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DURHAM, N.C. - An aggressive COVID-19 surveillance and testing effort at Duke University was highly effective in minimizing the spread of the disease among students on campus, according to a case study appearing Tuesday in the CDC's Morbidity and Mortality Weekly Report.

The successful Duke campaign was launched before the start of the semester. Ahead of arriving on campus, all enrolled students were required to self-quarantine for 14 days, sign a code of conduct pledge to obey mask-wearing and social distancing guidelines and have a COVID test.

Once classes started, the university conducted regular surveillance testing using pooled samples to conserve resources, daily symptom self-monitoring, contact tracing with quarantine, and regular testing for those who were symptomatic or had been exposed to someone with COVID-19.

The result: The average per-capita infection prevalence among students was lower than in the surrounding community, and large outbreaks seen on other campuses were avoided. Overall, combined testing approaches identified 84 cases among students, with 51% occurring among asymptomatic people.

"Our experience at Duke shows that combined risk reduction strategies and surveillance testing can significantly lower transmissions on college campuses and beyond," said lead author Thomas Denny, professor of medicine at Duke University School of Medicine and chief operating office at the Duke Human Vaccine Institute.

Denny said the Duke experience relied on a combination of strategies. In addition to the testing and quarantining before students arrived on campus, the measures included:

Creating a smartphone app for daily symptom self-monitoring and reporting;

Having students living on campus conduct twice-weekly tests themselves, using kits with prelabeled tubs, swabs and specimen bags; off-campus students tested at least once a week;

Strategically locating sites across campus to collect testing samples from students;

Batching samples in a process called pooled testing, with five samples grouped and analyzed for the presence of the virus. Batches that registered positives were then broken into individual samples and tested separately to identify the source of the positive. The Duke Human Vaccine Institute processed 80,000 samples from August-October.

"By late summer there were still things we didn't fully understand about SARS-CoV-2 transmission, so there was some uncertainty going into the fall semester," said Steve Haase, associate professor in Duke's departments of Biology and Medicine. "Over the course of the semester we've learned many things, including that it is possible to limit the spread of the virus and create a safer environment for our students to have that invaluable on-campus learning experience."

"Thanks to the collaboration of literally hundreds of dedicated individuals, along with the high level of engagement by our students, we have had a very positive fall," said co-author Kyle Cavanaugh, vice president of Administration at Duke University. "Our dynamic surveillance testing strategy has served as a key component of our experience that has also included very high compliance with masking, social distancing and other key public health behaviors."

WASHINGTON, November 3, 2020 -- During the first months of the COVID-19 pandemic, Joseph Lee McCauley, a physics professor at the University of Houston, was watching the daily data for six countries and wondered if infections were really growing exponentially. By extracting the doubling times from the data, he became convinced they were.

Doubling times and exponential growth go hand in hand, so it became clear to him that modeling based on past infections is impossible, because the rate changes unforeseeably from day to day due to social distancing and lockdown efforts. And the rate changes differ for each country based on the extent of their social distancing.

In AIP Advances, from AIP Publishing, McCauley explains how he combined math in the form of Tchebychev's inequality with a statistical ensemble to understand how macroscopic exponential growth with different daily rates arise from person-to-person disease infection.

"Discretized ordinary chemical kinetic equations applied to infected, uninfected, and recovered parts of the population allowed me to organize the data, so I could separate the effects of social distancing and recoveries within daily infection rates," McCauley said.

Plateauing without peaking occurs if the recovery rate is too low, and the U.S., U.K., and Sweden fall into that category. Equations cannot be iterated to look into the future, because tomorrow's rate is unknown until it unfolds.

"Modelers tend to misapply the chemical kinetic equations as SIR (Susceptible, Infectious, or Recovered) or SEIR (Susceptible, Exposed, Infectious, or Recovered) models, because they are trying to generate future rates from past rates," McCauley said. "But the past doesn't allow you to use equations to predict the future in a pandemic, because social distancing changes the rates daily."

McCauley discovered he could make a forecast within five seconds via hand calculator that is as good as any computer model by simply using infection rates for today and yesterday.

"Lockdowns and social distancing work," said McCauley. "Compare Austria, Germany, Taiwan, Denmark, Finland, and several other countries that peaked in early April, with the U.S., U.K., Sweden, and others with no lockdown or half-hearted lockdowns -- they've never even plateaued, much less peaked."

He stresses that forecasting cannot foresee peaking or even plateauing. Plateauing does not imply peaking, and if peaking occurs, there is nothing in the data to show when it will happen. It happens when the recovery rate is greater than the rate of new infections.

"Social distancing and lockdowns reduce the infection rate but can't cause peaking," McCauley said. "Social distancing and recoveries are two separate terms within the daily kinetic rate equations."

The implication of this work is that research money could be better spent than on expensive epidemic modeling.

"Politicians should know enough arithmetic to be given instruction on the implications," McCauley said. "The effect of lockdowns and social distancing show up in the observed doubling times, and there is also a predicted doubling time based on two days, which serves as a good forecast of the future."

Conservation of tropical peatlands could reduce the impacts of the COVID-19 pandemic and the likelihood of new diseases jumping from animals to humans, researchers say.

The scientists reviewed existing evidence and concluded the high biodiversity in tropical peat-swamp forests, combined with habitat destruction and wildlife harvesting, created "suitable conditions" for emerging infectious diseases (EIDs) that could jump to humans.

COVID-19 did not emerge in a tropical peatland area - but HIV/AIDS and the joint-first case of Ebola both originated in areas with extensive peatlands.

