Counterfeit polypropylene mesh products marketed as C. R. Bard/Davol

The U.S. Food and Drug Administration today warned health care providers and consumers about counterfeit surgical mesh being distributed in the United States under the C. R. Bard/Davol brand name. Surgical mesh products are used to reinforce soft tissue where weakness exists.

The warning is of particular significance to health care professionals and their patients with surgical mesh implants as well as hospitals and surgical centers, operating room medical professionals and staff, and purchasing and risk managers.

Investigations by the FDA and Bard show that the following products, sizes and lots of counterfeit flat sheet polypropylene surgical mesh are not manufactured by Bard. To date, four product sizes have been identified:0112650 – Bard Flat Mesh 2”x 4”
Lot 43APD007 Lot 48HVS036
0112660 – Bard Flat Mesh 10”x 14”
Lot HURL0336 Lot HUSD0629
0112680 – Bard Flat Mesh 3”x 6” Lot 43HPD027
Lot 43HPD032
Lot HUSG0540
Lot 43HDP027
Lot HUSE0532 Lot 43LPD507
Lot HUSF0763
Lot 43IOD011
Lot 43IPD038
0112720 – Bard Flat Mesh 6” x 6” Lot 43FQD327

The FDA is recommending that health care professionals:

Do not use any counterfeit Bard surgical mesh from the lots listed
Carefully examine all manufacturers’ polypropylene surgical mesh products and packaging for lot numbers and anything unusual that might indicate counterfeit mesh
Contact Bard at 800-556-6275 if they think they have one of the counterfeit products
Contact the particular manufacturer if they notice anything unusual or suspicious with any other brand of surgical mesh product or packaging.

The FDA also recommends that health care professionals continue to monitor patients for adverse events as they would any patient with an authentic polypropylene surgical mesh implant, if they suspect or know that counterfeit mesh has been implanted.

Patients should contact their surgeon if they experience problems that they think may be related to surgical mesh.

The FDA continues to gather information and data on the counterfeit mesh to better understand its potential public health impact. The agency also is working to determine who may be responsible and how the counterfeiting and distribution occurred.

At this time, the FDA does not know if the counterfeit surgical mesh meets the authentic product’s specifications, including its strength, sterility, or clinical performance. The FDA assessment of the counterfeit mesh and its potential risk to health is ongoing.

Health care professionals who believe they have received counterfeit or suspect product are asked to contact the FDA’s Office of Criminal Investigations at 800-551-3989 or by visiting the Web site at http://www.fda.gov/OCI.

Prompt reporting of adverse events can help the FDA identify and better understand the risks associated with medical devices. If you suspect a problem with this or any counterfeit surgical mesh, the FDA encourages you to file a voluntary report through MedWatch, the FDA’s Safety Information and Adverse Event Reporting Program.

Health care professionals and consumers are encouraged to report serious adverse events (side effects) that may be related to the use of these counterfeit products to the FDA’s MedWatch Adverse Event Reporting program either online, by regular mail, fax or phone.

Higher levels of naturally occurring estrogen are tied to a rising risk of stroke in postmenopausal women who aren’t on hormone therapy, a new study finds.

U.S. researchers analyzed medical histories and blood samples from more than 9,700 generally healthy postmenopausal white women recruited for an osteoporosis study in the late 1980s. None of the women were on hormone therapy.

During eight years of follow-up, 247 of the women suffered a first stroke. Those women were compared with 243 women who did not have a stroke.

The researchers found that women with the highest levels of estradiol (the most potent naturally occurring estrogen) were 2.3 times more likely to suffer a stroke than those with the lowest levels.

“These results raise the possibility that estradiol levels might be a decision-making tool for health care providers and their female patients when discussing stroke and weighing the option of estrogen therapy,” study leader Jennifer Lee, an endocrinologist and epidemiologist at the University of California, Davis Health System, said in a news release.

The researchers also found that women with waist sizes larger than 34 inches had higher estradiol levels and greater stroke risk than those with smaller waist sizes.

“In women with waist girths greater than 34 inches, high estradiol levels conferred a six-fold greater stroke risk over low levels,” Lee said. “This might be because fat around the midsection is a source of naturally occurring estrogen. Reducing waist size would be a good defense against future stroke.”

The study appears in a recent issue of the Archives of Neurology.

One of the world’s largest studies of the contraceptive pill has found that women who have taken it can expect longer lives and are less likely to die from any cause, including cancer and heart disease.

British researchers said their study, which should reassure many millions of women across the world who have taken oral birth control pills, found no link between the drugs and an increased long-term risk of dying sooner.

