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Monday, November 23, 2015

Health of the Healthcare System

Walking Faster or Longer Linked to Significant Cardiovascular Benefits in Older Adults

Newswise, November 23, 2015 In a large prospective community-based study of older Americans, modest physical activity was associated with a lower risk of cardiovascular disease (CVD). 

This was true even among men and women older than age 75 at baseline – a rapidly growing population for whom regular activity has been advised, but with little supportive empirical evidence.

Led by senior author, Dariush Mozaffarian, M.D., Dr.P.H., dean of the Friedman School of Nutrition Science and Policy at Tufts University, the researchers studied a group of American adults whose mean age was 73 at the start of the study and who were then followed for 10 years.

Information on various usual activities was assessed at baseline and regularly updated during follow-up. When the current study’s research team evaluated different aspects of physical activity by the men and women during this ten-year period -- a greater pace, walking distance, and leisure activity-- each was associated with a lower risk of cardiovascular disease.

The associations found include:
• After adjustment for other risk factors and lifestyle behaviors, those who were more active had significantly lower risk of future heart attacks and stroke.
• Adults who walked at a pace faster than three miles per hour (mph) had a 50%, 53%, 50% lower risk of coronary heart disease (CHD), stroke and total CVD, respectively, compared to those who walked at a pace of less than two mph.
• Those who walked an average of seven blocks per day or more had a 36%, 54% and 47% lower risk of CHD, stroke and total CVD, respectively, compared to those who walked up to five blocks per week.
• Those who engaged in leisure activities such as lawn-mowing, raking, gardening, swimming, biking and hiking, also had a lower risk of CHD, stroke and total CVD, compared to those who did not engage in leisure-time activities.
• The findings were similar in both men and women, in those above or below age 75 at baseline, and including only those with similarly good or excellent self-reported health.

The researchers studied 4,207 men and women who had been enrolled in the Cardiovascular Health Study (CHS). CHS is a National Heart, Lung, and Blood Institute of the National Institutes of Health-supported national cohort of U.S. men and women who were enrolled in 1989-90 from Medicare eligibility lists and whose health was followed over time.

The researchers used the information in the CHS database concerning physical activity, including walking, leisure-time activities and exercise intensity, and other health information coming from annual study visits such as physical exams, diagnostic testing, laboratory evaluations, personal health histories, and measured risk factors.
“Our study of older Americans shows that, even late in life, moderate physical activity such as walking is linked to lower incidence of cardiovascular disease,“ commented the first author Luisa Soares-Miranda, Ph.D., a member of the research team and currently a postdoctoral student with the Research Centre in Physical Activity, Health and Leisure, Faculty of Sport at the University of Porto, Portugal.

“It appears that whether one increases the total distance or the pace of walking, CVD risk is lowered. Fortunately, walking is an activity that many older adults can enjoy.”

“While national guidelines recommend that older adults engage in regular physical activity, surprisingly few studies have evaluated potential cardiovascular benefits after age 75, a rapidly growing age group,” said Mozaffarian.

 “Our findings confirm a beneficial relationship between walking and leisure activities and CVD late in life.

“These results are especially relevant because, with advancing age, the ability to perform vigorous types of activity often decreases. Our findings support the importance of continuing light to moderate exercise to improve health across the lifespan.”

Additional authors of this study are David F. Siscovick, M.D., M.P.H., senior vice president for research at the New York Academy of Medicine; Bruce M. Psaty, M.D., M.P.H., Ph.D., professor in the Departments of Medicine and Epidemiology at the University of Washington and a senior investigator in the Group Health Research Institute; and W.T. Longstreth, Jr., M.D., M.P.H, professor of neurology and adjunct professor of epidemiology in the Department of Neurology at the Harborview Medical Center at the University of Washington.

This research was supported by contracts from the U.S. Department of Health and Human Services: HHSN268201200036C and HHSN268200800007C; and awards from the National Heart, Lung, and Blood Institute of the National Institutes of Health: N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and HL080295. Luisa Soares-Miranda is supported by a grant funded by the Portuguese Foundation for Science and Technology (FCT).

Soares-Miranda, Luisa; Siscovick, David S.; Psaty, Bruce M.; Longstreth, W.T. Jr.; and Mozaffarian, Dariush, “Physical Activity and Risk of Coronary Heart Disease and Stroke in Older Adults: The Cardiovascular Health Study.” Circulation (published online before print November 4, 2015) doi: 10.1161/CIRCULATIONAHA.115.018323

About the Friedman School of Nutrition Science and Policy
The Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy at Tufts University is the only independent school of nutrition in the United States.
The school's eight degree programs – which focus on questions relating to nutrition and chronic diseases, molecular nutrition, agriculture and sustainability, food security, humanitarian assistance, public health nutrition, and food policy and economics – are renowned for the application of scientific research to national and international policy.

Sound Deprivation Leads to Irreversible Hearing Loss

Researchers show that chronic conductive hearing loss leads to cochlear degeneration

Newswise, November 23, 2015--Massachusetts Eye and Ear investigators have shown that sound deprivation in adult mice causes irreversible damage to the inner ear.

The findings, published in PLOS ONE, suggest that chronic conductive hearing loss, such as that caused by recurrent ear infections, leads to permanent hearing impairment if it remains untreated.

Sound waves travel through the ear canal before reaching the eardrum and the tiny bones of the middle ear. They are then converted into electrical signals within the inner ear and transmitted to the brain by the auditory nerve.

Conductive hearing loss occurs when sound transmission from the ear canal to the inner ear is impaired. It causes a reduction in sound level and an inability to hear soft sounds.

In this study, a team of researchers led by St├ęphane F. Maison, Ph.D., investigator in the Eaton-Peabody Laboratories at Mass. Eye and Ear and assistant professor of otolaryngology at Harvard Medical School, followed the inner ear changes in a group of mice with chronic conductive hearing loss in one ear.

