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The antidepressant fluvoxamine appears to prevent COVID-19 infections from worsening and may help keep patients out of the hospital, a trial based on research from the University of Virginia School of Medicine suggests.

The clinical trial, conducted by the Washington University School of Medicine in St. Louis, compared fluvoxamine with a placebo in 152 adult outpatients infected with the coronavirus. None of the participants who received fluvoxamine saw "clinical deterioration" after 15 days, while six patients who received placebo did. Of those six, four were hospitalized, for periods ranging from four to 21 days. One was on a ventilator for 10 days.

While the study size was small, the researchers say the results are statistically significant and that fluvoxamine warrants further study as a COVID-19 treatment. They plan to launch a larger trial in the next few weeks.

"The patients who took fluvoxamine did not develop serious breathing difficulties or require hospitalization for problems with lung function," said Eric J. Lenze, MD, of the Washington University School of Medicine. "Most investigational treatments for COVID-19 have been aimed at the very sickest patients, but it's also important to find therapies that prevent patients from getting sick enough to require supplemental oxygen or to have to go to the hospital. Our study suggests fluvoxamine may help fill that niche."

Fluvoxamine and COVID-19

The Washington University researchers launched the randomized, double-blind trial based on a discovery by UVA's Alban Gaultier, PhD, and former graduate student Dorian A Rosen, PhD. Gaultier and Rosen found last year that fluvoxamine may stop the deadly inflammation known as sepsis, in which the immune response spirals out of control. The drug, they determined, reduced the production of cytokines, which have been linked to potentially deadly "cytokine storms" thought to occur in severe cases of COVID-19.

That connection prompted the Washington University team to investigate the possibility that fluvoxamine could have a protective effect for patients with COVID-19. Perhaps, they thought, the drug could help prevent the immune system overreactions triggered by this strange new coronavirus. And their work suggests it may.

"Because elevated cytokines levels have been associated with COVID-19 severity, testing fluvoxamine in a clinical trial made a lot of sense to us," said Gaultier, of UVA's Department of Neuroscience and its Center for Brain Immunology and Glia (BIG). "We are still unclear about the mode of action of fluvoxamine against SARS-CoV-2, but research is under way to find the answer."

The Washington University team noted that recent research has raised questions about whether cytokines are really playing important roles in COVID-19 deaths. If not, the researchers say, fluvoxamine may be having beneficial effects by some other mechanism not yet understood.

"There are several ways this drug might work to help COVID-19 patients, but we think it most likely may be interacting with the sigma-1 receptor to reduce the production of inflammatory molecules," said Washington University's Angela M Reiersen, MD. "Past research has demonstrated that fluvoxamine can reduce inflammation in animal models of sepsis, and it may be doing something similar in our patients."

The researchers stressed that there were several limitations to their research. In addition to its small size, the trial was hampered by other factors, including that 20% of participants stopped answering surveys during the 15-day trial. (The researchers determined that none of those participants required hospitalization or emergency-department visits, but they could not rule out that the participants sought treatment elsewhere, such as at urgent-care clinics.)

Because of these limitations, the researchers say that the trial's results should not be treated as a measure of fluvoxamine's effectiveness against COVID-19 but as an encouraging indicator that the drug warrants further testing.

"If a larger clinical trial (phase III) confirms the results, fluvoxamine would be a perfect treatment for COVID patients newly diagnosed," Gaultier said. "Fluvoxamine is not an experimental drug, it is cheap and safe and could be available as a first line of defense to unburden the hospitals that are overwhelmed by the COVID health crisis."

A research team from the Universitat Rovira i Virgili (Tarragona - Spain) has observed that following a diet rich in fats and sugars from ultra-processed foods (such as sweet rolls and pastries) for a six-week period increases the number of inflammatory molecules in the organism, which increases the excitability of the muscle nerves. This is known as musculoskeletal neurotransmission.

The experiments were carried out in male Swiss mice. One group was given a typical cafeteria diet, high in added sugars (for example, sweet rolls and pastries), and another was given a high-fat commercial diet for a period of six weeks. The researchers then calculated the intramuscular adipocytes and used electromyography to assess musculoskeletal neurotransmission, the response of the muscle nerves.

The mice who had consumed a cafeteria diet showed more adipocytes in the muscle tissue but the same cannot be said for the fat-rich diet. However, both groups showed an increase in neuromuscular transmission which lasted for several weeks after the diets had been terminated. The study concludes that a six-week hypercaloric diet in mice increases neurotransmission, which leads to the development of muscle pain. After this period, the mice quickly regained their normal weight although the neurotransmission parameters remained high for several weeks.

In Western societies, the rate of obesity and overweight is clearly increasing. Between 1975 and 2016 the rate of world obesity tripled. In 2030 more than 38% of the world's adult population will be overweight and 20% will be obese. Obesity and overweight are regarded as an epidemic that is associated with the development of such pathologies as diabetes, cardiovascular disease, metabolic syndrome and musculoskeletal pain.

Studies indicate that there is a strong relationship between obesity and pain. Normally, the association between overweight and musculoskeletal pain has been attributed to an increase in mechanical stress caused by the extra weight that has to be supported by the weight-bearing joints. Nevertheless, that study that has just been published in the journal Nutrients "reveals an association between pain and overweight that is independent of mechanical overload and it is probable that it involves systemic phenomena of the organism" says Manel Santafe, one of the authors of the study.

Embargoed until 10:35 a.m. CT/11:35 a.m. ET, Friday, Nov. 13, 2020

DALLAS, Nov. 13, 2020 -- Omecamtiv mecarbil, a new, investigational heart medication, reduced the risk of heart failure-related events in patients with heart failure with reduced ejection fraction, according to late-breaking research presented today at the American Heart Association's Scientific Sessions 2020. The virtual meeting is Friday, November 13 - Tuesday, November 17, 2020, and is a premier global exchange of the latest scientific advancements, research and evidence-based clinical practice updates in cardiovascular science for health care worldwide. The manuscript of this study is simultaneously published today in The New England Journal of Medicine.

