Monday, March 31, 2008

ACC: Sudden Death May Follow on Anniversary of Parent's Demise

By Todd Neale CHICAGO, March 30 -- The anniversary of the loss of parent may cause enough distress to trigger sudden death, especially in men, researchers found.
In a study of 102 sudden deaths of patients ages 37 to 79, 13 (12.7%) occurred on the date of one or both of the patient's parents' deaths, Ivan Mendoza, M.D., of Central University of Venezuela in Caracas, reported at the American College of Cardiology meeting here.
Four patients died at the same age as the deceased parent, and 10 (77%) of the sudden deaths attributed to the so-called anniversary effect occurred in males, said Dr. Mendoza.
Sudden death was not associated with the deaths of any other close family members, he added.
He said that patients and physicians need to be aware that psychological factors can trigger sudden death.
Physicians, he said, should ask patients about the deaths of close family members and should take action to prevent sudden death, including psychological therapy, stress reduction, behavior modification, management of cardiovascular risk factors, and treatment with medications like beta-blockers or aspirin.
Recently, psychological and chronobiological factors -- including the anniversary effect -- have been identified as triggers for sudden death or lethal arrhythmia, he said. So he and colleagues examined the life circumstances surrounding the 102 sudden deaths in patients ages 37 to 79.
More than two-thirds (68%) of the cases had underlying coronary artery disease.
Seven patients died on the anniversary of their father's death, five on the anniversary of their mother's death, and one on the anniversary of the deaths of both parents.
"One of the worries we have is that with death we often grieve, and in some cultures we don't grieve openly," commented Janet Wright, M.D., a vice president for science and quality at the ACC, who moderated the session at which the results were discussed. "We're stoic about it. That sublimated grief can turn into depression, depression can lead to stopping medicines, withdrawing from friends, becoming more isolated, and we know that those factors all contribute to cardiac events."
Dr. Mendoza noted that he and his colleagues have conducted another study in which anger was identified as a trigger for sudden death in about 30% of patients.
Dr. Mendoza did not make any disclosures.
Primary source: American College of CardiologySource reference:Mendoza I, et al "Sudden death: the anniversary effect" ACC Meeting 2008; Abstract 1029-100.
ACC: ENHANCE Data on Ezetimibe/ Simvastatin (Vytorin) Reveal Wavy Bottom Line

By Peggy Peck
CHICAGO, March 30 -- A full-airing here today of findings of the ENHANCE trial did nothing to blunt the null finding for the combination of ezetimibe/simvastatin (Vytorin) that were prefaced in a press release in January.
That press release, issued by Merck and Schering Plough, described a significant reduction in LDL cholesterol with ezetimibe/simvastatin (Vytorin) without a significant slowing of atherosclerosis progression.
But today's "showcase" scientific presentation of the results at the American College of Cardiology meeting, along with an analysis of ezetimibe (Zetia) and ezetimibe/simvastatin (Vytorin) use in the United States and Canada, may help calm concerns that ENHANCE suggested cholesterol-lowering does not correlate with clinical outcomes.
A clear clinical message from the ACC presentation, plus a simultaneous online release of the ENHANCE results by the New England Journal of Medicine, as well as a marketing analysis and two editorials, however, left the issue clearly open to interpretation. Advocates on both sides of the ezetimibe issue offered conflicting views.
To recap the ENHANCE story, the trial found no significant difference in the primary endpoint -- mean change in carotid intima-media thickness -- between patients randomized to ezetimibe/simvastatin versus 360 control patients who received simvastatin alone (P=0.29).
The combination therapy led to a significantly greater decrease in LDLs, a 58% reduction in LDLs for the ezetimibe/simvastatin group versus 42% for simvastatin controls after 24 months (P<0.01), said principal investigator John Kastelein, M.D., of the Academic Medical Center in Amsterdam in Holland.
There were also significant reductions in triglycerides (6%) and C-reactive protein (25.7%) between the two groups and those were significant (P<0.01), he said.
Nonetheless, those reductions did not result in significant reductions in the surrogate endpoint of carotid intima-media thickness, which begs two questions. First, is LDL reduction an invalid clinical goal? Second, what is the clinical evidence to support the use of ezetimibe?
The second question becomes especially crucial in light of data reported online today in the NEJM by Cynthia A. Jackevicius, Pharm.D., of the Western University of Health Sciences in Pomona, Calif., and colleagues. They found that ezetimibe had captured more than 15% of the market for lipid-lowering medications by 2006. This translates in to 3.1 million prescriptions for ezetimibe or ezetimibe/simvastatin in December 2006.
Moreover, the increased use of ezetimibe appears to have gained market share by cutting into statin prescriptions, which declined by 6.5% since ezetimibe was introduced in 2006.
Ezetimibe use also increased in Canada but the rise was markedly less, from 0.2% of prescriptions for lipid-lowering drugs in 2003 to 3.4% in 2006.
Two factors, Dr. Jackevicius and colleagues said, may explain the difference between U.S. and Canadian use. The combination of ezetimibe and simvastatin is not approved in Canada, and Canada does not permit direct-to-consumer advertising of prescription drugs.
In the U.S., Merck and Schering Plough spent $200 million on marketing ezetimibe and the combination product and sales here have "eclipsed $5 billion," Dr. Jackevicius and colleagues said.
Addressing the issue of the clinical value of LDL cholesterol lowering, two editorials concluded that the ENHANCE data should not be taken as evidence that cholesterol doesn't really matter.
Rather, the editorials hinted, there is a need to broaden the message so that it encompasses both lower is better and how you get there counts.
A Multitude of Vaccine Benefits, Yet Controversy Persists

Vaccinations are among the most important health advances in history.Death rates for 13 diseases that can be prevented by childhood vaccinations were at all-time lows in the United States in 2007.Rumors persist that some immunizations, or the vaccine preservative thimerosal, cause autism.
Public health experts generally agree that after clean water and flush toilets, the most important health advances in history have been vaccinations.
Shots against measles, diphtheria, whooping cough, tetanus, polio, mumps, rubella, chicken pox, flu, hepatitis and some causes of childhood meningitis, pneumonia and diarrhea have saved more lives than all the “miracle drugs” of the latter half of the 20th century — antibiotics like penicillin, antivirals like drugs to fight AIDS and flu, and so on. In addition, vaccination is one of the leading reasons that many families in the West now feel comfortable having only two or three children: they can be reasonably certain that the children will survive childhood.
According to a large historical study by the Centers for Disease Control and Prevention released in November 2007, death rates for 13 diseases that can be prevented by childhood vaccinations were at all-time lows in the United States. The study looked at hospital and death records going back to 1900 and estimated death rates before various vaccines were invented. In nine of the diseases, rates of hospitalization or death had declined more than 90 percent. For three — smallpox, diphtheria and polio — death rates had dropped by 100 percent.
In the 1930s, the United States had about 30,000 diphtheria cases a year, and 3,000 of those succumbed to the disease as gray membranes formed in their airways and eventually choked them to death. Diphtheria is now virtually unknown in the West, but in the chaos following the breakup of the former Soviet Union, vaccinations broke down, and the Red Cross estimated there were 100,000 cases and 5,000 deaths from the disease.
Smallpox vaccine is no longer given to children because the disease has been eliminated from the world, except for stocks frozen in laboratories in the United States and Russia. The smallpox vaccine also carried some risks.
Since the 1990s, vaccines have become somewhat controversial, even in the United States. As diseases have disappeared, generations have grown up without ever seeing the sickness and death they caused. At the same time, new parents are often upset as their babies receive between 20 and 30 injections before age 2 and suffer the pain and mild fever that can accompany them as routine side effects.
In addition, rumors continue to spread that some vaccines, or a mercury antifungal vaccine preservative called thimerosal that was added to vaccines, cause autism. Numerous studies have shown no link between autism and either vaccines or the preservative. An active anti-vaccine lobby, however, keeps the issue alive. The lobby is a broad tent. A few members question even whether bacteria and viruses cause disease; most seek more research into safety and greater rights to refuse vaccination.
State and city health departments, recognizing that the risk of epidemics soars when children gather daily in school, generally require parents to prove that children have been immunized before they enroll. There are some exceptions. All states allow medical exemptions for children who are immunocompromised or allergic to vaccine components. Most allow religious objections. A few allow “personal or philosophical” ones; how hard it is to get one varies by state.
Health insurers pay for most vaccines, and public clinics offer them free to the uninsured, the cost paid by the federal government under the Vaccines for Children Program of 1994. Before that time, incomplete vaccination was most common among the poor. Now it is more common for children from wealthy or middle-class families to lack some or all shots, presumably because their parents objected.
More vaccines are being developed all the time. Some are aimed at teenagers because they thwart diseases spread by sex or common in student dorms and military barracks. These include vaccines for human papillomaviruses, which cause cervical cancer; herpes; and meningococcal B infections, the cause of sometimes deadly meningitis. Others, like those against flu, shingles and some bacterial toxins, are particularly aimed at older people, who have weaker immune systems and are more likely to be in hospitals or nursing homes.
Newer vaccines tend to be much more expensive than older ones, which were developed before the era of clinical trials costing hundreds of millions of dollars and before medical liability lawsuits were so common. But the cost of not vaccinating at all, as history has taught, can be very high.
Recalling the Madness

