Body

Researchers from Queen Mary University of London and Zhengzhou University have developed a personalised vaccine system that could ultimately delay the onset of pancreatic cancer. The study provides strong proof-of-concept for the creation of a vaccine for cancer prevention in individuals at high risk of developing this disease and to slow down tumour growth in patients who are affected by it.

The study reports the team's work with a pre-clinical model using mice. The research was published today in Clinical Cancer Research, a journal of the American Association for Cancer Research.

Although vaccines do exist for some cancers caused by known pathogens, such as the human papilloma virus in cervical cancer, vaccination against non-viral cancers has remained a challenge. In the study, researchers created a vaccine system that doubled the survival time of mice with pancreatic cancer. Importantly, the vaccine system can be personalised for the individual receiving it and could potentially be tailored to work against other types of cancer.

Vaccines work by training the immune system to recognise and kill pathogens within the body. To do this, immune cells must recognise molecules on the surface of the pathogens, called antigens. By injecting these antigens as a vaccine, the immune system can safely learn how to recognise them as foreign objects - and remember this should they be found in the body again.

Professor Yaohe Wang from Queen Mary University of London and the Sino-British Research Centre at Zhengzhou University in China, who led the study, said: "Development of a preventive vaccine against non-viral cancers is hugely limited by the lack of appropriate tumor antigens and an effective approach to induce robust anti-tumor immunity against those antigens. Through this international collaboration we have made progress towards the development of a prophylactic cancer vaccine against pancreatic cancer.

"This is preliminary data from tests on mice but it could be a platform for developing personalised and powerful cancer vaccines to reduce cancer incidence in at-risk individuals."

To make the vaccine, researchers took cells from mice and turned them into pancreatic cancer cells by adding two errors into their genetic code. These errors, or mutations, are known drivers of pancreatic cancer. The team then infected these cells with viruses, which have an important role in the vaccine system. Not only do the viruses kill the cells to remove their ability to form tumours within the body, but they do so in a way that activates the immune system against these cells.

As the cells die following injection into the subject, they release antigens specific to these pancreatic cancer cells, priming the immune system to recognise the initiation of cancer and prevent its development within the body.

By injecting these virus-infected cells into mice that were destined to develop pancreatic cancer, the team were able to delay the onset of disease, doubling their survival time when compared with mice who did not receive the vaccine.

The genetic makeup of cancer varies from individual to individual. That means treatments that are effective for one patient's cancer may not be effective against another's. Notably, because the cells were derived from the mice that were going to receive the vaccine, the cells created were genetically similar to the cancer that was going to develop in these mice. This suggests that cells could be taken from at-risk individuals and used to create matching tumour cells for use in a vaccine regime tailored to those individuals.

Pancreatic cancer has the lowest survival rate of all the common cancers, with less than 5% of those diagnosed surviving for longer than five years.

Dr Louisa Chard Dunmall, senior postdoctoral research fellow at Queen Mary, said: "One reason for this low survival rate is lack of symptoms, meaning diagnosis is often not made until the cancer is at an advanced stage. This suggests a window of opportunity for the application of preventative vaccine strategies. Although this research is at the early developmental stages, it provides strong evidence that the creation of a vaccine against pancreatic cancer is possible."
The research was undertaken by scientists from the Barts Cancer Institute at Queen Mary, the Sino-British Research Centre at Zhengzhou University and the Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences. The Sino-British Research Centre is a joint venture established by Queen Mary and Zhengzhou University.

The team will now look at different ways of improving the regime - including increasing the number of vaccinations or combining the vaccine with other therapies such as immunotherapies.

A recently discovered prostate cancer-selective antigen has been identified as a useful molecular imaging target for the detection and targeting of metastatic prostate cancer lesions, as reported in the November issue of The Journal of Nuclear Medicine. Using a novel radiotracer, researchers were able to effectively image STEAP1 (six-transmembrane epithelial antigen of prostate-1) in tumors and localize a large number of lesions.

Metastatic castration-resistant prostate cancer (mCRPC) is a significant health care problem, with more than 42,000 cases projected in 2020. "While significant strides have been made in detection of mCRPC with radiolabeled antibodies and small molecules that recognize prostate-specific membrane antigen (PSMA), other important potential targets, such as STEAP1, could be imaged to identify presence of mCRPC and possibly serve as therapeutic targets," said Jorge A. Carrasquillo, MD, who performed the study while an attending physician at Memorial Sloan Kettering Cancer Center in New York, New York. "89Zr-DFO-MSTP2109 represents a novel theranostic reagent to both identify the extent of metastatic prostate cancer and select patients for STEAP1-directed therapies."

The prospective single-phase study included 19 patients with histologically confirmed progressing mCRPC with documented metastatic disease on bone scans, computed tomography (CT) or magnetic resonance imaging. Patients received approximately 185 MBq/10mg of 89Zr-DFO-MSTP2109A and were imaged four to seven days after the injection. Uptake and localization in tumor were measured and compared with bone and CT scans. Bone and soft tissue biopsy samples also were evaluated.

