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Newswise — DURHAM, N.C. – Aspirin’s ability to reduce the risk of both cardiovascular disease and colon cancer has been a welcome, yet puzzling, attribute of the pain reliever that has been a mainstay in medicine cabinets for more than 100 years. Now researchers at Duke Healthhave identified a new mechanism of aspirin’s action that appears to explain the drug’s diverse benefits. Publishing in the journalEBioMedicine, the researchers describe how aspirin directly impacts the function of a gene regulatory protein that not only influences the function of platelets, but also suppresses tumors in the colon. “This research identifies a new way in which aspirin works that was not predicted based on the known pharmacology,” said lead author Deepak Voora, M.D., assistant professor in Duke’s Center for Applied Genomics & Precision Medicine. Voora said aspirin’s pain-reducing and blood thinning powers have long been traced to its ability to block COX-1, an enzyme involved in both inflammation and blood clotting. “But COX-1 has only partially explained how aspirin works for cardiovascular health,” he said, “and it has not been shown to be implicated in cancer at all.” Instead, Voora and colleagues focused on a pattern of gene activity they call an aspirin response signature the team had previously developed. The signature identified a network of genes that correlated with platelet function and heart attack. “This approach to comprehensively evaluate the actions of a drug using genomic data -- as we have done here with aspirin -- is a paradigm shift that could change how drugs are developed and positioned for clinical use, said co-author Geoffrey Ginsburg, M.D., director of the Center for Applied Genomics & Precision Medicine. “We intend to use this approach to explore the pleiotropic effects of drugs more broadly to anticipate their side effects and understand their full repertoire of actions clinically.” In addition to Voora and Ginsberg, study authors from Duke include Rachel Myers, Emily Harris and Thomas L. Ortel. They were joined by A. Koneti Rao and Gauthami S. Jalagadugula of Temple University. The National Institute of Health provided grant funding (RC1GM091083, R01HL109568, R01HL118049). ###    

Newswise — Living a heart healthy lifestyle is not about doing just one thing. Other steps are important too. “Diet, exercise and even a positive attitude are all factors that can help you avoid heart disease,” says Dr. Sheila Sahni, an interventional cardiology fellow at the David Geffen School of Medicine at UCLA. How to get started? Begin with small, incremental changes, Sahni says. Eat well. Go for nutrient-rich foods from a wide range of food groups. Focus on eating meals or snacks with high-protein such as white meat, fish, eggs, low-fat milk and soy. Good fats are OK. These include avocado, nuts and peanut butter. Don’t forget to eat at least five servings of fruits and vegetables a day. When it comes to starches, stick to complex carbohydrates such as whole grains, beans and most vegetables. They’ll keep you feeling full for a longer period of time. The best fish for heart health are firm, fatty, cold-water fish like salmon, halibut and tuna. These have the highest levels of heart healthy omega 3 fats. If you don’t like fish, use fish oil supplements. Limit or avoid certain foods. Saturated fat and trans fat can increase cholesterol, which can harm your heart. These are commonly found in margarines, partially hydrogenated vegetables fats, processed and fast foods. Red meats taste great but are associated with worse health outcomes. Choose white meat such as chicken or pork. Sweets, sugar-sweetened beverages and refined grains like white rice, white bread or sweetened cereals are associated with more weight gain and worse health outcomes. Instead, eat whole grain foods such as brown rice, whole wheat bread and oatmeal. Burn those calories throughout the day. Exercise is key! Taking the stairs, walking while you’re on the phone, parking further away at the shopping center or work can help you get more exercise. The American Heart Association recommends 150 minutes of moderately intense exercise or 75 minutes of vigorous activity each week. Intensity is defined relative to an individual’s capacity, but some examples of moderate intensity activity are walking briskly, water aerobics, ballroom dancing and gardening. Some examples of vigorous intensity activity include swimming laps, jumping rope, race walking or jogging, or hiking uphill. Remember that you are in control of how you fit movement into your daily schedule. Be optimistic!Optimism has been shown to be associated with better health. Many studies have shown that heart patients with a healthier psychological state have better outcomes. And people with a positive outlook tend to have better health behaviors, which tend to lead to better overall health outcomes. Know your heart’s health.The best way to know if you’re “heart healthy” is to see your doctor for a physical examination to determine any heart disease risk factors, such as high blood pressure, high cholesterol or a family history of premature heart disease or diabetes. “Once you know your risk factor profile, you can gauge your health by getting those risk factors under control,” says Dr. Gaurav Banka, a clinical cardiology fellow at UCLA. “For instance, if you have high blood pressure and you start to exercise and your blood pressure decreases, you know you’re moving in the “heart healthy” direction. Risk factor control and management is the optimum way to care for your heart because it’s a preventive measure against heart disease.”      