Viagra is just another pill in the medicine cabinet these days, one of three on the market to treat the once all-but-unmentionable problem of erectile dysfunction. But 10 years ago last week, when government regulators approved it for sale, Viagra became the first pill available to treat the problem. The reaction was, well... Here’s what reporters for The New York Times found in the drug’s first months.
Beginning another day on the front lines of what he refers to as “Viagra madness,” Dr. Stanley Bloom, urologist and impotence specialist, flexed his hand to steel it against writing cramps. Men’s redemption from sexual malfunction was exacting its physical toll on his already ragged penmanship. So many craved a prescription for the little blue Pfizer pill that was sweeping the country, but how much could a 60-year-old right hand take?
Some urologists had acquired stamps to apply their signature on Viagra prescriptions. Dr. Bloom had his nurse prepare a tidy stack of prescriptions in advance. Then he authenticated them the old-fashioned way as the men tumbled in.
“I’m burning out,” he lamented as the chronically jammed waiting room of his Physicians in Urology offices on East Northfield Road emptied into the hive of examination rooms, though he was sincerely gratified to see a breakthrough against an affliction that consumes his practice.
In trooped the patients, something like 25 a day in the last three weeks for the diamond-shaped miracle pill, extending Dr. Bloom’s daily office hours three hours beyond the norm. Reflecting the very height of exuberance and expectation, John Dowling, 69, a retired packaging foreman for Budweiser, only half-jokingly asked for a prescription for 1,000 pills.
“They’re $10 apiece,” Dr. Bloom replied.
“Five hundred, then?”
“That’s $5,000. You’ve got to be kidding.”
He settled for 20.
It was already his second prescription. He had been in two weeks ago and had tested the pill five times, with gratifying results.

Bob Dole, the 1996 Republican presidential candidate, disclosed on “Larry King Live” that he had participated in clinical trials for Viagra. “It’s a great drug,” he told Mr. King. A few days later, his wife visited New York City. Dan Barry was there.
It is not often that City Hall reporters dare to ask visiting dignitaries about their sex lives. But these are the days of Viagra, when frank discussions of impotence can seem as natural as talking about fiscal conservatism.
So when Elizabeth Dole, president of the American Red Cross, graced a City Hall news conference with her meticulous presence yesterday, everyone in the room knew for certain that one question would be asked — a rather indelicate question that had nothing to do with her organization ....
Mrs. Dole accepted a proclamation from Mayor Rudolph W. Giuliani. After talking passionately about how important the Red Cross’s efforts are in places like Rwanda and Bosnia, she invited questions. There was a brief inquiry about mudslides in Italy, and then The Question was posed.
“In a normal time, I would ask you what would be your view of the Presidential candidacy of Mayor Giuliani,” the reporter said. “But there are more pressing matters of national importance. And it seems your husband was one of the first people who used Viagra. What advice would you give to men and women in this nation about the use of that pill?”
Mr. Giuliani laughed nervously and shook his head in disgust. Mrs. Dole, however, had been prepped.
“I’ll make this statement,” she said, smiling without a hint of fluster. “He was in the protocol, and it’s a great drug, O.K.?”
Jon Nordheimer traveled to Miami to check the reaction there.
Retirement communities are buzzing with speculation on Viagra and its restorative promise.... But marriage and sex counselors are uneasy that men, whatever their age, are overhauling their sex lives without any guidelines to the possible earthquake they may introduce into their emotional lives....
“Many elderly couples are very active sexually, but there are those who have lost interest and haven’t been intimate for years,” said Dr. Elliot Klorfein, a Florida urologist, who has many retirees as patients. He said he has written “a zillion” prescriptions for Viagra in the last few weeks, and much of the demand is coming from retirees he’s never treated before.
“Typically, an older man is still interested in sex, and he jumps at an idea that here’s a pill he can take orally that will make him a new man,” Dr. Klorfein said. “The trouble is his wife is no longer interested .... So her husband is all dressed up with nowhere to go.”

A Wall Street titan was inspired to generosity, as Ian Fisher reported.
Alan C. Greenberg bettered his own life by becoming rich on Wall Street, and yesterday he gave away $1 million of that money to better the lives of other aging men in a very specific way: He will pay for Viagra prescriptions for people who cannot afford them.
“I guess you could say I’m kind of into basics,” said Mr. Greenberg, 70, the chairman of Bear, Stearns Companies, who received a $20 million bonus last year. “And I think it’s something that will give a lot of pleasure to a lot of people.”

Perhaps inevitably, women wondered what Viagra might do for them. Alex Kuczynski talked to a few of them, including a 42-year-old nurse in New Jersey who described the first time she took Viagra.
“I only see my boyfriend every two weeks because we live in different states,” she explained. “And if I’m not in the mood on one of those weekends, well, then there goes the month. I’ve been with him for about two and a half years, and it’s just not as exciting as it used to be.”
Last Saturday night, she swallowed a blue, diamond-shaped Viagra pill, which she sneaked from a cache in the office where she works. The dosage was 50 milligrams, the standard for male sexual dysfunction. She chose not to tell her partner. “We were watching television, just a regular movie,” she said, noting that after an hour she began to feel “a fullness. I can’t say it was a tingling, but it was some effect of the increased blood flow to the area.” The couple retreated to the bedroom, and the pill began to work its alleged magic.
“I have to say it was great,” the woman said. ”It was animalistic. I can definitely say it was not a placebo effect. I’m a nurse, and I’m trained to recognize those things.”
New gene clues to diabetes, colo-rectal cancer

Researchers have uncovered new genetic clues for diabetes and cancer of the colon and rectum, according to papers published on Sunday in the journal Nature Genetics.

A consortium of researchers, sifting through data from six major studies, found six previously unknown genetic variants that boost the risk of Type 2 diabetes, the commonest of the two forms of the disease and one that is spreading fast in developed economies.

Separately, investigators found that people with specific variants of genes located on Chromosomes 8, 10 and 11 were at increased risk of colo-rectal cancers.

The flawed genes were found in a wide trawl of the genome of tens of thousands of people.

They add to other genes associated with risk for these complex diseases, although many more remain to be discovered, scientists say.

Diabetes affects 246 million people worldwide and is expected to affect some 380 million by 2025, according to the International Diabetes Federation website.

Colo-rectal cancer causes 655,000 deaths a year, according to figures on the World Health Organisation (WHO) website.

Finding genes that cause or contribute to a disease is the first step towards diagnostic tests to identify people at risk. It also potentially opens the way to drugs that block or ease the activity of the culprit genes.

Sunday, March 30, 2008

Med School's Hot New Field: Personalized Medicine

By Bernadine Healy M.D.
What propels most students into medicine is the desire to relieve human suffering with knowledge, judgment, and skill. Noble aspirations quickly sour, however, when insurance companies deny care over the phone or when faceless bureaucrats penalize doctors' discretionary decisions on what's best for their patient based on some standardized guidelines. As pediatrician Mark Vonnegut stated recently in the New England Journal of Medicine, "U.S. doctors today have less and less to say about the care of their patients. All the complex lessons they learned in medical school are being swept aside for template care." Not much longer, I hope. Template care is increasingly at odds with the emergence of personalized medicine, a new discipline driven by the exploding knowledge of the human genome that guides treatment tailored to the individual patient. And this is what today's medical students will be practicing tomorrow.
Look at cancer, which offers a glimpse of what's to come. The wide arrays of genes that mastermind cancer have become targets for drug design. Herceptin, for example, counters a gene that occurs in 20 to 30 percent of women with breast cancer and makes it especially aggressive. For these women, Herceptin is lifesaving. For women who would not benefit and would face only side effects, the drug is avoided. This is what we want for every therapy. But the development of such personalized medicine requires that physicians actively integrate genomics into all fields, reaffirming the time-honored tenet that doctors always consider what's special about an individual patient as opposed to the textbook case.
Care would be easy if people fit some standard mold. When the sequence of the human genome was published in 2001, scientists pointed to our common humanity, with people being more similar than different. But seven years and a mountain of research show the opposite—an astonishing level of individual variety. In fact, Science magazine declared human genetic variation as the No. 1 breakthrough of 2007.
Thanks to ever better, faster, and cheaper sequencing technology, researchers have shown the many ways our 25,000 or so genes can vary. One little glitch—a misspelling, a hunk of DNA lost or added, or a gene altered by interplay with other genes or molecules—can affect disease susceptibility or treatment. Already, researchers have tied genetic differences to many diseases, including diabetes, heart failure, autism, restless leg syndrome, multiple sclerosis, and rheumatoid arthritis. Imagine this in medical practice. Knowing your patient's risk early on would bring more targeted prevention. And by knowing that some patients are more likely than others to become infected with certain viruses or other pathogens, patient care would be improved, as would the public-health management of epidemics—such as identifying priority groups for vaccination.
Case by case. It's downright humbling for physicians to learn that some patients with illnesses we label and treat as the same are just plain different and should not be expected to respond to standard therapy. These patients have not failed treatment; treatment has failed them. And so follows the mantra of the emerging personalized medicine industry in the hunt for personalized diagnostics and therapeutics: right treatment, right patient, right time—not one size fits all.
To the pharmaceutical industry, personalized medicine poses limitless opportunities. To insurers and government payers, it offers increased quality at lower cost, since treatments that don't work are not used. To patients, it's better care.
The medical establishment has been slow to catch on. As Ralph Snyderman, former chancellor at Duke University Medical Center, puts it, "physicians haven't yet grasped this as the great new wave in the practice of medicine." Although a few medical schools, including Duke, have developed programs in personalized medicine, they are scarce, as are the ranks of medical professionals trained in genetics.
But I have faith that personalized medicine will sweep the hallowed halls of medicine. A friend of mine in the telecommunications world tells me that all revolutions start with people in their 20s. Medicine is no exception. Students entering medical school now, encouraged by the needs of their patients, will be the ones to make personalized medicine happen. They will catch the wave and, no doubt, put an end to template care too.
Can you keep a medical secret?