“The results of this study are enormously reassuring and suggest that in the longer term the health benefits of the contraceptive pill outweigh any risks,” said Richard Anderson of Edinburgh University and the Medical Research Council human reproductive sciences unit, who was not involved in the study.

The research, published in the British Medical Journal on Friday, followed 46,000 women for nearly 40 years, creating “more than a million woman-years” of observation, according to Philip Hannaford from Aberdeen University, who led the study.

The results showed that in the longer term, women who used oral contraception had a significantly lower rate of death from any cause, including heart disease and all cancers, compared with women who had never taken it.

But the scientists said their findings may only be true for women who have taken older-style pills rather than those on more modern types of drugs, since their study began in 1968.

“Many women, especially those who used the first generation of oral contraceptives many years ago, are likely to be reassured by our results,” Hannaford and colleagues wrote.

Around 12 million women in the United States and some 3 million women in Britain take the contraceptive pill.

Earlier reports from the same study — known as the Royal College of General Practitioners’ Oral Contraception Study and one of the world’s largest ongoing investigations into the health effects of oral contraceptives — suggested the drugs may increase the risk of dying sooner, particularly in older women or those who smoked.

While the newest data also showed a slightly higher risk in women under 45 who are current or recent users of the pill, the researchers said the effects in younger women disappear after about 10 years and the benefits in older women outweigh the risks in younger women.

(Reporting by Kate Kelland; Editing by Jon Hemming)

Gene tests that combined over 100 genetic mutations proved ineffective at predicting a woman’s risk of a heart attack or stroke, U.S. researchers said on Tuesday.

They said high cholesterol, high blood pressure and a family history of heart disease were the strongest predictors of a woman’s heart disease risk.

Many variations of genes have been identified that are associated with a higher risk of heart disease, but combining them into a risk prediction score did not help researchers find which women in a study of 19,000 participants would eventually develop the disease.

They found that after adjusting for traditional heart risk factors, a genetic risk score that combined 101 so-called single nucleotide polymorphisms or SNPs — a single-letter change in the genetic code — was not useful in predicting heart disease risk.

For years, teams have been using a tool called a genome-wide association study, in which researchers compare the genomes of people with a disease to those of healthy people, to look for common genetic differences that could help predict disease.

“While multiple genetic markers associated with cardiovascular disease have been identified by genome-wide association studies, their aggregate effect on risk beyond traditional factors is uncertain, particularly among women,” Nina Paynter of Brigham and Women’s Hospital in Boston, and colleagues wrote in the Journal of the American Medical Association.

The team developed two genetic risk scores based on genetic markers known to be associated with either heart disease or factors that cause heart disease, such as high cholesterol.

During follow-up, women in the study had 199 heart attacks, 203 strokes, 63 deaths from heart disease and 312 procedures to open blocked arteries.

After adjusting for traditional heart disease factors, such as blood pressure and total cholesterol, the genetic risk score was not associated with heart disease risk.

Instead, they found that family history of an early heart attack was one of the biggest independent risk factors.

“Our findings confirm the importance of family history of cardiovascular disease, which integrates shared genetics, shared behaviors, and environmental factors,” Paynter and colleagues wrote.

“While the importance of genetic data in understanding biology and etiology is unchallenged, we did not find evidence in this study of more than 19,000 women to incorporate the current body of known genetic markers into formal clinical tools for cardiovascular risk assessment,” they wrote.

U.S. federal health authorities on Tuesday rolled out a new safety plan for the use of Procrit and similar anemia drugs by people with cancer.

These medicines — often used by cancer patients to lower the need for blood transfusions and improve quality of life — have been tied to stroke, heart failure, tumor promotion and death in recent studies.

“The plan requires the drug manufacturer to implement a program to ensure that health-care professionals understand the appropriate use of these drugs and adequately inform patients of the drugs’ risks,” said Dr. Richard Pazdur, director of the Office of Oncology Drug Products at the Center for Drug Evaluation and Research (CDER), part of the U.S. Food and Drug Administration (FDA), at an afternoon news conference.

Procrit is one of three so-called erythropoiesis-stimulating agents (ESAs) manufactured by Amgen (the other two are Epogen and Aranesp), all of which are covered under the new plan. All three drugs are FDA-approved for people battling cancer, those infected with HIV, people with kidney failure and certain patients undergoing surgery, and all three carry with them an elevated risk of blood clots, stroke, heart failure, tumor promotion and death.

The new rules do not apply to indications other than use by cancer patients.

