The Emotional and Psychological Aspects of Living with Diabetes

As millions of Americans with diabetes are making New Year’s resolutions to eat better and exercise, there is one organization focused on an often ignored area of treatment: the emotional and psychological issues surrounding both type 1 and type 2 diabetes.

The Behavioral Diabetes Institute (BDI) is the world’s first organization dedicated to tackling the unmet psychological needs of people with diabetes. The BDI offers an array of evidence-based clinical programs, all designed to help people overcome the emotional and behavioral obstacles to living well with diabetes. Based in San Diego, the Behavioral Diabetes Institute is committed to helping people master the unique challenges of diabetes, conducting behavioral research in diabetes, and providing health care providers with the specialty behavioral training necessary for managing diabetes effectively.

The Behavioral Diabetes Institute was founded five years ago by William Polonsky, PhD, CDE, an internationally known, Yale-trained clinical psychologist, certified diabetes educator, associate clinical professor at the University of California, San Diego (UCSD), and author of Diabetes Burnout: What To Do When You Can’t Take It Anymore. Formerly the senior psychologist at the famed Joslin Diabetes Center in Boston, Dr. Polonsky is an active researcher in behavioral diabetes and travels throughout the world speaking to patients and health care professionals about how to understand and address the emotional stresses of living with diabetes.

Diabetes is a tough disease that can be difficult for many people to handle. Managing one’s own diabetes takes time, knowledge, and effort. People often become overwhelmed or “burned out” by the unending, often burdensome self-care demands. Many report feeling angry, frightened, or unmotivated. Relationships with loved ones can become strained, creating further feelings of isolation. Addressing these real-life aspects of diabetes is critical for long-term success. Unfortunately, they are often given little attention in common medical practice.

Dr. Polonsky and his colleagues provide useful tools online at their website, www.behavioraldiabetes.org. They also offer small group workshops and programs for adults and adolescents with diabetes throughout the year, all at little or no cost. These include their core program, Getting on Track; the multi-week depression series, Feeling Good Again: Breaking the Depression/Diabetes Connection; and — new for 2010 — programs for eating disorders in diabetes.

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Stanford Study of Flies Raises Doubts About Fasting Leading to Longer Lives

They’re called “fruit flies” for a reason, and it sure isn’t for lack of appetite. But like most animals, the pests typically lose their appetite when they get infected. We humans go them one better: Even when bug-free and hungry, some of us are tempted to do some serious fasting, in hopes of living longer, healthier lives.

Many studies indicate that caloric restriction extends life spans in fruit flies, mice and, most recently, rhesus monkeys, apparently by slowing the aging process. But virtually all these studies have been performed in sterile environments, on animals raised under relatively pathogen-free conditions. So Stanford University School of Medicine researchers decided to see if reduced caloric intake also helps creatures cope with infection.

Appetite loss as a response to infection seems a bit paradoxical. “Mounting a robust immune response is very energy-consuming,” said David Schneider, PhD, associate professor of microbiology and immunology. “You might think an infected animal would be better off eating more, not less.”

Working with fruit flies, Schneider and his graduate student Janelle Ayres have shown that caloric restriction can indeed alter the flies’ response to infection, but in different directions depending on what they’ve been infected with. (Ayres has since received her PhD and is a now postdoctoral researcher at the University of California-Berkeley.) This has potentially significant implications for humans, since flies are an excellent model system for studying certain aspects of our immune response.

In their study, to be published online July 13 in PLoS-Biology, the researchers measured the appetites of infected versus uninfected fruit flies, as well as the effects that restricting food intake in advance of an infection might have on flies’ response to the infection.

Ayres had previously conducted a search for mutant fruit flies that died faster, or more slowly, than normal flies after being infected with pathogenic bacteria. That laborious operation required injecting so many tiny flies with a special syringe that, Ayres said, “at one point, my hand got stuck in injecting position and I had trouble unfolding it.”

One batch of mutant flies Ayres identified were super-light eaters due, it was found, to a faulty taste receptor. She and Schneider used these mutants for several of the experiments in the new study. In addition, to make sure that what they saw was really because of reduced caloric intake and not some other effect of the mutation, they repeated their experiments with normal flies that had been placed on caloric restriction for some time prior to being infected. The observed results were the same in either case.