Newswise — Hospitals on average charged more than 20 times their own costs in 2013 in their CT scan and anesthesiology departments ― suggesting that hospitals strategically use “chargemaster” markups to maximize revenue, according to new research from Johns Hopkins University. Appearing in the September issue of Health Affairs, the study notes that many hospital executives say the chargemaster prices determined by individual hospitals for billable items are irrelevant to patients. However, the relation between chargemaster markups and hospital revenue and the variation in markups across hospitals and departments show that the hospitals are still using their chargemaster markups to enhance revenues, say the study’s authors, Ge Bai of the Johns Hopkins Carey Business School and Gerard F. Anderson of the Johns Hopkins Bloomberg School of Public Health. “Hospitals apparently mark up higher in the departments with more complex services because it is more difficult for patients to compare prices in these departments,” states lead author Bai, a Carey Business School assistant professor whose expertise is in accounting issues within the health care industry. As the chart below indicates, average charge-to-cost ratios for hospital departments vary from a low of 1.8 for inpatient general routine care to a high of 28.5 for computed tomography (CT) scan, with anesthesiology right behind at 23.5. This means that a hospital whose costs in the CT department are $100 will charge a patient without health insurance and an out-of-network privately insured patient $2,850 for a CT scan. Anderson, a professor in the Bloomberg School’s Department of Health Policy and Management, says the impact of hospital markups is vast: “They affect uninsured and out-of-network patients, auto insurers and casualty and workers’ compensation insurers. The high charges have led to personal bankruptcy, avoidance of needed medical services, and much higher insurance premiums.” Hospitals with strong market power, through either system affiliations or dominance of regional markets, were more likely to set high markups, as revealed by financial data in 2013 collected by the authors from all Medicare-certified hospitals with more than 50 beds. In their paper, the authors examine the average hospital’s overall charge-to-cost ratio, which expresses the ratio of what the hospital charged compared to the hospital’s actual medical expense. In 2013, the average hospital with more than 50 beds had a charge-to-cost ratio of 4.32 ― that is, the hospital charged $4.32 when the cost was only $1. However, certain types of hospitals had higher markups. In government-run hospitals, the ratio was 3.47; in nonprofit hospitals, 3.79; and in for-profit hospitals, 6.31. System-affiliated hospitals had an average ratio of 4.76, versus 3.54 for independent hospitals, and hospitals with regional market power had an average ratio of 4.56, versus 4.16 for hospitals that lacked such clout ― supporting the researchers’ finding that hospitals that can mark up prices will do so. The markups help their bottom lines; a one-unit increase in markup, such as from 3.0 to 4.0, is linked with a $64 higher revenue per adjusted discharge. Besides the setting of a cap on the maximum markup hospitals can charge, Bai and Anderson recommend two solutions to high markups. First, improve the transparency of markups by requiring hospitals to provide a benchmark rate, such as what Medicare would pay for the same services, on all medical bills so that patients can compare the amounts, while also requiring hospitals to disclose the total charges as a separate line item on their annual income statements. Second, improve the consistency of the charge-to-cost ratios across all departments and services within each hospital. “Mandatory disclosure on medical bills and financial statements will be an important step toward markup transparency,” says Bai. “We realize that any policy proposal to limit hospital markups would face a very strong challenge from the hospital lobby,” says Anderson, “but we believe the markup should be held to a point that’s fair to all concerned ― hospitals, insurers, and patients alike.” “US Hospitals Were Still Using Chargemaster Markups to Maximize Revenues In 2013” was written by Ge Bai and Gerard F. Anderson and appears in the September 2016 issue of Health Affairs.------ Average Charge-to-Cost Ratios for Selected Hospital Patient Care Departments, 2013 RANK DEPARTMENT CHARGE-TO-COST RATIO*1 Computed tomography scan 28.52 Anesthesiology 23.53 Magnetic resonance imaging 13.64 Electrocardiology 12.4 5 Electroencephalography 9.36 Cardiac catheterization 8.77 Laboratory 8.58 Medical supplies charged to patients 8.39 Radioisotope 7.210 Renal dialysis 6.511 Radiology-diagnostic 6.412 Drugs charged to patients 5.913 Emergency 5.714 Respiratory therapy 5.515 Recovery room 5.316 Operating room 5.117 Occupational therapy 5.018 Speech pathology 4.819 Labor room and delivery room 4.420 Implantable device charged to patients 3.621 Clinic 3.022 Physical therapy 3.023 Nursery 2.724 Intensive care unit 2.125 Inpatient General routine care 1.8 * Charge-to-cost ratio is the dollar charge for every $1 of actual patient care cost incurred by the hospital. For example, a ratio of 7.2 means a hospital charge of $7.20 for every dollar of actual patient care cost. SOURCE: Authors’ analysis of data from Medicare cost reports and Final Rule Data obtained from the Centers for Medicare and Medicaid Services for 2013.   SEE ORIGINAL STUDY    

