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The nuclear accident in Fukushima remains etched into people's memories. It was a catastrophe that caused huge amounts of radioactively contaminated water to be released, which the operators of the nuclear power plant subsequently had to clean up. One of the methods they used was reverse osmosis but it wasn't particularly effective. Although it is possible to purify up to 70 percent of the contaminated water this way, radioactive elements accumulate in the remaining 30 percent. Some of these elements are highly radioactive and remain so for thousands of years. As things stand, the Japanese government is planning to dump this water - over one million litres in total - in the Pacific Ocean come 2022.

"If they used our filter, they wouldn't need to," says Raffaele Mezzenga, Professor of Food & Soft Materials at ETH Zurich. It was four years ago that he and his Senior Scientist Sreenath Bolisetty unveiled their invention of a filter membrane made primarily of denatured whey protein and activated carbon.

In a publication at the time, the researchers demonstrated how efficiently their product removes heavy metals, some radioactive elements such as uranium, and precious metals such as gold or platinum from water.

Filter also suitable for radioactive isotopes

Now, Mezzenga and Bolisetty have used their membrane to purify hospital effluents contaminated with radioactive elements. Over the course of their investigation, the two researchers discovered that their filter is efficient at removing these substances as well. Their study was recently published in the journal Environmental Science: Water Research & Technology.

Laboratory tests show that the membrane is able to remove radionuclides used in the medical field - technetium-?99m, iodine-?123 and gallium-?68 - from water with efficiencies of over 99.8% in just one filtration step.

The researchers also tested their filter membrane with a sample of real effluents from a Swiss hospital, which contained radioactive iodine-?131 and lutetium-?177. It removed both elements almost completely from the water.

Storage of radioactive material requires space

Medical professionals use radionuclides to treat cancer, for example, or as a contrast agent in imaging procedures. In most cases, these materials are only slightly radioactive and have a short half-?life of just a few hours or days.

Nevertheless, disposal in the sewerage system is not permitted either for hospital effluents that contain these substances or for human waste from patients treated with them. Hospitals must therefore store the effluents safely and securely in special containers until the radioactivity has dropped to a harmless level. This creates problems with space. But that's not the only issue. It's also necessary to ensure that personnel and the environment are protected from radiation.

Membrane massively reduces volumes of waste

"Thanks to our membrane, it's possible to enormously reduce the amount of waste and to store the radiating elements as compact, dry solids," Mezzenga says. Once the membrane has reached its full absorption capacity, it can be replaced and stored in a way that doesn't take up much space, he explains. The filtered liquids can then be discharged safely into the sewerage system.

The study's co-?author Bolisetty co-?founded BluAct Technologies GmbH four years ago. Now his company is preparing a pilot project with a large Swiss hospital that is keen to test the filtration of radioactive effluents. He is confident that the project will soon be up and running. Negotiations are currently underway to establish a safe way to implement the filters. 

Bolisetty is also holding negotiations with a Japanese company involved in the Fukushima clean-?up operation about using the filter membrane to treat a sample of the contaminated water. His aim is to find out if it reliably removes most of the radioactive elements and if it is suitable for treating large volumes.

Filter membrane effective on a broad scale

Based on the results of their current study, ETH Professor Mezzenga believes the product has what it takes. "The filter membrane eliminates radioactive isotopes on a broad scale," he says. In principle, all radioactive isotopes in the periodic table that lie between the extremes tested, i.e. technetium and uranium, bind to the membrane. These include radioactive caesium, iodine, silver and cobalt, all of which are present in the water leaked from Fukushima. Large quantities of tritium are also present; this is the only element that will likely not bind to the membrane because it is too small.

"If our assumption is correct, the filter membrane could massively reduce the volume of wastewater in Fukushima, meaning that no radioactive water would have to be dumped into the Pacific Ocean," Bolisetty says. He explains that the filters saturated with the highly radioactive elements can be stored as solids, for example in the same place as used fuel rods from nuclear power plants.

It is not particularly difficult to produce the filter membrane. The whey protein used is a waste product of the dairy industry, cheap and available everywhere. The activated carbon component is also readily available. "I'm positive that Japan could start using the filter membrane right now and, in doing so, solve a serious environmental problem," Bolisetty says.

Researchers at University of California San Diego report that while Kawasaki disease (KD) occurs in clusters, the traits, and thus the triggers of the inflammatory disease vary among clusters. The findings are published in the September 2020 online issue of The Journal of Pediatrics.

"The importance of this work is that it will take research on Kawasaki disease in a completely different direction. We now have firm evidence that there are different triggers for Kawasaki disease, which suggests slightly different genetic susceptibilities," said Jane C. Burns, MD, a pediatrician at Rady Children's Hospital-San Diego and director of the Kawasaki Disease Research Center at UC San Diego School of Medicine. "Over four decades of research, we have been lumping all these patients together and looking for a single cause. The analysis by our team now shows that we need to be looking for multiple causes of KD, not just one."

The data suggest that either different triggers or different intensities of environmental exposures result in clusters of KD cases that share a similar response pattern. This observation resonates with current observations linking SARS-CoV-2 virus to Multisystem inflammatory syndrome (MIS-C), a disease that shares many clinical features with KD.

In both KD and MIS-C, children are likely born with a genetic predisposition to react to something in their environment and develop severe inflammation. For MIS-C, we know the cause: It's SARS-CoV-2. For KD, we will now start analyzing our data in a completely new way, said Burns.

"This was an unusually fertile cross-disciplinary study. Results obtained could not have been achieved without intense collaboration among earth scientists, statisticians, and pediatric clinicians who care for patients with Kawasaki disease and MIS-C," said Jen Burney, associate professor at UC San Diego's School of Global Policy and Strategy.

Researchers at UC San Diego enrolled 1,332 patients with KD who met American Heart Association (AHA) guidelines for complete or incomplete KD and were diagnosed and treated at Rady Children's Hospital-San Diego between January 2002 and March 2019.

KD cases within a cluster were found to be more similar with respect to demographic and clinical features and levels of inflammation than would be expected by chance. As an example, markers of systemic inflammation when elevated were more likely to be associated with low hemoglobin levels and vice versa (lower measures of inflammation associated with normal hemoglobin).

"While this makes sense biologically, the important finding was that some clusters had this feature while other clusters did not," said Burns. "With respect to clinical features, cases manifesting 'strawberry tongue' or 'lymph node first presentation' also clustered, as did cases without these clinical features."

Important insight into the different etiologies of KD may be gained by focusing on patients who share the demographic and clinical phenotypes identified in our analysis, said Burns.

The clustered presence or absence of these phenotypes in KD patients differed significantly from the two control groups of synthetic clusters, which may indicate that the KD patients within these clusters were responding to different stimuli, resulting in different clinical presentations. Similarly, laboratory evidence of inflammation was either high or low in different clusters, again suggesting a non-random distribution of these features.

The indication that different KD clusters exhibit different physiological responses reinforces the team's prior findings.

"Our focus on clusters of KD cases was directed by our discovery that groups of these clusters are associated with distinct weather patterns", said Scripps Institution of Oceanography climate researcher Dan Cayan, PhD. "These prior results led to the hypothesis that rather than having a single causal mechanism, Kawasaki disease could have multiple environmental triggers. These triggers were evidenced by a combination of anomalous temperature, precipitation and wind patterns."

Kawasaki disease is the most common acquired heart disease in children. Untreated, roughly one-quarter of children with KD develop coronary artery aneurysms -- balloon-like bulges of heart vessels -- that may ultimately result in heart attacks, congestive heart failure or sudden death.

