FDA MedWatch, 10/10/08

FDA Licenses Drug to Prevent Joint Damage in Children with Hemophilia A

The U.S. Food and Drug Administration today approved a new use for the blood product Kogenate FS to reduce the frequency of bleeding episodes and prevent joint damage in children with the most severe form of hemophilia.

Hemophilia A is a rare, hereditary, bleeding disorder in which a protein needed to form blood clots, factor VIII, is missing or its level is reduced. The disorder affects about 15,000 individuals in the United States, nearly all of whom are male.

“Administering Kogenate FS to children with hemophilia A on a daily basis before a bleeding event occurs will reduce bleeding into joints and help prevent joint damage, a major cause of disability in hemophiliacs,” said Jesse Goodman, M.D., M.P.H., director, FDA’s Center for Biologics Evaluation and Research.

When individuals with hemophilia are injured, they bleed longer than a person without hemophilia. As a result, these individuals may experience serious bleeding episodes, often in the joints and muscles. Repeated bleedings increase the chance of joint damage.

Kogenate FS is a genetically engineered version of factor VIII. It was first licensed in the United States in 1993 for use during surgery and to prevent or control other bleeding episodes.

In a clinical trial, 65 boys under 30 months of age with severe hemophilia A and normal joints were observed for five years. The patients received either one daily dose of the drug, or three doses at the time of a bleeding episode. Joint damage during a bleeding episode was 6-fold lower, and the rate of bleeding 8-fold lower, in those boys who received the drug on a daily basis compared to those who received the drug only when a bleeding episode occurred. Most patients received the drug intravenously through a catheter.

The most common adverse events were infection at the catheter site and fever.

Medical News Today, 10/9/08 (http://www.medicalnewstoday.com/articles/124810.php)

Can honey treat a wound? What a sweet idea.

Smeared on a burn, the sticky elixir could reduce the time it takes for the wound to heal up to four days sooner in some cases a new review of studies suggests.

However, honey used with compression bandages does not significantly increase healing of venous leg ulcers and the jury is still out on honey’s effectiveness for other wounds, according to Andrew Jull and colleagues at the University of Auckland in New Zealand.

“The evidence currently does not support the use of honey on acute wounds such as abrasions and lacerations or on minor, uncomplicated wounds left to heal…following surgery,” Jull said.

The review appears in the latest issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews like this one draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

Honey’s history as a topical ointment for wounds stretches back into antiquity. An Egyptian surgical text, written on papyrus between 2600 and 2200 B.C., recommends the treatment, as do the Greek, Chinese and Ayurvedic medical traditions. Later, caregivers used honey-soaked bandages until topical antibiotics became widely available after World War II.

Jennifer Eddy, M.D., a University of Wisconsin researcher who is completing a study on honey treatments for diabetic foot ulcers, says patients might consider honey as part of an interest in alternative medicine or following a bad reaction to other topical treatments.

“Topical honey is cheaper than other interventions, notably oral antibiotics, which are often used and may have other deleterious side effects,” she said.

Honey can draws moisture out of cells and contains hydrogen peroxide, both of which help kill off infectious bacteria. Some varieties of honey have other antibacterial properties as well, the Cochrane researchers note.

The review included 19 studies with 2,554 participants. Although the honey treatment healed moderate burns faster than traditional dressings did, Jull recommends viewing the findings with caution, since a single researcher performed all of the burn studies.

For the moment, Jull said, “health services should refrain from providing honey dressing for routine use” for most other wounds until there are more studies that show its effectiveness.

At present, people most often use honey after trying other treatments, “when the wound was not improving with standard therapy,” Eddy said.

The review discloses that Cochrane authors were researchers in one of the leg ulcer studies included in the review and that the research unit that employs the authors received a small cash contribution from a manufacturer of honey dressings to conduct the ulcer study.

FOR MORE INFORMATION Health Behavior News Service: http://www.hbns.org.

Jull AB, Rodgers A, Walker N. Honey as a topical treatment for wounds. The Cochrane Database of Systematic Reviews 2008, Issue 4.

Medical News Today, 10/9/08 (http://www.medicalnewstoday.com/articles/124813.php)

The herbal medicine St. John’s wort appears to work just as well as some prescribed antidepressants for treating patients with major depression, a new review finds. However, patients in German-speaking countries might experience the best benefits.

