Researchers find delirium in hospitalized patients linked to mortality, disability

Researchers find delirium in hospitalized patients linked to mortality, disability

Delirium, a form of acute brain dysfunction, is widespread in critically ill patients in lower resourced hospitals, and the duration of delirium predicted both mortality and disability at six months after discharge, according to a study published in PLOS ONE.

Working with partners in Zambia, Vanderbilt University Medical Center researchers evaluated 711 hospitalized critically ill patients; delirium occurred in 48.5%. The findings shed light on the impact of delirium on a patient’s recovery—and even whether a patient is likely to live or die.

There have been limited data on the prevalence and outcomes of delirium in low- and middle-income countries, despite there being high numbers of critically ill patients. The mitigation of delirium and post-acute support of patients with delirium is a growing public health concern in the U.S. and Europe as the number of patients in intensive care units surged with the rise of COVID-19 cases.

“There is a driving unmet need to understand what happens with people’s brains in critical illness in low- and middle- income countries as well as with HIV in all settings. The necessity is now urgent because of the COVID-19 pandemic. Delirium has become the epidemic within the pandemic—and it’s the strongest predictor of long-term acquired cognitive impairment after critical illness. These are bread and butter issues people care about: will I live or die and if I live, what will I be like as a person,” said Wesley Ely, MD, MPH, co-director of the Critical Illness, Brain Dysfunction, and Survivorship Center at VUMC and senior author.

Patients with delirium had a higher six-month mortality, 44.6%, than patients without delirium who had a 20.0% six-month mortality. Compared to no delirium, presence of 1, 2 or 3 days of delirium predicted higher odds of six-month mortality of 1.43, 2.20, and 3.92, respectively. A similar relationship was found between duration of delirium and odds of worse six-month disability, assessed using the WHO Disability Assessment Schedule.

The study adjusted for age, sex, education, income, Universal Vital Assessment (UVA) severity of illness score, HIV status, and current antituberculosis treatment in adult patients who spoke English, Nyanja, or Bemba at the University Teaching Hospital, a 1,655-bed national referral hospital in Lusaka with about 17,500 acute admissions annually.

The prevalence of HIV in the study cohort was 45.4% while 27.2% of participants had a history of tuberculosis, suggesting delirium is an important clinical issue impacting the lives of hospitalized patients with HIV and tuberculosis in Sub-Saharan Africa. The high mortality and disability associated with delirium in this medically and socioeconomically vulnerable patient population spotlights an urgent global health issue.

“Acute brain dysfunction can have a variety of drivers, yet we know that delirium can itself lead to poor outcomes. In other parts of the world delirium is recognized as a major public health concern, while in lower resourced communities the magnitude of the problem has been obscured by acutely pressing issues such as HIV, malaria, and tuberculosis. Our research suggests it’s widespread and may present an opportunity to improve the lives of critically ill patients in low- and middle-income countries in the future as well as advocate for global critical care equity during the COVID-19 pandemic,” said Justin Banerdt, MD, MPH, internal medicine resident at Yale School of Medicine, and corresponding author who led the study on the ground in Zambia while a MD/MPH student at Vanderbilt University School of Medicine.

The next step is to see which interventions are effective in resource limited hospitals, said Douglas Heimburger, MD, MS, professor of Medicine and core faculty at the Vanderbilt Institute for Global Health. He leads projects with grant funding from the Fogarty International Center of the National Institutes of Health (NIH).

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Researchers discover energy drinks’ harmful effects on heart

energy drinks

A team of researchers, led by a Texas A&M University professor, has found that some energy drinks have adverse effects on the muscle cells of the heart.

The study, led by Dr. Ivan Rusyn, a professor in the Veterinary Integrative Biosciences (VIBS) Department at the Texas A&M College of Veterinary Medicine & Biomedical Sciences (CVMBS), was published in Food and Chemical Toxicology. In it, researchers observed cardiomyocytes—human heart cells grown in a laboratory—exposed to some energy drinks showed an increased beat rate and other factors affecting cardiac function.

When placed in the context of the human body, consumption of these beverages has been linked to improper beating of the heart, cardiomyopathy (disease of the heart muscle which makes it difficult for the heart to pump blood), increased blood pressure, and other heart conditions.

With the global sales of energy drinks estimated at $53 billion in 2018 and rapidly growing, it is important to understand the potential unintended health consequences associated with these beverages, according to Rusyn.

“Because the consumption of these beverages is not regulated and they are widely accessible over the counter to all age groups, the potential for adverse health effects of these products is a subject of concern and needed research,” Rusyn said. “Indeed, the consumption of energy drinks has been associated with a wide range of adverse health effects in humans, many of them are concerning the effects on the heart.”

Researchers evaluated 17 widely available over-the-counter brands. They then treated cardiomyocytes with each drink.

Researchers also studied the composition of the energy drinks using novel methods. By comparing the effects and differing ingredient concentrations in each drink, they were able to infer which ingredients may be contributing more to adverse effects on the treated cardiomyocytes. Using mathematical models, researchers determined that the possible presence of theophylline, adenine and azelate, substances which can have negative effects on the heart.