Although KD is estimated to affect fewer than 6,000 children in the U.S. each year, the incidence rate is rising in San Diego County. While the average incidence per 100,000 children less than 5 years of age residing in San Diego County was approximately 10 during the 1990s, the estimated incidence rate from 2006 to 2015 was 25.5.

Incidence rates in the U.S. are approximately 19 to 25 cases per 100,000 children under age 5 -- but are higher in children of Asian descent. Predictive models estimate that by 2030, one in every 1,600 American adults will have been affected by the disease.

HANOVER, NH - Results from the Phase 2 trial of the DAR-901 tuberculosis (TB) vaccine were announced today by investigators at Dartmouth's Geisel School of Medicine and published in the journal Vaccine. The three-year trial was conducted among 650 adolescents in Tanzania, a nation with high rates of TB infection, and showed that the vaccine was safe and induced immune responses against the disease.

Tuberculosis is most common infectious disease cause of death in the world (1.5 million deaths per year compared to 1 million to date from COVID-19) and a new preventive vaccine is a major global health priority. Ford von Reyn, MD, professor of medicine at the Geisel School of Medicine and lead for the vaccine development program, explained that the trial moves the Dartmouth TB vaccine one step closer to a full Phase 3 efficacy trial against TB disease. "Our collaborators in Tanzania deserve credit for their excellent work in conducting a clinical trial to rigorous international standards and moving DAR-901 forward to Phase 3," said Von Reyn.

The vaccine trial was a collaboration between Geisel, the Muhimibili University of Health and Allied Sciences (MUHAS) in Tanzania, the Tokyo Medical and Dental University in Japan, Tufts University School of Medicine, and the Boston University School of Public Health.

Tanzanian students age 13-15 with no evidence of prior TB infection were recruited from schools in Dar es Salaam to receive three injections of the DAR-901 vaccine or placebo in the double-blind trial. All participants had already received the current TB vaccine (BCG) at birth and DAR-901 was administered as a booster. After immunization all participants were followed for safety and re-tested for TB infection annually for three years.

Senior Tanzanian collaborator Kisali Pallangyo, MD, MMed, professor of internal medicine at MUHAS said, "The three dose schedule of DAR-901 was very well tolerated by the students with minimal local reactions and no serious side effects, a very positive result".

The study was conducted as a Prevention of Infection (POI) trial, a new design for TB vaccine trials. TB infection is the first phase of the human response to TB exposure. Because TB infection is not associated with symptoms it can only be detected by a skin test or an IGRA blood test. Development of TB infection is favorable in most people because it provides immunity against progression to TB disease. Among 100 people who acquire TB infection, 90-95% never develop TB disease; only 5-10% will progress to actual TB disease over a lifetime. Although it has been reasoned that if a vaccine can prevent TB infection it will also prevent TB disease, the Dartmouth trial raises questions about this assumption.

DAR-901 was manufactured from SRL172, an inactivated whole cell vaccine which had already been shown to reduce the risk of TB disease in a 2,000 subject Phase 3 trial among subjects with HIV. In the new Phase 2 trial DAR-901 did not reduce the risk of new TB infection, a finding that was not anticipated. Participants who received DAR-901 and did develop new TB infection had greater immune responses to TB than participants who received placebo. The investigators believe this finding suggests DAR-901 may prevent TB disease by inducing the favorable immune response that protects 90-95% of persons with TB infection from ever developing TB disease. This hypothesis will be tested in a large Phase 3 Prevention of Disease (POD) trial that would be required for licensure.

During COVID-19, artificial intelligence (AI) has been used to enhance diagnostic efforts, deliver medical supplies and even assess risk factors from blood tests. Now, artificial intelligence is being used to forecast future COVID-19 cases.

Texas A&M University researchers, led by Dr. Ali Mostafavi, have developed a powerful deep-learning computational model that uses artificial intelligence and existing big data related to population activities and mobility to help predict the future spread of COVID-19 cases at a county level.

The researchers published their results in IEEE Access.

The spread of pandemics is influenced by complex relationships related to features including mobility, population activities and sociodemographic characteristics. However, typical mathematical epidemiological models only account for a small subset of relevant features. In contrast, the deep-learning model developed by Mostafavi, associate professor in the Zachry Department of Civil and Environmental Engineering, and his UrbanResilience.AI lab, can explain the complex relationship between a larger number of features to forecast the range of increase in COVID-19 infections in future days.

"We immediately realized the potential for employing artificial intelligence to complement the existing mathematical epidemiological models," Mostafavi said. "We are living in the era of big data and leveraging these big data during crises is providing great opportunities for the development of models and data-driven tools to inform policies."

A deep-learning model is a subset of machine learning, a type of artificial intelligence, where computing systems, called neural networks, learn from large amounts of data. By training the deep-learning model with data from a certain time period, in this case from March through May 2019, the model identified features to predict the trajectories of another time period -- June 2019.

The researchers' deep-learning model accounts for features such as the movement of people within a community, census data, social-distancing data, past case count growth and social demographics to predict the growth of COVID-19 cases for each county with 64% accuracy, which is twice the accuracy of an untrained model. The model's greatest accuracy was for seven days into the future. The accuracy decreased the further into the future the model predicted.

"One aspect of modeling that is helpful is not the accuracy, but evaluating what factors drive the outcomes," Mostafavi said. "This model does not identify specific mitigation and response strategies, but it can help at different points in time to see which strategies could be effective based on various county-level features."

Knowing which features of the model have the most significant effect on the increase of cases, officials can inform developing policies that target those factors. If the most critical feature for a county is mobility, officials can implement policies like stay-at-home orders.

The model can also offer insight into the effectiveness of policies after they have already been in place. Mostafavi discovered that overall, the initial travel reduction orders were effective -- people from less populated counties traveled less to higher-populated cities, but the extent of travel in densely populated counties did not change drastically.

He said the influence of features can change over time for one county and vary from county to county. At the onset of the pandemic, the researchers saw travel-related and mobility-related factors were important predictors of cases, but as time went on, they saw other features such as travel to points of interests and social demographic characteristics were more important.

The outcome is that pandemic mitigation is complicated, and policies are not one size fits all.

In the future, Mostafavi's lab will use new data sets to develop different types of models. In addition to the current national-scale predictive surveillance model, the team is currently working on an artificial intelligence-based model for city-scale surveillance to predict cases at the zip-code level. More importantly, they want to predict the factors that influence each zip code so that officials can explore location-specific policies. Mostafavi said instead of closing restaurants in an entire county, officials may close restaurants in only high-risk zip codes.

His research shows big data and artificial intelligence have the potential to play a key role in improving pandemic surveillance, prediction and policy development.

"Significant opportunities exist using these big data and AI to contain the existing pandemic and also better prepare and mitigate the future pandemics," Mostafavi said.

Approvals of prescription opioids by the U.S. Food and Drug Administration over more than two decades have been based on evaluations in narrowly defined patient groups for which certain safety-related outcomes have been rarely systematically assessed, according to a new analysis from researchers at the Johns Hopkins Bloomberg School of Public Health.

For their study, the researchers examined clinical trial data provided by manufacturers to the FDA for all new opioid applications approved by the agency between 1997 to 2018, a total of 48 applications. The researchers found that for products labeled for the treatment of chronic pain, no trials lasted for longer than three months. These trials often excluded patients who could not tolerate the drugs and failed to systematically assess some important and well known opioid-related adverse events.

The study was published online on September 28 in Annals of Internal Medicine.

"While the FDA on the whole gets much more right than they get wrong in the approval process for prescription opioids, our findings suggest that over time the agency missed important opportunities to strengthen the regulation of opioid products," says study senior author G. Caleb Alexander, MD, professor in the Bloomberg School's Department of Epidemiology.