Ejection fraction is a measurement of the proportion of blood the heart pumps out with each contraction. Heart failure with reduced ejection fraction, or HFrEF, occurs when the left ventricle, the heart's largest pumping chamber, loses its ability to contract normally. The heart can't pump with enough force to push blood into circulation. An ejection fraction of 40% or less is used to define HFrEF. For this study, an EF of ? 35% was required.

The GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure) study assessed omecamtiv mecarbil, an investigational medication that was granted "fast track" designation as a new heart failure treatment option by the U.S. Food and Drug Administration in May 2020.

Omecamtiv mecarbil binds to cardiac myosin, the protein in the heart that transforms chemical energy into mechanical work, thus powering muscle contraction. In previous studies, it was found to improve cardiac function by increasing the effectiveness by which myosin interacts with actin, another protein involved in heart muscle contraction.

"Omecamtiv mecarbil is the first in a class of heart medicines called myotropes that selectively target cardiac muscle to improve cardiac performance," said John R. Teerlink, M.D., lead author of the study, director of heart failure and of the Echocardiography Laboratory at the San Francisco Veterans Affairs Medical Center and professor of medicine at the University of California San Francisco. "In the phase 2 study that led to GALACTIC-HF, omecamtiv mecarbil increased measures of cardiac performance and function. GALACTIC-HF focused on evaluating the effect of this potential medication on outcomes in patients with chronic heart failure."

GALACTIC-HF was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. The study enrolled more than 8,000 patients in 35 countries with chronic heart failure who were either currently hospitalized for heart failure or with a recent history of hospitalization or emergency department visit for heart failure within one year prior to screening.

Participants were predominantly male (79%) and white* (78%), with an average age of 66 years and average ejection fraction of 27%. In addition:

62% had coronary artery disease;

40% had Type 2 diabetes;

70% had high blood pressure;

36% had chronic kidney disease; and

25% were hospitalized at the time of enrollment.

* While only 7% of participants self-reported as Black, more Black patients were enrolled in GALACTIC-HF than in any contemporary, international heart failure trial.

Patients were randomized to receive either an oral placebo or omecamtiv mecarbil. The study investigated how much time passed before the first heart failure event such as hospitalization, an urgent visit requiring intravenous therapy for heart failure or cardiovascular death.

The study found that patients receiving omecamtiv mecarbil had less risk of experiencing a heart failure event or cardiovascular death. The medicine had a greater effect for patients with lower ejection fraction (ejection fraction ?28%), an indicator of more advanced heart failure. In addition, the concentration in the blood of N-terminal B-type natriuretic peptide, a hormone that is increased with worsening heart failure, was reduced in patients treated with omecamtiv mecarbil. There were no significant imbalances in adverse events between patients randomized to treatment or placebo. In addition, side effects that typically limit the use of current heart failure therapies, such as adverse effects on blood pressure, heart rate, potassium levels or kidney function, were not observed.

"This study provides substantial evidence characterizing the efficacy and safety of this novel therapy," said Teerlink. "The trial included a wide range of patients from both the inpatient and outpatient settings, and these findings will inform potential future implementation of omecamtiv mecarbil to treat chronic heart failure."

Embargoed until 12:30 p.m. CT/1:30 p.m. CT, Friday, Nov. 13, 2020

DALLAS, Nov. 13, 2020 -- More than 40% of middle-aged adults have silent coronary artery disease. Researchers have developed a new screening questionnaire to help identify individuals at the highest risk for coronary artery disease, according to late-breaking research presented today at the American Heart Association's Scientific Sessions 2020. The virtual meeting is Friday, November 13-Tuesday, November 17, 2020. It is a premier global exchange of the latest scientific advancements, research and evidence-based clinical practice updates in cardiovascular science for health care.

Coronary artery disease is caused by atherosclerosis, or deposits of fats, cholesterol and calcium in the blood vessels that supply blood to the heart. Early detection of coronary artery disease is possible by imaging blood vessels using coronary computed tomography angiography (CCTA) imaging; however, it can be expensive and requires specialized equipment.

"The buildup of plaque does not cause symptoms in the early phases of atherosclerosis yet may lead to reduced blood flow to the heart and result in a heart attack," said Göran Bergström, M.D., Ph.D., professor and lead physician at Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden and lead author of this study. "We investigated whether a personalized screening strategy using data easily measured at home could predict which patients are at high risk of developing heart disease."

The Swedish CArdioPulmonary BioImage Study (SCAPIS) included more than 30,000 men and women, ages 50-64 years, who had no history of prior heart attack or cardiac intervention. Participants were asked questions about gender, age, smoking, body measurements, cholesterol medication and blood pressure to predict their risk of coronary artery disease.

Researchers then used CCTA images to examine patients' arteries for the presence of plaque. More than 25,000 individuals from the original sample were successfully imaged. The imaging results found that silent coronary artery disease was common, with 42% of participants having plaque in their coronary arteries. A higher prevalence of atherosclerosis was observed in men and in older individuals.

In this Swedish cohort, responses to the screening questions successfully predicted which individuals had severe atherosclerosis and were at higher risk of developing cardiovascular disease.

"We were surprised that atherosclerosis was so widespread and that we could rather easily predict it with simple questions," Bergstrom said. "Our study lays the foundation for development of a home-based screening strategy to help combat cardiovascular disease. We can find people at high risk of having silent coronary artery disease using a simple screening questionnaire followed by a clinical visit to a health-care facility to define the risk further using CCTA imaging."

This study is the first report from SCAPIS, a collaborative project between six Swedish universities with the vision statement: to reduce the risk of cardiovascular and respiratory diseases for generations to come.

The turning point for people with COVID-19 typically comes in the second week of symptoms. As most people begin to recover, a few others find it increasingly difficult to breathe and wind up in the hospital. It has been theorized that those whose lungs begin to fail are victims of their own overactive immune systems.