All patients imaged with 89Zr-DFO-MSTP2109A were considered positive for bone lesions, and eight patients were considered to have soft-tissue disease. Localization of 89Zr-DFO-MSTP2109A in suspected bone metastases was observed in all patients; a total of 515 sites were recorded as positive. Analysis of bone lesions showed a median maximum SUV of 20.6, while an analysis of soft tissue lesions showed a median maximum SUV of 16.8.

Researchers also analyzed biopsies performed under other research protocols or for clinical indications either before or after imaging with 89Zr-DFO-MSTP2109A. High uptake values of 89Zr-DFO-MSTP2109A were noted in 11 of 12 bone sites biopsied and all five soft-tissue sites, each of which was confirmed as histologically positive. As researchers were unable to biopsy all cancerous lesions, a Bayesian approach was used to apply information gleaned from biopsied lesions to project the number of cancerous lesions in each patient. Use of this approach resulted in a best estimate of 86 percent of histologically positive lesions being true-positive on imaging with 89Zr-DFO-MSTP2109A.

"To our knowledge, this is the first study to report in detail on the imaging findings of targeting STEAP1," said Carrasquillo. "Given the high SUV in tumor and localization of a large number of lesions, this reagent warrants further exploration as a companion diagnostic in patients undergoing STEAP1-directed therapy."

He continued, "The difference we observed in targeting PSMA with various radiotracers in patients with prostate cancer may possibly reflect differences related to the biology of STEAP1-versus PSMA-positive prostate cancer. Furthermore, as radiolabeled anti-PSMA antibodies were superseded by small molecules for PSMA imaging, there is potential to develop small molecules to target STEAP1 as well."

Bottom Line: Examining life expectancy in the United States over nearly 60 years and identifying factors that contributed to recent increases in mortality were the focus of this expansive report. Researchers used data from the Centers for Disease Control and Prevention and the U.S. Mortality Database to analyze changes in life expectancy and mortality rates, and they reviewed epidemiologic literature to add context to the vital statistics and explore explanations for the trends. Life expectancy increased almost 10 years, from 69.9 years in 1959 to 78.9 years in 2016, but the pace slowed over time and life expectancy decreased in the U.S. for three consecutive years after 2014. Contributing to that decrease, the researchers report, was an increase in deaths among working-age adults, those ages 25 to 64, from causes such as drug overdoses, suicides, and a long list of organ system diseases. The report includes an analysis at the state level, showing that the trend was more concentrated in certain regions, notably the Industrial Midwest and northern New England. The authors discuss potential explanations for rising mortality, among them drugs, obesity, the health care system, mounting stress and the economy. Limitations of the report include mortality data that can be subject to errors such as an inaccurate determination of cause of death, race misclassification and undercounting.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: Steven H. Woolf, M.D., M.P.H., and Heidi Schoomaker, M.A.Ed., of the Virginia Commonwealth University School of Medicine, Richmond, Virginia.

(doi:10.1001/jama.2019.16932)

Editor's Note: The article includes funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Women with asthma who suffer severe symptoms while they are pregnant face higher risks of health problems both for themselves and their babies compared to women with well-controlled asthma, according to research published in the European Respiratory Journal [1].

The study, which included data on more than 100,000 pregnancies, showed that women with asthma who experienced severe symptoms were more likely to suffer with high blood pressure (known as pregnancy-induced hypertension) and a potentially serious condition called pre-eclampsia.

It also showed that babies born to women who suffered asthma attacks were at greater risk of having a low birth weight, or being born prematurely or with a congenital abnormality, such as a heart defect or cleft lip. The children's risk of having asthma and pneumonia was also higher in the first five years of life.

The researchers say these findings are important because a large proportion of women with asthma are known to decrease or stop taking asthma medication during pregnancy.

The research was led by Dr Kawsari Abdullah, currently a research fellow at the Children's Hospital of Eastern Ontario, Research Institute in Ottawa, Canada. While conducting the study, Dr Abdullah was working at The Hospital for Sick Children (SickKids) in the Child Health Evaluative Sciences (CHES) Program, in Toronto.

She said: "Asthma is the most common chronic disease in pregnant women, affecting 8-13% of pregnant women worldwide.

"If asthma is poorly controlled, patients can suffer with severe symptoms such as wheezing, coughing, or feeling breathless or tight-chested. Previous research has shown that one out of every three pregnant women with asthma will suffer severe symptoms, so we need to understand what this means for women and their babies."

Dr Abdullah and her colleagues studied 103,424 pregnancies in 58,524 women with asthma living in the province of Ontario in Canada between April 2003 and March 2012. This included 4,455 pregnancies in 2,663 women who experienced severe symptoms while pregnant. This means they either visited their doctor at least five times because of their asthma symptoms, or went to the emergency department or were admitted to hospital at least once for asthma during pregnancy.