The study also assessed the possible impact of COVID-19 on tropical peatland conservation and local communities - and identified "numerous potential threats" to both.

Led by the University of Exeter, the international study team comprised researchers from countries with large tropical peatlands, including Indonesia, DR Congo and Perú.

"We're not saying tropical peatlands are unique in this respect - but they are one important habitat where zoonotic diseases (those that jump from animals to humans) could emerge," said lead author Dr Mark Harrison, of the Centre for Ecology and Conservation on Exeter's Penryn Campus in Cornwall, UK and Borneo Nature Foundation International.

"Tropical peat-swamp forests are rich in fauna and flora, including numerous vertebrates known to represent zoonotic EID risk, such as bats, rodents, pangolins and primates.

"Exploitation and fragmentation of these habitats, as well as peat wildfires (ultimately driven by human activity) and wildlife harvesting bring more and more people into close contact with peatland biodiversity, increasing the potential for zoonotic disease transmission.

"Our review shows that protecting tropical peatlands isn't therefore just about wildlife and carbon emissions - it's also important for human health."

The study also notes "high impacts" of COVID-19 in some countries with large tropical peatland areas, some of which are relatively poorly resourced to tackle pandemics.

"Many communities in these areas are remote, relatively poor, disconnected, have limited infrastructure, sub-standard or non-existent medical facilities, and depend heavily on external trade," said Dr Ifo Suspense, of Université Marien, Republic of Congo, who contributed to the review.

"As a result, the direct and indirect impacts of COVID-19 may be particularly severe in these communities."

Dr Muhammad Ali Imron, from University Gadjah Mada in Indonesia, who was also involved in the study, said: "Additionally, major wildfires in peatland areas cause massive air pollution, particularly in South East Asia, increasing the threat to human health from respiratory diseases like COVID-19.

"In terms of the impacts on peatlands themselves, we reveal that conservation, research and training are all being affected by the pandemic, which may result in increased habitat encroachment, wildlife harvesting and fires started to clear vegetation".

The study concludes: "Sustainable management of tropical peatlands and their wildlife is important for mitigating impacts of the COVID-19 pandemic, and reducing the potential for future zoonotic EID emergence and severity, thus strengthening arguments for their conservation and restoration."

To help achieve this, the study identifies a number of opportunities and recommendations for researchers, field projects, policy makers and donors to help achieve this goal.

Boston, MA -- Falls are the leading cause of preventable injury, and while many strategies have been developed to try to stop them and their resultant injuries, they remain a persistent problem. Research by Brigham and Women's Hospital senior nurse scientist Patricia C. Dykes, PhD, MA, RN, and colleagues has been driven by the question: Why, after more than 30 years of research, do patients continue to fall? The answers that the team uncovered resulted in the creation of a toolkit that includes low-tech solutions, such as a laminated poster to display by patients' beds, tailored prevention plans that can be added to patients' electronic health records and printed out or displayed on a computer screensaver, and other interventions that engaged patients and their families in strategies to prevent falls. The investigators found that their program, which focused on tools that engage patients and families in the fall prevention process throughout hospitalization, was associated with significantly reduced falls and fall-related injuries at three different hospitals. The team's results are published in JAMA Network Open.

"Our study highlights just how important it is to engage with patients for prevention," said Dykes. "If you partner with your patient to identify the risks and talk about how we can prevent them as a team, then patients and families respond to this and rise to the occasion."

In 2007, Dykes and colleagues began developing the Fall TIPS (Tailoring Interventions for Patient Safety) Toolkit, a nurse-led, evidence-based fall prevention intervention. As part of the program, nurses helped develop a personalized fall prevention plan tailored to each patient and used bedside tools to communicate patient-specific fall risk factors. In a randomized controlled trial at four Mass General Brigham hospitals in 2009, Fall TIPS reduced patient falls by 25 percent, but there was no difference noted in fall-related injuries, likely due to patient non-adherence to fall prevention plans.

To overcome these challenges, and in collaboration with Northeastern University's Healthcare Systems Engineering Institute, Dykes and colleagues studied and conducted interviews with hospitalized inpatients, family members and providers. Based on insights from this research, they developed their toolkit to be more patient-centered and to address barriers for engaging patients and families in the fall-prevention process. This included a poster, hung at patients' bedsides, that contained information about fall prevention which nurses completed on admission and at each shift with patients and their families. The team examined whether posters were updated and whether patients and families could articulate the fall risk factors and fall prevention factors.

The team conducted a non-randomized trial at three academic medical centers, including 12 adult-medical units at the Brigham, one at New York Presbyterian Hospital and one at Montefiore Medical Center Hospital between September 2015 and November 2016. More than 37,000 patients were evaluated. The team found that after the fall prevention toolkit was implemented, sites saw a 15 percent reduction in falls and a 34 percent reduction in injurious falls. The original Fall TIPS Toolkit was most effective among older patients, but the new study found important progress in falls prevention among younger patients.

The toolkit has now been adopted at the Brigham and across Mass General Brigham. Dykes and colleagues continue to solicit feedback from nurses through practice councils to find even more opportunities for improvement. They have also made the toolkit freely available on the web, at http://www.FallTIPS.org, for all other acute care settings to use. Already, the toolkit has been adopted by 150 hospitals in the U.S. and around the world.

"This work represents a collaboration across disciplines and the input of nurses, patients and their families," said Dykes. "Falls take a staggering toll on patients and families, and we remain focused on continuing to decrease the rates of falls, especially injurious falls, at our hospital and globally."

