Culture

The investigational drug evinacumab reduced low-density lipoprotein (LDL) cholesterol to near-normal levels among patients with a rare cholesterol disorder, meeting the primary endpoint in the first randomized placebo-controlled trial of the drug, which is being presented at the American College of Cardiology's Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC).

Homozygous familial hypercholesterolemia (HoFH) is an inherited condition characterized by extremely high cholesterol levels from birth. Many patients with HoFH develop coronary artery disease and face a high risk of heart attacks and other cardiac events even before reaching age 20.

"For the first time, we were able to get these patients with HoFH to remarkably normal LDL cholesterol levels," said Frederick J. Raal, PhD, head of the Division of Endocrinology and Metabolism at the University of Witwatersrand, Johannesburg, South Africa, and lead author of the Phase 3 trial. "It's the most potent cholesterol-lowering drug we've seen for this very difficult-to-treat group of patients."

Patients with HoFH usually have two defective copies of the LDL receptor gene that is the main cause of the disorder and typically have LDL cholesterol levels that are increased four-fold or more compared to those with only one defective gene (heterozygous FH) whose LDL cholesterol are about twice normal. To keep LDL cholesterol levels in check, most patients with HoFH take a combination of three medications--a "triple therapy" that consists of a high intensity statin, a PCSK9 inhibitor and ezetimibe, a drug that limits the absorption of cholesterol from the intestine. If those measures are insufficient, patients undergo lipoprotein apheresis to mechanically remove excess LDL cholesterol from the blood, a costly procedure that many patients undergo several times per month.

Evinacumab is a monoclonal antibody that binds to angiopoietin-like protein 3 (ANGPTL3), a protein thought to play a role in cholesterol metabolism. Subjects with low or absent ANGPLT3 due to a genetic cause have very low cholesterol levels and rarely suffer from atherosclerotic cardiovascular disease. By targeting ANGPTL3, evinacumab is designed to reduce cholesterol through a different mechanism than any existing drug.

Researchers enrolled 65 patients with HoFH. About three-quarters of the patients were on triple therapy and one-third were also on regular apheresis at the start of the trial. Patients continued their regular therapy throughout the study. Two-thirds of patients were randomly assigned to receive evinacumab via intravenous infusion every four weeks for 24 weeks, while one-third of participants received placebo infusions.

Patients receiving evinacumab had a striking reduction in LDL cholesterol starting at week two. At week 24, average LDL cholesterol levels among those receiving evinacumab had plummeted by 47.1% while LDL cholesterol levels among those receiving placebo rose by 1.9%, resulting in an average relative reduction of 49% among those receiving evinacumab, meeting the trial's primary endpoint.

In terms of absolute LDL cholesterol levels, patients receiving evinacumab had an average drop of 132 mg/dL. Nearly a half of those receiving evinacumab achieved an LDL cholesterol below 100 mg/dL.

"The results are remarkable," Raal said. "This is a promising add-on therapy for individuals with homozygous FH that addresses the unmet need to further lower LDL cholesterol in these patients."

Reductions in LDL cholesterol with evinacumab were similar in HoFH patients with absent LDL receptor function (null/null) and in those with some residual LDL receptor function (non-null). This is of major clinical significance, as null/null HoFH patients have the highest cardiovascular risk and are least responsive to currently available lipid-lowering drugs, Raal said.

Adverse events were fairly common, occurring in 65.9% of patients receiving evinacumab and 81% of those receiving placebo. The most common adverse events were a cold, headache, fever, diarrhea and toothache. No serious adverse events were considered to be related to the study treatment, Raal said.

The relatively short duration of treatment and the small number of patients limit the trial's ability to draw conclusions regarding the long-term safety of evinacumab. The researchers plan to continue the study with an open-label extension to determine longer-term safety of evinacumab in this difficult-to-treat population.

Rochester, MN, March 30, 2020 - Patients with underlying health conditions such as hypertension, heart failure, and chronic kidney disease are at increased risk of severe coronavirus disease 2019 (COVID-19). Physicians, healthcare professionals, researchers, and patients are actively debating the potential influence of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients during the COVID-19 outbreak. One of the ways the virus enters the body is through ACE2, the enzyme that converts angiotensin I to angiotensin II in the lungs and other tissues and organs, suggesting to some that the drugs may increase susceptibility to the virus and severity of the disease.

In a new review published in Mayo Clinic Proceedings, published by Elsevier, a group of scientists who have been working on the frontlines fighting the deadly virus in Spain, Italy, and the United States, dissect the controversy in considerable detail, to explain the level of evidence on this topic for clinicians. "In agreement with current guidelines, we recommend patients with hypertension should continue taking anti-hypertensive medications without interruption," says lead author Fabian Sanchis-Gomar, MD, PhD, of the Department of Physiology, Faculty of Medicine, University of Valencia and INCLIVA Biomedical Research Institute, Valencia, Spain; and Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.

After in-depth review of more than 60 published studies, Dr. Sanchis-Gomar and his coauthors conclude that, importantly, no studies have reported an increase in circulating ACE2 levels or expression thus far, and increased expression would not necessarily imply an increased risk of infection or disease severity. Their research included studies that suggest that elevated levels of angiotensin II, the target of renin-angiotensin-aldosterone system (RAAS) inhibitors such as ACEIs and ARBs, may foster acute respiratory distress syndrome (ARDS) in COVID-19 patients. Other research suggests that RAAS inhibitors may have a role to play in the treatment of COVID-19. The authors note, however, that much more research and evidence are needed.

In a video accompanying the article, co-author Carl J. Lavie, MD, of the John Ochsner Heart and Vascular Institute, Ochsner Clinical School - University of Queensland School of Medicine, New Orleans, LA, USA, says, "Angiotensin II is known to foster inflammation, oxygenation, vasoconstriction, and fibrosis, so it is quite conceivable that a pharmaceutical agent that can inhibit the production of this hormone could actually be very beneficial for preventing lung injury and also for systemic health. Certainly, it is premature right now to start these agents as a preventive measure for COVID-19 in patients with no other indicator for RAAS inhibitors. However, this is an active area for investigation."