Prescription and illicit opioids led to an estimated 50,000 deaths in the United States last year. The ongoing surge of overdoses is part of a crisis that began in the late 1990s which has been fueled, in part, by overuse of prescription opioids. These drugs, like their street counterparts, hit receptors that are found on cells throughout the brain and body and affect a variety of functions, from mood and pain perception to respiration and digestion.

Prescription opioids have the potential not only to be strongly addicting but also to induce tolerance, such that higher doses are needed to achieve the same painkilling effect--and this escalation of dose may cause the fatal suppression of breathing reflexes.

For their study, the researchers looked at the FDA approval process, specifically at the quality of the safety and effectiveness data in New Drug Applications that the agency approved between 1997 and 2018. The study covered the 48 successful opioid painkiller applications during the period--9 for acute pain and 39 for chronic pain.

One key finding was that more than four-fifths of opioids approved for chronic pain based on new clinical trials--17 out of 21--were set up according to an "enriched enrollment with randomized withdrawal" design. In such trials, patients who cannot tolerate the drug being tested--for example, due to common opioid side effects such as nausea or constipation--are withdrawn from the study prior to full treatment and analysis. Alexander and colleagues determined that for the pivotal trials that had this design, a median of 37.2 percent of the initially enrolled patient sample was excluded in this way.

"This design essentially stacks the deck in favor of finding a medicine safe and effective," Alexander says, "because it starts by excluding a large group of people for which the drug is not safe or effective."

Another finding was that trials of opioids for chronic pain were relatively short and small-scale, considering the potential for these drugs to have side effects. The 28 clinical trials used for approval of the opioids labeled for chronic pain enrolled a median of only 299 patients each, and none of the trials lasted more than 84 days.

A third finding was that monitoring of safety issues, including the potential for non-medical use and the development of tolerance, relied too much on patients' spontaneous reports.

Only one of the 48 new drugs covered in the analysis was based on a new painkiller molecule--or "new molecular entity" as chemists call it--with the rest representing new dosages, methods of drug delivery or drug combinations of previously approved opioids such as morphine, oxymorphone, and fentanyl. However, when the researchers examined the original applications for those existing compounds, they found similar shortcomings in the clinical trials used to assess their safety and effectiveness.

Alexander and colleagues recommend in their paper that the FDA, using the relatively broad discretion it has by law, should no longer rely on pivotal trials with "enriched enrollment with randomized withdrawal" designs. The authors believe the FDA should also require that pivotal trials include more comprehensive and systematic assessments of how well the products are tolerated and what potential adverse effects they produce.

Looking ahead, the researchers suggest that FDA improve the rigor, transparency, and consistency of its regulatory reviews of drug applications by giving manufacturers more explicit requirements regarding the design of future trials, such as the populations, duration of therapy, and key safety and effectiveness outcomes that should be assessed.

NO BONES ABOUT IT: WILD GORILLAS DON'T DEVELOP OSTEOPOROSIS LIKE THEIR HUMAN COUSINS

Media Contact: Rachel Butch, rbutch1@jhmi.edu

In a study of gorilla skeletons collected in the wild, Johns Hopkins Medicine researchers and their international collaborators report that aging female gorillas do not experience the accelerated bone loss associated with the bone-weakening condition called osteoporosis, as their human counterparts often do. The findings, they say, could offer clues as to how humans evolved with age-related diseases.

The study was published on Sept. 21, 2020, in Philosophical Translations of the Royal Society B.

"Osteoporosis in humans is a really interesting mechanical problem," says Christopher Ruff, Ph.D., professor at the Center for Functional Anatomy and Evolution at the Johns Hopkins University School of Medicine. "In terms of natural selection, there is no evolutionary advantage in developing bone loss with aging to the point of a potential fracture. By looking at close relatives of humans on the evolutionary tree, we can infer more about the origins of this condition."

The Johns Hopkins research team worked with the Rwanda Development Board, Gorilla Doctors, the Dian Fossey Gorilla Fund International and George Washington University researchers to study the bone collection of mountain gorillas from Rwanda's Volcanoes National Park. The park is one of the few places in the world where conservationists can observe wild gorillas throughout their lifetimes. After a gorilla dies in the wild, its bones are carefully gathered, cataloged and added to the collection housed at the Fossey Fund's Karisoke Research Center.

"This detailed, long-term data on individual gorillas is critically important to this kind of anatomical research work," says Ruff. "Extensive demographic information, including the age at death, allows investigations that are difficult or impossible to carry out in other wild primate populations."

Ruff and his colleagues were able to analyze the bones of 34 wild mountain gorillas -- 16 females and 17 males, ages 11 to 43 years. This spans the full adult range of the species. Using a specialized CT scanner brought to Rwanda, the researchers examined the leg, arm and spine bones from each animal (including the femur, tibia, radius, ulna, humerus and lumbar vertebrae), taking measurements of bone density and geometry.

The researchers found some features of skeletal aging among the gorillas that are similar to those observed in humans, including a general widening of the diameter of long bones and thinning of the bone wall. However, the gorilla bones did not show any of the accelerated bone mineral loss associated with age-related osteoporosis in human skeletons. In humans, women tend to lose bone mineral density more than men. However, in the mountain gorillas, there was no significant difference in bone density or overall strength between older males and females.

These differences, Ruff says, may be explained by the fact that gorillas continue to have offspring throughout their lives, maintaining hormonal levels that help protect them from bone loss. Higher activity levels also may help grow and then maintain stronger bones.

Based on their study results, Ruff and his colleagues hypothesize that this new life stage in humans emerged after the evolutionary split between humans and African apes, and that it could be when some of our age-related diseases, including osteoporosis, originated.

HPV HOME TEST MAY REDUCE CERVICAL CANCER DISPARITY, IMPROVE OUTCOMES FOR BLACKS, LATINOS

Media Contact: Danny Jacobs, djacob41@jhmi.edu

David Sidransky, M.D., calls the Pap smear one of the "greatest successes" in cancer screening.

"Every woman in the United States is supposed to be going for a regular Pap smear exam, and if they do, the chance of developing cervical cancer is very low," says Sidransky, an expert in the molecular genetic detection of cancer and director of head and neck cancer research in the Department of Otolaryngology-Head and Neck Surgery at the Johns Hopkins University School of Medicine.

Despite the Pap smear's effectiveness, however, there are geographic and racial disparities regarding who takes the test and what is an appropriate follow-up. Studies have shown that older women who did not receive the vaccine for the human papilloma virus (HPV, a known cause of cervical cancer) have a higher risk for developing cervical cancer, while Black women have a higher incidence of the disease and do more poorly after diagnosis. Moreover, in many Latino communities, the test isn't widely accepted.

That's why Sidransky has been working with former Johns Hopkins Medicine researcher Rafael Guerrero-Preston, Dr.P.H., M.P.H., on another way to identify women at greatest threat from cervical cancer -- a home test they can do themselves. The self-administered screening tool can accurately identify a higher risk for future cervical cancer by finding methylated DNA segments.

Higher levels of methylation -- the addition of a methyl group (three hydrogen atoms bound to a carbon atom) to a DNA molecule -- are associated with a greater likelihood that cervical cells will progress to a cancerous state.

"If someone tests positive and the early steps of cancer development are detected, we can treat it before it becomes invasive," says Sidransky.

The new test involves a robust molecular process in which cells taken from a vaginal swab are used to detect both HPV and methylated DNA. While a Pap smear only analyzes a small sample of cells from a single spot on the cervix, Sidransky says the home test checks both the swab site and the surrounding region for cervical cancer's early warning signals.

"Even if you miss the presence of a tumor, sampling the larger area enables you to diagnose a problem and better estimate the likelihood that it will progress to cancer," he says.