Does a doctor treating you for a broken leg need to know you had an abortion 20 years ago?
Should your dentist have access to information about your visit to a psychiatrist?
Such questions are moving center stage as patients' medical records increasingly are transferred from manila folders to the Internet, allowing easier access to medical history that the patient may not want known.
In one of the latest examples of the debate over how much patient history doctors should have access to, Dr. Marc Overhage, chief executive of Indiana Health Information Exchange, cast the lone dissenting vote as a 17-member federal panel recommended that patients get more control over electronic health records.
Overhage is a member of the National Committee on Vital and Health Statistics, which sent its recommendations to the U.S. Department of Health and Human Services last month. The panel encouraged HHS to give patients the power to sequester from their online medical records certain sensitive information such as domestic violence-related treatment, reproductive health and genetic information.
"I certainly believe it's a patient's right to protect and control their information," said Overhage, a professor at the Indiana University School of Medicine.
However, he said physicians, in order to provide the best care possible, also need access to information -- sometimes including information that is more personal in nature. The fact that a woman takes birth control pills, he said, could have an effect on how a doctor would prescribe other medications.
He also said the recommendations he voted against leave too many unanswered questions and contain initiatives that could cost hundreds of millions of dollars to implement.
To best protect their privacy, Overhage said, patients should pick doctors and providers they trust. "They should be confident that the providers and those who work with those providers handle that information appropriately," he said.
The federal advisory committee's recommendation letter is part of the federal government's process in establishing guidelines and standards to develop a nationwide health information network.
Such a network would include initiatives such as Indiana Health Information Exchange, an Indianapolis-based nonprofit organization used by roughly 33 hospitals and 7,200 providers, which transmits lab results and other patient information for providers across Indiana.
The development of large health-data networks such as IHIE, and the increasing use of electronic medical records by doctors and hospitals, could lead to the compilation of highly detailed patient medical histories.
And that has some worried.
The strongest privacy rights Americans have are health privacy rights, said Dr. Deborah Peel, a practicing psychiatrist and founder of the Texas-based advocacy group Patient Privacy Rights. "It's the most sensitive personal data," she said.
Even in the Internet age, patients should have the right to withhold certain information, she said.
"People forget that patients have never told every doctor everything," Peel said. "Patients have always carefully sliced and diced who they tell what under what circumstances. That's what the right to privacy means."
The letter crafted by the federal advisory panel, sent Feb. 20 to U.S. Health and Human Services Secretary Mike Leavitt, noted that computerized health records hold great potential for improving the effectiveness and efficiency of health care. But the letter also noted that such records also mean that every doctor, nurse, pharmacist, chiropractor and dentist, and other health-care workers, have potential access to a patient's complete medical history.
The panel also recommended that health-care workers be able to "break the glass" and access private information if needed in an emergency.
Such measures are needed in a highly connected world, said Mark Rothstein, a member of the committee, which spent about 15 months crafting the recommendations letter.
"People are suddenly going to find there's no way to compartmentalize the sensitive things in their health histories from the nonsensitive things in their health histories," said Rothstein, a lawyer who also is director of the Institute for Bioethics, Health Policy and Law at the University of Louisville School of Medicine.
"Someone who is treating you for a broken leg doesn't need to know you had an abortion 20 years ago."
Rothstein said another worry he has about highly detailed electronic patient histories is the prospect of patients being rejected by employers or insurance companies because now-scattered details of their health histories would be more easily available.
Overhage, however, said he had concerns about giving patients the power to exclude certain aspects of their health histories from their records. He said doctors might need access to such information to make important decisions about care.
"I worry about how many will be harmed versus how many people will be protected by having this information protected," he said.
Local physicians also are weighing how to best protect patient privacy.
Dr. Ben Park, chief executive of the physician practice American Health Network, said he sees a need for physicians and hospitals to be able to exchange patient data among different computer systems.
However, Park said, "It creates this point of vulnerability from a privacy standpoint." He said his practice has begun surveying patients about whether they want their information shared with an outside health information exchange.
Park recently spoke with a woman who, during a visit to her gynecologist, heard her doctor remark about the results in the Indiana Health Information Exchange system from a previous test, ordered by another doctor, for a suspected lung disease. Although she did not have the disease, the recorded result did not make that clear, Park said.
Overhage said IHIE gets its information from the patient's own providers. He emphasized that the system is "almost paranoid" when it comes to security. The patient information is encrypted, and there are tight constraints on how health-care providers may access it, he said.
Yet the word "privacy" does not appear anywhere in its 17-page 2007 annual report. "I think it's a given in the work we do," Overhage said.
He said society must find ways to balance the benefits of providing doctors with greater access to people's personal information with protection of patients' privacy.
"You can go to extremes, and I think we need to find the right pathway forward. We do have to marry the development of the privacy policies and the technology going forward," Overhage said. "We need to use this information to improve the quality of care that patients get."
Electrocardiographic manifestations of pulmonary embolism

MD Edward Ullman
The electrocardiogram (ECG) may be entirely normal in the patient with pulmonary embolism (PE); alternatively, any number of rhythm and/or morphologic abnormalities may be observed in such a patient. The abnormal ECG may deviate from the norm with alterations in rhythm, in conduction, in axis of the QRS complex, and in the morphology of the P wave, QRS complex, and ST segment/T wave. The electrocardiographic findings associated with PE are numerous, including arrhythmias (sinus tachycardia, atrial flutter, atrial fibrillation, atria[ tachycardia, and atrial premature contractions), nonspecific ST segment/T wave changes, T wave inversions in the right precordial leads, rightward QRS complex axis shift and other axis changes, S1Q3 or S1Q3T3 pattern, right bundle branch block, and acute cor pulomnale. This review focuses on the ECG and the various abnormalities seen in the patient with PE.
Free drug samples cost more in the long run

By JoNel Aleccia
Leaving the doctor’s office with a bagful of free drug samples may seem like a good way to save money, not to mention an inconvenient trip to the pharmacy.
But people banking on the freebies need to think again, according to a new study that shows patients who get samples end up with significantly higher out-of-pocket costs than those who don’t.
On average, patients who got free prescription samples spent nearly 40 percent more for medication during the six months they received samples, and nearly 20 percent more in the six months afterward, than those who didn’t, according to University of Chicago researchers.
“The notion that people have is that if you receive samples, it helps with out-of-pocket costs because you don’t have to go out and buy the drugs,” said Anirban Basu, one of the study authors and an assistant professor of medicine at the University of Chicago.
“What we found, actually, was that their out-of-pocket expenditures increased. Most surprising was that those out-of-pocket expenditures continued even after the samples stopped.”
The study, published this week in the journal Medical Care, renews debate about the role of more than $18 billion in free pharmaceutical samples distributed each year, which drug industry representatives have described as a cost-saving safety net for the poor.
“This builds on a growing body of literature that shows that samples are not aimed to help the uninsured and the poor, but to increase the sales of the branded drugs,” said Dr. William Shrank, an instructor at Harvard Medical School, who has studied the issue.
The study comes on the heels of a January report that showed free samples are more likely to go to insured and wealthy patients than to the needy.
Drugmakers dispute criticsBut the Pharmaceutical Research and Manufacturers of America, a trade group representing most drugmakers, disputed those views. Free samples allow doctors to try new medicines and to implement them immediately in people of all income levels — including patients who lack prescription drug coverage, Ken Johnson, a PhRMA senior vice president, said in a statement.
Looking at samples in isolation “misses the point,” Johnson said. “Contrary to statements made by critics, American’s physicians prescribe medicines based on a wide range of factors, not simply receipt of free prescription drug samples,” he wrote.
Two out of every three drugs prescribed is generic, not branded, and drugmakers have offered struggling patients a range of options besides samples for receiving medication, Johnson added.
In the Chicago study, patients who never received free samples spent an estimated $178 out-of-pocket on prescription drugs over six months. By comparison, patients given free samples spent about $166 of their own money during the six months before they got the samples — but then $244 during the six months they received the samples and $212 in the six months after that, researchers found.
The study, billed as the first to examine the relationship between drug samples and patient expenses, followed more than 5,700 patients for two years using data from the 2002-2003 Medical Expenditure Panel Survey, a national poll conducted by the Agency for Healthcare Research and Quality. During that time, the patients received more than 2,300 free drug samples.
The results were “counter-intuitive,” said lead author Dr. G. Caleb Alexander, an assistant professor of medicine at the University of Chicago Medical Center. “We expected that free sample receipt would be associated with lower, not higher, cost,” he said.
Reason for higher costs isn't clearExactly why the costs rose wasn’t clear, said Alexander, who added that the study wasn’t designed to answer that question.
Patients who received samples may have been sicker than those who didn’t, which would explain the higher costs, a point emphasized by PhRMA representatives. But analysis showed that illness played a small part, at most, in the higher expenses, Alexander said.
Or, patients may have received higher-priced brand-name drugs — those ones most often given as samples — and then continued with the same pricey prescriptions, Alexander said.
That would be in line with what other studies have shown, said Dr. Andrew F. Leuchter, a professor of psychiatry who heads a committee on drug industry relations at the David Geffen School of Medicine at the University of California, Los Angeles.
“We have known for a while that sample use increases health care costs,” said Leuchter.
But the new study provides first details of out-of-pocket costs, including the fact that the medication expenses remained high even after the samples were finished.
That makes sense to patient J.W. Wright of Goodrich, Texas, who has lived with high blood pressure for 18 years. The 72-year-old retired aerospace engineer has received three different samples of medication in the past year alone. He didn't continue with any of them because they didn't work, but he said he understands how some patients could wind up paying more.
“When you get a sample and a prescription, first you find it works, then you get that brand without thinking the cost, UNLESS the pharmacist tells you the insurance company will only pay for the generic,” Wright wrote in an e-mail. "There's a trade-off. Do I buy the brand at $100 or do I take the generic at $5? I think I try the generic."
If the generic drug works, fine. But if it doesn't, or if no alternative is suggested, the patient — — or the insurer — has to foot the higher bill.
Doctors, patients need to consider larger costsThe solution is for doctors and consumers to be vigilant about the use of drug samples, said Shrank, of Harvard.
"Consumers just need to know that getting a free sample will not reduce their costs over time," he said.
Doctors and patients should discuss using more generic drugs, offering three-month instead of one-month supplies and discontinuing unnecessary medications, Alexander said.
At UCLA, the medical school has adopted guidelines that prohibit shipping drug samples to individual doctors and allow their use only in cases where a patient is indigent or where there’s another significant barrier to care, Leuchter said.
In cases where patients simply wants to avoid an insurance co-payment or a trip to the pharmacy, samples are discouraged.
Sample drugs do have the potential to help needy patients, and to expose doctors to innovative new treatments, Leuchter said. But there's no question indiscriminate use can drive up consumer health care costs, he said.
“We’re trying to do everything we can to encourage people to do the right thing,” he said.
Adderall: Weight Loss Fix of the Stars?

