May 25, 2007

Vitamin D, calcium reduce fracture risk, study says

Vitamin D supplements alone are not enough to lower the risk of hip fractures for the frail elderly and those with osteoporosis, new research indicates.

The risk of hip fractures decreases only if they take oral vitamin D supplements along with additional calcium, according to a report in The Journal of Clinical Endocrinology & Metabolism.

The risk of hip fracture was cut by 18% in study participants receiving vitamin D plus calcium, the report indicates. Vitamin D and calcium work together to restore calcium balance and reduce fracture risk restore bone health, researchers concluded.
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May 23, 2007

Popular diabetes drug could be dangerous, study finds

A widely prescribed drug to treat type 2 diabetes increases users' risk for heart attack, according to study findings released this week.

The U.S. Food and Drug Administration reacted to the report with a safety alert for the drug Avandia. It said, however, that more analysis was needed before it would make a decision about the drug from a regulatory standpoint. The generic name for the drug is rosiglitazone.

Researchers found those taking the drug increased their risk of heart attack by 43%. Also, there was a 64% increased risk of dying from cardiovascular causes, compared with patients not taking the drug. Findings will appear in the June 14 issue of the New England Journal of Medicine. More than two million people worldwide take Avandia for type 2 diabetes. Remember that loss of blood sugar control is more risky than the risk of this drug. Consult with your physician or consultant pharmacist as to your alternatives.
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May 3, 2007

Once-a-Year Treatment for Bone Loss, Promising

A simple annual infusion of a new drug is just as effective at reducing bone fractures as weekly or monthly bone loss drugs currently on the market, according to a study by researchers at the University of California San Francisco published today.

The findings on the drug -- called zoledronic acid and marketed as Reclast by Novartis Pharmaceuticals -- could offer millions of older women a more convenient alternative to preventing bone loss. Reclast has not yet been approved by the Food and Drug Administration.

Older women who took Reclast experienced a 70 percent reduction in the risk of spinal fractures and a 41 percent reduction in the risk of hip fractures. Risk of other types of fractures were also reduced, by about 25 percent.

Bone mineral density increased in the spine by 6.7 percent and in the hip by 6 percent among the women on Reclast, according to the study, published in the New England Journal of Medicine.

The three-year study involved 7,700 postmenopausal women with osteoporosis in 27 countries. About half of the women were given Reclast once a year for three years and the other half got a placebo.

The women had a mean age of 73 years and the study included women up to age 89.

"This drug could be quite effective, especially for people who don't tolerate other osteoporosis drugs well," said Dennis Black, professor of epidemiology and biostatistics at the UCSF School of Medicine and lead author of the study.

Common osteoporosis drugs -- such as Fosamax, Actonel and Boniva - - are typically administered in a weekly or monthly pill or liquid form. The medication must be taken on an empty stomach with a full glass of water and the person must sit upright for at least 30 minutes afterwards. A common side effect is an upset stomach.

About half of patients prescribed these oral treatments stop taking them after one year, previous studies have found.

"People just don't continue to take the oral medications," Black said. "Partially it's because it's a general problem of any preventative medicine that doesn't make you feel better when you take it."

Reclast is in this same class of drugs as Fosamax, called biophosphonates. It is given once a year in a 15-minute 5 milligram infusion that can be administered in a doctor's office or hospital.

It has been approved in Mexico and several other countries and is still in the FDA approval process.

Reclast leaves the bloodstream within 24 hours but the drug "has a high affinity to adhere to the bone and stays there," making the effect of the infusion long-lasting, Black said.

The drug remained effective for a year or more, according to the study.

About a quarter of the women in the study experienced mild side effects after their first Reclast infusion, including chills, nausea, bone pain and back pain. Those symptoms typically subsided within three days. On subsequent yearly infusions, side effects were far less common, Black said.

More worrisome, a small number of patients developed atrial fibrillation, a condition of abnormal heart rhythms that can lead to stroke. The risk of developing this heart problem was about 2.5 times higher in patients given Reclast than those in the control group.

Though rare -- one event in 150 women over the three years -- this result surprised researchers because previous studies where cancer patients were given higher doses of Reclast did not indicate atrial fibrillation as a side effect, Black said. More studies on this are forthcoming.

"To some extent, the jury is still out on whether it is a real finding." he said.

Fosamax has also been linked to a slight increase in incidence of atrial fibrillation.

Safety concerns that Reclast could cause kidney damage, osteonecrosis of the jaw, a rare jaw bone condition, or cause the bone to lose its ability to repair itself were not borne out by this study, which was funded by Novartis.

More than 50 million women in the United States, Europe and Japan have osteoporosis. Half of those women over age 50 will have a resulting hip fracture in their lifetime. One in five women over 65 who fracture a hip die within one year. Men also get osteoporosis but at much lower rates; there are 2 million men with the disease in the United States.

Reclast could be a good option for the growing number of very elderly women with osteoporosis, Dr. Juliet Compston, professor of bone medicine at the University of Cambridge School of Clinical Medicine in England, wrote in an editorial published with the study.

"The practicality and acceptability of annual intravenous therapy in large numbers of women remains to be tested," Compston wrote.

"Nevertheless, increased treatment choices for patients are to welcomed."
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May 3, 2007

Genetic flaws may point way on diabetes

Scientists find new risk factors for the disease

Decades after scientists first realized that the risk of getting diabetes was partially inherited, discoveries of real genetic defects are suddenly coming rapid-fire.

Yesterday, four separate scientific teams, including one led by Harvard researchers, reported three new genetic risk factors and confirmed five others identified over the last few years. An additional risk factor identified by one group has not yet been confirmed by others.

The discoveries open up new avenues to explain what breaks down in the body to cause type 2 diabetes. More than 20 million Americans suffer from diabetes and another 54 million are at risk. In the future, scientists said, the genetic findings may also help predict who will get the illness and lead to treatments tailored to each individual's genetic makeup.

"This is a milestone," said Dr. Larry C. Deeb, president for medicine and science of the American Diabetes Association, who was not involved in the research. "We're moving out of the darkness into understanding a lot more about diabetes."

The researchers identified some genetic areas that are not connected to any known mechanism behind diabetes, which harms the body's ability to control blood sugar and can lead to heart disease, blindness, and early death.

"No one had the first clue that these genetic changes were involved in the disease," said David Altshuler, associate professor of genetics and medicine at Harvard Medical School and a leader of one of the three collaborating teams.

Some of the genetic changes are in what scientists previously called "junk DNA," he said, areas of the genetic code that they previously thought were meaningless. "Our whole view of which parts of the human genome contribute to disease is being augmented."

Genetics accounts for about half the risk of getting type 2 diabetes, according to Altshuler. Environment and such behaviors as obesity and lack of exercise account for the remaining risk.

The eight confirmed genetic defects together account for about 5 percent of the risk of getting the illness, he said. "The picture that is emerging is of multiple genes, each with a modest effect" on diabetes, he added.

However, scientists from the National Institutes of Health found that in one group of subjects, people with the most defects had a four times higher risk of having diabetes than people with the fewest defects.

Scientists said much work remains before genetic testing for diabetes becomes useful for patients. Researchers also expect it may be up to a decade before new treatments result from the work.

"The pharmaceutical industry is absolutely salivating at all of these studies" because they suggest targets for new drugs, said Dr. Francis Collins, director of the National Human Genome Research Institute and a leader of another of the teams. "But there is a long lead time."

The results were published yesterday in the on line editions of the journals Science and Nature Genetics. They are based on a new research technique called genome wide association studies, in which scientists compare genetic samples from thousands of individuals who have a specific illness with those who don't.

The work is also unusual because three of the four scientific groups collaborated to confirm their results, drawing on the largest database of DNA ever used to study diabetes and making the findings extremely solid.

"Only five years ago this work would have been unthinkable," said Collins.

Each of the four groups used genetic material from a different population, totaling tens of thousands of subjects.

The three groups that coordinated to confirm each other's results were led by scientists from Britain; the National Institutes of Health and Finland; and the Broad Institute at Harvard and MIT, Sweden, and the pharmaceutical company Novartis.