Scientists have established a new method to image proteins that could lead to new discoveries in disease through biological tissue and cell analysis and the development of new biomaterials that can be used for the next generation of drug delivery systems and medical devices.

Scientists from the University of Nottingham in collaboration with the University of Birmingham and The National Physical laboratory have used the state-of-the-art 3D OrbiSIMS instrument to facilitate the first matrix- and label-free in situ assignment of intact proteins at surfaces with minimal sample preparation. Their research has been published today in Nature Communications.

The University of Nottingham is the first University in the world to own a 3D OrbiSIMS instrument. It is able to facilitate an unprecedented level of mass spectral molecular analysis for a range of materials (hard and soft matter, biological cells and tissues). The facility in Nottingham also has high pressure freezing cryo-preparation facilities that enable biological samples to be maintained close to their native state as frozen-hydrated to complement the more commonly applied but more disruptive freeze drying and sample fixation. When the surface sensitivity, high mass/spatial resolution are combined with a depth profiling sputtering beam, the instrument becomes an extremely powerful tool for 3D chemical analysis as demonstrated in this recent work.

Dr David Scurr from the University of Nottingham's School of Pharmacy led this latest study and was supported by PhD student Anna Kotowska. David said: "The design and innovation of the next generation of biomaterials is underpinned by the ability to accurately characterise biological tissue and materials. The challenge for scientists in this area has been unpicking the chemical complexity of such systems. This approach to protein analysis has been demonstrated using extreme examples to illustrate its sensitivity and specificity by chemically mapping a protein monolayer (protein biochip) and distribution of specific protein in human skin (complex multi-layered biological system) respectively. With the ability to chemically map proteins in this way we are a step closer to being able to understand fundamental biological processes and develop more effective systems for targeting drugs and providing coatings for medical devices."

The team in Nottingham have already applied biomaterials research to create a new type of urinary catheter in partnership with Camstent Ltd that is coated in a bacteria resistant material discovered by scientists from the University of Nottingham.

Professor Morgan Alexander is director of the EPSRC Programme Grant in Next Generation Biomaterials Discovery and the 3D OrbiSIMS facility, he said: "The research we are now able to do using this instrument is paving the way for step changes in how materials can be used in medicine to better treat disease and illness. The Catheter coating we have developed in partnership with Camstent has gone all the way from the discovery of a new class of materials that no one could have predicted all the way to clinical trials and is a great example of the application of this type of research."

Paula Mendes, Professor of Advanced Materials and Nanotechnology at the University of Birmingham, adds: "With these new capabilities to characterise proteins at surfaces comes also new exciting opportunities to engineer functional materials with predictable protein interactions for biosensor technology".

DALLAS - Nov. 17, 2020 - Being younger doesn't protect against the dangers of COVID-19 if you are overweight, according to a new study from UT Southwestern. While all adults who are overweight or obese are at greater risk for serious complications from the disease, the link is strongest for those age 50 and under.

More than 42 percent of American adults are now obese, according to the Centers for Disease Control and Prevention, and another 30 percent or so are overweight. Being overweight is defined as having a BMI (Body Mass Index) of 25-29, while those with a BMI of 30 or above are said to be obese.

"If you're young and obese, you're still at high risk despite your age," says Justin Grodin, M.D., senior author of the study published today in Circulation. (In the study, young is defined as age 50 or younger.)

"In general, obese individuals are more likely to be hospitalized with COVID-19 than normal weight individuals," adds Nicholas Hendren, M.D., a UTSW chief cardiology fellow and first author of the study, which will be presented this week at the American Heart Association Scientific Sessions 2020 conference. "In the hospital, obese individuals are at higher risk for death or the need for mechanical ventilation to help them breathe, even if they are young."

The study's findings should alert people who are overweight or obese - including those age 50 and under who may feel safe because of their age - that they are at greater risk from COVID-19, says Grodin, assistant professor of internal medicine at UT Southwestern. Those in the most severe category of obesity, called Class III and defined as having a BMI of 40 or higher, should be considered high risk and may warrant prioritization for a COVID-19 vaccine when it becomes available, Grodin adds. About 7 percent of the adult population falls into this category, according to the study.

While the numbers don't explain why obesity worsens outcomes for COVID-19 patients, the study suggests several possibilities.

First, obesity is associated with diseases that have been linked to worse outcomes for COVID-19, such as hypertension and diabetes, according to the study. Secondly, the SARS-CoV-2 virus uses an enzyme called ACE2 to enter and infect human cells, and that enzyme is abundant in fat tissue. In addition, simply having more weight on the chest may make it harder for COVID-19 patients to breathe, Grodin says.

Also, negative effects tied to obesity may be especially apparent in younger patients because older COVID-19 patients have so many other risk factors, he adds.

The Circulation study analyzed data from more than 7,600 patients at 88 U.S. hospitals who were enrolled in the American Heart Association's COVID-19 Cardiovascular Disease Registry. James de Lemos, M.D., a UTSW professor of internal medicine, helped create the registry along with volunteers and AHA staff. The Circulation study team adjusted its findings of risk to take into account patients' age, sex, race, and prior health problems.

Looking at patients age 50 and under hospitalized for COVID-19, the researchers found that the vast majority - 85 percent - were either overweight or obese. That compares with 54 percent of patients over age 70, making weight more of a risk marker for the younger group. Among patients 50 and under, those with severe obesity had a 36 percent greater risk of dying, compared with normal weight individuals, the study found. Overall, adult patients with severe obesity had a 26 percent higher risk of dying.