The investigators infected flies with three very different strains of bacteria, all of which can cause fatal disease in humans. Then they compared diet-restricted versus normally fed flies’ survival after infection.

Flies that had restricted caloric intake prior to infection with the pathogen, Enterococcus faecalis, ate no less than uninfected flies did. The “low-calorie flies” also survived for the same length of time as normal eaters.

Infecting mutant or previously diet-restricted “low-cal flies” with either of two other microbial menaces, Salmonella typhimurium and Listeria monocytogenes, did trigger appetite loss. But there the similarity ended. Injected with S. typhimurium, flies on prior caloric restriction outlived normal eaters, surviving about 15 days post-infection versus eight days for the control flies. Low-cal flies infected with L. monocytogenes, on the other hand, died faster than likewise infected normal eaters. They lived for only four days, as opposed to six or seven in the case of flies that had been on normal diets.

The Schneider lab is seeking physiological explanations for this divergent response. But taken as a whole, the results so far suggest that some skepticism might be in order regarding climbing aboard the caloric-restriction bandwagon, Schneider said. “There’s evidence that caloric restriction seems to rev up various individual components of the immune system,” he said, “but in the few studies where diet-restricted animals actually have been infected experimentally, they fared poorly.”

In their study’s conclusions, the authors write, “The work reported here should raise a cautionary flag, as it demonstrates that diet restriction can have complex effects on the realized immune response of a diet-restricted animal.” Attempts to extend life span through dietary restriction, or mimicking this process by gulping a pill, could thus be counterproductive, as the value of diminished appetite to an animal’s survival may vary with the infecting microbe.

There may be something to the celebrated admonition, “feed a cold and starve a fever,” after all. But much remains to be learned about exactly which infections can be fought best by gorging and which by fasting.

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National Survey Shows Consumers Prefer Agents When Shopping for and Purchasing Individual Medical Insurance

A recent online survey of more than 1,000 consumers found that those who purchased individual medical (IM) insurance through a professional agent were significantly more satisfied with their health plans than those who bought IM insurance online.  The independent study was commissioned by Milwaukee-based Assurant Health, a leading national provider of Individual Medical, Small Group and Specialty health insurance products. Some of its other key findings included:

  • 64% of those who bought through agents used the word “helpful” to describe their experiences while only 36% of online purchasers used this term.
  • 91% of those who purchased through an agent bought the plan their agent recommended.
  • 31% of those shopping online described the experience as “time-consuming.”
  • Despite the recent proliferation of Web-based insurance brokerages, 62% of the survey respondents bought their insurance through an agent.
  • In addition, consumers who purchased through an agent were significantly more satisfied in regard to how easy it was to understand their options and choose a plan that gave them the best coverage tailored to their needs than those who purchased online.
  • After being presented with information on how agents can help, and advised that purchasing through an agent does not increase their costs, nearly one out of four of those who purchased online reported that, if they were going to purchase IM insurance today, they would buy it through an agent.

“This study confirms our long-held belief that independent insurance agents play a vital role in educating consumers and helping them make informed decisions about their health plans,” said Don Hamm, President and CEO, Assurant Health. “It also shows that consumers greatly value agents’ personalized services and recommendations.”

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Obesity and Migraine Sufferers More Emotionally Traumatized than Those with Life-Threatening Conditions

Need another reason to commit to a healthy diet and exercise? Think migraines are just headaches? Migraine and obesity sufferers feel more emotional pain than those dealing with life-threatening conditions like congestive heart failure, prostate cancer, osteoporosis and high blood pressure. In fact, they tend to feel more pessimistic than those diagnosed with depression.

In a study about healthcare influencers, AdSAM, a non-verbal process of measuring emotional response, and TNS Healthcare found that people who suffer from some severe diseases accept and handle them better than other types of sufferers.

“People suffering from prostate cancer, seem to cope better than those suffering from migraine headaches,” said Jon Morris, Ph.D., the president of AdSAM® and a communications professor at the University of Florida.

Results showed that migraine, obesity and erectile dysfunction sufferers essentially feel afraid, disgusted and saddened by their situation. Understanding the emotional impact of these and other conditions is critical to the physician’s approach to condition management but also to those loved ones helping a patient through the condition.

Because of their embarrassed state-of-mind, those who suffer from obesity and erectile dysfunction often feel more comfortable talking with influencers – non-healthcare professionals such as relatives, friends, co-workers, etc., rather than physicians.