From crash diets to killer workouts, it's little secret that the weight loss regimens of the stars are not always healthy ones.
But a relative newcomer to the celebrity weight loss buzz  the attention deficit hyperactivity disorder (ADHD) drug Adderall  has a number of nutrition experts worried that those hoping to emulate their favorite celebrities could be putting their health at grave risk.
According to a report in the New York Daily News on Monday, a number of female celebrities have used prescription Adderall, even if they have not been diagnosed with ADHD. And reports also suggest that some of these starlets have resorted to crushing and snorting these pills as a way to deliver a quicker effect.
"Often, if we're just beginning to hear of stories about inappropriate use of drugs, like Adderall, for weight loss, it means it's already a significant problem," says Jackie Newgent, a registered dietitian and New York City-based nutrition consultant.
Connie Diekman, president of the American Dietetic Association and director of university nutrition at Washington University in St. Louis, says that "few of my clients report using Adderall for weight loss, but I am very aware of the existence of this problem.
"While these identified risks are significant, the risk that is of biggest concern is the implication that, because celebrities do this, it must be safe," Diekman adds. "Celebrities are viewed as role models  or at least idols  for many people, and ... such potentially harmful behavior puts them and others [at] unknown risk."
And as the number of legitimate prescriptions for the drug grows, some worry that the rates of its abuse could climb as well.
"I find the use of Adderall for weight loss particularly troubling," says June Stevens, chair of the department of nutrition at the University of North Carolina at Chapel Hill. "So many of our youth take Adderall for attention deficit disorder. I fear it may lead to eating disorders and dependency on the drug as a weight loss aid."
Adderall's Diet Drug Origins
The latest news about possible Adderall abuse by some celebrities should not be considered the drug's debut on the weight loss scene. In fact, Adderall  also known generically as amphetamine-dextroamphetamine  was first marketed in the 1960s and 1970s as a diet pill. Since then, however, it has seen its greatest use among those who have ADHD.
In someone with ADHD, the drug re-establishes the chemical balance in the brain that is needed for focus and concentration. For these users, the drug is completely safe. But for those using the drug inappropriately, health risks abound.
Long-term use of Adderall may create the potential for liver problems later on, Diekman says. Other potential risks may manifest themselves much more rapidly.
"Those that improperly use this drug need to know that some people may be allergic to it," Newgent says. "Some may become addicted to it. Dangerous interactions with other meds can occur. And improper use can cause serious heart problems  even death.
"We're not talking about candy here. Unfortunately, some legal drugs get passed around in certain circles like it's Halloween every day."
Does Hollywood Compound the Problem?
But while Adderall may be the newest shortcut to weight loss that has graced the Hollywood scene, it certainly is not the first. And some nutrition experts believe that a general obsession with impossibly trim figures could be fueling such unhealthy diet trends.
"The pressure on young female actresses to stay as thin as possible is only increasing," says Joanne Ikeda, nutritionist emeritus at the University of California in Berkeley. "I watched 'Atonement' last night and thought that Keira Knightley looked like she was a refugee from a concentration camp. Surely she is on a semi-starvation diet that will eventually cause her health to deteriorate."
But the presence of extremely slim actresses in movies could lead to an unhealthy perception of weight in the general public  and a corresponding de-emphasis of healthier means of weight control.
"Paying attention to diet and exercising are healthy behaviors that work," says Dr. Jana Klauer, a physician specializing in metabolism and weight control, and author of the upcoming book "The Park Avenue Nutritionist's Plan."
"Taking medication to get a few pounds off an already slim body are just not worth the risk," she says. "And they will not have the desired result."
A better bet, nutrition experts agree, is sensible calorie control with an emphasis on proper nutrition and exercise.
"The message consumers should take from this is healthy weight is a lifestyle, built around the right food choices, proper portions and regular physical activity  not a magic drug, laxative or cigarette," Diekman says.

Saturday, March 29, 2008

Are you following the rules you’ve set for supervising midlevels?

By Ann W. Latner, JD
If you’re not, you could land in court. These doctors found that out the hard way.
Dr. L and Dr. J weren’t always on site in their small family practice; at times their physician assistant, Ms. A, was the only clinician available. Such was the case when Mrs. Z came to see Dr. L, her regular physician, and was treated by Ms. A instead. It would turn out to be a fateful visit.
The patient, in her mid-50s, presented with severe headaches and nasal discharge. Ms. A prescribed intranasal steroids to treat the symptoms and advised Mrs. Z to return in a week for additional tests.
Five days later, Mrs. Z began exhibiting neurologic symptoms, including facial drooping and disorientation. An emergency CT scan at a local hospital revealed a brain abscess caused by a sinus infection. Mrs. Z was flown to another hospital for emergency surgery to remove a portion of her skull. But after the operation, she experienced respiratory distress and had to be put on a ventilator. More surgery followed, and part of Mrs. Z’s skull was eventually replaced with plastic.
The ordeal left Mrs. Z with serious, permanent impairment. She lost all peripheral vision on her left side and suffered nerve damage to her right leg. Because of balance problems, she had to undergo rehabilitation to learn how to walk again. She was unable to regulate her emotions, manage complex cognitive thinking, or perform many functions of daily living.
Mrs. Z and her husband believed the entire nightmare could have been prevented had she received adequate care from Ms. A at the outset. A plaintiff’s attorney agreed and filed a malpractice suit on their behalf against Ms. A and her two supervising physicians, Dr. L and Dr. J.
The case began with the exchange of relevant documents. During this “discovery phase,” the doctors gave copies of their practice agreement and similar papers to the plaintiff’s attorney. Next, depositions were taken from all the parties and experts. Subsequent negotiations to settle out of court failed. The trial lasted eight days. The plaintiff’s experts testified that Ms. A should have recognized Mrs. Z’s symptoms as a sinus infection and prescribed antibiotics. The steroids served only to mask and exacerbate the underlying problem, they said.
The plaintiff’s attorney also submitted the physicians’ practice agreement, which specified that either Dr. L or Dr. J would see every patient Ms. A treated. The doctors should be held liable for Mrs. Z’s condition, the lawyer argued, because they failed to follow their own rules.
Experts for the defense testified that headache and runny nose could indicate various conditions, not all of which require antibiotics, and that Ms. A acted properly in suggesting tests if Mrs. Z didn’t improve in a week. They also contended that there was no way to reasonably anticipate a brain abscess based on Mrs. Z’s symptoms when Ms. A examined her. After deliberating for five hours, the jury awarded the plaintiffs $3 million.
Legal background
Failure to diagnose accounts for about 40% of all medical malpractice lawsuits. In this case, the jury found that Ms. A’s failure led to Mrs. Z’s impairment and the financial burdens of extensive medical and rehabilitation costs.
However, in the absence of additional symptoms, headache and runny nose can be signs of other conditions. According to Ms. A’s clinical notes, Mrs. Z did not have a fever—a typical sign of an infection—nor did she complain of eye or cheek pain, common symptoms of sinusitis. Even if Ms. A had recognized Mrs. Z’s condition as a sinus infection, was she wrong in her treatment? The plaintiff’s attorney made much of the fact that Ms. A had not prescribed antibiotics, but would that have been good medicine?
The defense maintained that Ms. A’s “watch and wait” attitude was appropriate. If the patient’s condition didn’t improve, she was to return in a week for tests. The likelihood of a sinus infection spreading to the brain in that amount of time was so small that it was unreasonable to expect Ms. A to anticipate it.
The defense also refuted the plaintiff’s attorney’s claim that had Mrs. Z also been seen by one of the two supervising physicians, everything would have turned out differently. Both doctors completely stood behind their physician assistant, reiterating several times that they believed she had treated Mrs. Z adequately and appropriately.
In their turn, the two supervising physicians were found liable because they violated their own practice protocol, which stated that they would see every patient treated by their physician assistant. This protocol goes far beyond the supervision required by any state.
Cases such as this usually settle before trial. Insurance companies in particular will seek to resolve cases out of court if possible. In this case, the insurance carrier, like the physicians, believed in Ms. A’s professionalism as a physician assistant and viewed Mrs. Z’s situation as an unavoidable tragedy.
Panacea or placebo: electronic health records come to the US