“Little is known about the ingredients that may contribute to the adverse effects of energy drinks on the heart,” Rusyn said. “Specifically, the evidence for cardiovascular effects from studies in humans remains inconclusive, as the controlled clinical trials were largely limited in the number of participants. They were tested only a limited number of energy drink types, and are difficult to compare directly, because they employed different methods to evaluate the function of the cardiovascular system.”

Further research is warranted on the ingredients identified in this study to ensure the safety of their consumption, especially by consumers with pre-existing health conditions.

“This study shows that some of the tested energy drinks may have effects on human cardiomyocytes, and these data corroborate other studies in humans,” Rusyn said. “Therefore, we hope that the consumers will carefully weigh the performance-enhancing benefits of these beverages versus the emerging data that suggests that they may have real adverse effects.

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Researchers launch Spermine Risk Score for prostate cancer diagnosis

HKBU and CUHK launch Spermine Risk Score for prostate cancer diagnosis

Researchers from Hong Kong Baptist University (HKBU) and the Faculty of Medicine at The Chinese University of Hong Kong (CU Medicine) have jointly developed the Spermine Risk Score which, coupled with the use of a urine test, provides a non-invasive and more reliable method for the diagnosis of prostate cancer. In a study conducted by the researchers, about 37% of the patients, who were ultimately found to have no prostate cancer, can avoid undergoing a prostate biopsy procedure. The findings have just been published in the scientific journal Prostate Cancer and Prostatic Diseases.

Demand for more reliable and non-invasive diagnosis

Prostate cancer is the third most common and the fourth most fatal cancer for the male population in Hong Kong. It results from the abnormal and uncontrolled growth of the prostate gland. Two medical procedures are commonly used for its diagnosis, namely the digital rectal examination (DRE) and the serum prostate-specific antigen (PSA) test.

DRE is performed by a doctor who uses a gloved finger to check the back portion of the prostate. Its accuracy highly depends on the skill and experience of the doctor. The PSA test, a kind of blood test, is a more popular alternative. For the Asian population, individuals with a PSA level higher than 4 ng/mL are normally interpreted as having a high risk of prostate cancer, and a prostate biopsy for further confirmation is usually recommended. According to the Centre for Health Protection of the Department of Health, about three out of four men in this group do not have prostate cancer. However, the patients have to bear the risk of complications due to the invasive nature of the prostate biopsy procedure.

Prostate cancer patients have lower spermine levels

In search of a more reliable and non-invasive method for prostate cancer diagnosis, Professor Gary Wong Ka-leung, Professor and Head of the Department of Chemistry at HKBU, and Professor Ng Chi-fai and Dr. Peter Chiu Ka-fung, Professor and Associate Professor respectively of the Division of Urology in the Department of Surgery at CU Medicine, have collaborated since 2014 to identify a new biomarker to supplement the PSA test. They found that prostate cancer patients in general have lower levels of spermine, a biogenic molecule in their urine, which offers a clue for the diagnosis of prostate cancer.

To investigate the diagnostic performance of spermine, the research team recruited 905 patients between 2015 and 2019 to participate in a study. All of them had elevated PSA levels and/or abnormal DRE, with a prostate biopsy scheduled.

Score to estimate prostate cancer risk

Among the 905 patients, 600 of them who had PSA levels ranging from 4 to 20 ng/mL were included in the analysis. Their urine samples were collected before they underwent a biopsy procedure. The biopsy results showed that out of the 600 patients, 185 (30.8%) were diagnosed with prostate cancer.

At the same time, the urine samples of these 600 patients were also analyzed. The results found that about 49% of the patients with spermine levels in the lowest quartile had prostate cancer, which was nearly triple the number of patients in the highest quartile (17%). The research team then used the urine spermine level figures and three other clinical parameters, namely DRE, PSA level and prostate volume, to develop the Spermine Risk Score, with the objective of offering a more accurate estimation of patients’ prostate cancer risk.

The higher the Spermine Risk Score, the greater the patient’s risk of developing prostate cancer. Only patients with Spermine Risk Scores higher than 6.2 will be advised to undergo the biopsy procedure. Based on Spermine Risk Scores calculated with data collected from the study, about 37% of the non-cancer patients could have avoided the biopsy procedure. Moreover, the negative predictive value of the Spermine Risk Score for significant prostate cancer is 95%, which means the chance of no significant cancer is 95% if the value of the Score is negative.

Promising approach for prostate cancer diagnosis

Dr. Chiu concluded the findings by highlighting that, “This study confirms that urine spermine and the Spermine Risk Score are effective at identifying men at higher risk of prostate cancer and the test could help reduce the number of unnecessary biopsies.”

