Monday, 4 February 2019

Genetic testing to predict medication side effects

Lately, I’ve been checking the number of steps I take each day. It’s not hard to do. My phone tracks it without me even asking it to. It also tracks the number of flights of stairs I’ve climbed and the number of miles I covered. And there are other options: I could track how often I stand up, how many calories I’ve burned by being active, and how many minutes I’ve engaged in brisk activity.

Even my employer has gotten into the act. As is common in many workplaces, one of our hospital’s wellness programs has organized “walking clubs” with teams comparing and competing with each other based on the number of steps team members take each week. Some companies offer prizes, financial incentives, or reductions in health insurance premiums if an employee participates in such a program.
Why all this monitoring?

Technology we carry around with us — our phones, watches, or other gadgets — allows enormous amounts of data to be collected about us every day. It’s important to keep in mind that there is a purpose to all of this. The point of activity trackers is to become more aware of how much (or how little) activity we’re doing so that we can make positive changes. Since the health benefits of physical activity — and the health risks of being sedentary — are well established, increasing activity is a health priority (or should be) for millions of people. Activity trackers are the first, um, step (sorry, couldn’t resist).
Do activity trackers really improve health?

My guess is that most people take for granted that activity trackers are helpful in promoting more physical activity, but that’s based mostly on assumption. That’s why researchers at Duke-National University of Singapore Medical School designed a study to compare full-time employees who used activity trackers with those who did not. Each of the 800 employees enrolled in the study paid the equivalent of $7 to enroll and then were randomly assigned to one of four groups for one year:

    use of a Fitbit Zip, a popular clip-on activity tracker (with payment of $3/week to continue in the study regardless of the number of steps taken)
    a Fitbit plus a cash incentive ($11 for taking 50,000 to 70,000 steps each week, or $22 for more than 70,000 steps/week)
    a Fitbit plus a payment to a charity (which was larger with increased activity)
    a control group that did not use an activity tracker; this group also received the $3/week for participation regardless of activity levels.

Researchers monitored more than just the number of steps taken. Study participants also had monitoring of more vigorous exercise and physical activity, weight, blood pressure, fitness levels, and they were asked about quality of life as well.

So, what did they find?
First, the good news

The group receiving the cash incentive increased their daily steps compared to the start of the study. This group was more active than the control group at six months, and 88% of them were still using their Fitbits (compared with about 60% of the Fitbit only and charity incentive groups).
Say it isn’t so!

When incentives stopped, only one in 10 study subjects continued to use the Fitbit. And after a year, with incentives stopped, activity levels fell in the groups receiving an incentive compared to when they started. This is disappointing indeed, especially considering that the participants in this study were probably more motivated than most to focus on their activity levels. They went to the effort and expense of enrolling in the study and agreed to put up with all the monitoring. In addition, most people in the real world probably have no direct financial incentives to maintain a certain level of activity each week.

This study follows another one from the University of Pittsburgh that found less weight loss among young adults who used fitness trackers compared to those who didn’t.
What’s next?

As technology evolves and research provides more information about what works (and what doesn’t), I think we’ll see a new generation of devices that are more customized to individual needs and medical conditions. For example, a person with diabetes might monitor physical activity to provide information about how to coordinate insulin injections and meals.

In addition, activity trackers can do more than simply spit out information about how active you’ve been. A good example comes from another recent study in which activity trackers were incorporated into a competitive game, complete with signed commitments to specific activity goals, an elaborate point system, and reliance on team cooperation and rewards. The study found that those using game-based activity trackers were more active and achieved activity goals more often than those using activity trackers without the game. The study lasted only 12 weeks and improvements waned somewhat after it ended, so the long-term impact of such a program is uncertain.

Physical activity trackers have quickly become a multimillion-dollar product category. I don’t see them going away any time soon. But, to actually get people moving and have a positive impact on health, we’ll probably need to use them in more innovative ways. And if they claim to improve your health, we’ll need high-quality research to back that up. As they get older, do men with prostate cancer come to regret the treatment decisions they made? A new study of men diagnosed during the mid-1990s indicates that some of them will.

Richard Hoffman, a professor of internal medicine and epidemiology at the University of Iowa Carver College of Medicine in Iowa City, led a team that reviewed survey data that men filled out one, two, five, and 15 years after they were treated for prostate cancer. All 934 men included in the study were 75 or younger when diagnosed, each with localized tumors confined to the prostate gland. Approximately 60% of the men had low-risk prostate cancer that was expected to grow slowly, and the others had riskier cancers. Most of the men (89%) were treated with surgery or radiation. The rest were lumped together as having had conservative treatment: either medications to suppress testosterone (a hormone that makes prostate cancer grow faster), or “watchful waiting,” meaning doctors delayed treatment until there was evidence that the cancer was spreading.

Overall, 14.6% of the entire group expressed some treatment regret — 16.6% of the radiation-treated men, 15% of the surgically-treated men, and 8.2% of the men treated conservatively. Among the causes of regret, treatment-related bowel and sexual problems were cited most frequently. Surgically treated men reported the highest rate of significant sexual side effects (39%), while radiation-treated men reported the highest rate of significant bowl problems (15.6%). Remarkably, complaints over urinary incontinence differed little between the groups, ranging from a low of 15.5% for the conservatively-treated men to a high of 17.6% among men treated with radiation.