A new study from Washington University School of Medicine in St. Louis and St. Jude Children's Research Hospital in Memphis, Tenn., however, suggests that an out-of-control immune response is not the main problem for the vast majority of hospitalized COVID-19 patients. Only 4% of patients in the study had the sky-high levels of immune molecules that signify a so-called "cytokine storm." The rest had inflammation, but not a remarkably high amount for people fighting infection. If anything, the COVID-19 patients had less inflammation than a comparable group of influenza patients.

The findings, published Nov. 13 in Science Advances, help explain why anti-inflammatory medications such as dexamethasone benefit only a fraction of people with severe COVID-19, and suggest that more research is needed to identify the causes of respiratory failure in COVID-19 patients.

"One of the very first papers published on COVID-19 patients in China reported high levels of cytokines in people in intensive care, what we might call a cytokine storm," said co-senior author Philip Mudd, MD, PhD, an assistant professor of emergency medicine who sees patients at Barnes-Jewish Hospital. "We wanted to have a better idea of what this cytokine storm looked like, so we began looking for it in our patients, and we were very surprised when we didn't find it. We found that cytokine storm does happen, but it's relatively rare, even in the COVID-19 patients that go on to have respiratory failure and require a ventilator. But now this idea has gotten established that respiratory failure in COVID-19 is driven by cytokine storm, and lots of unproven anti-inflammatory treatments are being given to critically ill COVID-19 patients in an attempt to suppress the cytokine storm. That worries me because such treatments are unlikely to help most people with COVID-19."

Before the pandemic, Mudd started investigating the immune response to influenza infection, using blood samples obtained, with consent, from flu patients who seek care in the Barnes-Jewish Hospital emergency department. In late March, as COVID-19 patients began filling the emergency department, Mudd and co-senior author Ali Ellebedy, PhD, an assistant professor of pathology and immunology and a fellow influenza expert, realized they could use the same approach to investigate how the immune response goes awry in severe cases of COVID-19.

The researchers analyzed immune cells and molecules in blood samples from 168 COVID-19 patients, 26 influenza patients and 16 healthy people. The samples were drawn from influenza patients in 2019 or 2020, and from COVID-19 patients and healthy controls this year. They also collected information about how each patient fared -- whether a patient ended up needing intensive care or mechanical ventilation -- and whether he or she survived. Along with Mudd and Ellebedy, the research team included co-senior author Paul Thomas, PhD, and co-first author Jeremy Crawford, PhD, both of St. Jude, among others.

The numbers of inflammatory cells in the blood of COVID-19 and influenza patients were about the same. Seven of the COVID-19 patients (4%) showed signs of a cytokine storm, with extremely high levels of cytokines even when compared to other severely ill patients. The majority of the COVID-19 patients with acute respiratory failure not only did not have a cytokine storm, they had less inflammation than influenza patients who were equally ill.

A few clinical trials have shown that some severely ill COVID-19 patients improve on steroid drugs such as dexamethasone that suppress inflammation. A meta-analysis published in September placed the percentage who benefit between 2% and 9%. Those results jibe with the findings of this study, Mudd said.

"It could be that the 4% of people who have cytokine storm are the ones who benefit from steroids in those clinical trials," Mudd said. "I think our work helps explain why steroids help some people. But from our data, it doesn't look like most COVID-19 patients have a deficiency of steroids. If you're giving steroids to someone who already has a lot of steroids in their body, that might not be good for them."

The key will be to find a way to identify the people at high risk for a cytokine storm when they first arrive at the hospital, so that steroid treatment can be appropriately targeted to the ones most likely to benefit and least likely to be harmed. The researchers ran a panel of routine lab tests -- blood cell counts, measurements of common inflammatory markers -- but could not find a signature of an impending cytokine storm. They are pursuing more in-depth analyses to find a way to predict who will develop a cytokine storm.

"The subjects in the cohort with the 'true' cytokine storm phenotype are such outliers immunologically compared to the others, it seems likely that there are significant differences in multiple immune pathways driving this phenotype," Thomas said. "If we can identify features of those pathways that can be assessed quickly in a clinical setting, it could be useful for patient stratification."

With cytokine storm largely ruled out, the cause of most cases of respiratory failure in COVID-19 patients remains unknown, Mudd said.

"In the population we studied, 24% died but only 4% had a cytokine storm," Mudd said. "Most people who died of COVID-19 died without a cytokine storm. Severe flu is more inflammatory than severe COVID-19. So what's causing their lungs to fail? We still don't know. We're trying to find out."

Published today in the EClinicalMedicine Journal, a study from the University of Minnesota found that the first four months of the Minnesota Mobile Resuscitation Consortium (MMRC) was 100% effective in cannulation for out-of-hospital sudden cardiac arrests. Cannulation is when tubes are placed in large veins and arteries in the legs, neck or chest in a patient by a health care provider.

This Minnesota-based program began last December by launching three SUVs that brought proper medical equipment to emergency departments in Twin Cities metro area locations that are served by the program's health care system partners: Fairview Health Services, Regions Hospital (HealthPartners) and North Memorial Health Care System.

The study's findings concluded that MMRC is the first community-wide ECMO-facilitated resuscitation program in the U.S. that has:

demonstrated 100% successful cannulation;

functionally favorable survival rates;
good safety;
and
the potential to be replicated in other states.

"A sudden cardiac arrest is when the heart stops and blood flow to the heart and the whole body stops, leading to oxygen deficit and, eventually, death unless treated immediately," said Demetri Yannopoulos, director of the Center of Resuscitation Medicine and a professor in the Medical School.

"With our mobile teams and cardiac arrest toolkits, we are able to deliver the expertise and equipment needed to stabilize people suffering cardiac arrest within as little as 30 minutes. The ability to deliver these life-saving capabilities so quickly and reach patients across the Twin Cities is a game changer in the treatment of cardiac arrest," said Jason Bartos, president of the Minnesota Mobile Resuscitation Consortium and assistant professor in the Medical School.