The three variations they found are near genes that appear to be related to regulation of insulin, which controls blood sugar, and to growth of the cells in the pancreas that produce insulin. In diabetes, the body becomes resistant to insulin or fails to make enough insulin, causing a problematic build-up of sugar in the blood stream. The actual effect of the genetic defects has yet to be determined.

Separately, deCODE Genetics , a company in Iceland, reported finding one of the same genes in an Icelandic population and confirming it in samples of people from other nations. The Harvard research also identified a genetic defect linked to high trigyclerides in the blood, a risk factor for heart disease. The NIH team identified an additional genetic link to diabetes that was not confirmed by the other groups. And the British and NIH groups confirmed a genetic change tied to obesity.

Using the same technique, a French consortium reported finding two diabetes-related genes in February, and deCODE reported finding the genetic variation most strongly linked to the disease in January 2006. Two other genes were identified in 2000.
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May 2, 2007

Study offers hope for memory restoration in Alzheimer's patients

The use of certain cancer drugs or a stimulating environment appear to restore the memories of laboratory mice that have symptoms mimicking Alzheimer's disease, researchers say.

The results offer hope for people with dementia, according to researchers at the Massachusetts Institute of Technology's Picower Institute of Learning and Memory.

For the study, bioengineered mice got their memories back after either being placed in stimulating environments or given a drug most commonly used to fight cancer. An "enriched" environment had shelves, perches, nesting material and tunnels. The study results were published online in the Journal Nature.
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April 27, 2007

Many Stop Drug After Adverse Reaction

Ninety-four percent of U.S. adults who have had an adverse reaction to a prescription drug say they stopped taking a medication, a survey found.

Forty-six percent of U.S. adults currently taking prescription medications report they are only fairly confident, somewhat confident, or not at all confident that their prescribed medications are safe, according to a poll of 1,726 adults interviewed online by Harris Interactive for the Pharmaceutical Safety Institute.

Almost one-half of patients polled report they are concerned about adverse reactions, and more than one-third report having had an adverse reaction to a prescription medication.

More than one-third of all adults who have ever taken a prescription medication report having had an adverse reaction, according to the survey.

These concerns and experiences lead to prescription-drug non-adherence. Thirty-five percent of people who have ever taken a prescription medication reported they had decided not to take a prescription drug because they had a concern about a potential adverse reaction.
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April 24, 2007

No Generic Substitution of AEDs Without Physician and Patient Consent, Says AAN

Generic substitution of antiepilepsy drugs (AEDs) should not occur without the full knowledge and consent of both the treating physician and the patient, according to a position statement released by the American Academy of Neurology (AAN).

Published in the April 17 issue of Neurology, the paper addresses the long- standing issue of whether generic substitution of AEDs places patients with epilepsy at undue risk for breakthrough seizures in the name of reducing health costs.

According to the AAN position statement, the US Food and Drug Administration (FDA) allows for significant differences between name-brand and generic drugs.
However, for some patients with epilepsy, even minor differences in the composition of anticonvulsant drugs can make a big difference.

All-or-Nothing Phenomenon

"Epilepsy is unlike other disorders. The marker for success is whether or not you're having seizures and whether or not you're having side effects. So unlike a condition such as hypertension, where, if you make a change in dose you can monitor blood pressure to determine whether it's working or not, with epilepsy you have an all-or-nothing phenomenon — you're either seizure free or you're not," Gregory Barkley, MD, from Wayne State University in Detroit, Michigan, one of the AAN position statement authors, told Medscape.

"As an organization whose goal is to improve the lives of people with neurologic problems in general, and the lives of people with epilepsy in particular, the AAN feels it is important we speak out on behalf of patients who we know have had problems because they have been switched [to generic AEDs], frequently without their knowledge," he added.

Dr. Barkley also pointed out the consequences of switching to a generic anticonvulsant that results in subsequent breakthrough seizures or adverse events can be devastating.

"Having a breakthrough seizure could mean a person could lose their driver's license or their job or injure themselves or someone else. This has to be weighed against the potential cost savings of switching to a generic anticonvulsant," he said.

Adverse Events Underreported?

In an accompanying editorial, Michel Berg, MD, from the University of Rochester School of Medicine and Dentistry, in New York, suggests one of the reasons the FDA remains unconvinced there is an equivalency issue between generic and brand-name AEDs is because physicians are not reporting such events through MedWatch, the FDA's voluntary drug-reporting system.

According to Dr. Berg, several surveys have shown that the majority of physicians and patients perceive that generic AEDs are not always equivalent to the brand-name drug. But this is not reflected in case reports to MedWatch. He suggests this may, in part, be due to a lack of physician awareness of the MedWatch system.

Dr. Barkley added that underreporting of such events might also be due to the fact that in many cases, physicians are simply not aware that their patients have been switched to a generic agent.

"Unless a patient specifically says to a doctor that their pills look different or they know for a fact that they've been switched [to a generic drug], physicians may attribute a breakthrough seizure or increased side effects to the brand-name drug," he said.

In addition to opposing generic substitution without physician and patient consent, the AAN statement also supports the use of newer-generation anticonvulsant drugs, which generally have a much more favorable adverse-event profile but tend to be more expensive.

"The AAN believes that physicians should make every effort to identify when patients may be effectively treated with less expensive alternatives. However, the discretion for this decision should remain with the prescribing physician and should not be determined by coverage limitations," the authors write.

According to Dr. Barkley, because of the higher cost of these agents, some insurers are putting up "roadblocks" to prevent physicians from prescribing them by imposing a painstaking and protracted approval process.

As a result, he said, the AAN's position statement also opposes prior authorization requirements by public and private formularies.
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April 23, 2007

Studies examine link between HRT and cancer risks

An analysis published in the NEJM suggests that the decline in the use of hormone replacement therapy in 2002 is the most likely explanation for the "sharp" decline in the rate of breast cancer cases in the US in 2003. Use of HRT began to decline in the US after concerns over the drugs' safety emerged from the Women Health Initiative study.

In the initial analysis of data from the National Cancer Institute's registries, the findings showed that the breast cancer rate in the US decreased by 6.7 percent between 2002 and 2003, and that the rate for 2004 remained almost unchanged. Between 2001 and 2004, the breast cancer rate fell 8.6 percent, with the decrease evident in women 50 years and older, and "more evident in cancers that were oestrogen-receptor positive." The analysis also showed that prescriptions for Wyeth's HRT drugs Prempro and Premarin decreased to 27 million prescriptions in 2003, compared to 61 million in 2001.

"The missing cancers, the ones that don't seem to have occurred, are the kinds that are responsive to hormone therapy,'' remarked lead author, Peter Ravdin. "The decline was not a one-year wonder, a short-lived anomaly.'' The researchers added that "the contributions of other causes to the change in incidence seem less likely to have played a major role but have not been excluded."

Wyeth's senior vice president of global medical affairs, Joseph Camardo, stated that the company disagrees "with the conclusion that links the decrease in breast cancer rates with the decline in hormone therapy usage. It might be prudent to look for a broader explanation for the trend in 2003 and 2004." Hugh Taylor, of Yale University, added that "even if there was a cause-and-effect, you wouldn't expect it to show up for five or 10 years. It just doesn't fit with what we know about the basic biology of breast cancer."

Separately, in a study published in The Lancet, researchers examined data from about 950 000 postmenopausal women in the UK who had not previously had cancer. The results demonstrated that for every 1000 women taking HRT, 2.6 developed ovarian tumours over five years, compared with 2.2 cases in every 1000 women who did not use HRT. The death rates from ovarian cancer over five years were 1.6 cases per 1000 and 1.3 cases per 1000 for those taking HRT and those not taking HRT, respectively.

"The effect of HRT on ovarian cancer should not be viewed in isolation especially since the use of HRT also affects the risk of breast and endometrial cancer," the researchers noted. "The total incidence of these three cancers in the study population is 63 percent higher in current users of HRT than never users.
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April 22, 2007

Baby boomers less healthy than parents, study finds

For the first time in history, the next generation reaching retirement - the baby boomers - may actually be less healthy than their parents were at the same age, according to new study results.

While baby boomers tend not to smoke as much and describe themselves as healthy and vibrant, researchers at the University of Texas at Austin found that they are more likely to report difficulty climbing stairs, getting up from a chair and doing other routine activities. In addition, the study, which was reported in the Washington Post, shows that more boomers have chronic problems that include diabetes, high cholesterol and high blood pressure.

