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Newswise — COLUMBUS, Ohio – A new study by researchers at The Ohio State University Wexner Medical Center  and The Ohio State University College of Medicine documents a clear link between the stress hormone cortisol and higher blood sugar levels in people with type 2 diabetes. The study published online in the journal Psychoneuroendocrinology. “In healthy people, cortisol fluctuates naturally throughout the day, spiking in the morning and falling at night,” said Dr. Joshua J. Joseph, an endocrinologist and researcher at The Ohio State Wexner Medical Center’s Diabetes and Metabolism Research Center who led the study.  “But in participants with type 2 diabetes, cortisol profiles that were flatter throughout the day, had higher glucose levels.” Previous research has shown that stress and depression are two of the major causes of a flatter cortisol profile. These sustained levels of cortisol make it much more difficult to control blood sugar and manage the disease, which is why it is so important for those with type 2 diabetes to find ways to reduce stress. “We have begun a new trial to examine if mindfulness practices can lower blood sugar in those with type 2 diabetes,” said Joseph, an assistant professor in the College of Medicine.  “But this isn’t the only effective form of stress relief. It’s important to find something you enjoy and make it a part of your everyday routine.” The relationship of cortisol with glucose levels was only observed in those with diabetes. However, Dr. Joseph and his team believe the stress hormone likely plays an important role in diabetes prevention and they continue to research the connection between cortisol and the development of diabetes and cardiovascular disease. More than 30 million Americans have Type 2 diabetes, according to the Centers for Disease Control and Prevention. With Type 2 diabetes, your body doesn’t use insulin properly. Some people can manage their blood sugar levels with healthy eating and exercise, while others may need medication or insulin to help manage it. “Most people with Type 2 diabetes know the importance of exercising regularly, eating a healthy diet, and getting plenty of rest. But stress relief is a crucial and often forgotten component of diabetes management,” Joseph said. “Whether it’s a yoga class, taking a walk or reading a book, finding ways to lower your stress levels is important to everyone’s overall health, especially for those with type 2 diabetes.” Joseph collaborated with researchers at Johns Hopkins University; University of Maryland School of Medicine; University of California, Los Angeles; University of Michigan; Boston University and the National Institute on Aging, National Institutes of Health.   Photo credit: The Ohio State University Wexner Medical Center

A persistent cough and fever have been confirmed as the most prevalent symptoms associated with COVID-19 according to the new international research Data analysed from over 24,000 patients from nine countries including the UK, China and the US University of Sheffield medical student helped conduct the study, which is one of the biggest reviews (or meta data analysis) into COVID-19 symptoms  Newswise — A persistent cough and fever have been confirmed as the most prevalent symptoms associated with COVID-19, according to a major international review of patient data. Other major symptoms include fatigue, losing the ability to smell and difficulty in breathing.   The study ratifies the list of symptoms compiled by the World Health Organisation at the start of the pandemic. A team of researchers including a final year medical student from the University of Sheffield combined data from 148 separate studies, to identify the common symptoms experienced by more than 24,000 patients from nine countries including the UK, China and the US.  The study - published in the online journal PLoS One - is one of the biggest reviews, or meta analysis, ever conducted into COVID-19 symptoms.  Of the 24,410 cases, the study found: *78 per cent had a fever. Although this tended to vary across countries, with 72 per cent of fever reported by patients in Singapore and 32 per cent in Korea. *57 per cent reported a cough. Again, this varied across countries, with 76 per cent of patients reporting a cough in the Netherlands compared to 18 per cent in Korea.  *31 per cent said they had suffered fatigue.  *25 per cent lost the ability to smell.  *23 per cent reported difficulty breathing.  The researchers believe the variation in the prevalence of symptoms between countries is due, in part, to the way data was collected.  Of those patients who needed hospital treatment, 17 per cent needed non-invasive ventilation; 19 per cent had to be looked after in an intensive care unit, nine per cent required invasive ventilation and two per cent needed extracorporeal membrane oxygenation (an artificial lung).  Michael Grant, a final year medical student from the University of Sheffield, said: “The impact of COVID-19 on daily activities has been immense.  “An accurate estimation of symptom prevalence, as provided by this study, is essential to combat COVID-19” “As a medical student, it has been a tremendous opportunity and a great privilege to contribute to research that will be used to inform public health opinion.” Mr Ryckie Wade, a surgeon and Clinical Research Fellow at the Leeds Institute of Medical Research, who supervised the research, said: "This analysis confirms that a cough and fever were the most common symptoms in people who tested positive with COVID-19. "This is important because it ensures that people who are symptomatic can be quarantined.  "The study gives confidence to the fact that we have been right in identifying the main symptoms and it can help determine who should get tested."  The study involved academics from the University of Leeds with colleagues from the University of Sheffield, University of Bristol, Imperial College, London, and the Belgium Cancer Centre. The research was funded by the UK's National Institute for Health Research and VALCOR, in Belgium. The researchers acknowledge there are people who had the virus but did not display any symptoms. Additional information  The University of Sheffield’s Medical School trains world class clinical and researchers who prolong and improve lives everyday. The vision of the Medical School is to achieve research excellence and impact by translating scientific discoveries into meaningful advances that can benefit patients and the general population. This vision is supported by competitive funding from major national and international research bodies including Government, Research Councils, industry and charities.  