The study observed 63 consecutive patients enrolled in MMRC ages 18-75 from December 1, 2019, to April 1, 2020. The study authors observed:

58 patients met the criteria and were treated by the MMRC SUV response team;

the mean age was approximately 57;

46 of 58 patients were male;

100% of patients were successfully cannulated, with no identified safety issues;
and
of the 58 patients treated, 43% were discharged from the hospital with either a return to normal daily living or with minimal disruption to their daily life.

The MMRC mobile ECMO program relaunched this September, following a disruption caused by COVID-19. Since then, the MMRC SUV response team has continued to serve cardiac arrest patients and expand the number of centers where cannulation services are provided.

"Our goal has been to improve cardiac arrest survival, and the early results from the MMRC's efforts show more people are alive today because of the hard work of all involved," said Walter Panzirer, a trustee of The Leona M. and Harry B. Helmsley Charitable Trust, which helped launch the program with an $18.6 million grant. "The success of the SUV-based teams shows the way we treat cardiac arrest has changed. We are excited to see this game-changing work continue and shared broadly."

In early 2021, the MMRC plans to launch a larger mobile ECMO truck that will be outfitted with medical equipment and virtual reality technology to help experts attend to patients remotely. This approach will allow experts to administer treatment on-site in the vehicle -- shortening the time to treatment and broadening the area served by the program.

(MEMPHIS, Tennessee -- November 13, 2020) Rather than life-threatening hyperinflammation, most adults with moderate-to-severe COVID-19 have a suppressed viral immune response when compared to adults with another viral respiratory infection, influenza. St. Jude Children's Research Hospital and Washington University School of Medicine in St. Louis led research that suggests most COVID-19 patients are not candidates for treatment with steroids such as dexamethasone. The research appears today in Science Advances.

Fewer than 5% of the COVID-19 patients in this study, including some of the sickest individuals, had the life-threatening, hyperinflammatory immune response known as cytokine storm syndrome. Cytokines are small proteins secreted by blood cells that help coordinate the immune response and trigger inflammation. Cytokine storms develop when excess or abnormally regulated cytokine production leads to hyperinflammation and tissue damage. While dexamethasone and other steroids are prescribed to treat cytokine storms, the drugs can backfire in patients whose immune response is already suppressed.

Cytokine storms have been proposed as the cause of respiratory failure in COVID-19 patients.

"We did identify a subset of COVID-19 patients with the broadly upregulated array of cytokines, which is a hallmark of cytokine storm," said co-corresponding author Paul Thomas, Ph.D., of the St. Jude Department of Immunology. "But, overall, the average person with COVID-19--even patients with moderate-to-severe disease--had less inflammation than the average person with flu.

"The findings suggest that treatment suppressing inflammation might only be effective in that minority of patients with the hyperinflammatory profile," Thomas said. He, Ali Ellebedy, Ph.D., and Philip Mudd, M.D., Ph.D., of Washington University School of Medicine, are corresponding authors of the study.

What's needed, researchers said, is a fast, reliable and inexpensive test to measure cytokines and identify patients who are most likely to benefit from immunosuppressive treatment.

"Current clinical studies do not adequately target these therapies to the patients who many benefit the most," said Mudd, a scientist and emergency medicine physician who treats patients with COVID-19 at Barnes-Jewish Hospital in St. Louis. "Directing immunosuppressive therapies to the small subset of COVID-19 patients who have an overactive immune response is the only way to know if these approaches are ultimately helpful."

Immune responses: COVID-19 vs flu

What's also needed is a better understanding of the immune response to COVID-19, including the cause of respiratory failure that has been reported in as many as 8% of patients.

Researchers sought to do that in this report, which stems from one of the largest and most comprehensive comparisons yet of the human immune response to flu and SARS-CoV-2, the virus that causes COVID-19. Unlike COVID-19, the immune response to flu has been studied for decades and is better understood.

The research included 168 adults with COVID-19, 26 adults with flu and 16 healthy volunteers. More than 90% of the COVID-19 patients were hospitalized, about half in the intensive care unit. Twenty-three percent of those hospitalized died. More than half of flu patients were hospitalized, 35% in the ICU, and 8% of those hospitalized died.

To understand the immune response, researchers measured a variety of immune cells and factors, including 35 different cytokines. Seven COVID-19 patients, or 4%, met the study definition of cytokine storm, meaning that about half or more of the 35 cytokines were significantly elevated compared to patient averages. Statistically, the elevation was defined as at least two standard deviations above the mean.

Patients with cytokine storm syndrome had individual cytokine levels as much as 10- to 100-times higher than the average. But when researchers included age and other factors, COVID-19 patients had lower overall cytokine levels than flu patients.

If not cytokine storm, what?

"The lack of hyperinflammation in most COVID-19 patients does not mean they had less disease," said co-first author Jeremy Chase Crawford, Ph.D., of St. Jude Immunology. "We are saying that in most cases the disease was not caused by broad hyperinflammation from cytokine storm, which has important implications for developing generalizable COVID-19 therapeutics."

The analysis revealed that the antiviral immune response was profoundly suppressed in COVID-19 patients compared to flu patients. Along with measuring cytokines, researchers analyzed cytokine transcription in individual blood cells in patients with flu, COVID-19 and healthy volunteers. COVID-19 was associated with significantly reduced production of and response to Type I and Type II interferons, cytokines that play a central role in the antiviral immune response.

Researchers also found evidence that SARS-CoV-2 alters pathways controlling the immune response to promote steroid production by patients. "Our results suggest that most COVID-19 patients are perhaps already producing high levels of glucocorticoids prior to treatment, possibly leading to the blunted immunity we see in most of them," Thomas said. "These patients may need therapy to turn up their immune response to knock the virus down."

Politicians and governments are suppressing science, and when good science is suppressed, people die, argues a senior editor at The BMJ today.

Executive editor, Dr Kamran Abbasi, argues that covid-19 "has unleashed state corruption on a grand scale, and it is harmful to public health."

Politicians and industry are responsible for this opportunistic embezzlement, he writes. So too are scientists and health experts. "The pandemic has revealed how the medical-political complex can be manipulated in an emergency--a time when it is even more important to safeguard science."