Obesity sufferers in particular feel most relaxed when discussing healthcare decisions with influencers. For men or women, the research shows that influencers are most often the women in sufferers’ lives, such as their spouses, mothers, sisters or female friends.

“Understanding the emotions surrounding the condition and the patients’ emotions towards the physician, as well as other influencers, has a major impact on how to communicate effectively with a patient,” Morris said.

TNS Healthcare also conducted research into communications in healthcare. The results indicated that an integrated communications program targeted to patients, physicians and influencers is needed to reach and impact people most effectively, especially in today’s digital age.

There are countless opportunities to seek healthcare information through the Internet and other channels. Discovering people’s true emotions can help physicians identify individual needs and information-seeking preferences.

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Seeking to Eat Better but Finding the Maze of Products, Claims and Labels at the Grocery Store Confusing?

You know the drill. You walk into your favorite grocery store, grab a cart and begin navigating through aisles laden with thousands of products – each with various claims of quality, taste, value and nutrition. As you find your way through the immense product array, you continually remind yourself of the goal to make healthy grocery purchases.

You try to recall the last you heard or read about what constitutes good nutrition. What about fats? Sugars? Carbohydrates? Calories? Natural or organic ingredients? The mind reels. With more than 45,000 product offerings in the average grocery store and approximately 17,000 new items introduced each year, you wonder if its even possible to achieve a healthy and balanced trip to the grocery store.

“When presented with conflicting nutrition information, marketing claims and confusing product packaging and labeling, what should be a routine trip to the store can easily become confusing and frustrating when it comes to the pursuit of healthy foods,” said Tom Nikkola, Life Time Fitness Nutrition Program Manager.

In the face of this challenge, here are some ‘nutrition smart’ tips to help guide you:

  • Visit the outside first!: Most grocery stores place whole, natural and unprocessed foods in the perimeter aisles of the store. The bulk of your purchases should come from these areas.
  • Get to know fruits and vegetables: Produce should command a fair share of your shopping cart space. The more fruits and vegetables, the less room you have for processed, less healthy options.
  • Choose protein wisely: Seek out “free-range,” “grass-fed,” “free of hormones,” “wild,” etc. options in the meat section. If you’re a vegetarian, good sources of proteins include nuts and seeds, tofu, soy milk, free-range eggs and some dairy products.
  • Be selective with dairy: Choose hormone-free and organic dairy and eggs.
  • Fats or no fats: Fat is an essential part of the diet. The key is the right types of fat such as non-saturated fat which has numerous health benefits or fats/oils that come from UNREFINED vegetable sources or oily fish such as salmon or tuna.
  • Reward yourself: There is no crime in treats but moderation is key.
  • Don’t forget to supplement: Try to consume the best diet possible, but a high-quality multivitamin and omega-3 fish oil should still be a regular part of your diet. We just don’t get enough of the vitamins and minerals we should, even when we try to be perfect with our diets.

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Data Says Uninsured Account for Nearly One-Fifth of Emergency Room Visits

HHS Secretary Kathleen Sebelius today released new data from the Nationwide Emergency Department Sample — the largest, all-payer emergency department database in the United States. The Nationwide Emergency Department Sample is designed to help public health experts, policymakers, health care administrators, researchers, journalists and others find the data they need to answer questions about care that occurs in U.S. hospital emergency departments.

These data indicate that uninsured persons accounted for nearly one-fifth of the 120 million hospital-based emergency department visits in 2006.

“Our health care system has forced too many uninsured Americans to depend on the emergency room for the care they need,” said Secretary Sebelius. “We cannot wait for reform that gives all Americans the high-quality, affordable care they need and helps prevent illnesses from turning into emergencies.”

The database is managed by HHS’ Agency for Healthcare Research and Quality (AHRQ) and generates national estimates on the number of emergency department visits in all community hospitals, by region, urban/rural location, teaching status, ownership and trauma designation. It also provides in-depth information on acute management of patients for all visits, including why patients were seen in the emergency department, the treatments they received, what happened to them at the end of the visit (admitted to the hospital, discharged home, transferred to another hospital, died in the emergency room or left against medical advice), the charge for their care and who was billed.