While there is public interest in the United States about whether St. John’s wort adequately treats depression, in some countries, like Germany, doctors commonly prescribe it for mild symptoms. Authors of the review found that studies with German patients did, in fact, have the best results.

“The most striking finding from our review is that trials from German-speaking countries have clearly more positive effects, both compared to placebo and standard antidepressants, than trials from elsewhere,” said lead reviewer Klaus Linde of the Centre for Complementary Medicine Research at Technical University in Munich. “In principle, we can say that hypericum extracts work in German-speaking countries, but we are less certain for other countries.”

The review appears in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates research in all aspects of health care. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing trials on a topic.

A person could be experiencing major depression when depression symptoms interfere with his or her ability to work, sleep, eat and take pleasure in activities previously enjoyed. The symptoms usually last for at least two weeks, but can often last longer than several months. St. John’s wort (an extract of the plant Hypericum perforatum L.) is an herbal alternative for patients who do not want prescribed antidepressants.

Exactly how the herb works to treat depression is unclear, partly because the extracts can contain at least seven groups of components, according to the reviewers. There is also no regulation on what the extract must contain.

“There is no patent protection on herbs; therefore, more or less anyone can market hypericum extracts,” Linde said. “The products on the market vary enormously in their quality and content in active ingredients.”

Linde added that consumers should be aware that many St. John’s wort products on the market have very low concentrations (such as dosages of less than 300 milligrams per day), and therefore, probably act only by placebo effects.

In the United States, the National Center for Complementary and Alternative Medicine (NCCAM), a division of the National Institutes of Health, reports that St. John’s wort is “of minimal benefit in treating major depression.” A study co-funded by NCCAM, found St. John’s wort to be no more effective than placebo in treating major depression of moderate severity.

Linde and his colleagues wrote a previous Cochrane review in 2005 on St John’s wort and concluded that it did reduce symptoms of mild to moderate depression. The significant difference between the 2005 review and the current one is the reviewers now include only studies restricted to major depression, while the older version included all depressive disorders.

“Compared to 2005, the evidence that hypericum extracts are effective is better now,” said Linde. “The new version also for the first time shows significantly fewer side effects associated with hypericum extracts compared to selective serotonin reuptake inhibitors.”

The current review evaluated 29 studies from a variety of countries with 5,489 patients and all trials were randomized and double blind. The reviewers compared treatment of patients with major depression with extracts of St. John’s wort for four to 12 weeks with either placebo or tri- or tetracyclic antidepressants and selective serotonin reuptake inhibitors.

According to the reviewers, the St. John’s wort products tested in the trials were high- quality products and the daily extract dosages were between 500 and 1,200 milligrams.

The Cochrane reviewers concluded the available evidence suggests that hypericum extracts are superior to placebo in treating patients with major depressions and are “similarly effective” as standard antidepressants.

John Williams, M.D., director of the Duke Evidence-based Practice Center at Duke University and Durham VA Medical Center, has also done research on the use of St. John’s wort for depression and disagreed that patients with major depression should turn to the product.

“Given the inconsistent evidence about efficacy in major depression and the questionable quality of over-the-counter products, St. John’s wort should not be a first or second choice for U.S. patients with moderate to severe major depression,” he said.

Williams added, however, that for patients with minor depression, where the evidence for St. John’s wort “is more robust,” it might be an option for patients who can find quality products.

The review disclosed that each author has received speaking or travel reimbursement fees from German drug manufacturer Schwabe.

The Cochrane Collaboration is an international nonprofit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. Visit http://www.cochrane.org for more information.

Linde K, Berner MM, Kriston L. St John’s wort for major depression. Cochrane Database of Systematic Reviews 2008, Issue 4.

Medical News Today, 10/9/08 (http://www.medicalnewstoday.com/articles/124814.php)

A new meta-analysis of existing research finds that patients who have immobilized lower legs due to a plaster cast or brace can greatly reduce their risk of a dangerous blood clot if they take a common anticoagulant drug.