“After a year of sound deprivation, we observed dramatic changes in the inner ear — notably, a significant loss of the synaptic connections through which the sensory cells send their electrical signals to the brain,” Dr. Maison said.

“Although there have been many studies of acoustic deprivation on the auditory system, few have looked at adult-onset deprivation, and none, to our knowledge, has documented changes in the inner ear.”

Leading causes of conductive hearing loss include earwax blockage, otitis media (ear infections) and otosclerosis.

“Although these conditions are routinely treated in industrial societies, a number of patients choose not to receive treatment, particularly when their medical condition affects only one ear,” Dr. Maison said.

“For instance, patients with unilateral atresia, a condition in which the ear canal is closed or absent, see limited benefits of undergoing surgery when they can simply use their good ear.”

At least 80 percent of children will experience one or more bouts of otitis media before they reach 3 years of age. Ear infections are the most common cause for physician visits and medication prescriptions among children in the United States.

These bouts can persist for many months in some cases, and deficits in communication abilities can persist for years after the middle-ear pathology has resolved.

Data from the present study suggest that the auditory deprivation, in itself, damages the inner ear in ways similar to that seen in age-related and noise-induced hearing loss.

Although the mechanisms underlying this inner ear damage following sound-deprivation are not known, the authors suggest that its effects need to be considered in the management of chronic conductive hearing loss in clinic.

“Our findings suggest that audiologists and physicians should advocate for early intervention and treat these middle ear conditions,” Dr. Maison said.

Co-authors of this PLOS ONE paper are Leslie D. Liberman, Laboratory Manager at the Eaton-Peabody Laboratories at Mass. Eye & Ear and M. Charles Liberman, Ph.D., Director of the Eaton-Peabody Laboratories at Mass. Eye and Ear and the Harold F. Schuknecht Professor of Otolaryngology at Harvard Medical School. This work was supported by the National Institute on Deafness and Other Communication Disorders (Grants RO1 DC 0188 and P30 DC 05209).

About Massachusetts Eye and Ear 

Mass. Eye and Ear clinicians and scientists are driven by a mission to find cures for blindness, deafness and diseases of the head and neck. Now united with Schepens Eye Research Institute, Mass. Eye and Ear is the world's largest vision and hearing research center, developing new treatments and cures through discovery and innovation. Mass. Eye and Ear is a Harvard Medical School teaching hospital and trains future medical leaders in ophthalmology and otolaryngology, through residency as well as clinical and research fellowships. 

Internationally acclaimed since its founding in 1824, Mass. Eye and Ear employs full-time, board-certified physicians who offer high-quality and affordable specialty care that ranges from the routine to the very complex. U.S. News & World Report’s “Best Hospitals Survey” has consistently ranked the Mass. Eye and Ear Departments of Otolaryngology and Ophthalmology as top in the nation. For more information about life-changing care and research, or to learn how you can help, please visit

Viruses Can Spread When Jack Frost Nips at Your Nose

Saint Louis University Infectious Diseases Physicians Answers Flu Season Questions
 Newswise, November 23, 2015 -- A cure for the common cold isn’t in the crystal ball of an infectious diseases researcher and physician at Saint Louis University’s Center for Vaccine Development.

“There’s not likely to be a vaccine or cure developed because colds don’t kill people or make them seriously ill,” says Donald Kennedy, M.D., professor of internal medicine at Saint Louis University and a SLUCare infectious diseases expert.

“They don’t have a major impact on overall health or the economy because many people keep on working even if they have a cold.”

In addition, many strains of rhinovirus and coronavirus -– which are sources of respiratory infections -– also cause colds, so there is no one single virus to target.

“That helps explain the reason people can get repeated colds. They’re probably getting a different virus from the last one, a virus they’re not immune to,” Kennedy says. “You also can get two viruses at the same time, with overlapping symptoms.”

Not all respiratory infections are the same. Some have more debilitating symptoms and serious health consequences than others. Some are seasonal, others occur at any time of the year.

As anyone who has spent a vacation on the beach with the sniffles knows, colds can occur at any time of year. They know no season.

Seasonal influenza -– as the name implies -– is another matter, Kennedy says, typically occurring in the U.S. between October to February, for six to eight weeks. And as it infects 60 to 70 million people a year, influenza kills an estimated 40,000 U.S. residents each year. Funded by the National Institutes of Health, Saint Louis University’s Center for Vaccine Development conducts extensive research on influenza vaccines because protecting people from flu is a significant public health initiative.

So as patients get their annual influenza vaccines because flu season is around the corner, Kennedy answers questions about the invasion of the viruses that can make us feel miserable.

How can you tell the difference between the flu and a cold?

If you have to ask, you don’t have influenza, Kennedy says.

“A cold is just a runny nose. Typically, you don’t even cough,” Kennedy says. “You carry Kleenex and you blow your nose. Maybe you don’t feel perfect, but colds are not that big of a deal. Most people get a couple colds a year, and they last for about a week.”

Influenza is an entirely different story.

“If you get the real flu, you are achy, run a high fever and feel as if you can’t get out of bed. You won’t be able to come into work, and you shouldn’t want to transmit influenza to others,” Kennedy says.

“You could have fever, chills, muscle aches all over your body, fatigue, a cough, sore throat and a headache. And you could have a runny or stuffy nose, which you also get with a cold.”

Maybe you feel that you are able to function, yet more miserable than just having a stuffy nose. You might have parainfluenza, which is a respiratory virus with symptoms that include fever, runny nose, sore throat and cough.

Anyone can get parainfluenza, but it is most common in children, those with weakened immune systems or older adults. Parainfluenza can lead to bronchitis, croup and pneumonia.

