes, so several strategies aimed at shortening ventilator time have been studied.
"In general the weaning period, the period following fulminate disease, is considered the most amenable to shortening," he said.
Previous studies have investigated weaning with trials of spontaneous breathing, in which the ventilator is turned off or very low and the patient is observed to see if he or she is able to breathe on his or her own. Typically, this test is conducted by a respiratory therapist.
Other studies have investigated spontaneous awakening in which sedation is turned off and the patient is observed for signs of agitation or other problems. Such sedation management is usually handled by nurses.
The two processes are not necessarily coordinated.
In this study, "we developed a very streamlined process that combined both sedation and mechanical support," Dr. Girard said.
The patient was first evaluated to determine if he or she was a candidate for a trial of awakening using a safety screen that evaluated use of paralytics, pain, agitation, whether the patient was suffering alcohol withdrawal, and other factors.
If the patient passed the safety screen, "we had the green light to turn off the sedation," he said. A patient passed this stage of the protocol if he could respond to a simple command to open his eyes.
Patients who failed the trial were again sedated and the protocol was attempted again the following day.
Patients who passed the wake-up stage proceeded to the "breathe" stage of the protocol. Again they were evaluated with a safety screen that assessed weaning risks.
If they passed that safety screen, the ventilator was turned off or to a very low level, and the patient was closely observed for two hours. Patients who completed the two-hour trial without incident were extubated, those who had difficulty were returned to increased or full ventilator support.
The study endpoint was number of days free of ventilator support.
The trial, which was conducted at four participating centers, enrolled 335 mechanically ventilated patients, including 147 who were 65 or older. Consent, Dr. Girard said, was usually obtained from a family member because most patients could not communicate.
Patients were randomized to the wake up and breathe intervention or to usual care in which both ventilator weaning and sedation were managed based on sporadic clinical observation.
Overall, the intervention was associated with a three-day reduction in ventilator time and, for the oldest patients, "those in their 70s, the reduction was four days, which was statistically significant (P=0.04)," Dr. Girard said.
Average coma time was two days shorter (P=0.03) for the intervention patients and ICU stay was seven days shorter (median stay six days versus 13 days P=0.02), he said.
One-year mortality was also lower in the intervention group (37 deaths versus 52 in the control group), but that difference was not statistically significant.
Most importantly, Dr. Girard said, was "the homogeneity tests for treatment interaction with age. The treatment effects in older patients did not differ significantly from those observed in younger patients."
The study was funded by the Saint Thomas Foundation, Hartford Geriatrics Health Outcomes Research Scholars Award Program, Vanderbilt University, and the National Institutes of Health.
Dr. Girard reported no conflicts of interest.

Primary source: American Geriatrics SocietySource reference:Girard TP, et al "Outcomes among older mechanically ventilated icu patients treated with a wake up and breathe protocol" P 34.

Pelvic floor maladies can impact women's sex life


By Amy Norton

09 may 2008--Incontinence and other disorders of the pelvic organs can take a toll on a woman's sex life, a new study suggests.
Researchers found that among 300 women age 40 and older, those with symptoms of a pelvic floor disorder were more likely to have a diminished libido, pain during sex, or problems reaching orgasm.
Pelvic floor disorders refer to problems with a woman's pelvic organs -- the uterus, bladder and rectum -- and the muscles and connective tissue that support them. Among the most common of these are urinary incontinence and pelvic organ prolapse, where weakened muscles and supporting tissue allow one or more pelvic organs to drop down and protrude into the vagina.
Some symptoms of prolapse include pressure in the vagina, pain in the lower abdomen or lower back, and chronic constipation.
It has been estimated that one-third of U.S. women have at least one type of pelvic floor disorder, but studies have come to conflicting conclusions as to whether the conditions hinder women's sex lives.
The new findings, reported in the journal Obstetrics & Gynecology, suggest that many women with these disorders do, in fact, have problems with sexual function.
However, the risk of sexual dysfunction was not elevated among women who had mild prolapse that was not causing symptoms, lead researcher Dr. Victoria Handa told Reuters Health.
This is important, she explained, because it indicates that women who have sexual complaints but no other potential symptoms of pelvic organ prolapse do not need to be evaluated for the disorder.
"Sexual function is unlikely to be impacted by mild prolapse," said Handa, an associate professor of gynecology and obstetrics at Johns Hopkins University in Baltimore.
The findings are based on 301 patients recruited from gynecology offices affiliated with Johns Hopkins. Eighty women were seeking care for a pelvic floor disorder, including bladder control problems and pelvic organ prolapse. The rest of the women had other conditions or were getting a routine checkup.
All of the women completed questionnaires on their overall health, pelvic symptoms and sexual function.
Overall, the researchers found, women with pelvic floor disorders were more likely to have symptoms of a decreased sex drive, pain during sex and infrequent orgasms -- regardless of age and whether they had gone through menopause.
The study does not prove that the pelvic floor disorders caused the women's sexual problems, Handa said. However, the conditions could impair women's sexual function for a number of reasons, from diminished body image to problems with muscle and nerve function.
According to Handa, women with pelvic floor disorders should talk with their doctors about any sexual difficulties they have.
In an earlier study, she and her colleagues found that women's sexual function often improved after having surgery to correct significant prolapse. But more research is needed into this area, Handa said.
If certain treatments for pelvic floor disorders are better than others for improving sexual function, she noted, that will be important to know.
SOURCE: Obstetrics & Gynecology, May 2008.
More than half of US diabetics have arthritis