Current evidence indicates that RAAS inhibitors significantly reduce mortality in cardiovascular disease, reduce the progression of chronic kidney disease, and are the cornerstone of treatment for heart failure and hypertension. "ACEIs or ARBs therapy should be maintained or initiated, as indicated, in patients regardless of COVID-19," notes Dr. Sanchis-Gomar.

While no differences exist between ARBs and ACEIs in terms of efficacy to decrease blood pressure and improve other outcomes, a cough sometimes associated with the use of ACEIs, and withdrawal rates due to adverse events are lower with ARBs. "Given the equal efficacy but fewer adverse events, ARBs could potentially be a more favorable treatment option in COVID-19 patients at higher risk for developing severe forms of the disease," says Dr. Sanchis-Gomar.

GAINESVILLE, Fla. --- The mighty Calusa ruled South Florida for centuries, wielding military power, trading and collecting tribute along routes that sprawled hundreds of miles, creating shell islands, erecting enormous buildings and dredging canals wider than some highways. Unlike the Aztecs, Maya and Inca, who built their empires with the help of agriculture, the Calusa kingdom was founded on fishing.

But like other expansive cultures, the Calusa would have needed a surplus of food to underwrite their large-scale construction projects. This presented an archaeological puzzle: How could this coastal kingdom keep fish from spoiling in the subtropics?

A new study points to massive structures known as watercourts as the answer. Built on a foundation of oyster shells, these roughly rectangular enclosures walled off portions of estuary and likely served as short-term holding pens for fish before they were eaten, smoked or dried. The largest of these structures is about 36,000 square feet - more than seven times bigger than an NBA basketball court - with a berm of shell and sediment about 3 feet high. Engineering the courts required an intimate understanding of daily and seasonal tides, hydrology and the biology of various species of fish, researchers said.

The watercourts help explain how the Calusa could rely primarily on the sea.

"What makes the Calusa different is that most other societies that achieve this level of complexity and power are principally farming cultures," said William Marquardt, curator emeritus of South Florida Archaeology and Ethnography at the Florida Museum of Natural History. "For a long time, societies that relied on fishing, hunting and gathering were assumed to be less advanced. But our work over the past 35 years has shown the Calusa developed a politically complex society with sophisticated architecture, religion, a military, specialists, long-distance trade and social ranking - all without being farmers."

The fact that the Calusa were fishers, not farmers, created tension between them and the Spaniards, who arrived in Florida during the 16th century when the Calusa kingdom was at its zenith, said study lead author Victor Thompson, director of the University of Georgia's Laboratory of Archaeology.

"The Spanish soldiers, priests and officers were used to dealing with agriculturalists, such as the people they colonized in the Caribbean who grew maize surpluses for them," Thompson said. "This would not have been possible with the Calusa. In fact, in a late 1600s mission attempt by the Franciscans, hoes were unloaded off the ship, and when the Calusa saw this, they remarked, 'Why didn't they also bring slaves to till the ground?'"

Thompson, Marquardt and colleagues analyzed two watercourts along the southwest shore of Mound Key, an island in Estero Bay off Florida's Gulf Coast and the seat of Calusa power for about 500 years.

These courts, still visible today, flank the grand canal, a marine highway nearly 2,000 feet long and averaging 100 feet wide, which bisects the key. Both have yards-long openings in the berms along the canal, possibly to allow Calusa to drive fish into the enclosures, which could then be closed with a gate or net.

The team studied the watercourts and surrounding areas using remote sensors, cores of sediment and shell and excavations. The bisected key features two large shell mounds, one on either side of the island. Remote sensing showed slopes leading from the watercourts to the top of the mounds, which may have been causeways for transporting food. On the shoreline, researchers found evidence of burning and small post molds, possibly for racks used to smoke and dry fish.

Radiocarbon dating suggests the watercourts were built between A.D. 1300 and 1400 - around the end of a second phase in the construction of a king's manor, an impressive structure that would eventually hold 2,000 people, according to Spanish documents.

A.D. 1250 also corresponds to a drop in sea level, which "may have impacted fish populations enough to help inspire some engineering innovation," said Karen Walker, Florida Museum collection manager of South Florida Archaeology and Ethnography.

Fish bones and scales found in the western watercourt show the Calusa were capturing mullet and likely pinfish and herring, all schooling species. Florida Gulf Coast University geologist Michael Savarese's analysis of watercourt core samples revealed dark gray sediment that was rich in organic material, suggesting poor circulation. High tide would have refreshed the water to some extent, Marquardt said.

"We can't know exactly how the courts worked, but our gut feeling is that storage would have been short-term - on the order of hours to a few days, not for months at a time," he said.

While researchers previously hypothesized watercourts were designed to hold fish, this is the first attempt to study the structures systematically, including when they were built and how that timing correlates with other Calusa construction projects, Marquardt said.

The Calusa dramatically shaped their natural environment, but the reverse was also true, Thompson said.

"The fact that the Calusa obtained much of their food from the estuaries structured almost every aspect of their lives," he said. "Even today, people who live along coasts are a little different, and their lives continue to be influenced by the water - be it in the food they eat or the storms that roll in on summer afternoons in Southwest Florida."

When news of the coronavirus emerged from Wuhan, China, Kunlin Jin, PhD, and a team of international researchers quickly joined forces to fight the mysterious disease.

Dr. Jin relied on his more than 20 years of knowledge about stem cells to work with an international team driven to save lives. He used the messaging app WeChat to bridge the distance between his laboratory at The University of North Texas Health Science Center at Fort Worth, and experts in China.

"A lot of people are trying find the answers," said Dr. Jin, who spends most of his time working alongside graduate students on stem cell therapies to fight strokes at the HSC Institute for Healthy Aging.

Dr. Jin and his colleagues used a 21st century solution to address an unfolding pandemic. Instead of finding the next Tamiflu, they started testing whether stem cells can be used to boost a person's immune system to ward off COVID-19 pneumonia.

Dr. Jin said early findings are promising, and their international effort to test this treatment continues as a long-term study with more patients in China.