He points to examples of suppression of science or scientists during the UK's pandemic response, including inappropriate involvement of government advisers in the Scientific Advisory Group for Emergencies (SAGE), attempts to withhold information on covid-19 and inequalities, block publication of a study on point-of-care antibody testing for covid-19, and instruct scientists not to talk to the media.

In the US, President Trump's government manipulated the Food and Drug Administration to hastily approve unproved drugs such as hydroxychloroquine and remdesivir, he adds. Globally, people, policies, and procurement are being corrupted by political and commercial agendas.

Abbasi argues that the UK's pandemic response "relies too heavily on scientists and other government appointees with worrying competing interests, including shareholdings in companies that manufacture covid-19 diagnostic tests, treatments, and vaccines."

So how might science be safeguarded in these exceptional times?

The first step is full disclosure of competing interests from government, politicians, scientific advisers, and appointees, such as the heads of test and trace, diagnostic test procurement, and vaccine delivery. The next step is full transparency about decision making systems, processes, and knowing who is accountable for what.

Governments and industry must also stop announcing critical science policy by press release, he adds. "Clear, open, and advance publication of the scientific basis for policy, procurements, and wonder drugs is a fundamental requirement."

Politicians often claim to follow the science, but Abbasi says a better approach is for politicians, the publicly appointed decision makers, to be informed or guided by science when they decide policy for their public.

"Science is a public good. It doesn't need to be followed blindly, but it does need to be fairly considered," he writes.

"Importantly, suppressing science, whether by delaying publication, cherry picking favourable research, or gagging scientists, is a danger to public health and maladministration of taxpayers' money when entangled with commercial decisions," he argues. "When good science is suppressed, people die."

A University of Cincinnati immunologist is recommending that individuals with contact dermatitis choose facial masks made without elastic or rubber that allow them to stay safe in the midst of COVID-19 while avoiding possible allergic reactions.

Yashu Dhamija, MD, a first-year fellow in the UC Division of Immunology, Allergy, and Rheumatology, presented his findings in an abstract while discussing a medically challenging case at the virtual American College of Allergy, Asthma and Immunology (ACAAI) scientific meeting held November 13-15.

"How do you help patients manage a condition that puts them at risk for something like COVID-19?" asked Dhamija. "We definitely want our patients to use masks and apply social distancing. That's a must. But they can avoid elastic components and use face masks that use the knot tie method around the back of the head to keep the masks up."

Dhamija treated a patient who had been diagnosed with contact dermatitis, a reaction to allergens that touch or have contact with the skin. It is different from allergies to things such as dog or cat dander because with contact dermatitis the body's response is not immediate."

"What makes contact dermatitis tricky is that it can be delayed so you may expose your skin to something and a reaction may not occur until days later," said Dhamija. "Intermittent reactions can be tricky because you don't know what the patient is exposing themselves to and the allergen could be at work or home."

Contact dermatitis can affect up to 6% of the U.S. population.

The case report Dhamija discussed before the ACAAI involved a patient who visited a hospital emergency room three times during the spring with complaints of a facial rash and eyelid swelling. The patient was sent home with prednisone and was seen one to two weeks later during a telemedicine appointment during which he reported the rash had been going on for two weeks.

Physicians realized the rash occurred where the elastic parts of his facial mask would rest, explains Kristin Schmidlin, MD, an assistant professor in the UC Division of Immunology, Allergy, and Rheumatology and co-author of the abstract at ACAAI.

Schmidlin said physicians reduced the amount of prednisone and advised use of topical triamcinolone, a steroid that helps reduce inflammation and is commonly used in treating mouth sores. She said the patient was also advised to use a cotton-based, dye-free mask without elastic.

The patient was able to find a cloth mask and reported improved symptoms a week later, said Schmidlin.

The Centers for Disease Control and Prevention offers some guidelines for making masks at home and that's a starting point for individuals with contact dermatitis.

"Instead of using elastics in a facial mask, I would modify it and use cotton-based knot ties around the back of the head to hold the mask in place," says Dhamija. "We also advise patients to call companies that make facial masks to find out what's in the product if labeling does not contain enough details."

"There are immune reactions to allergens that can be life-threatening but when it comes to contact dermatitis, it doesn't escalate that far. We can quickly identify the allergen and stop the offending agent. But, some cases can be severe," said Dhamija. "Treatment usually means avoiding the agent or we can use a topical or oral steroid if needed. It depends on how severe the reaction is and how much of the body is affected. We also take into account how it is impacting the patient's life or ability to work, for example."

"Patch testing is a tool we use to detect contact dermatitis," said Dhamija. "It's good to speak with your primary care doctor or ask for a referral to an allergist if you have concerns. Patch testing involves placing a compound we suspect is a problem to your skin. We have you return a few days later and we see if there is a reaction."

Dhamija said there is abundant literature documenting patients with contact dermatitis because of allergens such as elastic bands in FFP2 masks, N95 respirators, neoprene rubber masks and medical masks containing formaldehyde or rubber components using carbamates or thiurams.

Each year, health care practitioners at Brigham and Women's Hospital place over a million orders through the electronic health records (EHR) system. Even though studies indicate that practitioners place more than 99.9 percent of orders for the correct patients, researchers at the Brigham analyzed that remaining 0.1 percent to determine and address the root causes of wrong-patient order errors. In an effort to improve patient safety, the Brigham required headshots for participating patients to be displayed in their EHR as part of a quality improvement program in the Emergency Department. Analysis of the millions of orders placed for participating patients over a two-year span showed the rate of wrong patient order entry to be 35 percent lower for patients whose photos were included in their EHR. Results are published in JAMA Network Open.

"There's one specific solution to mitigating wrong-patient errors that turned out to be really effective: displaying patient's photos in their electronic chart. As a provider, these are patients that you know personally -- you've cared for them and you're going to quickly recognize that face," said Hojjat Salmasian, MD, MPH, PhD, of the Department of Quality and Safety at the Brigham.

