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Wednesday, April 10, 2019

Benefits men with locally advanced prostate cancer

When I talk to parents who are hesitant about vaccines, what they most want to talk to me about are possible side effects of the vaccine. They worry about everything from fevers and soreness to additives to possible links to autism. They rarely worry about the diseases that vaccines prevent—and that’s what worries me most of all.

It is the inconvenient truth of vaccine refusal: when you don’t get vaccinated against an illness, you are more likely to catch it.

A study just released in the Journal of the American Medical Association (JAMA) makes this very clear. Researchers looked at information about recent measles and pertussis outbreaks. They found that unvaccinated people made up the majority of those who caught measles and a large proportion of those who caught pertussis (waning immunity from the pertussis vaccine plays a role in those outbreaks). Some weren’t old enough to be vaccinated—but of those who were old enough, most came from families who had chosen not to vaccinate.

We developed vaccines for a reason: to stop children from getting sick and dying. This was not a money-making stunt by drug companies, as some claim. Here in the United States, vaccines have done such a great job that we have literally forgotten about the ravages of measles, polio, pertussis, diphtheria, and the many other illnesses that we can now prevent.

They truly were ravages. Who even remembers diphtheria? Between 1936 and 1945, there were about 21,000 cases and 1,800 deaths a year of diphtheria. In those same years, paralytic polio affected 16,000 and killed 1,900 each year. And for measles and pertussis, the numbers are even higher. Every year 530,000 people caught measles and 440 people died from it; 200,000 caught pertussis and 4,000 died from it.

Four thousand died every year from pertussis. In 2014, that number was 13. We simply cannot ignore that vaccines are incredibly effective, and save thousands and thousands of lives.

It’s the scarcity of the illnesses that has made some parents comfortable with the decision not to vaccinate. If you are unlikely to run into anyone with measles or chickenpox, why take any chances with side effects?

There are two problems with that argument. First, as more people have chosen not to vaccinate, there have been more outbreaks. And when those who choose not to vaccinate live in the same communities, as a study out of Kaiser Permanente showed was the case in California, it can create the perfect environment for a vaccine-preventable germ to spread.

Second, we live in a global community. Travel is relatively easy, and lots of people do it. And while we may have done a great job eradicating vaccine-preventable diseases here in the U.S., they certainly haven’t been eradicated from the world. Diphtheria is still alive and well, affecting 50,000 people a year and killing half of them. There are 344,000 cases of measles—and 145,000 deaths from it. For pertussis, the numbers are even higher: 30-50 million cases, and 300,000 deaths.

People are often contagious before they even know they are sick. Someone could bring measles to a community without knowing it—and 90% of the unvaccinated people who are exposed to the measles virus will get sick (the virus can even hang out in a room for two hours after the person with measles leaves). Half of the babies who catch pertussis end up hospitalized—and of those who are hospitalized, three out of five have trouble breathing, and one in 100 die despite the best possible care.

We just can’t say that it’s safe to be unvaccinated. It’s not safe for the child whose parents choose not to vaccinate—and it’s really not safe for the infants or people with immune problems who cannot be vaccinated, who need vaccinated people around them to keep them well.

Vaccines are a medical treatment, and like any medical treatment, they can have risks and side effects. So much has been done, and is still being done, to make vaccines as safe as possible. It’s always important to ask questions and be careful in making decisions.

But when making those decisions, it’s crucial to think not just about the vaccine—but about the disease it can protect you from. A new study has shed light on one of the long-term effects of proton pump inhibitors (PPIs). These drugs are commonly used to treat gastroesophageal reflux disease (GERD), heartburn, and peptic ulcers. PPIs (omeprazole, lansoprazole, esomeprazole, pantoprazole, and others) help reduce the amount of stomach acid made by glands in the lining of the stomach.

Research published online on February 15 in JAMA Neurology showed that there may be an association between chronic use of PPIs and an increased risk of dementia. Experts compared prescription PPI intake and diagnosis of dementia among approximately 74,000 adults ages 75 and older. In the study, chronic PPI use was defined as at least one prescription every three months in an 18-month window. The most common PPIs in use were omeprazole (Prilosec), pantoprazole (Protonix), and esomeprazole (Nexium). All participants were free of dementia at the study’s beginning. Yet, after the eight-year follow-up, chronic PPI users had a 44% increased risk of dementia compared with those who did not take any medication. Men were at a slightly higher risk than women. Occasional users of PPIs had a much lower risk.
Putting the results in perspective

The researchers were quick to stress that this study only provided a statistical association between PPI use and risk of dementia, and that taking PPIs does not automatically mean you will get dementia. However, the study continues the ongoing discussion about the impact of long-term medication use, according to Dr. Houman Javedan, clinical director of inpatient geriatrics at Harvard-affiliated Brigham and Women’s Hospital. “Older adults take more medications as they age, and often continue them long after they are still necessary,” he says. “They either get used to taking it, and do not think to ask their doctor if they should stop, or they are afraid of what might happen if they do.”