Results also showed that regret tends to increase with time, suggesting that when initial concerns over surviving prostate cancer wear off, the quality-of-life consequences of treatment become more apparent. Regrets were especially pronounced among men who felt they hadn’t been sufficiently counseled by their doctors before settling on a particular treatment option, and also among men who were preoccupied with changing levels of prostate-specific antigen, a blood test used to monitor cancer’s possible return.

Given these findings, the authors emphasized how important it is that men be counseled adequately and informed of the risks and benefits associated with various treatments. But men should also be reassured that treatment for prostate cancer has improved since the mid-1990s, and that bowel and urinary side effects in particular “don’t occur as frequently now as when the men in this study were diagnosed,” says co-author Peter Albertsen, a professor of surgery and chief of the division of urology at UConn Health in Farmington, Connecticut. Stress accounts for between 60% and 80% of visits to primary care doctors. Chronic stress has been linked to accelerated biological aging, and increased chronic inflammation and oxidative stress, two processes that cause cellular and genetic damage. Scientists refer to chronic, low-grade inflammation in the body as “inflammaging.” Inflammaging has been associated with conditions like diabetes, heart disease, stress, depression, and a weakened immune system.

Several recent studies suggest that yoga could slow the harmful physical effects of stress and inflammaging. There are many different types of biomarkers in the blood that can be used to measure the level of chronic inflammation and stress in the body. Cortisol varies throughout the day based on the circadian rhythm, and a higher baseline level of cortisol is one indicator of high chronic stress. Cortisol becomes less variable throughout the day in people who are chronically stressed, signaling an overactive fight-or-flight or sympathetic nervous system. Another biomarker is brain derived neurotrophic factor (BDNF), a naturally occurring protein in the body that regulates neuroplasticity and promotes brain development. People who have depression, anxiety, or Alzheimer’s disease have been found to have lower levels of BDNF.
Studying yoga’s effects on stress

In an exploratory study published in Oxidative Medicine and Cellular Longevity, researchers found that 12 weeks of yoga slowed cellular aging. The program consisted of 90 minutes of yoga that included physical postures, breathing, and meditation five days a week over 12 weeks. Researchers found indications of lower levels of inflammation and significantly decreased levels of cortisol. The study also found higher levels of BDNF after the yoga program, suggesting that yoga could have potential protective effects for the brain as well.

In another recent study published in Frontiers in Human Neuroscience, researchers found that a three-month yoga retreat reduced inflammation and stress in the body. The yoga retreat incorporated physical postures, controlled breathing practices, and seated meditations. Participants did two hours of sitting meditation, one to two hours of moving practice, and one hour of chanting daily. Levels of protective anti-inflammatory markers increased after the retreat, while harmful pro-inflammatory markers decreased. Researchers also found that BDNF levels tripled. Participants felt less depressed, less anxious, and had fewer physical symptoms.

These studies suggest that yoga could slow down the harmful effects of chronic stress at both the psychological and physical levels. It also indicates the benefits of a yoga practice that incorporates more than just poses by including yoga breathing and meditation or deep relaxation.

There are many simple yoga breathing (pranayama) techniques that can lower your stress levels that you can do at home for as little as a few minutes a day. Yoga breathing types can be calming or activating, depending on the type. One example of a calming yoga breath is alternate nostril breathing. You can practice it for as little as one to two minutes at home.  If you want to stop your child from being bullied — or better yet, prevent it in the first place — there is a very simple thing you can do: talk to your child.

I don’t so much mean talk to your child about standing up to bullies, or about letting a teacher know if they see or experience bullying, although both of those are important messages for your child to hear. I mean literally just talk to your child, so that you can better get to know him or her — and better get to know what their daily life is like.

As parents, we like to think that we know this already. But the reality is that once our children head off to school we don’t know everything about them. We don’t know what all of their interactions with others are like; we don’t know all the details, such as who they sit with at lunch, what happens in the locker room, or what happens when they get on the bus.

That’s where the talking comes in. According to stopbullying.gov, talking to your child for 15 minutes a day can make all the difference when it comes to helping keep them safe from bullying.

As any parent will attest, talking with our children doesn’t always go the way we think or hope it will. The answers to “How was your day?” or “What did you do today?” tend to be “Fine” and “Nothing,” neither of which are conversation starters. In general, our interactions often tend to be logistical and closed-ended, like “Did you get your homework done?” or “What time does practice end?”

The conversations that make a difference are more open-ended ones. “Tell me about your day,” for example, or “Did anything good happen today? Anything bad?” Asking open-ended questions about teachers, classes, the lunchroom, sports teams, and any other parts of your child’s life can get conversations started. You can and should ask follow-up questions, but as much as you can, try not to be interrogatory. The more you let your child tell you things the way they want to, the more you keep it comfortable and build trust, both of which are crucial. “Tell me more about that” and “What happened next?” are good ways to keep your child talking.