With nearly sixty percent of American adults now taking prescription medications—from antidepressants to cholesterol treatments—there is growing concern about how many drugs are flowing through wastewater treatment facilities and into rivers and lakes. Research confirms that pharmaceutical pollution can cause damage to fish and other ecological problems—and may pose risks to human health too. Scientists have assumed that people flushing their unused medications down the drain or toilet was a major source of these drugs in the water. But a new first-of-its-kind study tells a different story. “Less than one percent of students we surveyed report flushing any drugs down the drain in the last year,” says University of Vermont scientist Christine Vatovec. And what she and her colleagues found in the water backs up the students’ self-reporting. In Burlington, Vermont, Vatovec co-led a team of five scientists from the University of Vermont and the United States Geological Survey who sampled wastewater outflow for ten days during the spring when students from UVM and Champlain College were moving out. They detected fifty-one pharmaceuticals pouring into Lake Champlain—and they expected to see a spike in concentrations of some of these drugs as students dumped unused meds down the drain while they were departing their dorm rooms and apartments. But they didn’t see it. Concentrations of caffeine and nicotine decreased slightly after the students left (no surprise), but there was no data suggesting that students were flushing their unwanted medications. Many students reported having leftover prescription meds, but only a small portion of them disposed of these drugs, mainly in the trash. “This contradicts the common assumption that down-the-drain disposal is an important source of pharmaceuticals to the wastewater stream in the environment,” the team writes in their study, published August 29 in the journal Science of the Total Environment. A surprise “Our study is the first time that scientists have correlated data about how people are purchasing, using and disposing of their pharmaceuticals with data on what's actually coming down the pipe,” Vatovec says. Several surveys in recent decades indicated that a majority of Americans flush unfinished or unwanted medications. But the new study found a very different result in its survey of more than 300 students. “Flushing does not appear to be an important source,” says Patrick Phillips, a hydrologist with the US Geological Survey who co-led the new study. “I was surprised.” The scientists did detect a rise in allergy medications in the water that correlated to a rise in seasonal pollen. They also saw a relative rise in drugs used by older people—like diabetes and heart medications—after the younger people moved out. Current advice encourages people to take unneeded medications to drop-off days at police stations and pharmacies so they can be incinerated, and almost none of the students indicated that they were in the habit of tossing unwanted meds down the drain. However, some people who were, in earlier decades, encouraged to flush may still be doing that. “So we have more to learn about other parts of the population,” Vatovec says, but education efforts with students may not be the best investment since excretion and other sources of drugs, like pharmaceutical manufacturing, appear to be much more important sources of drugs in wastewater. Safe to drink Vatovec—who holds a joint faculty appointment in UVM's Rubenstein School of Environment and Natural Resources and the College of Medicine—is quick to note that there is no evidence that the extremely low concentrations of pharmaceuticals found in their survey and other similar studies pose any direct risk to human health. “These results should not make people nervous about swimming or drinking water,” she says, “because, to the best of scientific knowledge we have available right now, the concentrations are so low that you’d need to drink about the football field’s worth of lake water to get an actual dose of any one individual pharmaceutical.” And the team’s results in Burlington for Lake Champlain are not unusual. “Pharmaceuticals are found in about eighty percent of the surface waters tested in the United States,” Vatovec says. Which is one reason why she is eager to see the development of practices to help people manage their health with fewer medications—and to see the development of “green pharmacy” drugs that fully break down in the body. “We know these drugs in our surface waters can create ecological problems and there are more and more of them,” she says. Though there is no evidence yet that human health is threatened by pharmaceutical pollution, “there are many unanswered questions,” she says. SEE ORIGINAL STUDY