Baby boomers tend to be less physically active than their parents and grandparents. Increasingly sedentary lifestyles and work routines are largely to blame, according to the report.
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April 17, 2007

Drug monograph update on Zanaflex®

AcordaTherapeutics the makers of Zanaflex® announced changes along with the FDA to the“ Contraindications and Warnings” statements in the Zanaflex monograph on April 11, 2007.

Recent postmarketing studies have shown that when co-administered with CYP 1A2 inhibitors the serum concentrations of tizanidine(Zanaflex®) are significantly increased. This serum level increase raises the potential for adverse effects of sedation and hypotension. Use with the following agents should be avoided especially in the geriatric population.
Explanation: CYP 1A2 are the isozymes (chemicals in the liver) that breaks down and metabolizes the drug (Zanaflex). There are multitudes of the different chemicals with different names that breakdown many different drugs. Subjecting more than one drug to that named isozyme chemical causes stress and unpredictable outcomes when co-administered together. Therefore any of the drugs listed below act on the same chemical and may cause very unpredictable outcomes and side effects.

CYP 1A2 inhibitors:

antiarrythmics

amiodarone

atazanavir

cimetidine

ciprofloxacin

citalopram

clarithromycin

diltiazem

echinacea

enoxacin

erythromycin

ethinyl estradiol

famotidine

fluvoxamine

fluroquinolones isoniazid

ketoconazole

methoxsalen

mexiletine

nalidixic acid

norethindrone

omeprazole

oral contraceptives

paroxetine

tacrine

ticlopidine

tipranavir

troleandomycin

zileuton
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April 13, 2007

FDA: Bladder Drug Needs Stronger Warning

Johnson & Johnson's Ditropan, used to calm an overactive bladder, should have stronger warnings that the drug may cause hallucinations and agitation in children, U.S. regulators said.

The frequency of these side effects is "disproportionately higher" among children taking Ditropan than adults, said a review posted Monday on the Food and Drug Administration's Web site. The medicine's labeling already lists general precautions about central- nervous system side effects.

The agency staff said it will suggest the new age-specific warnings at an advisory panel meeting scheduled Wednesday to discuss the drug, which is approved for use by children over age 5. Since 2002, about 1.3 million Americans under age 17 have filled prescriptions for oxybutynin, the active ingredient in Ditropan, according to data compiled by Verispan LLC.

Regulators reviewed 1,667 reports of side effects in Ditropan users, including 116 reports from children, at the request of the FDA's Pediatric Advisory Committee. At least 31 percent of reports from children involved hallucination, agitation or another problem with the central nervous system, while only 11 percent of adult cases included these events.
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April 3, 2007

Oral Alzheimer's vaccine shows promise

Humans will test a new oral vaccine for Alzheimer's as early as next year, according to the director of a Japanese research institute that is testing the vaccine.

The vaccine has proven effective and safe in mice, said Takeshi Tabira, director of the National Institute for Longevity Sciences in Aichi, central Japan. It reduced the amount of amyloid plaques - which characterize Alzheimer's disease - in the brain and improved mental function. The treatment did not cause inflammation or bleeding in the brains of the mice, Tabira noted.

Research on this project is expected to be published by the Federation of American Societies for Experimental Biology in July. Another Alzheimer's vaccine ACC-001, by U.S. drugmaker Wyeth and its Irish partner Elan Corp, is in early stage human trials
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March 30, 2007

Pergolide Withdrawn From US Market

March 29, 2007 — The manufacturers of pergolide in its brand-name (Permax; Valeant Pharmaceuticals) and generic forms have agreed to take it off the market after a pair of studies implicated the dopamine agonist in causing serious heart valve damage, the US Food and Drug Administration (FDA) has announced [1].

Two case control studies published in the January 4, 2007 issue of the New England Journal of Medicine (NEJM) found significantly increased rates of valvular dysfunction in patients with Parkinson's disease taking pergolide and another dopamine agonist, cabergoline [2,3]. As reported at the time by heartwire, the findings were consistent with abundant clinical and mechanistic evidence that activators of the serotonin receptor 5-hydroxytryptamine 2B (5-HT_2B), such as pergolide and cabergoline, cause a histologically distinct form of fibrotic valvulopathy. Cabergoline is approved in the US for the treatment of hyperprolactinemic disorders at doses much lower and safer than those used in Parkinson's disease, according to the FDA statement, which was published online today.

Those NEJM studies, along with the availability of other dopamine agonists for Parkinson's disease, have led pergolide manufacturers to withdraw the drug voluntarily, which will have a delayed effect on pharmacy inventories, according to the FDA: "This delay will allow time for healthcare professionals and patients to discuss appropriate treatment options and to change treatments." Manufacturers of the generic products, the agency notes, include Par Pharmaceutical Companies and Teva Pharmaceutical Industries.

The FDA recommends that patients currently taking pergolide contact their healthcare providers to discuss alternative treatments but not go off the drug on their own. Clinicians are urged to assess alternatives and, if necessary, substitute another dopamine agonist; others remaining on the market have not been linked to valve disease. Current pergolide therapy should not be stopped abruptly but should be gradually tapered, the agency cautions.

http://www.fda.gov/cder/drug/advisory/pergolide.htm

Schade R, Andersohn F, Suissa S, et al. Dopamine agonists and the risk of cardiac-valve regurgitation. N Engl J Med 2007; 356:29-38.
Zanettini R, Antonini A, Gatto G, et al. Valvular heart disease and the use of dopamine agonists for Parkinson's disease. N Engl J Med 2007; 356:39-46.
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March 30, 2007

Novartis suspends US sales of Zelnorm over safety concerns

In a public health advisory, the FDA stated that Novartis agreed to stop selling irritable bowel syndrome drug, Zelnorm (tegaserod), after a new safety analysis revealed an increased risk of heart attack, stroke and worsening chest pain in patients receiving the drug. Novartis indicated that it is complying with the agency's request. The company's shares fell as much as 4 percent on the news.

The FDA asked the drugmaker to halt marketing and sales of the compound after a retrospective analysis of data from 29 clinical trials of Zelnorm showed a statistically significant imbalance in the incidence of cardiovascular ischemic events such as heart attack, stroke and unstable angina in patients who received the drug, compared to patients who took placebo. Cardiovascular ischemic events occurred in 13 of 11 614 patients treated with Zelnorm, compared to one case in 7031 patients administered placebo.

James Shannon, global head of development at Novartis Pharma, stated that "although we have complied with the FDA's request and are collaborating with the agency, we continue to believe that Zelnorm provides important benefits for appropriate patients." In its advisory, the FDA specified that it is willing to consider a limited re-introduction of Zelnorm sometime in the future if a patient population for whom the benefits of the drug outweigh the risks can be identified. -------------------------------------------------------------------------

March 29, 2007

Angioplasty No Better Than Drugs, Study Says

A large and long-awaited study finds that angioplasty works no better than medication at preventing heart attacks or death, a finding that could slow the growth of one of medicine's most common cardiac interventions.

The research comes on the heels of a growing debate over whether some patients are getting unnecessary angioplasty, a procedure that involves using a tiny balloon and metal scaffolds called stents to prop open clogged arteries.

Angioplasty is recommended for those with fully blocked arteries or who have had a heart attack. But the new study, presented at the American College of Cardiology's annual meeting in New Orleans yesterday, should give doctors and their patients with partially obstructed arteries the confidence to put off angioplasty or to skip surgery altogether, according to the researchers.

"The results are very striking," said Dr. Steven Nissen , president of the American College of Cardiology, who was not involved in the study. "This is important for patients because it does now mean patients have choices. If your symptoms aren't so severe and aren't interfering with your lifestyle, you can afford to wait."

Half of the 2,300 patients studied underwent angioplasty and took heart drugs, and were told to make lifestyle changes, such as exercising, losing weight, and giving up smoking. The other half received only lifestyle counseling and medication, including drugs to lower cholesterol, relax blood vessels, slow heart rate, and prevent blood clots. Both groups fared equally well after an average of 4 1/2 years, according to the study, also published online yesterday in The New England Journal of Medicine.