“A flu shot won’t protect you from parainfluenza because it is a different virus than influenza,” Kennedy says.

Should I stay home?
Not if you have a cold. Wash your hands, bring your tissues and persevere, Kennedy says.

Absolutely, if you have influenza, Kennedy says. “We don’t want you transmitting the virus to others.”

Maybe, if you have parainfluenza or another type of respiratory infection. Let your symptoms guide you.

“Whether to stay home really is based on if you have a disease that is going to be communicable to others. If you have a fever of 100.5 degrees Fahrenheit, that’s usually significant for a systemic illness,” Kennedy says.

“But use your judgment. Your temperature fluctuates throughout the day, depending on when you take it. So there’s really no set number that is the magic ‘you’re sick’ indicator.”
Why does flu occur in winter?

“Nobody really knows,” Kennedy says. “It stands to reason that we are in closer contact indoors with each other in the winter, but we really don’t know.”

Influenza is transmitted in the air when someone coughs or sneezes and those droplets land in the mouths or noses of someone nearby. It also spreads the same way colds are transmitted –- through hand-to-hand contact. Someone who is infected touches his nose or mouth, touches someone else’s hand and that person touches her nose or mouth.

Why do some people seem to get sicker with upper respiratory infections than others?

Two things likely are at play, Kennedy says, dose and host.

“You’re more likely to get a bad case of flu sleeping next to someone who is coughing and sneezing all night rather than riding the bus for 15 minutes next to someone who has influenza. It’s the amount of virus that you’re exposed to,” Kennedy said.
“The host’s ability to fight this off also is relevant. Someone who has a compromised immune system -– who is fatigued, doesn’t eat right, is pregnant or has an underlying health problem -– is likely to get sicker as well.”

Is there anything you can do to make a cold go away?

Not really. Drink a lot of fluids and treat your symptoms. The infection will run its course in about a week.

If you have the flu, you may shorten its duration by 24 hours if you call your doctor at the first sign of symptoms to get a prescription for Tamiflu or Relenza, which are antiviral medications.

“These drugs reduce symptoms slightly but only if they are taken early,” Kennedy says. “And you have to be careful not to overuse them because the virus can become resistant to the medicine.”

Is there a silver lining in getting the flu?

“If you get the flu this year, the chance of getting it next year is less likely because you boosted your immunity,” Kennedy says.

And if you really hate the possibility of getting the flu, get vaccinated. It’s the one thing you can do to reduce your odds of being laid up for days with influenza, he says.

Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level.

Research at the school seeks new cures and treatments in five key areas: infectious disease, liver disease, cancer, heart/lung disease, and aging and brain disorders.

SLUCare Physician Group is the academic medical practice of Saint Louis University, with more than 500 health care providers and 1,200 staff members in hospitals and medical offices throughout the St. Louis region. SLUCare physicians are among the most highly trained in their fields -— more than 50 specialties in all -— and are national and international experts, renowned for research and innovations in medicine.

Thursday, November 19, 2015

College Studies May Reduce Risk of Dementia for Older Adults, Research Finds

Going back to school could boost cognitive capacity

Newswise, November 19, 2015 — Older adults who take college courses may increase their cognitive capacity and possibly reduce their risk for developing Alzheimer’s disease or other forms of dementia, according to new research published by the American Psychological Association.

An Australian study called the Tasmanian Healthy Brain Project recruited 359 participants ages 50 to 79 who took a series of cognitive tests before completing at least a year of full-time or part-time study at the University of Tasmania.
Participants were reassessed annually for three years following their studies. More than 90 percent of the participants displayed a significant increase in cognitive capacity, compared with 56 percent in a control group of 100 participants who didn’t take any college courses.

“The study findings are exciting because they demonstrate that it’s never too late to take action to maximize the cognitive capacity of your brain,” said lead researcher Megan Lenehan, PhD.

“We plan to follow these participants as they age to see if college studies could help delay the onset or reduce the debilitating effects of dementia.”

Previous studies have examined how exercise, brain games and an active social life may boost cognitive capacity and possibly stem cognitive decline associated with aging. This study is the first to examine similar positive effects from college courses taken by older adults, said Lenehan, of the University of Tasmania.

The study participants, who were screened to exclude people who had dementia, completed a baseline series of tests to measure cognitive capacity, or an individual’s ability to use brain networks efficiently in areas such as memory, information processing, decision making and planning.

The participants in the college studies group took a wide range of courses, including history, psychology, philosophy and fine art. Most of the students took courses on campus, but some completed online classes.

The researchers suspect that campus study may provide greater benefits in boosting cognitive capacity because of social interaction with professors and fellow students, but the study didn’t analyze any differences between on-campus or online courses.

The participants completed the same cognitive tests each year during the four-year study, with 92 percent of the college-studies group displaying a significant increase in cognitive capacity, while the remaining 8 percent generally maintained their cognitive capacity.

For the control group, 56 percent displayed a significant increase in cognitive capacity, while 44 percent had no change. The participants’ age, gender, feelings of well-being or level of social connectedness didn’t affect the find .

Prior research has shown that college study earlier in life may increase cognitive capacity, and it appears the same may be true for older adults, Lenehan said.

“It is possible that any mentally stimulating activity later in life may also enhance cognitive capacity, such as other adult-education classes or programs to increase social interaction,” she said.

The control group was significantly older than the college studies group, but there were no significant differences in baseline cognitive capacity scores, the study noted.

The researchers also didn’t find any correlation between age and cognitive capacity scores at any point during the study. Some participants in the control group may have been doing crossword puzzles or other mentally stimulating activities that boosted their cognitive capacity, Lenehan said.

The participants who took college classes volunteered for the study so they probably had a greater interest in continuing education that the general senior population, the journal article noted.