The researchers took account of other factors that can influence the health of the mother and baby, including the mother's age, whether she had been pregnant before, whether she smoked and her socioeconomic status.

They compared pregnant women with asthma who had experienced severe symptoms with pregnant women whose asthma was well-controlled. They found that those who had asthma attacks were around 30% more likely to suffer with pre-eclampsia and around 17% more likely to suffer with high blood pressure during pregnancy.

The results showed that babies born to mothers who had asthma attacks while pregnant were around 14% more likely to have a low birth weight, also around 14% more likely to be born prematurely, and around 21% more likely to have a congenital abnormality.

Children's risk of asthma up to the age of five years was 23% higher if their mother had experienced severe asthma symptoms in pregnancy, and their risk of pneumonia was around 12% higher.

Dr Teresa To, the senior researcher on the study and Senior Scientist at SickKids, said: "This is the biggest study looking at the risks associated with severe asthma symptoms in pregnancy and it's also the first to show the longer-term impacts on children up to the age of five years. Our results reinforce the findings of smaller studies that uncontrolled asthma can be bad for mothers and their babies.

"Nearly 40% of pregnant women decrease or stop taking asthma medication because they are worried that it could be harmful to their unborn babies. However, our study indicates that severe asthma symptoms present the greater risk to mother and baby.

"This study does not explain why asthma attacks contribute to all these health issues, but the likely mechanism is reduced oxygen supply for the mother and subsequently to the baby in the womb."

Professor Jørgen Vestbo is Chair of the European Respiratory Society's Advocacy Council, based at the University of Manchester and was not involved in the study. He said: "This large and important study suggests that asthma that is not well controlled may have serious effects on pregnant women and their children. This highlights the importance of carefully maintaining asthma control and managing asthma symptoms during pregnancy. Pregnant women who have asthma need regular antenatal care to discuss their symptoms and ensure their medication is effective."

Several years of hospitalisation, one example of muscle inactivity, causes a disproportionate decline in the muscle strength known to affect balance, increase the risk of joint injuries, and hinder movements involved in sports. That's according to research from the University of Roehampton, published today in Experimental Physiology. Thus, rehabilitation programmes should work to build the strength involved in these types of activities, using typical resistance exercises (e.g., leg press), but with the attention of lifting the resistance as rapidly as possible.

The effects of long-term muscle inactivity (via e.g., sedentary behaviour, hospitalisation, or space travel) have proven difficult to study in a laboratory environment, as there are ethical issues with enforcing prolonged physical inactivity. Previous research has shown that the thigh muscles of individuals with an amputation below the knee are used less during movement and therefore become weak.

Amy Sibley, Neale Tillin and colleagues at the University of Roehampton therefore used below-knee amputees as a model to understand muscular changes that happen with long-term inactivity. Similar changes might happen in the muscles of someone who is hospitalised, sedentary, or travelling in space.

Scientific studies have previously defined two main types of strength: maximum and explosive. Maximum strength is what it sounds like, the maximum capacity of your muscles for producing force. People rarely need to utilise this maximum capacity in daily activities.

Explosive strength is the ability to quickly produce force, and is relevant during many daily activities such as recovering from a loss of balance, avoiding joint injuries, and when playing sports. The researchers showed that when they compared maximum and explosive strength, amputees lost comparatively more explosive strength.

They also found that the muscular changes that accompanied this reduction in strength could not have been anticipated from the typical short-term bedrest studies, and were specific to the type of strength examined.

Therefore, rehabilitation regimens (for amputees or other populations who have experienced inactivity) should be tailored to help them recover explosive strength specifically.

Amy Sibley, first author of the study said:

"This research has exciting potential to help people who have been inactive long-term, due to hospitalisation for example, regain the strength they need for daily activities such as avoiding falls. To achieve this aim, clinicians need to be specific about the type of strength training they use, for example typical resistance exercises (e.g., leg press) should be performed with the intention of lifting the resistance as rapidly as possible."

Children's deaths from choking on small objects dropped by 75 percent from 1968 to 2017, according to a report published in JAMA. Various choking hazard regulations enacted during the past 50 years may have played a role in the large decline in choking deaths, although the study design cannot establish a direct causal link. However, despite warning label legislation and other regulations, 184 children in the U.S. died from choking in 2017.

"While we see substantial progress in reducing choking deaths in children over the years, we need to do more to keep young children safe," says study co-author Jennifer Lavin, MD, pediatric ENT specialist at Ann & Robert H. Lurie Children's Hospital of Chicago and Assistant Professor of Otolaryngology - Head and Neck Surgery at Northwestern University Feinberg School of Medicine. "We urge parents to be extra careful in keeping small objects away from children under 3 years old, especially when there are older siblings playing with toys that have small parts, which pose a choking hazard to younger kids."

In 1969, the Child Safety and Protection and Toy Safety Act set the groundwork for prohibiting products designed for children under 3 years old to contain parts that are smaller than the airway of a child that age (or parts fitting in what is known as a small parts test cylinder). This prohibition was enacted in 1979. In 1994, came the requirements for explicit choking hazard warning labels on toys and regulations were tightened for small parts cylinder tests.