Newswise — CLEVELAND – Case Comprehensive Cancer Center researchers, a research collaboration which includes University Hospitals Seidman Cancer Center and Case Western Reserve University, who last year identified new gene mutations unique to colon cancers in African Americans, have found that tumors with these mutations are highly aggressive and more likely to recur and metastasize. These findings partly may explain why African Americans have the highest incidence and death rates of any group for this disease. The study is published online (http://jnci.oxfordjournals.org/content/108/12/djw164.full.pdf+html) and will be printed in the December 2016 issue of the Journal of the National Cancer Institute (JNCI) by members of a research team that a year ago found 15 genes in African Americans that are rarely or never detected as mutated in colon cancers from Caucasians. The current study investigated the outcomes associated with these mutations in African American colorectal cancer. The researchers examined 66 patients who had stage I – III colorectal cancer and found those patients positive for the mutations had an almost three times higher rate of metastatic disease, and stage III patients positive with mutations were nearly three times more likely to relapse compared to patients without the mutations. “This study is significant because it helps shed further light on why colorectal cancers are more aggressive in African Americans compared to other groups,” said the study’s senior author Joseph E. Willis, MD, Chief of Pathology at University Hospitals Case Medical Center and Professor of Pathology at Case Western Reserve School of Medicine. “While mortality rates for Caucasian men with colorectal cancer have decreased by up to 30 percent, they have increased by 28 percent for African American men since 1960,” said Dr. Willis, who is also director of tissue management in the Case Comprehensive Cancer Center. These findings and the earlier study only became possible because of technological advances in gene sequencing and computational analysis. These studies ultimately involved review of 1.5 billion bits of data. “This study builds on our previous genetic research on colorectal cancer,” said Sanford Markowitz, MD, PhD, a co-author and principal investigator of the $11.3 million federal gastrointestinal cancers research program (GI SPORE) that includes this project. ”It illustrates the extraordinary impact that dedicated, collaborative teams can make when they combine scientific experience and ingenuity with significant investment.” Announced in 2011, this GI SPORE program is one of just five in the country. Dr. Markowitz, Ingalls Professor of Cancer Genetics at Case Western Reserve School of Medicine and a medical oncologist at UH Seidman Cancer Center, included studies of the disease’s behavior in minority patients as part of his team’s original grant application. The disparity between colorectal cancer rates in African Americans and other groups has long existed; the most recent federal statistics, for example, put age-adjusted incidence at 46.8 cases for every 100,000 African Americans, and 38.1 cases for every 100,000 Caucasian Americans. Yet scientists have struggled to determine what factors — biological, economic, environmental, or others — account for this disparity. From the very start, Dr. Markowitz and colleagues believed the answer to this question would be found through genetic analysis.“Identifying gene mutations has been the basis of all the new drugs that have been developed to treat cancer in the last decade,” Dr. Markowitz said. “Many of the new cancer drugs on the market today were developed to target specific genes in which mutations were discovered to cause specific cancers.” “We wondered if colon cancer is the same disease molecularly in African American individuals as it is in Caucasian individuals. Or could colon cancer be the same disease behaving differently in one population compared to another,” he said. “This study gave us our answer. Colon cancer in African American patients is a different disease molecularly.” The scientists made their discovery by using DNA sequencing to compare 103 colorectal cancer samples from African American patients with 129 colorectal cancer samples from Caucasian patients, all of whom had received care at UH Case Medical Center in Cleveland. The scientists examined 50 million bits of data from 20,000 genes in every cancer. This research was supported by Public Health Service Awards Case GI SPORE P50 CA150964 and KO8 CA148980 and Career Development Program of Case GI SPORE Awards P50 CA150964; R21 CA149349, and P30 CA043703. Substantial and generous gifts also came from the Marguerite Wilson Foundation, the Leonard and Joan Horvitz Foundation, and the Richard Horvitz and Erica Hartman-Horvitz Foundation. Other collaborating authors for this paper were Zhenghe Wang, PhD; Li Li, MD, PhD; Kishoe Guda, PhD; Zhengyi Chen, PhD; Jill Barnholtz-Sloan, PhD; and Young Soo Park, PhD.# # #

Newswise — Heavy drinking frequently causes liver inflammation and injury, and fatty acids (FAs) involved in pro- and anti-inflammatory responses could play a critical role in these processes. This study evaluated heavy drinking and changes in levels of omega-6 (ω-6, pro-inflammatory) and omega-3 (ω-3, anti-inflammatory) FAs in alcohol dependent (AD) patients who showed no clinical signs of liver injury. Researchers assigned 114 heavy drinking AD patients recruited from an AD treatment program to one of two groups based on the levels of a specific liver enzyme, alanine aminotransferase--ALT, elevated levels of which reflect liver injury. The patients were aged 21–65 years and showed no signs of liver injury. Patient group one (34 males, 24 females) had normal levels of ALT and patient group two (40 males, 16 females) had mildly elevated ALT levels. Results indicated that changes in the ω-3 and ω-6 FA levels and the ω-6:ω-3 ratio reflected a pro-inflammatory shift in patients with elevated ALT—mild liver injury. At comparable levels of alcohol consumption, women in the study showed greater liver injury than men. The authors speculated that women may be at greater risk of developing alcoholic liver disease than men, even when consuming less alcohol. SEE ORIGINAL STUDY