By MIKE STOBBE
09 may 2008--More than half of U.S. adults with diabetes also have arthritis, raising a serious obstacle for diabetic patients urged to exercise, according to a government study.
The survey of nearly 800,000 people is the first extensive look at the overlap between the two conditions, said Dr. John Klippel, president of the Arthritis Foundation.
And its findings highlight a significant challenge: Most diabetics are told exercise is important to their health, but experts say many of them don't do it.
People with diabetes who exercise have better control of their blood sugar and a much lower risk of heart disease complications. But the new research suggests many diabetics see themselves as unable to exercise because of arthritis, said Julia Simard, a Harvard School of Public Health researcher who has studied rheumatoid arthritis and diabetes.
"If you have this perception of ill health, it may affect your willingness to be active," said Simard, who was not involved in the new research.
More than 46 million Americans have some form of arthritis, and nearly 21 million have diabetes. Other research indicates exercise is important in managing both conditions.
The study found that 52 percent of diabetics said they also had arthritis. The conditions and the overlap were most common in Americans 65 and older.
The analysis was based on telephone surveys in the years 2005 and 2007 by the Centers for Disease Control and Prevention. Researchers relied on what people said about their health, and did not verify diagnoses.
The researchers also asked about exercise and physical activity. People with both diabetes and arthritis were 30 to 40 percent more likely to be physically inactive than those who had diabetes alone.
"If we're ever going to successfully control a disease like diabetes, we're going to have to pay a lot of attention to arthritis," Klippel said.
Exercise that put less stress on joints, such as walking, biking and aquatics, are recommended for people with arthritis, said Dr. Chad Helmick, a CDC epidemiologist who co-authored the study.
Breast Tumors Grow More Slowly with Age

By Crystal Phend
OSLO, Norway,09 may 2008 -- In women between 50 and 70, breast tumor growth is faster in those at the younger end of the spectrum, which may have implications for sensitivity of breast cancer screening programs, researchers said.The estimated time for a tumor to double in diameter from 10 to 20 mm was 1.4 years in women ages 50 to 59 compared with 2.1 years for women 60 to 69, reported Harald Weedon-Fekjær, Ph.D., of the Cancer Registry of Norway and University of Oslo, and colleagues, online in Breast Cancer Research.The sensitivity of mammographic screening would rise with tumor size from 26% at 5 mm to 91% at 10 mm, according to a mathematical model developed in the large registry study.
Tumor growth rates are important for determining intervals between mammographic screening and ages at which mammography is recommended for women, the researchers said.
Previous studies have found decreasing tumor progression with older age, but this measure of growth rates was indirect, typically used a model without "explicit relation to the biological process of tumor growth," and was often difficult to compare between different countries, they said.
To develop a model directly connected to tumor measurements, the researchers examined data from the Cancer Registry of Norway. The analysis included first mammograms for 395,188 women ages 50 to 69 and clinical data from tumors found through screening.
The mean time for tumors to grow from 10 to 20 mm was estimated at 1.7 years, but growth varied widely, with a standard deviation of 2.2 years.
Time for a tumor to double in diameter from 15 to 30 mm ranged from an average 41 to 234 days for the first and last quartiles, respectively.
The mammography screening test sensitivity estimates increased sharply with tumor size, reaching 26% at 5 mm and 91% at 10 mm.
However, estimated sensitivity did not differ by age (P=0.83 at 5 mm), which Dr. Weedon-Fekjær and colleagues said was surprising.
According to simulations using the model and data for another group of women with clinically detected breast cancer, almost all cancers among women in the screening population would have been visible at mammography before reaching clinical detection.
The mean time tumors would be visible at screening before clinical detection was 2.9 years overall and significantly longer in older women.
The model developed in the study appeared to be a better fit to the registry data than the classical Markov model (P<0.0001) and increased the predictive power for observed versus predicted number of cases by 85%.
Estimates in the new model did not appear to be biased by missing tumor measurements in the registry, the researchers said.
However, the model appeared to be less effective at predicting cancer incidence on subsequent rounds of screening.
It predicted a 71% drop in detected cancers from the first to second screening whereas as decline of 46% was observed.
"In addition to possible problems with the model itself," the investigators said, "this can be an effect of changes in hormone replacement therapy use in the study period, of increased sensitivity in the second round due to use of earlier mammograms, of better training of staff with time, or of an overrepresentation of communities with high cancer risk in the second screening round."
The relatively high rate of hormone therapy use, which increases breast density, during the study period may have affected tumor growth as well as mammographic screening sensitivity, they noted.
The project received financial support from the Norwegian Cancer Society. The researchers reported no conflicts of interest.
Additional source: Breast Cancer ResearchSource reference: Weedon-Fekjær H, et al "Breast cancer tumor growth estimated through mammography screening data" Breast Cancer Res 2008; DOI: 10.1186/bcr2092.
APA: Bipolar Disorder Both Under- and Overdiagnosed