The study was too short to reveal any long-term effects so the researchers plan to follow the participants as they age to provide additional evidence of whether college studies may reduce the risk or delay the onset of dementia.

Monday, November 16, 2015

Stony Brook Docs Says Small Steps May Help When Dealing with a Growing Diabetes Problem

Newswise, November 16, 2015 —– There are currently 29 million Americans living with diabetes and the World Health Organization predicts that by 2050 one in every three people will have this disease.

Recent data shows that pre-diabetes, a condition that puts you at great risk for developing diabetes, exists in 37 percent of the population— meaning that nearly 50 percent of Americans are dealing with the risks and implications of diabetes.

With those devastating statistics— and with November being National Diabetes Month— it is an increasingly important time to raise awareness about this disease as it reaches epidemic proportions.

Endocrinologist and diabetes expert Joshua D. Miller, MD, MPH, takes a unique approach with his patients, advocating for small, achievable changes that can make a big difference.

“I always start off by giving my patients the facts,” says Dr. Miller. “The number of Americans with diabetes is astounding and I think shocking to most people. The second thing I tell them is that diabetes affects nearly every system in the body and every other disease.”

Dr. Miller says that it is important to be proactive with self-management when it comes to diabetes and that making lifestyle changes to either prevent diabetes from developing or to better control an existing condition is key.

“I encourage patients to focus on small, achievable changes to improve quality of life,” says Dr. Miller. “I help patients identify ways to make seemingly insurmountable tasks such as weight loss and physical activity become more manageable.”

And for his patients that do not exercise, Dr. Miller encourages them to take a brisk walk around the block – starting with just once or twice a week. “These small steps help because they are doable. Even the smallest changes can make a difference in a person’s health. ”

Studies show that people have better success achieving goals when they have a partner on board, which also adds a level of accountability.

“When I consult with a patient with diabetes, I also emphasize the problem-solving nature of self-management and ask them to work with me and their other doctors, on achievable, shared goals that both physician and patient can get behind,” says Dr. Miller.

“At Stony Brook, we have looked into novel approaches to secondary prevention, education and outreach for both type 1 and type 2 diabetes including one-on-one nutrition counseling available; supporting self-managed diabetes care for patients hospitalized for other conditions; and creating diabetes discharge tools,” says Dr. Miller.

Learning about your disease and available treatment for it is another step. “It's important for patients and their loved ones to have informative conversations about the various medication and lifestyle options with their doctors to help identify the best treatment with the greatest chances of success,” says Dr. Miller.

“The number of new medications available to treat type 2 diabetes including newer insulins for people with both major types of the disease is growing exponentially. Endocrinologists are recognizing more and more that treatment for patients with diabetes should be individualized as each patient is unique.”

Stony Brook Medicine has made diabetes a priority and have taken the lead in population health initiatives in Suffolk County to overhaul the management of chronic conditions in the Medicaid population.

On the fourth Monday of the month, Stony Brook holds free seminars in the hospital’s cafeteria on all kinds of topics— from the latest research to the best approaches to individualized self-management.

“If someone is concerned about their risk for diabetes, I would tell them to have a conversation with their doctor and ask about screening,” says Dr. Miller. “Then start making small changes, every little bit helps.”

About Stony Brook University Hospital:

Stony Brook University Hospital (SBUH) is Long Island’s premier academic medical center. With 603 beds, SBUH serves as the region’s only tertiary care center and Regional Trauma Center, and is home to the Stony Brook University Heart Institute, Stony Brook University Cancer Center, Stony Brook Children’s Hospital, Stony Brook University Neurosciences Institute, and Stony Brook University Digestive Disorders Institute. SBUH also encompasses Suffolk County’s only Level 4 Regional Perinatal Center, state-designated AIDS Center, state-designated Comprehensive Psychiatric Emergency Program, state-designated Burn Center, the Christopher Pendergast ALS Center of Excellence, and Kidney Transplant Center. It is home of the nation’s first Pediatric Multiple Sclerosis Center. To learn more, visit

Barriers to Health Care Increase Disease, Death Risk for Rural Elderly

Newswise, November 16, 2015 - A new study of adults ages 85 or older has found that rural residents have significantly higher levels of chronic disease, take more medications, and die several years earlier than their urban counterparts.

The findings were just published in The Journal of Rural Health by researchers from Oregon State University and the Oregon Health & Science University.

The research confirms some of the special challenges facing older populations in rural or remote areas, who often have less access to physicians, long distances to travel for care, sometimes a lower socioeconomic and educational level, and other issues. 

It also reflects health problems that might have been reduced if they were treated earlier or more aggressively, researchers say.

Data from several different study groups found that rural residents measured significantly higher on the Modified Cumulative Illness Rating Scale, with about an 18 percent higher disease burden.

"It's been known for some time that health care is harder to access in rural areas, and this helps us better understand the extent of the problem," said Leah Goeres, a postdoctoral scholar who led the research at the Oregon State University/Oregon Health & Science University College of Pharmacy.

"Many physicians do the best they can in rural areas given the challenges they face," Goeres said.

"But there are fewer physicians, fewer specialists, a higher caseload. Doctors have less support staff and patients have less public transportation. A patient sometimes might need to wait months to see a doctor, and have to drive significant distances. Adverse effects can increase from taking multiple medications.

"These are real barriers to choice and access, and they affect the quality of care that's available."

Also worth noting, Goeres said, is that especially in very old populations, illness can lead to more illness and quickly spiral out of control. A patient in an urban setting might receive prompt treatment for a mild ulcer, whereas the same person in a rural setting might have to wait while the condition worsens and may even lead to cancer.

"It's of particular concern that rural older adults start with more disease burden, which significantly increased over the next five years, but the average number of medications they used decreased over the same time period," said David Lee, an assistant professor in the OSU College of Pharmacy who oversaw the research.