For more information please visit: https://www.sheffield.ac.uk/medicine The University of Sheffield With almost 29,000 of the brightest students from over 140 countries, learning alongside over 1,200 of the best academics from across the globe, the University of Sheffield is one of the world’s leading universities. A member of the UK’s prestigious Russell Group of leading research-led institutions, Sheffield offers world-class teaching and research excellence across a wide range of disciplines. Unified by the power of discovery and understanding, staff and students at the university are committed to finding new ways to transform the world we live in. Sheffield is the only university to feature in The Sunday Times 100 Best Not-For-Profit Organisations to Work For 2018 and for the last eight years has been ranked in the top five UK universities for Student Satisfaction by Times Higher Education. Sheffield has six Nobel Prize winners among former staff and students and its alumni go on to hold positions of great responsibility and influence all over the world, making significant contributions in their chosen fields. Global research partners and clients include Boeing, Rolls-Royce, Unilever, AstraZeneca, Glaxo SmithKline, Siemens and Airbus, as well as many UK and overseas government agencies and charitable foundations.

A new study reveals that the common asthma drug salbutamol may offer potential as a treatment for Alzheimer's disease Newswise — A new study reveals that the common asthma drug salbutamol may offer potential as a treatment for Alzheimer's disease. Alzheimer's disease is the most common form of dementia, affecting 47 million people worldwide and its prevalence is expected to triple to more than 130 million cases by 2050. No effective treatments that cure the disease or slow down its progression have been discovered. However, this new early-stage study has revealed that repurposing an existing drug, salbutamol, offers significant potential as a low cost and rapid response option. Extensive analytical in-vitro experiments conducted by the research team show that salbutamol is effective at reducing the accumulation of insoluble fibres of the tau protein - which is found in the brains of people with Alzheimer's disease. These microscopic fibres accumulate into neurofibrillary tangles and can cause neuron destabilisation, brain cell death, and are a key characteristic of the disease's progression. Much Alzheimer's disease research has focused on the build-up of amyloid plaques, caused by misfolding of the amyloid-β protein. However, because of disappointing results from numerous therapies targeting Aβ aggregation, more attention is shifting towards tau. This study, led by researchers at Lancaster University, used a new automated 'high throughput' screening approach to study the structure of the misfolding tau protein with a special analytical technique called 'Synchrotron Radiation Circular Dichroism' (SRCD) at Diamond Light Source, the UK national synchrotron light source in Oxfordshire. With this powerful technique they were able to look at a selection of more than 80 existing compounds and drugs simultaneously to determine their effectiveness at preventing the formation of tau fibrils. This method confirmed the compound epinephrine, more commonly known as adrenaline, was effective at stabilising the tau proteins and preventing the formation of tau tangles. However, our bodies do not easily absorb epinephrine and it rapidly gets metabolised, so the scientists then looked at a range of readily available compounds with similar chemical structures. This search revealed four current drugs as possible candidates - etamivan, fenoterol, dobutamine and salbutamol. Etaminvan and fenoterol were found to have little effect on the assembly of tau tangles. Dobutamine, which is used for the rapid treatment of heart attacks and heart failure, was found to have some benefit. However, because its effects are very short-lived, and because it needs to be administered intravenously, it is not ideal as a basis for treatment of Alzheimer's disease. Further tests using a range of analytical techniques all revealed salbutamol could inhibit tau aggregation in vitro. Tests where salbutamol was added to solutions containing tau resulted in drastically reduced density of fibrous tau structures responsible for the tau neurofibrillary tangles. The researchers believe that salbutamol interacts with an early stage of tau fibril formation, reducing their ability to form an initial nucleus which drives the aggregation process. Because it is easily ingested, absorbed into the brain, and remains in the body for several hours, salbutamol has attractive properties as a research avenue for potential new treatment for Alzheimer's. Dr David Townsend, of Lancaster university and lead author of the research, said: "Our work highlights the potential impact of repurposing drugs for secondary medical uses, by discovering a novel therapeutic strategy that impedes the molecular pathology of Alzheimer's disease, and which may have otherwise gone unstudied. "Salbutamol has already undergone extensive human safety reviews, and if follow up research reveals an ability to impede Alzheimer's disease progression in cellular and animal models, this drug could offer a step forward, whilst drastically reducing the cost and time associated with typical drug development." Professor David Middleton, co-author of the research, said: "This work is in the very early stages and we are some way from knowing whether or not salbutamol will be effective at treating Alzheimer's disease in human patients. However, our results justify further testing of salbutamol, and similar drugs, in animal models of the disease and eventually, if successful, in clinical trials." Dr Rohanah Hussain, of Diamond Light Source, Senior Beamline Scientist and co-author said: "Diamond B23 beamline unique micro-collimated beam has made high throughput CD possible allowing the screening of many compounds through structural activity correlation crucial in drug discovery." The researchers say that current asthma inhalers result in only a small amount of salbutamol reaching the brain and so, if further research is successful, a new delivery method would also need to be developed. They add that future research could also focus on other asthma drugs that are chemically similar to salbutamol, but which circulate in the bloodstream for much longer.