Newswise — To treat or not to treat? That is the question researchers at the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) hope to answer with a new advance that could help doctors and their cancer patients decide if a particular therapy would be worth pursuing. Berkeley Lab researchers identified 14 genes regulating genome integrity that were consistently overexpressed in a wide variety of cancers. They then created a scoring system based upon the degree of gene overexpression. For several major types of cancer, including breast and lung cancers, the higher the score, the worse the prognosis. Perhaps more importantly, scores could accurately predict patient response to specific cancer treatments. The researchers said the findings, to be published Aug. 31 in the journal Nature Communications, could lead to a new biomarker for the early stages of tumor development. The information obtained could help reduce the use of cancer treatments that have a low probability of helping. Overtreating Cancer “The history of cancer treatment is filled with overreaction," said the study's principal investigator, Gary Karpen, a senior scientist in Berkeley Lab’s Division of Biological Systems and Engineering with a joint appointment at UC Berkeley’s Department of Molecular and Cell Biology. "It is part of the ethics of cancer treatment to err on the side of overtreatment, but these treatments have serious side effects associated with them. For some people, it may be causing more trouble than if the growth was left untreated." One of the challenges is that there has been no reliable way to determine at an early stage if patients will respond to chemotherapy and radiation therapy, said study lead author Weiguo Zhang, a project scientist at Berkeley Lab. "Even for early stage cancer patients, such as lung cancers, adjuvant chemotherapy and radiotherapy are routinely used in treatment, but overtreatment is a major challenge," said Zhang. "For certain types of early stage lung cancer patients, there are estimates that adjuvant chemotherapy improves five-year survival only about 10 percent, on average, which is not great considering the collateral damage caused by this treatment.” The researchers noted that there are many factors a doctor and patient must consider in treatment decisions, but this biomarker could become a valuable tool when deciding whether to use a particular therapy or not. Study co-author Anshu Jain, an oncologist at the Ashland Bellefonte Cancer Center in Kentucky and a clinical instructor at the Yale School of Medicine, added that the real value of this work may be in helping doctors and patients consider alternatives to the typical course of treatment. “These findings are very exciting,” said Jain. “The biomarker score provides predictive and prognostic information separate from and independent of clinical and pathologic tumor characteristics that oncologists have available today and which often provide only limited clinical value.” Hunting for New Biomarkers The study authors focused on genes regulating the function of centromeres and kinetochores – the essential sites on chromosomes that spindle fibers attach to during cell division – based upon results from earlier research by the Karpen group and other labs in the field. In normal cell division, microtubule spindles latch on to the kinetochores, pulling the chromosome's two chromatids apart. What the Karpen team previously found in fruit flies is that the overexpression of a specific centromere protein resulted in extra spindle attachment sites on the chromosomes. "This essentially makes new centromeres functional at more than one place on the chromosome, and this is a huge problem because the spindle tries to connect to all the sites," said Karpen. "If you have two or more of these sites on the chromosome, the spindles are pulling in too many directions, and you end up breaking the chromosome during cell division. So overexpression of these genes may be a major contributing factor to chromosomal instability, which is a hallmark of all cancers." This chromosomal instability has long been recognized as a characteristic of cancer, but its cause has remained unclear. To determine if centromeres play a role in chromosome instability in human cancers, the researchers analyzed many public datasets from the National Center for Biotechnology Information, the Broad Institute and other organizations that together contained thousands of human clinical tumor samples from at least a dozen types of cancers. The researchers screened 31 genes involved in regulating centromere and kinetochore function to find the 14 that were consistently overexpressed in cancer tissue. The extensive records included information on DNA mutations and chromosome rearrangements, the presence and levels of specific proteins, the stage of tumor growth at the time the patient was diagnosed, treatments given, and patient status in the years following diagnosis and treatment. This allowed the researchers to correlate the centromere and kinetochore gene expression score (CES) with patient outcomes either with or without treatments. Genome Instability and Cancer Therapy "We were surprised to find such a strong correlation between CES and things like whether the patient survived five years later," said