"This may be due to difficulty accessing health care, leading to more disease burden over time, yet less use of medications," Lee said. "The opposite trends are seen in urban older adults."

This research was done in Oregon with three cohorts of older adults, one rural and two urban, and 296 people altogether. It was supported by the Oregon Alzheimer's Disease Tax Checkoff Fund and the National Institutes of Health.

The findings of the new study include:

  • The rural population of Oregon contains a greater proportion of older adults than the urban population.
  • The use of many medications can be especially risky for people in their 80s and 90s, leading to a concern called "polypharmacy" when a person takes five or more medications.
  • Rural participants were found to use an average of 5.5 medications, compared to 3.7 for urban participants.
  • At baseline measurements, valuable medications to aid bone mineralization were often used less in rural populations, but pain-killing opioids were used more often.
  • Medication use for high blood pressure went up significantly over time for rural populations, but not urban ones, in which their use had already been higher.
  • The rate of disease accumulation was significant in the rural cohort, and negligible in their urban counterparts.
  • The median survival time of the rural cohort was 3.5 years, compared to 7.1 years for the urban older adults.
  • Risk factors of chronic diseases were low education, poor socioeconomic status, a history of chronic disease, being female, and older age. These factors are associated with a typical rural population.
  • Living with someone, and/or having a large social network are protective factors against chronic disease, and may be more common in an urban or suburban population.
  • Both urban and rural residents used a large number of over-the-counter agents, including vitamins, minerals and herbal supplements.

Increased access to health care, health education, increased supervision from clinicians, and better management of both prescription and over-the-counter medications could all be of value in helping rural residents to live longer and healthier livers, the researchers said in their conclusion.

Friday, November 13, 2015

Melanoma’s Genetic Trajectories Are Charted in New Study

Study Confirms ‘Intermediate’ Disease Stage Between Benign Moles and Malignancy

Newswise, November 13, 2015 — An international team of scientists led by UC San Francisco researchers has mapped out the genetic trajectories taken by melanoma as it evolves from early skin lesions, known as precursors, to malignant skin cancer, which can be lethal when it invades other tissues in the body.

By tracing the genetic changes that take place over time in the development of the disease, the research reaffirms the role of sun exposure in the emergence of precursor lesions, such as the common moles known as nevi, but also suggests that continued ultraviolet radiation (UV) damage to benign precursor lesions may push them on a path toward malignancy.

More significantly, the study provides new evidence that genetic and cellular characteristics of skin lesions that are neither clearly benign moles nor malignant melanoma place them in a distinctive intermediate category, the existence of which has been hotly debated among dermatologists and pathologists.

“What happens to patients now is totally unstandardized,” said Boris Bastian, MD, PhD, the Gerson and Barbara Bass Bakar Distinguished Professor of Cancer Research at the UCSF Helen Diller Family Comprehensive Cancer Center (HDFCCC), and senior author of the new study. “Some doctors consider these ‘intermediate’ types of lesions to be entirely benign, or shave off only part of the lesion and leave some behind. But others treat it as an early melanoma. This work should open the door to understanding how risky these lesions are and when they should be completely removed.”

When a melanoma is diagnosed, its precursor lesion is sometimes still present on the skin adjacent to the cancer. As reported in the November 12, 2015 issue of The New England Journal of Medicine, the research team took advantage of this unique feature of the disease to identify the genetic differences between precursors and melanoma.

Led by A. Hunter Shain, PhD, a postdoctoral fellow in the Bastian laboratory and HDFCCC member, the scientists gathered skin samples containing both precursor lesions and melanoma that had been obtained from 37 patients, and they then sequenced 293 cancer-causing genes in 150 distinct areas micro-dissected from those samples.

In a clever study design, to determine how genetic analysis would align with standard techniques used in melanoma diagnosis, each of these 150 areas was independently examined through microscopes by eight pathologists 
specializing in skin disease. 

The pathologists assigned each area to four main categories ranging from “benign” to “invasive melanoma” based on their judgments of how far the cells in each area had progressed toward malignancy.

Intriguingly, in all of the 13 areas that were unanimously assessed as benign by the pathologists, the researchers found only a single pathogenic mutation, one called BRAF V600E, which has long been associated with melanoma. Based on these data, this single alteration in the BRAF gene appears to be sufficient for the formation of a nevus, the term for a common mole that can sometimes progress to melanoma.

Likewise, there was quite good agreement among the pathologists regarding invasive melanomas, which on genetic analysis were found to contain a large number of point mutations—alterations of a single genetic “letter”—affecting many genes, as well as a significant number of copy-number alterations, in which sizeable segments of the genome containing genes are either deleted or duplicated.

As expected, most disagreement among the pathologists was seen in their assessments of non-invasive melanomas (known as “in situ” melanomas) and so-called intermediate lesions, which were sub-classified as “probably benign” or “probably malignant.”

But the genetics of these lesions presented a clearer picture: in most cases, BRAF mutations, most often the V600E mutation seen in the benign lesions, were accompanied by additional pathogenic mutations, but not the full set observed in invasive melanoma. 

In particular, many BRAF mutations in the intermediate lesions were accompanied by mutations in a gene known as TERT. The TERT gene helps to set the limits of cell division, and the gene has been implicated in a number of types of cancer.

Moreover, while the researchers found more point mutations in intermediate lesions than in benign moles, there were far fewer point mutations in intermediate lesions than in invasive melanomas, and copy-number alterations were rare.

“There’s good agreement between the pathologists’ assessments at the extremes of the spectrum, but less so with intermediate lesions,” said Shain. 

“On a genetic level, however, this work clearly shows that there are intermediate lesions. These things really exist—it’s not a binary situation.”
Mutations caused by UV damage have a distinctive genetic “signature,” and in another significant finding, the researchers observed this signature in cancer-causing genes at every stage of melanoma progression.