Sidransky envisions that a woman could swab herself, mail the sample and get results back in less than two weeks, similar to the process for home colon cancer screening kits already in use.

"I think for us to succeed, ultimately the test must be able to be done in any lab," he says. "The goal of this is to make this as low-cost and distributable as possible, including to lower income countries worldwide."

The methylation test was licensed through Johns Hopkins Technology Ventures to LifeGene BioMarks, a Johns Hopkins spinoff company. Guerrero-Preston, the firm's founder and chief scientific officer, worked in Sidranksy's lab for a decade.

LifeGene BioMarks and Sidransky recently received two grants totaling more than $1.5 million through the U.S. Small Business Administration's Small Business Innovation Research program. The grant funds will be used to first make the test more robust for improved cell sampling and then to enable clinicians to examine a larger number of samples for clinical validation.

"I think there is an excitement in terms of what this test could bring in advancing self-screening for cervical cancer and in bridging the disparity gaps that currently keep quality screening from all women," Sidransky says.

STUDY FINDS OBESITY MEDICINE SPECIALISTS ARE USING EVIDENCE-BASED CARE

Media Contact: Michel Morris, melben1@jhmi.edu

The United States obesity rate is now more than 40%, and physicians are looking for new and more effective ways to treat the problem. In 2013, the American Medical Association recognized obesity as a complex, chronic disease that requires medical attention. However, past research studies showed that the percentage of physicians providing adequate counseling and treatment to patients with obesity remains low.

Additionally, patients with obesity are often unaware that such services even exist.

To better understand the state of obesity medicine in the United States, Johns Hopkins Medicine researchers surveyed physicians certified in the discipline by the American Board of Obesity Medicine (ABOM) found that these practitioners, whose numbers are low, commonly offer key services supported by scientific research and clinical trials.

This suggests that primary care clinicians can be increasingly confident that their patients will receive this "evidence-based care" when referred to an obesity specialist. Overall, most of the respondents endorsed the use of nutrition, behavioral services, weight-loss surgical care and anti-obesity medications approved by the U.S. Food and Drug Administration (FDA).

The findings were published online on Sept. 10, 2020, in the journal Clinical Obesity.

"Modifications are key to losing weight," says study lead author Kimberly Gudzune, M.D., M.P.H., associate professor of medicine at the Johns Hopkins University School of Medicine, and director of both the Johns Hopkins Healthful Eating, Activity and Weight Program and the Johns Hopkins Obesity Medicine Fellowship. "A lot of physician training doesn't include obesity treatments such as lifestyle counseling and medication management, and without it, you're unlikely to help patients lose weight. We want to ensure that obesity medicine providers are providing great care to help patients achieve long-term success."

Through ABOM, Gudzune surveyed over 490-obesity medicine certified physicians. The physicians were asked about their current clinical practices in the hope of learning if the services they offer are in line with currently accepted science.

Gudzune and her colleagues found that the majority of ABOM physicians responding to their survey offered nutritional (90%), exercise (68%) and mental health (77%) counseling to their patients. Only a few offered minimally invasive procedures (24%), but most provided care before and after surgery (63%). Most (83%) prescribed FDA?approved medications -- both short? and long?term agents (71%).

Gudzune's team concluded that most of the survey participants' obesity medicine services are evidenced based.

Gudzune plans to use the study's findings to raise patient awareness that there are health care providers specifically trained to help with obesity and its consequences, such as a greater risk of cardiovascular disease, diabetes, certain cancers and premature death. She also hopes the study results can be used to identify where gaps may exist in obesity care and to support development of more comprehensive treatments.

TEMPERATURE-SENSITIVE, LONGER-LASTING EYEDROPS MAY MEAN LESS APPLICATIONS, BETTER THERAPY

Media Contact: Rachel Butch, rbutch1@jhmi.edu

Johns Hopkins Medicine researchers have created a gel-based eyedrop that responds to the eye's temperature and allows drugs to remain longer on the eye surface, penetrating tissues more effectively without obscuring vision. Tested in mice, rabbits and pigs, the formulation could reduce the number of times a day that patients need to reach for the eye dropper.

The study was published Sept. 7, 2020, in Nature Biomedical Engineering.

"The main problem with conventional liquid eye drops is that they are very short lasting and not very much drug gets into the eye because the watery substance is blinked away quickly," says Laura Ensign, Ph.D., associate professor of ophthalmology at the Johns Hopkins Wilmer Eye Institute. "So, eye drops often have to be applied multiple times per day to be effective."

More than 90% of drugs for eye conditions are delivered by liquid eyedrops, say the researchers. For people with irritation, glaucoma or dry eye, drops are required multiple times per day. Each dose comes with a small risk of side effects, which can cause patients to skip doses and reduce the treatment's effectiveness. Patients who do so risk additional problems such as prolonged discomfort and vision loss.

In the study, the team of biomedical engineers and ophthalmologists used a compound, called Pluronic F127, a polymer that responds to body temperature and creates a gel. Currently, Pluronic F127 is a component in various over-the-counter lubricating eye drops, but at very low concentrations. These formulations do not become a gel on contact with the eye. Previous tests in animals of a gel-forming concentration often resulted in clumpy, uneven layers on the eye that quickly got caught up in the lids and lashes. Vision also was obscured.

To solve the clumping problem, the researchers needed to create a drop with enough Pluronic F127 molecules to form a gel, but fluid enough to spread across the eye. They landed on an ionic carrier solution that could be absorbed into cells on the eye's surface, leaving behind the Pluronic F127 polymers. The solution keeps the gelling molecules apart long enough for them to spread out and bind together in a uniform layer.

"It's a simple modification as far as composition, but it causes the drops to behave very differently when applied," says Ensign.

In tests on rabbits, the drops were administered five times each day for two weeks without any adverse effects seen in the rabbits' behavior (such as increased blink rate or eye rubbing) or on eye tissues examined under a microscope. Tests on pigs, whose eyes are more like human eyes in size and composition, showed similar results.

The researchers were surprised to see that since the gel-based drops remained on the eye longer than liquid drops, the treatments could reach the eye's notoriously hard to penetrate back layers. Tissues in these layers -- such as the retina, choroid and macula -- are sites for some of the most common blinding diseases, including diabetic retinopathy and macular degeneration.

In pigs induced by a laser to develop symptoms similar to human macular degeneration, the researchers applied a daily dose of their new eye drops carrying a drug called sunitinib that slows the disease's progression. This cut in half the amount of vision-blocking blood vessel overgrowth in the retina when compared with pigs receiving drops without the drug.

The researchers caution that while promising, more tests are needed before the drops can be tested in humans. They intend to create a company to explore further applications for the drops, including their use with other medications.

Ensign and Hanes are working with Johns Hopkins Technology Ventures to form a startup to license the technology.

BALANCING OLDER PATIENTS' RISK REDUCTION WITH AUTONOMY AND RESPECT

Media Contact: Michel Morris, melben1@jhmi.edu

Many people will become caregivers informally at some point, and geriatrician Mattan Schuchman, M.D., hopes to start a discussion -- among them, the love ones for whom they care and the doctors who work with them -- about the considerations that should be made. When an older patient's safety and independence are in conflict, Schuchman encourages clinicians to weigh several factors: the patient's perspective, the perspectives of other major stakeholders, clinician biases, liability, and the magnitude of the patient's risk and risk to others.

Schuchman and his colleagues discuss these considerations in a commentary in the September 2020 issue of Medical Clinics of North America.

"We should consider both a person's autonomy and ability to make their own choices, and try to balance that with concerns for the person's safety and well-being. It may not always be concordant," says Schuchman, medical director of Johns Hopkins Home-based Medicine and an assistant professor of medicine at the Johns Hopkins University School of Medicine.