“Amgen will ensure that only certified health-care professionals may dispense and prescribe ESAs to patients with cancer and that all certified prescribers are trained to understand and communicate to patients the increased risk of tumor growth that these drugs present to patients with cancer,” Pazdur said.

“The risks for cancer patients are much different,” he added. Nor are the risks equal for all cancer patients, with the agency making a distinction between patients being treated with an aim to a cure and those receiving only palliative care.

Specifically, the plan requires that Amgen develop and disseminate a medication guide informing all cancer patients of the drugs’ risks and that doctors not only discuss the risks with patients but also obtain patients’ signatures.

Amgen is also obligated to ensure that all health-care providers prescribing and dispensing ESAs be trained and certified, and maintain active enrollment in the APPRISE (Assisting Providers and Cancer Patients with Risk Information for the Safe Use of ESAs) program. Providers not enrolled in the program will not be able to prescribe ESAs to cancer patients and they must re-enroll every three years, Pazdur said.

Amgen will be required to provide progress reports on the program, which will then be reviewed by the FDA, said Dr. Patricia Keegan, director of CDER’s Division of Biologic Oncology Products.

“We understand that the requirements of the safe use program will create new responsibilities for busy health-care providers and will require additional time for training, record keeping and other tasks, but we are not doing this to make things more difficult for health-care providers,” Pazdur said. “We are doing this to make absolutely certain that patients are fully informed related to the use of these drugs before they begin treatment.”

The new rules take effect in March, although providers will have a year to come up to speed.

These heavily promoted medicines have come under fire before. In 2007, the FDA added a black box warning to the drugs, which has been “updated several times as new studies and new information has been made available,” Keegan said. The FDA also recommended that the medications be prescribed at the lowest doses possible because trials generally indicated an increased risk when blood levels were raised above 12 grams per deciliter.

The U.S. Food and Drug Administration today approved a risk management program to inform healthcare providers and their patients about the risks of a class of drugs called Erythropoiesis-Stimulating Agents (ESAs). For patients with cancer, the program is also designed to help ensure the appropriate administration of these drugs, which they receive to treat anemia that can occur as a result of chemotherapy.

ESAs, which include epoetin alfa (marketed as Procrit and Epogen) and darbepoetin alfa (marketed as Aranesp), are manufactured by Amgen Inc. ESAs are forms of the human protein erythropoietin, which stimulates bone marrow to make red blood cells.

In April 2008, FDA required Amgen Inc. to establish this risk management program based on studies that found that ESAs caused tumors to grow faster and resulted in earlier deaths in some cancer patients.

Amgen’s risk management program, referred to as a REMS or Risk Evaluation and Mitigation Strategy, requires health care professionals to provide their patients receiving an ESA with a Medication Guide that contains information for patients on how to safely use a drug.

In addition, the company’s APPRISE (Assisting Providers and Cancer Patients with Risk Information for the Safe Use of ESAs) program, which is part of the REMS, requires specific training and certification of health care professionals who administer chemotherapy to patients with cancer and counseling of their patients. It does not apply to patients being treated with an ESA for anemia due to other circumstances.

“Evaluation of Erythropoiesis-Stimulating Agents has been an ongoing and intensive process since 2004, involving a series of public meetings, labeling changes, and a required Medication Guide,” said Richard Pazdur, M.D., director of the Office of Oncology Products in the FDA’s Center for Drug Evaluation and Research. “This new risk management program will help ensure that patients and their health care professionals have fully considered the benefits and risks of using ESAs.”

Through the risk management program, Amgen must ensure that health care professionals who treat patients with cancer do the following:
Register and maintain active enrollment in the ESA APPRISE program,
Complete a special training module on how to use ESAs in patients with cancer, and
Discuss the risks, benefits, and FDA-approved uses of ESAs with patients who have cancer before beginning a course of ESA treatment and document this discussion with a written acknowledgement from the patient.

Amgen is also required to oversee and monitor health care professionals and hospitals that use ESAs for patients with cancer to ensure that these caregivers are fully compliant with all aspects of the overall risk management program.

ESAs are approved for the treatment of anemia that may occur as a result of kidney failure, from certain kinds of chemotherapy, from the drug AZT, which can be used for the treatment of HIV infection, and for the treatment of anemia among certain patients undergoing surgery.

Procrit, Epogen and Aranesp are manufactured by Thousand Oaks, Calif-based Amgen.