By John Gever
WASHINGTON, 09 may 2008-- More than half the patients who were told they have bipolar disorder may have been misdiagnosed, even as it goes unrecognized in a substantial number of those who really do have it, a researcher said here.
In 145 psychiatric outpatients who said they had been previously diagnosed with bipolar disorder, the condition was ruled out in 56.6% after they underwent the Structured Clinical Interview for DSM-IV, the diagnostic "gold standard," said Mark Zimmerman, M.D., of Brown University in Providence, R.I.
The structured evaluation also revealed that, of 555 other patients who had not previously received a diagnosis of bipolar disorder, 27 actually did have the condition, Dr. Zimmerman told attendees at the American Psychiatric Association meeting.
All told, out of 700 psychiatric outpatients, 90 were diagnosed with bipolar disorder with the structured interview. The disorder had gone unrecognized in nearly one-third of them, Dr. Zimmerman said.
The research was also published simultaneously online in the Journal of Clinical Psychiatry.
Dr. Zimmerman blamed the overdiagnosis of bipolar disorder on drug companies and others seeking to reduce under-diagnosis, which he said was also a real problem.
"I think there has been a marketing campaign and it has had an impact," Dr. Zimmerman said.
Noting the frequency with which patients ask if they are bipolar, he added, "I've never had a patient come into my office and ask, 'Do I have borderline personality disorder?'"
The study was part of a larger investigation in which 2,500 patients presenting at an outpatient psychiatric clinic filled out questionnaires. For the most recent 700 patients, the questionnaire asked whether the patient had previously received a diagnosis of bipolar disorder.
Dr. Zimmerman acknowledged that the reliance on self-reports, without review of clinical records, was a limitation of the study.
All patients were subsequently evaluated with the Structured Clinical Interview for DSM-IV and other validated instruments.
The evaluation confirmed the diagnosis of bipolar disorder in only 63 of the 145 patients reporting a previous bipolar diagnosis.
The investigators examined family histories of those who did not have a bipolar diagnosis. They found no differences in the prevalence of bipolar disorder in first-degree relatives between those never diagnosed with the condition and those whose initial diagnosis was overturned in the structured interview.
Dr. Zimmerman said the finding confirmed the validity of the structured evaluation process.
He said that overdiagnosis of bipolar disorder leads to over-treatment with mood stabilizers, putting patients at risk for liver, kidney, and metabolic side effects. Patients with such diagnoses may also be more likely to receive drug therapies than counseling.
Although Dr. Zimmerman's presentation was titled "Is Bipolar Disorder Overdiagnosed?", he said the study also supported the more prevalent view that it is under-diagnosed, given that bipolar disease had been missed in 27 of 90 genuinely bipolar patients.
He said bipolar disorder may go unrecognized for a variety of reasons. Depression symptoms typically last much longer than mania, hypomanic patients usually don't seek treatment, and clinicians often fail to ask enough questions to arrive at a correct diagnosis.
The study's single-center design was a limitation, Dr. Zimmerman said. Patients were predominantly white and female, and 40% were college graduates, so it may not be entirely generalizable to other populations.
Funding information was not provided. No potential conflicts of interest were reported.
Primary source: Journal of Clinical PsychiatrySource reference:Zimmerman M, et al "Is bipolar disorder overdiagnosed?" Journal of Clinical Psychiatry 2008; 69:e1-e6/pii: ej07m03888.
Living Therapists Outclass Robots in Post-Stroke Rehab