"In the 1990s, there was a sharper decline in choking deaths in children younger than 3 years, exceeding 8 percent annually, compared to over 2 percent annual decrease in the years before and after," says Dr. Lavin. "The warning label legislation certainly appears to have made a difference. More national efforts are needed to make an even greater impact toward eliminating deaths from choking in young children."

Dr. Lavin and colleagues highlight the need to reconsider the design of the small parts cylinder, given that 23 percent of object-related choking deaths in children result from objects that passed the current small parts cylinder test.

GALVESTON, Texas - New findings from The University of Texas Medical Branch at Galveston show that patients qualifying for Medicare because of a disability have the highest rates of opioid overdose deaths compared with older Medicare beneficiaries and commercial insurance beneficiaries. The findings are now available in JAMA Network Open. The study, led by Yong-Fang Kuo, UTMB professor in the department of preventive medicine and population health, found that Medicare beneficiaries who qualify because of a disability are a growing group of patients hospitalized for opioid or heroin overdose and account for 25 percent of deaths from prescription opioid overdose each year. Previous research shows that not many of these patients make use of opioid treatment programs.

In the study, the researchers analyzed a nationally representative sample of Medicare data, including 1,766,790 people who qualified for Medicare because of a disability to assess the rate of opioid overdose deaths and identify its associated risk factors. Although these disability patients account for only 14.9 percent of the entire Medicare population, they were also found to represent 81 percent of all opioid-related deaths among this group.

"We found that among the patients who have Medicare because of disability, the rates of opioid overdose deaths were higher among people who grapple with substance misuse, psychiatric diseases or chronic pain," said senior author Kuo of UTMB.

"Right now, there's a large federal push to increase access to opioid misuse treatment programs and these efforts work more effectively with accurate targeting of high-risk populations. Our findings suggest that Medicare data can help to identify people who can really benefit from these programs."

Point-of-care (POC) testing is a rapidly growing sector, bringing medical testing from central laboratories to where the patient is receiving care.

Researchers from the University of Helsinki have developed a novel diagnostic method coined RFS (Rapid FRET serodiagnostics) for the rapid on-site measurement of antibodies from patient samples. This technology could revolutionize the serodiagnosis of microbial, autoimmune and allergic disorders.

Now this team of researchers have applied the new concept for diagnostics of celiac disease.

MOST PATIENTS ARE UNAWARE OF THEIR CELIAC DISEASE

Celiac disease is an autoimmune disorder typically presenting as non-specific gastrointestinal symptoms. It affects approximately 1 % of world population, with more than 90 % of patients undiagnosed. Even in affluent countries, more than half of celiacs are unaware of their disease. Delayed diagnosis is associated with impaired quality of life and persistent symptoms even after treatment.

Screening of celiac disease is recommended for patients with e.g. gastrointestinal symptoms or other autoimmune diseases as well as for the first-degree relatives of celiac patients. The screening test involves measurement of disease-specific antibodies from a blood sample.

EASY AND FASTER DETECTION OF CELIAC DISEASE ANTIBODIES

The researchers gathered samples from 70 celiacs at the Kuopio University Hospital, half from children and half from adults. Control samples from healthy donors were also collected. The samples were measured using the new assay and results compared with two currently used methods.

"The performance of the test was comparable to that of current methods. The prevailing method involves transporting the sample to a central laboratory and a multi-step procedure taking hours. With the new method, results can be achieved in less than half an hour by simply combining the sample and a reagent mix, waiting for a while and reading the result.", Juuso Rusanen, MD, explains. He continues:

"We hope our rapid method could lower the threshold for screening of celiac disease and thus help overcome the vast underdiagnosis of this relatively common condition."

"Additionally, this is the first time the new method has been used for diagnostics of autoimmune disease. This is a promising result, and prompts the development of similar tests for diagnostics of other autoimmune disorders", Rusanen points out.

Oak Brook, IL - The December issue of SLAS Discovery features part two of the two-part special issue, "Membrane Proteins: New Approaches to Probes, Technologies and Drug Design."

In this issue, Guest Editor Veli-Pekka Jaakola, Ph.D., (Confo Therapeutics, Belgium) includes a series of articles focused on new screening tools and assays that find new chemical matter for medically relevant membrane protein targets. In addition, an overview of a new and emerging protein-lipid reconstitution methodology utilizing Styrene Maleic Acid (SMA) polymers is featured.

