Update From the Medical Journals: December 2011 - What Your Doctor Is Reading - Harvard Commentaries

What's the latest news in the medical journals this month? Find out what your doctor is reading.

Warfarin Users Should Test Blood at Home
Low-Risk Prostate Cancers May No Longer Be Considered Cancers
More News in Brief: Vitamin D Needs Calcium to Work; Gene Therapy Treats Hemophilia Patients; Sexual Violence is Widespread

Warfarin (Coumadin) is a blood thinning medicine. It is an important treatment for people who have blood clots in the leg or lung, atrial fibrillation (an abnormal heart beat), or a mechanical heart valve (where clots tend to form). Warfarin requires regular blood tests to find the right dose for each person. Over time, the dose needs to be adjusted due to changes in diet, in other medications and in the way you metabolize the drug. If the dose is too low, a clot could develop. This could cause a stroke. A dose that's too high can lead to dangerous bleeding.

Doctors check for the correct dose by measuring a blood clotting marker known as the "International Normalized Ratio" (INR). Usually, the INR needs to stay between 2.0 and 3.0. This test is typically done once every three weeks. A new study, published online by Lancet November 30, analyzed the results of 11 other studies that compared people who got standard office blood tests with those who tested at home. The home test uses a special meter to test a drop of blood. The studies included a total of 6,400 people.

People who used office or home testing had similar risks of excess bleeding or death. For some groups, blood clot risk was cut in half or more with home tests. Those who benefited the most were people with mechanical heart valves and people under age 55. People over age 85 had lower death rates with home tests.

This study supports the widespread use of self-testing for people who take blood thinners. That would be a big change from current practice. In the United States, only 1% of patients taking blood thinning pills self-test.

Prostate cancer is frequently diagnosed in a very early stage using a blood test that measures prostate specific antigen (PSA). Two ways to treat prostate cancer are surgery or radiation. These can cause long-term side effects, including impotence or leakage of urine.

Doctors can't predict which cancers will become aggressive and spread. For this reason, most men who are diagnosed with prostate cancer choose to treat the cancer right away, even if it's classified as "low grade" (not aggressive).

But an expert panel organized by the National Institutes of Health (NIH) reported online December 7 that they think most men with prostate cancer should delay radiation or surgery. The panel says most men with low-risk prostate cancer would do best with either surveillance or watchful waiting. The experts reviewed evidence from existing studies to reach this conclusion. If their recommendations are followed, far fewer men would have treatment for prostate cancer.

The surveillance option is not yet standardized. So how it's used varies from doctor to doctor. But it typically includes yearly biopsies of the prostate and its cancer area, PSA blood tests every six months, and digital rectal examinations by a doctor every six months. In one clinical study, 320 men with prostate cancer tried this "active waiting" strategy. About one out of three did end up with worrisome changes in their cancers within the first several years of surveillance. These men then chose surgery or radiation to treat their cancer. The men who waited until "if and when" their cancers changed before having surgery were compared with men who had similar low-risk cancers and chose immediate surgery. The outcomes for these two groups were similar. In other words, there was no harm in waiting if your prostate cancer was low risk.

Watchful waiting, the other strategy, involves no tests or treatment unless symptoms occur. Researchers studied this approach in 2008 in older men (average age of 75). It seemed to work well for older patients, as it spared many men from unnecessary treatment and its side effects. About 90% of them were either alive or had died of something other than prostate cancer ten years after the trial began. Cancer deaths occurred in only 3% of the men with low-grade prostate cancer.

A prostate cancer is low risk if a PSA result is less than 10 milligrams/dL and a Gleason score (a finding from a biopsy) is less than 6. More than half of prostate cancers that are found by PSA testing are low risk.

The NIH panel members think we should stop referring to low-risk prostate cancer as "cancer." They did not give specific suggestions for a new name. They think too many men are afraid to "leave a cancer alone," even though this approach makes sense for many men who have prostate cancer.

Vitamin D Needs Calcium to Work. Vitamin D is essential to maintain bone health. As many as one out of three people in the United States have low blood levels of vitamin D. Taking vitamin D pills reduces the risk of fracture in adults over 65. And it can help to prevent osteoporosis. But a review of evidence from 50 smaller studies shows that this benefit occurs only for people who also take calcium. The report came from the U.S. Preventive Services Task Force. This is an expert group that provides advice to health professionalson preventive care. The Annals of Internal Medicine published the report December 20.

People in the studies took from 300 to 1,100 international units of vitamin D. The calcium doses they took daily ranged from 500 to 1,200 milligrams. The current advice is 1,000 to 1,200 milligrams total calcium per day for adults, which can come from a combination of diet and supplements.

Gene Therapy Treats Hemophilia Patients. People with hemophilia B bleed easily after even a minor injury. An abnormal gene causes the disease. It makes a person unable to make enough of a protein that helps blood clot. The protein is called factor IX ("factor nine"). A remarkable new study took normal genes associated with factor IX production and joined them to particles of a harmless virus. Then researchers delivered the virus into the bloodstream of six people with hemophilia using an intravenous (IV) line. This gene therapy study was published December 22 in the New England Journal of Medicine.

The virus was a modified form of adenovirus. (Adenovirus in its original form can cause a common cold or stomach flu). Researchers predicted that the virus particles would move to the liver and "contaminate" the liver cell DNA by adding the new genes. This is in fact what happened — and in turn these patients began to produce more factor IX. The "delivered" genes seemed to become a permanent fixture. Before the study, these patients needed to have IV infusions of manufactured factor IX several times per month. After 6 to 15 months, 4 out of these 6 patients no longer needed to have factor IX infusions because they made enough of their own. The other 2 study participants needed fewer treatments than they did before. The therapy has great promise for treatment of hemophilia, and is a good demonstration of how gene therapy may be applied to difficult-to-treat illnesses.

Sexual Violence is Widespread. Almost all physicians have underestimated how common sexual violence is. The Centers for Disease Control and Prevention issued a press release December 14 with the sobering findings of a survey about sexual violence, stalking and intimate partner violence. This survey, from 2010, included more than 18,000 interviews. According to the survey, almost 1 in 5 women has been raped at some time in her life, 1 in 4 women has been a victim of severe violence by her intimate partner, and 1 in 6 women has been stalked (either physically or by unwanted phone calls or text messages by someone the woman felt to be a stalker). It was rare for these sexual violence attacks to involve a stranger. The abuser or attacker was usually someone the girl or woman knew. The majority of women had their first experience with rape or intimate partner violence when they were younger than age 25. Men were also surveyed, but they reported less violence than women.

Mary Pickett, M.D. is an Associate professor at Oregon Health & Science University where she is a primary care doctor for adults. She supervises and educates residents in the field of Internal Medicine, for outpatient and hospital care. She is a Lecturer for Harvard Medical School and a Senior Medical Editor for Harvard Health Publications.