By Todd Neale
CHICAGO, 09 may 2008-- A human touch appears to be better than robotic manipulation in helping stroke patients with hemiparesis improve their ability to walk, a small randomized study found.Those assisted by the warm hand of a therapist during locomotion training had greater improvements in walking speed and time spent standing on the impaired leg than those who were helped by an inanimate motorized apparatus, found T. George Hornby, Ph.D., of the University of Illinois at Chicago, and colleagues.Immediately following 12 half-hour training sessions on a treadmill, patients who were assisted by a therapist almost doubled the gains in normal walking speed made by those given robotic assistance (0.13 ± 0.11 versus 0.07 ± 0.07 m/s, P=0.04), they reported online in Stroke: Journal of the American Heart Association.
Therapist-assisted training was also associated with greater improvements in the amount of time spent standing on the impaired limb while walking at maximum speed (2.5 ± 3.7% versus 0.1 ± 0.6%, P<0.01) immediately following training.
The device consists of a harness that is attached at the patient's trunk and pelvis, with attachments down to the legs, and computer-controlled motors to move them in a way that approximates a normal human gait.
"Given the cost and continued development of rehabilitation devices, it is imperative to identify patients who may benefit from robotic-assisted training," the researchers said.
They said that stroke patients with chronic hemiparesis who can walk independently -- even slowly -- may be the right candidates for therapist-assisted training and that those who are nonambulatory may derive more benefit from robotic assistance.
Robotic devices were developed to aid locomotion training because it can be physically demanding on a therapist to provide assistance in walking, the researchers said, but the effectiveness of these devices has not been well established.
There are also some drawbacks to their use, including a possible decrease in aerobic stimulus and the reduction of the muscular activity needed to maintain a stable walking posture, they said.
To compare the benefits of each type of training, Dr. Hornby and colleagues recruited 48 stroke patients with hemiparesis lasting more than six months and with moderate to severe gait dysfunction for a randomized, controlled study.
Those who had an initial walking velocity of £0.5 m/s were considered to have severe impairments and those with a velocity of >0.5 and £0.8 m/s were classified as having moderate impairments.
All participants (mean age 57) were given 12 half-hour training sessions on a treadmill, in which they were partially supported by a harness. Half received assistance from a therapist as needed and half had constant guidance from a robotic orthosis called Lokomat.
Training speed was slightly faster in the therapist-assisted group (P=0.01) and training duration was slightly longer in the robotic-assisted group (P=0.01).
The greater improvements in normal and maximum walking speed and time spent standing on the impaired limb while walking at maximum speed in the therapist-assisted group persisted to six months after the training sessions, but the differences failed to reach statistical significance.
Overall, patients with moderate impairments at baseline had significantly greater gains in normal (P=0.03) and maximum (P=0.04) walking velocity than those with severe deficits.
Patients who had severe walking impairments and who were given therapist-assisted training were the only participants who had improvements in scores on an assessment of their quality of life relating to fewer physical limitations.
One of the possible reasons greater improvements were found in the therapist-assisted group, the researchers said, may be that the patients were expending more energy.
"Reduced metabolic activity during robotic-assisted [locomotor training] may limit adaptations which occur during treadmill exercise in individuals post-stroke, which are thought to be a primary factor contributing to improved ambulation," they said.
Also, they said, robotic-assisted training may reduce the volitional drive of patients and impair motor memory consolidation.
Finally, patients are free to make more errors in walking in therapy-assisted training than in robotic-assisted training, allowing them to learn from the mistakes.
The researchers acknowledged that the study was limited by the small size and the inability to blind the investigators or patients to the therapy received.
The study was funded by grants from the National Institute on Disability and Rehabilitation Research. The authors made no disclosures.
Primary source: Stroke: Journal of the American Heart AssociationSource reference:Hornby T, et al "Enhanced gait-related improvements after therapist- versus robotic-assisted locomotor training in subjects with chronic stroke: A randomized controlled study" Stroke 2008; DOI: 10.1161/STROKEAHA.107.504779.

Thursday, May 08, 2008


Smoking Cessation Leads to Early and Late Mortality Benefits


By Charles Bankhead

BOSTON, 08 may 2009--Within five years of a woman's last cigarette, excess vascular risk has virtually disappeared, but lung mortality remains elevated for 15 additional years, according to the Nurses' Health Study.
After 22 years of follow-up, data from the study showed that smoking cessation reduced the risk of every cause-specific mortality outcome evaluated, Stacey Kenfield, Sc.D., of the Harvard School of Public Health, and colleagues reported in the May 7 issue of the Journal of the American Medical Association.
The full mortality benefit of smoking cessation accrued over 20 years, but over a variable timeframe, they added.
"Our findings indicate that 64% of deaths in current smokers and 28% of deaths in past smokers are attributable to smoking," they added. "Quitting reduces the excess mortality rates for all major causes of death examined."
Launched in 1976, the Nurses' Health Study originally involved 121,700 female RNs in the United States, ages 30 to 55. Participants provided detailed information about their medical history and risk factors for cancer, heart disease, and other conditions. In 1980, 28% of the participants were smokers, 26% former smokers, and 46% never smokers. By 2002, only 8% of surviving participants were smokers.
From the outset, the information has been updated by biennial questionnaires. After 12 years of follow-up, the data showed that current smoking and starting at a younger age increased the risk of all-cause and cause-specific mortality. With an additional 10 years of follow-up, the current study had the statistical strength to characterize smoking's effect on more causes of death, particularly respiratory disease and cancer.
Dr. Kenfield and colleagues analyzed data comprising 12,483 deaths: 4,485 (35.9%) among never-smokers, 3,602 (28.9%) among smokers, and 4,396 (35.2%) among former smokers. The total number of deaths consisted of:
2,957 vascular deaths
759 respiratory deaths
1,237 lung cancer deaths
2,104 smoking-related cancer deaths (including lung)
3,805 deaths due to other types of cancer
2,858 deaths due to other causes
Current smokers had almost a three-fold greater mortality risk compared with never-smokers (HR 2.81, 95% CI 2.68 to 2.95). There was a similar difference in analyses limited to major cause-specific mortality. Risks increased significantly with the number of cigarettes smoked daily. Former smokers had a 23% excess mortality risk.
Smokers had a seven-fold greater risk for smoking-related cancer deaths, as identified by the 2004 surgeon general's report (HR 7.25, 95% CI 6.43 to 8.18) and a 60% greater risk for other cancer deaths. The hazard ratios for former smokers were 2.33 and 1.09, respectively.
For all respiratory causes of death, smoking increased the risk 10-fold compared with never smokers. Former smokers had a four-fold greater risk.
Smokers had more than a three-fold greater risk of vascular death compared with never smokers. Most of the excess risk had disappeared in former smokers, whose hazard ratio was 1.32 versus never smokers.
The authors reported no financial disclosures.
Primary source: Journal of the American Medical AssociationSource reference:Kenfield SA, et al "Smoking and smoking cessation in relation to mortality in women" JAMA 2008; 299: 2037-2047.
Several Therapies Show Promise for Vascular Depression