Other reviews and original research papers included in the special issue include:

Visualization and Exploitation of Ex Situ Lipid-Protein Complexes in Native Nanodiscs

Understanding Structure-Function Relationship of Equilibrative Nucleoside Transporter Family

Screening of Chemical Libraries Using a Yeast Model of Retinal Disease

Live In-cell Membranome cDNA Screen: A homogenous In-Cell Binding Assay to Study Membrane Protein-Ligand Interaction

Development of a Cell-Based Assay Using Large-Scale Transient Transfections and High Content Imaging (HCI) to Detect Extracellular Binding Events

Functional Expression of MRP4

Stabilization of MRP4 Using Novel Solubilization Agents

Dr. Jaakola received his Ph.D. from the Institute of Biotechnology at the University of Helsinki (Finland). He joined the Oulu Biocenter at the University of Oulu (Finland) as a junior group leader in 2009, became an adjunct professor of biochemistry and molecular medicine in 2011 and transitioned to the Membrane Protein Lab Head at Novartis (Switzerland) in 2013. Jaakola is currently Head of Structural Biology at Confo Therapeutics (Belgium) where he continues to work in structural biology, structure-based drug discovery and development for GPCR targets.

Access to December's SLAS Discovery issue is available at https://journals.sagepub.com/toc/jbxb/24/10 through December 20. For more information about SLAS and its journals, visit http://www.slas.org/journals.

EAST LANSING, Mich. - Each year millions of Americans become sick with the flu, hundreds of thousands are hospitalized and tens of thousands die. Getting the flu shot can reduce the chances of infection. But, at best, the vaccine is only effective 40% to 60% of the time, according to the CDC.

Now Michigan State University researchers have data that show how cellular RNA levels change following infection or vaccination. Their work could help make future flu vaccines work better or even aid in the design of a universal vaccine.

"Understanding these differences could help us identify new targets for building better vaccines as well as help us figure out better ways to treat the disease," said George Mias, assistant professor of biochemistry and molecular biology and chief of the Systems Biology Division at the Institute for Quantitative Health Science and Engineering at MSU.

Mias and his co-authors reanalyzed data from 18 previously published studies where scientists had taken blood samples from flu patients and vaccine recipients and studied those samples for gene expression. Gene expression can be measured by looking for the levels of RNA in cells. When a gene is expressed in a cell it means the DNA has been used to produce RNA for this gene. The gene expression in cells can change in response to stimuli, including disease.

"The motivation for combining the different datasets is that typically the smaller datasets will be underpowered statistically to detect significant differences," Mias said. "By combining multiple studies, we're increasing our power and ability to detect gene expression differences between the variables that we're interested in."

The researchers found 978 genes with changed expression for flu infection and flu vaccination. Roughly a third of those genes, 334, overlapped while about two-thirds, 644, were unique to either flu infection or flu vaccination.

The distinct genes were involved in different processes in the body. Several genes that were expressed differently in flu infection, for example, are involved in the body's defensive mechanisms. On the flip side, genes exclusively expressed in vaccination were involved in antigen processing, which stimulates the body's immune response.

The investigators also found 907 genes related to age and 48 related to sex that affect disease/vaccine gene expression changes. Understanding these differences could help scientists in their quest to develop a universal vaccine.

"We especially need to find something that works across ages better," Mias said.

At present, the CDC recommends a high-dose vaccine for people over the age of 65 because their immune systems need more stimulation in order to create the necessary antibodies to protect them from flu viruses.

Mias and his co-authors hope their results will serve as a starting point for future studies by providing gene targets that could be further explored through animal models or human research using newer RNA-sequencing technology.

"We found things that are specific to the flu or to the vaccine, so we need to ask, 'What are the effects of those genes?'" Mias said. "For instance, if the vaccine is activating additional genes and pathways that the disease itself is not activating, we should be asking, 'Are they relevant and could they be linked to any side effects?' Those are questions that deserve to be answered."

BOSTON - Long-term exposure to environmental noise - think planes, trains, and automobiles -- has been linked in multiple studies to adverse health effects such as poor sleep, psychiatric disorders, diabetes, and cardiovascular disease (CVD). However, the mechanisms linking noise to such diseases has not been well understood. Now, investigators at Massachusetts General Hospital (MGH) and colleagues have identified a potential mechanism through which long-term exposure to noise leads to inflammation, blood vessel damage, and heart disease.

"We observed that stress-associated brain centers, specifically the amygdala, potentially serve as the conduit by which noise triggers changes that lead to disease," says lead author Michael T. Osborne, MD, from the Cardiac Imaging Research Center and division of Cardiology at MGH.

In a study published in the European Heart Journal, Osborne and colleagues report that high noise levels lead to activation of the amygdala, a deep brain structure that plays a central role in processing emotions and responding to stress.

They used radiotracer-enhanced positron-emission tomography/computed tomography (18F-FDG-PET/CT) imaging to study the brains and arteries of 498 adults at study outset and followed them for 5 years to see whether higher levels of noise exposure associated with a major adverse cardiovascular event, commonly abbreviated as "MACE." MACE was defined as CVD-related death, heart attack (myocardial infarction), severe uncontrolled chest pain (unstable angina), stroke, heart failure, or need for an intervention to reopen blocked coronary or peripheral arteries (revascularization).