“It is the first prospective study to investigate the efficacy of urine spermine in prostate cancer detection. It successfully demonstrated that the Spermine Risk Score, developed based on patients’ urine spermine levels and other clinical parameters, can serve as a novel and promising approach to address the limitations of the diagnostic methods currently in use,” said Professor Wong.

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Researchers map heart recovery after heart attack with great detail

Researchers map heart recovery after heart attack with great detail

Researchers from the Hubrecht Institute have mapped the recovery of the heart after a heart attack with great detail. They found that heart muscle cells called cardiomyocytes play an important role in intracellular communication after a heart attack. The researchers documented their findings in a database that is accessible for scientists around the world. This brings the research field a step closer to the development of therapies for improved recovery after heart injury. The results were published in Communications Biology on the 29th of January.

In the Netherlands, an average of 95 people end up in the hospital each day because of a heart attack. During a heart attack, the blood supply to a part of the heart is blocked, for example, due to a blood clot in a coronary artery. Attempts to restore the blood supply known as reperfusion, are made as soon as possible. However, a part of the heart has already been without oxygen for some time. Depending on the size and duration of the infarction, this causes cardiomyocytes to die. This can result in the formation of scar tissue, which is stiffer than normal heart tissue and therefore makes it more difficult for the heart to properly contract. This can cause the pumping function of the heart to deteriorate, which can eventually lead to heart failure.

In other words, insight into the recovery of the heart after a heart attack and how this leads to the formation of scar tissue is extremely important. However, much is still unknown. Researchers from the lab of Eva van Rooij have therefore examined this further. They studied how the hearts of mice recover at three different time points following a heart attack. To this end, they used single-cell sequencing, a technique that enables the examination of the RNA of individual cells. The researchers generated an enormous dataset with information about the role of different types of cells during the recovery process after a heart attack.

Communication network

Consequently, they used the data to map a communication network. Louk Timmer, researcher on the project, says, “Cells communicate with each other by secreting molecules. These molecules then trigger the recipient cell to take a specific action, which may be important for the recovery process. We have now mapped with great detail how different cells communicate with each other at different time points after a heart attack. That had never been done so thoroughly before.” This communication network is now documented in a database and accessible to scientists around the world.

Formation of scar tissue

The role of cardiomyocytes in the recovery following a heart attack has been largely unknown, partly because of technical difficulties. However, another recent paper from Van Rooij’s lab overcame these obstacles, allowing the researchers to specifically study the function of cardiomyocytes in the recovery process. “We noticed that at the earliest time point measured after the heart attack, cardiomyocytes were secreting increased amounts of a molecule called B2M. Subsequent experiments showed that the secretion of B2M can result in the activation of so-called fibroblasts—cells responsible for the formation of scar tissue,” says Timmer. Cardiomyocytes thus seem to indirectly stimulate the production of scar tissue early in the recovery process. “Intuitively, we already thought that cardiomyocytes play an important role in intracellular communication during heart recovery, and it is great that we have now been able to confirm that.”

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Researchers develop a model that predicts whether COVID-19 restrictions have any effect

Researchers develop a model that predicts whether COVID-19 restrictions have any effect

What happens when municipalities in the Copenhagen area experience a COVID-19 flare-up? Would closing the schools have any effect, or would a better choice be directing the parents to work from home? Due to the COVID-19 pandemic, authorities worldwide have several times implemented steps to keep the pandemic in check.

Now, researchers from the Department of Computer Science at Aalborg University have come forward with a new agent-based model that can be used as a tool for making even better, informed choices regarding which restrictions to implement.

The background of using agent-based modeling to analyze, predict and control the rapid spreading of COVID-19 is described in the paper Fluid Model-Checking in UPPAAL for COVID-19 published in the distinguished conference proceedings series Lecture Notes in Computer Science.

167 fewer new cases a day

In the new model, the researchers simulate interactions between specific agents or in other words, individuals. Based on data from Statistics Denmark, the Danish Building and Housing Register (BBR), the Central Business Register and the State Serum Institute of Denmark, the researchers have used the agent-based technic to construct a model of Northern Jutland, with more than 500,000 individuals.

The region was placed under lockdown in November due to the fear of spreading the cluster-5 variant of the coronavirus, circulating primarily in farmed minks.

In the model, each individual is assigned a state of health, which is combined with general data on addresses, places of employment, family sizes and commuting patterns to calculate realistic simulations of the mobility patterns of all Northern Jutland inhabitants.

Project head, Professor Kim Guldstrand Larsen, explains that the researchers have simulated the case numbers in the region over the course of 100 days based on two different scenarios: One scenario in which no lockdown was implemented, and the actual scenario where schools and municipal boundaries, etc. were closed:

“The model enables us to simulate real chains of infection. In our assessment, over a period of two months the lockdown resulted in around 10,000 fewer cases in Northern Jutland,” says Kim Guldstrand Larsen.

In the context of the model predicting that the region would have experienced around 70,000 cases in that period if no lockdown had been implemented, this equals a percentual reduction of 14 percent in the total number of cases over the period of two months. This equals 167 fewer new cases a day.