Olafur Palsson, PsyD, professor of medicine in the UNC School of Medicine, led a study investigating the emotional and mental impact of the COVID-19 pandemic in the U.S. The study authors are releasing their findings directly to the public in an effort to provide guidance and understanding to individuals and clinicians as the pandemic evolves. Newswise — CHAPEL HILL, NC – The findings of a nationwide survey assessing the effects of the COVID-19 pandemic on the emotional wellbeing of the U.S. adult population have been released online. The survey was a collaboration between UNC School of Medicine and Harvard Medical School, and was quickly organized to gain an understanding of how individuals are responding to the stressors of isolation and quarantine, record unemployment levels, and the virus’ threat to their health. “We were very careful to balance the demographics and geographic distribution of survey respondents so that it is an accurate representation of the U.S., and essentially a snapshot of the population,” said principal investigator Olafur Palsson, PsyD, professor of medicine in the division of gastroenterology and hepatology in the UNC School of Medicine. The study consisted of a nationwide internet survey of 1,500 people conducted during the second half of May, when the pandemic was just beyond its peak in the nation. It is worth noting that the survey ended on May 30, five days after George Floyd was killed by a police officer in Minnesota. Nearly 90 percent of survey responses were collected before the movement across the U.S. to increase recognition of systemic racism. “We saw that levels of concern or worry differed among different demographics including age and race,” Palsson said. “Women and men tended to experience similar degrees of emotional impact associated with the pandemic on average, but younger people were more affected by it than older individuals, and the Hispanic population seemed to be the most impacted emotionally when comparing ethnic groups.” The study assessed a broad range of specific emotional effects related to the pandemic, and found that there were stressors that seemed to affect a majority of the population. Nearly 80 percent of respondents were frustrated on some level with not being able to do what they normally enjoy doing.  Around the same number were worried about their own health, and nearly 90 percent of those surveyed were more worried about the health of loved ones than before the COVID-19 pandemic. “Most people have family or friends with chronic illness or health conditions that would make them more vulnerable to the virus, so worry about loved ones seems to be a shared feeling no matter who you are,” Palsson said. The emotional and mental impact of the pandemic could have long-term implications on well-being. Palsson and co-authors Sarah Ballou, PhD, instructor in medicine at Harvard Medical School and director of gastrointestinal psychology at Beth Israel Deaconess Medical Center, and Sarah Gray, PsyD, instructor in psychology at Harvard Medical School and practicing psychologist at Massachusetts General Hospital, wanted to get the results of the study out as quickly as possible to aid in addressing what could be a growing mental health crisis. “Understanding the psychological side of this pandemic has been somewhat neglected because there is so much else that is of concern right now,” Palsson said. “Our survey findings indicate that the anxiety and depression related to the emotional impact of these events are pushing more and more people into the clinical category of what is diagnosable as a mental health condition. We want people to seek the help they need.” A list of resources is available on the study’s website (http://pandemicimpactreport.com/index.html), along with a downloadable version of the study’s findings.   Photo credit: UNC School of Medicine Olafur Palsson, PsyD

Newswise — TALLAHASSEE, Fla. — Social distancing during the COVID-19 pandemic has not led to an overall increase in loneliness among Americans.  That’s the takeaway from a comprehensive, nationwide study by Florida State University College of Medicine researchers who surveyed more than 2,000 people before and during the enactment of stay-at-home policies in response to the COVID-19 pandemic.  The study on how loneliness and perceived support has changed from before to during the pandemic is published in American Psychologist.  “There has been a lot of worry that loneliness would increase dramatically because of the social distancing guidelines and restrictions,” said lead author Martina Luchetti, an assistant professor at the College of Medicine. “Contrary to this fear, we found that overall loneliness did not increase. Instead, people felt more supported by others than before the pandemic. Even while physically isolated, the feeling of increased social support and of being in this together may help limit increases in loneliness.”  The paper is part of a larger study College of Medicine researchers are doing on COVID-19 to look at changes in mental health during the COVID-19 crisis and how psychological factors contribute to various aspects of response to the pandemic.  The study involved a nationwide panel of adults ages 18 to 98. Participants first completed a survey in early February unrelated to COVID-19, before the virus was widely known to be a threat to the U.S.  As the threat was being realized, researchers contacted participants again for two more surveys — one in mid-March during the 15-day period to slow the spread based on White House guidelines and another in late April as the guidelines were about to expire. More than 2,000 responses to the surveys were included in the findings.  