Karpen. "Another finding – one that is counterintuitive – is that high expression of these centromere genes is also related to more effective chemotherapy and radiation therapy." The researchers hypothesized that the degree of chromosomal instability may also make cancer cells more vulnerable to the effects of chemotherapy or radiation therapy. "In other words, there's a threshold of genome instability," said Zhang. "At low to medium-high levels, the cancer thrives. But at much higher levels, the cancer cells are more susceptible to the additional DNA damage caused by the treatment. This is a really key point." The researchers pointed out that they found no link between very high levels of genome instability and improved patient survival without adjuvant treatments. Translating these findings into clinical advice and practice will take more research, the study authors caution. They are working to find that threshold of genome instability so that in the future, doctors and patients can make informed decisions about how to move forward. “Future steps will include investigating the CES in prospective clinical studies for validation in carefully selected patient cohorts," said Jain. "By establishing the clinical significance of the CES, oncologists will have greater confidence in guiding cancer patients toward treatments with the greatest benefit.” Other co-authors of the study are Jian-Hua Mao at Berkeley Lab’s Division of Biological Systems and Engineering; Wei Zhu at the Cellular Biomedicine Group in Shanghai; and Ke Liu and James Brown at Berkeley Lab's Division of Environmental Genomics and Systems Biology. Mao and Zhu provided critical expertise in bioinformatics for this research. The National Institutes of Health supported this work. ###

MEDFORD/SOMERVILLE  – Starting dialysis treatment for end-stage renal disease (ESRD) should be a shared decision made by an informed patient based on discussions with a physician and family members. However, many older dialysis patients say they feel voiceless in the decision-making process and are unaware of more conservative management approaches that could help them avoid initiating a treatment that reduces their quality of life, according to a study led by Tufts University researchers. The study, published online in Nephrology Dialysis Transplantation in advance of print, also found that patients who perceived they did not have a choice in starting dialysis reported low satisfaction with the treatment, despite acknowledging its life-extending benefits. The research coincides with the recent increase of attention to poor end-of-life care in the United States. The study’s link between the process of decision-making and satisfaction with treatment choices affirms the need to prioritize better understanding of shared decision-making in the older patient population. The findings also highlight how decisions about dialysis initiation are made by members of the growing dialysis population in the United States, which has increased nearly 60 percent between 2000 and 2012, most dramatically among those aged 75 and older, according to the U.S. Renal Data System’s 2014 Annual Data Report. The study also demonstrates that patients who actively engage in decision-making are more satisfied with their outcomes, according to researchers. “For some patients, dialysis may be the best treatment that aligns with their preferences and goals. But our study found that many of our respondents did not know that starting dialysis was voluntary and that they had a different option,” said Keren Ladin, Ph.D., first author on the paper. Ladin is an assistant professor in the Department of Occupational Therapy at the Graduate School of Arts and Sciences and the Department of Public Health and Community Medicine at Tufts University School of Medicine. “Patient-centered care requires better communication between patients and providers, including better understanding how potential treatments may affect patients’ goals of care and lifestyle preferences.” Recent studies show that for elderly ESRD patients, dialysis and conservative management are similarly effective at extending life, although dialysis significantly impacts quality of life. Consequently, the decision to start dialysis for elderly patients should be driven by their priorities and personal goals, said Ladin. The study found that key decision-making factors for patients include: independence, ability to travel, social participation, not burdening loved ones, continuing meaningful activities, and avoiding pain and fatigue. The qualitative study, which focused on 31 patients in greater Boston age 65 and older with an average age of 78, found multiple barriers to shared decision-making, including: • A perception among patients that dialysis was necessary to prevent imminent death; • A perception among patients that the decision to begin dialysis was solely up to their physicians;• A lack of communication of important prognostic information for the patient from a doctor; and• A patient’s deference to the views of clinicians and family members who often override a patient’s expressed preferences, fueled by a desire to be a “good patient.” As a result, most patients who said they felt less engaged in the decision-making process reported feeling dissatisfied with their treatment outcomes. Many focused on unexpected setbacks from dialysis and expressed feelings of distress about the impact of the treatment on their independence