Body

Almost a year ago, COVID-19 began its global rampage, going on to infect about 69.5 million people and kill about 1.6 million as of early this month. From the beginning, most scientists have said that COVID-19 is deadlier than the seasonal flu, while fringe theories have circulated widely, suggesting it is less deadly or flu's equal.

Evidence is accumulating, however, to show just how much deadlier COVID-19 is compared with the flu and the extent of complications related to the two illnesses.

The new research -- a deep dive into federal data by researchers at Washington University School of Medicine in St. Louis and Veterans Affairs St. Louis Health Care System -- reveals a clearer distinction between the two contagious viruses: Among hospitalized patients, COVID-19 was associated with an increased need for ventilators, more admissions into intensive care units (ICUs), longer hospital stays and nearly five times the risk of death than faced by those with the flu.

And although both illnesses attack the lungs, the analysis showed COVID-19 also can damage other organs. It revealed that COVID-19 was associated with a higher risk of complications such as acute kidney and liver damage, as well as heart disorders, stroke, severe septic shock, low blood pressure, excessive blood clotting and new-onset diabetes.

The findings are published online Dec. 15 ET in the journal The BMJ.

"Many high-profile, public comparisons between COVID-19 and the flu have been made; however, those comparisons mostly were drawn using disparate data and statistical methods that have resulted in a lot of conjecture," said senior author Ziyad Al-Aly, MD, an assistant professor of medicine at Washington University. "Our research represents an apples-to-apples comparison between the two diseases."

The U.S. is experiencing its highest surge in COVID-19 cases -- and at the same time flu season typically begins.

"Having a uniform comparison of data helps with disease prediction models, preparation and prevention efforts," Al-Aly added. "The findings may inform the discussion in the U.S. and abroad about the comparative risks of COVID-19 and seasonal influenza, and may help the ongoing effort to manage the COVID-19 pandemic."

For the study, the researchers analyzed de-identified medical records in a database maintained by the U.S. Department of Veterans Affairs, the nation's largest integrated health-care delivery system. The researchers examined information involving 3,641 patients hospitalized in the U.S with COVID-19 at some point from Feb. 1 through June 17, as well as 12,676 patients hospitalized with the flu at some point from Jan. 1, 2017, through Dec. 31, 2019. The average age of patients with either COVID-19 or the flu was 69.

Among patients hospitalized for either COVID-19 or the flu, those infected with the novel coronavirus were nearly five times more likely to die than those with influenza. Of the 12,676 patients with flu, 674 (5.3%) died, and of 3,641 patients with COVID-19, 676 (18.5%) died.

In addition, on average, the COVID-19 patients were four times more likely to require breathing machines and almost 2.5 times more likely to be treated in the ICU. Also, COVID-19 patients were more likely to be hospitalized longer, an average of three extra days.

One of the biggest surprises in the study was the finding of a higher risk of developing diabetes among COVID-19 patients than flu patients -- nine more cases per 100 people. "These patients didn't have diabetes until they got COVID-19," Al-Aly said. "Then their blood sugar spiked, and they needed huge doses of insulin. Is the diabetes reversible, or will it require long-term management? Will it be Type 1 or Type 2 diabetes? We just don't know because COVID-19 barely existed a year ago."

The data analysis also showed that the COVID-19 patients most at risk for death were those 75 years old and older who also had chronic kidney disease or dementia; and African Americans who were considered medically obese, or who had diabetes or kidney disease.

"A deeper understanding of the health risks of COVID-19 helps to anticipate demand for health-care services and to project mortality with greater accuracy," Al-Aly added. "We know so little about COVID-19 because of its newness. I'm not sure why Black patients suffer and die more. My hunch is that the cause relates to racial disparities in health care, but there could be other factors that we don't yet know."

The researchers also found that, when compared with the flu, COVID-19 was associated with a higher risk of acute kidney damage and severe sepsis shock -- both at six more cases on average per 100 hospitalized patients.

Compared with flu patients, people with COVID-19 also required more medications to treat severely low blood pressure, a condition that can lead to organ damage and death - 11.5 more people per 100 people.

"We can call COVID-19 a respiratory virus all we want, but if you look at the associated clinical consequences, it can cause significant damage to the brain, liver, heart, kidneys and blood-clotting systems," Al-Aly said. "It's a destructive virus."

Al-Aly continued: "It's quite possible that a year or five years from now there could be COVID-19 complications that we haven't considered. Already, we're aware of the long-haulers, or people who get COVID-19 but never fully recover. They might feel an ongoing malaise or extreme fatigue or experience appetite changes. Is it a lingering infection? Low-grade inflammation? An autoimmune disease? We are still learning. Even for people who are fortunate to survive the acute COVID-19 illness, they may be forever scarred by the lasting impact of its long-term clinical complications. The more we understand, the better we can benchmark health-care resources and treat patients."