The Nationwide Emergency Department Sample contains 26 million records from emergency department visits from approximately 1,000 community hospitals nationwide. This represents 20 percent of all U.S. hospital emergency departments. The database also provides weighted calculations for national estimates of the 120 million emergency department visits in 2006.

“AHRQ has a long history of supporting health services research related to emergency medicine, and the richness of these new data will increase our capacity for research and decision making,” said AHRQ Director Carolyn M. Clancy, M.D. “The new database will give emergency planners and other policymakers the data they need to help improve the quality, safety and effectiveness of emergency medical care.”

AHRQ also released its latest Nationwide Inpatient Sample — the largest, most powerful database on hospital care in the United States, covering all patients, regardless of their type of insurance or whether they were insured. The 2007 Nationwide Inpatient Sample provides users with an in-depth look at why patients were hospitalized, the treatments and procedures they received and what happened to them at discharge. Researchers can use the Nationwide Inpatient Sample to examine trend data as far back as 1988. The 2007 Nationwide Inpatient Sample is based on discharge data from 8 million hospital stays at more than 1,000 community hospitals.

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US Physicians Do Not Endorse House Healthcare Bill

This past week the AMA issued formal endorsement of the House Healthcare Bill. According to Sermo, the largest online community of physicians in the US, AMA’s endorsement does not reflect the position of practicing physicians.

The healthcare concerns of US physicians have been well documented in thousands of online discussions on Sermo. Most notably, these concerns were outlined in “An Open Letter from America’s Physicians” which details the physician community’s concerns with the US healthcare system and how these concerns impact physicians’ ability to provide quality care for their patients. The letter, originally published on Sermo, has been signed by over 13,000 US physicians and is now available to the public at www.doctorsunite.org.

“Physicians are the only true advocates for their patients and this bill fails to meet what physicians need to improve the quality of care they deliver,” said Dr. Daniel Palestrant, Sermo CEO. “By endorsing a bill that does not adequately address concerns of physicians in this country, the AMA shows again that it is out of touch with physicians and is conflicted by its own business model. We welcome both Democratic and Republican lawmakers to engage with real physicians who actually practice medicine to get real-time feedback on how to reform healthcare.”

In a recent post on Sermo, Palestrant called for the AMA to resolve its conflicts of interest by shedding its relationships with insurers and abandoning tactics that take advantage of physicians and their patients to generate millions of dollars in revenue. Palestrant continued, “Physicians have voted with their feet with AMA membership now estimated at only 15-20% of US physicians.”

Just last week, Sermo released results of a new survey indicating US physicians—at least a representative sample of the more than 100,000 who use Sermo—no longer want the AMA to represent them and question the conflict of interest the AMA’s current business model creates in this debate (www.sermo.com/blog). More specifically:

  • 75% of physicians surveyed are not members of the AMA.*
  • 89% of physicians claim, “The AMA does not speak for me.”*
  • 91% of physicians surveyed do not believe the AMA accurately reflects their opinion as physicians.*
  • 87% of physicians surveyed think it is wrong that the AMA makes more money from insurance companies than it does from membership dues.**
  • 93% of physicians surveyed stated that they did not believe that the government should continue to support the AMA’s monopoly on billing codes**

* 4,156 physicians responded to a survey, conducted between July 1 and July 7, 2009; ** 1,957 physicians responded to a survey, conducted between July 8 and July 16, 2009. Respondents to Sermo online surveys span 68 specialties and all 50 states. The average age of physicians is 49 years old, with a median of 13 years experience in practice. The demographics of physician respondents is representative of the US physician population with respect to geographic distribution, most specialties and age. All respondents are verified and credentialed, ensuring they have valid, active licenses to practice medicine in the United States. Physician respondents work in practices of all sizes in all major urban and remote rural locations across the Unites States.

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California’s Cost of Obesity Climbs to $41 Billion

More than just unhealthy, California’s increasing girth is crippling the state’s economy, according to a study of the economic cost of obesity in California released today by the California Center for Public Health Advocacy (CCPHA). In just six years, reported economic costs of adult overweight, obesity and physical inactivity have nearly doubled and are now costing California an estimated $41 billion a year.

An update of a 2000 report, the study shows a 33 percent rise in obesity rates contributed to sharp increases not only in health care costs but also in lost productivity. The report is based on the latest available data and scientific research on the relationship between overweight, obesity, and physical activity, and their collective impact on health care expenditures and worker productivity.

