Sunday, March 5, 2017

Teens and medicines that cause birth defects: Do doctors drop the ball?


buy accutaneMy 14-year-old daughter recently started taking isotretinoin, a medication that can help severe acne — and that can cause severe birth defects. I knew that there was a process in place for preventing pregnancy in girls taking it, but I was caught off guard by just how many hoops we had to jump through to get her prescription.

There were two pregnancy tests a month apart at the beginning, continued monthly pregnancy tests as well as monthly online questions about contraception and her understanding of the effects of the medicine, and a special ID card that has to be brought to the pharmacy within a very short window after the monthly blood tests. I’d never seen anything like it, and I’m a doctor. It got me thinking: Why don’t we do this kind of thing for all the medications that cause birth defects? Are we dropping the ball?

The answer, says a recent study published in the journal Pediatrics, is yes.

For the study, researchers looked at 4,172 visits to a large Midwestern academic pediatric center. They found that 1,694 girls ages 14 to 25 got 4,506 prescriptions for Category D or X medications. Category D medications can cause birth defects, but in some cases the benefits outweigh the risks for a pregnant woman; for Category X medications, it’s felt that the risks outweigh the benefits.

There were all sorts of Category D and X medications prescribed, mostly by neurologists, dermatologists, and hematologist-oncologists. The five most common were topiramate, methotrexate, diazepam, isotretinoin, and enalapril. And here’s the scary part:

Less than a third of the girls got a prescription or referral for birth control, or even counseling about birth control.
Less than a quarter were asked questions about sexual activity.
Less than a sixth were asked questions about their period (like when they last got it).

What was particularly interesting was that when girls were in programs like the one my daughter is in, they got asked about sex and periods even less. That certainly is true for us: the dermatologist has yet to ask those questions of my daughter — or even to ask to meet with her alone, which is usually the best way to have a confidential conversation with a teen. I suppose she thinks that the monthly pregnancy test and online quiz is enough — but everybody knows how to lie on an online test, and the idea is to prevent the monthly pregnancy test from becoming positive, not just check to see if it is.

Nobody likes to think about their teen daughter having sex. In general, both parents and doctors do a not-so-great job of talking to girls about sexuality and contraception, despite the fact that by their senior year in high school, roughly two-thirds of U.S. teens have had sex. But what worries me is that many of the girls taking these medications might not fully understand the risks — or might have misconceptions about sex or birth control — and unwittingly cause harm to a baby.

Clearly, we doctors have got to get our act together. We need to be more conscientious, ask the awkward questions, offer the education and birth control. But parents can make a difference, too. Here’s what they can do:

Always ask about all the side effects of any medication your child is prescribed — including whether it causes birth defects.
Make sure your daughter has the facts when it comes to sex and birth control. Yes, it’s important to pass on your values — but be sure she has the information she needs. Whether she needs it at age 15 or 30, she still needs it. Do it on the early side. Better safe than sorry.
Encourage your daughter to meet alone, confidentially, with her health care providers. The most important thing isn’t that you know everything; the most important thing is that your daughter be safe and well.


Thursday, February 2, 2017

Drug combination effective against chikungunya arthritis in mice


Combining a drug for rheumatoid arthritis with one that targets the chikungunya virus can eliminate the signs of chikungunya arthritis in mice in the disease's earliest stage, according to researchers at Washington University School of Medicine in St. Louis.

The findings could lead to a drug therapy for the painful, debilitating condition for which there currently is no treatment.

"We found that combining these two drugs could abolish the signs of arthritis in mice during the acute phase," said Deborah Lenschow, MD, PhD, an associate professor of medicine and the study's co-senior author, referring to the phase in the first weeks after infection.

The study is published Feb. 1 in Science Translational Medicine.

Until about a decade ago, chikungunya virus, which is transmitted by mosquitoes, mainly was restricted to East Africa and South Asia. But in recent years the virus has spread around the world. The first case originating in the Western Hemisphere was reported in late 2013, and by the end of 2015, the virus had infected an estimated 1.8 million people in the Americas.

Chikungunya infection causes fever and severe joint pain, as well as rash, muscle pain and fatigue. The majority of patients continue to experience joint pain six months after infection, and for some, the arthritis continues for years.

"We were seeing people at our rheumatology clinic whose signs and symptoms really mimicked rheumatoid arthritis but who had been infected with chikungunya," Lenschow said. "This raised the question in our minds, 'Would therapeutics we use to treat rheumatoid arthritis be of any benefit to patients with chikungunya arthritis?'"

To find out, Lenschow, co-senior author Michael Diamond, MD, PhD, and colleagues tested a panel of six rheumatoid arthritis drugs - all approved by the Food and Drug Administration for use in patients - on mice infected with chikungunya virus.

All six drugs work by suppressing the activity of the immune system. Although different in many ways, rheumatoid arthritis and chikungunya arthritis both involve out-of-control immune activity in the joints.

The researchers injected seven groups of mice with the virus and three days later administered one of the six arthritis drugs or a placebo to each group of mice. A week after infection - when the mice's arthritis signs were at their peak - the researchers measured the amount of swelling around the joints as well as the numbers of immune cells and molecules in the affected areas.

Two of the drugs - abatacept and tofacitinib - significantly reduced the swelling and the levels of immune cells and molecules. Importantly, the levels of live virus did not increase in the animals given the immunosuppressive arthritis drugs.

"There was a significant concern that administering any immunosuppressive drug would allow the virus to escape from immune control, leading to worse outcomes in the long term," said Diamond, the Herbert S. Gasser Professor of Medicine. "We've seen that with other viruses, but in this case, none of the drugs seemed to exacerbate viral replication. This raises the possibility that these drugs can be safely investigated in humans."

The treatment was only partially successful at resolving the arthritis, however, which led the researchers to test whether adding a human antibody against chikungunya virus could improve the effectiveness.

As before, the researchers infected mice with the virus and three days later dosed them with the arthritis drug abatacept, the antiviral drug or both. Each drug individually reduced joint swelling a week after infection. But when abatacept and the antiviral drug were used together, the joint swelling and the infectious virus in the animals' joints were eliminated.

"We saw real improvement in the acute phase, but unfortunately, the drug interventions we tried failed to correct the chronic phase," Diamond said.

In humans, the chronic phase of chikungunya arthritis starts three weeks after initial infection and lasts as long as the patient continues to experience joint pain, which can be three or four years. During the chronic phase, infectious virus is no longer detectable in the joints, but viral genetic material persists and may be sufficient to trigger an ongoing immune response, causing the tissue damage that patients perceive as arthritis.

The researchers found a similar pattern in the mice treated with the drug combination: By four weeks after infection, live virus was no longer present in the animals' joints, but viral genetic material remained, suggesting that the drugs had not eliminated the chronic phase of the disease.

It is possible that a treatment that reduces arthritis symptoms in the first weeks after infection could lower the chance that the disease becomes chronic, but no data has yet been published for or against the possibility. Still, any effective treatment, even if short-lived, would be a boon for chikungunya patients, who currently have no proven treatment options. Lenschow has discussed beginning a human study with colleagues in Brazil, but plans are not yet finalized.

"In those first weeks, people are really very sick with a high fever and a lot of pain, so if further studies show that this combination treatment is effective in humans, that will have real benefits for patients," Diamond said. "As for the chronic phase, we're going to continue looking for other treatment strategies."