“We can draw up accurate scenarios for how the disease will spread under different conditions. If we turn back time a few months, we would also have been able to predict the probability of the cluster-5 variant spreading across the regional boundary,” says Kim Guldstrand Larsen.

Weather forecast for COVID-19 spread

The model of Northern Jutland is based on open data—in other words, the researchers have no access to sensitive personal data. If they had precise data on, for instance, where people live and where they work, they would be able to predict very accurately whether each person would be infected in the near future.

“The authorities have access to the actual numbers and will be able to use the model for making very accurate simulations of the real-world situation. With the current data, the model should be seen as a tool for a more nuanced predictive contagion tracing—a kind of weather forecast for the spread of COVID-19. We have used Northern Jutland as our point of departure, but the model can be used anywhere with a certain amount of data,” says Kim Guldstrand Larsen.

Computing power required

To develop the model, the researchers have used the software tool UPPAAL, which they themselves have developed over the last 20 years. The tool has been used to analyze several real-world complex systems, including heating and traffic control systems, where the behavior of the overall system is given by the complex interaction of its components. In the new setting, the components of the model are people interacting through contagion.

“Prior to this, we have worked with systems of 2,000 components, so of course, it was quite a leap to the 500,000 components we are working with now. This requires a whole lot of computing power, and as far as I know, we are part of a limited group of researchers currently capable of making this kind of simulation,” says Kim Guldstrand Larsen, pointing to the work of American colleagues who have recently published an equivalent study in Nature.

The Danish authorities have shown great interest in the Danish researchers’ work, and Kim Guldstrand Larsen has high expectations of the model being used by the State Serum Institute of Denmark.

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This is your brain on code: Researchers decipher neural mechanics of computer programming

By mapping the brain activity of expert computer programmers while they puzzled over code, Johns Hopkins University scientists have found the neural mechanics behind this increasingly vital skill.

Though researchers have long suspected the brain mechanism for computer programming would be similar to that for math or even language, this study revealed that when seasoned coders work, most brain activity happens in the network responsible for logical reasoning, though in the left brain region, which is favored by language.

“Because there are so many ways people learn programming, everything from do-it-yourself tutorials to formal courses, it’s surprising that we find such a consistent brain activation pattern across people who code,” said lead author Yun-Fei Liu, a Ph.D. student in the university’s Neuroplasticity and Development Lab. “It’s especially surprising because we know there seems to be a crucial period that usually terminates in early adolescence for language acquisition, but many people learn to code as adults.”

The findings are published today in the journal eLife.

Researchers have long known what happens in the brain when someone reads, plays music or does math. But despite our increasing reliance on technology, almost nothing is known about the neural mechanisms of computer programming.

“People want to know what makes someone a good programmer,” Liu said. “If we know what kind of neuro mechanisms are activated when someone is programming, we might be able to find a better training program for programmers.”

Many people assume techies have math-centric minds, and think the brain region for programing would be the same as the one used when solving math problems, Liu said. Others believe that programming languages are called languages for a reason and the neural mechanism underlying programming would be shared with language processing. Or it could be parts of the brain used for logical reasoning or the type of problem-solving known as ‘executive control.’

To get to the bottom of it, Liu had 15 experienced programmers, each highly proficient in the programming language Python, lie in an fMRI scanner so he could measure their brain activity while they worked on coding questions.

In each case, the same part of the brain lit up: the area responsible for logical reasoning. And though the act of logical reasoning has no brain hemisphere preference, coding strongly favored the left hemisphere, the area that correlates with language.

Next, the lab hopes to determine if learning to code, like learning a language, is easier for the young.

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Researchers find face masks don’t hinder breathing during exercise

A new University of Saskatchewan (USask) study has found that exercise performance and blood and muscle oxygen levels are not affected for healthy individuals wearing a face mask during strenuous workouts.

Questions have been raised as to whether mask wearing during vigorous exercise might compromise oxygen uptake or increase the rebreathing of carbon dioxide, leading to a condition (hypercapnic hypoxia) whereby increased carbon dioxide displaces oxygen in the blood.

But the study, published Nov. 3 in the research journal International Journal of Environmental Research and Public Health, did not find evidence to support these concerns.

“Our findings are of importance because they indicate that people can wear face masks during intense exercise with no detrimental effects on performance and minimal impact on blood and muscle oxygenation,” the researchers state.

“This is important when fitness centers open up during COVID-19 since respiratory droplets may be propelled further with heavy breathing during vigorous exercise and because of reports of COVID-19 clusters in crowded enclosed exercise facilities.”

The study evaluated use of a three-layer cloth face mask—the type recommended recently by Dr. Theresa Tam, Canada’s Chief Public Health Officer. “Results using a single-layer cloth mask may differ,” the researchers note.

The study, involving 14 physically active and healthy men and women, controlled for the effects of diet, previous physical activity, and sleep during the 24 hours prior to the test.