By Jonathan M. Gitlin
Doctors' poor handwriting might be a cliché, but being able to accurately read medical records can often be a matter of life and death. The ubiquity of the personal computer has allowed the clinic to enter the digital age, and given that computers excel at managing information, the development of electronic health records (EHR) has been a no-brainer. Despite this, EHR adoption in the US and elsewhere has been slower than some might like, and at least one presidential candidate has made their widespread adoption a healthcare policy platform plank, promising widespread savings through increased efficiency.
Unlike other software markets, where a single player controls the market (such as Microsoft with Office), or where there are but a few solutions, the EHR field is one of byzantine complexity. There are dozens of different software packages and competing products. In this article, we'll look at the state of the EHR field, along with some of the benefits and problems associated with their use.
Inefficiencies in the system
Despite the US' position as the world's largest and most advanced economy, the US health care system is a model of inefficiency. Costs are more than twice those of any other nation in the Organization for Economic Co-operation and Development; the US spends more than $6,000 per patient per year. Despite this expenditure, health outcomes are, by most metrics, worse than almost every other OECD nation, whether it be life expectancy, infant mortality, years lived free of disease, and so on.
Part of this inefficiency is related to the availability of records. Currently, it's estimated that 20 percent of medical tests ordered by clinicians are repeats of previous tests, conducted because the originals have been lost. When those tests include expensive CT and MRI scans, you can see where some of those massive costs come from.
It's not just money-saving either; medical errors due to incomplete, inaccurate, or illegible records are a serious problem, and patients moving from one care provider to another can encounter problems if their records don't follow them.
To this end, a recent study by the RAND Corporation suggests that widespread adoption of EHRs could save as much as $81 billion each year, thanks to fewer redundant tests and procedures and fewer errors in treatment. But EHR adoption in the US lags behind other countries, with adoption rates by physicians' practices at less than 20 percent. By way of contrast, over 90 percent of primary care practices in Scandinavian countries have adopted EHRs.
An example of an Electronic Health Record
So, by increasing the uptake of EHRs, practices should be able to cut their costs, and do away with the mountains of paper records, along with reducing errors and duplicate tests. But even if every doctor in the land adopted EHRs tomorrow, that's no guarantee that things would magically be all right.
Illegible handwriting, digital style
Working in an office, if someone sends you a file you can't open, it's not usually a matter of life or death. On the other hand, an incompatible medical record file moves the problem of illegible handwriting into the digital age. A common complaint among doctors that Ars spoke to was that of EHR format incompatibility; it's no good having a file you can't read. Unlike productivity software, where programs with differing file formats—such as Word versus WordPerfect—get sorted out in the marketplace, with EHRs, there is a real need for common standards.
In 2004, the US government created, via executive order, the National Coordinator for Health Information Technology within the office of the Secretary of the Department of Health and Human Services. The Office of the National Coordinator exists to provide "counsel to the Secretary of HHS and Departmental leadership for the development and nationwide implementation of an interoperable health information technology infrastructure."
Part of that job is to ensure that interoperability standards exist within the health IT industry. I spoke with Dr. John Loonsk, director of the Office of Interoperability and Standards, about the some of the issues surrounding standards. Ongoing issues with competing standards in EHRs have led to the creation of the Healthcare Information Technology Standards Panel, a public-private partnership that works to harmonize standards within health IT.
In addition, another body, the Certification Commission for Healthcare Technology, provides a "seal of approval" of interoperability; solutions certified by the commission can be bought safe in the knowledge that they won't speak Greek to each other. The positives, Loonsk told Ars, will be "having EHRs that can follow the patients and can be accessible by two providers to support care is going to be helpful to improve quality of care, efficiency of care and reduce errors."
In order to help the spread of such standards among EHRs, the federal government has mandated that standards recognized by HHS have to be incorporated into federal contracts. This is designed to provide a base level of compatibility between the dozens of different solutions without dictating to the market in a way that would stifle innovation.
Dr. Loonsk acknowledged that there is still more work needed in this area; some of the pieces of the challenge are that health information is a broad information space. Unlike banking,which deals in numbers, health IT involves lots of complicated concepts, and there are different ways to communicate those concepts. Your bank balance is your bank balance, but your health records need to relate what a patient is feeling, where they're feeling it, and so on.
Who Does Your Doctor Really Work For?

By Scott Haig
Early March was not a good time to break a bone. You might have had a difficult time finding someone to fix it, since thousands of orthopedists were otherwise occupied in San Francisco, at the 75th annual meeting of the American Academy of Orthopaedic Surgeons (AAOS).
The mood there wasn't entirely jubilant. The past year has been a tough one for the business of orthopedics, one in which it has taken a hard, public slap from the U.S. Department of Justice (DOJ).
The DOJ, you see, has discovered the "relationships" that so many orthopedic companies have established with orthopedic surgeons. Companies give money to doctors to test products, to help design or tout products and sometimes just to use a particular product (as in kickback). Orthopedists are hardly the only doctors paid by medical companies, but when the sheer amount of money being given to orthopedists came out of the shade into the sharp San Francisco sunshine last week, it did make quite a few of us blink.
The DOJ's slap was felt acutely by everyone at the convention. No more free dinners, shoulder bags, flashlights and pens. Way fewer models in leotards draped across operating tables and traction equipment. A new ruling requires every research presentation to begin with full disclosure of all monetary relationships the speaker has with any company. Every single fully trained doctor I heard speak was getting paid by a company; many of the bigger-name doctors were getting paid by three or four. How much money was still the subject of gossip — the exact amount is not required to be broadcast in these podium confessionals. The DOJ has, however, ordered companies to list the doctors in their employ, as well as the amounts paid them, on their websites. Judging by those figures, it adds up to plenty. And it got our attention at AAOS. Some doctors thought it immoral; others lamented the doubt it cast on the integrity of research. But I think most just wanted in.
If there's one thing that a life spent mending broken bodies makes you, it's realistic. Most surgeons are quite realistic about capitalism. We see its very essence, the power of monetary incentive, over nearly everyone in our world. We see it in the extra lab tests that please patients as well as pay (and protect) doctors, in the fleet of blank-faced bureaucrats floating to their next paychecks on rivers of inane hospital regulations, and in the TV drug ads for restless legs, erectile errors and feminine itches. We know what they're after.
Not that these shenanigans are completely new to us. When you spend your life outfitting patients with the Joe Dokes Knee Prosthesis, you get a glimmer that Joe Dokes himself must be making some money on the thing. But there are 17,000 orthopedists in the U.S., and with this convention a large fraction of us came to the simultaneous realization that just about all of our teachers and mentors — the surgeons we hold in high regard, who do the important research, who work in the teaching programs, who write the papers and give us these lectures — are "consultants."
Maybe it's part of growing up as a doctor — to put away childish notions like "pure academics." Or, perhaps, we should be reassured by the peer-review process, which all the papers must undergo: papers get chosen for publication only after impartial, third-party doctors have read and vetted them. The vast majority of the time this is pretty good proof that researchers aren't just company shills. But that mandatory confessional is still required in print, stark like the warning on a pack of cigarettes: "This guy is taking money from a company so take what he says with a grain of salt."
It's not just uncertainty about the legitimacy of the new research that rankles. It's also the fact that most of our research is probably legitimate, but unfortunately real doubt is being cast on the basic truths and actual progress of our practice. The ultimate cost of this will likely be borne by our patients. Take the small-town surgeon, who goes to the convention in San Francisco and hears the financial disclaimers. Like many others, his own practice at home is floundering financially. Between his natural envy of the corporate money and the doubt it casts on what he's supposed to be learning, he goes home disillusioned and probably less well educated — and with so few orthopedists in so many small towns, his patients lose out too.
Orthopedists know about fixing bones, but there is no operation to fix fractured trust. We take medical lies personally. They are, like all lies, offensive, even poisonous, to something deep within. It's surely not a physical poison; while our brains can be hurt by chemicals, our minds are only made of (true) ideas. Lies (untrue ideas) can rot the substance of a mind. Insofar as human life is different from the life of a mindless thing, like a tree, lies — even little lies about new pills and braces — are things that kill us. That's why they're so offensive.
An administrative judge, facing a moral dilemma of greater than medical proportions, once asked his defendant, "What is truth?" The famous silence of that defendant's reply might have been an answer, an eloquent one in fact. Truth standing right there, knowable, yet, as then by Pilate, it was, for reasons of expediency, or money, ignored. Yet the truth did win out. It's a lot like this in surgery now. Our consultants might have conflicts, but sooner or later they will have to come back to us; if you really are a doctor, the truth is where the fun is. That's why I know they'll get around, eventually, to teaching us what we need.
How to Get Into Dermatology: A Life Hack