The study also looked for increased loneliness in specific at-risk groups, finding only modest evidence of a small increase in loneliness among older adults. Older adults reported less loneliness overall compared to younger age groups, despite an increase in loneliness during the acute phase of the outbreak. That increase in feelings of loneliness among older adults was temporary, leveling off after the issuance of stay-at-home orders.  Individuals living alone and those with at least one chronic condition reported feeling lonelier at the outset but did not increase in loneliness after social-distancing measures were implemented.  “Despite a small increase among some individuals, we found overall remarkable resilience in response to COVID-19,” said Angelina Sutin, associate professor of Behavioral Sciences and Social Medicine and senior author.  Loneliness already was a known health risk before the pandemic, and it has been linked to increased risks of morbidity and mortality. Surveys have found that 35 percent of adults 45 and older report feeling lonely and 43 percent of those over 60 report experiencing loneliness at least some of the time.  Some studies suggest that loneliness is even more pervasive among younger adults.  “In the context of the coronavirus pandemic, it may be particularly difficult to reconnect with others given the restrictions on in-person social gatherings,” Luchetti said. “Even these transient feelings of loneliness can have a negative effect on health, meaning there could be dangerous unintended consequences if loneliness increases in response to the restrictive measures taken as a result of the pandemic.”  Yet from the start of the pandemic, there have been anecdotal reports of people calling their family and friends more often and finding creative ways to stay connected. This outpouring of support may have shielded them from potential increases in loneliness.  The pandemic is also something that everybody is going through.   “Just knowing that you are not alone and that everyone is going through the same restrictions and difficulties may be enough in the short term to keep feelings of loneliness down,” Sutin said.

Study of over 900 U.S. metropolitan counties suggests that metropolitan size matters more than density in the spread of COVID-19 pandemic Newswise — A new study suggests that denser places, assumed by many to be more conducive to the spread of the coronavirus that causes COVID-19, are not linked to higher infection rates. The study, led by a researcher at the Johns Hopkins Bloomberg School of Public Health, also found that dense areas were associated with lower COVID-19 death rates. The study was published online June 18 in the Journal of the American Planning Association. For their analysis, the researchers examined SARS-CoV-2 infection rates and COVID-19 death rates in 913 metropolitan counties in the U.S. When other factors such as race and education were taken into account, the authors found that county density was not significantly associated with county infection rate. The authors also found that denser counties, as compared to more sprawling ones, tended to have lower death rates—possibly because they enjoyed a higher level of development including better health care systems. On the other hand, the authors found that higher coronavirus infection and COVID-19 mortality rates in counties are more related to the larger context of metropolitan size in which counties are located. Large metropolitan areas with a higher number of counties tightly linked together through economic, social, and commuting relationships are the most vulnerable to the pandemic outbreaks. “These findings suggest that urban planners should continue to practice and advocate for compact places rather than sprawling ones, due to the myriad well-established benefits of the former, including health benefits,” says study lead author Shima Hamidi, PhD, a Bloomberg Assistant Professor of American Health in Environmental Challenges in the Department of Environmental Health and Engineering at the Bloomberg School. Recent polls suggest that many Americans now consider an exodus from big cities likely, possibly due to the belief that more density equals more infection risk. Some government officials have posited that urban density is linked to the transmissibility of the virus. Hamidi, whose research background is in urban planning and architecture, and colleagues found otherwise. She and her colleagues, Sadegh Sabouri, a doctoral student, and Reid Ewing,  Distinguished Professor of City and Metropolitan Planning at the University of Utah, examined data from January 20 through May 25 on 913 metropolitan U.S. counties, using an approach known as Structural Equation Modeling and taking into account factors such as population size, education levels, and demographic variables including age and race, and health care infrastructure such as ICU bed capacity. The researchers determined from this analysis that, when controlling for other factors, a measure of density that they termed the “activity density”—which takes into account both residents and workers in a given area—did not have a significant association with SARS-CoV-2 infection rates. Higher activity density did, however, have a significant association with COVID-19 death rates, but an unexpected one. "The fact that density is unrelated to confirmed virus infection rates and inversely related to confirmed COVID-19 death rates is important, unexpected, and profound,” says Hamidi. “It counters a narrative that, absent data and analysis, would challenge the foundation of modern cities and could lead to a population