In a new Cochrane Library review, the researchers suggest that adult patients whose upper or lower legs are in casts or braces should have routine treatment with the drug known as low-molecular-weight heparin. The risk of bleeding, a side effect of anticoagulant drugs, is low in such patients, the researchers report…

At issue is the risk that a kind of blood clot known as a deep vein thrombosis will form in an immobilized leg and travel to the lungs, where it could clog vessels that bring oxygen to the heart.

Clots in the lungs, known as pulmonary emboli, kill about 300,000 people a year in the United States, said Dr. Victor Tapson, director of the Center for Pulmonary Vascular Disease at Duke University Medical Center. Other estimates vary, starting at 50,000 such deaths a year.

“That may not be as many as heart attacks, but it often is more sudden,” Tapson said. “Someone with an embolism can be a young, apparently healthy patient, although more often it’s someone with clearly defined risk factors.”

People with hip fractures, hip replacements and any kind of reduced mobility are at special risk, Tapson said. Airplane passengers are in danger of pulmonary emboli because their legs are often immobile and cramped for long periods.

“The less mobile the legs are, the more likely you are to get a clot,” Tapson said. “Blood isn’t much like water. If it can’t flow and move, it will be more susceptible to thickening and clotting.”

In the new review, researchers in the Netherlands examined six randomized controlled studies in which 1,490 patients with immobilized lower legs received either low-molecular-weight heparin or a placebo or no preventive treatment. In all cases, plaster casts or braces immobilized the legs of the patients.

The review appears in the latest issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

The researchers conducted a meta-analysis, pooling the findings from the studies.

The rate of blood clots for patients who were in a cast or brace for at least one week ranged between 4.3 percent and 40 percent among those who received no anti-clotting treatment. However, the rate fell by about one-half in those who received daily injections of low-molecular-weight heparin.

The drug can cause excessive bleeding because it is more difficult for blood to coagulate and block holes in vessels. Still, “major bleeding events” were very rare in the patients who took heparin, striking about one in every 300, the reviewers found. Up to 8 percent of the patients who took heparin had “minor” bleeding problems.

The researchers recommend low-molecular-weight heparin as a routine treatment for patients with upper- or lower-leg casts or braces, but point out that blood clots are still a risk, even when the drug is used.

When patients have leg injuries, “immobilization should be avoided as much as possible, and treatment requiring less immobilization should always be considered,” the researchers write.

Tapson was impressed with the review and said he hopes it provide new insight for doctors.

Currently, doctors routinely do not give anticoagulants to everyone in a leg cast, Tapson said. “There aren’t really clear recommendations,” he said. “If you’ve got someone 70 years old in a cast, you’re much more likely to consider [an anticoagulant]. A 25 year old may not be as high risk.”

Even in light of the findings of the review, he said, doctors are not likely to give anticoagulants to all patients in casts, but instead consider it depending on their individual circumstances, he said.

Another pulmonary specialist said the review appears to be “sound.” Dr. Kenneth. Leeper Jr., associate professor of medicine at Emory University, added that immobilized patients “probably” should receive low-molecular-weight heparin routinely, unless there is a good reason not to administer the medication.

The Cochrane Collaboration is an international nonprofit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. Visit http://www.cochrane.org for more information.

SOURCE:  Testroote M, et al. Low molecular weight heparin for prevention of venous thromboembolism in patients with lower-leg immobilization. Cochrane Database of Systematic Reviews 2008, Issue 4.

The CBS Evening New (10/9, story 7, :30, Couric) reported that on Thursday, the Centers for Disease Control and Prevention (CDC) released its “first report card on the new” human papillomavirus (HPV) vaccine, Gardasil.  In its Morbidity & Mortality Weekly Report, it was reported by Katie that since its approval two years ago, approximately “one in four teenaged girls has been immunized.”

Saleem S, et al “Ginkgo biloba extract neuroprotective action is dependent on heme oxygenase-1 in ischemic reperfusion brain injury” Stroke 2008; DOI: 10.1161/STROKEAHA.108.523480.
ABSTRACT

TITLE:  Ginkgo Biloba Extract Neuroprotective Action Is Dependent on Heme Oxygenase 1 in Ischemic Reperfusion Brain Injury

Background and Purpose—Ginkgo biloba extracts are now prescribed in several countries for their reported health benefits, particularly for medicinal properties in the brain. The standardized Ginkgo extract, EGb761, has been reported to protect neurons against oxidative stress, but the underlying mechanisms are not fully understood.