“If people wear face masks during indoor exercise, it might make the sessions safer and allow gyms to stay open during COVID,” said Phil Chilibeck, a professor in the USask College of Kinesiology, who was a co-author of the study. “It might also allow sports to continue, including hockey, where transmission of COVID-19 appears to be high.”

Participants were required to do a brief warm-up on a stationary bike. The exercise test involved a progressive increase in the intensity on the bike while they maintained a required pedal rate. Once they could not sustain the pedal rate the test was over.

“Usually a participant reaches exhaustion on this test in six to 12 minutes depending on their fitness level,” said Chilibeck.

The team assessed the participants, who did the test three times each, once wearing a surgical face mask, once wearing a cloth face mask and once with no face mask. The team recorded the participants’ blood oxygen levels and muscle oxygen levels throughout the test using non-invasive measurement tools.

Chilibeck notes the study is timely, as Saskatchewan has recently issued new public health orders that go into effect this week making masks mandatory in indoor public spaces in Regina, Saskatoon and Prince Albert to help curb the spread of COVID-19.

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Researchers advance drug delivery systems to treat connective tissue disorders

University of Delaware Professor Kristi Kiick is leading collaborative research to create new drug delivery systems with the potential to improve treatment for diseases that affect connective tissues, such as osteoarthritis or rheumatoid arthritis, which is an autoimmune disease.

The UD researchers have devised tiny cargo-carrying systems many times smaller than a human hair. These systems, or carriers, are made from molecules called peptides that help provide structure for cells and tissues.

The research team is working to program these nanoparticle carriers to selectively bind to degrading collagen in the body. Collagen is a protein that helps plump up or provide structure to connective tissue—everything from our skin to our bones, tendons and ligaments.

When collagen degrades, as a result of disease or injury, the nanoparticles designed by the Kiick lab can attach and remain at the injury site longer than many current treatment options. This allows for the possibility of delivering site-specific medicines over longer periods of time—from days to weeks.

In one collaborative project that involves this work, Kiick is trying to develop drug carriers that could be useful in treating osteoarthritis. Osteoarthritis is a degenerative joint disorder characterized by inflammation, pain and stiffness. According to the Centers for Disease Control and Prevention, it affects 32.5 million Americans.

Early studies with Christopher Price, an associate professor in biomedical engineering, suggests that these nanoparticles can be retained in tissue and knee joints. In other related studies, Kiick and her students have shown that drugs can be encapsulated and retained in the nanoparticles, until released by changes in temperature.

“We are interested in learning how to release drugs that can help not just with pain management, but also with slowing down disease progression,” said Kiick, Blue and Gold Distinguished Professor of Materials Science and Engineering. “It has been key that we have been able to collaborate with the Price laboratory in this type of work.”

For a long time, small molecule corticosteroids have been a standard of care for managing pain in osteoarthritic joints. Because the joint is full of thick, sticky fluid and is under constant mechanical stress and motion, these small-molecule drugs get expelled from the fluid around the knee pretty quickly, in minutes.

“We are hopeful that by controlling the nanoparticle composition and structure,” said Kiick, “we will be able to finely control, or tune, the drug delivery behavior to provide longer-lasting relief for people with inflammatory conditions, such as osteoarthritis.”

Kiick and colleagues reported advances on the nanoparticle design on Wednesday, Oct. 7, in a paper published in Science Advances, a peer-reviewed journal of the American Association for the Advancement of Science. Co-authors on the work include Jingya Qia, a graduate student in the Kiick lab, and Jennifer Sloppy, a senior microscopy specialist in UD’s Harker Interdisciplinary Science and Engineering Laboratory.

The paper’s key findings demonstrate the research team’s ability to control the shape of the nanoparticles, which will impact how well they can bind to tissue in the body and stay in a particular location. The research team also can precisely control the size of the nanoparticles, which has implications for how they might be retained at the injection site and also how they may be used by particular cells before being removed from the body. Finally, the paper describes some of the very fine details of how the specific building blocks inside these peptide molecules can affect the temperature at which those different shaped and sized nanoparticles can be disassembled to release a medicine.

The research builds on Kiick’s previous patented and patent-pending work in this area, but she said it is collaboration with others that is driving forward promising results. While the Kiick lab brings expertise in creating novel materials that can be used as delivery systems; Arthi Jayaraman, Centennial Term Professor for Excellence in Research and Education in the Department of Chemical and Biomolecular Engineering, is helping the team understand factors related to temperature sensitivity of the delivery vehicles and to develop computational tools that can help the research team characterize the vehicle’s shape.

Meanwhile, Price’s expertise in understanding post-traumatic osteoarthritis has been key to developing methods to use these nanoparticles to potentially treat disease. Price is exploring how particular drugs and cells interact, which may inform what specific classes of medicines are useful in treating osteoarthritis that develops following traumatic injury. The collaboration will help the Kiick lab tailor what types of nanoparticle devices can be used to deliver these different classes of medicines.