"I am proud to be part of the team I work with to fight COVID-19," Dr. Jin said. "Our study showed that intravenous infusion of clinical-grade human mesenchymal stem cells is a safe and efficient approach for treating patients with COVID-19 pneumonia, including in elderly patients displaying severe pneumonia."

Dr. Jin and his colleagues worked in real time. He said they had a sense of urgency because the outbreak "posed great threats to global public health."

As part of the experimental treatment, stem cells were injected intravenously into the bloodstream of seven patients in Beijing who were severely sick. Three patients were injected with a placebo, the study states.

The people tested were patients at YouAn Hospital in Beijing, Dr. Jin said. Testing began on Jan. 30, according to the study.

The seven patients who received stem cells were successfully treated and were discharged from the hospital within 14 days, Dr. Jin said. Of the patients who received the placebo, one died, one became severe and the third had Acute Respiratory Distress Syndrome (ARDS).

Before stem cells can be used in the United States to fight the virus, there would have to be clinical trials in this country and approval from the U.S. Food and Drug Administration.

The team's findings will be included in the upcoming April 2020 issue of Aging and Disease." The article is titled: "Transplantation of ACE2-Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia."

As international headlines about the virus evolved, research and clinical colleagues from several countries, including the United States, United Kingdom, South Korea, China and Russia pooled their expertise.

The team is made up of medical researchers who meet at conferences and often discuss science, aging and health-related issues. They work together as part of the International Society on Aging and Disease, which was founded by Dr. Jin.

When coronavirus strikes, it can result in a virus-induced cytokine storm - the term used when the immune system is so triggered that fluids fill the lungs and tissues are damaged.

"This is thought to be one of the main reasons why the COVID-19 pneumonia actually kills an individual - this storm of activity trying to fight the virus," said David P. Siderovski, PhD, Professor and Chair Pharmacology & Neuroscience in HSC's Graduate School of Biomedical Sciences.

"No specific drugs or vaccines are available to cure the patients with COVID-19 infection," according to the journal article. "Hence, there is a large unmet need for a safe and effective treatment for COVID-19 infected patients, especially the severe cases."

Additionally, finding antivirals for patients with COVID-19 is a difficult task, Dr. Siderovski said.

"When HIV broke in the 1980s, we scrambled to make AZT (azidothymidine)," he said, adding that researchers are trying different ideas to combat the virus. "There is a desperate need for anything - anything experimental, anything that could be tried off the shelf to address COVID-19 pneumonia."

A majority (56%) of New York City residents did not think the assistance provided by the federal government for NYC and the state as a whole is sufficient to manage the current coronavirus crisis. Only 22% thought assistance was sufficient, with the remaining 23% unsure. The findings are part of the third week of data from a city and statewide CUNY Graduate School of Public Health & Health Policy (CUNY SPH) tracking survey conducted March 27-29.

As social distancing extends under Governor Cuomo's PAUSE order, the number of New Yorkers who reported feeling "not at all" socially connected in the past week rose to 43%, nearly doubling the percentage (22%) of those who felt similarly isolated the previous week.

The strain of the pandemic is taking its toll on the mental health of New York residents; 44% reported feeling nervous, anxious or on-edge more than half the time (at least 3-4 days a week or more often), while 35% reported similar levels of feeling down, depressed, or hopeless.

Health concerns

As the number of confirmed cases in the city and state surged this week, perceived risk of contracting COVID-19 also increased, with well more than half the respondents (55%) thinking they have a high or very high risk of getting sick with coronavirus, compared to 39% the previous week.

Similarly, consistent with the mounting number of confirmed cases, another major shift in the latest tracking survey saw 28% of respondents reporting they personally knew someone who tested positive for coronavirus, double the result (14%) from the previous week.

In an additional a new finding, one in eight New Yorkers (12%) reported that someone in their household was sick at home with symptoms of COVID-19. This was even higher among respondents in the 18-29 age group, with nearly one in six (15.9%) reporting someone sick at home with a fever or other symptoms.

"We continue to see a generational divide in our tracking survey," said Scott Ratzan MD, distinguished lecturer at CUNY SPH and editor in chief, Journal of Health Communication. "Younger New Yorkers believe they have a significantly higher chance of getting sick than their older counterparts, and this finding has been consistent for the last three weeks."

"As older people are most likely to suffer serious health consequences from COVID-19, we would expect them to be most concerned about their risk," Dr. Ratzan explained. "It may be that our public health communication on risk and consequences of getting COVID-19 are not reaching older people adequately."

The pandemic is impacting the healthcare of New Yorkers in ways unrelated to the COVID-19 illness. More than a third (35%) of respondents reported the cancellation of medical care for other health problems due to the epidemic, and almost one respondent in 10 (9%) reported losing their health insurance as a result of virus-related job loss.

Economic concerns

Job loss is an escalating problem, with 36% in the city reporting that someone in their household had lost their job as a result of the virus, almost a 25% increase over the job loss of 29% reported in the previous week. Job losses continued to affect the Hispanic community disproportionately, with 46% reporting a household job loss. Women (42%) were more affected by job loss than men (29%), a significantly different finding from last week's survey results. Lower income (less than $50,000) workers were almost twice as likely to report household job loss at 41%, than the highest earners (more than $100,000), 24% of whom reported job loss.

"It is clear that the economic burden of coronavirus is falling disproportionately on the people in our city who are least able to afford it," said Dr. Ayman El-Mohandes, dean of CUNY SPH. "It remains to be seen how well we can address these disparities."

More than two in five New Yorkers (44%) say they are concerned about their housing situation; 27% said they would not be able to pay next month's rent and 17% said they could not meet next month's mortgage payment. A substantial majority (59%) of those unable to pay rent fear they will be evicted.

About a third of residents (33%) are considering moving out of the city, with 12% saying they would move within New York state and 21% considering moving out of state, a troubling finding considering the current importance of people staying at home as much as possible. Two-thirds (67%) said they were not considering moving out of the city.

Other key findings

Despite respondents reporting an increased perception of the likelihood of contracting the virus, only 22% of respondents sought healthcare or advice from a health professional about coronavirus this past week, down by one-third from the two previous weeks, when 34% reported seeking medical care or advice.