“A lot of melanomas have been sequenced at this point, and while it’s clear they carry UV-induced mutations, no one knew when they occurred,” Bastian said.

 “This study shows that they occur in benign moles, in the melanoma that arises from these moles, and in intermediate lesions. UV both initiates and causes the progression of melanoma, so exposing even benign moles to the sun is dangerous.”

According to Shain, the new study’s findings on UV-induced mutations provides additional grounding to well-documented aspects of melanoma epidemiology.

“Kids who are in the sunlight more tend to have a greater number of benign moles, and if they continue to stay in the sunlight, those moles are more likely to progress to melanoma,” Shain said.

 “This study shows that UV-radiation-induced mutations start to accumulate before a benign mole forms, and that UV-radiation-induced mutations continue to drive the progression of some benign and intermediate lesions towards melanoma. So exposing even benign moles to UV is not without risk.”

In addition to Bastian and Shain, UCSF researchers participating in the study included Iwei Yeh, MD, PhD, assistant professor of dermatology; Eric Talevich, PhD, programmer and analyst in the department of pathology; Alexander Gagnon, BA, a former research assistant in the Department of Pathology and Department of Dermatology, now at Genia Technologies in Oakland, Calif.; Jeffrey North, MD, assistant professor of dermatology and pathology; Laura Pincus, MD, assistant professor of dermatology and pathology; and Beth Ruben, MD, professor of clinical dermatology and pathology. 

They were joined by colleagues from the Cleveland Clinic, in Ohio; Orlando Health, in Florida; University Hospital of Zurich, in Switzerland; Dorset County Hospital, in Dorchester, England; and St. John’s Institute of Dermatology, in London, England. 

The work was supported by grants from the National Institutes of Health and the Gerson and Barbara Bass Bakar Distinguished Professorship in Cancer Research.

UC San Francisco (UCSF) is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

 It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy, a graduate division with nationally renowned programs in basic, biomedical, translational and population sciences, as well as a preeminent biomedical research enterprise and two top-ranked hospitals, UCSF Medical Center and UCSF Benioff Children’s Hospital San Francisco.

Wednesday, November 11, 2015

Orchestra Helps Boost Confidence and Mood for Those with Dementia

Newswise, November 11, 2015 — A special orchestra for people with dementia has helped boost their confidence and mood, according to a new research project.

The orchestra group has been set up by the Bournemouth University Dementia Institute (BUDI) in Dorset to create a sense of community among participants and also includes professional musicians, carers and students.

A screening of performances from the BUDI Orchestra will be showcased at an event as part of the annual Economic and Social Research Council’s (ESRC) Festival of Social Science.

The orchestra was initially set up in partnership with Bournemouth Symphony Orchestra (BSO) with a repertoire ranging from Ravel’s Bolero to Henry Mancini’s Moon River.

Rehearsals have demonstrated a positive effect on all participants who have also learned new skills and rediscovered old ones.

“Music touches everyone in some way, either by listening or playing – and the BUDI Orchestra has been a life-enhancing project which has benefited everyone,” says Professor Anthea Innes, Head of BUDI.

“Performing and showcasing skills of those with dementia creates a well-deserved opportunity for them to demonstrate their abilities and to challenge the negative public perceptions that surround the diagnostic label of ‘dementia’.

Working together to produce a collaborative output is a powerful way to bring out the best in people - not just in terms of their musical skills, but their communication skills, friendships, care and support for one another.”

Around 850,000 people in the UK currently live with dementia, a figure which is estimated to double by 2050. Dorset has one of the oldest populations in England, so many people in the local community can relate to the challenges caused by the condition.

The arts are being used increasingly to support health and wellbeing, both in healthcare settings and in the community for people with dementia and their families. 

Research has already shown that arts activities, especially music, can reawaken and exercise the brain.

The BUDI Orchestra, funded by Dorset County Council, is one of BUDI’s numerous ongoing creative projects to demonstrate that people with dementia can have fun while learning.

A total of eight people with dementia and seven carers were involved in a course of eight weekly two-hour sessions led by Andy Baker, a former BSO community musician and double bass player. They were also supported by two additional professional musicians, Bournemouth University students and staff volunteers.

Previous workshops with the orchestra have identified that most of the people with dementia learned a new skill and the sessions were highly enjoyed by all who took part.

One of the participants was Jack, a professional bass player who was forced by eye cancer and dementia to leave his bands. His wife also joined BUDI and played the violin for the first time since school.

Both found that the orchestra helped overcome feelings of loneliness, and Jack’s confidence returned as a result of being part of the sessions.

The project has also highlighted that the musicians’ and volunteers’ preconceptions of music learning were positively challenged as a result of their experiences with the BUDI Orchestra.

Professor Innes and her research team have produced a guide in collaboration with the professional musicians for those interested in setting up their own community-based music group.

Dr Michelle Heward, also from BUDI, says: “Our creative projects show that it is possible for people with dementia to take part, learn something new and have fun, all at the same time.”

Extra Holiday Stress Could Be Rough on a Woman’s Heart

Newswise, November 11, 2015 — Many women put a lot pressure on themselves to make the holidays perfect for everyone. Everything from cooking to buying presents to organizing family gatherings can add a lot of unnecessary stress that can damage their hearts.

“We have seen more than a few cases of stress-induced cardiomyopathy around the holidays,” said Dr. Karla Kurrelmeyer, a cardiologist with Houston Methodist DeBakey Heart & Vascular Center.

“This occurs when women are under great amounts of stress for a short period of time and that stress is compounded with another traumatic event such as a death in the family, a car accident, loss of money, etc. If it is ignored it can be fatal.”

Stress-induced cardiomyopathy is a weakening of the left ventricle, the heart’s main pumping chamber.