08 may 2008-- New treatments for a type of depression in the elderly related to blood vessels -- called vascular depression -- are under development, and researchers have discovered why some patients with this condition fail to respond to current medications.
Details of the findings were to be presented Wednesday during a news conference by researchers taking part in U.S. National Institute of Mental Health symposiums at the annual meeting of the American Psychiatric Association, in Washington, D.C.
Vascular depression is a recently recognized type of depression that usually develops in patients older than age 60. The condition is associated with loss of blood supply to the brain.
"Mental health practitioners and patients should be aware of the relationship between vascular problems and depression, and should understand the value of preventing vascular changes that might lead to difficult-to-treat depressions, for example, through early recognition and treatment of high blood pressure," Dr. John Newcomer, of Washington University in St. Louis, said in a prepared statement.
Several research teams are reporting progress in understanding and treating vascular depression.
Dr. George Alexopoulos of Weill Cornell Medical College in White Plains, N.Y., and colleagues are investigating the specific brain abnormalities associated with blood vessel problems. Using a new MRI technique called diffusion tensor imaging, the researchers found that, in late life depression, higher blood pressure readings are linked to tiny white matter abnormalities, mainly in the brain's frontal lobes and in subcortical areas. Some of these abnormalities are associated with impairment in specific frontal lobe functions.
The same team also found that patients with major depression treated with the antidepressant citalopram were less likely to recover if they had cardiovascular disease or did poorly on a test of cognition requiring frontal lobe function.
They also found that patients with major depression who took the antidepressant escitalopram (which is more potent than citalopram) were less likely to recover if they had more of the tiny structural abnormalities in several areas of the frontal lobes and in subcortical structures.
"With further refinement, the findings may improve physicians' ability to predict who will fail to respond to antidepressants. Such patients may need close follow-up and different treatments such as psychotherapy or novel medications. Second, our findings can be used in the development of new treatments for those who do not respond to classical antidepressants," Alexopoulos said in a prepared statement.
He and his team are currently studying how parts of the frontal lobes are activated when depressed patients do cognitive tasks that activate this area.
Preliminary findings show that depressed older patients cannot activate these frontal lobe parts as efficiently as non-depressed older adults," Alexopoulos said.
In other research, a team at the University of Iowa found that vascular depression can be treated with an experimental technique called repetitive transcranial magnetic stimulation (rTMS). They found that rTMS led to better remission rates than standard medication treatment, and that increasing the number of magnetic pulses significantly improved remission rates.
"These findings suggest that this new method of treatment may be particularly useful for these late life onset depressions and that even greater response rates might be achieved by utilizing more pulses of magnetic stimulation," Dr. Robert Robinson, a professor of psychiatry, said in a prepared statement.
In other reports presented at the conference, scientists urged caution in the use of antipsychotic drugs in elderly people and other patients in order to minimize metabolic, heart and stroke risks.
Alzheimer's disease risks are gender specific

08 may 2008--The risks of developing Alzheimer's disease differ between the sexes, with stroke in men, and depression in women, critical factors, according to a French study.
Dr. Karen Ritchie at La Colombiere Hospital in Montpellier and colleagues studied 6892 adults age 65 and older. At the start of the study between 1999 and 2001, none had dementia, but 42 percent were deemed to have mild cognitive impairment.
In all, just over 6.5 percent of those deemed to be cognitively impaired developed dementia over the next four years, whereas 37 percent returned to normal levels of functioning. In just over half, no change was seen.
Progression from mild cognitive impairment to dementia was more likely among those who were depressed and who were taking so-called anticholinergic drugs, which influence chemical signaling in the brain.
A variation in the ApoE gene -- a known risk factor for dementia -- was also more common among those whose mild cognitive impairment progressed to dementia.
But risk factors also differed between the sexes, the results showed.
Men with mild cognitive impairment were more likely to be overweight, diabetic, and to have had a stroke. Men who had had a stroke were almost three times as likely to progress.
Women with mild cognitive impairment, on the other hand, were more likely to be in poorer general health, disabled, suffering from insomnia and to have a poor support network.
Women incapable of performing routine daily tasks, which would allow them to live without assistance, were 3.5 times as likely to progress. And those who were depressed were twice as likely to do so.
Stroke was not a risk factor for progression to dementia in women.
According to the investigators, novel risk factors for impaired cognition were recent anesthesia, less consumption of caffeine, tobacco and alcohol, appetite loss, and in women, less use of hormone replacement therapy.
SOURCE: Journal of Neurology, Neurosurgery and Psychiatry, online May 1, 2008.
Chantix recommended to quit smoking despite safety concerns