Looking at all adult patients, the risk of being sick enough to require a ventilator rose in lock-step as weight increased from overweight to Class III obesity, according to the study. The risk of death also rose for those who had Class III obesity.

"There is a greater proportion of obese people among those hospitalized for COVID-19," says Grodin, "and obese patients are at higher risk for complications."

In addition to greater risk for death and the need for ventilation, higher BMI also was linked to the need for kidney dialysis and the development of blood clots in deep veins and the lungs, according to the study.

Other studies are underway to examine how various patient characteristics affect COVID-19 risk, using the AHA’s COVID Registry, Grodin says.

DALLAS, Nov. 16, 2020 -- A novel diabetes medication significantly reduces the risk of hospitalization for heart failure, heart attack and stroke, in patients with Type 2 diabetes and chronic kidney disease, according to late breaking research presented today at the American Heart Association's Scientific Sessions 2020. The virtual meeting is Friday, November 13-Tuesday, November 17, 2020, and is a premier global exchange of the latest scientific advancements, research and evidence-based clinical practice updates in cardiovascular science for health care worldwide.

SGLT2 inhibitors are a class of medications that are prescribed to lower blood sugar in adults with Type 2 diabetes. Sotagliflozin is the first dual SGLT2/1 inhibitor developed for the management of both Type 1 and Type 2 diabetes.

"People with Type 2 diabetes have higher rates of cardiovascular and kidney disease and more serious complications," said lead study author Deepak L. Bhatt, M.D., M.P.H., FAHA, executive director of interventional cardiovascular programs at Brigham and Women's Hospital Heart & Vascular Center and professor of medicine at Harvard Medical School. "Recent trials of other SGLT2 inhibitors have consistently shown reductions in heart failure, and we wanted to assess the safety and efficacy of sotagliflozin in adults with Type 2 diabetes and chronic kidney disease."

Researchers conducted a randomized, placebo-controlled, multicenter study to investigate the effects of sotagliflozin. In the SCORED trial, more than 10,000 people (average age 69, 45% women, 17% non-white) with Type 2 diabetes and chronic kidney disease were randomized to receive either sotagliflozin or placebo.

Although the trial ended earlier than planned due to loss of funding during the COVID-19 pandemic, results after an average follow up period of 16 months indicate numerous benefits for patients receiving sotagliflozin:

There was a significant 26% decrease in the total number of cardiovascular deaths, hospitalizations for heart failure or urgent visits for heart failure.

A significant reduction in the total number of heart attacks and strokes was achieved.

There was a significant reduction in blood glucose levels in patients with moderately to severely reduced kidney function.

Bhatt added, "Sotagliflozin is the first SGLT2 inhibitor to show a beneficial effect on stroke among patients with diabetes, suggesting that it may also affect atherosclerosis, or plaque build-up in the coronary and brain arteries. SCORED is also the first trial to show the benefits of SGLT2 inhibitors across the full range of albuminuria, or leakage of protein in the urine, which is common in people with Type 2 diabetes.

"This is a major advance for patients with Type 2 diabetes and advanced kidney disease, and these results clearly demonstrate that SGLT2 inhibitors should become part of the standard of care," he said.

DALLAS, Nov. 16, 2020 -- The investigational medication finerenone reduced the risk of heart attack, stroke, heart failure and other negative cardiovascular events in patients with chronic kidney disease and Type 2 diabetes, according to late-breaking research presented today at the American Heart Association's Scientific Sessions 2020. The virtual meeting is Friday, November 13-Tuesday, November 17, 2020, and is a premier global exchange of the latest scientific advancements, research and evidence-based clinical practice updates in cardiovascular science for health care worldwide. The manuscript of this study is simultaneously published today in Circulation, journal of the American Heart Association.

In the largest trial of its kind to-date, the study, "Finerenone and Cardiovascular Outcomes in Patients with Chronic Kidney Disease and Type 2 Diabetes" (FIDELIO-DKD), found that finerenone reduced the risk of cardiac events for patients regardless of whether they had a history of heart disease or not. Finerenone - a novel, nonsteroidal, selective mineralocorticoid receptor antagonist - reduced both the risk of worsening kidney disease and risk of death related to heart problems.

"We are pleased to see that finerenone could provide a meaningful treatment option for patients who are battling chronic conditions," said Gerasimos Filippatos, M.D., the study's lead author and a professor of cardiology at the National and Kapodistrian University of Athens in Greece.

The FIDELIO-DKD study is a phase III, randomized, double-blind, placebo-controlled trial that enrolled nearly 6,000 patients (average age 66; 70.2% male) at more than 900 sites in 48 countries. The goal was to investigate finerenone in patients with chronic kidney disease and Type 2 diabetes since these patients face significant risk of cardiovascular disease and death. Cardiovascular events like heart attacks, heart failure and stroke are some of the leading causes of death in this patient group.

After follow-up of more than 2-1/2 years, researchers found a daily, oral treatment at 10 mg or 20 mg with finerenone reduced by 14% the risk of cardiovascular events for patients who already had a history of heart disease and for those who had no previous history. It also reduced the rate of death, heart attack, stroke and hospitalization for heart failure among patients with chronic kidney disease and Type 2 diabetes.