There was an increase in those who said they were tested, with 5% reporting they had a nasal or throat swab performed by a medical professional; about one-fourth of those tested reporting testing positive for the virus.

A majority (62%) of New York City residents said they would take a vaccine for coronavirus right now if it were available; 19% would not and an additional 19% were unsure.

A majority (56%) think that asking New Yorkers who leave the state to self-quarantine for two weeks is helpful in containing the spread, 23% are unsure and 21% think it is not helpful.

Stress restructures the brain by halting the production of crucial ion channel proteins, according to research in mice recently published in JNeurosci.

Stress harms the brain and body in profound ways. One way is by altering astrocytes, the brain's housekeepers tasked with mopping up neurotransmitters after they've been released into the synapse. On the cellular level, stress causes the branches of astrocytes to retract from the synapses they wrap around.

Bender et al. investigated what controlled astrocyte changes after mice experienced exposure to the urine of a fox, their natural predator. This single stressful event caused quick but long-lasting retraction of the astrocyte's branches. Stress induces this change by halting the production of GluA1, an essential subunit of glutamate receptors. During a stressful event, the stress hormone norepinephrine suppresses a molecular pathway that normally culminates in the protein synthesis of GluA1. Without functional GluA1 or glutamate receptors, neurons and astrocytes lose their ability to communicate with each other.

LAWRENCE -- In the midst of a global pandemic, a lot of people rightly will be reluctant to offer food from their plate to another person, or accept such an offer due to the fear of contamination.

But for people with "attachment avoidance," a psychological term for reluctance to form close personal relationships, this was true long before anybody had heard the term "COVID-19."

"When we share food, it shows trust -- it shows we're willing to give up some of our resources, and it shows we want to get close with someone," said Omri Gillath, professor of psychology at the University of Kansas. "Think about the psychological aspect of comfort food. When people are feeling down, when they're upset, when they're stressed, food is a source of comfort. We think in part this is because of the connection between food and love. If you think about breastfeeding, babies are getting both the food and the nutrition they need, and the warmth and love from their mom, this creates a strong connection between food and love."

Gillath is a co-author of a new paper, led by KU doctoral student Sabrina Gregersen, that examines the links between food-sharing and styles of attachment. It was just published in the peer-reviewed journal Appetite.

"'Attachment' is a theory that explains how people bond to each other and how they regulate their emotions," Gillath said. "People have an attachment style based on early interactions with their primary caregivers -- parents usually. The three main styles are secure, anxious and avoidant. If you have parents that were supportive and sensitive and find a good balance between helping you on the one hand and providing autonomy on the other, you're more likely to be secure. If you had parents that were insensitive and intrusive and weren't consistent about the help they provided, you're more likely to be anxious. And then if you had parents that were cold and rejecting, you are more likely to develop an avoidant attachment style. These differences that people develop pretty early predict a lot of relational behaviors and outcomes."

To see how these attachment styles affected people's food-sharing behaviors, the KU researchers conducted several studies. In one study, participants answered a battery of questions, many of which touched on how food preferences might be tied to romantic or dating behavior for people with various attachment styles. In a different study, participants were placed in a situation where they interacted with another person while one of them had a pack of fruit snacks.

"We brought people to the lab and had them fill out a few questionnaires, then we exposed them to either attachment-security-related cues or control cues," Gillath said. "For example, we asked them to think about a secure relationship, which activated their security-related models. Then we asked them to wait outside in a waiting area. In both studies they happened to meet another 'participant' in that area. In one study, we gave the participant a bag of treats and wanted to see if they would share it, and in the other study, we gave our confederate, who was supposedly another participant, a bag of treats and they offered to share. We wanted to see whether participants would accept the food offering. Many participants were reluctant to take food or give it. However, some people -- those who were exposed to security-related cues -- were more likely to share their treat with a stranger."

From the first study, the researchers found people high on attachment avoidance were less likely to share food or date a potential partner who had dissimilar food preferences. In the second study, they found enhancing attachment security increased the tendency to offer one's food to a fellow participant. In the final study, the team found the tendency to accept food from a fellow participant was positively associated with attachment anxiety, but security priming did not affect this tendency.

Gillath said a better understanding of the links between attachment and food could potentially help inform efforts to extend help to people during the current coronavirus pandemic -- particularly among people with high attachment avoidance, who, the authors wrote, "were less likely to engage in food sharing behaviors with current romantic partners and less likely to cook and eat meals with their partners."

"We could also use the findings to better understand people's tendencies when it comes to prosocial behavior," he said. "Right now, with the coronavirus crisis, trust -- or the lack of -- is a major obstacle. On the one hand, some people don't have food, they don't have a job, they don't have the means to support themselves. On the other hand, there are people who want to help others by giving them food or other resources but are afraid of the consequences. Fear and confusion -- of contamination or starvation -- may lead people to hoard, preventing them from sharing resources -- not giving to those who need them, or buying too much and not leaving to people who also might need -- see the rush to buy toilet paper. How can we fix that? If people aren't taking food because of trust issues, we should ask, 'Are you guys willing to starve (or not getting the right treatment because of your fears)?' I'm not saying we want to make people trust anyone and everyone; however, we do want to reduce anxiety, increase security and facilitate food -- and resource sharing -- in a safe way."

According to Gillath, in a crisis situation sharing and accepting food and other resources could have psychological benefits beyond just making sure people have enough to eat.

"Not having food and feeling insecure about the whole situation is definitely going to increase mental health issues -- whereas having food and having people looking out for you can not only keep people from starving but also potentially help with their mental health and anxieties," he said. "It is in times like these when we need to find a way to come together, reduce anxiety and help each other out. Making people feel secure can help with that."

Patients who underwent transcatheter aortic valve replacement (TAVR) did not have a higher rate of death at one year compared with those who had their heart valve replaced via open-heart surgery, according to research presented at the American College of Cardiology's Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC).