By CARLA K. JOHNSON
08 may 2008--The federal government's new advice to doctors for helping smokers quit recommends the drug Chantix, which has recently been linked with depression and suicidal behavior. The new guidelines mention the psychiatric risks but also say the popular Pfizer Inc. drug is the most effective at helping people get off cigarettes.
The guidelines mention other options, too, and highly recommend combining counseling and medication. But doctors are encouraged to talk to all smokers who want to quit about trying medication.
Consumer advocates cautioned that the safety picture on Chantix is incomplete because it's a relatively new drug, on the market just since 2006.
"It is somewhat better than other therapies; on the other hand, it appears to have more risk," said Dr. Sidney Wolfe of the watchdog group Public Citizen. "That part of the risk-benefit equation is missing, and it's changing rapidly."
Another issue with the quit-smoking guidelines, released this week by the U.S. Public Health Service, is the lead author's past connections with Pfizer. Dr. Michael Fiore, an expert on smoking and health issues, was a consultant to the maker of Chantix. But he said he cut those ties in 2005.
Fiore's views are shaped by his past ties to the drug industry, and those ties still pose a conflict, at least one consumer advocate said. John Polito, a smoking cessation educator who runs the WhyQuit.com site advocating quitting "cold turkey," called the revised guidelines "a sales pitch" for the drug industry.
The task force overlooked research showing that quitting cold turkey works, Polito said, and studies showing Chantix is superior don't reflect how it's used "in the real world."
"People are quitting smoking to save their lives," Polito said. If Chantix's risks outweigh its benefits, "then it's insane for people to risk their lives" by using it, he said.
The guidelines are based on an extensive review of scientific evidence, were reviewed by 90 independent experts and were endorsed by 60 public health entities, Fiore said, adding that his past financial ties to the drug industry had no influence.
"Independent reviewers of it came to the conclusion that this is a document that reflects the science, and that's what we were charged to do," Fiore said.
The guideline authors analyzed 83 studies and found that Chantix helped 33 percent stay off tobacco for six months after quitting, compared with a nearly 14 percent abstinence rate for dummy pills.
The guidelines recommend combining counseling and medication as the most effective way to kick the tobacco habit, stating "both counseling and medication should be provided to patients trying to quit smoking."
Medications have not been shown to be effective in certain groups, the guidelines say. Those groups include pregnant women, smokeless tobacco users, light smokers and adolescents.
The guidelines say doctors should consider asking about their patients' psychiatric history before prescribing Chantix. Doctors also should monitor patients for changes in mood and behavior while on the drug.
Lois Biener, a researcher of tobacco use and control efforts at the University of Massachusetts in Boston, said most people who quit do so without smoking-cessation drugs.
There's little evidence that these drugs are superior in the long run to quitting without help, and while a few studies have shown some benefit, it's "way less than what is claimed" by medication advocates, Biener said.
Three of 24 panelists who wrote the guidelines reported "significant financial interests" in the pharmaceutical industry, including speaking fees and stock ownership.
Five percent of breast tumors may double in month

By Michael Kahn
08 may 2008--Five percent of breast cancer tumors appear to double in size in just over a month, Norwegian researchers said on Thursday in a study underscoring the potential benefits of more frequent screening.
The study published in the journal Breast Cancer Research also suggested detection rates of just 26 percent for a 5 mm tumor, and 91 percent for a 10 mm tumor.
The researchers used a computer model fed with national screening and cancer data to calculate how quickly tumors grow and estimate the proportion of breast cancers detected at screening.
This data on nearly 400,000 women aged 50 to 69 helped them estimate that about 5 percent of tumors may double in just over a month, growing from 10 mm to 20 mm. This was mainly among younger women in the study's age group.
Another 5 percent of tumors took more than six years to grow to the same size, according to the data collected before and after Norway began national breast cancer screening in 1995. This was mostly among older woman in the study.
"The variation was larger than what I was expecting," said Harald Weedon-Fekjaer, a statistician at the Cancer Registry of Norway, who led the study.
"Now we can be more certain about estimates."
The researchers used a complex formula that took into account what size tumors were when detected, measurements of surgically removed tumors and other data.
They said their findings could help in the debate over how often women should get mammograms. Some countries offer mammograms only once every three years and studies have provided conflicting evidence over whether mammograms save lives.
There is no question, experts say, that breast cancer detected earlier is far easier to treat, however.
Breast cancer is the leading cause of cancer deaths among women worldwide, according to the American Cancer Society. The group estimates about 465,000 women died from it globally in 2007, with 1.3 million new cases diagnosed.
Declining death rates from breast cancer in developed countries have been attributed to early detection through mammography screening and to improved treatment, it said.