shift from urban centers to suburban and exurban areas." The analysis found that after controlling for factors such as metropolitan size, education, race, and age, doubling the activity density was associated with an 11.3 percent lower death rate. The authors say that this is possibly due to a faster and more widespread adoption of social distancing practices and better quality of health care in areas of denser population. The authors conclude that a higher county population, a higher proportion of people age 60 and up, a lower proportion of college-educated people, and a higher proportion of African Americans were all associated with a greater infection rate and mortality rate. The researchers have been updating the data as the pandemic progresses, and are finding that the associations they have uncovered are becoming even stronger, Hamidi says. The team is also conducting a longitudinal study that tracks the relationships among density, the county-level SARS-CoV-2 infection rates and mortality rates, and explanatory factors as they change over time, and have found consistent results regarding the inverse relationship between density and the COVID-19 mortality rate. “Does Density Aggravate the COVID-19 Pandemic? Early Results and Lessons for Planners” was written by Shima Hamidi, Sadegh Sabouri, and Reid Ewing.

UT Southwestern Medical Center Diffusion tractography uses the movement of water molecules to identify tracts that connect different parts of the brain. It can be used to pinpoint the part of the thalamus to treat with focused ultrasound. DALLAS – June 14, 2020 – Recently developed MRI techniques used to more precisely target a small area in the brain linked to Parkinson’s disease and essential tremor may lead to better outcomes without surgery and with less risk of negative effects, a new study led by UT Southwestern researchers suggests. The study, published today in Brain, describes recently refined MRI methods designed to allow neuroradiologists to zero in on a pea-sized region in the brain’s thalamus involved in movement. Using the images, doctors then can use high-intensity focused ultrasound (HIFU) to ablate, or burn away, problem tissue, says Bhavya R. Shah, M.D., first author of the study and an assistant professor of radiology and neurological surgery at UT Southwestern’s Peter O’Donnell Jr. Brain Institute. “The benefit for patients is that we will be better able to target the brain structures that we want,” Shah says. “And because we’re not hitting the wrong target, we’ll have fewer adverse effects.” The procedures are already Food and Drug Administration-approved for use in patients, and UTSW plans to begin employing them to treat patients when its Neuro High Intensity Focused Ultrasound Program opens this fall.  Adverse effects from imprecise targeting include problems walking or slurring words. While such effects are usually temporary, they can be permanent in 15 to 20 percent of cases, says Dr. Shah. According to the National Institutes of Health, essential tremor affects up to 10 million Americans and Parkinson’s disease impacts more than 1 million. Both are neurologic diseases thought to have genetic links. The first line of treatment for the involuntary trembling or shaking seen with these diseases is medication. However, approximately 30 percent of patients do not respond well to drugs, according to the study. In the late 1990s, neurosurgeons began using a procedure called deep brain stimulation, opening the skull to permanently implant metal electrodes that could then be stimulated via a battery pack. About a decade ago, a new MRI-guided procedure emerged that uses high-intensity ultrasound waves to heat and eliminate a small section of the thalamus linked to the disorders. MRI-guided HIFU is currently approved for treatment of essential tremor and tremors seen in Parkinson’s disease patients. The outpatient procedure does not require opening the skull, and the patient is awake while it is performed, says Dr. Shah. “No cuts. No anesthesia. No implanted devices.” A challenge in both procedures has been locating the precise area inside the brain’s thalamus to treat – the pea-sized ventral intermediate nucleus, says Dr. Shah. Traditionally, doctors have relied on either landmarks or maps of the brain drawn from cadavers to help them pinpoint the correct location. However, every brain is different, Dr. Shah says, and tiny errors can lead to damage in surrounding tissue, or to missing portions of the correct target. Three newly refined MRI techniques are better at delineating the target tissue, according to the study. The most widely studied and perhaps most promising imaging method is called diffusion tractography, says Dr. Shah. It creates precise brain images by taking into account the natural water movement within tissues. The other methods described are quantitative susceptibility mapping – which creates contrast in the image by detecting distortions in the magnetic field caused by substances such as iron or blood – and fast gray matter acquisition TI inversion recovery – which operates much like a photo negative, turning the brain’s white matter dark and its gray matter white in order to provide greater detail in the gray matter. Dr. Shah and his team plan to participate in a multicenter clinical trial with collaborators at the Mayo Clinic in Rochester, Minnesota, testing the diffusion tractography method in patients. Senior author of the study was Rajiv Chopra, Ph.D., director of image-guided therapy development and associate professor of radiology in the Advanced Imaging Research Center at UTSW. Researchers at the Mayo Clinic also participated in the study.