The trial compared approaches to replacing the aortic valve in patients with severe aortic stenosis, a condition in which the valve becomes narrowed, impeding the proper flow of blood. Untreated, aortic stenosis causes breathlessness, fatigue and other symptoms and increases the risk of other heart problems. Traditionally, surgeons have replaced the valve via open-heart surgery, but the less invasive TAVR approach, in which clinicians thread the new valve through a small tube inserted into an artery in the groin, underarm or chest into the aorta and up to the heart, has rapidly become more common in recent years.

Previous clinical trials have found TAVR to be non-inferior or superior to open-heart surgery for various patient groups, but most trials have been limited to medical centers that perform a high volume of procedures or focus on the use of specific types of replacement valves. The new trial involved a broad group of patients who were treated at every medical center that performs TAVR across the United Kingdom.

"The importance of this trial is that it confirms the effectiveness of the TAVR strategy in a real-world setting," said William D. Toff, MD, professor of cardiology at the University of Leicester and the study's lead author. "It wasn't only conducted at the best centers, and it wasn't limited to a particular valve under ideal conditions. This was TAVR as it is in the real world compared with surgery as it is in the real world."

The trial enrolled 913 patients referred for treatment of severe aortic stenosis at 34 U.K. sites from 2014-2018. Half were randomly assigned to receive TAVR and half underwent open-heart surgery. Enrollment was limited to participants age 70 years or older (with additional risk factors) or age 80 years or older (with or without additional risk factors).

Overall, participants were at intermediate to low risk from surgery, with a median Society of Thoracic Surgeons risk score of 2.6% (a score below 3% is considered low risk). However, researchers did not specify a particular risk score cut-off for enrollment. This allowed the trial to evolve along with changes in guidelines and practice regarding TAVR over the course of the study and to reflect physicians' nuanced, real-world approach to considering risk in decision-making rather than taking a formulaic approach, Toff said.

At one year, the rate of death from any cause was 4.6% among patients undergoing TAVR and 6.6% among those undergoing open-heart surgery, a difference that met the trial's pre-specified threshold for non-inferiority of TAVR. Rates of death from cardiovascular disease, stroke and a composite of those two outcomes were similar between the two groups.

Patients who received TAVR had a significantly higher rate of vascular complications, which occurred in 4.8% of TAVR patients and 1.3% of those receiving surgery. TAVR patients were also more likely to have a pacemaker implanted, which was necessary in 12.2% of TAVR patients and 6.6% of those receiving surgery. In addition, patients who underwent TAVR had a higher rate of aortic regurgitation (blood leaking through the valve), a finding that might, in some cases, adversely affect long-term outcomes. Mild aortic regurgitation occurred at one year in 38.3% of patients undergoing TAVR and 11.7% of patients undergoing surgery, while moderate regurgitation occurred in 2.3% of TAVR patients and 0.6% of surgery patients.

On the other hand, patients undergoing TAVR had a significantly lower rate of major bleeding complications, which occurred in 6.3% of TAVR patients and 17.1% of those undergoing surgery. TAVR was also associated with a shorter hospital stay, fewer days in intensive care, and better functional capacity and quality of life measures at six weeks after the procedure. Functional capacity and quality of life were similar between the two groups at one year, however.

Toff said that the results reflect only a relatively short follow-up period, and that longer-term outcomes could reveal important differences. The researchers plan to continue to track outcomes for a minimum of five years.

"I think it's important that we take a measured approach and individualize the decision-making for these patients, factoring in the patient's preference and attitude to risk," Toff said. "The results from our trial and others are encouraging, but patients need to be fully informed and know that the long-term durability of the TAVR valves and the long-term implications of the increased risk of aortic regurgitation are still uncertain."

We live in a time of unprecedented access to information. And in this era of sheltering-in-place around the nation and the globe, the desire for news may be higher than ever - at least for some people. But do we really want all this information, all the time? Some may indeed prefer to think happier thoughts and maintain an (overly) optimistic outlook about the health threat we face. On the other hand, others may prefer not to know what the swings in the market are doing to their retirement savings.

Recent work has found that people at times prefer less information, even when this means they might not be able to make fully informed decisions. However, little is known about the prevalence of such avoidance. Who are the people who choose blissful ignorance over facing reality?

While previous work has looked at isolated decisions, researchers from Carnegie Mellon University, Northwestern and Harvard Universities set out to measure the desire for information across different areas of life. Are some people generally averse to learning information that could be painful, or do most people have some areas of their lives in which they would like to face the truth and others in which they would rather remain uninformed? To address questions such as these, and measure individual preferences for obtaining or avoiding information, they crafted 11 scenarios involving three domains - personal health, finances and other people's perceptions of oneself - in which there was information that could help the respondent to make better decisions but might be painful to learn. For each scenario, over 2,000 respondents indicated whether they would want to receive information or to remain ignorant.

To see the scenarios for yourself and how you compare to others who have responded to the questionnaire, go to this link:

Test Your Own Information Preferences

"Economists have long thought 'the more, the better', when it comes to information," said George Loewenstein, the Herbert A. Simon University Professor of Economics and Psychology at Carnegie Mellon. "This thinking doesn't fully reflect people's complex relationship with information. We wanted to create a way to measure an individual's tendency to pursue or shy away from information."

In one scenario, for example, participants had the option to learn as part of a routine medical exam the extent to which their body had suffered lasting damage from stress: a third of respondents preferred not to learn this information. And if they had gifted their favorite book to a close friend, 1 in 4 participants would rather not learn whether their friend had read and enjoyed the book.

"This work is a first step to understanding the pervasiveness and features of information avoidance in many real-life contexts," said Emily Ho, the lead author of the paper and an incoming assistant research professor at Northwestern University School of Medicine's Department of Medical Social Sciences.

The study showed that the desire to avoid information is widespread, and that most people had at least some domains, be it their health, finances or perception by others, in which they preferred to remain uninformed. The study also showed that the desire for information was consistent over time; those who expressed a preference for avoiding information at one point in time expressed similar preferences when asked again weeks later. Furthermore, how people responded to the hypothetical scenarios predicted real consequential decisions they were presented with to receive or avoid obtaining information.