Salmasian had previously collaborated on a project in which pop-up alerts were used to reduce wrong-patient errors. Unlike interruptive pop-up alerts, including patient photos in EHRs enables uninterrupted navigation and utilizes the natural human affinity for facial recognition. Promising results from smaller-scale studies looking at the implementation of patient photos to decrease wrong patient order entry (WPOE) inspired Salmasian and his colleagues to pursue this larger-scale test at the Brigham.

The researchers focused on the Emergency Department, where providers often multitask and, consequently, have a higher rate of errors. In a retrospective cohort of patients admitted between July 2017 and June 2019, photos taken of willing patient participants and corresponding orders placed were analyzed for error. Of 2.5 million total orders placed across 71,851 unique patients, there was a decrease in errors of 35 percent. Salmasian emphasized the sheer volume of orders this 35 percent amasses to when considering the millions of orders placed per year at the Brigham, saying without this photo implementation an estimated 2 in every 1,000 orders may be placed incorrectly in the ED.

This improvement in error risk was slightly more detectable in white patients, a finding that illuminates implicit bias, treatment inequities, and the patient care impact of having a predominantly white patient population. The Brigham and Mass General Brigham have plans to include photos of all participating patients in their electronic health records. Despite the barrier COVID-19 has caused, with masks being required of all patients, hospitals locally and across the country plan to integrate this photo feature as soon as they are able. As requests to include a headshot in one's electronic health record increase, patients will begin to realize their actions -- even as small as uploading a headshot to a healthcare portal -- can have a huge impact on their health outcomes.

"It's important for all of us to realize that there are things that we can do as patients that directly impact the appropriateness and safety of care that we receive," said Salmasian. "If more patients engage in the care they receive, our health care system improves in both safety and quality."

Exercising more than once per week is associated with a lower risk of developing Alzheimer's disease in patients with mild cognitive impairment, research published in the open access journal Alzheimer's Research and Therapy suggests. Mild cognitive impairment is a condition that causes people to have more problems with memory and thinking than is normal for someone their age. People with mild cognitive impairment have a ten-fold higher risk of developing Alzheimer's disease than the general population.

A team of researchers from Yonsei University College of Medicine, Republic of Korea, found that compared with people with mild cognitive impairment who did not exercise, those who carried out vigorous or moderate physical activity for at least ten minutes more than once per week had an 18% lower risk of developing Alzheimer's disease. Among those who exercised more than once per week, people with mild cognitive impairment who exercised three to five times per week had a 15% lower risk of developing Alzheimer's disease than those who exercised less than three to five times per week.

Those with mild cognitive impairment who started exercising after their diagnosis had an 11% lower risk of developing Alzheimer's disease than people who did not exercise at all. Stopping exercise after being diagnosed with mild cognitive impairment was associated with the same risk of developing Alzheimer's disease as not exercising before or after diagnosis.

Hanna Cho, the corresponding author said: "Our findings indicate that regular physical activity may protect against the conversion of mild cognitive impairment to Alzheimer's disease. We suggest that regular exercise should be recommended to patients with mild cognitive impairment. Even if a person with mild cognitive impairment did not exercise regularly before their diagnosis, our results suggest that starting to exercise regularly after diagnosis could significantly lower their risk of developing Alzheimer's disease."

The authors used electronic health record data of people diagnosed with mild cognitive impairment from the National Health Insurance Service cohort of Korea from 2009 to 2015. The average age of participants was between 64 and 69 years. Physical activity was measured using a questionnaire asking participants how much they had exercised in the previous seven days.

Out of the 247,149 participants included in the study, 99,873 (40%) did not exercise regularly, 45,598 (18%) began exercising after being diagnosed with mild cognitive impairment, 45,014 (18%) stopped exercising after diagnosis and 56,664 (23%) exercised more than once per week before and after diagnosis. By the end of the follow-up period, 8.7% of those who did not exercise were diagnosed with Alzheimer's disease compared with 4.8% of those who exercised more than once per week. Of those who began exercising after diagnosis, 6.3% went on to develop Alzheimer's, compared to, 7.7% of those who stopped exercising after diagnosis.

The authors suggest that regular exercise may increase the production of molecules that support the growth and survival of neurons or increase blood flow to the brain, which could prevent a reduction in brain volume that is often associated with dementia.

The authors caution that as information on physical activity was collected at two time points during the study, it is unknown whether the type, intensity, duration or frequency of participants' exercise changed at any other points during the study period. Further research is needed to assess how long the protective effect of regular physical activity against Alzheimer's disease lasts and to investigate the biological mechanisms underlying the protective effect.

Researchers at Helmholtz Zentrum München together with LMU University Eye Hospital Munich and the Technical University of Munich (TUM) created a novel deep learning method that makes automated screenings for eye diseases such as diabetic retinopathy more efficient. Reducing the amount of expensive annotated image data that is required for the training of the algorithm, the method is attractive for clinics. In the use case of diabetic retinopathy, the researchers developed a screening algorithm that needs 75 percent less annotated data and achieves the same diagnostic performance of human experts.

In recent years, clinics have taken first steps towards artificial intelligence and deep learning to automate medical screenings. However, training a deep learning algorithm for accurate screening and diagnosis prediction requires large sets of annotated data and clinics often struggle with expensive expert labelling. Researchers were therefore looking for ways to reduce the need for costly annotated data while still maintaining the high performance of the algorithm.

Use case diabetic retinopathy

Diabetic retinopathy is a diabetes-related eye disease damaging the retina and can ultimately lead to blindness. Measuring the retinal thickness is an important procedure to diagnose the disease in risk patients. To do so, most clinics take photographs of the fundus - the surface of the back of the eye. In order to automate the screening of these images, clinics started to apply deep learning algorithms. These algorithms require large sets of fundus images with expensive annotations in order to be trained to screen correctly.

The LMU University Eye Hospital Munich owns a population-size data set containing over 120,000 unannotated fundus and co-registered OCT images. OCT (optical coherence tomography) allows for precise information about the retinal thickness but is not commonly available in every eye care center. The LMU provided their data to researchers from Helmholtz Zentrum München pioneering in the field of artificial intelligence in health.