Stent manufacturer Boston Scientific Corp. of Natick criticized the study yesterday as not breaking any new ground, and said stents improve quality of life for patients with clogged arteries. The authors said their research suggested that improvements in quality of life were not statistically significant over the course of the study.

The use of angioplasty to open clogged arteries has taken off since the mid-1990s, increasing from about 430,000 procedures in 1995 to nearly 1.3 million in 2004, with many of the more recent surgeries being done proactively, rather than after a life-threatening event.

The popularity of angioplasty has spurred debate among cardiologists, some of whom think the procedure is overused.

Dr. William Boden of Buffalo General Hospital said he designed the new study to determine how much added benefit angioplasty provided for people with few symptoms -- and was surprised to discover that, statistically, there was none.

The good news for patients, he said in a news conference: "You are no more or less at risk of developing a heart attack or dying if you defer angioplasty until some time down the road."

Angioplasty did provide a better quality of life than drugs alone for patients experiencing angina, the discomfort or chest pain that occurs when the heart muscle is deprived of oxygen.

Nissen said that angioplasty remains the treatment of choice for patients with a fully blocked artery, and that campaigns are underway to make sure patients having heart attacks are taken to hospitals that can swiftly perform an angioplasty.

Nissen and others said they think the procedure is probably done more often than needed, though the study's authors said they did not want to speculate about the amount of overuse.

Dr. William Maisel, a cardiologist at Beth Israel Deaconess Medical Center, said the bottom line is that patients and doctors need to make sure they're using angioplasty for the right reasons.

"To place a stent to reduce the chances of a heart attack or to prevent someone from dying, those are not reasons to put in a stent," said Maisel, chairman of a federal panel that examined stent safety.

Boston doctors tend toward the conservative, so they probably use the procedure less often than doctors elsewhere, according to Dr. Frederic S. Resnic, director of the cardiac catheterization laboratory at Brigham and Women's Hospital. Roughly 30 percent of the Brigham patients who get angioplasty have heart disease but are not in immediate danger of having a heart attack, he said.

"We have always been very careful to have detailed discussions with our patients with stable coronary artery disease, to make sure that they are comfortable and understand that we are considering the procedure to relieve the symptoms of angina, and reduce the number and amount of medications needed," he said.

The team of researchers, which included several from Hartford Hospital and the VA Connecticut Healthcare System, said their study may offer fresh evidence that heart disease is more of a systemwide than a localized problem in the body.

Using a stent addresses just one problem spot, but fails to correct other potentially more dangerous fat deposits in the diseased arteries.

The study, known as COURAGE, was paid for by the US Department of Veterans Affairs and the Canadian Institutes of Health Research, as well as 11 pharmaceutical companies, including Pfizer Inc., the maker of the world's top-selling drug, the cholesterol-lowering pill Lipitor.

The researchers acknowledge that one significant limitation of their study was that 85 percent of the patients were men and only 14 percent were non white.

Boston Scientific, which makes drug-coated stents, was sharply critical of the study.

"The results of the COURAGE trial don't really tell us much we didn't already know about the relative benefits of stents over drug therapy in the treatment of cardiovascular disease," the company said in a statement. "Stents have improved the lives of millions of patients, as amply demonstrated by a broad range of clinical trials and real-world experiences, but their benefits are found in safe, durable, and minimally-invasive relief of angina, rather than in further improving the already good survival of stable angina patients on medical therapy."

The company also criticized the study for failing to include drug-coated stents, which were not on the market when the study began.

Boden said that because drug-coated stents have not been shown to improve lifespan, using them instead of bare-metal stents would not have changed the study's results.
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March 27, 2007

Antidepressants might improve brain function in stroke victims

The use of antidepressants appears to boost brain function affecting overall reasoning and functioning in stroke victims, whether or not they had symptoms of depression, according to new research.

Researchers randomly assigned 47 stroke patients admitted to a rehabilitation center to one of two antidepressants, nortriptyline and Prozac, or an inactive placebo. While researchers observed no differences among the treatment groups at 12 weeks, 21 months later they found that those given an antidepressant experienced noticeable improvement in executive function. The condition of the majority of patients given the placebo had deteriorated significantly, researchers at the University of Iowa Carver College of Medicine found.

The study was published in the March issue of the British Journal of Psychiatry.
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March 18, 2007

Heart disease, diabetes, depression could be deadly combo

Heart disease, diabetes, depression. It's the recipe for a lethal cocktail, according to new research findings.

The presence of all three diseases can boost a patient's death by 20% to 30%, says researcher Anastasia Georgiades, of Duke University in Durham, N.C. The Duke team followed 933 heart patients for more than four years. During that time, there were 135 deaths among patients with type 2 diabetes and/or depression, the researchers found. There was a higher risk of dying among patients with moderate-to-severe symptoms of depression who were also diabetics, compared with patients with either depression alone or diabetes alone.

The reason for the increased risk is unclear, "but it could either be that depression influences crucial aspects of self-care behaviors needed to manage diabetes or that a more severe disease process is reflected in more depressive symptoms," Georgiades said.
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March 16, 2007

FDA Says Pills Can Cause 'Sleep-Driving'

WASHINGTON - All prescription sleeping pills may sometimes cause sleep-driving, federal health officials warned Wednesday, almost a year after the bizarre side effect first made headlines when Rep. Patrick Kennedy crashed his car after taking Ambien.

It's a more complicated version of sleepwalking, but behind the wheel: getting up in the middle of the night and going for a drive - with no memory of doing so.

The Food and Drug Administration wouldn't say exactly how many cases of sleep-driving it had linked to insomnia drugs, but neurology chief Dr. Russell Katz said the agency uncovered more than a dozen reports - and is worried that more are going uncounted.

Given the millions of prescriptions for insomnia drugs, Katz called the problem rare, and said he was unaware of any deaths. But because sleep-driving is so dangerous - and there are precautions that patients can take - the FDA ordered a series of strict new steps Wednesday.

First, the makers of 13 sleep drugs must put warnings on their labels about two rare but serious side effects:

-sleep-driving, along with other less dangerous "complex sleep-related behaviors" - like making phone calls, fixing and eating food, and having sex while still asleep.

-and life-threatening allergic reactions, as well as severe facial swelling, both of which can occur either the first time the pills are taken or anytime thereafter.

Next, doctors this week will begin getting letters notifying them of the new warnings.

Later this year, all prescription sleeping pills will begin coming with special brochures called "Medication Guides" that spell out the risks for patients in easy-to-understand language.

Sleep-driving made headlines last May when Kennedy, D-R.I., crashed his car into a security barrier outside the U.S. Capitol after taking Ambien and a second drug, Phenergan, an anti-nausea pill that also acts as a sedative. Kennedy has said he had no memory of the event. He pleaded guilty to driving under the influence of prescription drugs, and was sentenced to court-ordered drug treatment and a year's probation.

Ambien isn't the only insomnia drug that can cause sleep-driving - any of the class known as "sedative-hypnotics" can, FDA's Katz stressed Wednesday.

To lower the risk of a sleep-driving episode, he advised patients to never take any prescription insomnia drug along with alcohol or any other sedating drug. Also, don't take higher-than-recommended doses of the pills.

"We really want people to know these things can occur, and these sleep behaviors can be perhaps to a large extent mitigated by behaviors the patients can control," he said.

Some of the insomnia drugs may be riskier than others, so FDA also recommended that manufacturers conduct clinical trials to figure that out.

The drugs are: Ambien; Butisol sodium; Carbrital; Dalmane; Doral; Halcion; Lunesta; Placidyl; Prosom; Restoril; Rozerem; Seconal; Sonata.

Fewer than one in 1,000 patients in studies of Ambien reported somnambulism - a scientific term that includes the sleep behaviors flagged by the FDA - said Lisa Kennedy, a spokeswoman for manufacturer Sanofi-Aventis SA, who is not related to the congressman. The side effect has remained similarly rare since widespread sales began, she said.
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March 5, 2007

FDA Warns Migraine Medicine Makers

WASHINGTON - The government said Thursday it had warned the world's largest maker of generic drugs and 19 other companies that they are illegally selling migraine medicines without federal approval.

The Food and Drug Administration said the 20 warning letters were part of an effort to halt the marketing of unapproved and potentially dangerous drugs. The goal is to get the unapproved drugs off the market, agency officials said. The manufacturers could seek agency approval for the products.