Obesity is a serious global health problem and a risk factor for diseases such as type II diabetes, heart disease and fatty liver disease. A central element in the development of obesity is adipose tissue, which comprises fat cells (so-called adipocytes, specialised to store fat) and macrophages (immune system scavenger cells, which are typically associated with the destruction of microbes). Together with researchers from Poland, Germany, Australia and Austria, a team of MedUni Vienna scientists has now discovered the signalling pathways responsible for the development of a valuable type of adipose tissue macrophage (ATM) in obesity, which prevents lipotoxicity. Lipotoxicity is the process whereby fat molecules are deposited in non-adipose tissues. This study has now been published in the top journal Nature Metabolism.

In this study, the researchers, including some from CeMM (Research Center for Molecular Medicine of the Austrian Academy of Sciences) and the University of Graz, specifically studied the PI3K signalling pathway. This is a major metabolic regulator, since it regulates fat storage and plays a major role in the cellular reaction to the hormone insulin. In obesity, diminished insulin action or insulin resistance leads to type II diabetes, which is linked to high blood glucose levels.

Gernot Schabbauer from the Institute of Vascular Biology and Thrombosis Research at MedUni Vienna's Center for Physiology and Pharmacology and senior author of the study has been studying the PI3K signalling pathway in immune cells for several years now: "The key role of PI3K in metabolic processes is proven but its role in adipose tissue macrophages was hitherto unclear." Julia Brunner, co-lead author of the study, adds: "ATMs are like Dr Jekyll and Mr Hyde - in obesity, they can either be good or bad. We assumed that an active PI3K signalling pathway could tip the balance in favour of 'good'."

Using techniques such as multicolour flow cytometry, lipidomics, cellular respiration tests and several animal models, the scientists discovered that sustained activity of the PI3K signalling pathway can tip the balance within macrophages for the better: this notably produces specialised ATMs, which are characterised by increased numbers of MARCO (macrophage receptor with collagenous structure) scavenger receptors on their surface.

"We discovered that these MARCO-expressing ATMs are professional lipid scavengers. These cells absorb fat MARCO-dependently and break it down, thereby preventing it from finding its way into the bloodstream," explains Andrea Vogel, co-lead author of the study and PhD student in immunology at MedUni Vienna. Omar Sharif, co-senior author of the study, adds: "Metabolic syndrome and lipotoxicity are characteristic features of obesity. Our work indicates that a higher lipid intake and improved energy metabolism of the ATMs helps to maintain systemic metabolic health. This can have far-reaching impacts for a number of metabolic diseases."

Subsequent studies will now be conducted to establish whether PI3K signalling can also have a lasting influence on the ATM population in humans as well. "Although moderate inhibition of PI3K has already been discussed as a therapeutic strategy for treating metabolic diseases, our data point to potential unexpected side-effects. These might include altered blood lipid levels, caused by the reduced fat absorption of the ATMs," says Schabbauer.

New research by University of Georgia scientists sheds light on why people with obstructive sleep apnea may have associated autoimmune disorders. The results could lead to better approaches to treatment and possibly new drug therapies.

The study, led by Bradley Phillips, builds on previous research showing that obstructive sleep apnea increases the risk for autoimmune diseases. Immune system disorders are a result of either low activity or over activity of the immune system and include well known conditions such as lupus and rheumatoid arthritis.

"This paper looks at what may be the underlying mechanisms that increase someone's risk for autoimmune disorders because they have untreated obstructive sleep apnea," said Phillips, director of UGA's Biomedical and Health Sciences Institute.

Obstructive sleep apnea, or OSA, is a disorder that occurs when throat muscles relax temporarily, narrowing or collapsing the airway and momentarily cutting off breathing during sleep. The main treatment for OSA is continuous positive airway pressure, or CPAP, which pumps air through a mask to keep the airway open. About 40% of patients can't tolerate CPAP.

OSA damages the health of 35% of Americans and results in increased risk of several autoimmune disorders, like rheumatoid arthritis and psoriasis, for example, but the molecular links to autoimmunity are poorly understood.

Phillips and the team looked at four cytokines--proteins involved in cell signaling--associated with autoimmune disease. They evaluated the cytokines in three groups of adults: patients with untreated OSA, patients with OSA who were receiving treatment, and people who did not have OSA. The study results revealed abnormal levels of the four cytokines in patients with untreated sleep apnea, suggesting that poor sleep and inadequate oxygen supply may affect the cytokines.

This study, published in Clinical Immunology, is one of four investigating possible links between obstructive sleep apnea and specific diseases. In addition to autoimmune disorders, the team is also looking at neurodegenerative disorders, cardiovascular disease and renal disease.

"The relationship between OSA and other diseases is always complex to study. OSA in adults is commonly first diagnosed in midlife, but increases with age," said Phillips, professor in the College of Pharmacy. "With increased age, you are also at risk for other diseases, and it's very challenging for clinicians and researchers to determine if it's OSA alone that causes other disorders, or if OSA only worsens the severity and progression of an underlying disease. In the case of high blood pressure, we know untreated OSA can cause hypertension and make blood pressure drug therapy ineffective. If obstructive sleep apnea is a key player, then it should be evaluated and treated along with other conditions."

In a new editorial in the Journal of the American Geriatrics Society, Kathleen Unroe, M.D., MHA, a geriatrician, is advocating for stronger relationships between health systems and nursing homes to provide better care for patients in times of crisis and during day-to-day operations.

"Close associations between nursing homes and health systems can greatly enhance patient care and support for staff," said Dr. Unroe, who is a Regenstrief Institute research scientist and an Indiana University School of Medicine associate professor of medicine.

The COVID-19 pandemic has devastated nursing homes. Nursing home residents account for around 25 percent of COVID-19 deaths in the United States, according to data from the Centers for Medicare and Medicaid Services.

