Friday, 8 February 2019

Good news about the HPV vaccine

In 2015, the opioid crisis was escalating to emergency-level proportions, claiming as many lives as car accidents. As the daughter of a longtime drug addict, the current burgeoning opioid epidemic managed to be both familiar and strange to me at the same time. My mother developed her addictions during the height of drug epidemics that occurred in New York City in the mid-1980s. The timeframe also marked the infancy of the AIDS crisis and the height of Reagan-era “Just Say No” programs. Back then, addiction was treated and viewed more as a crime than a disease, supposedly committed by scoundrels and misfits. The theory held that respectable people did not associate with addicts, much less share their homes and their blood with them.

The intense societal shaming and criminalization of her addictions led to more resistance by my mother to seek the treatment she needed, until she eventually stopped trying to quit altogether. The stigmatization of her disease impacted me profoundly as a child — almost as much as the regular abuses I endured from her due to her addictive behavior. Whether it was being the regular target of smacking, lying, spitting, stealing, or vicious name-calling, it stung all the more because society made me feel complicit by relation. I had no healthy outlet to vent my escalating outrage at my own victimization, at an age when I was too young to properly process or even fully understand what was happening. I learned to stay silent, to repress my feelings, and to isolate myself, so as not to mistakenly disclose our family secret and be swept away into the foster care system, potentially separated forever from my younger brother.

Nowadays, when I see the constant commercials and articles offering support and compassion to those suffering from opioid addiction, I am struck by ambivalence. While I feel both heartened and relieved that addiction is finally being treated as a disease for which such supports can exist, I am also embittered that it did not happen when I needed it. I am angry that the shift in dialogue around addiction — and the companion funding being offered for programs that stress rehabilitation over incarceration for those afflicted — is likely due to the demographic differences in race, class, and regional areas impacted by this epidemic as opposed to the epidemic that claimed my mother. My family was poor, undereducated, and hailed from a low-income inner-city neighborhood where most residents were not white. Thus, we were ignored.

As noted by the National Survey on Drug Use and Health, 75% of all opioid misuse starts with people using medication that wasn’t prescribed for them. Furthermore, 90% of all addictions begin either in adolescence or early adulthood, while most of those who misuse opioids already have a prior history of abusing alcohol and other drugs. In my mother’s case, she began experimenting with cocaine first before jumping to injecting heroin in her mid-twenties; there was no prescription medication involved. My uncle (who was also my godfather) died of an overdose of Xanax (which is a benzodiazepine, not an opioid) after mixing it with too much alcohol. My brother became addicted to my mother’s prescription Dilaudid (a class of opioid) while she was in the late stages of terminal cancer; this occurred in his mid-twenties, after he had struggled for more than a decade with alcoholism.

I personally decided to opt out of using opioids for long-term management of my own pain symptoms because I did not want to risk becoming addicted, considering my own substantial family history and potential genetic predisposition to the disease. However, I understand my decision is a personal one and not something I can or should expect of other people who live with chronic pain. For some patients, long-term opioid treatment can provide adequate pain relief without detracting from their quality of life, but for others it can do more harm over time.

When I hear of people with pain being shamed and stigmatized for trying to fill prescriptions for medications many of them have been using responsibly for years and even decades, it reminds me of the same shame that was thrust onto my mother and family, while we were also deprived of comprehensive and humane treatment for, and even genuine acknowledgement of, our disease. I hope the medical field will work to adopt more nuanced and individualized approaches to treating both pain and addiction that do not cater to one demographic at the expense of the other.
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. In the late 1980s, psychologist James Pennebaker developed a form of writing therapy called expressive writing. When you engage in expressive writing, you write about your deepest thoughts and feelings without concern for spelling, grammar, or sentence construction. It is free-flowing and unfocused self-expression.

Although not everybody benefits from expressive writing, recent studies have shown that expressive writing helps anxious individuals perform better on tests. We’re not sure exactly why this is, but one leading theory is that writing about test anxiety “offloads” worrisome thoughts, thereby freeing up mental resources to concentrate on the test.

While this theory is appealing, more data was needed to substantiate it. That’s what psychology graduate student Hans S. Schroder and his colleagues set out to explore. Their study involved people who had been preoccupied by worry for a long time. The team looked for brain wave changes as a result of expressive writing to see how the writing was helping, if at all.
Worried people and their brain waves

Your brain is constantly creating electrical signals. You can see these signals when you place electrodes on the scalp and connect them to a monitoring device called an electroencephalogram (EEG). They look like waves. Every time you encounter any stimulus or event (e.g., a frightening sound, an unusual thought, or a reason to move), these brain waves change. And you can see this response on the EEG as well.

One important type of brain wave is a sharp negative (downward) signal that occurs when you make an error, even if you are not aware of it. And in people who worry, this negative signal is much larger. The larger signal reflects the compensatory effort that anxious people need to make when tuning out distracting worries. This extra effort uses thinking resources that could otherwise be better used to focus on other activities, for example answering test questions.