ATS Drug shortages exacerbated by COVID-19. Newswise — June 11, 2020─ A new paper published online in the Annals of the American Thoracic Society examines the nation’s current shortage of vitally needed medications, and how this dangerous situation is being made worse by the COVID-19 pandemic.  The authors provide recommendations on how clinicians and institutions might address potential scarcities of essential medications during the current public health crisis. In “Preparing for COVID-19 Related Drug Shortages,” Andrew G. Shuman, MD, and co-authors discuss how the federal and state governments, as well as health care providers, need to develop ethically sound policies that address already perilously low supplies of certain commonly-used medications, which are dwindling further due to resources needed to combat COVID-19. “It is critical that these conversations occur now due to current shortages, as well as the necessary lead time to plan for future shortages,” said Dr. Shuman, co-chief of the Clinical Ethics Service, Center for Bioethics and Social Sciences in Medicine, University of Michigan Medical School.  “Drug shortages have been a national emergency for years and are currently exacerbated due to COVID-19.  Issues related to supply chain and anticipated increased ICU needs over the course of the pandemic are worsening the problem.” Yoram Unguru, MD, MS, MA, a physician-ethicist at The Herman and Walter Samuelson Children’s Hospital at Sinai and Johns Hopkins Berman Institute of Bioethics, who is a co-author of the paper, added, “As of today the American Society of Health-system Pharmacists (ASHP) reports 213 drugs shortages in the United States. It is not just patients with COVID-19 who are affected.  One example of a current drug with a critically short supply is Erwinia asparaginase, a life-saving chemotherapeutic agent for both children and adults with cancer.” Among medical specialties severely affected are oncology, critical care and infectious disease. The authors stated that regional communication among hospitals is an important first step — helping determine how local drug supply chains are affected — and that coordination and sharing mechanisms are also critical.  This information sharing would ideally occur via a central repository or clearinghouse.  Both the FDA and ASHP also maintain databases of current drug shortages, and independent health care companies maintain their own databases that can provide invaluable information.    “Sharing information is an important first step,” the authors stated.  “The second and more difficult step involves actual sharing of medications among hospitals and health systems.” There are a number of barriers to this taking place, among others, the need for cooperation among competing health systems, concerns about potential liability, and legal regulations that affect the transfer of drugs. Erin Fox, PharmD, a co-author who is director of drug information and support services for Utah Health noted, “Tantamount to this effort is facilitating communication between pharmacists — those tasked with maintaining supplies, as well as those embedded within clinical teams — in order to inform the clinical team how supply may impact care delivery.” She continued, “Pandemic-era strategies for conservation of commonly used critical care agents at risk of shortages should be noted, recognizing that these shortages are often regional and unpredictable, and intensive care protocols and strategies are highly individualized.” A list of these commonly used drugs is included in the paper. The authors noted that communication should not be limited to discussions among pharmacists, hospitals, and health systems.  Open discussions with patients who are most affected by drug shortages are essential.  In the spirit of openness, the authors recommended that hospitals consider publicly posting information about drug shortages.  Dr. Shuman and colleagues called upon stakeholders, from governments to clinicians, to refocus some of their efforts in managing shortages of ventilators during the COVID-19 crisis to develop workflows and rationing criteria for essential medicines.  “Even if there are sufficient ventilators, a critical shortage of sedatives, paralytics and/or opioids will obviate the ability to keep patients safely intubated.  Data suggest that these shortages have already been associated with inadvertent extubations.”  The authors have also identified hoarding of drugs thought to be potential COVID treatments as a problem. “Once effective treatments and/or vaccines for COVID-19 are available, prioritizing nascent supplies will present a formidable challenge,” they predicted.  “In the coming days and months, this matter demands global attention. Only with clear lines of communication and a proactive, collaborative approach can we weather this impending storm.”  

