nd01.jpg (9585 bytes)Study shows CRP is stronger predictor than LDL of first cardiovascular events
A study appearing in the November 14, 2002 issue of The New England Journal of Medicine concludes that the C-reactive protein level is a stronger predictor of cardiovascular events than the LDL cholesterol level, but that both biologic markers together provide better prognostic information than screening for either alone.

The study followed nearly 28,000 healthy American women aged 45 and older for a mean of eight years to record the occurrence of myocardial infarction, ischemic stroke, coronary revascularization, or death from coronary causes. The researchers, from Brigham and Women’s Hospital in Boston, concluded that women with high levels of CRP in their blood, as an indicator of inflammation were twice as likely to have a heart attack or stroke as women with high cholesterol. The results are thought to be equally applicable to men, and are important because half of all people who have heart attacks in the U.S. have normal cholesterol levels. The researchers estimate that 25 million to 30 million Americans have elevated CRP levels, but normal cholesterol, and may be unaware that they are at risk of heart disease.

In an accompanying editorial, Dr. Lori Mosca, director of preventive cardiology at New York Presbyterian Hospital, said that routine CRP screening was not yet recommended because studies had not been done to verify that lowering CRP levels would correspond with lowering a person’s risk. Premature treatment could lead to unnecessary side effects, without proof that medication is effective.

The methods for lowering CRP would be the same as those for lowering cholesterol. In the study, CRP identified a risk group of women with normal cholesterol levels who went on to have cardiovascular events. Until now, physicians have looked primarily at the role of cholesterol in leaving fatty deposits to clog arteries; the value of CRP testing may signal a shift toward including examination of inflammation’s role in weakening fatty buildups and leaving them susceptible to rupture and clotting that can trigger a heart attack or stroke.


CRP and albumin levels predict heart attack or stroke in dialysis patients
In a study conducted at Johns Hopkins and presented at the November 2002 meeting of the American Heart Association, C-reactive protein(CRP) and albumin, were shown to be accurate predictors of heart attack or stroke in kidney dialysis patients. The research team found that high levels of C-reactive protein, a marker of inflammation, and low levels of albumin, a sign of malnutrition, had strong ties to heart disease in these patients, who are many times more likely to develop heart problems than the general population.

“Both inflammation and malnutrition play an important role in the high risk of cardiovascular disease among dialysis patients,” says Josef Coresh, M.D., Ph.D., lead author of the study and associate professor of epidemiology, medicine and biostatistics at Hopkins. “


HHS Secretary urges company to initiate waiver review process for rapid HIV test
nd01.jpg (9585 bytes)The FDA has approved a new rapid HIV diagnostic test kit that provides results with 99.6 percent accuracy in as little as 20 minutes (see cover). Using less than a drop of blood collected, this test can quickly and reliably detect antibodies to HIV-1, the HIV virus that causes infection in most cases in the U.S. Unlike other antibody tests for HIV, this test can be stored at room temperature, requires no specialized equipment, and may be considered for use outside of traditional laboratory or clinical settings. The newly approved HIV test is called The OraQuick Rapid HIV-1 Antibody Test, manufactured by OraSure Technologies, Inc., Bethlehem, Penn.

To perform the test, a fingerstick sample of blood is collected from an individual and transferred to a vial where it is mixed with a developing solution. The test device, which resembles a dipstick, is then inserted into the vial. In as little as 20 minutes, the test device will indicate if HIV-1 antibodies are present in the solution by displaying two reddish-purple lines in a small window on the device. Although the results of rapid screenings will be reported in point-of-care settings, as with all screening tests for HIV, if the OraQuick test gives a reactive test result, that result is subject to confirmatory testing. The OraQuick test has not been approved to screen blood donors.

The FDA currently categorizes the OraQuick test as “moderate complexity” under the Clinical Laboratory Improvements Amendments of 1988 (CLIA). If the test manufacturer applies for a CLIA waiver, the FDA can evaluate it for use under less stringent conditions.