To determine noise exposure, they estimated average transportation noise over 24 hours at each subject's home address with United States Department of Transportation Data and adjusted their findings for potential contributors to CVD and MACE such as air pollution (a known risk factor for heart and lung disease), socioeconomic factors, and existing CVD risk factors.

Over a median of 4 years, 40 of the 498 subjects (8%) experienced MACE, and when the investigators looked at noise exposure for these individuals, they found that every 5 decibel increase in noise predicted MACE. The association between noise levels and MACE remained strong even when they took into account other potential risk factors for CVD.

Importantly, PET-CT imaging showed that higher levels of noise exposure were associated with an increase in activity in the amygdala and an increase in inflammation of arteries, an early and critical event in the development of CVD.

"These findings suggest a need to help people who may be at risk for CVD understand that chronic noise exposure where they live may increase their risk of disease," Osborne says.

Based on their findings, the investigators plan to further study the link between noise exposure and other diseases (including diabetes and obesity) with an eye towards developing interventions to mitigate disease.

Cognitive impairment without dementia (CIND), or mild cognitive impairment, is a condition that affects your memory and may put you at risk for Alzheimer's disease and dementia. According to the U.S. National Library for Medicine, signs of mild cognitive impairment may include frequently losing things, forgetting to go to events and appointments, and having more trouble coming up with words than other people of your age.

Some experts believe that risk factors for heart disease also are risk factors for dementia and late-life cognitive decline and dementia. Recently, researchers examined two potential ways to slow the development of CIND based on what we know about preventing heart disease. They published the results of their study in the Journal of the American Geriatrics Society.

The research team had a theory: That the healthy lifestyle behaviors that slow the development of heart disease could reduce heart disease risk and also slow cognitive decline in older adults with CIND. These behaviors include regular exercise and a heart-healthy diet, such as the DASH (Dietary Approaches to Stop Hypertension) diet.

In order to investigate their theory, the researchers designed a study titled "Exercise and NutritionaL Interventions for coGnitive and Cardiovascular HealTh EnhaNcement" (or ENLIGHTEN for short). The goal of the study was to examine the effects of aerobic exercise (sometimes known as "cardio" or "cardiovascular" exercise because it involves activities that increase the circulation of oxygen through the blood) and the DASH diet on cognitive functioning in older adults with CIND.

The ENLIGHTEN study examined 160 adults 55-years-old or older. The study participants were older adults who didn't exercise and had memory problems, difficulty thinking, and making decisions. They also had at least one additional risk factor for heart disease, such as high blood pressure (also known as hypertension), high cholesterol, diabetes, or other chronic conditions.

Participants took a number of tests to measure their heart disease risk factors and cognitive ability. Researchers also assessed participants' dietary habits and ability to perform daily activities. The participants were then randomly assigned to one of four groups: a group doing aerobic exercise alone, a group following the DASH diet alone, a group doing aerobic exercise and following the DASH diet combined, or a group receiving standard health education.

People in the exercise group did 35 minutes of moderate intensity aerobic exercise (including walking or stationary biking) three times per week for six months. They were supervised for three months and then exercised unsupervised at home for three months. Participants in the exercise group did not receive any counseling in the DASH diet and were encouraged to follow their usual diets for six months.

People in the DASH eating plan group received instruction about how to meet DASH guidelines in a series of weekly sessions for three months and then bi-weekly for the remaining three months. Participants in the DASH group were asked not to engage in regular exercise until the completion of the six-month study.

People in the exercise and DASH group followed the exercise and DASH programs for six months. The participants who were enrolled in the health education group received weekly educational phone calls for three months and then bi-weekly calls for three months. Phone calls were conducted by a health educator on health topics related to heart disease. Participants were asked to maintain their usual dietary and exercise habits for six months until they were re-evaluated.

At the conclusion of the six-month intervention and assessment, participants were free to engage in whatever activity and dietary habits they desired, with no restrictions.

The results of the research team's study showed that exercise improved the participants' ability to think, remember, and make decisions compared to non-exercisers, and that combining exercise with the DASH diet improved the ability to think, remember, and make decisions, compared to people who didn't exercise or follow the diet--even though they didn't perfectly follow the programs they were assigned to during the six-month interventions.

The researchers concluded that their findings are promising proof that improved ability to think, remember, and make decisions can last one year after completing a six-month exercise intervention. They suggested that further studies would be needed to learn more.

Research Highlights:

One in 8 adults with common heart diseases skip medications, delay filling prescriptions or take less medication than prescribed because of concerns about cost.

Not taking medications as prescribed because of cost is 3 times more common in people under 65 years of age than in older people covered by Medicare.

DALLAS, Nov. 25, 2019 -- One in 8 adults with common heart diseases and stroke skip taking medications, delay filling prescriptions or take lower doses than prescribed because of concerns about cost, according to new research published today in the American Heart Association's journal Circulation.