Because, really, that’s what you want to do. You want to keep the lines of communication open, and make it clear to your child that you are interested in the details of his daily life and that you care about what makes him happy, angry, or sad. By talking for 15 minutes a day, you can learn a lot — including about bullying or circumstances that might lead to bullying.

Those 15-minute conversations can help you help your child navigate difficult situations and help you troubleshoot and problem-solve together. They can also help you understand better what your child enjoys, which helps you guide him toward people and activities that can bolster his self-esteem and build friendships — and can help you understand who the important people are in his life, so you can get to know them better.

Our lives are busy, but 15 minutes aren’t hard to find. Eat dinner together (cook together, too) or have an afternoon snack together. Talk during car rides. Hang out on the couch before bedtime. Shut off the devices and concentrate on each other instead. It truly can make all the difference, in so many ways.

To learn more about who is at risk for bullying, warning signs that your child is being bullied (or is a bully), and what you can do, check out all the really helpful information on stopbullying.gov, and learn more about KnowBullying, a free smartphone app for parents and caregivers. Medication side effects are a big problem. It’s estimated that about half of filled prescriptions are not taken as directed, and a major reason for this is side effects. If you’ve ever had diarrhea, felt sleepy, or developed a rash after taking a new medication, you know how unpleasant side effects can be. And sometimes it’s much worse than unpleasant: drug side effects can cause permanent damage and even be deadly.
Predicting success… and side effects

Wouldn’t it be great if your doctor could predict which medication is most likely to work for you and least likely to cause side effects? Pharmacogenetics — the use of genetic information to predict the risks and benefits of a medication — could do just that. The idea is that your genes may provide helpful clues regarding which medication is best in your particular case. There are already examples of this, such as:

    Azathioprine: this is an immune-suppressing medication that some people have trouble metabolizing due to the genes they inherited; a blood test prior to the start of treatment can identify those most at risk.
    Allopurinol: certain ethnic groups (e.g., those of Han Chinese or Thai extraction) are more likely to carry a gene that increases the risk of a severe allergic reaction to allopurinol, a medication primarily used to treat gout.

While these examples deal with medication risks, individual genetic testing may also be able to identify which medications are most likely to help a person based on their genes.
A new study looks at statins

Statin drugs are among the most widely prescribed medications in the world. They lower cholesterol, reduce inflammation, and have been proven to reduce the risk of heart attack and stroke in those at high risk for these conditions. However, a limiting side effect is muscle pain, an annoying symptom that may require discontinuation of the drug. (A more serious muscle disease may develop, especially when statins are combined with other drugs, but fortunately these more serious reactions are rare.) As there are several formulations of statin drugs, for any given person one statin drug might cause trouble while another might not. These variations might also be determined, at least in part, on that person’s genes.

Prior research has suggested that people who carry certain genes are more likely to develop muscle pain when taking statins, and certain statins might cause more trouble than others for people with a higher-risk gene. These genes direct the synthesis of a protein involved in transporting drugs into liver cells.

A new study enrolled 159 people who had previously developed muscle pain when taking a statin to determine whether sharing the results of their genetic tests could be helpful in choosing a statin drug that would not cause muscle pain.

The researchers divided study subjects into two groups:

    One group was provided with the results of their genetic testing. If a high-risk gene was found, they were offered a statin considered to be less risky; for those without the high-risk gene, the group was offered any of several statins.
    The other group (the “usual care” group) wasn’t told their genetic test results until the study was completed. For this group, decisions regarding statin choice were based on “standard guidance regarding statin selection and dosing.”

In the first three months, nearly 60% of those in the first group decided to take a statin; only a third of those in the other group did so. As a result, within eight months cholesterol levels tended to be better in those receiving their genetic test results. The impact of this approach could be large, as all of the study subjects had previously stopped statin medications due to side effects.
Is it in the genes… or the “nocebo effect”?

One interesting aspect of this study is that the “nocebo effect” could have been responsible for at least some of the study subjects’ past side effects. The nocebo effect is a phenomenon in which the expectation of a side effect makes it more likely to occur, similar to how the expectation of benefit may make a placebo more likely to work. People who had previously had muscle pain with a particular statin might have the expectation of recurrence with any statin, but armed with genetic information that might help reduce risk, that expectation of trouble might be lessened. Genetic testing could lead to fewer side effects, not only by directing the choice of medications but also through a reduction in the nocebo effect.
We’re not there yet

Here’s the part where I’m obligated to mention the limitations of using genetic testing to direct drug treatment. First, in most cases, prediction isn’t perfect. Some people with a high-risk gene are fine when they take the medication; similarly, those lacking the high-risk gene can still react badly to the drug. One reason for this is that the benefits and risks of drugs are rarely determined by a single gene and many other factors matter, such as other medications taken and other medical problems. Another concern is cost. Many genetic tests are costly and it’s often unclear whether the benefits (which may be modest) are worth the expense. It’s possible that as genetic testing becomes more common and extensive, costs will come down; and as more genes are studied, the benefits of testing may become clearer (and, hopefully, more robust).

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