Pre-training under "self-supervision"

"Our goal was to use this uniquely large set of fundus and OCT images to develop a method which will reduce the need of expensive annotated data for algorithm training", says Olle Holmberg, first author of the study from Helmholtz Zentrum München and TUM School of Life Sciences.

The group of researchers developed a novel method called "cross modal self-supervised retinal thickness prediction" and applied it to pre-train a deep learning algorithm with the LMU data set. In this use case, cross modal self-supervised learning allowed the algorithm to teach itself to recognize unannotated fundus images with different OCT-derived retinal thickness profiles, predicting the thickness information directly from the fundus. By accurately predicting retinal thickness, a key diagnostic feature for diabetic retinopathy, the algorithm was then able to learn how to predict screening outcomes.

High performance with a quarter of training data

This novel method shrunk the need for expensive annotated data to train the deep learning algorithm significantly. When applied in automated screenings for diabetes retinopathy, it achieved the same diagnostic performance, both, compared to previous algorithms which had required much more training data and compared to human experts.

"We reduced the need for annotated data by 75 percent", states Prof. Fabian Theis, who led the study as Director of the Institute of Computational Biology at Helmholtz Zentrum München and Scientific Director of Helmholtz AI, the artificial intelligence platform of the Helmholtz Association. "Sparse annotated data is a grand challenge in medicine. It is one of our goals to develop methods that work with less data and that can then potentially be applied in many settings. Our use case in diabetic retinopathy is ready for immediate use in clinics and is a perfect example of how AI can improve the daily business of clinics and thus everybody's health."

"Automated detection and diagnosis of sight-impairing diabetic retinopathy with widely available fundus photography is a big improvement for screenings. Patient referrals to partly overcrowded specialized eye care centers could thus be reduced as well" says Dr. med. Karsten Kortuem, LMU University Eye Hospital Munich, who was responsible for the clinical side of this study.

Moreover, an additional reduction in size, meaning number of parameters, was achieved in the algorithm itself. The novel method enables up to 200 times smaller algorithms. This could be a crucial benefit to deploying them on mobile and embedded devices which is also important in clinical settings.

Applications beyond diabetic retinopathy

Beyond diabetic retinopathy, the novel method allows for further clinical applications where much unannotated data is available but expert annotations are scarce, such as age-related macular degeneration (AMD).

In a preliminary study of COVID-19 patients with mild-to-moderate disease who were attempting to recover in their homes, researchers at Washington University School of Medicine in St. Louis have found that the drug fluvoxamine seems to prevent some of the most serious complications of the illness and make hospitalization and the need for supplemental oxygen less likely.

The study, a collaboration between the university's Department of Psychiatry and Division of Infectious Diseases, involved 152 patients infected with SARS-CoV-2, the virus that causes COVID-19. Researchers compared the outcomes of those treated with fluvoxamine to the outcomes of those given an inactive placebo. After 15 days, none of the 80 patients who had received the drug experienced serious clinical deterioration. Meanwhile, six of the 72 patients given placebo (8.3%) became seriously ill, with four requiring hospitalization.

The study is published online Nov. 12 in the Journal of the American Medical Association.

"The patients who took fluvoxamine did not develop serious breathing difficulties or require hospitalization for problems with lung function," said the paper's first author, Eric J. Lenze, MD, the Wallace and Lucille Renard Professor of Psychiatry. "Most investigational treatments for COVID-19 have been aimed at the very sickest patients, but it's also important to find therapies that prevent patients from getting sick enough to require supplemental oxygen or to have to go to the hospital. Our study suggests fluvoxamine may help fill that niche."

Fluvoxamine is used commonly to treat obsessive-compulsive disorder (OCD), social anxiety disorder and depression. It is in a class of drugs known as selective serotonin-reuptake inhibitors (SSRIs), but unlike other SSRIs, fluvoxamine interacts strongly with a protein called the sigma-1 receptor. That receptor also helps regulate the body's inflammatory response.

"There are several ways this drug might work to help COVID-19 patients, but we think it most likely may be interacting with the sigma-1 receptor to reduce the production of inflammatory molecules," said senior author Angela M Reiersen, MD, an associate professor of psychiatry. "Past research has demonstrated that fluvoxamine can reduce inflammation in animal models of sepsis, and it may be doing something similar in our patients."

Reiersen said the drug's effects on inflammation could prevent the immune system from mounting an overwhelming response, which is thought to occur in some COVID-19 patients who seem to improve after a few days of illness and then worsen. Many of those patients end up hospitalized, and some die.

In an innovative twist to research during the pandemic, the study was conducted remotely. When a symptomatic patient tested positive and enrolled in the study, research staff delivered the medication or inactive placebo to them, along with thermometers, automatic blood pressure monitors and fingertip oxygen sensors.

"Our goal is to help patients who are initially well enough to be at home and to prevent them from getting sick enough to be hospitalized," said Caline Mattar, MD, an assistant professor of medicine in the Division of Infectious Diseases. "What we've seen so far suggests that fluvoxamine may be an important tool in achieving that goal."

For two weeks, subjects took either the antidepressant drug or placebo sugar pills while having daily interactions with members of the research team -- via phone or computer. That allowed patients to report on their symptoms, oxygen levels and other vital signs. If patients suffered shortness of breath or were hospitalized for pneumonia, or their oxygen saturation levels fell below 92%, their conditions were considered to have deteriorated.

"The good news is that not a single person taking the active medication experienced deterioration," Reiersen said. "We believe this drug may be the reason, but we need to study more patients to make sure."

The researchers will begin a larger study in the next few weeks. Lenze, the director of the Healthy Mind Lab at the School of Medicine, is an expert in using mobile and internet technology to conduct clinical trials. He said that although this initial study involved patients in the St. Louis region, the next phase of the research will involve patients from throughout the country.

"We bring the study to the patients, giving them tools to monitor their health at home," Lenze said. "Our hope is that we can keep these patients healthy enough to avoid hospitalization."