"The out-of-pocket cost of medications is a huge issue for millions of high-risk patients with cardiovascular diseases such as heart attacks, stroke, angina and other conditions. When faced with the expenses of taking lifesaving medications as prescribed or not taking them because they are too costly, many choose not to take them," said Khurram Nasir, M.D., M.P.H., M.Sc., senior author of the study, chief of the division of cardiovascular prevention and wellness and co-director of the Center for Outcomes Research at Houston Methodist DeBakey Heart & Vascular Center in Texas.

Not taking pills at the dose or the interval prescribed, called medication non-compliance, is a known problem for people with cardiovascular diseases. It often means they need more expensive care later because they become sicker and are more likely to need care in an emergency room, be hospitalized or have more frequent doctor's appointments.

"While non-compliance has several causes, in recent years the rising share of health care costs paid directly by patients has become a concern. We wanted to understand the scope of medication non-compliance due to costs," said Nasir.

The investigators analyzed survey responses from 14,279 adults (average age 65, 44 % female) who took part in the National Health Interview Survey between 2013 and 2017. All had previously been diagnosed with coronary heart disease, heart-related chest pain, a heart attack or a stroke.

The researchers found that, during the previous year:

1 in 8 people with these common heart diseases (corresponding to nearly 2.2 million people nationwide) had not taken their medication as prescribed because of cost concerns;

Cost-related, medication non-compliance was 3 times more common in people under 65 years of age, with nearly 1 in 5 reporting cost-related non-compliance;

Among those under 65, larger proportions of women (1 in 4), patients from low-income families (1 in 3) and patients without health insurance (more than half) reported not taking their medications as prescribed in order to save money;

Race and level of education did not have a significant effect on the proportion of patients with cost-related non-compliance; and

People who did not take medications as prescribed due to cost concerns were 11 times more likely to request low-cost medication and 9 times more likely to use alternative, non-prescription therapies, compared to people who reported that financial concerns did not impact their decision.

"Patients should not be afraid to speak with their health care provider if they are not able to afford a prescribed medication since there are many lower-cost generic drugs which might also be effective for their condition," said Nasir.

"As health care providers, we should also consider advocating for changes in national health care policy, such as capping out-of-pocket expenses for low-income families. We also need to recognize that out-of-pocket medical costs may have a cumulative effect on a patient's family who may also have difficulty paying for housing, transportation and food. Health care providers can play an active role in working with our local health system and community financial assistance support programs to provide financial assistance and resources to those who need it the most," Nasir added.

The study did not examine the specific medications patients were prescribed and which were more likely to result in cost-related non-compliance.

As an evidence-based patient advocacy organization dedicated to improving the cardiovascular health of all Americans, the American Heart Association has a unique role in advocating for treatments, including medicines that are available, affordable and accessible to patients. Our 2017 Presidential Advisory on the accessibility and affordability of prescription drugs and biologics lays out the principles that guide our engagement in pursuit of this goal.

As you grow older, you're more likely to develop health conditions that require taking multiple medications--some of which you may take for a long time. Many older people also take over-the-counter (or "OTC") medications, vitamins, or supplements as part of routine care. As a result, older adults have a higher risk of overmedication, also known as "polypharmacy"--the medical term for taking four or more medications at the same time. Polypharmacy can increase your chances of unwanted reactions (also called "adverse drug reactions") due to medications taken on their own or together.

To address this increasingly common problem, healthcare providers are focusing on how to reduce the number of medicines older adults are using through a practice called "deprescribing," which is when health professionals work with patients to decide to stop the use of one or more medications for which the benefits no longer outweigh the potential harms.

Getting both patients and health professionals on board with deprescribing can be key to its success, however. In order to learn more about physicians' attitudes and approaches to deprescribing medications for older adults, a team of researchers designed a survey. They published their investigation in the Journal of the American Geriatrics Society.

The researchers aimed to learn how frequently physicians from different specialties said they deprescribed cardiovascular medications (drugs for heart conditions) in their practices. Cardiovascular medications, such as blood thinners and medications for lowering blood pressure and cholesterol, are among the most commonly prescribed medication classes in the United States. Although the benefits of these medications for reducing heart attacks and stroke are proven, these treatments also have contributed to rising rates of polypharmacy and adverse drug events in older adults.

The research team was interested in learning why different specialists deprescribed some of these medications, and what difficulties they faced when they did so. The researchers also wanted to know about the priorities different specialties considered when deprescribing. The research team surveyed 750 geriatricians, general internists, and cardiologists.

The response rate to the survey was 26 percent for geriatricians, 26 percent for general internists, and 12 percent for cardiologists.

Over 80 percent of the physicians who responded reported that they had recently considered deprescribing a cardiovascular medication. Adverse drug reactions were the most common reason cited by all the specialties for deprescribing a drug.

Barriers to deprescribing were shared across specialties. One concern was about interfering with another physician's treatment plans, since some medications may be prescribed or recommended by several different providers who don't always work together. Another concern was patient reluctance to stop taking prescribed medications.