Schuchman says these challenges commonly arise in decisions about living environment and driving. From physical rehabilitation to installing home modifications to changing the residence (with a change in the level of care), many decisions about health care for vulnerable adults focus on safety.

In some situations, Schuchman says, clinicians' ethical obligations to promote health and prevent harm may be at odds with their desire to respect the patient's determination to be self-sufficient.

Finding the right answer is not the goal, Schuchman says. He wants clinicians to find fair, transparent ways to choose among morally acceptable alternatives. He hopes patients and their providers can fashion agreements that optimize both safety and independence.

A major national study led by experts from Bristol and Nottingham has found that oral antibiotics are just as effective as intravenous antibiotics in killing a common germ that causes dangerous complications in cystic fibrosis (CF) patients.

The study looked at the effectiveness of the two types of treatment in tackling Pseudomonas aeruginosa, which causes a chronic destructive lung infection in CF patients and which cannot be eradicated unless it is caught in the early stages.

Dr Simon Langton Hewer, a consultant respiratory paediatrician at University Hospitals Bristol and Weston NHS Foundation Trust (UHBW) and chief investigator of the study with colleagues at the University of Nottingham, said: "I'm very excited to be able to share the results of this very important study which has implications for adults and children with CF who have a new infection of Pseudomonas aeruginosa.

"Our study found that traditional oral antibiotics are just as effective as intravenous antibiotics, which means that CF patients who have a new Pseudomonas aeruginosa can be treated at home and saved the inconvenience of having to be admitted to hospital for treatment.

"The results of the study provide evidence to guide practice in CF centres and will help to reduce unnecessary hospital admissions."

Pseudomonas aeruginosa is a bacterium that lives in the environment, lurking in places such as sink drains. Most CF patients have chronic lung infection with the germ by their late teens. Oral and nebulised (inhaled) antibiotics have mainly been used to eradicate Pseudomonas, but are only effective if the infection is caught in time.

Intravenous antibiotics are used commonly to eradicate the infection, however until now there was no clear scientific evidence that intravenous treatment is any better than oral. The TORPEDO trial has shown that routine use of intravenous antibiotics, to eradicate Pseudomonas, is not justified. However, there will still be circumstances (such as a worsening cough or drop in lung function) where intravenous treatment will be needed. Intravenous treatment means that patients with CF need to spend up to two weeks in hospital.

The 10 year trial was sponsored by UHBW and funded with £1.5 million from the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme. In total 286 patients took part in the study at 70 CF centres and clinics around the UK and two in Italy. The findings of the study will be published in The Lancet Respiratory Medicine.

Professor Alan Smyth, from the University of Nottingham's School of Medicine and a co-chief investigator in the TORPEDO clinical trial, said: "For many years we felt we should admit children with cystic fibrosis for intravenous antibiotics when they first had a Pseudomonas infection.

"This can be upsetting for the child and their family and can disrupt school and family life. Thanks to the TORPEDO trial, we now know that oral and inhaled treatment is at least as effective as intravenous, in most cases. In future, we can give this treatment at home and avoid the inconvenience and expense of a hospital admission."

The results of the study have been welcomed by the families of patients and the Cystic Fibrosis Trust.

Adele Farrow's daughter Niamh, who is aged 13 and who has Cystic Fibrosis, took part in the trial.

Adele, from Pilning, South Gloucestershire, said: "This is an amazing result that would really change life for Niamh and us as a family if Niamh developed Pseudomonas.

"Not having to go into hospital and have intravenous medication is a big thing and it's really positive that the results would mean she could stay at home for antibiotics if she developed this infection."

Dr Keith Brownlee, director of policy, programmes and support at the Cystic Fibrosis Trust, said: "This is great news for people with cystic fibrosis. These findings may reduce the time spent in hospital, where they and their families are forced to take time off work and school. This will ultimately improve quality of life for many people with CF."

About 22 percent of women between the ages of 15 and 44 report having used emergency contraception. But even though the Food and Drug Administration approved levonorgestrel--more commonly known as Plan B--for over-the-counter use for women of all ages in 2013, it's not always easy to get--especially at local, mom-and-pop drug stores.

According to a new study led by West Virginia University researcher Amie Ashcraft, chain pharmacies in West Virginia--like CVS and Walmart--are much more likely to stock emergency contraception than smaller independent pharmacies. It was available at 76.3 percent of the chain pharmacies her research team queried, whereas only 14.6 percent of independent pharmacies had it on hand.

"We knew there would be a disparity but not to that degree," said Ashcraft, a research assistant professor and director of research in the School of Medicine's Department of Family Medicine. "We were shocked."

To assess the availability of emergency contraception at pharmacies across the state, Ashcraft and her colleagues trained women in undergraduate- and graduate-level courses at WVU to call pharmacies and--using a planned script--ask if emergency contraception was currently available.

In one call, each woman introduced herself as a researcher and explained that she was gathering information for a study. In a second "mystery shopper" call, she pretended to be a 16-year-old seeking Plan B for herself.

"Some of the pharmacies--especially the ones in the really small towns--physically aren't very big," she said. "They might choose to use their shelf space for medications for diabetes and COPD and choose not to carry Plan B. But reproduction should be a basic part of health that they address."

Availability isn't the only issue, however. Just because a pharmacy stocks Plan B doesn't mean customers can get it conveniently.

For instance, a pharmacy might keep it under lock and key, requiring customers to ask that the shelf be unlocked. Or a pharmacy employee might say--erroneously--that the customer needs to have a prescription or show an ID to get it.

To gauge how accessible pharmacies made emergency contraception, callers also asked about its location in the store and any restrictions to buying it.

The researchers deemed Plan B "completely accessible" if a pharmacy had it in stock at the time of the call, enforced no age restrictions, did not require an ID or parental approval and made it available without help from the pharmacy staff.

Less than half of chain pharmacies--46.5 percent--made Plan B completely accessible. Far fewer independent pharmacies did: just 2.7 percent.

Ashcraft attributes this disparity--at least in part--to corporate policy.

"Chain pharmacies have their policy set at the corporate level, whereas independent pharmacies have more variability in their policies and procedures and may be less current in their knowledge of emergency contraception restrictions, or place a lower priority on such information," she said.

"It was alarming how many times we heard answers like, 'We don't know. The laws just keep changing, and we can't keep up with them,'" she said. "But it's been available over the counter in all 50 states since 2013. If pharmacy staff doesn't know, how is your average 16-year-old supposed to?"

And sometimes a pharmacy didn't give any information at all.

"During the first couple of weeks of the study, one of our research assistants called me and said, 'I'm so sorry. I don't think I'm doing a good job. I think I'm messing up,'" Ashcraft said. "I asked, 'What do you mean?' And she said, 'Well, they keep hanging up on me as soon as I ask for emergency contraception.' And I was like, 'No, no, no, no. This is exactly what we want to know.' Imagine being a scared teen who genuinely needed emergency contraception and was intimidated by the process of getting it. How would you feel if the pharmacy staff hung up on you? It could shut you down."

Not only were chain pharmacies more likely to make emergency contraception completely accessible, but overall, they were also more knowledgeable about its effectiveness.

For instance, when employees at chain pharmacies were asked how long Plan B could be taken after unprotected sex and still work, only 14 percent of the employees said they didn't know. But at independent pharmacies, that number rose to 40 percent. (The correct answer: it's most effective within 72 hours.)

Ashcraft and her team are now examining the differences between how pharmacy employees responded to callers who identified themselves as researchers and those who said they were teenagers in need of emergency contraception.

They're also turning from the quantitative data to the qualitative. They've begun to parse the words pharmacy employees chose, evaluate their content and look for themes.