Dermatologists love to cite that the most difficult specialty to get into is dermatology. There is no way to prove this and of course other specialties such as Plastic and Orthopaedic Surgery are also highly competitive.
But just how competitive is it to get into dermatology?
According to the The New York Times, medical students who matched into dermatology had the most research experience, the second highest board scores, and the highest percentage of students in the Alpha Omega Alpha honor society, yet they had the lowest match rate of the specialties reported.
Only 61 percent of seniors at American medical schools whose first choice was dermatology received a residency in that field last year, compared with 98 percent for those whose first choice was internal medicine and 99 percent for those seeking family medicine ….
So how do you get into dermatology? The same way that you achieve any other monumental goal in life:
Work harder than everybody around you.
Imagine yourself the Tiger Woods or Lance Armstrong of your medical school class. Be the first one in and the last one to leave the gross anatomy lab. Round on your surgery patients at 4.30 AM. (Yup, that means getting up at 3.30 AM). Know the surgeries you will participate in that day. Know the anatomy you will see in the OR like you know your own name.
Be generous with your knowledge and your time.
Share notes with your classmates. Help out your teammates when their patient load gets too heavy. You can never get to be number one if you’re all alone.
Accept criticism gracefully.
If your resident says you’re wrong, then you’re wrong. Move on.
Never complain. Never, never, never complain.
Not to your classmates, not to your intern or resident, not to your attending, not to your girlfriend or boyfriend, not even to your mom.
Realize that life isn’t fair.
Sometimes you will deserve to get a question correct or will deserve a better grade. It’s part of the game; it’s part of life. Just pick your ball up and move on to the next tee.
Believe that you can be number one.
Really believe it.
Be confident without being arrogant.
When someone beats you, take your hat off and congratulate her or him.
Be funny.
Humor goes a long way in building rapport with people, and it’s hard for people to be “gunning for you” if they really like you.
Elevate the game of everyone around you.
Lead. Make your study group the best in the class, your team the best team on the wards, your class, the best class in the school.
Take care of your patients. In the end, it’s all about them (and about what you do for others).
If, after all the above, you give up your precious exam study time to sit with a lonely patient for 10 minutes, then you have what it takes to get into dermatology.
Parkinson's Association with Pesticide Exposure Gains Strength

By Crystal Phend
MIAMI, March 28 -- Pesticide exposure may boost the risk of developing Parkinson's disease over and above genetic factors, according to a case-control study here. Parkinson's disease patients were 61% more likely to report direct contact with pesticides than their unaffected relatives, reported William K. Scott, Ph.D., of the University of Miami, and colleagues online in BMC Neurology. There was a significantly higher dose-dependent relationship for frequency, duration, and cumulative exposure among Parkinson's patients compared with relatives (P<0.013), the study found. Insecticides and herbicides appeared to be primarily responsible, particularly organochlorines and organophosphate insecticides, the researchers said.
However, it's still too early to make recommendations on avoiding exposure for patients who may be at already elevated Parkinson's risk because of a family history, said co-author Dana B. Hancock, of Duke University.
And, the findings certainly don't discount the contribution of genetics to Parkinson's risk, she said.
Genetic variants known to cause Parkinson's disease are rare and account for only a small fraction of cases. The majority of cases are likely the result of environmental exposure and the interaction between genes and exposures, Hancock said.
The researchers conducted clinical exams and detailed interviews with 319 Parkinson's patients and 296 of their relatives and spouses.
Parkinson's patients were 1.61 times more likely to report ever personally using pesticides compared with their unaffected relatives (62.7% versus 49.7% exposed, 95% confidence interval 1.13 to 2.29).
Those who were exposed through direct pesticide application on more than 10 days a year were 2.07 times more likely to have Parkinson's disease than those who were never exposed (95% CI 1.26 to 3.42).
Likewise, participants in the highest duration category with more than 26 years of exposure through direct pesticide application were 1.87 times more likely to have Parkinson's than those who were never exposed (95% CI 1.16 to 3.00).
The highest exposure category for cumulative exposure was also positively associated with Parkinson's (OR 2.37, 95% CI 1.42 to 3.94).
Frequency, duration, and cumulative exposure were all associated with Parkinson's disease in a dose-dependent manner.
Although women generally had lower exposures, the highest frequency of pesticide application was associated with Parkinson's for both sexes (OR 2.15 for men, 95% CI 1.06 to 4.35 and OR 2.43 for women, 95% CI 1.18 to 5.01).
There was a dose-response association for both women (P=0.0058) and men (P=0.021 for duration and P=0.036 for cumulative exposure).
Notably though, family history appeared to be a more important factor than pesticide exposure among patients with a family history of Parkinson's. None of the associations was significant in this group.
The associations were even stronger in those without a family history. Parkinson's disease patients were 3.25 times more likely to report the highest cumulative exposure levels of at least 179 days than their unaffected relative (95% CI 1.84 to 5.73).
Herbicides were as strongly associated with Parkinson's as other pesticides, but among the pesticides only insecticides were significantly associated with the condition. Among the classes of chemicals participants reported using, only application of organochlorines and organophosphates were significantly linked to Parkinson's.
The most common of these chemicals were the agricultural insecticide chlordane, the now-banned insecticide dichloro-diphenyl-trichloroethane (DDT), the home-and-garden insecticide chlorpyrifos, the household insecticide diazinon, and the agricultural insecticide malathion.
Potential exposure routes other than direct application, such as well-water consumption and living or working on a farm, were not significantly associated with Parkinson's disease.
Although the findings supported pesticides as a contributor to Parkinson's risk, the case-control study could not establish a causal association and was also limited by potential recall bias, the researchers noted.
The study was supported by grants from the National Institutes of Health, National Institute on Neurological Disorders and Stroke. The researchers reported no conflicts of interest.
Additional source: BMC NeurologySource reference: Hancock DB, et al "Pesticide exposure and risk of Parkinson's disease: A family-based case-control study" BMC Neurol 2008; DOI: 10.1186/1471-2377-8-6.
PET Tracer Picks Up Alzheimer's Plaques in Live Patient

PITTSBURGH, March 28 -- Beta-amyloid plaques were successfully visualized with a PET scan in a living Alzheimer's disease patient, researchers here said. With a fluorescent tracer called Pittsburgh Compound-B used to highlight beta-amyloid plaques, a 64-year-old woman with clinically diagnosed Alzheimer's disease underwent a PET scan 10 months before her death, with plaques then conclusively identified at autopsy, reported Steven T. DeKosky, M.D., and colleagues at the University of Pittsburgh, online in Brain. The autopsy findings showed that the regions visualized in the PET scans were the same as the beta-amyloid plaques. Furthermore, the autopsy-confirmed plaques all showed up on the scans, except for a few in the cerebellum.
"This is final confirmation of what we have believed all along, that Pittsburgh Compound-B allows us to accurately assess the amount of beta-amyloid plaques in brains of people afflicted with Alzheimer's," Dr. DeKosky said.
The researchers said the findings could be useful for clinical diagnosis and monitoring, and also as a surrogate marker of treatment response in clinical trials of new Alzheimer's drugs.
Pittsburgh researchers had reported a similar finding in a 76-year-old man a year ago, but said it needed to be confirmed in additional patients (See: Imaging Exposes Alzheimer's-Like Plaque in the Human Brain)
In the new study, Dr. DeKosky and colleagues also reported that Pittsburgh Compound-B bound almost exclusively to beta-amyloid plaques and large amyloid-laden blood vessels when it was applied to brain tissue taken post-mortem from 27 patients with clinical Alzheimer's disease.
Pittsburgh Compound-B is a thioflavin derivative first identified in 2001 as a potent and selective binding agent for amyloid protein in the insoluble beta-sheet configuration.
It penetrates the blood-brain barrier, and hence can be administered intravenously before PET scanning.
The PET scan gives quantitative readings of the amount of the tracer retained in brain tissue. The Pitt researchers believe that it therefore indicates the amount of insoluble beta-amyloid protein present.
Dr. DeKosky and colleagues determined in the new study that the agent does not allow good visualization of diffuse plaques, such as those found in the caudate nucleus and presubiculum.
It also did not highlight amorphous amyloid plaques in the cerebellum at all, they reported.
The researchers also said a small subset of tau protein-based neurofibrillary tangles were labeled by Pittsburgh Compound-B. "These resembled extracellular 'ghost' neurofibrillary tangles," Dr. DeKosky and colleagues wrote.
In a further test of the tracer's specificity, they treated plaque-heavy tissue sections with formic acid, which disrupts the beta-sheet conformation. The treatments abolished binding by Pittsburgh Compound-B.
But they said their most important findings were in the woman who underwent PET scanning with Pittsburgh Compound-B before her death.
The autopsy revealed that beta-amyloid plaques had infested much of her brain, confirming the clinical diagnosis of Alzheimer's disease.
More to the point, the researchers found that the amount of insoluble beta-amyloid protein closely matched the levels of Pittsburgh Compound-B at the same locations as measured with the PET scan 10 months earlier.
"These results demonstrate, in a typical Alzheimer's disease brain, that Pittsburgh Compound-B binding is highly selective for insoluble (fibrillar) beta-amyloid deposits," the researchers wrote.
Moreover, the tracer had not highlighted neurofibrillary tangles in the woman's brain, showing that it is specific for beta-amyloid and not other aspects of Alzheimer's pathology.
However, as in the studies with brain tissue from the 27 patients post-mortem, the researchers found that the tracer did not bind well to plaques in the cerebellum.
Pittsburgh Compound-B did bind strongly to areas of cerebral amyloid angiopathy, potentially a problem in clinical situations. But such structures, which are distinct from plaques, are uncommon in Alzheimer's patients, they said.
"This work is an important step forward in the development of new tools for both research and clinical care," said Neil Buckholtz, Ph.D., chief of the Dementias of Aging Branch of the National Institute on Aging, which helped fund the study.
He added that it further supports the tracer's validity in detecting beta-amyloid deposits in live patients.
If confirmed once and for all, Pittsburgh Compound-B could also be useful "as an outcome measure in clinical trials of anti-beta-amyloid therapeutics," Dr. Buckholtz said.
The study was funded by the National Institutes of Health, the Department of Energy, the Alzheimer's Association, and the Dana Foundation.
No potential conflicts of interest were disclosed.
Additional source: BrainSource reference: Ikonomovic M, et al "Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease" Brain 2008; DOI: 10.1093/brain/awn016.
Aging Lungs Fail Faster with Type 2 Diabetes