“I strongly urge the OraSure company to apply for a CLIA waiver,” said Secretary Tommy Thompson, “If the FDA finds that the company’s data proves that the OraQuick test is both easy and safe to use, it can get a CLIA waiver. Then the test could be given in many more health care settings, perhaps even administered by social workers in HIV counseling centers. But the process can’t begin until OraSure applies for the waiver, so I ask them to please apply now!”

The Centers for Disease Control and Prevention (CDC) has estimated that one fourth of the approximately 900,000 HIV-infected people in the U.S. are not aware that they are infected. Because of the potential public health benefits of rapid HIV testing, the CDC and the Centers for Medicare and Medicaid Services (CMS) are working with state and other health officials to make the test widely available and to offer technical assistance and counseling training for its use.

“This test will be a great help in identifying pregnant HIV-infected women going into labor who were not tested during pregnancy so that precautionary steps can be take to block their newborns from being infected with HIV,” said FDA Deputy Commissioner Dr. Lester M. Crawford. “It will also be a critical resource in helping identify HIV infection in health-care and emergency workers who are accidentally exposed to HIV-infected blood while doing their job.


A new HIV vaccine is now in clinical trials
Clinical tests have begun for a novel vaccine directed at the three most globally important HIV subtypes, or clades. Developed by scientists at the Dale and Betty Bumpers Vaccine Research Center (VRC), part of the National Institute of Allergy and Infectious Diseases (NIAID), the vaccine incorporates HIV genetic material from clades A, B and C, which cause about 90 percent of all HIV infections around the world.

“This is the first multigene, multiclade HIV vaccine to enter human trials,” notes NIAID Director Anthony S. Fauci, M.D. “It marks an important milestone in our search for a single vaccine that targets U.S. subtypes of HIV as well as clades causing the global epidemic,” he adds.

The trial vaccine is a DNA vaccine, a kind shown to be very safe in previous clinical trials. It incorporates parts of four HIV genes. While these gene fragments can stimulate an immune response, they cannot reconstitute themselves into an infectious virus. A person cannot become infected with HIV from this vaccine, emphasizes Gary Nabel, M.D., Ph.D., who heads the VRC.

Efforts to develop a broadly effective vaccine against HIV are complicated not only by the many clades, but also by the virus’ ability to elude immune system defenses through rapid mutation. “Any HIV vaccine must hit a constantly moving target,” says Dr. Nabel. “Essentially, we are trying to enlarge that target through a multiclade vaccine.”

The public plays a critical role in this ongoing research, says Barney Graham, M.D., Ph.D., chief of the VRC’s clinical trials core and lead investigator in the multiclade vaccine trial. “We want the community to understand and support the process of vaccine development so that together we can attain the goal of stopping or slowing the AIDS pandemic,” he says. “Although thousands have already volunteered to take part in HIV vaccine trials, many more are needed. The importance of community participation cannot be overemphasized,” says Dr. Graham.

The first phase of the trial, which is being conducted at the National Institutes of Health in Bethesda, Md., is meant to determine the vaccine’s safety and will enroll 50 healthy, HIV-negative volunteers. Following an extensive informed consent process, volunteers, who must be between 18 and 40 years old to participate, will be vaccinated with either the test vaccine or an inactive saline solution in a series of increasing doses. Neither the participants nor the researchers will know which group a participant is in. During the yearlong trial, scientists will assess the vaccine’s safety and note if it induces any immune response in the vaccines. Expanded tests conducted through NIAID’s HIV Vaccine Trials Network are planned for several domestic sites as well as sites in Haiti and South Africa.

For more information about the trial, including ways to volunteer, interested persons can call toll-free 1-866-833-LIFE (5433), e-mail [email protected]  or visit http://www.clinicaltrials.gov  or http://www.niaid.nih.gov/vrc.


Test helps guide tailored drug therapy that may reduce cardiovascular events
In a study conducted at the University of Virginia (UVA) Medical School with results published in the October 15, 2002 issue of The American Journal of Cardiology, the Vertical Auto Profile Expanded Cholesterol Test was shown to successfully steer physicians toward customized drug therapy to fix multiple cholesterol abnormalities rather than just treating elevated LDL cholesterol. Such therapy could reduce cardiovascular event rates by up to 70 percent, according to the researchers.