Although information may feel painful in the moment, such knowledge often leads to better decisions in the future. The researchers found that people who are more impatient are also more likely to avoid learning information, preferring to avoid the prospect of immediate pain rather than make better long-term decisions. Information is also uncertain in that it can be either good news or bad news, and survey respondents who were more willing to take risks with monetary stakes were also more likely to want to learn information, risking bad news for the possibility of good news.

Were certain demographics more information-avoidant than others? "It is tempting to think that people on the opposite end of the political spectrum from you are the ones engaging in information avoidance," said David Hagmann, a fellow at the Harvard Kennedy School and a Carnegie Mellon graduate. "But we find no differences in information avoidance by political ideology, income, gender or - perhaps surprisingly - education. Trading off the potential pain from receiving bad news against the uncertain and delayed benefits from making more informed decisions is something we all seem to do."

Being able to measure people's preferences for obtaining and avoiding information has wide-ranging implications in many areas of public life, from financial decision-making to health interventions. "If there are some individuals who just won't respond to informational campaigns, and you can assess who they are, you might design a different intervention just for them," said Ho. "This can be for reducing an unwanted behavior, such as smoking, or to encourage a positive behavior, such as obtaining a vaccine or exercising regularly. Just as personalized medicine has the promise to revolutionize treatment, so can informational interventions be tailored to take into account an individual's desire for information."

INDIANAPOLIS -- An editorial challenges physicians and the U.S. healthcare system to reconsider the current "one size fits all" care for diverticulitis and to employ a precision medicine approach to determine which patients should be referred for colonoscopy.

The editorial, by Regenstrief Institute research scientist Thomas F. Imperiale, M.D., the Lawrence Lumeng Professor of Gastroenterology and Hepatology and Eddie Krajicek, M.D., a fellow in gastroenterology, both at Indiana University School of Medicine, highlights what they term "sign posts" to support individualized decision-making and strongly recommends their use.

"While national guidelines equivocate, conventional care is to refer all individuals with diverticulitis for a colonoscopy," said Dr. Imperiale, who is a practicing gastroenterologist. "But employing the tools of health information technology, we can and should consider sign posts - such as the specific nature of the diverticulitis episode, preceding changes in bowel habit or other symptoms, personal and family medical histories, the dates and findings of previous colonoscopies - before making a decision to refer the patient for colonoscopy.

"While an episode of diverticulitis may be a sentinel event that brings someone who may have been avoiding routine screening into the doctor's office and subsequently gets them into the colonoscopy suite, many patients who are automatically referred for a colonoscopy may not need one, which wastes colonoscopy resources. Taking a personalized, precision medicine approach uses healthcare resources wisely and provides better patient care," he said.

If a patient's primary care physician orders a colonoscopy without first asking sign post questions, Dr. Imperiale encourages patients to start a discussion to determine if colonoscopy is necessary.

The editorial, "Colonoscopy After Acute Diverticulitis: From Clinical Epidemiology to Clinical Management. Are We There Yet?" is published in the peer-reviewed journal Gastrointestinal Endoscopy.

What is diverticulitis?

Diverticulitis may follow diverticulosis, one of the most common medical conditions in the United States and other developed countries. Diverticulosis is a condition in which small pouches form and push outward through weak spots in the wall of the colon, the final portion of the intestinal tract. According to the National Institutes of Health, diverticulosis exists in about a third of U.S. adults age 50 or younger and more than half of people older than age 60. When one or more of these pouches becomes inflamed, the condition is called diverticulitis, which causes abdominal pain, usually with fever. A computed tomography (CT) scan of the abdomen is used to diagnose diverticulitis. There is no clear cause and effect relationship between diverticulitis and colon cancer.

Coughing fits, anxiety and paranoia are three of the most common adverse reactions to cannabis, according to a recent study by Washington State University researchers.

The researchers surveyed more than 1,500 college students on the type and frequency of adverse reactions they had experienced while using cannabis for their study in the Journal of Cannabis Research. They also collected information on the students' demographics, personality traits, cannabis use patterns and motives for using the drug.

"There's been surprisingly little research on the prevalence or frequency of various adverse reactions to cannabis and almost no research trying to predict who is more likely to experience these types of adverse reactions," said Carrie Cuttler, assistant professor of psychology and an author on the paper. "With the legalization of cannabis in Washington and 10 other states, we thought it would be important to document some of this information so that more novice users would have a better sense of what types of adverse reactions they may experience if they use cannabis."

More than 50% of the study participants reported having experienced coughing fits, anxiety and/or paranoia while using cannabis. On the other end of the spectrum, the three least-common reported reactions were fainting/passing out, non-auditory/visual hallucinations and cold sweats.

The researchers found the most frequently occurring adverse reactions were coughing fits, chest/lung discomfort and body humming, which a subset of the study group reported occurring approximately 30-40% of the time they were using cannabis.

Panic attacks, fainting and vomiting were considered the most distressing of the 26 possible adverse reactions.

"It is worth noting even the most distressing reactions to cannabis were only rated between moderately' and quite distressing," Cuttler said. "This suggests cannabis users do not, in general, find acute adverse reactions to cannabis to be severely distressing."

The least distressing reactions were reported to be body humming, numbness and feeling off balance/unsteady, the researchers found.

The study showed less frequent users are more likely to report negative effects. Additionally, individuals who reported using cannabis to try to fit in with friends, displayed cannabis use disorder symptoms or had anxiety sensitivity--a tendency to imagine the worse possible outcome--were more likely to report adverse reactions as well as experiencing a greater amount of distress.

"Interestingly, we didn't find that quantity of use during a single session predicted very much in terms of whether or not a person was going to have a bad reaction," Cuttler said. "It was the people who smoke on a less frequent basis who tend to have these bad experiences more often."

Moving forward, Cuttler hopes the results of the study will be put to use by doctors, medical cannabis distributors and even bud tenders to give people a better idea of what could go wrong when they get high.

"When you get any other kind of medication, there will be a leaflet or a warning printed on the bottle about the drug's potential side effects," Cuttler said. "There really isn't very much out there on this for cannabis, and we think that it is important for people to have access to this kind of information."