It is brought on by the release of stress hormones that shock the heart, causing changes in the heart muscles that then cause the left ventricle to not work properly. The vast majority of people who are affected by this condition are women in the late 50s to mid-70s.

“Someone experiencing this condition might develop chest pains or shortness of breath after severe stress, either emotional or physical,” Kurrelmeyer said.

“In most cases, it is treated with medication such as beta blockers or ACE inhibitors. It’s important to have an echocardiogram as soon as possible if you are experiencing any symptoms.”

A spike in blood pressure is also seen a lot around the holidays. Kurrelmeyer says many women end up in the ER with chest pains or palpitations and, in the most severe cases, can suffer a stroke.

If a woman has a history of high blood pressure it’s important to monitor it closely, especially during those times when the stress level rises.
Heart problems in women are not usually as recognizable as they are in men.

Some of the symptoms for women include:
• Extreme weakness, anxiety, or shortness of breath.
• Discomfort, pressure, heaviness or pain in the chest, arm, below the breastbone or in the middle of the back.
• Sweating, nausea, vomiting, dizziness.
• Fullness, indigestion, a tightness in the throat area.
• Rapid or irregular heartbeats.

“It’s important to take time for yourself during the holiday season and do things that will help relieve your stress,” Kurrelmeyer said. “Exercise, either walking or running, yoga, meditation, a nice walk with a loved one, whatever it takes, make it happen. The holidays should be a joyous time spent with family and friends at home, not with doctors in an emergency room.”

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Tuesday, November 10, 2015

How Low to Go for Blood Pressure? Lower Target Could Affect Millions of Americans

Systolic Blood Pressure Intervention Trial recommendations may have broad impact

Newswise, November 10, 2015 - A new study finds that at least 16.8 million Americans could potentially benefit from lowering their systolic blood pressure (SBP) to 120 mmHg, much lower than current guidelines of 140 or 150 mmHg.

The collaborative investigation between the University of Utah, University of Alabama at Birmingham, and Columbia University, will be published Nov. 9 online in the Journal of the American College of Cardiology (JACC).

The scientists calculated the potential impact of preliminary results from the Systolic Blood Pressure Intervention Trial (SPRINT) that will be presented in full at the American Heart Association meeting and published online in the New England Journal of Medicine, also on Nov. 9.

The initial analysis of SPRINT, reported in September, 2015, showed that using antihypertensive medications to reach a lower SBP target of 120 mmHg could greatly reduce risk for heart failure, heart attack, and death, compared to a target of 140 mmHg (SBP is the top number in a blood pressure reading).

 It’s estimated that one in three U.S. adults have high blood pressure, or hypertension, a significant health concern.

“SPRINT could have broad implications,” says lead author Adam Bress, Pharm.D., M.S., assistant professor of pharmacotherapy at the University of Utah College of Pharmacy. “Millions of Americans whose blood pressure is under control according to current guidelines may be considered uncontrolled if new guidelines adopt the intensive target of less than 120 mmHg studied in SPRINT.”

While new medical guidelines for treating hypertension could be months to years away, this research finds that more than 16.8 million Americans, 7.6 percent of the population, could be recommended for intensive blood pressure management if guidelines incorporate a new, lower, SBP target based on SPRINT results. The number represents Americans who meet the same criteria as SPRINT participants: they are age 50 or older, have an SBP between 130-180 mmHg, are at high risk for cardiovascular disease, and do not have diabetes or a history of stroke, among other inclusion and exclusion criteria.

The current study also reports that new guidelines may affect some segments of the population more than others. Compared to Caucasians, African Americans and Hispanics were less likely to meet SPRINT eligibility criteria (9 percent vs. 4.8 percent, 4.3 percent).

The differences are largely due to the fact that these minority populations have a higher prevalence of diabetes and other health conditions that could preclude them from being SPRINT eligible. Men were also more likely to be eligible for SPRINT than women (8.8 percent vs. 6.5 percent), in part because unlike men, women tend not to show increased risk for cardiovascular disease until they are over 65.

However in practice, it’s common for physicians to prescribe treatments to patients who may have not been eligible for a clinical trial that demonstrated the efficacy and safety of a particular treatment.

For example, some physicians may deviate from SPRINT eligibility by aggressively treating the blood pressure of any adult over 50, even if they do not have a high risk of cardiovascular disease. “Physicians are going to need to decide how far outside the SPRINT inclusion criteria to go,” says co-author Rachel Hess, M.D., M.S., also a professor of internal medicine and population health sciences at the University of Utah School of Medicine. “It’s going to be a tough decision.”

The numbers of Americans meeting each sequential SPRINT eligibility requirement are:
• 219 million adults
• 95.1 million age 50 or older
• 37.3 million with elevated blood pressure (≥130 mmHg)
• 26.4 million at high risk for cardiovascular disease
• 16.8 million with no diabetes, history of stroke, or other SPRINT exclusion criteria

Potential impacts of SPRINT results on the U.S. population were based on analyzing data from the 16,260 participants in the National Health and Nutrition Examination Survey (NHANES) between 2007 – 2012 who met certain SPRINT inclusion and exclusion criteria. NHANES includes a representative cross-section of the American population, allowing for projection of these findings to the overall population.

Most, but not all, SPRINT inclusion and exclusion criteria were accounted for in NHANES. For example information on subclinical cardiovascular disease and a history of medical non-adherence are not represented in the national survey.

New blood pressure guidelines will have to weight potential adverse effects that could overshadow its benefits, and whether increasing blood pressure medications over the course of multiple years is cost-effective.

But the numbers obtained in this study offer a glimpse into the potentially wide ranging impact of changing blood pressure guidelines.

“Given that millions of U.S. adults meet SPRINT eligibility criteria, the implementation of SPRINT recommendations could have a profound impact on how blood pressure is treated in this country,” says senior author Paul Muntner, Ph.D., a professor of epidemiology at the University of Alabama.