Physicians at the University of Virginia School of Medicine routinely use the VAP (Vertical Auto Profile) Test to measure cholesterol subclasses––detailed information that is not measured by routine cholesterol tests. Researchers found that treatment with multiple cholesterol-lowering medications tailored to the individual patient’s cholesterol subclasses can correct many cholesterol subclass abnormalities. Such therapy has the potential to significantly reduce cardiovascular events. Current heart disease prevention emphasizes reducing only LDL cholesterol with statins as the primary form of treatment.

“The study results are significant because they illustrate how tailored patient treatment may lead to a marked decrease in heart and blood vessel disease,” said Christopher M. Rembold, M.D., lead study author and professor of internal medicine and physiology at the University of Virginia School of Medicine. “The patient outcomes achieved in this study suggest that the VAP Test, coupled with lipid therapy tailored to the patient’s abnormal lipids, is essential in detecting and treating the No. 1 cause of death in this country.”

The VAP Expanded Cholesterol Test, developed by Atherotech of Birmingham, Ala., complies with updated National Cholesterol Education Program (NCEP) guidelines, which call for improved patient identification and more aggressive treatment of heart disease. Importantly, many of the lipid subclasses measured by the VAP Test have been identified in the NCEP guidelines as emerging risk factors and secondary targets of therapy for heart disease, and a growing body of scientific evidence reinforces the need for expanded cholesterol testing.

The retrospective analysis of data from 39 patients showed that treatment with multiple drugs altered a number of cholesterol subclasses measured by the VAP Test. Specifically, treatment increased “good” cholesterol subclasses such as HDL, small HDL3, and large HDL2, while significantly reducing disease-causing cholesterol subclasses including IDL, total VLDL, small VLDL3, and triglycerides. Multiple therapy also increased LDL particle size (small LDL size is associated with increased risk of heart attack). In summary, the analysis found that using combination therapy has the potential to reduce cardiovascular events as much as 60 percent based on the increase in HDL cholesterol and its subclasses, and up to 70 percent based on changes in LDL particle size.


New FDA law aims for faster approvals and stricter requirements for single-use devices
nd03.jpg (6664 bytes)The Medical Device User Fee and Modernization Act of 2002 (MDUFMA) was signed into law by President Bush on October 26, 2002. MDUFMA has three particularly significant provisions: user fees for premarket reviews of new devices and tests; the ability of a third party to conduct inspections of manufacturing facilities; and new regulatory requirements for reprocessed single-use devices.

User fees: PMAs and 510(k)s are now subject to fees paid by manufacturers. The revenues from these fees are intended to enable the FDA to provide patients earlier access to safe and effective technology, while providing more interactive and rapid review to the medical device industry. A small business may pay a reduced fee for a review.

The payment of a premarket review fee is not related in any way to the FDA’s final decision on a submission.

Manufacturing inspections: FDA-accredited persons can now inspect qualified manufacturers of class II and class III devices. These provisions are intended to help the FDA focus its limited inspection resources on higher-risk inspections.

Reprocessed single-use devices: Under the new law, reprocessors of some exempt devices will no longer be exempt from the 510(k) submission requirements but rather will need to submit 510(k)s that include validation data. Validation data will also be required for many reprocessors of single-use devices that are currently the subject of cleared 510(k)s. Finally, reprocessors of class III devices will need to submit a premarket report (a new type of premarket application).


FDA clears new lab test for Group B Strep in pregnant women
The Food and Drug Administration today cleared for marketing a new laboratory test for Group B Streptococcus in pregnant women.

The new test, the IDI-Strep B test, made by Infectio Diagnostic, Inc., of Quebec, can provide results in one hour, if facilities can provide round-the-clock testing. In contrast, the standard method of culture testing takes 18 to 48 hours for results. The new test is performed using a Cepheid Smart Cycler instrument on a swab sample taken from the vagina and rectum.

