Wednesday, April 10, 2019

Taking new aim at cancer in the body

My 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.
We moms tend to worry about our kids a fair amount, and think up ways to help them, even when they’re older. Case in point: I’m itching to tell my college-age son Chris about my latest helpful-because-I-care idea. It stems from an incident last year where Chris had the flu and wound up going to the local emergency room because the university clinic had a two-day wait. This year, I’m going to arm Chris with a back-up: retail health clinics.

Retail health clinics are part of the big trend to make health care more convenient. “Twenty years ago you had to go to an emergency department if you got sick and needed immediate care. Now we have an explosion of options, such as retail health clinics,” says Dr. Ateev Mehrotra, a researcher on the topic and an associate professor of health care policy at Harvard Medical School.
The clinics

Retail health clinics began showing up 15 years ago. Today, there are about 2,000 clinics across the United States, located mostly in drugstores, supermarkets, “big box” stores, and other large retail chain settings. The clinics are usually open from 7 a.m. to 7 p.m., seven days a week, and they’re staffed by a nurse practitioner or a physician assistant. They offer all kinds of health services: everything from treating minor illnesses like colds, pinkeye, and urinary tract infections, to complete physicals (including lab work and screenings), to vaccinations and even help with smoking cessation.
The pros

Retail health clinics have many perks. They’re easy to get into, with extended hours and no appointments necessary.

They have set prices for each service, which you can see in advance on their website. For example, a wellness visit is $59 at Walmart. A cholesterol screening at CVS is $59 to $69. “We have found in our data that clinics are 30% to 40% cheaper than a doctor’s office visit, and 80% cheaper than an emergency room visit,” says Dr. Mehrotra. The clinics also take private insurance and Medicare.

But does the lower price translate into poorer-quality care? “We’ve found that the quality of care at retail clinics is equal to or superior to some doctor’s offices, because the clinics are more likely to follow national guidelines of care,” says Dr. Mehrotra.
The cons

Despite all the perks, retail health clinics may not be right for everyone. “Health care is different for older adults. The care you’ll need for even a simple problem might be more complicated. For example, a urinary tract infection will affect an older woman much differently than a younger woman, putting the older woman at risk for dehydration, confusion, falls, and even sepsis,” says Dr. Mehrotra. And if you have a chronic health condition, a simple illness might signal something bigger that might only be caught by a clinician who sees you regularly, such as your primary care doctor.

Geriatrician Dr. Suzanne Salamon, an assistant professor at Harvard Medical School, is concerned that the details of a patient’s visit to a retail health clinic might not be sent to her. Although clinics offer this service, not everyone takes them up on it. “The risk with that is, scattered care from multiple places can lead to mix-ups,” says Dr. Salamon. “And if people don’t bring their complete medication lists to a clinic, the clinic may prescribe something that will interact with medications they’re taking.”
What you should do

A report from the American College of Physicians published recently in Annals of Internal Medicine maintains that retail clinics are fine for a short-term illness or as a back-up when you can’t see your doctor. But they should not replace a long-term relationship with a primary care physician. “Going to a retail clinic is fine for minor issues like a flu shot or a sore throat, particularly if you’re generally healthy,” says Dr. Mehrotra.

That means a retail health clinic would be a great option for my son Chris, or for anyone who’s generally healthy and needs to see a health care professional right away. But there are still a few things to keep in mind if you do visit a retail health clinic, even for a flu shot:

    Bring a complete list of your medications with you.
    Tell the clinician about your medical history and any other health conditions you have.
    Ask the clinic to send details of the visit to your doctor.
    Consider a follow-up appointment with your doctor when you have time, so that everyone is on the same page when it comes to keeping you healthy.

Follow that advice, and you’ll likely give yourself, your doctor, and even good ol’ Mom a little peace of mind. Right, Chris?  By the second half of the 20th century, hospital birth had become the norm in most Western countries. Hospital birth offers monitoring and interventions, many of which saved the lives of mothers and babies. At the same time, births became increasingly — and some would say unnecessarily — medicalized.

Many would also argue that the pendulum of intervention has swung too far. For example, from 1970 to 2010, the rate of U.S. cesarean delivery doubled — but (although both are low) the risk of a baby dying during the course of delivery remained unchanged, and the risk of a mother’s dying slightly rose. In an effort to avoid seemingly unnecessary intervention, and seeking an alternative to the environment of the hospital ward, it is not surprising that some women have turned again to home birth.
Is home birth safe?

We don’t have the best data to answer this question. The ideal way to answer would be a randomized controlled trial. But the randomized part (the place for delivery would essentially have to be decided by the flip of a coin) would be unacceptable to most women. So instead, women and their doctors have had to rely on after-the-fact analyses of large administrative data sets (e.g., information recorded on birth certificates).

There are a few problems with this type of analysis.

There may be differences between the women who give birth at home and those who deliver in the hospital that are not accounted for when drawing conclusions. For example, a woman might decide to give birth at home because she doesn’t have access to care, and so might be more likely to experience complications. On the flip side, perhaps the woman who chooses home birth emphasizes a lifestyle intended to avoid health problems and interventions in general (healthy diet, not smoking, etc.). So when evaluating the outcomes of home birth, it is possible that the results are due to factors about the woman herself as much as the place she has her baby. One of the things that make teasing out the data so difficult is that until recently, there was no way to distinguish between planned home births and unplanned home births. Unplanned home births may include factors that make home birth look riskier than it may actually be (for example, birth due to unexpected emergencies or among women who have not had access to regular prenatal care). On the other hand, counting complicated deliveries that start at home but can’t be completed there as “hospital births” might hide home birth risk.