The prescription migraine treatments contain a drug called ergotamine tartrate. Ergotamine is derived from a rye fungus called ergot, from which a separate drug, the illegal hallucinogen LSD, also can be synthesized. Ergotamine is a vasoconstricting drug, meaning it narrows the blood vessels when taken.

The letters - dated Monday but not publicly disclosed until Thursday - went to companies that include a U.S. subsidiary of Israel's Teva Pharmaceutical Industries Ltd., the world's largest generics manufacturer. Other recipients included Iceland's Actavis and Sandoz Inc., a pioneer in the marketing of ergotamine tartrate that is now part of Switzerland's Novartis AG.

Messages left with all three companies were not immediately returned Thursday.

The FDA said the companies have 60 days to stop making the drugs and 180 days to stop distributing them. Otherwise, the companies are subject to seizure or injunction, the FDA said.

"Because these drugs don't have approval, we don't know how they were formulated or manufactured. We don't know if they are safe or effective," Deborah Autor, director of the office of compliance within the FDA's Center for Drug Evaluation and Research, told reporters.

The FDA said the labels of the drugs failed to warn consumers of dangerous interactions if taken with other medications, including some HIV drugs, antibiotics and anti-fungal agents.

There are five ergotamine tartrate drugs on the market that have FDA approval, including one made by Sandoz. The labels of those approved medications carry "black-box" warnings, the most severe the government can require, about the risk of drug interactions.

The FDA stepped up last year its efforts to get drugs without agency approval off the market. Under guidelines issued in June, the FDA said those unapproved drugs most likely to pose a risk to public health would be the highest priority for enforcement action.
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March 2, 2007

Don't Let your Jewelry KILL you !

That magnetic brooch or necklace may set off more than your eyes or sweater-it could also set off, or turn off, your pacemaker or implanted cardioverter/defibrillator(ICD).

Jewelry, reading glasses, name tags, and even some clothing now sport a new breed of magnet. Called rare earth or neodymium-iron-boron magnets, they are more powerful than the traditional magnets used to stick things to a refrigerator or found inside stereo speakers

Swiss researchers tested two jewel-sized pieces as well as a necklace and a name tag-all made of neodymium-iron- boron magnets-in 70 volunteers with a pacemaker or ICD. All four pieces interfered with the heart device at a distance of an inch or so. They made the pacemakers generate “beat now” signals at a fixed rate regardless of the heart’s activity. More worrisome, they turned off the ICD’s ability to detect and stop a potentially deadly heart rhythm.

People with pacemakers and ICDs are advised to keep magnets a least a few inches from their device. That’s generally not a problem, but these new magnets are showing up in products that can potentially sit right on top of the device.
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February 16, 2007

Researchers offer hope for stroke victims with vision impairments

A new device that uses light stimulation could help enlarge the visual field of stroke victims who have been left with vision impairments, according to researchers.

The visual field of about three quarters of the patients treated using Vision Restoration Therapy improved on average by nearly 15%. These patients suffered a stroke or other brain injury causing impaired vision. The complete Vision Restoration Therapy program, a custom-designed pattern of bright and dim light stimulation, delivered to the edges of the visual field of the affected eye, consists of six four-week treatment modules.

For some, the improvement may make the difference between not reading and having the ability to read. The research results were presented during the American Stroke Association's International Stroke Conference 2007 in San Francisco. The findings are being used to seek approval for Medicare reimbursement for the device, according to researchers.
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February 11, 2007

Lucentis Linked to Stroke Risk in Elderly

January 30, 2007 — Genentech, Inc, has warned healthcare professionals regarding the potential increased risk for stroke associated with use of ranibizumab (Lucentis) in the treatment of neovascular (wet) age-related macular degeneration in elderly patients.

The warning was based on interim data from an ongoing safety study (SAILOR) showing that the risk for stroke was significantly higher in patients receiving the recommended dose of ranibizumab (0.5 mg) compared with a 0.3 mg dose (1.2% vs 0.3%; P = .02) at an average follow-up of 230 days. Patients with a history of stroke appeared to be at increased risk for subsequent stroke, the company said.

The 0.3- and 0.5-mg doses were not statistically different in terms of incidence of myocardial infarction or vascular death, and their overall safety appeared to be consistent with that observed in phase 3 studies submitted as part of the drug approval process.

Ranibizumab was approved by the US Food and Drug Administration in June 2006. The recommended dosing regimen is 0.5 mg administered by intravitreal injection once a month.

Additional information regarding use of ranibizumab injection may be obtained from the company by calling 1-800-821-8590.

Adverse events potentially related to use of ranibizumab should be reported to the company by phone at 1-888-835-2555. Alternatively, this information may be communicated to the FDA's MedWatch reporting program by phone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, MD 20852-9787.
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February 10, 2007

Lonely adults twice as likely to develop Alzheimer’s disease, researchers find:

Social and emotional isolation in elderly people increase their risk of developing dementia by about 51%, according to new research.

The risk of developing Alzheimer’s disease among 823 elderly people was about twice as great in subjects who reported a high degree of loneliness, said researchers at Rush University Medical Center in Chicago. They studied participants for four years.

Social isolation in old age includes being single, having few friends and participating in few activities with others, researchers said in their study report. They also note that it seems unlikely that dementia causes loneliness, because loneliness levels remained relatively stable even in subjects who developed dementia. The study appears in the Archives of General Psychiatry.
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February 9, 2007

Study: Older adults can handle bad news better than younger people

A new study has uncovered revealing findings about perception and age: Older people, investigators found, can take bad news better than their children or grandchildren. As a result, they can be more risky gamblers because losses don’t affect them as much.

Older adults process negative information differently from their younger counterparts, according to research funded by the National Institute on Aging. They respond less strongly to unpleasant information.

When they were shown a series of images, including dead animals and ice cream, they were less likely to be depressed and affected by negative or unpleasant information. They also were less likely to react to gambling losses. Still, their lack of responsiveness did not make them any happier, said lead researcher Dr. Stacey Wood, neuropsychologist and associate professor at California's Scripps College.
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February 8, 2007

Elderly women with kidney disease at greater risk of hip fractures

Even mild kidney dysfunction in elderly women raises their risk of hip fracture, according a new study.

Researchers at the VA Medical Center in Minneapolis found that mildly impaired kidney function increased the risk of hip fracture among older women by more than 50%. Moderately impaired kidney function increased the risk of hip fractures by more than 100%. Researchers studied nearly 700 women 65 and older, either with hip fractures, vertebral fractures or no broken bones.

Kidney function did not have an effect on vertebral fractures, according to the research. The study was published in the Archives of Internal Medicine.
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February 7, 2007

Lucentis Linked to Stroke Risk in Elderly

January 26, 2007

Lyrica (pregabalin) Problems

The FDA Medical Officer who was the primary reviewer for the applications for approval of pregabalin for diabetic neuropathy and postherpetic neuralgia concluded that the drug should not be approved for these indications. Concerning the application for postherpetic neuralgia, he stated that "overall the risk of adverse effects of treatment approach or exceed the likelihood of treatment benefit." In similarly recommending against the approval for diabetic neuropathy, he stated that "it does not appear that the benefits of the drug in patients with diabetic neuropathy outweigh the risks. I therefore do not recommend approval of this application."

His concerns about risks involved statistically significant increases in visual abnormalities in patients using pregabalin as well as increased numbers of accidental
injuries and edema. For blurred vision, there was a 4.3-fold increase in pregabalin users compared with those taking a placebo and for double vision, a 6.7 fold increase. Accidental injuries occurred nine times more frequently in pregabalin users. One possible explanation for the increased injuries is significant increases in dizziness and abnormal gait in people using pregabalin.

Despite the concerns of the FDA Medical Officer, he was overruled by his supervisors and the drug was approved for these two indications. After its approval, one review of the drug's performance rated the evidence for pregabalin for neuropathic pain as limited.

Pregabalin may control, but does not cure, these conditions, nor any off-label conditions for which it may be prescribed. It belongs to the same family as gabapentin (NEURONTIN), a drug that was illegally promoted for many off-label uses despite a lack of evidence of its effectiveness.