Group B strep is a leading cause of illness and death among newborns in the United States. It can be acquired during birth from mothers who unknowingly have the organism. An estimated 10 percent to 30 percent of pregnant women have Group B strep. However, antibiotic treatment of the mother during labor can prevent transmission to the newborn.

Pregnant women are typically screened for Group B strep two to four weeks before labor begins using the standard culture method, as recommended by the Centers for Disease Control and Prevention (CDC). If the test is positive for Group B strep, the woman is given four hours of antibiotic treatment during labor.

Use of this standard screening method has led to a 70 percent decline in the incidence of Group B strep during the past decade. However, because of the time needed to culture samples and the four hours needed for antibiotic treatment, it is only useful for women who are tested at least several days before labor begins—not those who start labor early, or who do not have the advantage of prenatal care. The new IDI-Strep B test, with timely results meets CDC performance criteria of 85 percent sensative, and could be particularly beneficial for these women when they first go into labor.

FDA cleared the IDI Strep B test based on clinical studies conducted by the manufacturer of 802 women at five medical centers in the United States and Canada. The studies showed that the test detected approximately 94 percent of Group B strep in pregnant women.


Listeriosis outbreak traced to sliceable turkey
nd04.jpg (8767 bytes)CDC, state and local health departments, and the United States Department of Agriculture (USDA) Food Safety and Inspection Service (FSIS) have been investigating an outbreak of listeriosis primarily affecting persons in the northeastern United States. Fifty ill persons infected with the outbreak strain of Listeria have been identified since mid-July; most were hospitalized, seven have died, and three pregnant women have had miscarriages or stillbirths. Epidemiologic data indicate that precooked, sliceable turkey deli meat is the cause of this outbreak.

As part of the ongoing outbreak investigation, USDA-FSIS has been investigating turkey processing plants. Listeria bacteria have been found in turkey products from two plants. USDA-FSIS laboratories performed DNA fingerprinting on these bacteria. Comparison of strains was conducted through PulseNet, a network of public health and regulatory laboratories coordinated by CDC that perform DNA fingerprinting of bacteria and electronically share results.

The affected patients live in 8 states: Pennsylvania (14 cases), New York (11 cases in New York City, 9 in other locations), New Jersey (5 cases), Delaware (4 cases), Maryland (2 cases), Connecticut (1 case), Michigan (1 case), and Massachusetts (3 cases).

About 2,500 cases of listeriosis occur each year in the United States. The initial symptoms are often fever, muscle aches, and sometimes gastrointestinal symptoms such as nausea or diarrhea. The illness may be mild and ill persons sometimes describe their illness as flu-like. If infection spreads to the nervous system, symptoms such as headache, stiff neck, confusion, loss of balance, or convulsions can occur. Most cases of listeriosis and most deaths occur in adults with weakened immune systems, the elderly, pregnant women, and newborns. However, infections can occur occasionally in otherwise healthy persons. Infections during pregnancy can lead to miscarriages, stillbirths, and infection of newborn infants. Previous outbreaks of listeriosis have been linked to a variety of foods especially processed meats (such as hot dogs, deli meats, and paté) and dairy products made from unpasteurized milk.

Information on specific products and brands that have been recalled is available at: [removed]http://www.fsis.usda.gov/OA/recalls/prelease/pr090-2002.htm[/removed]   and [removed]http://www.fsis.usda.gov/OA/recalls/prelease/pr098-2002.htm[/removed].


BD sends recall letter for some Microtainer EDTA tubes
BD of Franklin Lakes, N.J. issued a recall letter dated October 16, 2002, for BD-Microtainer Ethylenediaminetetraacetic Acid (EDTA) Tubes with Microguard Closures Lot No. 2098765, for units distributed in the U.S. and internationally between May 28 and October 21, 2002. These capillary tubes may contain an insufficient quantity of EDTA. As a result, the blood may clot, leading to an erroneously low platelet count that could be reported without detection by the laboratory or the clinician. BD will send a recall packet to customers who have purchased affected product within the dates specified above and will ship replacement product directly to customers. BD customer service can be reached by telephone at (888) 237-2762 within the U.S. or at (201) 847-6800 outside the U.S.