For more information:

FDA Office of Oncology Drug Products
http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm091745.htm

Drug Safety Communication: Erythropoiesis-Stimulating Agents (ESAs): Procrit, Epogen and Aranesp
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm200297.htm

The counterfeit products contain controlled substance sibutramine

The U.S. Food and Drug Administration is today warning consumers about a counterfeit and potentially harmful version of Alli 60 mg capsules (120 count refill kit).

Preliminary laboratory tests conducted by GlaxoSmithKline (GSK)—the maker of the FDA approved over-the-counter weight-loss product— revealed that the counterfeit version did not contain orlistat, the active ingredient in its product. Instead, the counterfeit product contained the controlled substance sibutramine. Sibutramine is a drug that should not be used in certain patient populations or without physician oversight. Sibutramine can also interact in a harmful way with other medications the consumer may be taking.

Consumers began reporting suspected counterfeit Alli to GSK in early December 2009. GSK has determined that the counterfeit product has been sold over the internet. However, there is no evidence at this time that the counterfeit Alli product has been sold through other channels, such as retail stores.

The counterfeit Alli product looks similar to the authentic product, with a few notable differences. The counterfeit Alli has:
Outer cardboard packaging missing a “Lot” code;
Expiration date that includes the month, day, and year (e.g., 06162010); authentic Alli expiration date includes only the month and year (e.g.,: 05/12);
Packaging in a plastic bottle that has a slightly taller and wider cap with coarser ribbing than the genuine product;
Plain foil inner safety seal under the plastic cap without any printed words; the authentic product seal is printed with “SEALED for YOUR PROTECTION”;
Contains larger capsules with a white powder, instead of small white pellets.

Consumers who believe they have received counterfeit Alli are asked to contact the FDA’s Office of Criminal Investigations (OCI) by calling 800-551-3989 or by visiting the OCI Web site (http://www.fda.gov/OCI).

Health care professionals and consumers are encouraged to report adverse events that may be related to the use of these counterfeit products to the FDA’s MedWatch Program by phone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, or by mail at: MedWatch, HF-2, FDA, 5600 Fishers Lane, Rockville, MD 20852-9787.

Beta cell impairment may play a larger role in type 2 diabetes than previously recognized, the authors suggest. Also, the environment may contribute to insulin resistance more than it does to insulin secretion. Learning how the genes influence cell signaling and development, glucose sensing, and hormonal regulation will assist the development of targeted methods to prevent and treat diabetes, they conclude.

“Our study shows that genetic studies of glycemic traits can identify loci for type 2 diabetes risk,” says lead co-author Jose Florez, M.D., Ph.D., of Massachusetts General Hospital and Harvard Medical School. “However, not all loci that influence blood glucose regulation are associated with greater risk for type 2 diabetes. Some loci elevate fasting glucose slightly but do not raise diabetes risk. It appears that it’s not the mere elevation in glucose, but how glucose is raised, that determines type 2 diabetes risk.”

In the second paper, MAGIC researchers evaluated genetic associations with glucose levels 2 hours after an oral glucose challenge in a subset of 15,234 participants. They found that a genetic variant in the gene GIPR, which codes for the receptor of gastric inhibitory polypeptide, a beta cell regulating hormone, influences blood glucose levels after a glucose challenge, or sugary meal. Individuals with the risk variant have reduced beta cell function.

The discovery highlights the role of incretin hormones, which are released from endocrine cells in the gut. “This finding adds to a growing body of evidence implicating the incretin pathways in type 2 diabetes risk. These pathways, which stimulate insulin secretion in response to digestion of food, may offer a potential avenue for therapeutic intervention,” said senior author Richard Watanabe, Ph.D., of the University of Southern California.

The variants were found in populations of European descent, but the researchers expect that some will have similar effects in other populations. Future research will attempt to answer that question. “Even with the discovery of these variants, we’ve only explained about 10 percent of the genetic contribution to fasting glucose in people who do not have diabetes,” Florez cautioned. Yet undiscovered genes may be found by studies that increase sample sizes to detect smaller effects and look for less common variants as well as non-SNP variants — for example, insertions, deletions, and duplications of DNA that haven’t been well studied yet.

About 24 million people in the United States have diabetes. Worldwide, about 285 million people have the disease, according to the International Diabetes Federation. Diabetes is the main cause of kidney failure, limb amputations, and new onset blindness in adults and is a major cause of heart disease and stroke. Type 2 diabetes, which accounts for up to 95 percent of all diabetes cases, becomes more common with increasing age. It is strongly associated with obesity, inactivity, family history of diabetes, history of gestational diabetes, impaired glucose metabolism, and racial or ethnic background. The prevalence of diagnosed diabetes has more than doubled in the last 30 years, due in large part to the upsurge in obesity. For more information about diabetes, visit http://diabetes.niddk.nih.gov/index.htm.