Patients with acute coronary syndrome (ACS) who stopped taking aspirin three months after the insertion of a coronary stent and then took the anti-platelet medication ticagrelor alone for nine months had fewer episodes of bleeding and no increase in heart attacks, stroke or other adverse events caused by blockages in the arteries, compared with patients who took both aspirin and ticagrelor for a year. The research was presented at the American College of Cardiology's Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC).

"This is the first randomized trial to compare ticagrelor monotherapy with dual antiplatelet therapy--the standard of care--exclusively in a population with acute coronary syndrome," said Yangsoo Jang, MD, PhD, professor of cardiology at Yonsei University College of Medicine in Seoul, South Korea, and senior author of the study. "Our findings suggest that for patients with ACS who are treated with stents, ticagrelor monotherapy could be an optimal strategy for reducing bleeding risk without increasing the risk for adverse events caused by arterial blockages."

Most heart attacks and strokes are caused by a blood clot in an artery that's been narrowed by a buildup of fatty deposits, or plaque. ACS is an umbrella term used to describe problems that occur when there isn't enough blood flow to the heart. Examples are heart attack and unstable angina, a condition in which blood clots form, dissolve and form again in an artery carrying blood to the heart.

Blood cells known as platelets help the blood to clot. Both ticagrelor and aspirin stop platelets from forming a clot that can block blood flow. Use of the two drugs together is known as dual antiplatelet therapy, or DAPT. Aspirin, however, also heightens the risk of bleeding, particularly in the gastrointestinal tract.

Stenting, also known as coronary angioplasty or percutaneous coronary intervention, is a minimally invasive procedure in which a flexible tube (catheter) is threaded through an artery under local anesthesia. At the site of the blockage, a tiny balloon at the tip of the catheter is inflated to unblock the artery and a stent, a tiny mesh tube, is inserted to prop it open.

This trial, known as TICO, enrolled 3,056 patients with ACS whose average age was 61 years; 79% were men, 39% were aged over 65 and 27% had diabetes. Everyone received ticagrelor plus aspirin for three months, then the patients were randomly assigned to one of two groups. For nine months, one group continued treatment with ticagrelor and aspirin, while the second group received ticagrelor alone. The study was conducted at 38 centers in South Korea. The primary study endpoint was the combined occurrence of death, heart attack, stroke, a blood clot inside a stent, the need for a second procedure to unblock the same artery or major bleeding (defined as fatal bleeding, bleeding inside the skull or symptomatic internal bleeding) 12 months after stenting.

After a median follow-up of 12 months, 59 patients (3.9%) who had been randomly assigned to ticagrelor alone had a primary-endpoint event, compared with 89 patients (5.9%) who had continued treatment with both ticagrelor and aspirin, a statistically significant difference. This difference was driven by a reduced risk of major bleeding in the group treated with ticagrelor alone (1.7%), compared with the group treated with ticagrelor and aspirin (3%). Rates of other adverse events were similar in the two groups.

A limitation of the study is that patients with an elevated risk for bleeding (defined as aged 80 years or older, having had a stroke within the past year, or having had brain surgery or a traumatic brain injury within the past six months) were excluded, Jang said, adding that such patients account for about 40% of patients undergoing stenting outside of clinical trials.

"Our results cannot be extrapolated to this group of patients," he said.

Women who suffer from psychiatric disorders such as depression, anxiety, mania and schizophrenia following the live birth of their first child are less likely to go on to have more children, according to the first study to investigate this in a large nationwide population.

The study, which is published today (Monday) in Human Reproduction [1], one of the world's leading reproductive medicine journals, found that 69% of women who experienced postpartum psychiatric disorders within the first six months after the birth of their first baby went on to have further children; this contrasts with 82% of mothers who did not experience psychiatric problems.

However, Dr Xiaoqin Liu, a post-doctoral researcher at the National Centre for Register-based Research at Aarhus University (Denmark), who led the study, said: "An important message to women who have a history of severe postpartum psychiatric disorders is that it is possible to prevent relapse. We recommend that they seek help from their family doctors or psychiatrists if they want to have another child, so that plans for treatment that are specific for their individual needs can be made to reduce the risk of relapse, and so that their health, well-being and symptoms can be closely monitored and treated."

Previous research has shown that, overall, around three percent of women develop psychiatric disorders in the first three months after childbirth. These disorders encompass a wide range of mental health problems and usually involve a combination of abnormal thoughts, behaviours and relationships with other people. To date, there has been little research into whether or not this affects women's subsequent reproduction.

Dr Liu said: "We wanted to explore whether women with postpartum psychiatric disorders had a reduced possibility of having a second child. Furthermore, we considered whether a reduction in the live birth rate was due to personal choices or decreased fertility, as these are important issues to consider."

Dr Liu and her colleagues analysed data from Danish registries for 414,571 women who had their first live birth between 1997 and 2015 in Denmark. They followed the women for a maximum of 19.5 years until the next live birth, emigration, death, their 45th birthday or June 2016, whichever occurred first.

They identified women with postpartum psychiatric disorders by seeing if they were given prescriptions for psychotropic medications or had hospital contact for psychiatric disorders during the first six months after the live birth of their first child.

A total of 4,327 (1%) of women experienced psychiatric disorders following the birth of their first child. These women were a third less likely to have a second live birth compared to women who did not experience psychiatric disorders. If the first child died, the difference in subsequent live birth rates disappeared. However, if the psychiatric problem required hospitalisation, the likelihood of a woman having a second child nearly halved and this remained the case irrespective of whether the first child survived or not.

Dr Liu said: "Although fewer women with postpartum psychiatric disorders had subsequent children, it is noteworthy that about 69% of these women still chose to have a second child. For the remaining 31% of women, we need to differentiate the reasons why they did not have another child. If they avoided another pregnancy due to fear of relapse, an important clinical message to them is that prevention of relapse is possible.

"Women whose first child died were nearly four times as likely to have a subsequent live birth as women whose first child survived. These findings suggest that the overall reduced rate of subsequent live births among women who experienced psychiatric disorders after the birth of their first child is, at least in part, voluntary."

The researchers say that other possible explanations for the reduction in the subsequent live birth rate may be that women with postpartum psychiatric disorders are less able to conceive or have more problematic relationships with partners.