Newswise — Population-wide use of facemasks keeps the coronavirus ‘reproduction number’ under 1.0, and prevents further waves of the virus when combined with lockdowns, a modelling study from the universities of Cambridge and Greenwich suggests. The research suggests that lockdowns alone will not stop the resurgence of SARS-CoV-2, and that even homemade masks with limited effectiveness can dramatically reduce transmission rates if worn by enough people, regardless of whether they show symptoms.  The researchers call for information campaigns across wealthy and developing nations alike that appeal to our altruistic side: “my facemask protects you, your facemask protects me”. The findings are published in the Proceedings of the Royal Society A. “Our analyses support the immediate and universal adoption of facemasks by the public,” said lead author, Dr Richard Stutt, part of a team that usually models the spread of crop diseases at Cambridge’s Department of Plant Sciences. “If widespread facemask use by the public is combined with physical distancing and some lockdown, it may offer an acceptable way of managing the pandemic and re-opening economic activity long before there is a working vaccine.” Dr Renata Retkute, coauthor and Cambridge team member, said: “The UK government can help by issuing clear instructions on how to make and safely use homemade masks.” “We have little to lose from the widespread adoption of facemasks, but the gains could be significant.” The new coronavirus is transmitted through airborne droplets loaded with SARS-CoV-2 particles that get exhaled by infectious people, particularly when talking, coughing or sneezing. For the latest study, Cambridge researchers worked to link the dynamics of spread between individuals with population-level models, to assess different scenarios of facemask adoption combined with periods of lockdown. The modelling included stages of infection and transmission via surfaces as well as air. Researchers also considered negative aspects of mask use, such as increased face touching. The reproduction or ‘R’ number – the number of people an infected individual passes the virus onto – needs to stay below 1.0 for the pandemic to slow. The study found that if people wear masks whenever they are in public it is twice as effective at reducing ‘R’ than if masks are only worn after symptoms appear. In all modelling scenarios, routine facemask use by 50% or more of the population reduced COVID-19 spread to an R less than 1.0, flattening future disease waves and allowing less-stringent lockdowns. Viral spread reduced further as more people adopted masks when in public. 100% mask adoption combined with on/off lockdowns prevented any further disease resurgence for the 18 months required for a possible vaccine.    The models suggest that – while the sooner the better – a policy of total facemask adoption can still prevent a second wave even if it isn’t instigated until 120 days after an epidemic begins (defined as the first 100 cases). The team investigated the varying effectiveness of facemasks. Previous research shows that even homemade masks made from cotton t-shirts or dishcloths can prove 90% effective at preventing transmission. The study suggests that an entire population wearing masks of just 75% effectiveness can bring a very high ‘R’ number of 4.0 – the UK was close to this before lockdown – all the way down to under 1.0, even without aid of lockdowns. In fact, masks that only capture a mere 50% of exhaled droplets would still provide a “population-level benefit”, even if they quadrupled the wearer’s own contamination risk through frequent face touching and mask adjustment (a highly unlikely scenario). The researchers point out that crude homemade masks primarily reduce disease spread by catching the wearer’s own virus particles, breathed directly into fabric, whereas inhaled air is often sucked in around the exposed sides of the mask. “There is a common perception that wearing a facemask means you consider others a danger,” said Professor John Colvin, coauthor from the University of Greenwich. “In fact, by wearing a mask you are primarily protecting others from yourself.” “Cultural and even political issues may stop people wearing facemasks, so the message needs to be clear: my mask protects you, your mask protects me.” “In the UK, the approach to facemasks should go further than just public transport. The most effective way to restart daily life is to encourage everyone to wear some kind of mask whenever they are in public,” Colvin said. Prof Chris Gilligan, coauthor from Cambridge’s Epidemiology and Modelling Group in the Department of Plant Sciences, added: “These messages will be vital if the disease takes hold in the developing world, where large numbers of people are resource poor, but homemade masks are a cheap and effective technology.”