Women, and those who care for and about their health, have been in desperate need of better data and analysis.
A unique data set offers some insight

A recent article in The New England Journal of Medicine describes a study in which researchers in Oregon were able to overcome some of these data problems. Oregon birth certificates now record whether a mother planned to give birth at home or in the hospital. The researchers also had access to information about a mother’s health conditions (e.g., diabetes or high blood pressure) that put her at higher risk for problems during labor and birth. For the study, the researchers excluded unplanned home births and included only what seemed to be healthy singleton deliveries (not twins or more).

In their analysis, the risk of a baby’s dying was low in each setting, but higher among the group that intended home delivery: 1.8 per 1,000 for planned in-hospital births as compared with 3.9 per 1,000 for planned out-of-hospital births. Planned out-of-hospital birth was also associated with lower Apgar scores as well as a greater likelihood of a baby having a seizure or needing a ventilator, and of a mother needing a blood transfusion. Yet, planning delivery at home was also associated with lower rates of a baby’s needing admission to an intensive care unit and a lower rate of obstetrical interventions, including the use of medicines or other means to start (induce) or strengthen (augment) labor, forceps or vacuum vaginal delivery, or cesarean delivery, and severe tears of the vagina.
What does this mean for women and their doctors?

These results are consistent with those from other studies and make sense to me, as they will to many obstetricians. Sometimes emergencies happen, and having the tools, medicines, and facilities to respond quickly can make a difference. But having all those things at hand means they will also be used in cases in which doing nothing would have been just fine.

It is important to recognize that while the risk for problems for babies was “higher” in the home birth group, it’s not “high” in either group. The difference judged in absolute terms was on the order of 0.5 to 2 newborn deaths per 1,000 births. This risk is similar to other accepted options in obstetrical care, such as a trial of labor after past cesarean delivery. The home birth group had lower rates of cesarean delivery and other complications that can affect a mother’s health.

The risks to consider for each option are very different, but this data can help women make choices based on what they value most.

Finally, roughly 15% of women planning home birth will require transfer to the hospital. Keep in mind that right now, there are no U.S. national standards for integrating home birth into a continuum of care. There are no agreed-upon criteria to help identify good candidates for home birth, nor are there standards to ensure adequate training of those attending home births. We need those systems and criteria before the U.S. should consider matching the recent call in Britain to encourage and support home birth. You may have heard that former President Jimmy Carter’s melanoma, which had previously metastasized to his brain, has vanished. This news has cast light on a type of cancer treatment called immunotherapy, which helps the body’s own immune system fight cancer cells.

The drug used for President Carter, pembrolizumab (Keytruda), is designed to block a cellular pathway known as PD-1, which hinders the immune system’s ability to attack melanoma cells. It was approved last year by the FDA and, so far, has proven to be successful in melanoma and other cancers. In clinical trials, tumors shrank in more than 30% of people who received the drug.

President Carter also received radiation as part of his treatment (along with surgery to remove cancer that had spread to his liver). So it is difficult to say if pembrolizumab alone wiped out the tumors in his brain, or if it was the combination of the two treatments, says Dr. Patrick Ott, clinical director of both the Melanoma Center and the Center for Immuno-Oncology at Harvard-affiliated Dana-Farber Cancer Institute. Though pembrolizumab has been tested for treating melanoma, it has not yet been formally studied for the treatment of melanoma that has metastasized to the brain.

“Melanoma in the brain is the hardest to treat. Most cancer drugs do not work in the brain to the same extent as other parts of the body because the brain has a barrier that prevents drugs from reaching it. So in this way, this type of treatment is quite promising,” says Dr. Ott.
The pros and cons of targeted therapies

Immunotherapy is often included in a group of cancer treatments called targeted therapy. These treatments work in different ways to either block a tumor’s blood supply, kill cancer cells directly, trigger the cancer cell death process, or, as in the case of immunotherapy, boost your immune system to attack cancer cells.

The kind of drug a person gets depends on his or her individual cancer and its stage (how far it has spread). Treatment is often given one to two times a day for three months to a year.

Targeted therapy has advantages over chemotherapy. For example, chemotherapy attacks cancer cells, but also damages nearby healthy cells in the process. It is like hosing down a large area of a yard just to water a tree.

In comparison, targeted therapy focuses on the cancer cells’ inner workings — the programming that sets them apart from normal cells. This way, surrounding healthy cells are often spared, and the result is more attention given to the cancer cells, with less severe side effects.

Targeted therapies do have their limits. For one, they do not work for everyone, or for every kind of cancer. For instance, right now, only about 10% of people with lung cancer are candidates for targeted therapy. This is because current targeted therapy focuses on a mutation that is found in only 10% of lung cancers.

Cancer cells also can become resistant to targeted therapy, either because the original target changes through mutation, the tumor finds a new pathway to grow, or both. “This is why therapies often work best in combination — either with other targeted therapies or one or more traditional chemotherapy drugs,” says Dr. Bruce Johnson, professor of medicine at Harvard Medical School.

Still, these targeted therapies may offer better options for certain cancer patients. “These are not miracle treatments,” says Dr. Ott. “But they can have good outcomes in the right situation.”

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