Methods—To characterize the oral consumption of EGb761 in transient ischemia, we performed the middle cerebral artery occlusion (MCAO) filament model in wild-type and heme oxygenase 1 (HO-1) knockouts. Mice were pretreated for 7 days before the transient occlusion or posttreated acutely during reperfusion; then neurobehavioral scores and infarct volumes were assessed. Furthermore, primary cortical neuronal cultures were used to investigate the contribution of the antioxidant enzyme HO-1 in the EGb761-associated cytoprotection.

Results—Mice that were pretreated with EGb761 had 50.9±5.6% less neurological dysfunction and 48.2±5.3% smaller infarct volumes than vehicle-treated mice; this effect was abolished in HO-1 knockouts. In addition to the prophylactic properties of EGb761, acute posttreatment 5 minutes and 4.5 hours after reperfusion also led to significant reduction in infarct size (P<0.01). After our previous demonstration that EGb761 significantly induced HO-1 levels in a dose- and time-dependent manner in neuronal cultures, here we revealed that this de novo HO-1 induction was required for neuroprotection against free radical damage and excitotoxicity as it was significantly attenuated by the enzyme inhibitor.

Conclusion—These results demonstrate that EGb761 could be used as a preventive or therapeutic agent in cerebral ischemia and suggest that HO-1 contributes, at least in part, to EGb761 neuroprotection.

HealthDay, 10/9/08 (http://www.healthday.com/Article.asp?AID=620032)

Three leading medical associations have created guidelines to help heart disease patients cut their risk of ulcers and gastrointestinal bleeding from the condition’s most common treatments — antiplatelets and nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin.

The American College of Cardiology, the American College of Gastroenterology and the American Heart Association guidelines call on doctors to better assess the patient’s risk factors before treatment starts. These include considering:

• age,
• previous history of ulcers or bleeding,
• presence of H. pylori (a common bacteria that contributes to the development of stomach ulcers), and,
• acid reflux symptoms.

Doctors are also advised to review the patient’s use of other NSAIDs, anticoagulants and/or corticosteroids.

Having several of these risk factors greatly increases the person’s chance of gastrointestinal bleeding, a major and potentially life-threatening complication.

“These recommendations represent the collective expertise of leading cardiologists and gastroenterologists, as well as an extensive review of the literature, and provide specialists with practical measures to manage competing risks and help improve patient safety,” Dr. Deepak L. Bhatt, document co-chair and chief of cardiology at the VA Boston Healthcare System, said in a news release.

Antiplatelets, which reduce the blood’s ability to clot, are key to preventing a cardiovascular event in people with atherosclerotic disease. The treatment is usually prescribed with daily low-dose aspirin, a NSAID.

NSAIDs, one of the most widely used classes of drugs in the United States, help reduce fever, pain and inflammation. These drugs — which include aspirin, ibuprofen, ketoprofen and naproxen — are often used to treat other common conditions, including arthritis, inflammation and related musculoskeletal pain.

People on low-dose aspirin plus NSAIDs have a two- to fourfold increased risk of gastrointestinal bleeding compared with those not taking these medications, the specialists said.

“The recommendations will help physicians evaluate the risk profile for each patient and either change medications or provide appropriate therapies to help reduce GI complications,” Dr. Elliott Antman, a member of the writing group and a professor of medicine at Harvard Medical School, said in the same news release.

“We must be more proactive in assessing individual patient risk to be able to prevent gastrointestinal problems as antiplatelet therapy is actually initiated,” Dr. David A. Johnson, immediate past president of the American College of Gastroenterology, said in the same news release. “Communication among cardiologists, gastroenterologists and primary care physicians is critical. At the same time, patients must tell their doctors about any and all medications they are taking — prescription and over-the-counter medicines — so appropriate measures can be taken to reduce risk.”

As more Americans survive and live with heart disease, in addition to conditions such as arthritis and related musculoskeletal pain that require them to take NSAIDs, managing gastrointestinal risk will become an increasingly important part of cardiovascular care, the doctors said.