By Michael Smith
BALTIMORE, March 28 -- Lung function declines faster in type 2 diabetes patients than in those without the disease, according to researchers here.
Point out that the study is subject to residual confounding and cannot prove causality.
The finding -- from the long-running Atherosclerosis Risk in Communities (ARIC) study -- implies that clinicians should pay attention to pulmonary function in diabetic patients, said Frederick Brancati, M.D., of Johns Hopkins and colleagues.
It also may have implications for the use of inhaled forms of insulin, Dr. Brancati and colleagues said in the April issue of Diabetes Care.
"The results suggest that doctors and patients should keep an eye on the literature about diabetes and the lung down the road, since there's a stronger connection than we previously thought," Dr. Brancati said.
"Manufacturers of inhaled insulin should find these data useful as they study potential long-term effects of their product on lung function," Dr. Brancati added.
For this analysis, he and colleagues looked at lung function in 1,100 middle-age patients with diabetes and 10,162 persons without it enrolled in the ARIC study. Key measures were forced vital capacity (FVC) and one-second forced expiratory volume (FEV1), measured at baseline and after three years.
At baseline, the researchers found:
FVC in men and women with diabetes was 4.2 and 3.0 liters, respectively, compared with 4.6 and 3.3 in non-diabetic men and women. The differences were significant at P<0.001.
Similarly, FEV1 in men and women with diabetes was 3.2 and 2.3 liters, respectively, compared with 4.3 and 2.5 in non-diabetic volunteers. Again the differences were significant at P<0.001.
FVC percentage predicted and FEV1 percentage predicted were also significantly lower in patients with diabetes.
When the researchers stratified the diabetic patients according to fasting glucose levels, duration of diabetes, and use of diabetic medications at baseline, they found a graded inverse association between those characteristics and FVC and FEV1. In all cases, the trend was significant at P<0.001.
Three years further on, Dr. Brancati and colleagues found the non-diabetics has suffered an average decline of 58 mL per year in FVC, compared with 64 mL a year for the diabetics. The difference was significant a P<0.01.
The non-diabetics had also lost 47 mL per year of FEV1 compared with 49 for the diabetics, but the difference was not significant.
FVC percentage predicted declined significantly (P=0.009) but FEV1 percentage predicted was no longer significantly different. Also, fasting glucose levels and duration of diabetes were no longer significantly associated with most lung function measures.
However, the use of insulin (compared with no medications or the use of oral agents) remained significantly associated (Ptrend =0.001) with lower FVC, the researchers found.
The study "essentially confirms" some previous research, commented Connie Hsia, M.D. and Philip Raskin, M.D., both of the University of Texas Southwestern Medical Center in Dallas, in an accompanying editorial.
But other studies have suggested that the difference between diabetics and non-diabetics in lung function does not continue to increase over time, they wrote.
If Dr. Brancati and colleagues are correct, they said, the lung should be thought of as a "as a crime victim who unwittingly abets the perpetrator to hasten the demise of the host."
In other words, cumulative loss of lung function eventually worsens tissue hypoxia associated with angiopathy in distant organs and increases diabetic morbidity and mortality, they said.
But proving that model is correct "beyond reasonable doubt remains a daunting challenge, they concluded.
They also pointed out some important limitations. They noted that there were more African Americans (37% versus 21%, P<0.001) and a higher mean BMI (30.9 versus 27.2, P<0.001) among the diabetic patient group,
They noted that "average FVC and FEV1 are lower in African Americans than in Caucasians after adjustment for sex, age, and height," and that "adiposity independently impairs lung function."
The authors also noted the importance of the difference in BMI stating that "given the strong relation between type 2 diabetes and central adiposity, even the most meticulous adjustment for BMI and waist circumference leaves some concern about the possibility of residual confounding."
The ARIC Study is supported by the National Heart, Lung, and Blood Institute, the National Institute of Diabetes, Digestive, and Kidney Diseases NIDDK). Individual researchers were supported by the NIH, the Brazilian National Research Council, and the NIDDK. Analysis of this manuscript was partly supported by Pfizer. Dr. Brancati reported no conflicts.
Dr. Raskin reported financial links with Novo Nordisk, Pfizer, and MannKind.
Primary source: Diabetes CareSource reference:Yeh H-C et al "Cross-sectional and prospective study of lung function in adults with type 2 diabetes: The atherosclerosis risk in communities (ARIC) study" Diabetes Care 2008; 31: 741-746. Additional source: Diabetes CareSource reference: Hsia CW, Raskin P "Lung involvement in diabetes: Does it matter?" Diabetes Care 2008; 31: 828-28.
Once-Daily Insulin More Convenient but No More Effective