If expressive writing frees up mental resources, we would expect the negative signal to be reduced, as there would be fewer distracting worries stored in the brain.
The experiment: brain waves, worry, and writing

Schroder and his colleagues conducted an experiment on 44 female students from a midwestern university. They chose females because prior studies had shown that women in particular show the exaggerated negative signal when they worry. Also, women in general have more anxious apprehension than men.

One group of participants was asked to engage in expressive writing about their worries, while the comparison group was asked to engage in writing unrelated to their worries. Then they were also given a computer task designed to elicit the negative-signal brainwaves.
How expressive writing changes the brain waves of worriers

Compared to writing about things other than one’s worries, expressive writing about one’s worries did in fact reduce the size of the negative brain wave signal in people who worried a lot. This implied that “offloading” your worries into free-form writing frees up mental resources that you can then use to complete tasks more easily.

What can you do if you worry a lot? Based on this study, expressive writing about your worries will help you become less distracted, thereby making your brain less reactive and more focused. It is this unfocused activity — free-flowing writing that documents whatever comes to mind without concern for technical errors — that will help your brain become more focused, thereby allowing you to complete tasks more successfully. In fact, many other forms of unfocus can help you focus more easily too.

So, before you have to concentrate on anything, spend eight to 10 minutes writing out your worries. When you do, your worry is less likely to get in your way, and you will likely complete tasks more easily, with your worries out of your brain and on the task at hand instead. 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). Did you know certain viruses can cause cancer? Two common examples include hepatitis C (which is linked with liver cancer) and human papilloma virus (HPV, which causes cervical cancer). The discovery of these virus-cancer connections is particularly important, because if a vaccine can prevent these viral infections it may also prevent cancer. And there is preliminary evidence that the HPV vaccine is making this happen. More on that in a moment.
What is HPV?

HPV is a group of viruses that may cause warts (papillomas) and a variety of cancers, including those involving the throat, rectum, penis, and cervix. HPV can spread between people by skin-to-skin contact, mostly during sexual activity. There may be no symptoms or signs of any illness at the time you get it. In some people, it sticks around and causes trouble years or decades later. HPV infection is quite common: an estimated 80 million people in the US are currently infected.
The HPV vaccine

Most people are exposed to HPV at some point in their lives through sexual activity. That’s why the vaccine is routinely recommended for teenagers, to protect them before they become sexually active. Specifically, the vaccine is recommended for:

    kids (girls and boys), ages 11 to 12
    women through age 26 and men through age 21 if they did not receive it earlier
    men who have sex with men (or intend to) through age 26
    transgender adults through age 26
    young adults with diseases that suppress the immune system (such as HIV) through age 26.

Does the HPV vaccine work?

Past studies have demonstrated that the HPV vaccine is highly effective, with protection rates of 97% or higher for the strains covered. And it’s estimated that with widespread vaccination, more than 90% of the 31,000 HPV-related cases of cancer that occur each year in women and men could be prevented. Studies have already shown a drop in precancerous abnormalities in the Pap smears of women in recent years, as well as a reduction in genital warts among young adults.
More good news

A recent study reports some impressive trends in the years since HPV vaccinations began:

    Between 2009 and 2015, HPV infections among women 18 to 59 fell by 32%; and the drop in infection rates was most dramatic (65%) among women 18 to 26.
    And… rates of HPV infection fell even among women who were not vaccinated. Among unvaccinated women 18 to 26, HPV infections fell by 50% (from nearly 20% to about 10%).
    Rates of other sexually transmitted diseases (such as gonorrhea and herpes) did not fall during the years of this study, so the use of condoms or other changes in sexual practices were considered unlikely causes of the drop in HPV.

It may seem strange that unvaccinated women experienced fewer HPV infections since approval of the vaccine. The likely explanation is “herd immunity.” When an infection becomes less common in a population, there is less opportunity for that infection to spread; when the drop is significant enough, even unvaccinated people benefit.
Room for improvement

Recent estimates suggest that only 60% of children are being vaccinated for HPV as recommended, and the rate is much lower for boys than girls. As with any new vaccine, it takes time for widespread acceptance, but as more studies (like this one) demonstrating effectiveness and longer-term studies of safety are published, vaccination rates are expected to increase. If they do, the impact on cancer prevention should be even greater than found in this recent study. This includes not only cervical cancer, but other cancers in men and women (such as those involving the throat and rectum) linked to HPV.
The news may get even better

It can take decades for cancer to develop among people with HPV infection. Since the vaccine has only been available for about 10 years, we won’t know for a while just how helpful it is at preventing infections and the cancers to which they are linked. So, stand by. The full benefits of HPV vaccination aren’t yet known. Of course, future research will also be needed on any potential risks of HPV vaccination that have not yet been recognized. So far, the news has been good, and likely will keep getting better.

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