“To put this in perspective, the economic cost to California of adults who are obese, overweight and physically inactive is equivalent to more than a third of the state’s total budget,” says California State Controller John Chiang. “Think of the programs we could protect, the children we could educate and the families we could help if we could recapture those dollars by investing in prevention. These figures demonstrate the real and very unsettling financial impact of the obesity epidemic on a California economy already in crisis.”

A leading national health econometrics consulting firm based in North Carolina, Chenoweth & Associates, was commissioned by the California Department of Health Services in 2000 to generate the first cost of obesity study. CCPHA hired the firm to update the study to get a more contemporary picture. Chenoweth and Associates found that overweight and obesity claimed a slightly larger percentage of the annual costs ($21 billion) than did physical inactivity ($20.2 billion). They also predict that the trend for dramatic growth in costs will continue and conservatively project that by the year 2011 costs will climb to $53 billion.

“These rapidly escalating costs paint an alarming picture for our state,” says Dr. Harold Goldstein, executive director of the CCPHA, which commissioned the study. “They underscore the need to build community health and prevention into public policies at every level, from national health care reform and the state’s use of federal stimulus funding to regional growth and local policies that help people to eat healthy food and be more physically active.”

In addition to a new statewide figure, today’s study provides an accounting of obesity costs by county. While it is not surprising that the largest counties have the largest costs, the numbers nevertheless are staggering: Los Angeles County – $11.9 billion; Orange County – $3.3 billion; San Diego County – $3 billion; Alameda County – $2.2 billion; Santa Clara County – $2.1 billion; and Sacramento County – $1.7 billion.

As dire as the report’s findings may be, the authors point out that even small improvements in health can have a considerable impact. A 5 percent improvement in the rate of physical activity and healthy weight over five years could trim almost $12 billion from the state’s obesity costs.

“The obesity crisis may seem overwhelming, but California has successfully tackled big health issues before,” says, Kim Belshé, Secretary of California Health and Human Services Agency, who helped design and lead the state’s nationally recognized tobacco programs. “The key is to establish concrete changes at the federal, state, and local level to make it easier for people to make healthier choices. This study shows that if those changes can help just one Californian in twenty reduce their weight and become more physically active, we could realize significant savings and begin to turn this crisis around.”

Echoing the need to address environmental issues that encourage poor diet was the study’s funder. “There are many communities where it is easier to get a cheeseburger than an apple. Communities such as these are designed for disease because of poor planning and policies that actually contribute to the epidemic,” says Robert K. Ross, M.D., president and CEO of The California Endowment, which funded the study. “In order to address the obesity epidemic effectively we must take a cogent look at what is driving it. We must move toward local, state and federal policies that seek to improve community environments and develop opportunities for physical activity.”

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U.S. Medical Bankruptcies a Myth; Personal Bankruptcy Rate Higher in Canada

The idea that large numbers of Americans are declaring bankruptcy due to medical expenses is a myth and the introduction of government-run health insurance in the U.S. will do nothing to reduce personal bankruptcies, concludes a new study from the Fraser Institute, a leading free-market think tank with offices in Canada and the United States.

The current debate about reforming U.S. health care policy has included suggestions that nearly two-thirds of personal bankruptcies in the U.S. result from uninsured medical expenses or loss of income due to illness. Advocates of socialized medicine argue that this would not occur if the U.S. adopted a government-run health system similar to Canada’s.

But Brett Skinner, author of Health Insurance and Bankruptcy Rates in Canada and the United States and Fraser Institute director of bio-pharma, health and insurance policy research, says the evidence doesn’t support the bankruptcy claim.

“If socialized medicine played a role in reducing personal bankruptcies, we would expect to see a lower rate of personal bankruptcy in Canada compared to the United States. Yet the reverse is true. The personal bankruptcy rate is actually higher in Canada than it is in the U.S.,” he said.

Skinner compared bankruptcy data in the U.S. and Canada from 2006 and 2007, and found that personal (non-business) bankruptcy filings as a percentage of the population were 0.2 percent in the U.S. during 2006 and 0.27 percent in 2007. In Canada, the numbers are 0.3 percent in both 2006 and 2007. The complete study is available at www.fraseramerica.org.

“There is no evidence to support the idea that a government-run health care system in the U.S. will reduce personal bankruptcies,” Skinner said.