According to Kiick, thinking big, the team could imagine loading a custom cocktail of medicines into the drug-delivering nanoparticles capable of delivering relief over varying timescales and temperatures. The researchers already have the right material nanostructure that can allow this to happen; now they are exploring how to trigger the nanoparticles to release specific medications under particular conditions.

“You could imagine injecting these encapsulated medications at the knee,” she explained. “Then, when you want one medication to be released, the patient could ice their knee. If another drug is needed to provide relief over a longer time-period, heat could be applied.”

It could be a really simple way to help people manage chronic conditions that cause a lot of pain and reduce mobility. And because the treatment is local, it could reduce side effects that can occur when drugs have to be taken at high doses or over prolonged periods of time.

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Researchers warn of COVID-19 and flu ‘twindemic’

Even as the first wave of the pandemic still roils, fears are rising of a second crush of COVID-19 infections. But because the novel coronavirus is, well, novel, no one can yet say if that will happen. One thing is certain, though, another viral wave is coming: flu season.

Influenza season occurs during the cold half of the year in each hemisphere. In the United States, that’s generally October to May, with peak activity December through February. After early hopes that the novel coronavirus might burn itself out in the summer heat, SARS-CoV-2 now appears more likely to be a year-round phenomenon.

“Many factors influence the prevalence of viruses,” said Pascal Gagneux, professor of pathology and evolutionary biologist at University of California San Diego School of Medicine. “These range from the behaviors of their human hosts and the vectors that transmit them to environmental conditions and their own adaptations.

“Coronaviruses have a genome almost three times as big as influenza A viruses so that gives them a larger and more complex bag of tricks to manipulate their hosts and evade their protective immune response. My guess at the moment is that SARS-CoV-2 will continue to remain a significant public health threat until there is an effective vaccine and some degree of herd immunity.”

If humans face the prospect of living with the dual threats of COVID-19 and influenza for at least part of every year, there are things to know and things to do to reduce risk of infection or, possibly, co-infection (a simultaneous infection of COVID-19 and the flu). Most immediately, that means getting this year’s flu vaccination.

“There isn’t a vaccine for COVID-19,” said Dr. Davey Smith, a translational research virologist and head of the Division of Infectious Diseases and Global Public Health at University of California San Diego School of Medicine. “A lot of people, including myself and colleagues at UC San Diego, are working very hard to develop one or more vaccines proven safe and effective. But that goal is months away. Right now, though, there is a readily available flu vaccine.”

First, some things to know and remember

Both influenza and COVID-19 can result in severe illness and death, though the latter has proven more deadly. The 2019-2020 flu season resulted in 39 to 56 million cases and an estimated 24,000 to 62,000 deaths. The U.S. Centers for Disease Control and Prevention (CDC) originally projected that the 2019-2020 flu season would be among the worst in recent history, but a late, sharp drop in cases ended the season six weeks earlier than normal.

The COVID-19 pandemic emerged as flu season closed. It continues, with at last count 6.3 million cases and 189,000 deaths in the United States; 27.4 million cases and 898,000 deaths worldwide since January.

Older adults, persons with certain underlying medical conditions, such as diabetes, heart problems, cancer, obesity and chronic kidney disease, are at highest risk for developing severe COVID-19 complications. Other suspected factors may be asthma, hypertension, HIV, liver disease, smoking and pregnancy. Young children appear to be at least risk for severe COVID-19 complications, with the exception of multisystem inflammatory syndrome in children, a rare but dangerous respiratory condition.

For the flu, unvaccinated young children are at higher risk of severe illness, as are adults age 65 and older, pregnant women and persons with underlying medical conditions, such as chronic heart disease, disorders of the kidneys, liver or blood, obesity or a weakened immune system.

Most people who contract COVID-19 or the flu recover fully in a few weeks. However, there are accounts of some seriously ill COVID-19 patients surviving, but then struggling with residual symptoms and effects lasting weeks or months.

“A small percentage of patients with severe COVID-19 pneumonia and ARDS (acute respiratory distress syndrome) may develop scarring in the lungs that creates long-term lung problems,” said Dr. Jess Mandel, chief of the Division of Pulmonary, Critical Care and Sleep Medicine at UC San Diego Health. “The vast majority do not have long-term lung problems. People may take several months to recover fully, but that is usually a consequence of being in an intensive care unit (ICU) for weeks, with loss of muscle mass and other issues. Most people with COVID-19 infections have some fatigue for a few weeks and then are back to normal.”

COVID-19 appears to attack other organs beyond the lungs, including kidneys and the heart. Dr. Eric Adler, cardiologist and director of Cardiac Transplant and Mechanical Circulatory Support at UC San Diego Health, said it’s an evolving issue. A significant number of COVID-19 patients show signs of heart damage, he said, but it is not yet clear how often the damage is severe or long lasting. The risk of COVID-19-related heart damage appears greatest in older persons or those with pre-existing cardiovascular disease.

How do I know if I have the flu or COVID-19?