"Health leaders need to learn from what has happened so far and implement new practices to prevent more deaths," continued Dr. Unroe. "Relationships between nursing homes and health systems are not only crucial in times of crisis, such as the COVID-19 pandemic, but are also beneficial in addressing other challenges regularly faced by nursing homes, such as transitions of care."

In the editorial, which accompanied a paper from the University of Michigan, Dr. Unroe discussed how three well-contained COVID-19 outbreaks provide a model for leveraging relationships between health systems and nursing homes to improve care and prevent the spread of infection. The three long-term care facilities that successfully contained outbreaks had a pre-existing relationship with a health system, and that connection helped leaders coordinate a response and gain additional expertise.

"These examples demonstrate the power of investing in collaboration," said Dr. Unroe. "It is heartening to see these affiliations leveraged to improve care for nursing home residents as well as to support the facility staff. The benefits extend outside of crises like the current pandemic to everyday situations that arise within nursing homes."

Dr. Unroe has been working as a geriatrician in nursing homes throughout the pandemic and has personally witnessed the misery suffered by both people living in nursing homes and those who care for them.

In the editorial, she urged health systems to be receptive to nursing homes asking for support and also to reach out proactively to area nursing facilities.

"No nursing home administrator, medical provider or frontline worker should feel they are fighting this alone," said Dr. Unroe. "These relationships can be mutually beneficial and do improve patient care. Nursing home staff and leaders are experienced in care for older adults. Health systems can provide support in the form of infectious disease and palliative care expertise, personal protective equipment and access to COVID-19 testing."

She also stated that the pandemic has highlighted the importance of integrating nursing home data sources with other healthcare data. Linking datasets from nursing homes with datasets from hospitals is helpful for public health officials in cases of infectious disease outbreaks, such as COVID-19. Integration would also support implementation of automated data exchange when a patient is moved to a different setting to receive care, helping to improve communication between providers.

DALLAS, Nov. 17, 2020 -- People with heart disease can receive either the high-dose or standard-dose flu vaccines for protection from heart or lung-related deaths or hospitalizations, according to late breaking research presented today at the American Heart Association's Scientific Sessions 2020. The virtual meeting is Friday, November 13 - Tuesday, November 17, 2020, and is a premier global exchange of the latest scientific advancements, research and evidence-based clinical practice updates in cardiovascular science for health care worldwide.

People with heart disease are at increased risk for complications from influenza, including heart attacks, hospitalizations for heart failure and death. Researchers for the Influenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated Heart Failure (INVESTED) study, funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health, set out to evaluate whether a higher dose flu vaccine offered more protection against those complications, compared to a standard-dose flu vaccine. The high-dose vaccine is currently approved in the United States for people ages 65 or older and has been shown to reduce the incidence of influenza infection in these patients.

"Since people with chronic conditions have been shown to exhibit reduced immune responses to the flu vaccine, we conducted a trial to determine if a higher dosage would overcome the lower response and better protect high-risk individuals," said Orly Vardeny, Pharm.D., M.S., lead researcher of the study and an associate professor at the University of Minnesota Medical School and in the College of Pharmacy in Minneapolis. "We found that the higher dose influenza vaccine was not more effective than the standard dose in lowering the risk of death or hospitalizations from heart or lung-related illnesses."

INVESTED is a randomized, double-blind, active-controlled trial that enrolled more than 5,000 (5,260) participants across 157 clinical sites in the U.S. and Canada. Eligible participants had a recent heart attack or were hospitalized for heart failure in the previous two years. They also had at least one additional risk factor such as kidney disease, diabetes, stroke, peripheral artery disease, a weak heart muscle or current use of tobacco.

Researchers randomized participants equally to receive either a high-dose trivalent influenza vaccine, which contained higher doses but only three strains of the inactive flu virus, or a standard-dose, quadrivalent vaccine including four strains of influenza. Participants could remain in the study for up to three years, between the 2016 and 2019 flu seasons, and received the same type of vaccine each year they were in the study. There was no difference in the rates of mortality or hospitalizations for cardiac or pulmonary causes between vaccine formulations (44.5 per 100 patient years for those who received the high-dose vaccine, compared with 41.9 per 100 patient years for those who received standard-dose).

"There are several possible explanations for our findings. First, we enrolled people at high risk for heart and lung-related hospitalizations, and there were many of these types of hospitalizations during the trial. However, only a small number of those hospitalizations were identified as caused by influenza," said Vardeny who is also a core investigator with the Center for Chronic Disease Outcomes Research at the Minneapolis VA Health System. "It is possible that since all participants received the flu vaccine, both formulations similarly reduced the risk for heart and lung hospitalizations. Another possibility is that since participants were already at a very high risk for hospitalization due to their pre-existing heart conditions, and most of the hospitalizations were not attributable to influenza, the incremental benefit of one vaccine over the other would not have overcome the high underlying risk in this population."

She also noted it is possible that the extra influenza strain present in the standard-dose vaccine might have offset the benefit of the higher dose.

Researchers did not collect information on how many participants became sick with the flu, so they do not know if the higher dose of the vaccine reduced overall flu infections more than the standard dose in study participants.

Vardeny said future research should examine whether other types of the flu vaccine may be more protective for patients with high-risk conditions or whether the high-dose vaccine is more effective in low-risk cardiac patients.

"Most importantly, these data don't detract from the extremely strong recommendation that all patients with heart disease get vaccinated for influenza. This is especially the case this year, when influenza will be co-circulating with SARS-CoV-2, the virus that causes COVID-19," Vardeny said. "Our study showed that vaccine dose may not be as important as getting vaccinated."