Wednesday, May 07, 2008


AGS: A Little Anticholinergic Burden Can Be Disabling

By Peggy Peck
WASHINGTON, 06 may 2008 -- Drugs not usually thought of as anticholinergics -- such as furosemide (Lasix) and diltiazem (Cardizem) -- could lead to functional impairment when taken in combination, researchers reported here.
Each drug has anticholinergic properties and taken together they have an additive effect such that "it would add about four years to functional ability; a 70-year-old would function as a 74-year-old," Kaycee Sink, M.D., of Wake Forrest University in Winston-Salem, N.C., told attendees at the American Geriatrics Society meeting.
Patients who were taking one moderately anticholinergic drug, such as cimetidine (Tagamet), or two mildly anticholinergic drugs -- such as furosemide and diltiazem -- were about 30% more likely to have problems with activities such as dressing or bathing versus same-age people who took no anticholinergic drugs (OR 1.31, 95% CI 1.00 to 1.72), Dr. Sink said.
And they were about 35% more likely to have difficulty with more complex tasks like meal preparation or medication management (OR 1.35, 95% CI 1.07 to 1.72).
Likewise, as anticholinergic burden increased gait speed decreased from 0.89 meters/sec to 0.86 meters/sec, which was statistically significant (P =0.02), Dr. Sink said.
Those findings emerged from the Ginkgo Evaluation of Memory Study (GEMS) study, which recruited 3,070 individuals 75 or older at participating centers in California, Maryland, North Carolina, and Pennsylvania.
Anticholinergic drugs have been associated with poorer cognition and diminished strength in older adults, but, Dr. Sink said, "many drugs have anticholinergic effects, but are not considered anticholinergic drugs and there has been little investigation of the potential anticholinergic burden of these drugs."
This analysis sought to determine what effect -- if any -- the anticholinergic burden of these drugs would have on function.
At baseline, participants were asked about exposure to drugs "on a short list of 52 drugs in which anticholinergic burden had been assessed." A drug with no anticholinergic burden was rated "0", mildly anticholinergic drugs were scored as 1, moderately anticholinergics were rated 2, and highly anticholinergic drugs were classified as 3.
Using this scoring system, fuorsemide received a 1, as did diltiazem. Cimetidine was rated 2 and oxybutynin (Ditropan) received a 3.
To gauge functional level, participants were asked a series of questions about activities of daily living, which were also assessed by a series of observational measures including gait speed.
The researchers determined that 40% of participants were taking one or more drugs with anticholinergic burden, and a small number were taking nine drugs with some anticholinergic properties.
"When the anticholinergic burden score was 2 or higher, which often meant just taking two seemingly innocuous drugs, there was a clear increase in risk of functional impairment," Dr. Sink said.
She noted that the study was limited by its cross-sectional design, which cannot completely rule out confounding by indication for use of anticholinergic medications and by the lack of consideration for dose of anticholinergic drugs.
Nevertheless, Dr. Sink said, clinicians need to be aware of anticholinergic burden even in drugs that are not usually considered anticholinergic medications.
She said that the list of 52 anticholinergic drugs used for the study was based on an expert consensus (Schubert CC, et al JAGS 2006; 54: 104-109) and she suggested that it would be useful "to use this list when assessing medications used by elderly patients."
GEMS, which is assessing the effect of ginko use on memory function, is ongoing and results are expected later this year.
The study was supported by the National Institute on Aging and the National Center for Complementary and Alternative Medicine. Dr. Sinks received support from the Hartford Geriatrics Health Outcomes Research Scholars, the WFU Pepper Center, and the Kulynych Center for Research in Cognition.
Primary source: American Geriatrics Society MeetingSource reference:Sink K, et al "Antihcolinergic burden is associated with worse physical function: Results from the GEM study" AGS Meeting 2008.Complete AGS Coverage
Short Limbs Associated with Risk of Dementias