Many older adults also take multiple drugs at one time, a situation known as polypharmacy. In fact, an estimated 44% of men and 57% of women older than age 65 take five or more medications; 12% of both men and women in this age group take 10 or more. “How different drugs interact with each other, and what the consequences of long-term use are, continues to be explored by scientists, as the researchers tried to do in this case with PPIs,” says Dr. Javedan.

It is not clear how PPIs might make a person more vulnerable to dementia. Evidence suggests parts of the drug may cross the blood–brain barrier, which becomes more porous as a person ages, and interact with brain enzymes. In initial animal studies, PPIs were shown to increase levels of beta amyloid in the brains of mice, and higher amounts of this protein have been linked to dementia and Alzheimer’s disease. Other research has shown a possible connection between chronic PPI use and vitamin B12 deficiencies, as well as an increased risk of osteoporosis. “There still may be other mechanisms at work that are unknown,” says Dr. Javedan. “But this study raises the question whether chronic PPI usage is safe, especially among the older population.”
What you should do if you take PPIs

If you currently take PPIs every day, or have for more than 18 months, you should consult with your doctor about whether to continue at your current dosage, Dr. Javedan suggests. “You only may need it when you have symptoms and not endlessly.” I take care of adults in primary care and I treat addictions. So when I was sent a journal article titled “Daily Physical Activity and Alcohol Use Across the Adult Lifespan,” it piqued my interest. This paper describes the drinking and exercise habits of 150 largely white, low-risk, community-dwelling adults (meaning it didn’t include people who were in the hospital or a nursing home) in central Pennsylvania. In this study, volunteers used a smartphone to record their daily drinking and exercise habits in 3-week blocks. This smartphone technique made it possible to get good information and to analyze daily variations for each individual. What is clear from the analysis is that people tend to drink more alcohol on days when they exercise more. This is true whether they’re young, old, male, or female.

This is not a study of problem drinkers or risky drinkers, nor of people with alcohol use disorders (what we used to call alcohol abuse or alcohol dependence). This is also not a study of the effect of an intervention to change lifestyle behavior. That is to say, this study does not tell me what happens if I advise a patient to exercise more or to drink less. The study also does not suggest that if you decide to exercise more, it’s likely you will drink more. It is solely an observational study, not a study of change over time.

These are healthy people in general. The mode and median number of drinks per day was zero. That is to say, among this group, there was no drinking at all on half or more of the days recorded. So the results may have been different in a different population (for instance, a more economically challenged or urban population). The results of a similar study, I expect, would be different were it conducted among a high-risk group; for example, people working to drink less or exercise more might engage in a “virtuous cycle” whereby the enjoyment of a sense of more energy, less fatigue, or better physical strength would provide the power to make further healthy choices. Increased exercise might be linked to decreased drinking in this kind of population.
The challenge of making — and keeping — healthy lifestyle changes

What I’ve observed in my practice is that significant changes in health-related behaviors travel in packs: people who adopt healthier drinking habits (for instance, reducing their intake to one drink per day if female or two per day if male, on average) also get off the couch, walk more, lose a pound or two, and generally pay more attention to their health. The challenge for them — and me — is to sustain these healthy changes.

There is a lot of seriously unhealthy sedentariness among adults in this country. Many people do not move around this planet under their own steam other than to go to the car, fridge, or couch. No joke. Hours are spent every day sitting in front of a lit screen. We come home from work, having been typing and mousing, straining our neck and back and keyboarding muscles, only to collapse on the couch to click around on the remote. Maybe we’re tense, so we have a drink. When it’s time to go to bed, we’re not physically tired, so we’ll have a few more drinks. So we won’t sleep efficiently (because alcohol disrupts healthy sleep cycles). And then we’ll do it all again the next day.