"Plenty of them would say, 'Oh, we don't do that here,' or, 'We don't mess with that stuff,'" Ashcraft said. "Or we would have staff say, 'We have condoms. You might want to think about that next time' in a judgmental tone."

Emergency contraception is the only form of contraception that works after the risk of exposure. For that reason, it's an important tool for preventing unintended pregnancy following unprotected sex, sexual assault or suspected contraceptive failure.

"Easily accessible emergency contraception could help to reduce teen and unintended pregnancy in West Virginia," Ashcraft said. "The state has some of the highest rates of teen pregnancy and poverty in the country. Emergency contraception may be an important component in helping to break the state's generational cycle of poverty, unintended pregnancy and poor educational, social and health outcomes."

People with generalized epilepsy who have seizures arising from both sides of the brain simultaneously, have a higher risk of obstructive sleep apnea (OSA) compared to patients who have focal epilepsy where seizures emanate from one area of the brain, according to a Rutgers study.

The study, published in the October issue of the journal Epilepsy & Behavior, will help physicians better understand who is most at risk for OSA and therefore, may be most likely to benefit from treatment. Treatment of OSA may help patients feel better, be healthier and may be an important part of epilepsy treatment.

"OSA is common in patients with epilepsy and treatment may improve seizure control. However, this condition is often undiagnosed in patients with epilepsy, and understanding of the risk profile for OSA is important," said lead author Matthew Scharf, an assistant professor of medicine and neurology at Rutgers Robert Wood Johnson Medical School.

The researchers looked at 115 patients from a Level 4 Epilepsy Center -- 27 with generalized epilepsy and 88 with focal epilepsy -- to understand the relationship between their seizure frequency, epilepsy type and results on a standard screening tool to assess obstructive sleep apnea risk.

They also found that older age, a higher body-mass index and a history of high blood pressure were associated with a higher risk of obstructive sleep apnea in people with epilepsy.

The researchers found no significant difference in excessive daytime sleepiness -- a common symptom of people with obstructive sleep apnea and epilepsy -- between the types of epilepsy.

An estimated 22 million Americans suffer from sleep apnea, with 80 percent of the cases of moderate and severe obstructive sleep apnea going undiagnosed. More than three million Americans have epilepsy, with more than 80 percent experiencing focal-onset seizures. About two-thirds of patients with epilepsy can have their seizures controlled with medication. Sleep apnea can be treated in a variety of ways, such as use of continuous positive airway pressure (CPAP), wearing an oral appliance to keep the throat open while sleeping and weight loss.

"Possible reasons for higher risk of OSA in people with generalized epilepsy include greater brainstem dysfunction, altered control of the muscles of the upper airway, instability in the respiratory control system and differences in the anatomy of the upper airway," Scharf said.

Although the number of antiepileptic medications used was similar between the two groups, patients with generalized epilepsy may have started these medications at a younger age and have used them longer, which also could be a factor, he said.

Many of South Carolina's nicotine addiction researchers are in Charleston. But many of the smokers who need to quit live elsewhere in the state.

This poses a dilemma for researchers and smokers alike. Researchers can't enroll large and representative groups of smokers into their trials. And smokers who would like to quit cannot easily access investigational treatments that could help them to do so.

In many cases, remote trials could offer an answer. A suite of new technologies enables researchers in Charleston to reach out to smokers throughout the state, including those in rural areas hardest hit by smoking.

Ten years ago, lack of broadband internet access would have been an obstacle for enrolling participants in rural areas in remote trials. Although that remains an issue, one which the MUSC Telehealth Center of Excellence is seeking to address, the widespread adoption of smartphones among rural populations has begun to chip away at this challenge.

"The days of doing research in our ivory towers are over, as it should be," said Matthew J. Carpenter, Ph.D., a professor in the Department of Psychiatry and Behavioral Sciences at MUSC and co-director of the Cancer Control Research Program at MUSC Hollings Cancer Center. "The days are past when we would just wait for people to knock on our door. We should be going out to folks. Ten years ago, technology was not there to do that, but now we have all these capabilities, and we're starting to break down that ivory tower barrier."

Carpenter and fellow addictions researcher Jennifer Dahne, Ph.D., an assistant professor in the Department of Psychiatry and Behavioral Sciences, recently published an article in Nicotine & Tobacco Research, discussing new technologies that improve the feasibility of remote smoking cessation trials.

"We're trying to bring our clinical trials to our research participants," said Dahne. "And by doing that, we hope to ensure a more representative, diverse sample for our research studies that more accurately reflects the true population of smokers."

Carpenter and Dahne also co-direct the Remote and Virtual Trials program for the South Carolina Clinical & Translational Research (SCTR) Institute -- the Clinical & Translational Science Awards (CTSA) hub with an academic home at MUSC. Together, they are working across specialties to develop technologies to facilitate remote clinical trials and plan to share them with the broader CTSA consortium.

Running a clinical trial is a complicated endeavor. The study leader has to "cast" the trial with appropriately selected and consented patients, and study staff has to assess patients' status and medication adherence during the trial. Now, there's a suite of technologies to help to meet each of those challenges, and study participants can achieve remotely what they once would have had to do in person.

Previously, potential participants had to come to MUSC to be screened and consented for a trial. Geography, time and transportation all presented barriers. Now, thanks to electronic consent, participants can consent from home, using either e-consent functionality embedded within REDCap -- a widely used Vanderbilt-developed tool that is made available to MUSC researchers through SCTR -- or an online platform known as doxy.me, created by MUSC Biomedical Informatics Center researcher Brandon Welch, Ph.D. In partnership with Dahne and Carpenter, BMIC also created a REDCap plug-in that ensures each trial enrolls participants with the exact demographic profile the study team is seeking, helping to guard against the risk that younger, more tech-savvy participants could be overrepresented.

In the past, participants would then have needed to return to MUSC for all scheduled study visits. Now, much of the data can be gleaned remotely. Participants answer REDCap surveys about their symptoms, and those data are collected for review by researchers and clinicians. Participants can also provide objective data about their health status by using a fleet of smartphone-enabled devices, such as the carbon monoxide monitor, integrated with REDCap by Dahne for smoking cessation studies. This quantitative data can be used to confirm self-reported data about participants' efforts to quit.

Other devices, such as Smart Caps, which can track when a pill bottle is opened, could one day be integrated into REDCap and be used to monitor how well participants adhere to prescribed medication regimens.

"The biggest hurdle for remote trials has been the ability to obtain objective data on behavior remotely," said Carpenter. "So being able to collect those data using these smartphone-enabled devices is what I am most excited about."

Dahne has received a number of small business grants to develop app-based treatments for depression, another research interest. Most recently, Dahne received a small business technology transfer grant from the National Institutes of Health to integrate a mobile app-based intervention she developed for depression, called Moodivate, into the electronic health record. The app is intended to address a treatment gap for primary care physicians when it comes to depression.

"Primary care providers can't deliver psychological depression treatment on the spot during regular primary care visits," explained Dahne. "The app gives patients access to evidence-based treatment without having to use up the limited time they have with their doctors."

The integration with the electronic health record means that physicians will be able to access the data from the app and see if patients are improving. If not, they can alter their treatment plans. The grant will also fund a 600-person clinical trial that will test whether patients benefit more from the app alone, the app plus provider review via the electronic health record or usual care.

Carpenter recognizes the value that Dahne brings to the remote trial effort at MUSC. "Jen has a flair for technology, and we benefit from her passion and vision," said Carpenter. "She's an innovator."

Not only could these new technologies facilitate remote clinical trials, they could also provide a means for researchers to share the results of trials with participants.