Ongoing support for several years and focus on the individual. These are success factors that make physical activity on prescription a workable concept for patients, including those who, after six months, have not reached their desired physical activity level, a University of Gothenburg thesis shows.

The thesis concerned comprises studies of 444 patients in Sweden who were offered what is known as "physical activity on prescription" (PAP) in primary care. These patients attended 15 different health centers in Gothenburg.

After six months, 73% had increased their physical activity (PA) and 42% had reached an adequate activity level -- that is, 150 minutes or more weekly. Brisk walks were the most common form of activity.

Overall for the group, positive effects were verified for weight, waist measurement, blood pressure, blood sugar, and lipids (blood fats) -- and also for their assessed quality of life. These effects were most pronounced in the patients who initially had the lowest PA level.

For the first time in a research context, the scientists then studied the 190 patients whose PA, after six months' PAP treatment at a health center, was still inadequate -- that is, those who were physically active less than 150 minutes a week.

These patients were randomly selected for a further two years' PAP, supported by either the health care center or a physiotherapist. Both treatments boosted the patients' PA levels, metabolic health, and quality of life, with equivalent cost-effectiveness. The positive health effects also seemed to be independent of changes in their medication.

"Nor did we see any worsened metabolic rates at the two-year follow-up point. That's important because this patient group has elevated risks of developing metabolic syndrome, type 2 diabetes, and cardiovascular disease," says Stefan Lundqvist, PhD at Sahlgrenska Academy, University of Gothenburg, and physiotherapist at the Center for physical activity, Region Västra Götaland; an organization providing education, working materials, a register of local availability of PA, and helping co-workers organize the structure of PAP routines in the primary health care units,.

"In our view, the continuous support, individualization, and long duration of the treatment are key factors in the patients' success in increasing and maintaining their physical activity."

PAP treatment comprises three main parts: individual consultation with the patient, tailored physical activity with a written prescription, and structured follow-up. The purpose is to increase PA in physically inactive patients with, for instance, metabolic risk factors such as obesity, abdominal obesity, high blood pressure, and disorders in blood-sugar levels and lipid balance.

How well the patients manage with the PAP treatment is affected by confidence in their own ability to change PA, according to the thesis. This confidence was measured by means of a 100-mm visual analog scale (VAS) that, according to Lundqvist, is both simple and practical to use in clinical practice.

"Measuring the patient´s confidence in readiness to change PA, at the start of PAP treatment, can give both the patient and me, as a care provider, vital information that enables better adaptation of support for the patient," Lundqvist says.

In his opinion, the thesis findings can facilitate implementation of PAP as an important healthcare method for attaining the positive health effects in physically inactive patients subject to metabolic risk factors.

"Our experience in this research field shows that optimizing patient support requires trained, skilled co-workers with good knowledge of PAP treatment, but also orderly routines and support from the organization and management," Lundqvist concludes.

A growing body of evidence points to the health risks of using e-cigarettes (or "vaping"). But because e-cigarettes are marketed as a less harmful alternative to traditional cigarettes, it has been difficult to tell whether the association between vaping and disease is just a matter of smokers switching to vaping when they start experiencing health issues.

Now, a study by researchers from the Boston University School of Public Health (BUSPH) and School of Medicine (BUSM) is one of the first to look at vaping in a large, healthy sample of the population over time, independently from other tobacco product use.

Published in JAMA Network Open, the study found that participants who had used e-cigarettes in the past were 21% more likely to develop a respiratory disease, and those who were current e-cigarette users had a 43% increased risk.

"This provides some of the very first longitudinal evidence on the harms associated with e-cigarette products," says corresponding author Dr. Andrew Stokes, assistant professor of global health at BUSPH.

"In recent years we have seen dramatic increase in e-cigarette use among youth and young adults which threatens to reverse decades of hard-fought gains," Stokes says. "This new evidence also suggests that we may see an increase in respiratory disease as youth and young adults age into midlife, including asthma, COPD, and other respiratory conditions."

Most previous research on the respiratory health effects of vaping have used animal or cell models, or, in humans, only short-term clinical studies of acute conditions.

For this study, the researchers used data on 21,618 healthy adult participants from the first four waves (2013-2018) of the nationally-representative Population Assessment of Tobacco and Health (PATH), which is the most comprehensive national survey of tobacco and e-cigarette-related information to date.

To make sure they weren't simply seeing cigarette smokers switching to e-cigarettes specifically because of health issues (rather than vaping itself causing these issues), the researchers only included people with no reported respiratory issues when they entered PATH, and adjusted for a comprehensive set of health conditions. They also adjusted for having ever used other tobacco products (including cigarettes, cigars, hookah, snus, and dissolvable tobacco) and for marijuana use, as well as childhood and current secondhand smoking exposure. They repeated the analyses among subgroups of healthy respondents who had no self-reported chronic conditions, and whose self-rated overall health was good, great, or excellent.

Adjusting for all of these variables and for demographic factors, the researchers found that former e-cigarette use was associated with a 21% increase in the risk of respiratory disease, while current e-cigarette use was associated with a 43% increase. Current e-cigarette use was associated with a 33% increase in chronic bronchitis risk, 69% increase in emphysema risk, 57% increase in chronic obstructive pulmonary disease (COPD) risk, and 31% percent increase in asthma risk.

"With a longitudinal study design and extensive sensitivity analyses, the study adds to a growing body of evidence indicating long-term health risks of e-cigarette use to the respiratory system," says study lead author Wubin Xie, a postdoctoral associate in the Department of Global Health at BUSPH.

Evidence of the health effects of vaping, from this and other studies, also "highlight the importance of standardizing documentation of e-cigarette product use in electronic health records, and pushing the CDC to develop International Classification of Diseases codes for e-cigarette product use, so that providers can facilitate cessation discussions and identify adverse events related to e-cigarette use," says study co-author Dr. Hasmeena Kathuria, associate professor of pulmonary medicine and a member of the Pulmonary Center at BUSM.