Making even a small sustainable dent in this cycle can be challenging. The positive effects may not be evident quickly. Only patience and commitment are rewarded. But the rewards, accumulating bit by bit, can be great.
A few ways an “exercise prescription” can make a difference

Although this study wasn’t intended to look at addiction, I’d like to mention the role of exercise in the treatment of mood disorders and addiction. There is evidence that aerobic and muscle-building exercise have positive effects on depression; research is ongoing on their effects on addiction. The attractive aspects of a sensible “exercise prescription” include its relative “safety profile” (meaning lack of negative side effects), its known positive effects on brain health, and the ability to customize it to whatever a person’s favorite activity might be. Of course, pacing oneself is paramount so as not to over-train or sustain injury. Some of the changes in the central nervous system due to exercise — for instance, increases in some dopamine activity (similar to the effects of intoxicants) enhanced blood flow, and glial cell proliferation — may also be related to improvements in mood and cognitive function.

People who have substance use disorders often suffer from a lack of joy (other than the chemical high) and from isolation. Isolation both permits the use of drugs or alcohol without bothering others, and may drive the use of them as a salve for loneliness. So combatting isolation is part of addressing addiction. Exercise (in groups) is a pro-social activity: the sense of community, and the positive emotional impact of interpersonal contact (that is, the simple joy of being with others), may be essential ingredients of getting — or staying — on the road to recovery. It’s hard to maintain the lifestyle changes you want to make. It doesn’t matter whether your goal is weight loss, exercise, normal blood sugar, or decreasing stress — research has shown that simply learning about the value of lifestyle changes is insufficient on its own to help people maintain their goals.

Of course, few people are actually ignorant about the number of calories in a chocolate truffle, the benefits of exercise, or the incredible danger, discomfort, and inconvenience of diabetes and stress. Still, despite this awareness, maintaining these changes is an uphill battle. And that’s largely because habits are hard to kick.

The rewards of the changes themselves have their limits. On a cold, snowy day in February, going to the gym is far less appealing than staying in bed for one more hour. And when you return home tired from a day of work, the calories in that extra glass of wine may in fact suddenly turn invisible. So how can you get that extra motivation?
The two types of rewards — and what they can do for you

Despite a growing body of evidence on the value of reward-based systems in promoting health behaviors, they are notoriously ineffective. But these studies generally focus on one kind of reward. Having an understanding of the other category of rewards may provide additional motivation to maintain the changes that you want.

There are two kinds of rewards: hedonia and eudaimonia. Hedonia (H-rewards) includes superficial pleasures such as weight loss, looking good, and acceptance by others. These rewards are more concrete and often short-lived. Eudaimonia (E-rewards), on the other hand, refers to a sense of meaning and purpose that contributes to overall well-being. Connecting your lifestyle goals to E-rewards may help motivate you even more.

The greater the size of a self-processing region in your brain called the insula, the higher your E-rewards. Specifically, if you have a large insula, your senses of personal growth, positive relations with others, and personal purpose are high. It’s not hard to imagine how feeling this way can help motivate you in many different ways, let alone when it comes to making specific lifestyle changes.

E-rewards also motivate you by activating the brain’s reward region, the ventral striatum. You feel less depressed when this part of the brain is activated. In contrast, when you satisfy only your H-rewards (e.g., looking good and getting a massage), this can actually make you more depressed and less motivated in the longer term.

See the video below where I explain in more depths about the different types of rewards.
What are your E-rewards?

To stay motivated, ask yourself how you will enhance your sense of meaning and purpose. They can be strong motivators for achieving your goals. The following are all examples of people with strong E-rewards motivating their decisions:

    A college sophomore obsessed with pizza and beer starts to eat and drink healthily when she realizes that her career in broadcast journalism will probably require her to be on camera day in and day out, so she needs to look (and feel) her best.
    A grandfather won’t let anything stop him from going to the gym so that he can have the longest possible time alive to be with his grandchildren.
    A doting husband ignores most of the buffet table at a cocktail party (except for the veggies and dip) because he knows that he wants to be there for his wife and kids.
    A young woman decides to start skipping dessert when she recognizes that her work on eliminating poverty is too important for her to undermine her own well-being in any way.

It’s not just the service or job that inspires E-rewards either. The story is a little more complex.

The concept of E-rewards can be traced back to Aristotle, who believed that the highest level of human good was not about satisfying one’s appetites, but about striving to express the best that is within us. This could only really be achieved by self-realization, a continuous process that looks different for each person, depending on his or her unique talents and dispositions.