By Todd Neale
BOSTON, 06 may 2008 -- A man with a 32-inch sleeve has a greater risk of developing Alzheimer's disease and other dementias than a man with a 35-inch sleeve.
So it seems from a prospective, longitudinal study showing that for both men and women, having shorter limbs is associated with increased risks for Alzheimer's and other dementias.
Women in the lowest quartile of arm span had a 1.42-fold greater risk of dementia and a 1.72-fold increased risk of Alzheimer's disease compared with other women, reported Tina Huang, Ph.D., of the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts, and colleagues in the May 6 issue of Neurology.
Every one-inch increase in knee height in women was associated with a 16% lower risk of dementia and a 22% reduced risk of Alzheimer's disease.
For men, every one-inch increase in arm length was associated with a lowering of the risk of dementia by 6% and the risk of Alzheimer's by 7%, they said.
"Our findings with knee height and arm span are consistent with previous reports and suggest early life environment may play an important role in the determination of future dementia risk," they said.
Anthropometric measures can be used as markers of childhood environment, and may reflect nutritional or other deficits during early development, the researchers said.
Several studies have linked early environmental factors and susceptibility to disease in later life, they said, and some, including three on Korean populations, have made the connection between shorter leg and arm lengths and cognitive impairment.
For an American population, Dr. Huang and colleagues turned to the Cardiovascular Health Cognition Study, which followed 2,798 patients (mean age 72; 41% male; 89.5% white) for an average of 5.4 years.
Knee height was measured three years before the study started and arm span was measured four years after baseline.
Cerebral MRI was performed at the start of the study and at five years. Cognitive function was measured at baseline and then at each follow-up visit using the Modified Mini-Mental State Examination.
During follow-up, 480 participants developed dementia for an incidence of 31.9 cases per 1,000 person-years: 245 were possible or probable Alzheimer's disease, 213 were possible or probable vascular dementia, and 22 were other dementias.
The association of a lower risk of dementia and Alzheimer's with greater knee height was only significant in women, after controlling for age, race, and presence of the APOEe4 allele, which is known to increase the risk for dementia and Alzheimer's disease.
For women, every one-inch increase in arm length was associated with a lowering of the risk of dementia by 6% (HR 0.94, 95% CI 0.89 to 0.99) and the risk of Alzheimer's by 9% (HR 0.91, 95% CI 0.85 to 0.97).
"Differences in limb length," the researchers said, "could reflect differences in genetics, environment, or both."
Insufficient nutritional intake during childhood could cause stunted growth, which is reflected in shorter height and limb length, and impaired brain development, they said.
"Thus," they continued, "it is possible that early nutritional deficits, exposure to environmental toxins, or other unaccounted-for residual confounders could influence intelligence, cognitive functioning, level of educational attainment, or vulnerability to dementia."
The authors acknowledged that the study was limited by the measurement of arm length four years after the start of the study and the possibility of misclassification of dementia outcome.
Strengths of the study included the length of follow-up, the longitudinal, prospective design, the "state-of-the-art adjudication of incident dementia, Alzheimer's, and vascular dementias," and the high number of dementia cases.
"These reasons, plus the fact that our studies have now replicated previous findings," they concluded, "increase our confidence in concluding that the shorter a woman's knee height, or the shorter the arm span of either gender, the greater the risk of developing dementia or [Alzheimer's disease]."
They called for further studies to explore gender differences in the associations of knee height and arm span with dementia.
Dr. Huang was supported by grants from the NIH, the National Institute of Diabetes and Digestive and Kidney Diseases, and the Charles A. King Trust, and the U.S. Department of Agriculture Agricultural Research Service. The study was supported by contracts from the National Heart, Lung, and Blood Institute and a grant from the National Institute on Aging.
The authors reported no conflicts of interest.
Primary source: NeurologySource reference:Huang T, et al "Knee height and arm span: a reflection of early life environment and risk of dementia"Neurology 2008; 70: 1818-1826.Additional Dementia Coverage
APA: Deep Brain Stimulation Lifts Depression in Multicenter Trial

By Michael Smith
WASHINGTON, 06 may 2008-- Deep brain stimulation relieved depression in 56% of patients treated in a multicenter Canadian trial.
Six months after the treatment, nine of 16 patients had at least a 40% improvement on the Hamilton Rating Scale for Depression, according to Sidney Kennedy, M.D., of the University Health Network in Toronto.
The "findings are robust," Dr. Kennedy said at the annual meeting of the American Psychiatric Association, adding that they should be followed up with a double-blind randomized trial.
The study follows the technique used in a pilot study three years ago, led by Helen Mayberg, M.D., of Emory University, but uses a different device, Dr. Kennedy said.
That earlier study sparked an outburst of interest in the idea of stimulating brain areas as a possible therapy for major depression. Dr. Mayberg discussed the technique with MedPage Today in an exclusive interview. Dr. Mayberg and colleagues have since expanded their initial study to 20 patients and a paper detailing their results is in press, she said, but she was reluctant to give details until the paper is published.
The 20-patient study reported by Dr. Kennedy was intended to show that the results obtained by the Toronto group could be reproduced by doctors elsewhere. (Dr. Mayberg was consulted on its design but was not otherwise involved, she said.)
"We wanted to show it wasn't just a Toronto effect," Dr. Kennedy said.
The method involves inserting electrodes into the subgenual cingulate cortex Brodmann Area 25, which is part of a brain circuit thought to be disregulated in depressed patients.
Because the treatment has only been used a few dozen times -- one estimate says about 50 cases worldwide -- the patients selected are usually highly refractory to treatment, Dr. Kennedy said.
In his study, volunteers had to have documented resistance to at least four types of treatment, including cognitive behavioral therapy. They also had to be in a depressive episode at least two years long and have a score on the Hamilton scale of 20 or higher.
The researchers treated five cases in Vancouver, six in Montreal, and nine in Toronto, but several patients had not yet reached the six-month landmark when the poster was prepared, Dr. Kennedy said.
When the researchers considered the latest follow-up, rather than the six-month mark, 15 of 19 (or 79%) had at least a 40% improvement on the Hamilton scale, he said. (The 20th patient was not included because the implant was too recent.)
The results are "exciting," said Thomas Insel, M.D., director of the National Institute of Mental Health, and the whole approach "could be tremendously informative" about which brain circuits are involved in depression.
"What you really want to know," Dr. Insel said, "is how these interventions affect the circuitry."
"I think we're going to get closer to that with (deep brain stimulation) than with pharmacotherapy," he added.
One of the next steps is to combine the intervention with neuroimaging to pin down exactly which brain regions are involved in depression and how they interact to cause the disease.
"I think that's where this will have to go," Dr. Insel said.