and overall energy. By contrast, the research found that patients reported actively making choices between peritoneal dialysis and hemodialysis. In this process, most patients reported their choice involved careful research and conversations with clinicians and family members. Ladin said the research illustrates the value of delivering the highest quality care while respecting patient autonomy. “While we cannot cure ESRD at this point, we can help patients achieve their goals and live out their last state of life according to their wishes,” said Ladin. Additional authors of this study are Naomi Lin, a graduate student in the Department of Occupational Therapy at the Graduate School of Arts and Sciences and the Research on Aging, Ethics and Community Health (REACH Lab) both at Tufts University; Emily Hanh and Gregory Zhang, both former undergraduate students in the Department of Community Health and research assistants in the REACH Lab, who graduated in 2016; Susan Koch-Weser, Ph.D., of the Department of Public Health and Community Medicine at Tufts University School of Medicine; and Daniel E. Weiner, MD, MS, of the Department of Medicine at Tufts Medical Center. This study was funded by the National Center for Advancing Translational Sciences, National Institutes of Health, Award Number KL2TR001063 and the Neubauer Faculty Fellowship at Tufts University. Dr. Weiner receives indirect salary support for research projects from Dialysis, Inc. paid through Tufts Medical Center. Keren Ladin, Naomi Lin, Emily Hahn, Gregory Zhang, Susan Koch-Weser, Daniel E. Weiner, “Engagement in decision-making and patient satisfaction: a qualitative study of older patients’ perceptions of dialysis initiation and modality decisions,” Nephrology Dialysis Transplantation, published online August 30 in advance of print, DOI: 10.1093/ndt/gfw307.

Newswise — Researchers at the University of California San Diego School of Medicine have identified 34 neural factors that predict adolescent alcohol consumption. The list, based upon complex algorithms analyzing data from neuropsychological testing and neuroimaging studies, was significantly more accurate —approximately 74 percent — than demographic information alone. The findings are published in the current issue of American Journal of Psychiatry. “Underage alcohol consumption is a significant problem in this country,” said senior author Susan F. Tapert, PhD, professor of psychiatry. “Being able to identify at-risk children before they begin drinking heavily has immense clinical and public health implications. Our findings provide evidence that it’s possible to predict which adolescents are most likely to begin drinking heavily by age 18.” Underage drinking is common in the United States, with approximately two-thirds of 18-year-olds reporting alcohol use. Though illegal, the Centers for Disease Control says drinkers between the ages of 12 and 21 account for 11 percent of all alcohol consumed in the United States. The adverse consequences of adolescent drinking are well-documented: higher rates of violence, missing school, drunk driving, driving with a drunk driver, suicide and risky sexual behavior. Alcohol consumption accounts for more than 5,000 adolescent deaths each year in the U.S. Individual consequences are no less onerous, with adolescent drinking contributing to memory, learning and behavioral problems, changes in brain development with long-lasting effects and greater likelihood for abuse of other drugs. A mix of social, psychological and biological mechanisms are believed to contribute to alcohol use during adolescence. Demographic risk factors include being male, having higher levels of psychological problems and associating positive outcomes with alcohol (i.e. drinking is fun). The authors note that past neuropsychological and neuroimaging studies have suggested it might be possible to quantify the underlying behavioral mechanisms of risk for substance abuse. These include poorer performance on tests of executive functioning, comparatively less brain activation of working memory, inhibition and reward processing and less brain volume in regions associated with impulsivity, reward sensitivity and decision making. In the American Journal of Psychiatry study, 137 adolescents between the ages of 12 and 14 who were “substance-naïve” (97 percent had never tried alcohol) underwent a battery of neuropsychological tests and functional magnetic resonance imaging of their brains. They were then assessed annually. By age 18, just over half of the youths (70) were moderate to heavy users of alcohol (based on drinking frequency and quantity); the remaining 67 study participants continued to be nonusers. The scientists employed a machine learning algorithm known as “random forests” to develop a predictive model. Random forest classification is capable of accommodating large sets of variables while using smaller study samples to produce consistently robust predictions. Among the findings, 12- to 14-year-olds were more likely to begin drinking by age 18 if: They were male and/or came from a higher socioeconomic background   They reported dating, possessed more externalized behaviors, such as lying or cheating, and believed alcohol would benefit them in social settings   They performed poorly on executive function tests   Their neuroimaging results indicated thinner cortices – the outer layer of neural tissue covering the brain   The authors said neuroimaging significantly