Dr. M. Monjur Alam, is a primary care physician at UC San Diego Health. He has seen and treated hundreds of patients with viral infections, of known and unknown origin.

For a patient with symptoms that might be flu or COVID-19, Alam said the first step is to inquire of any known exposures to the latter within the past 14 days and any travel history to or from an area where confirmed COVID-19 cases are high. He would ask too whether the patient has been vaccinated in the past for influenza or pneumonia.

COVID-19 and influenza have different incubation periods—the time between first exposure and onset of symptoms, if symptoms actually appear. (Up to 40% of infected persons carrying the coronavirus—and thus potentially spreading it—are asymptomatic.) The incubation period for COVID-19 is two to 14 days; for the flu, one to four days. (The common cold, which can be caused by other types of coronavirus, incubates one to three days, on average.)

“Both flu and COVID-19 cases can present with fever, shortness of breath, body ache, diarrhea, fatigue and other symptoms,” said Alam. “With the flu, patients can experience a rapidly rising, high-grade fever with shaking chills within the first couple of days. From a clinical standpoint, new-onset loss of smell or loss of taste, with or without other viral symptoms, would put COVID-19 on the top of my list of probable causes.”

At this point, experts say contracting the flu seems more likely than getting COVID-19. The CDC estimates that, on average, 8% of the U.S. population gets sick from the flu each season, with a historical range of 3 to 11%, depending on the season and the virulence of prevailing flu strains.

It is more difficult to measure the incidence of COVID-19, partly because it is a brand-new pathogen and partly because so many infected persons never display symptoms. Current estimates of cases and deaths are almost definitely undercounts. They do not include probable cases or cases not reported or diagnosed. CDC director Robert Redfield has estimated 10 additional infections for every reported COVID-19 case, which extrapolates to approximately 30 million cases or 10% of the U.S. population.

Incidence is uneven, however, with some regions of the country harder hit. The U.S. has reported roughly one-quarter of all COVID-19 cases worldwide, though it accounts for just 4% of global population.

Dr. David Pride, an infectious disease specialist and director of the molecular microbiology laboratory at UC San Diego Health, said test manufacturers are developing assays to detect and differentiate between flu and novel coronaviruses, though he said it’s unlikely they will be widely available this season or “game-changers.”

At UC San Diego Health, Pride said patients presenting symptoms that might be flu or COVID-19 may be tested for both illnesses, with results back within 24 hours. “We expect demand for flu and COVID-19 testing to be high this flu season,” he said. “The one thing that can reduce the demand is continuing the current masking and social distancing practices. If people follow these practices, this could be one of the lightest flu seasons in a long time.”

What is standard of care for the flu and COVID-19?

For the flu, usual treatment is bed rest, plenty of fluids, perhaps over-the-counter medications for fever and body aches. Doctors may prescribe antiviral medications, such as Tamiflu, Relenza, Rapivab or Xofluza, for persons at heightened risk. These drugs shorten the duration of illness and help prevent complications.

“I highly encourage people to consult with their primary care physician so that they can receive timely medical advice, especially if symptoms are worsening after five to seven days,” said Alam. “I also advise patients to complete their annual influenza immunization and pneumonia vaccination if they are of certain age groups (65 and older) and if they have chronic diseases like diabetes, heart disease, kidney diseases, lung disease or an immunocompromised state.”

COVID-19 can look a lot like the flu—at least in the beginning. If symptoms are not serious, diagnosed patients are advised to quarantine at home, with treatment similar to flu infections. There are currently no proven COVID-19-specific home treatments, and no standard outpatient treatment. The CDC recommends patients self-isolate at least 10 days after symptoms appear.

“I would say the main difference between the flu and COVID-19 treatments is that we do routinely use antiviral medication for the flu, such as Tamiflu, but there is no standard treatment for COVID-19 at this time other than supportive care,” said Dr. Michele Ritter, an infectious disease specialist at UC San Diego Health and director of its COVID-19 outpatient clinic. “So the main issue is that it’s important to know if someone has flu because it means they may get an actual antiviral treatment.”

For UC San Diego Health patients diagnosed with COVID-19 and recuperating at home, Ritter’s team monitors them closely, with daily calls to assess progress and determine if worsening symptoms might require hospitalization.

Roughly 20% of persons with COVID-19 require hospitalization, with 5% of these patients in ICUs, perhaps requiring a mechanical ventilator to breathe.

There are few approved treatments specifically for COVID-19. Remdesivir, an investigational antiviral, has been shown to modestly reduce symptoms and shorten the duration of COVID-19 in some patients, and may be prescribed under an FDA emergency use authorization (EUA). Numerous clinical trials are on-going to assess its efficacy.

Dr. Amy Bellinghausen, a pulmonologist at UC San Diego Health, said dexamethasone, a corticosteroid commonly used to treat inflammatory conditions like arthritis, has shown promise in treating the sickest COVID-19 patients.