“Bankruptcy and lack of health insurance coverage are both caused by the same thing: insufficient income, which is most often the result of unemployment. The majority of debt among bankrupt consumers in both America and Canada is composed of non-medical expenditures and therefore, has little to do with health insurance coverage.”

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Stanford Study Bolsters Case for Preventive Prostate Cancer Treatment

For the last six years, doctors have faced a dilemma about whether to treat men at risk of prostate cancer with the drug finasteride. On one hand, the drug had been shown to prevent cancer in about one of every four patients who received it. On the other, those who did develop cancer while on the drug were 25 percent more likely to have a more aggressive form of the disease.

Now new research from Stanford University School of Medicine appears to show that the drug did not cause those more aggressive forms of prostate cancer but simply made them easier to diagnose. The findings, which are to be published July 7 in Clinical Cancer Research, suggest that doctors can be less cautious in use of finasteride.

The questions about finasteride treatment can be traced to 2003 when researchers published results from the Prostate Cancer Prevention Trial, a 7-year study that tracked 18,882 healthy men over age 55. That study assigned some of the participants to take finasteride and some to take a placebo. Finasteride, which reduces levels of the male hormone dihydrotestosterone and shrinks the prostate, was found to decrease the prevalence of prostate cancer by about 25 percent. But the drug also seemed to increase the chances that if a cancer was found, it would be fast-growing and likely to spread, again by about 25 percent. As a result, doctors rarely prescribe the drug as a preventive measure.

In reviewing this study, however, a number of researchers, including Stanford’s Joseph Presti Jr., MD, noticed that the initial analysis failed to detect a subtlety in the data: The increase in fast-spreading “high-grade” cancers wasn’t consistent across all groups and occurred disproportionately in those men who had developed warning signs of the disease.

In men who went through the study without developing any cancer warning signs, finasteride use made no difference in the rate of high-grade cancers diagnosed upon an exit biopsy. But the results were quite different for men who were biopsied after an abnormal digital rectal exam or because of a test showing elevated levels of prostate-specific antigen, a protein also known as PSA that can be unusually high in prostate cancer. Of those men, the ones on finasteride had an 11.5 percent rate of high-grade cancer, compared with 7.7 percent in the placebo group.

That inconsistency suggested something wrong with the initial study analysis, not the drug. Others, including the original study authors, had found evidence that prostate-specific antigen screening works better in men taking finasteride, but no one knew why.

Presti, the Thomas A. Stamey Research Professor in Urology and director of the urologic oncology program at Stanford, and other researchers wondered if it was because of finasteride’s propensity to shrink the prostate. A malignant growth in a large, mostly non-cancerous prostate would be easier to miss, they reasoned. If the rest of the prostate tissue was smaller, biopsies would more easily pick up on the cancer tissue left behind.

To test the idea, Presti and his colleagues analyzed a database of 1,304 men who had been referred to Stanford after an abnormal digital rectal exam or high PSA test results—the same conditions as in the original study, except none were on finasteride. Nearly 500 of them were eventually diagnosed with prostate cancer, 247 of which had the aggressive, high-grade disease.

The team found that the smaller the prostate, the more likely a biopsy would result in a diagnosis of high-grade cancer—and the more likely a high PSA level would predict the disease. In men with prostates between 20 cubic centimeters and 29.9 cubic centimeters, for example, the diagnostic rate for one level of high-grade cancer was 29.7 percent. For men with prostates larger than 80 cubic centimeters, it was just 6.5 percent.

“We’re showing that this is all related to size,” said Presti, who is a member of Stanford’s Cancer Center.

The original cancer trial researchers reached similar conclusions after analyzing their own results, said Catherine Tangen, DrPH, the statistical principle investigator for the Prostate Cancer Prevention Trial and a member at Fred Hutchinson Cancer Research Center in Seattle. Tangen warned that without removing and analyzing the prostates of the men in Presti’s study, the true prevalence of undetected prostate cancer remains unknown, leaving the actual sensitivity of the prostate-specific antigen test open to question. But, she said, “Their observations are consistent with everything we found,” and suggest that men “should be given the opportunity” to take finasteride if they and their doctors deem it necessary. Prostate cancer affects one in 15 men ages 60 to 69, and one in six men overall will someday get the disease.

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