In 2018, West Virginia had the highest rate of acute hepatitis Brate of acute hepatitis B in the nation. That same year, the state had the highest rate of opioid prescriptions per 100,000 people. That's not a coincidence: drug use--including opioid misuse--raises a person's risk of contracting the hepatitis B virus.

A study led by Stacy Tressler--who earned her doctorate in epidemiology from the West Virginia University School of Public Health--suggests that local health departments are vital to getting the hepatitis B vaccine to the people who need it most.

Her findings appear in the American Journal of Preventive Medicine.

"I don't think people realize the amount of health care that local health departments provide across West Virginia," Tressler said. "They really reach some of our most vulnerable populations, they do a lot of really great work and they've already built a lot of relationships in the community."

Now an epidemiologist with the Pennsylvania Department of Health, Tressler previously worked for the West Virginia Department of Health and Human Resources. During her 10 years of public health work in West Virginia, she "worked, for the most part, with local health departments. And the work that the local health departments do is really overlooked," she said.

Tressler and her colleagues at WVU analyzed data from local health department clinics that participated in the West Virginia Hepatitis B Vaccination Pilot Project. The pilot project distributed more than 10,000 doses of the hepatitis B vaccine to at-risk adults in West Virginia from 2013 to 2015.

The data encompassed 1,201 at-risk adults vaccinated at local health department clinics or through local health departments' outreach efforts to correctional facilities and substance use treatment centers.

Participants who received the vaccine at substance use treatment centers or local health departments' family planning clinics were significantly more likely to complete the series of injections--which consists of three shots--than people vaccinated at local health departments' sexually-transmitted-infection clinics.

"People who receive services through substance use treatment centers have a relationship with that facility," Tressler said. "Even if--for some reason--they're not in treatment anymore, I think those facilities can continue to work with people to try to get them the resources they need."

She credits these relationships--between facility staff members and the clients they serve--with increased odds of vaccine completion.

The researchers also found that participants vaccinated at substance use treatment centers, correctional facilities and local health departments' family planning clinics were much more likely to receive at least two doses of the hepatitis B vaccine.

That's important because it can be hard to get people to complete any vaccination that involves multiple shots, spread out over weeks or months. That's the case whether it's people with substance use disorders being vaccinated against the hepatitis B virus or middle-schoolers receiving the three-shot HPV vaccine.

"It's always a challenge getting people back in to finish the series--especially if you're trying to reach people who may have life circumstances that prevent them from engaging with the healthcare system," Tressler said. "There are going to be issues with trying to keep those people on your radar and being able to get them back in and to finish the series."

But even two doses of the three-dose hepatitis B vaccine impart some protection in most healthy adults. And in 2017, the Food and Drug Administration approved a new hepatitis B vaccine that requires just two shots.

"The high uptake of hepatitis B vaccine when health departments partnered with local drug treatment programs is very encouraging, as West Virginia has the highest rate of new hepatitis B infections in the U.S.," said Judith Feinberg, vice chair of research for the School of Medicine and a member of Tressler's research team. "People who are engaged in a treatment program have the opportunity to reliably receive the multiple vaccine doses required: three doses over six months for the older vaccine, and two doses over two months for a newer version."

The team also included School of Public Health researchers Christa Lilly, Diane Gross and Thomas Hulsey.

"This study shows that you can create partnerships with local health departments to provide healthcare for at-risk people," Tressler said. "People who may be at risk of contracting the hepatitis B virus might not access a primary care provider. You have to meet people where they are."

Researchers affiliated with the Center for Cell-Based Therapy (CTC) in Ribeirão Preto, Brazil, have identified for the first time a non-hereditary mutation in blood cells from a patient with GATA2 deficiency, a rare autosomal disease caused by inherited mutations in the gene that encodes GATA-binding protein 2 (GATA2). GATA2 regulates the expression of many genes that play a key role in developmental processes and cell renewal.

The researchers believe the non-hereditary (somatic) mutation may have acted as a kind of natural gene therapy, preventing the disease from damaging the process of blood cell renewal (hematopoiesis), so that the patient did not develop such typical clinical manifestations as bone marrow failure, hearing loss and lymphedema (blockage of the lymphatic system).

An article on the study is published in the journal Blood, featuring on the cover and with an editorial commentary.

The findings pave the way for the use of gene therapy and changes in genetic counseling for families with the hereditary disorder. “When a germline [inherited] mutation in GATA2 is detected, the patient’s family has to be investigated because there may be silent cases,” Luiz Fernando Bazzo Catto, first author of the article, told Agência FAPESP.

CTC is a Research, Innovation and Dissemination Center (RIDC) funded by FAPESP and hosted by the University of São Paulo’s Ribeirão Preto Medical School (FMRP-USP), where Catto is a PhD candidate. His thesis advisor is Professor Rodrigo Calado, corresponding author of the article and a member of CTC.

The patient was identified when his two sons were undergoing medical treatment at the blood center of the hospital run by FMRP-USP. One of the siblings was diagnosed with moderate aplastic anemia (a bone marrow disorder in which the body stops producing enough new blood cells) and psoriatic arthritis. His low red blood cell count and immune cell deficiency worsened over the following five years and he died aged 27 from a lung infection. Post-mortem DNA sequencing confirmed his germline mutation and GATA2 deficiency diagnosis.