"The reason why women with postpartum psychiatric disorders choose to have fewer children needs to be explored further," said Dr Liu.

A limitation of the study is that, although the researchers had an almost complete follow-up of the women through the Danish registries, they did not have accurate information on stillbirths or miscarriages; only pregnancies that led to a live birth were included in the study. Another limitation is that not all women with psychiatric disorders might have received medications or hospital treatment. In addition, it might not be possible to generalise the findings of the study to populations in other countries.

"Denmark offers free and easily available healthcare to all individuals, so we believe our results can inform other, similar populations, although we cannot rule out local differences," concluded Dr Liu.

Women undergoing radiotherapy for many cancers are more likely than men to be cured, but the side effects are more brutal, according to one of Australia's most experienced radiation oncology medical physicists.

University of South Australia (UniSA) Professor of Medical Radiation, Eva Bezak, says women are generally more sensitive to radiation than men, but this is not considered in international guidelines for radiation dosages.

Current guidelines are generally based on a person's height, weight or BMI, and radiobiological responses of the general population.

In a paper published in Critical Reviews in Oncology/Hematology, Professor Bezak and her colleagues Louis de Courcy from University College Dublin and Professor Loredana Marcu from the University of Oradea in Romania highlight the need for gender to be taken into account when administering radiation.

"It is clear that gender plays a role in the occurrence and response to therapy of many diseases," Professor Bezak says.

"For example, it is already well established that men are more susceptible to head, neck and blood cancers and women are more prone to auto immune diseases as well as developing osteoporosis."

Scientists also know that individual responses to radiotherapy are up to 80 per cent determined by genetics.

So, where do we start with gendered medicine?

"The next step is to ensure that we use both male and female mice even in our pre-clinical testing so we can get a better understanding of how gender influences treatment outcomes.

"It is also important to collect data retrospectively so we can compare the radiotherapy outcomes for men and women who were prescribed radiotherapy for the same cancer."

It is a double-edged coin for men, too. Because they are more radio-resistant than women, their healthy tissues are better protected when receiving radiotherapy with fewer side effects, but their long-term survival rates are shorter.

The differences in radiation responses are highlighted by two major events in history: the Chernobyl nuclear reaction disaster in 1986 and the atomic bombings of Hiroshima and Nagasaki in 1945.

Professor Bezak says following Hiroshima and Nagasaki, the incidence of cancer in Japan was much higher in women (58 per cent) compared to men (35 per cent).

Likewise, after the Chernobyl nuclear accident, millions fewer girls were born to irradiated men and women were at greater risk of endocrine imbalance, thyroid cancer and brain tumours.

The one area that does appear to give women some protection against radiation is the female hormone oestrogen, which has a neuroprotective effect during head irradiation.

"As healthcare becomes progressively more tailored to the individual, gender is a factor that can no longer be disregarded. It needs to be taken into account as an independent prognostic factor," Prof Bezak says.

A video explaining the differences in radiation outcomes between men and women can be viewed at https://youtu.be/BtDniRA7DMs

Doctors and nurses in emergency departments at four academic centers and four community hospitals in the Northeast reported a wide range of emotions triggered by patients, hospital resources and societal factors, according to a qualitative study led by a University of Massachusetts Amherst social psychologist.

While they expressed awareness of the possible impact on patient safety, most ER health care providers described strategies they used to regulate their emotions in an effort to keep their feelings from compromising quality of care. The issue of emotion in the ER intensifies as medical workers face additional stresses associated with the Covid-19 pandemic.

"ER providers are on the front line of this pandemic, and stress, anxiety and anger are increasing," says Linda Isbell, professor of psychology in the College of Natural Sciences. "As we all face anxiety about the fallout of this pandemic, anger about a healthcare system that was already stretched thin and under-resourced is likely to grow. It is important to be mindful that these emotions might impact patient care."

Isbell interviewed 86 experienced ER health care providers - 45 physicians and 41 nurses - in what is believed to be the first comprehensive, data-driven study of the triggers and consequences of ER providers' emotions. She collaborated with colleagues at UMass Amherst and the University of Massachusetts Medical School in Worcester for the study published in the journal BMJ Quality and Safety.

The researchers, who carried out the face-to-face interviews between February and August in 2018, say the study highlights the need for emotional intelligence training in healthcare education and a shift in the culture of the medical field to promote meaningful discussion about emotions. "A comprehensive research agenda to understand the role of emotions in patient safety is long overdue," the study concludes.

While patients sparked both positive and negative emotions, hospital and societal/system issues - such as understaffing, overcrowding and limited resources for homeless and mentally ill patients - elicited overwhelmingly negative emotions among the doctors and nurses, according to the study.

"These physicians care deeply about their patients. They're working in a health care system that makes it really hard for them to practice the way they envisioned," Isbell says. "They are asked to handle and solve problems that are incredibly trivial or incredibly serious, and some aren't even medical problems. There is awareness that emotions could influence what they do with the patients," even when the caregivers aren't consciously in touch with their feelings.

Said one ER specialist, "Emotions subconsciously play a role in every single patient and how you work them up, and how you diagnose them, and what you do for them."

In interviews with Isbell, doctors and nurses said encounters with angry, difficult or unreasonable patients may lead caregivers to spend less time at the bedside or to order the types of tests that could resolve the medical issue quickly.

"...I do think it is likely that when you have significantly contentious relationships with patients that ... you don't gain as much data [and to an] extent that could lead to diagnostic error," one doctor stated.

Doctors and nurses said their coping strategies include suppressing or ignoring their emotions when working in the ER, which Isbell says may allow them to perform effectively at the time. "But we know from the emotion literature that's not a good strategy," Isbell says. "It tends to rebound. You may take it out later on your kids or your spouse or dog. It's bad for your body physically and for your mental health."

It may also be bad for the patients. The study calls for further research to help determine whether ED providers' strategies to regulate their emotions are effective at reducing the risk to patient safety.

"Obviously, we need system-wide health care reform, more staffing and more community services for vulnerable populations," Isbell says. "There's a lot of work to be done."