DO NOT USE Until 2012: Pregabalin for Partial-Onset Seizures

Pregabalin was approved as an adjuvant treatment for partial-onset seizures, meaning it can be used along with other anti-seizure medications such as carbamazepine, lamotrigine, phenytoin, or valproate in order to increase their overall effectiveness.

Many patients who experience partial-onset seizures have inadequate response to available drugs. Up to 12 percent of adults facing this condition may become seizure free with pregabalin.

Concerns When Taking Pregabalin

Adverse effects, including muscle twitches, happen more with higher doses. Pregabalin may decrease platelets or cause you to retain fluid. Common adverse effects include dizziness, vision changes, and weight gain. This drug is a controlled substance with a potential for abuse.

In March 2006, evidence of erectile dysfunction in five men using pregabalin was published in a journal article co-authored by a researcher from Pfizer, manufacturer of both pregabalin and VIAGRA. In the report are previously unpublished Pfizer data showing significant increases, compared to a placebo, in sexual dysfunction in both men and women using pregabalin. For men, there were significant increases in impotence and decreased libido. For women, there were significant increases in anorgasmia (failure to have an orgasm) and decreased libido.

Patients taking pregabalin should start with the lowest recommended dose. If necessary, the prescribing physician should increase the dose gradually. Be advised that it takes at least one week to experience a decrease in pain. For neuropathic pain, doses of 600 mg have more adverse effects and no additional benefit occurs compared to doses of 300 mg. People with kidney problems or on dialysis may need dose adjustments. If stopping, follow your doctor's instructions to lower the dose of pregabalin gradually over a week. Otherwise, seizures may occur. There have been reports of brain swelling due to abrupt stopping of pregabalin.

See the complete review of LYRICA here: http://www.worstpills.org/member/drugprofile.cfm?m_id=312
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January 19,2007

Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trialSummary

Background

Low folate and raised homocysteine concentrations in blood are associated with poor cognitive performance in the general population. As part of the FACIT trial to assess the effect of folic acid on markers of atherosclerosis in men and women aged 50–70 years with raised plasma total homocysteine and normal serum vitamin B12 at screening, we report here the findings for the secondary endpoint: the effect of folic acid supplementation on cognitive performance.

Methods

Our randomised, double blind, placebo controlled study took place between November, 1999, and December, 2004, in the Netherlands. We randomly assigned 818 participants 800 μg daily oral folic acid or placebo for 3 years. The effect on cognitive performance was measured as the difference between the two groups in the 3-year change in performance for memory, sensorimotor speed, complex speed, information processing speed, and word fluency. Analysis was by intention-to-treat. This trial is registered with clinicaltrials.gov with trial number NCT00110604.

Findings

Serum folate concentrations increased by 576% (95% CI 539 to 614) and plasma total homocysteine concentrations decreased by 26% (24 to 28) in participants taking folic acid compared with those taking placebo. The 3-year change in memory (difference in Z scores 0·132, 95% CI 0·032 to 0·233), information processing speed (0·087, 0·016 to 0·158) and sensorimotor speed (0·064, −0·001 to 0·129) were significantly better in the folic acid group than in the placebo group.

Interpretation

Folic acid supplementation for 3 years significantly improved domains of cognitive function that tend to decline with age.

Affiliations

a. Division of Human Nutrition, Wageningen University, 6700 EV Wageningen, Netherlands
b. Wageningen Centre for Food Sciences, Wageningen, Netherlands
c. Department of Psychiatry and Neuropsychology, Brain and Behaviour Institute, Maastricht University, Maastricht, Netherlands

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January 15, 2007

New gene linked to Alzheimer's, data

Researchers identified a new gene that may be linked to late-onset Alzheimer's disease. The findings are published in the current issue of Nature Genetics.

In the study, researchers examined DNA samples from 6000 people with different ethnic backgrounds. The results showed that certain variations of the SORL1 gene occurred more often in people with late-onset Alzheimer's disease than in healthy people. The researchers also remarked that SORL1 appears to affect how amyloid beta protein builds up in brain cells, which many scientists believe plays a key role in causing Alzheimer's.

Study co-author and University of Toronto researcher Dr. Peter St. George-Hyslop indicated that "what we found is this gene is robustly associated with increased risk for common forms of late-onset Alzheimer's disease in several different ethnic groups. [The gene] is likely to be a significant contributor to the causes of Alzheimer's," he said, The Toronto Star reports.

Meanwhile, Dr. Sam Gandy, chairman of the American Alzheimer's Association medical and scientific advisory council, noted that although SORL1 probably does not play as much of a role in the onset of Alzheimer's as previous genetic discoveries, "it does dovetail with the main hypothesis for how Alzheimer's starts. It tells us we are on the right track with drug discovery efforts."
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January 3, 2007

Parkinson's Drugs Linked to Heart Problem
Publication date: 2007-01-03

The use of common agents used in treating Parkinson's disease may be associated with a heart-valve abnormality, European researchers say.

Researchers said Wednesday they found that 12 of 31 patients newly diagnosed with a heart-valve regurgitation -- a failure of the valve to operate correctly -- were taking either pergolide (Permax) or cabergoline (Dostilex), medicine used in treating patients with Parkinson's symptoms or other conditions such as restless leg syndrome.

In a companion study that will also be published in Thursday's editions of the New England Journal of Medicine, researchers in Milan, Italy, also discovered that patients taking either of the drugs had elevated rates of heart-valve regurgitation.

About 23 percent of those on pergolide and 28 percent of those on cabergoline showed evidence of serious heart-valve regurgitation compared with 5.6 percent of other patients who were on a different class of Parkinson's drug or who were not taking any anti-Parkinson's medication.

There was no evidence of such an increase in risk with the use of other dopamine agonists (used in treating Parkinson's disease), said Rene Schade, a clinical pharmacologist at Charite-University Hospital in Berlin, Germany.

The Italian researchers suggested that follow-up echocardiograms be performed on patients being treated with the drugs.
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December 2006

Merry Christmas and Happy New Year!

November 29, 2006

METHADONE -- Death, Narcotic Overdose, and Serious Cardiac Arrhythmias

FDA has reviewed reports of death and life-threatening adverse events such as respiratory depression and cardiac arrhythmias in patients receiving methadone. These adverse events are the possible result of unintentional methadone overdoses, drug interactions, and methadone’s cardiac toxicities (QT prolongation and Torsades de Pointes). Physicians prescribing methadone should be familiar with methadone’s toxicities and unique pharmacologic properties. Methadone’s elimination half-life (8-59 hours) is longer than its duration of analgesic action (4-8 hours). Methadone doses for pain should be carefully selected and slowly titrated to analgesic effect even in patients who are opioid-tolerant. Physicians should closely monitor patients when converting them from other opioids and changing the methadone dose, and thoroughly instruct patients how to take methadone. Healthcare professionals should tell patients to take no more methadone than has been prescribed without first talking to their physician.

Considerations

Methadone is an effective analgesic and may provide pain relief when other analgesics are ineffective. However, methadone can cause significant toxicities. We are highlighting important safety information from the new label about using methadone for pain. See the methadone label (Dolophine) for more details.

Methadone’s elimination half-life (8-59 hours) is longer than its duration of analgesic action (4-8 hours). Methadone’s peak respiratory depressant effects typically occur later, and persist longer than its peak analgesic effects. During treatment initiation, methadone’s full analgesic effect is usually not attained until 3-5 days of dosing. Initiation and titration to analgesic effect and dose adjustments should be done cautiously and in consideration of these properties. In chronic use, methadone may be retained in the liver and then slowly released, prolonging the duration of action despite low plasma concentrations.

Cross-tolerance between methadone and other opioids is incomplete. This incomplete cross-tolerance makes the conversion of patients on other opioids to methadone complex and does not eliminate the possibility of methadone overdose, even in patients tolerant to other opioids. Deaths have been reported during conversion from chronic, high-dose treatment with other opioid agonists to methadone. It is critical to understand the pharmacokinetics of methadone when converting patients from other opioids to methadone. Particular vigilance is necessary during treatment initiation, during conversion from one opioid to another, and during dose adjustments.

Methadone can cause serious cardiac conduction effects, including QT interval prolongation and Torsades de Pointes.

There are pharmacokinetic and pharmacodynamic drug interactions between methadone and many other drugs. Drugs administered concomitantly with methadone should be evaluated for interaction potential.