His brother began treatment at the hospital aged 25, with a history of recurrent lung infections, hypothyroidism, deep-vein thrombosis and deafness. Sequencing of his leukocytes and skin fibroblasts also confirmed an identical germline mutation.

To find out from which parent the brothers inherited the mutation, the researchers sequenced the mother’s and father’s DNA. The mother did not have the mutation. The 61-year-old father had exactly the same mutation as his sons in sperm and skin fibroblasts. He was asymptomatic, and his blood count and lymphocytes were within the normal range.

“This discovery raised the question whether the father transmitted the mutation or acquired it but didn’t pass it on to his sons,” Catto said.

In search of an answer, the researchers used next-generation sequencing to estimate the proportion of normal blood cells in the father’s bone marrow, preventing clinical manifestations of GATA2 deficiency, and of cells similar to his children’s.

The results showed that 93% of his leukocytes had the somatic mutation that confers protection from the clinical manifestations of GATA2 deficiency. The remaining 7% carried the mutation associated with the disorder. “This 7% were a remnant of the original clone,” Catto said.

Treatment prospect

The researchers also sequenced the father’s T-lymphocytes, which are long-lived, to find out whether his somatic mutation could induce normal cell production for a long time. The analysis showed that the somatic mutation occurred early in their lives and in the development of hematopoietic stem cells, which have the potential to form blood. “It’s very likely that the father had acquired the somatic mutation in his blood a long time ago,” Catto said.

To see if the father’s blood cells could maintain the activity for a long time, they measured the telomeres of his peripheral blood leukocytes. Telomeres are repetitive sequences of non-coding DNA at the tip of chromosomes that protect them from damage. Each time cells divide, their telomeres become shorter. They eventually become so short that division is no longer possible, and the cells die or become senescent.

The telomeres analyzed by the researchers were long. “This indicates that these blood cells can remain active for a long time,” Catto said.

A hypothesis formulated in the article is that the existence of the somatic mutation in the father’s blood cells, and its restoration of the blood cell renewal process, may have contributed to the non-manifestation of extra-hematological symptoms of GATA2 deficiency such as deafness, lymphedema, and thrombosis. Early hematopoietic recovery in patients with the disease, via a bone marrow transplant or in future via gene therapy, could be beneficial and avoid other clinical complications, the authors suggest in the article on the study.

“A sort of natural gene therapy occurred in this patient,” Calado said. “It’s as if he embodied an experiment and a medium-term prospect of analogous gene therapy treatment in patients with GATA2 deficiency.”

Besides contributing to an advance in treatment of the disease and genetic counseling, the study also provides new knowledge about the biology of hematopoietic stem cells. “The findings help us understand better how stem cells can recover by repairing an initial genetic defect,” Calado said.

DALLAS, Nov. 17, 2020 — A novel patient engagement tool led one in five patients with heart failure to a more effective treatment regimen of generic medications, according to late- breaking research presented today at the American Heart Association’s Scientific Sessions 2020. The meeting is virtual, Friday, November 13-Tuesday, November 17, 2020, and is a premier global exchange of the latest scientific advancements, research and evidence-based clinical practice updates in cardiovascular science for health care. The manuscript for this study is published simultaneously today in Circulation, the American Heart Association’s flagship journal.

In the study, “Electronically Delivered Patient-Activation Tool for Intensification of Medications for Chronic Heart Failure with Reduced Ejection Fraction: The EPIC-HF Trial,” patients were randomized into two groups – those who had a regularly scheduled cardiology clinic visit versus those who received an additional engagement and education tool before the visit. The patients assigned to the patient engagement tool, called EPIC-HF, received access to a three-minute video and a one-page checklist, delivered electronically by text or email, at one week, three days and 24 hours prior to a cardiology clinic visit .

Patients with heart failure with reduced ejection fraction (HFrEF) have a weak left ventricle, so the body is receiving less blood than needed. Multiple medications have been shown to improve heart function, and when used together at doses that can help them meet treatment goals, these medicines may help people with HFrEF feel better, live longer and improve their condition. Unfortunately, most people with HFrEF are not getting all of medications at the right doses. Often, the ones prescribed are dosed too low.

EPIC-HF’s goal was to help patients understand their medication options and encourage them to collaborate with their health care professionals to “make one positive change” in their HFrEF treatment.

Research analyzed the outcomes of 290 patients, of whom half received the patient EPIC-HF education tools. Average patient age was 65 years, and 29% were female. Average left ventricular ejection fraction was 32%. At the beginning of the study, none of the 290 patients were receiving optimal HFrEF treatment (current standard of care for HFrEF includes goal doses of a beta-blocker; sacubitril/valsartan; and spironolactone or eplerenone).

The study’s results show:

Nearly half (49%) of the EPIC-HF intervention group had a change in their medications for HFrEF to improve therapy compared to 29.7% in the control group.
Most changes were increases in the doses of generic HFrEF medications already prescribed, not new medications.
Increase in medication doses did not cause obvious problems in the 30 days after the clinical visit.

“We are pleasantly surprised that this fairly simple tool lead so many patients to better care. It’s promising that patients were able get better treatment,” said the lead study author Larry A. Allen, M.D., M.H.S., the associate division head for Clinical Affairs in Cardiology and co-director of the Colorado Program for Patient-Centered Decision at the University of Colorado School of Medicine in Aurora, Colorado. “This approach validates and promotes a culture of collaboration between patients and their doctors and leads to more productive clinic visits with optimized medication prescribing, which can ultimately improve patient outcomes.”

The researchers believe patient-centered tools that inform and encourage people to become active participants in their health will improve overall care and outcomes.