increased predictive accuracy, both in terms of clarifying implicated brain morphology and noting the activation of 20 diffusely distributed brain regions involved in alcohol initiation. The study did not extend to the question of early marijuana use because only 15 percent of the sample reported eventually using marijuana more than 30 times, but the authors said it was possible that the reported risk factors for alcohol use also apply to marijuana and other illicit substances. They said further and larger studies are necessary. “The value of this particular study is that it provides a documented path for other researchers to follow, to replicate and expand upon our findings,” said Tapert. “Ultimately, of course, the goal is to have a final, validated model that physicians and others can use to predict adolescent alcohol use and prevent it.” Co-authors include: Lindsay M. Squeglia, Medical University of South Carolina; Tali M. Bali, Stanford University; Joanna Jacobus, Ty Brumback, and Scott F. Sorg , UC San Diego and VA San Diego Healthcare System; Benjamin S. McKenna, and Tam T. Nguyen-Louie, UC San Diego; and Martin P. Paulus, Laureate Institute for Brain Research, Tulsa, OK. Funding for this research came, in part, from the National Institute on Alcohol Abuse and Alcoholism (R01 AA13149, U01 AA021692, T32 AA013525, R01 DA016663, P20 DA027843) and the National Institute on Drug Abuse (U01 DA041089, K12 DA031794, T32 DA031098). ###

Newswise — Westminster, Colo. — The popular Paleo diet is based on eating foods thought to be available to our ancestors during the Paleolithic era, before the advent of dairy or processed grains. Findings from a small study suggest that people who followed the Paleo diet for only eight weeks experienced positive effects on heart health. Preliminary findings from this research will be presented at the American Physiological Society’s Inflammation, Immunity and Cardiovascular Disease conference. “Very few studies have examined the Paleo diet in seemingly healthy participants, despite the prevalence of this dietary practice in health and fitness enthusiasts,” said study author Chad Dolan, a graduate student researcher at University of Houston Laboratory of Integrative Physiology. The researchers asked eight healthy people who normally consumed a traditional Western diet high in processed foods to switch to the Paleo diet—which consists of minimally processed foods—for eight weeks. The participants received a sample Paleo diet menu and recipe guide, as well as initial counseling on how to incorporate the Paleo diet into their everyday lives. They were told to eat as much food as they wanted while following the diet. The researchers found that the study participants experienced a 35 percent increase in levels of interlukin-10 (IL-10), a signaling molecule secreted by immune cells. A low IL-10 value can predict increased heart attack risk in people who also have high levels of inflammation. Scientist think that high IL-10 levels may counteract inflammation, providing a protective effect for blood vessels. Although the researchers have not yet analyzed inflammation levels in the study participants, the increase in IL-10 could suggest a lower risk for cardiovascular disease after following the Paleo diet. The researchers also observed changes in other biomarkers of inflammation, but further investigation is needed to understand whether these changes indicate increased inflammation or a protective mechanism at work. Even though the study was not designed to promote weight loss, the participants did drop some pounds during the eight-week trial. Compared with what they regularly ate before the study, participants reported consuming around 22 percent fewer calories and 44 percent fewer grams of carbohydrates on the Paleo diet. This preliminary feasibility study did not include a control group of people not following the diet, making it difficult to determine if the changes observed in inflammation biomarkers resulted from specific food choices, reduced calories, fewer carbohydrates or weight loss. “This study’s findings add to the possibility that short-term dietary changes from a traditional Western pattern of eating to foods promoted in the Paleo diet may improve health—or, at the very least, the diet does not have negative health implications in terms of the parameters we studied,” Dolan said. “If our research continues to show that the Paleo diet produces detectable changes in healthy individuals, it will substantiate claims made by those supporting this diet for the past few decades and provide preliminary evidence for another therapeutic strategy for cardiovascular disease and coronary artery disease prevention.” The researchers caution that the current findings are both preliminary and incomplete in this group of participants. They plan to conduct a study with a greater number of people who follow the diet for a longer period of time to analyze how it affects various risk factors for cardiovascular and coronary artery disease, cellular immune function and metabolic health. The study was a collaborative effort between the Human Performance Laboratory at Chatham University in Pittsburgh and the University of Houston Laboratory of Integrative Physiology. Dolan will present “Effects of an 8-week Paleo dietary intervention on inflammatory cytokines” at a poster session on Friday, Aug. 26, from 12:45 to 2:45 p.m. in the Westminster IV room of the Westin Westminster Hotel.