Methadone is secreted into human milk.

What should physicians do?

Read and follow the prescribing information for methadone.
Carefully weigh methadone’s risks with its potential benefits before prescribing methadone.
Avoid prescribing methadone 40 mg dispersible tablets for pain. This product is only FDA-approved for detoxification and maintenance treatment of narcotic addition.
Closely monitor patients who receive methadone, especially during treatment initiation and dose adjustments.

What should healthcare professionals tell patients when prescribing methadone for pain?

Pain relief from methadone does not last as long as methadone stays in your body. Therefore, do not to take more methadone than prescribed because methadone could build up in your body and cause death.
Methadone can cause life-threatening changes in breathing (it may slow or stop).
Methadone can cause life-threatening changes to the heart beat that may not be felt.
Seek medical attention right away if you experience symptoms suggestive of an arrhythmia such as palpitations, dizziness, lightheadedness, or fainting or if you experience symptoms suggestive of a methadone overdose such as slow or shallow breathing; extreme tiredness or sleepiness; blurred vision; inability to think, talk or walk normally; and feeling faint, dizzy or confused.
Directions you should follow if your pain is not controlled after taking the prescribed amount of methadone.
Pain relief from methadone should last longer after you have taken it for awhile.
Tell your doctor if you start or stop other medicines because other medicines can interact with methadone and possibly cause death or life threatening side effects, or result in less pain relief from methadone.
Tell your doctor if you are breastfeeding because methadone is secreted into human milk. Babies can experience the same serious side effects from methadone as the mother.

Data and Background Information

There have been reports of serious adverse events such as death, respiratory depression, and serious cardiac arrhythmias in patients receiving methadone. Fatalities have been reported in patients who were switched from chronic, high-dose treatment with other opioids to methadone and in patients initiating treatment with methadone. These adverse events may have resulted from unintentional methadone overdoses, drug interactions, and/or methadone’s cardiac toxicities (QT prolongation and Torsades de Pointes). Some of the unintentional overdoses were due to prescribers not being aware of methadone’s pharmacokinetics and potential adverse effects.

FDA recently updated the methadone label following an extensive review of the medical literature and other available information. The new label provides new information on methadone’s pharmacology, drug interactions, and instructions on converting patients from other opioids to methadone and dosing methadone based on a synthesis of recommendations from several palliative care organizations and treatment centers.
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November 13, 2006

FDA staff recommends updating Tamiflu label over neuropsychiatric events

FDA staff recommended that a advisory committee consider updating the label for Roche's Tamiflu, to caution that there have been postmarketing reports of neuropsychiatric events in patients who have taken the antiviral drug. The recommendations were posted to the US agency's Web site ahead of a paediatric advisory committee meeting scheduled for November 16.

In a briefing document dated September 20, the US regulatory staff noted that between August 29, 2005 and July 6, 2006, 103 cases of neuropsychiatric events have been reported in people who received Tamiflu. The agency staff said that about 67 percent of cases occurred in U.S. patients, and 95 out of the 103 cases came from Japan.

As a result, the agency staff suggested that the drug's precautions section be updated to state that people receiving treatment with Tamiflu, particularly children, geriatric and adolescent patients, should be "monitored closely" for abnormal behaviour such as hallucinations, delusions, aggression and suicidal ideation.
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November 12, 2006

Polypharmacy and Prescribing Quality in Older People

In a recent study published in the Journal of the American Geriatrics Society, researchers found that both inappropriate use and underuse of medications are evident among 40% of older patients taking five or more medications. Vitamins and minerals, topical and herbal products, and as-needed medications were all excluded from the study. To determine appropriateness, researchers used the 2003 update of the Beers’ criteria and subscales of the Medication Appropriateness Index. The mean age of study participants was 74.6, and patients used a mean of 8.1 ± 2.5 medications (range 5-17). Use of one or more inappropriate medications was documented in 128 patients (65%), including 73 (37%) taking a medication in violation of the Beers drugs-to-avoid criteria and 112 (57%) taking a medication that was ineffective, not indicated, or duplicative. Medication underuse was observed in 125 patients (64%). Together, inappropriate use and underuse were simultaneously present in 82 patients (42%), whereas 25 (13%) had neither inappropriate use nor underuse. When assessed by the total number of medications taken, the frequency of inappropriate medication use rose sharply from a mean of 0.4 inappropriate medications in patients taking five to six drugs, to 1.1 inappropriate medications in patients taking seven to nine drugs, to 1.9 inappropriate medications in patients taking 10 or more drugs. In contrast, the frequency of underuse averaged 1.0 underused medications per patient and did not vary with the total number of medications taken. Overall, patients using fewer than eight medications were more likely to be missing a potentially beneficial drug than to be taking a medication considered inappropriate.
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November 12, 2006

CDC Advisory Panel Votes to Recommend New Shingles Vaccine for Vaccination of Adults Age 60 and Older
The Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) recently voted unanimously to recommend that adults 60 years of age and older be vaccinated with Zostavax® to help prevent shingles (herpes zoster). Zostavaxâ was approved by the U.S. Food and Drug Administration (FDA) on May 25 for the prevention of shingles in individuals 60 years of age and older. Zostavaxâ is given by a single dose by injection. The ACIP recommendations do not result in requirements for vaccine coverage by insurers; however, private insurers typically follow the Committee’s guidance. Details of the ACIP recommendations for Zostavaxâ soon will be available from the CDC. The recommendations are under review by the director of the CDC and the Department of Health and Human Services and will become official when published in the CDC's Morbidity and Mortality Weekly Report.
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November 11, 2006

Evaluating Risks of Surgery for Sleep Apnea

Individuals with obstructive sleep apnea repeatedly stop breathing during the night due to upper airway obstruction. This condition is very common, as common as adult diabetes, and affects more than 12 million Americans, according to the National Institutes of Health. Risk factors include being male, overweight and over the age of 40, but sleep apnea can strike anyone at any age, even children.

Untreated, sleep apnea can cause high blood pressure and other cardiovascular disease, memory problems, weight gain, impotence, headaches and even death. Moreover, untreated sleep apnea may be responsible for job impairment and motor vehicle accidents.

Although the risk of serious complication following corrective surgery for sleep apnea is relatively low, the surgery is more risky in certain groups of patients with other medical problems, high body mass index (a measure of obesity) and more severe obstructive sleep apnea, according to a study led by UCSF Assistant Professor in Residence Eric J. Kezirian, MD, MPH, in the October issue of Archives of Otolaryngology – Head and Neck Surgery, published by the Journal of the American Medical Association.

A procedure known as uvulopalatopharyngoplasty (UPPP), during which surgeons remove the uvula and other soft tissues at the back of the throat to help clear the airway, is the most common operation performed to alleviate sleep apnea. Earlier work from Kezirian and his colleagues had shown that about 1.6 percent of all patients undergoing such procedures have serious complications, including 0.2 percent who die within 30 days. Previous reports about the risk factors for complications had been conflicting.

In Kezirian and his colleagues’ latest research, they studied 3,130 patients who underwent UPPP between 1991 and 2001 at United States Veterans Affairs medical centers. The researchers utilized data about participants’ surgeries and characteristics from medical records.

Data on body mass index, other illnesses and the severity of sleep apnea were collected from the medical charts of a smaller group of patients, including 51 (1.6 percent) who had serious complications and 212 others who did not have serious complications, but were the same sex and age, had the same number of procedures performed at the same time and had surgery the same year as those who did have serious complications.

In the larger group of 3,130 patients, the most important risk factor for serious complication was the presence of other serious medical conditions at the time of surgery. For each additional serious illness – besides sleep apnea – that a patient had, his or her risk for complications almost doubled. In the smaller group of patients, more severe sleep apnea, higher body mass index and the presence of other illnesses were associated with a higher risk for complication.

“While most patients do not have complications following sleep apnea surgery, it is important to know which patients may be at greatest risk,” Kezirian said. “I hope this research will improve the ability of surgeons to discuss the potential risks with patients and, in many cases, take additional steps or precautions to make the surgery even safer.”