"Too often as researchers, we do our study, finish up the analysis and publish it. And then we're done," said Carpenter. "We scientists need to do a better job of telling the folks about the relevance of research to them. Remote platforms could be harnessed to do that."

"In a nutshell, we're making trials and their results more accessible for everyone by doing them remotely," said Dahne.

BOSTON (September 28, 2020) - A study published today in the Journal of the American Medical Association Internal Medicine revealed that older persons are highly likely to be excluded from the majority of COVID-19 trials that seek to establish effective treatments, as well as find a preventive vaccine. This is despite the fact that older persons are overwhelmingly impacted by COVID-19. Globally persons 65 and older make up nine percent of the population, yet account for 30 - 40 percent of COVID-19 cases and 80 percent of COVID-19 deaths. Sharon K. Inouye, M.D., M.P.H., Director of the Aging Brain Center in the Hinda and Arthur Marcus Institute for Aging Research at Hebrew SeniorLife, is senior author on the study.

Researchers viewed how often all the COVID-19 clinical trials registered in https://www.clinicaltrials.gov/ from October 1, 2019 to June 1, 2020 did not include older people. This was determined by reviewing direct age-based exclusions or exclusions that preferentially affect older persons, such as the presence of other diseases, or requiring Internet or smart phones to participate. Their findings indicate that older adults are highly likely to be excluded from more than 50 percent of COVID-19 clinical trials and 100 percent of vaccine trials. Inclusion of older adults in clinical trials is critical to ensure equitable access to these treatments.

According to the study, it is important that COVID-19 clinical trials enroll older persons to ensure effectiveness of treatments and to find the proper dosing in this age group, which can be different from other age groups due to physiological changes that come with age. The researchers who participated in this study are particularly concerned that exclusion of older adults from clinical trials may lead to treatments that are ineffective but may even be toxic for older adults.

"To be sure, some exclusions are needed to protect the health and safety of older adults-- such as poorly controlled comorbidities," said Dr. Inouye. "However, many are not well-justified, and appear to be more for expediency or convenience of the trialists. We are concerned that the exclusion of older adults from clinical trials will systematically limit our ability to evaluate the efficacy, dosage, and adverse effects of COVID-19 treatments in this population."

Scientists at the Centro Nacional de Investigaciones Cardiovasculares (CNIC) have designed an algorithm that provides a personalized estimate of cardiovascular risk in healthy middle-aged individuals based on a range of variables including age, blood pressure, diet, and blood and urines markers. The EN-PESA algorithm is an affordable tool for estimating the severity of subclinical atherosclerosis--characterized by the deposition of fatty substances in the arterial walls--especially in individuals at higher risk. The researchers conclude that EN-PESA will "help to personalize the estimation of cardiovascular risk, leading to tailored treatments and follow-up plans."

The study, published today in The Journal of American College of Cardiology (JACC), forms part of the PESA-CNIC-SANTANDER partnership project, which is led by Dr Valentín Fuster. The PESA study was launched in 2010 and was recently extended until 2030, and is one of the most important cardiovascular prevention studies in the world.

"Machine learning algorithms are set to revolutionize clinical practice in the coming years, impacting everything from diagnosis to prevention and treatment. More accurate risk quantification will allow highly precise, personalized risk estimates based on the totality of available information about each individual," says Enrique Lara Pezzi, principal investigator on the current study and leader of the Molecular Regulation of Heart Disease laboratory at the CNIC.

The success of machine learning algorithms derives from the analysis and systematic processing of huge quantities of data collected from a large number of individuals. According to the Head of CNIC Bioinformatics Unit Dr Fátima Sánchez Cabo, "PESA-CNIC-SANTANDER has been a pioneering study collecting large amounts of detailed phenotypical information from all participants of the study."

Atherosclerosis is usually detected at advance stages, when it has already caused clinical events such as a heart attack or stroke. Treatment of atherosclerosis at this stage, after it has shown symptoms, is of limited success. A high proportion of surviving patients experience a decline in their quality of life, and the diminished patient health incurs increased costs for health systems. This is why it is so crucial to detect the disease at the earliest stages.

Since its launch in 2010, the PESA-CNIC-SANTANDER study has characterized more than 4000 parameters related to atherosclerosis. A central feature of the study is its use of advanced imaging techniques, and PESA-CNIC-SANTANDER also collects data on lifestyle parameters, biochemical and molecular markers, and the medical health of more than 4000 employees of Santander Bank who volunteered to participate in the study.

Sifting through this immense quantity of information, the CNIC algorithm identified a small set of variables that are easily measured in primary care centers. Dr Xavier Rosselló, a CNIC researcher and cardiologist at Son Espaces university hospital in Mallorca, explained that these variables "provide an accurate prediction of the extent of subclinical atherosclerosis and disease progression in middle-aged individuals classed as being at low or intermediate risk according to established cardiovascular risk scales."

The parameters include age, blood pressure, data collected in routine blood and urine analysis, and answers to dietary questionnaires.

Dr Sánchez Cabo explained that "EN-PESA uses a machine learning algorithm called Elastic Net, which permits the unbiased analysis of a large number of variables. In this way, this system can identify new predictors not considered in established risk scores." Moreover, EN-PESA treats the predictor variables quantitatively, "avoiding simplistic dichotomies such as 'high cholesterol: yes/no'. This improves prediction and takes account of the specific characteristics of each individual to produce a personalized cardiovascular risk profile."

The authors conclude that "this algorithm will improve the clinical management of apparently healthy individuals with a low cardiovascular risk according to established risk scores but who have a generalized extent of subclinical atherosclerosis or a high short-term risk of significant disease progression."

The study is the product of a multidisciplinary effort involving physicians, mathematicians, chemists, biologists, statisticians, bioinformaticians, nurses, and many other professionals who, together with the volunteers and other staff at Santander bank, made this project possible.

A type of anti-bacterial T cells, so-called MAIT cells, are strongly activated in people with moderate to severe COVID-19 disease, according to a study by researchers at Karolinska Institutet in Sweden that is published in the journal Science Immunology. The findings contribute to increased understanding about how our immune system responds against COVID-19 infection.

"To find potential treatments against COVID-19, it is important to understand in detail how our immune system reacts and, in some cases, perhaps contribute to worsening the disease," says Johan Sandberg, professor at the Department of Medicine, Huddinge, at Karolinska Institutet and the study's corresponding author.

T cells are a type of white blood cells that are specialized in recognizing infected cells, and are an essential part of the immune system. About 1 to 5 percent of T cells in the blood of healthy people consist of so-called MAIT cells (mucosa-associated invariant T cells), which are primarily important for controlling bacteria but can also be recruited by the immune system to fight some viral infections.

In this study, the researchers wanted to find out which role MAIT cells play in COVID-19 disease pathogenesis. They examined the presence and character of MAIT cells in blood samples from 24 patients admitted to Karolinska University Hospital with moderate to severe COVID-19 disease and compared these with blood samples from 14 healthy controls and 45 individuals who had recovered from COVID-19. Four of the patients died in the hospital.

The results show that the number of MAIT cells in the blood decline sharply in patients with moderate or severe COVID-19 and that the remaining cells in circulation are highly activated, which suggests they are engaged in the immune response against SARS-CoV-2. This pattern of reduced number and activation in the blood is stronger for MAIT cells than for other T cells. The researchers also noted that pro-inflammatory MAIT cells accumulated in the airways of COVID-19 patients to a larger degree than in healthy people.

"Taken together, these analyses indicate that the reduced number of MAIT cells in the blood of COVID-19 patients is at least partly due increased accumulation in the airways," Johan Sandberg says.