As Aristotle points out, the first and foremost ultimate goal of all living humans is this feeling of well-being, which must be the primary focus if we are to achieve any of our health-related goals. Contrary to other theorists on the subject, Aristotle points out that H-rewards — good friends, wealth, and power — help as well. Yet, there is more to it than that. To truly feel E-rewards, you need to feel like you are flourishing in your life. In this inspired state, you are more likely to be motivated to achieve your goals.

To start this process, ask yourself how much of your day you spend in activities that nurture this sense of self. According to Carol Ryff, there are six areas of your life that you can reshape to enhance these E-rewards: greater self-acceptance, higher-quality relationships, being in charge of your life, owning your own opinions even when others oppose them, personal growth, and having a strong intrinsic sense of purpose. If you work on these factors, you will likely feel more intrinsic reward, and therefore enhance your motivation to accomplish your lifestyle changes as well.

We tend to focus on H-rewards to motivate ourselves to achieve our goals. But E-rewards may offer an additional focus to maintain your motivation for the lifestyle changes you desire. Hormonal therapy, also known as androgen-deprivation therapy, can be a powerful weapon in the fight against prostate cancer because it deprives malignant cells of the fuel they need to grow. Androgens — meaning the family of male sex hormones that includes testosterone — contribute to physical characteristics such as a deeper voice, thick facial hair, and increased muscle strength and bone mass. But when prostate cancer develops, testosterone also contributes to tumor growth and progression. Depending on the specific treatment used, hormonal therapy can either stop the body from making testosterone or prevent it from interacting with cancer cells.

Though it was once reserved solely for treating prostate cancer that has spread, doctors now also combine hormonal therapy with radiation to treat locally advanced tumors that have not yet spread to more distant locations, such as the bones. Hormonal therapy reduces the chance that a tumor will progress or return, and it makes radiotherapy more effective at controlling prostate cancer. But it also causes side effects such as weight gain and bone loss, and the optimal duration of treatment remains an open question.
The latest study results are promising

Studies have consistently shown that the longer a man receives hormonal therapy, the better his chances for extended survival. Now, results from a phase 3 clinical trial suggest that men with locally advanced prostate cancer should get at least 2 years of additional hormonal therapy after finishing their initial combined treatment. “Our question was simply: is a short course or a long course of treatment better for the patient?” said Dr. Colleen Lawton, clinical director of radiation oncology at Milwaukee’s Medical College of Wisconsin, who led the research. “And we found that the survival benefits of long-term hormonal therapy outweigh the risks.”

The study, known as RTOG 9202, was launched in 1992. It enrolled approximately 1,500 men with cancer confined to both lobes of the prostate, or cancer that had spread into nearby tissues, such as the bladder. All the patients had prostate-specific antigen (PSA) levels lower than 150 nanograms per milliliter, and their Gleason scores — which describe the aggressiveness of a prostate tumor — ranged from 6 (not aggressive) to between 8 and 10 (highly aggressive). The participants’ ages ranged from 43 to 88, with a median of 70 years, and the vast majority of participants were white.

During the study, half the men got only four months of hormonal therapy, starting 2 months before radiation treatment and continuing for two months during radiation treatment. The other half got that treatment plus 2 years of additional hormonal therapy.

Lawton presented the results (which have not yet been published) last November at the annual meeting of the American Society for Radiation Oncology. The data show that after a median follow-up of 20 years, men who got the long-term treatment had a 40% lower risk of the cancer spreading and a 33% lower risk of dying from prostate cancer than the men who were given hormonal therapy for just 4 months. And in a subset analysis of men with the highest-risk prostate cancer, long-term hormonal therapy dropped the odds of metastasis and death from prostate cancer even further: by 48% and 45%, respectively.

According to Lawton, the side effects of the hormonal treatment were manageable with diet, weight-bearing exercise, and drugs that boost bone density. But she emphasized that researchers are still grappling with how to define long-term hormonal therapy. As an example, she mentioned that a different study of men with locally advanced prostate cancer presented at a medical meeting in 2013 had found that disease-specific survival rates were nearly identical whether hormonal therapy lasted 18 or 36 months.

“The duration of treatment for localized prostate cancer is complicated and controversial, especially with the known cardiovascular side effects of some types of hormonal therapy,” said Dr. Marc Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, and editor in chief of HarvardProstateKnowledge.org. “Few would argue with the view that for patients with high-risk features, such as high PSA and Gleason scores, longer is better. But we still need more clarity on the lower-risk patient populations.”

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