By Crystal Phend
GIESSEN, Germany, March 28 -- Once-daily injections of insulin glargine (Lantus) may control type 2 diabetes as well as multiple injections of insulin lispro (Humalog) and reduce side effects at the same time, researchers here found.
Basal insulin therapy had a similar effect on glycosylated hemoglobin A1c levels as prandial insulin (1.7% versus 1.9% reduction) but yielded 78% fewer hypoglycemic events, less weight gain, and greater patient satisfaction, reported Thomas Linn, M.D., Ph.D., of Justus Liebig University Giessen, and colleagues in the March 29 issue of The Lancet.
"Insulin glargine provides a simple and effective option that is more satisfactory to patients than is lispro for early initiation of insulin therapy," they wrote.
The findings also help address the ongoing debate over whether to target therapy to fasting glucose or postprandial glucose, said Yogish C. Kudva, M.B.B.S., and Victor M. Montori, M.D., of the Mayo Clinic in Rochester, Minn., in an accompanying editorial.
But the issue will not be settled until studies link improvements to outcomes that matter to patients, such as diabetes complications, Drs. Kudva and Montori said.
The APOLLO (A Parallel design comparing an Oral antidiabetic drug combination therapy with either Lantus once daily or Lispro at mealtime in type 2 diabetes patients failing Oral treatment) was a non-inferiority study funded and done by the makers of the basal insulin under evaluation.
It included 205 type 2 diabetes patients randomly assigned to open-label insulin glargine once daily at the same time every day and 210 patients randomized to insulin lispro three times daily before meals.
All the patients had hemoglobin A1c concentrations between 7.5% and 10.5% and fasting blood glucose concentrations of 6.7 mmol/L or more despite being on stable doses of oral antidiabetic agents.
Most patients in both groups remained on metformin (74% to 76%) and glimepiride (Amaryl, 93% to 94%) throughout the trial.
After 44 weeks of treatment, mean hemoglobin A1c decreased from 8.7% to 7.0% in the insulin glargine group and from 8.7% to 6.8% in the insulin lispro group (P<0.0001 for both).
The similar adjusted mean change between groups met criteria for noninferiority in both the per protocol and intent-to-treat analyses (0.137% difference, 95% CI -0.022 to 0.297, P=0.0908).
Despite the debate about whether fasting or postprandial blood glucose concentrations have a greater effect on hemoglobin A1c, the researchers said, "our data suggest that the reduction of hemoglobin A1c is more dependent on targeted insulin therapy per se rather than on a specific glucose profile."
As expected, though, insulin glargine reduced nocturnal blood glucose and morning fasting glucose better whereas postprandial glucose levels were better with insulin lispro.
More patients in the insulin lispro group than in the insulin glargine group reached hemoglobin A1c targets, including:
7% or less (69% versus 57%)
6.5% to 7% (30% versus 27%)
Less than 6.5% (38% versus 30%)
But more patients reached target fasting blood glucose concentrations of 5.5 mmol/L or less with insulin glargine than with insulin lispro by the end of the study (35% versus 5% in the intent-to-treat analysis, P<0.0001).
Insulin lispro better controlled postprandial blood glucose throughout the day (P<0.0001).
Hypoglycemia events were substantially less common with insulin glargine than with insulin lispro (4.27 versus 19.46 per patient, P<0.0001), although severe events were not significantly different between groups.
Weight gain from baseline tended to be lower with insulin glargine (3.01 versus 3.54 kg, P=0.23).
While patients in both groups reported a fairly high level of satisfaction with treatment, insulin glargine-treated patients had significantly greater increases in satisfaction than lispro-treated patients (P<0.0001).
Notably, satisfaction scores related to convenience of treatment worsened in the lispro group compared with baseline but improved in the glargine group.
These advantages for insulin glargine may help poorly controlled patients accept making a timely shift from oral agents alone to the addition of insulin, the researchers concluded.
The study was funded by sanofi-aventis, which makes insulin glargine.
Dr. Linn reported receiving an unrestricted research grant from sanofi-aventis. His co-authors reported conflicts of interest for sanofi-aventis, Bayer, Develogen, GlaxoSmithKline, Lilly, MSD, Novo Nordisk, Pfizer, Roche, and Novartis. One of the authors reported holding a copyright for the diabetes treatment satisfaction questionnaire and being director of Health
Psychology Research that licenses questionnaires to pharmaceutical companies.
Dr. Kudva reported receiving funding for a research trial from sanofi-aventis. Dr. Montori declared no conflicts of interest.
Primary source: The LancetSource reference:Bretzel RG, et al "Once-daily basal insulin glargine versus thrice-daily prandial insulin lispro in people with type 2 diabetes on oral hypoglycemia agents (APOLLO): An open randomized controlled trial" Lancet 2008; 371: 1073-84. Additional source: The LancetSource reference: Kudva YC, Montori VM "Patient-centered treatments for type 2 diabetes" Lancet 2008; 371: 1047-48.

Friday, March 28, 2008

Dengue claims 54 lives in Brazil

A dengue epidemic has claimed at least 54 lives in Rio de Janeiro state since January, health officials said Thursday.
Hospitals have reported a total of 114 deaths from the mosquito-borne disease, but 60 of those cases are still being investigated.
Brazilian Health Care Secretary Jose Noronha said that 1,200 soldiers from the army, air force and navy would be deployed next week to set up three field hospitals, while an additional 500 would spray insecticide and place poison in standing puddles of water where the mosquitoes breed.
"The intensity of the epidemic has brought intolerable death tolls," Noronha told reporters after a meeting with armed forces commanders.
The majority of the confirmed deaths, 31, have been in the city of Rio de Janeiro — Brazil's biggest resort city. Rio has seen a 25 percent drop in tourism as a result, the Brazilian Hotel Association said.
About half of the victims were children under the age of 13.
More than 43,000 people have contracted disease since January in Rio de Janeiro state — nearly double the 25,107 cases reported in all of 2007. The state is home to 16 million people.
State health official Victor Berbara said the outbreak highlights the importance of fighting the dengue-carrying Aedes aegypti mosquito all year — not just between November and May when most infections occur.
"If nothing is done ... next year is going to be much worse," he told reporters.
Earlier this week, federal officials sent hundreds of health workers to Rio de Janeiro state to help care for victims in the state's overcrowded emergency rooms, and set up special tents with extra hospital beds in the city.
On Wednesday, Rio de Janeiro state Gov. Sergio Cabral ordered health officials to break into homes suspected of containing standing bodies of water if the owners could not be found.
Dengue, which has no vaccine, can incapacitate patients for over a week with severe headaches and joint pains, but is not usually fatal.
FDA Warns of Possible MI Risk Associated with Two HIV Drugs

By Michael Smit
ROCKVILLE, Md., March 27 -- Two HIV drugs may increase the risk of heart attacks, the FDA cautioned today.
In an alert characterized as an early communication about recent findings of the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study, and the agency said data collected through Feb. 1, 2007 appeared to show an increased risk of MI associated recent use of abacavir (Ziagen) or didanosine (Videx).
The study found:
The excess risk of heart attack in patients taking at least some nucleoside reverse transcriptase inhibitors -- the class including the two drugs -- appears to be greater in patients with other risk factors for heart disease.
Some analyses found the risk of heart attack rose by 49% in patients taking didanosine and 90% in patients taking abacavir.
The risk did not appear to increase over time and appeared to be reversible after abacavir or didanosine was stopped.
But the agency said data from the D:A:D study -- an observational study of 33,347 HIV patients -- remains "incomplete."
In particular, the researchers did not evaluate the risk of heart attack when patients take tenofovir (Viread) or emtricitabine (Emtriva), two other drugs in the same class as abacavir and didanosine.
The agency also said the makers of the two drugs -- GlaxoSmithKline and Bristol-Myers Squibb -- had analyzed their own databases and found no indication of an increased risk.
Both results are "inconclusive," the agency said.
Nonetheless, the agency said, if the findings hold up, it may require revised labeling for the products. In the meantime, clinicians should "evaluate the potential risks and benefits" of each anti-HIV drug their patients are taking, the agency said.
Excess Cancer Deaths Prompt FDA Review of Becaplermin Gel Safety

By John Gever
ROCKVILLE, Md., March 27 -- The FDA said today it was reviewing the safety of becaplermin gel (Regranex) after learning it may increase cancer deaths in patients with diabetes.
The agency identified no single type of cancer from use of the topical form of recombinant platelet-derived growth factor, which is indicated for healing of persistent diabetic leg and foot ulcers.
It said only that a study of insurance plan data showed that deaths from all types of cancer combined were increased.
While the review is underway, the FDA recommended that physicians discuss the potential risks and benefits of the drug with their patients. The agency noted that non-healing ulcers also carry risks for the patient.
The agency said the study found that deaths from cancer were higher for patients given three or more becaplermin prescriptions compared with similar patients not treated with the drug.
There was not enough information to say whether there was an increase in the number of patients who developed new cancers, according to the FDA.
The agency said an earlier study completed in 2001 had found more cancers in patients using becaplermin compared with those not using it, prompting the follow-up analysis of insurance plan data.
FDA Probes Merck Drug, Possible Suicides

WASHINGTON (AP) -- The Food and Drug Administration said Thursday it is investigating a possible link between Merck's best-selling Singulair and suicide.
FDA said it is reviewing a handful of reports involving mood changes, suicidal behavior and suicide in patients who have taken the popular allergy and asthma drug.
With sales of $4.3 billion last year, Singulair is used by millions of patients in the U.S, according to Merck. First approved in 1998, it's part of a class of asthma and allergy drugs that includes AstraZeneca's Accolate and Critical Therapeutics's Zyflo.
Merck officials stressed that the FDA's inquiry is based on reports, not clinical studies -- which are the standard tool for evaluating drug safety. The company said none of the 11,000 patients enrolled in 40 Singulair trials has committed suicide.
''We have no indication that anything about the mechanism of Singulair is consistent with these events,'' said George Philip, director of research and product development. ''But because suicide is a life-threatening event we thought it was important to provide this information in the product label.''
''Patients should not stop taking Singulair before talking to their doctor,'' FDA said in its statement, adding that doctors should monitor patients for suicidal behavior and mood changes.
FDA said it asked the Whitehouse, N.J.-based company to dig deeper into its data on Singulair for evidence of possible links to suicide. The agency said it has not established a ''causal relationship'' between Merck's drug and suicidal behavior. An agency spokeswoman said the review was prompted by three to four suicide reports it received before October.
It could take up to nine months before agency scientists can draw any conclusions, FDA said in a posting to its Web site.
The agency recently began notifying the public earlier about possible safety issues. The policy change came after the FDA was criticized for acting too slowly on information about the risks of Merck's painkiller Vioxx and GlaxoSmithKline plc's diabetes pill Avandia.
Merck has updated the drug's labeling four times in the past year to include information on a range of reported side effects: tremors, anxiousness, depression and suicidal behavior.
The company said it recently added reports of suicide to Singulair's label, which already listed suicidal thinking and behavior as reported side effects.
In clinical trials of asthma patients, the most common side effects were headache, flu, abdominal pain and cough.
FDA said it is also reviewing reports of side effects with rival drugs, such as Accolate and Zyflo. Their labeling does not contain language about suicide.
Dr. Rauno Joks, an allergy specialist, said Thursday Singulair is generally well tolerated by his patients.
''Some of them have headaches with it but nothing I could imagine developing into depression or suicide,'' said Joks, head of the allergy division at State University of New York's Downstate Medical Center.
Joks said he will continue prescribing the drug because there are few alternatives for asthma patients beyond inhalable steroids, the standard treatment for the disease.