In convalescent patients, the number of MAIT cells in the blood recovered at least partially in the weeks after disease, which can be important for managing bacterial infections in individuals who have had COVID-19, according to the researchers. In the patients who died, the researchers noted that the MAIT cells tended to be extremely activated with lower expression of the receptor CXCR3 than in those who survived.

"The findings of our study show that the MAIT cells are highly engaged in the immunological response against COVID-19," Johan Sandberg says. "A likely interpretation is that the characteristics of MAIT cells make them engaged early on in both the systemic immune response and in the local immune response in the airways to which they are recruited from the blood by inflammatory signals. There, they are likely to contribute to the fast, innate immune response against the virus. In some people with COVID-19, the activation of MAIT cells becomes excessive and this correlates with severe disease."

University of Texas at Dallas researchers have designed a wearable device that monitors sweat for biomarkers that could signal flare-ups of inflammatory bowel disease (IBD).

A team of bioengineers demonstrated the wristwatch-like device in a proof-of-concept study funded by the Crohn's & Colitis Foundation and published online July 28 and in the October print edition of the foundation's journal, Inflammatory Bowel Diseases.

A sensor in the device detects and quantifies the presence of two key biomarkers associated with inflammatory bowel disease: interleukin-1β and C-reactive protein (CRP). The study is the first to establish that CRP is present in human sweat and the first to show that the two biomarkers can be detected in sweat.

Dr. Shalini Prasad, department head and professor of bioengineering in the Erik Jonsson School of Engineering and Computer Science and the study's principal investigator, said the technology could provide a warning but not a diagnosis of inflammatory bowel disease. The ultimate goal of the work is to develop a device to help patients gain more control over IBD, which can be unpredictable.

"It's like the check-engine light in a car," said Prasad, the Cecil H. and Ida Green Professor in Systems Biology Science. "The warning signal doesn't mean a patient is having a flare-up, but it could give the person the chance to intervene earlier, when the symptoms may be more responsive to treatment. The device also could help doctors understand sooner whether a treatment is working."

The researchers monitored the levels of the two biomarkers in 20 healthy volunteers to show that the biomarkers could be tracked and to establish the levels of biomarkers in people without IBD.

The researchers used what is called passive sweat, which means that the wearer did not need to engage in physical activity or have their sweat glands expressed to generate a sample. The sweat is collected on a removable strip incorporated into the wrist device that must be changed daily. That the device collects passive sweat is important because people with IBD may be unable to exercise at levels needed to generate active sweat, Prasad said.

The prototype will be tested on patient volunteers in a second phase of the research, also funded by the foundation, and must undergo further testing before it can become available to patients.

The device has the potential to track other diseases and conditions marked by an inflammatory response. Prasad's team is investigating whether it could alert people to increases in cytokines, which are proteins released by the immune system at the early stages of a viral infection, such as COVID-19.

Prasad's team previously developed a biosensor that analyzes sweat to detect levels of certain chemicals, such as glucose and cortisol, that could indicate diabetes. In 2014 she co-founded a company called EnLiSense in Allen, Texas, to develop lifestyle-based sensors and devices. Based on Prasad's successful work on the glucose tracker, the Crohn's & Colitis Foundation partnered with her to apply the concept to develop a noninvasive monitor for IBD, said Dr. Gerard Honig, associate director of research innovation for the foundation.

"We've seen extraordinary revolutions in a number of fields, such as bioengineering, and dramatic events relating to medical devices, and we have not necessarily seen those ideas applied to IBD," Honig said.

IBD, which affects millions of people in the U.S., is characterized by chronic or recurring immune response wherein the cells lining the intestines are attacked when the body mistakes food, bacteria and other materials for foreign substances, causing inflammation. Symptoms include fatigue and abdominal pain, with diarrhea in patients with Crohn's disease and stool urgency in those with ulcerative colitis.

Currently, doctors measure intestinal inflammation through endoscopy, which involves the insertion of a long, thin tube into the body to view internal organs or tissue. The procedure is too invasive to be feasible for frequent monitoring of the disease, which creates challenges in recruiting patients for clinical drug trials, Honig said.

"A wearable microsensor device would have the potential to empower patients to be actively engaged in monitoring their disease and managing it," Honig said. "It would greatly facilitate clinical research and potentially could be used in the long term to facilitate proactive management, where you have a target biomarker level you're trying to achieve over a certain period of time and you optimize care to get there."

September 28, 2020 - Beyond the tragic surges in hospitalizations and deaths, the first months of the COVID-19 pandemic disrupted healthcare for people with a wide range of medical conditions - including cancer. For women recovering after breast cancer treatment, COVID-19-related interruptions in rehabilitation care led to emotional distress and other effects on health and well-being, reports a study in the October issue of Rehabilitation Oncology, official journal of the APTA Oncology, an Academy of the American Physical Therapy Association. The journal is published in the Lippincott portfolio by Wolters Kluwer.

"Increased distress is one potential negative effect arising from reducing or eliminating rehabilitation services, effects known to cause their own adverse health effects," according to the new research by Erin Helm, PT, DPT, PhD, Director of Oncology Rehabilitation Services at Helen F. Graham Cancer Center and Mary Lou Galantino, PT, MS, PhD, MSCE, FAPTA, of Stockton University, Galloway, N.J. With their interprofessional team, including Katelyn A. Kempski, OTR/L, the researchers examined the impact of cancelled appointments among women receiving ongoing rehabilitation services for lymphedema after treatment for breast cancer.

Missed Rehab Appointments Affected Mental and Physical Health for Breast Cancer Survivors

The study included 15 breast cancer survivors undergoing therapy for lymphedema: a common complication of cancer treatment that occurs due to damage to lymph nodes or lymphatic vessels. Damage to the lymphatic system results in swelling and tissue changes in the affected limb. Patients with lymphedema experience swelling and limitation of function of the limbs or other areas and are at increased risk of infection. (The APTA has information on physical therapy for lymphedema: PDF link)

Rehabilitation therapy for lymphedema incudes manual lymphatic drainage, compression bandaging, and other approaches to prevent progressive lymphedema with chronic pain and disability. Dr. Helm and colleagues were concerned that mandated closures due to COVID-19 were affecting health and well-being for these patients.

The patients were surveyed as they resumed rehabilitation care after COVID-19 closures. Most of the women had a diagnosis of lymphedema after mastectomy, with symptoms of shoulder pain and stiffness. The study assessed the emotional impact of the disruption in care, along with effects on various aspects of quality of life.

On a standard "distress thermometer," the patients reported significantly increased levels of emotional distress at the time of COVID-19 closures, which decreased when they returned to rehabilitation care. Increased distress at the time of closure was associated with reduced physical activity; the reductions in distress after resuming care were related to reductions in fatigue.

The increase in distress at the time of closure, and the reduction in distress on resuming care, tended to be greater in older women. Emotional distress was unrelated to sleep quality.

Five women had telehealth visits during the closure. While this was not enough patients for statistical analysis, women receiving telehealth tended to have lower fatigue and increased physical activity. Since therapists were unable to provide manual lymphatic draining or other hands-on therapy, rehabilitation therapists had to develop "creative strategies for self-management" for their telehealth patients.

"Rehabilitation services have been shown to improve physical, psychosocial, and emotional constructs of cancer survivorship," Dr. Helm and coauthors write. Although a growing number of studies have focused on the emotional impact and psychological responses to the COVID-19 pandemic, the new study is one of the first to assess the unique implications for health and well-being in cancer survivors.

"Prevalence of distress during a cancer diagnosis and reduced physical activity and decreased quality of life in breast cancer survivors are compounded when uncertainty prevails," Dr. Galantino comments. "Interprofessional teams via telehealth may assist in mitigating the distress during a pandemic and these researchers are exploring further best practices in telehealth with this primary goal in mind."