" Risk Factors for Serious Complications After Uvulopalatopharyngoplasty "
Eric J. Kezirian, MD, MPH; Edward M. Weaver, MD, MPH; Bevan Yueh, MD, MPH; Shukri F. Khuri, MD; Jennifer Daley, MD; William G. Henderson, PhD
Archives of Otolaryngology – Head and Neck Surgery October 2006;132:1091-1098
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November 10, 2006

Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study

Summary
Background

Lifestyle interventions can prevent the deterioration of impaired glucose tolerance to manifest type 2 diabetes, at least as long as the intervention continues. In the extended follow-up of the Finnish Diabetes Prevention Study, we assessed the extent to which the originally-achieved lifestyle changes and risk reduction remain after discontinuation of active counselling.

Methods

Overweight, middle-aged men (n=172) and women (n=350) with impaired glucose tolerance were randomly assigned to intensive lifestyle intervention or control group. After a median of 4 years of active intervention period, participants who were still free of diabetes were further followed up for a median of 3 years, with median total follow-up of 7 years. Diabetes incidence, bodyweight, physical activity, and dietary intakes of fat, saturated fat, and fibre were measured.

Findings

During the total follow-up, the incidence of type 2 diabetes was 4·3 and 7·4 per 100 person-years in the intervention and control group, respectively (log-rank test p=0·0001), indicating 43% reduction in relative risk. The risk reduction was related to the success in achieving the intervention goals of weight loss, reduced intake of total and saturated fat and increased intake of dietary fibre, and increased physical activity. Beneficial lifestyle changes achieved by participants in the intervention group were maintained after the discontinuation of the intervention, and the corresponding incidence rates during the post-intervention follow-up were 4·6 and 7·2 (p=0·0401), indicating 36% reduction in relative risk.

Interpretation

Lifestyle intervention in people at high risk for type 2 diabetes resulted in sustained lifestyle changes and a reduction in diabetes incidence, which remained after the individual lifestyle counselling was stopped.

October 29, 2006

Doctors Prescribing Medications without explaining effects to patient

Many doctors, a new study reports, prescribe medicine without explaining its purpose, discussing its side effects, offering instructions about its use or even mentioning its name.

Researchers audiotaped 45 doctors during their encounters with 909 patients, identifying 185 visits in which 243 medications that had not been used before by the patient were prescribed. The average age of the patients was 55, half of them were men, and most had some college education. Almost all had health insurance. About three-quarters of the doctors were men, and 89 percent were white.

Although there were variations, depending on the type of medicine prescribed, 74 percent of the doctors mentioned the trade or generic name of the medicine, and 87 percent stated its purpose. Sixty-six percent said nothing about how long to take the medicine, 45 percent did not say what dosage to take and 42 percent failed to mention the timing or frequency of doses. Physicians mentioned adverse side effects only 35 percent of the time.

The authors noted that the results may not be applicable to other groups of patients, and that the presence of recording equipment may have influenced what doctors said during the patient visits.

Still, Dr. Neil S. Wenger, the senior author on the study, said, “The problems we’re seeing are exactly the things we see going wrong in clinical practice.

“You prescribe a cholesterol-lowering medicine, a medicine that has to be taken for a lifetime, and the person never refills the first prescription. And we wonder why. Now it’s clear why: we never told them that they were supposed to keep taking it.”

Dr. Wenger is a professor of medicine at the University of California, Los Angeles.

The study was published Sept. 25 in Archives of Internal Medicine.

Correction: Oct. 4, 2006

A report in the Vital Signs column in Science Times yesterday, about a study that says many doctors prescribe medicine without giving patients basic information, omitted the journal that published the study. It was The Archives of Internal Medicine.
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October 25, 2006

Adverse Drug Events an Important Cause of Illness: Report

NEW YORK (Reuters Health) Oct 18 - Each year, an estimated 700,000 Americans experience adverse reactions to prescribed drugs that necessitate a trip to the emergency department (ED), according to a report in the October 18th issue of the Journal of the American Medical Association.

"Adverse drug events among outpatients that lead to emergency department visits are an important cause of morbidity in the United States, particularly among individuals aged 65 years or older," write Dr. Daniel S. Budnitz, of the Centers for Disease Control and Prevention, Atlanta, and colleagues.

During the two-year period from January 1, 2004 to December 31, 2005, a total of 21,298 adverse drug event (ADEs) cases were reported to a national surveillance system, yielding weighted annual estimates of 701,547 persons, or 2.4 persons per 1000 population, treated in EDs for adverse drug reactions.

Adverse drug events included allergic reactions, unintended overdoses, adverse effects, secondary effects, and vaccine reactions. Such events accounted for 2.5% of estimated ED visits for all unintentional injuries and 6.7% of estimated ED visits leading to hospitalization. Adverse drug events were also responsible for 0.6% of estimated ED visits for all causes.

Individuals aged 65 and older, who make up 12% of the US population, accounted for 25% of adverse drug events overall, and half of these events required hospitalization. This "highlights the importance of directing ADE prevention efforts to this vulnerable population," the authors write.

Emergency department visits for ADEs in individuals 65 and older were nearly as common as those for motor vehicle occupant injuries, Dr. Budnitz and colleagues point out.

Most ADEs were the result of unintentional overdoses and involved acute toxicity from drugs requiring regular outpatient monitoring such as antidiabetic agents, warfarin, several anticonvulsants, digitalis, glycosides, theophylline, and lithium.

"Ongoing, population-based surveillance can help monitor these events and target prevention strategies," Dr. Budnitz and colleagues conclude.

JAMA 2006;296:1858-1866.
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October 22, 2006

Tamoxifen Should I or Shouldn't I Use???

Post-menopausal women who take tamoxifen to treat breast cancer face a greater risk of recurrence if they have a specific genetic variation, federal health advisers said Wednesday in recommending that a warning be added to the drug's label.

Recent studies have found tamoxifen does not work as well in women with breast cancer who carry a variant of a gene called CYP2D6. An estimated 7 percent to 10 percent of women with breast cancer may have that special form of the gene, which affects how their bodies process the drug.

A panel of Food and Drug Administration advisers recommended the agency change tamoxifen's label to warn post-menopausal women of that potential risk.

"The bottom line is, the consensus was that the information is important enough to be included in the label," said FDA pharmacology chief Dr. Lawrence Lesko.

However, the clinical pharmacology panel left it to the FDA to decide whether the drug's label should recommend genetic testing of post-menopausal breast cancer patients before they are prescribed tamoxifen. Still, the FDA will consider adding such language - perhaps in the form of a suggestion - to the label, Lesko said.

The FDA first approved tamoxifen in 1977. It is made in generic form by multiple drug companies.

The drug is now use to both treat breast cancer and to prevent the disease in women who may be predisposed to it. The drug blocks estrogen, a hormone that stimulates the growth of most tumors after menopause.

Lesko said the label changes could take six months to put in place. Since 2003, the FDA has taken three other drugs before the panel to discuss adding genetic-specific information to their labels. They include the blood-thinner warfarin; updates to its label are forthcoming, Lesko said.
So to be on the safe side if Tamoxifen (Nolvadex) is prescribed for you, as a cancer prophylaxis treatment, I would definitely ask the physician to run the genetic test necessary to determine the safety of the use of this drug.
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October 20, 2006

Few Older Patients Get Appropriate Drugs

Doctors are as likely to under-prescribe medications for elders as they are to over-prescribe, say researchers at the San Francisco VA Medical Center.

Forty-two percent of patients studied were taking at least one inappropriate medication and simultaneously not taking one or more other medications that could have helped them, according to lead author Dr. Michael Steinman.

It's not just a question of, 'are you taking too much or too little,' physicians need to look at both sides of the equation, and be attentive to different kinds of prescribing problems.

The researchers observed 196 outpatients -- 194 of them male -- ages 65 or older who were taking five or more prescribed medications and receiving care at a Veterans Affairs Medical Center.

Sixty-five percent of patients were taking a drug that was ineffective, not indicated, duplicative of another medication, or considered generally inappropriate for older persons. Sixty-four percent were not taking a drug that would have been appropriate for a medical condition they had.

Together, 42 percent were simultaneously taking an inappropriate drug and not taking an appropriate drug. Only 13 percent were taking all drugs appropriate for their conditions and not taking inappropriate drugs, according to the study published in the Journal of the American Geriatrics Society.
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October 14, 2006