“Even more important, is its potential for greatly reducing the incidence of cardiovascular disease.”

In addition to Bress, Hess, and Muntner, the co-authors are Rikki Tanner and Lisandro Colantonio from the University of Alabama, and Daichi Shimbo from Columbia University.

“Generalizability of results from the Systolic Blood Pressure Intervention Trial (SPRINT) to the US adult population” will be published online in the Journal of the American College of Cardiologists on Nov. 9, 2015

First, Do No Harm: Hospital Patients Given Anti-Heartburn Drugs Have Higher Risk of Dying, Study Finds

U-M/VA computer model suggests that common use of acid-reducing medicine to prevent stomach bleeding increases mortality from infections

Newswise, November 10, 2015 — Right now, in any American hospital, about half of the patients have a prescription for an acid-reducing drug to reduce heartburn or prevent bleeding in their stomach and gut.

But that well-intentioned drug may actually boost their risk of dying during their hospital stay, a new study finds – by opening them up to infections that pose more risk than bleeding would.

In fact, according to a computer simulation based on real-world risk and benefit data, around 90 percent of hospital inpatients who were first prescribed these drugs in the hospital have a higher risk of dying when they’re taking them, compared with their risk if they hadn’t gotten the prescription.

And for around 80 percent of patients who were already on these common drugs, called proton-pump inhibitors or PPIs, when they arrived at the hospital, staying on them also may lead to a small increase in the risk of dying.

The extra risk of death comes from the fact that reducing acid in the stomach can increase the risk of infections – especially pneumonia and Clostridium difficile, both of which pose a serious risk to hospitalized patients who develop them.

The study, which uses a computer model to achieve a result that otherwise would require an impractically large clinical trial, is published in the Journal of General Internal Medicine by a team from the University of Michigan Medical School and VA Ann Arbor Healthcare System.

“Many patients who come into the hospital are on these medications, and we sometimes start them in the hospital to try to prevent gastrointestinal, or GI, bleeds,” says lead author Matthew Pappas, M.D., MPH.

“But other researchers have shown that these drugs seem to increase the risk of pneumonia and C. diff, two serious and potentially life-threatening infections that hospitalized patients are also at risk for,” he continues. 

“Our new model allows us to compare that increased risk with the risk of upper GI bleeding. In general, it shows us that we’re exposing many inpatients to higher risk of death than they would otherwise have – and though it’s not a big effect, it is a consistent effect.”

As a result of the new findings, he says, very few hospital patients should start taking or continue on PPIs as a preventive measure against gastrointestinal bleeding.

Pappas, a hospitalist physician at U-M with an engineering background and a VA Health Services Fellow, worked with Sandeep Vijan, M.D., MPH, who treats patients at the VAAHS and is a member of the VA Center for Clinical Management Research and U-M’s Institute for Healthcare Policy and Innovation.

 Pappas is a clinical lecturer, and Vijan a professor, in the U-M Medical School’s Division of General Medicine. The project’s only funding was Pappas’s fellowship support.

Cutting PPI use to cut infection risk

Pappas notes that nationally, some efforts have already shown ways to reduce the rate of new PPI prescriptions to hospitalized patients – about 20 percent of whom receive such orders right now.

But truly reducing PPI use in hospitals to the most appropriate patients – those with existing GI bleeding – will take more effort, Pappas predicts.

That’s because PPIs are built into many heuristics, or rules of thumb, that guide much hospital care. For instance, when a patient receives high-dose steroids in the hospital, the physician may automatically also prescribe a PPI to prevent the GI bleeding that steroids can cause.

“In fact, in running our simulation, we thought we would find some populations such as those on steroids or other medications often prescribed together with PPIs, who would not experience the increased mortality risk,” Pappas says. 

“But that turned out not to be the case.” GI bleeds are risky, it’s true. But hospital-acquired pneumonia and C. diff are much more common.
Although research is still needed on why PPI use increases a patient’s vulnerability to hospital-acquired pneumonia and C. diff infection, the effect of the acid-reducing drugs on gut bacteria likely has a direct impact. In the case of pneumonia, suppressing acid production may increase the amount of bacteria in the stomach and throat, which can then get into the lungs and cause pneumonia.

Model can be used for other risk-benefit balancing

Pappas notes that the model he developed with Vijan and recent U-M Ford School of Public Policy graduate Sanjay Jolly could be applied to many other situations where a common preventive or treatment measure in medicine also carries with it an increased risk of an unwanted effect.

Using such models, based on data from observational studies, could answer important questions in medicine without needing to carry out massive prospective clinical trials. 

To answer the question of whether the predicted increase in mortality risk caused by PPIs in inpatients is real, he says, would take a clinical trial of more than 64,000 patients randomly assigned to receive PPIs or not. Since PPIs are available as generic medications, the likelihood of such a study being funded and performed is nearly zero.

“Any time there are complex risk/benefit tradeoffs, without the possibility of a high-quality trial, this kind of simulation can help us come up with answers to inform clinical care,” he says.

For instance, he’s now studying the issue of “bridging” medication in patients who have been prescribed blood-thinning medications to prevent a stroke. Such patients often receive a prescription for an injected drug that will reduce stroke risk during the week or two before their regular oral drugs take effect. 

But that injection carries its own risk.

“Humans aren’t very good at recognizing very rare events, and reacting appropriately to things that are unlikely to happen,” says Pappas. 

“Physicians have an instinct to want to prevent very bad, though rare events – but everything we do carries risks. We need to be mindful of the things we are doing to prevent rare outcomes, and keep the risks in perspective. Computers can help.”

Reference: Journal of General Internal Medicine, DOI:10.1007/s11606-015-3536-7