The MAGIC studies required extensive collaboration by many researchers on both sides of the Atlantic.* The consortium found the genes and replicated the findings by analyzing genetic samples from up to 122,743 individuals who took part in 54 different studies funded by many publicly and privately funded sources in Europe, Australia, Canada, and the United States. Ten of these studies** were funded by components of the NIH, including the National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, the National Human Genome Research Institute, and the National Center for Research Resources. One study, the National Health and Nutrition Examination Survey, is conducted by the National Center for Health Statistics, a part of the Centers for Disease Control and Prevention.

The National Institutes of Health (NIH) — The Nation’s Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

An international research consortium has found 13 new genetic variants that influence blood glucose regulation, insulin resistance, and the function of insulin-secreting beta cells in populations of European descent. Five of the newly discovered variants increase the risk of developing type 2 diabetes, the most common form of diabetes.

The results of two studies, conducted by the Meta-Analyses of Glucose and Insulin Related Traits Consortium (MAGIC), provide important clues about the role of beta cells in the development of type 2 diabetes. The studies, funded in part by the National Institutes of Health, appear online Jan. 17, 2010, in Nature Genetics.

“The findings from these ambitious, large-scale studies represent an enormous achievement in international cooperation involving hundreds of researchers and many thousands of individuals who contributed genetic samples for the study. The results give us exciting new directions for future research in the biology of type 2 diabetes, which poses a major and growing public health problem worldwide,” said NIH Director Francis S. Collins, M.D., Ph.D., an author of both papers.

In one paper, the MAGIC investigators set out to find genes that influence metabolic traits, including fasting glucose and insulin levels and measures of beta cell function and insulin resistance. About 2.5 million genetic variants were analyzed in 21 genome-wide association studies (GWAS) that had enrolled 46,186 individuals who did not have diabetes and had been tested for measures of glucose and insulin regulation. GWAS look for common genetic associations by scanning the DNA of thousands of individuals. The huge numbers of genetic samples boosts the chances of finding subtle associations of genetic variants with specific diseases or traits. The most common variation is a change in a single nucleotide polymorphism (SNP), or single base pair change, in one of the building blocks of DNA.

The initial analysis yielded 25 candidate SNPs that were further tested in genetic samples from about 77,000 additional individuals. This step led to 16 SNPs that were clearly associated with fasting glucose and beta cell function and two SNPs associated with fasting insulin and insulin resistance. The investigators then asked whether any of the SNPs raise type 2 diabetes risk by comparing gene variants from thousands of people with and without type 2 diabetes.

Among the five variants that raise type 2 diabetes risk, one of the more intriguing SNPs is in the region of ADCY5, which influences fasting and postprandial glucose levels. Another is in FADS1, which is linked with fasting glucose as well as lipid traits. None of the variants found in the MAGIC studies were associated with type 1 diabetes, an autoimmune disease that has been traced mainly to genes that regulate immune function.

“The hallmarks of type 2 diabetes are insulin resistance and impaired beta cell function. We were intrigued to find that most of the newly found variants influence insulin secretion rather than insulin resistance. Only one variant, near IGF1, is associated with insulin resistance,” said lead author Inês Barroso, Ph.D., of the Wellcome Trust Sanger Institute, Cambridge, England.

U.S. hospital emergency departments treated 3.5 million motor vehicle crash victims who had injuries ranging from bruises and scrapes to life-threatening trauma in 2006, a new government study finds.

About 85 percent (3 million) of the patients were treated and released, 321,000 were admitted or transferred to another acute care hospital for inpatient care, and about 8,000 patients died in the emergency department, according to the latest News and Numbers, released Wednesday by the Agency for Healthcare Research and Quality.

The analysis of 2006 data also found that:
37 percent of crash victims were treated in hospital trauma centers equipped to provide comprehensive emergency medical care to patients with life-threatening injuries, while the rest were treated in hospitals not designated as trauma centers.
About 55 percent of the patients had private health insurance, 25 percent were uninsured, 10 percent had Medicaid coverage, 4 percent had Medicare coverage, and 7 percent had other types of coverage.
44 percent of the injuries treated were sprains, 35 percent were superficial injuries such as scrapes, 15 percent were fractures, 10 percent were open wounds, 5 percent were head injuries, and 3 percent were internal injuries of the thorax, abdomen and pelvis.

SOURCE: U.S. Agency for Healthcare Research and Quality.