The FDA has also issued an EUA for convalescent plasma (CP) therapy, which involves infusing patients with antibodies extracted from the blood of donors who have successfully recovered from COVID-19, with the hope that the resulting boost to their immune systems will shorten the length and reduce the severity of the disease.

Evidence that CP therapy works is mixed, and a National Institutes of Health panel recently advised doctors to not treat CP as a standard of care until more research is done. Like remdesivir, clinical trials to test CP’s safety and efficacy continue, including at UC San Diego Health.

Most COVID-19 treatment in hospitals, said Bellinghausen, is supportive, including supplemental oxygen and extracorporeal membrane oxygenation. “These interventions and others help keep the patient alive while the medication has time to work,” Bellinghausen said.

Is it possible to get the flu and COVID-19 at the same time?

The answer is yes, maybe, probably not. SARS-CoV-2 and the flu are different viruses. They infect host cells using different methods; they behave differently within cells and inside the human body.

There have been documented cases of patients testing positive for both COVID-19 and seasonal influenza. Some early studies suggested co-infection was rare; later studies indicate it might be more common than previously thought.

“We simply don’t know because COVID hit at the end of the flu season and then with all of the public health measures, transmission of all respiratory viruses went down,” said Dr. Francesca Torriani, program director of Infection Prevention and Clinical Epidemiology and an infectious disease specialist at UC San Diego Health. “What we can say is that the populations at risk for severe disease and death are the same, so you want to avoid an additional infection that can be mitigated by vaccination.”

Last, some things to know and do (they should sound familiar)

  1. Wear a mask and save a life
  2. Socially distance
  3. Wash your hands frequently

These three basic acts of social responsibility and compassion fundamentally slow and reduce the spread and incidence of COVID-19. They work equally well against the flu and, in fact, are credited with shortening the 2019-2020 flu season earlier this year.

While the world waits for a scientifically validated vaccine for COVID-19, the flu vaccine for this season is already widely available. In most cases, the cost is covered by health insurance, nominal or free.

The CDC recommends everyone over the age of six months be vaccinated. Exceptions are children under the age of six months and persons with severe, life-threatening allergies to the flu vaccine or any of its ingredients, which might include gelatin or antibiotics. Such persons should consult a physician.

“We live in uncertain times,” said Torriani. “We don’t know when a COVID-19 vaccine will become available or how much and how quickly it will help end this pandemic. But we do know a lot about flu vaccines, which have been around for almost a century.

“Every year’s flu vaccine is different, formulated to anticipate the season’s most likely strains of the virus. Their effectiveness can vary from year to year—influenza viruses are moving targets, always changing due to a genetic phenomenon called antigenic shift—but in most years they prove a good match against circulating strains. And even in mismatched years, they provide some protection.”

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Researchers succeed with a more inclusive approach to heart transplants

Doctors at Yale New Haven Hospital used a more aggressive selection process to more than quadruple the number of heart transplants performed there while maintaining positive patient outcomes, according to a new study.

The findings suggest that a more inclusive approach to selecting donor hearts and transplant recipients can enable hospitals to successfully treat more patients in need of transplants. The study appears online Sept. 18 in the journal JAMA Network Open.

The study looked at short-term patient outcomes for two groups: 49 patients who received heart transplants from 2014 to 2018, and 58 patients who had their heart transplants in the year after the hospital adopted a more aggressive selection process for donor recipients (2018-2019).

The more aggressive selection process significantly shortened the waiting period for heart patients, from 242 days to 41 days, the researchers said. Importantly, patients’ survival rate at 180 days after the transplant remained nearly unchanged.

The expansion of heart transplant procedures at the hospital, in September 2018, coincided with the implementation of the new United Network for Organ Sharing (UNOS) donor heart allocation system in the United States.

“I think this is the takeaway for other centers—that such a change in the approach could create opportunities for patients in need while maintaining outcomes in the short term,” said Makoto Mori, M.D., a surgical resident at Yale and first author of the study.

The senior author of the study was Harlan Krumholz, M.D., the Harold H. Hines Jr. Professor of Medicine (cardiology) and director of Yale’s Center for Outcomes Research and Evaluation.

In practical terms, the expansion of heart transplant procedures at Yale New Haven Hospital meant accepting hearts from older donors with additional medical conditions, as well as accepting transplant recipients with more severe illnesses.

Yale New Haven Hospital also changed the surgical leadership of its advanced heart failure program, hired a dedicated procurement surgeon and an additional transplant coordinator, and increased the involvement of surgical attending physicians.

The researchers noted that Yale’s increase in heart transplant cases was significantly larger than the volume change seen at other heart transplant centers in the same region during the same period, including Hartford Hospital, Tufts Medical Center, Brigham and Women’s Hospital, and Massachusetts General Hospital.

“We used a multidisciplinary approach and made strategic changes in donor and recipient selection, which allowed us to increase the number of heart transplants performed and therefore help more patients with advanced heart failure in a safe and an effective manner,” said co-author Arnar Geirsson, M.D., chief of cardiac surgery at Yale New Haven Hospital.

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