A majority of geriatricians (73 percent) said they might deprescribe a medicine that was not expected to benefit patients who had a limited life expectancy. This is compared to 37 percent of general internists and 14 percent of cardiologists.

More geriatricians (26 percent) reported concerns about cognition (the ability to think and made decisions) as a reason for deprescribing, compared to 13 percent of general internists and nine percent of cardiologists.

The researchers concluded that their survey showed that geriatricians, general internists, and cardiologists frequently consider deprescribing cardiovascular medications. They noted that successfully implementing patient-centric deprescribing will require improved communication between all physicians and their patients. "We hope our study will contribute to advancing deprescribing as a patient-centered strategy that can improve the safety of medication prescribing practice and improve the wellbeing of older adults," said the researchers.

If you take multiple medications, you may have questions about your own treatment plans and how they can be changed or improved to better suit your needs. HealthinAging.org offers a range of resources for learning more about how medications affect us differently as we age, as well as steps you can take to discuss medication management with your health professionals. Remember: Never discontinue using a prescribed treatment or make changes to your medications without speaking to a health professional first. If you experience a serious side effect or adverse event related to medications you may be taking, call 911 immediately.

There are numerous things to dislike about going to the doctor: Paying a copay, sitting in the waiting room, out-of-date magazines, sick people coughing without covering their mouths. For many, though, the worst thing about a doctor's visit is getting stuck with a needle. Blood tests are a tried-and-true way of evaluating what is going on with your body, but the discomfort is unavoidable. Or maybe not, say Caltech scientists.

In a new paper published in Nature Biotechnology, researchers led by Wei Gao, assistant professor of medical engineering, describe a mass-producible wearable sensor that can monitor levels of metabolites and nutrients in a person's blood by analyzing their sweat. Previously developed sweat sensors mostly target compounds that appear in high concentrations, such as electrolytes, glucose, and lactate. Gao's sweat sensor is more sensitive than current devices and can detect sweat compounds of much lower concentrations, in addition to being easier to manufacture, the researchers say.

The development of such sensors would allow doctors to continuously monitor the condition of patients with illnesses like cardiovascular disease, diabetes, or kidney disease, all of which result in abnormal levels of nutrients or metabolites in the bloodstream. Patients would benefit from having their physician better informed of their condition, while also avoiding invasive and painful encounters with hypodermic needles.

"Such wearable sweat sensors have the potential to rapidly, continuously, and noninvasively capture changes in health at molecular levels," Gao says. "They could enable personalized monitoring, early diagnosis, and timely intervention."

Gao's work is focused on developing devices based on microfluidics, a name for technologies that manipulate tiny amounts of liquids, usually through channels less than a quarter of a millimeter in width. Microfluidics are ideal for an application of this sort because they minimize the influence of sweat evaporation and skin contamination on the sensing accuracy. As freshly supplied sweat flows through the microchannels, the device can make more accurate measurements of sweat and can capture temporal changes in concentrations.

Until now, Gao and his colleagues say, microfluidic-based wearable sensors were mostly fabricated with a lithography-evaporation process, which requires complicated and expensive fabrication processes. His team instead opted to make their biosensors out of graphene, a sheet-like form of carbon. Both the graphene-based sensors and the tiny microfluidics channels are created by engraving the plastic sheets with a carbon dioxide laser, a device that is now so common that it is available to home hobbyists.

The research team opted to have their sensor measure respiratory rate, heart rate, and levels of uric acid and tyrosine. Tyrosine was chosen because it can be an indicator of metabolic disorders, liver disease, eating disorders, and neuropsychiatric conditions. Uric acid was chosen because, at elevated levels, it is associated with gout, a painful joint condition that is on the rise globally. Gout occurs when high levels of uric acid in the body begin crystallizing in the joints, particularly those of the feet, causing irritation and inflammation.

To see how well the sensors performed, the researchers ran a series of tests with healthy individuals and patients. To check sweat tyrosine levels, which are influenced by a person's physical fitness, they used two groups of people: trained athletes and individuals of average fitness. As expected, the sensors showed lower levels of tyrosine in the sweat of the athletes. To check uric acid levels, they took a group of healthy individuals and monitored their sweat while they were fasting as well as after they ate a meal rich in purines, compounds in food that are metabolized into uric acid. The sensor showed uric acid levels rising after the meal. Gao's team also performed a similar test with gout patients. Their uric acid levels, the sensor showed, were much higher than those of healthy people.

To check the accuracy of the sensors, the researchers also drew blood samples from the gout patients and healthy subjects. The sensors' measurements of uric acid levels strongly correlated with levels of the compound in the blood.

Gao says the high sensitivity of the sensors, along with the ease with which they can be manufactured, means they could eventually be used by patients at home to monitor conditions like gout, diabetes, and cardiovascular diseases. Having accurate real-time information about their health could even allow a patient to adjust their own medication levels and diet as required.

"Considering that abnormal circulating nutrients and metabolites are related to a number of health conditions, the information collected from such wearable sensors will be invaluable for both research and medical treatment," Gao says.