Newswise — The country’s first convalescent plasma transfusion trial results have been peer-reviewed and published, showing 19 out of 25 patients improving with the treatment and 11 discharged from the hospital. On March 28, Houston Methodist became the first academic medical center in the nation to transfuse plasma from recovered COVID-19 patients into two critically ill patients.  With no adverse side effects caused by the plasma transfusion, the study concluded that convalescent plasma is a safe treatment option for patients with severe COVID-19 disease. To date, this is the largest cohort worldwide assessed for outcomes pertaining to convalescent plasma transfusion for COVID-19. The findings are described in a paper appearing in press May 26 (online May 28) in The American Journal of Pathology. This is the first peer-reviewed publication on convalescent plasma use in the U.S.  James M. Musser, M.D., Ph.D., chair of the Department of Pathology and Genomic Medicine at Houston Methodist, is the corresponding author on the study, titled “Treatment of COVID-19 patients with convalescent plasma.” Eric Salazar, M.D., Ph.D., assistant professor of pathology and genomic medicine with the Houston Methodist Research Institute, is the principal investigator who led the project to treat critically ill COVID-19 patients with convalescent plasma.  “While physician scientists around the world scrambled to test new drugs and treatments against the COVID-19 virus, convalescent serum therapy emerged as potentially one of the most promising strategies,” Musser said. “With no proven treatments or cures for COVID-19 patients, now was the time in our history to move ahead rapidly.”  Patients were first treated under emergency use guidelines (eIND) from the U.S. Food and Drug Administration and then received approval April 3 from the FDA to open up the trial to more patients as an investigational new drug (IND). This extraordinarily rapid approval granted by the FDA opened up access to convalescent plasma treatment for COVID-19 patients.  The century-old therapeutic approach dates back to at least as early as 1918 to fight the Spanish Flu and more recently was used with some success during the 2003 SARS pandemic, the 2009 influenza H1N1 pandemic and the 2015 Ebola outbreak in Africa. Following a study early on in the COVID-19 pandemic, where a handful of critically ill patients in China showed improvement, an interdisciplinary team of Houston Methodist physician scientists and health care workers rapidly targeted the COVID-19 virus with convalescent serum therapy.  Additional findings during this trial revealed patient outcomes following plasma therapy were very similar to recently published results of patients treated on a compassionate-use basis with the antiviral drug remdesivir. The research team also concluded that any observed complications were consistent with findings reported for COVID-19 disease progression and did not result from the plasma transfusions. The study’s overall findings were consistent with several other small case studies of convalescent plasma use for severe COVID-19 that have been recently reported.  Ultimately, although the convalescent plasma therapy administered on the front lines at Houston Methodist was implemented for emergency treatment, the study’s authors recognize the important need for controlled clinical trials to determine its therapeutic efficacy. A randomized controlled trial is currently being considered at Houston Methodist where they would also look more closely at variables such as timing of the transfusion after the onset of symptoms, the number and volume of transfusions adjusted for patient biometrics, antibody levels in donor plasma and numerous other parameters needed to effectively evaluate how to optimize this therapy. This would help address some questions, including whether patients would have better outcomes if plasma transfusions were administered sooner after the onset of symptoms.  Not all plasma recipients transfused so far at Houston Methodist were part of this first trial. Since late March, when the first patients were infused with convalescent plasma, Houston Methodist has treated 74 critically ill COVID-19 patients, 50 of whom have been discharged from the hospital and are recovering. More than 150 recovered COVID-19-infected individuals donated their plasma, many of them continuing to do so frequently.  AJP, an Elsevier journal, is the official journal of the American Society for Investigative Pathology and publishes high-quality original research reports, reviews and commentaries related to the molecular and cellular basis of disease.  In addition to Musser and Salazar, other collaborators on this study were Katherine K. Perez, Madiha Ashraf, Jian Chen, Brian Castillo, Paul C. Christensen, Taryn Eubank, David W. Bernard, Todd Eagar, S. Wesley Long, Sishir Subedi, Randall J. Olsen, Christopher Leveque, Mary R. Schwartz, Monisha Dey, Cheryl Chavez-East, John Rogers, Ahmed Shehabeldin, David Joseph, Guy Williams, Karen Thomas, Faisal Masud, Christina Talley, Katharine G. Dlouhy, Bevin Lopez, Curt Hampton, Jason Lavinder, Jimmy D. Gollihar, Andre C. Maranhao, Gregory C. Ippolito, Matthew Ojeda Saavedra, Concepcion C. Cantu, Prasanti Yerramilli and Layne Pruitt. This study was supported by funding from the National Institutes of Health (grants AI146771-01 and AI139369-01), the Fondren Foundation, the National Institute of Allergy and Infectious Diseases (Contract Number 75N93019C00050), the Army Research Office (Cooperative Agreement W911NF-12-1-0390), Houston Methodist Infectious Diseases Research Fund, Houston Methodist Hospital and Houston Methodist Research Institute.    Photo: Houston Methodist Houston Methodist physician scientists (left to right) Eric Salazar, MD, PhD, and James M. Musser, MD, PhD, discuss their convalescent plasma trial for treating COVID-19, the results of which were the first in the U.S. to be peer-reviewed and published.