Philadelphia, December 15, 2020 - Researchers from Children's Hospital of Philadelphia (CHOP) and the University of Pennsylvania School of Nursing (Penn Nursing) found that nearly half of adolescents who sought specialty care for a concussion were back to driving when asked approximately two weeks after the injury, even though few had returned to exercise and sports. The findings raise important concerns about the need for evidence-based guidance on safely returning to driving for adolescents with concussion. In the absence of standardized guidelines, providers should include driving as part of post-injury discussions with families.

The findings were published online today by the Journal of Adolescent Health.

More than 1.9 million children sustain a concussion each year, with adolescents representing more than 50% of these injuries. Concussions affect cognition and oculomotor function and thus can impair abilities essential to safe driving such as visual scene assessment, processing environmental risks and executing complex tasks.

"We're looking at this intersection of driving and concussion and see teen drivers returning to what is already a very high risk behavior for them and doing so with an injury known to cause cognitive impairment," said first author Catherine McDonald, PhD, RN, FAAN a Senior Fellow with CHOP's Center for Injury Research and Prevention (CIRP) and an Associate Professor of Nursing in the Department of Family and Community Health at Penn Nursing. "This study sought to provide information on what teens and families are actually doing in the absence of structured clinical guidelines."

Data from the Minds Matter Concussion registry were collected on 332 drivers between the ages of 16 and 19 who had been diagnosed with a concussion within 28 days of injury and seen between January 31, 2018 and August 31, 2018 at CHOP's specialty care concussion program. On average, they were seen 12 days post-injury. Patients answered questions about driving as part of an intake questionnaire, including whether they made changes to their post-injury driving behaviors as well as their return to school, exercise and sports behaviors.

Of these 332 drivers seeking specialty care for concussion, nearly half (47%) had already returned to driving since their injury. Of those who had returned to driving, three out of five reported no changes in their driving behavior. The remaining drivers made changes that reduced exposure to driving such as limiting the number of trips, limiting the distance of trips and avoiding driving at night.

Among those who had returned to driving since their injury, only 28% had returned to exercise, and only 11% had returned to playing an organized sport, while 79% had returned to school. Thus, families who are making school and sports accommodations for their teen's injury may not be considering driving in similar light as a cognitively demanding and high-risk activity.

There were indications of symptom-based self-regulation among those who returned to driving. Those who made changes to limit time spent behind the wheel also had higher symptoms scores as compared to those who returned to driving without modifying their driving.

However, among those teens who were "driving without changes," about three quarters were ultimately recommended for cognitive rest or return to school with accommodations after the clinician's assessment, suggesting that a staged approach to cognitive activities is needed.

"In the absence of structured recommendations for returning to driving, we believe that young drivers may be getting behind the wheel too soon after their injury," said senior author Kristy Arbogast, PhD, Director of Engineering at CIRP and Co-Director of the Minds Matter Concussion Research Program at CHOP. "The management of concussion is evolving, and since driving may pose even more risks than exercise or sports, this study makes it clear that evidence-based guidelines are needed."

Meanwhile, researchers recommend that clinicians and families implement a gradual return to driving similar to, or more conservative than, the gradual return to school protocol. Teens who drive with cognitive, oculomotor and neurophysiologic deficits likely increase their risk of crashing and causing injuries to themselves and others on the road.

This research was supported by the National Institute of Nursing Research of the National Institutes of Health (R01NR018425) and the National Science Foundation (EE-1460927). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Durham, NC - Intraventricular hemorrhage (IVH) - or bleeding in the brain - is a devastating condition common to premature babies, especially those born more than 10 weeks early. Injuries to the brain induced by severe IVH and the ensuing pressure caused by fluid buildup (known as post-hemorrhagic hydrocephalus, or PHH) can result in seizures, cerebral palsy, developmental retardation and an increased mortality rate. There is currently no effective treatment for IVH, but a study released today in STEM CELLS Translational Medicine provides information that might change that.

The study, by researchers at Sungkyunkwan University in Seoul, shows how extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) can ease IVH-induced brain injuries. It also reveals that a protein-coding gene called brain-derived neurotrophic factor (BDNF), secreted by MSCs and transferred through EVs, is likely the key factor behind these beneficial effects.

MSCs are multipotent adult stem cells present in umbilical cord, bone marrow, fat, dental and other body tissues. Their ability to secrete biologically active molecules that exert beneficial effects on injured tissues makes them a promising target in regenerative medicine. Recent studies and clinical trials have shown that MSC-derived EVs (membranes that contain proteins, lipids and RNAs) can safely recreate the therapeutic efficacy of parent MSCs in various neonatal disorders. Moreover, as these MSC-derived EVs are a cell-free therapy, they bypass many concerns associated with MSC transplantation, such as the potential to form tumors or cause pulmonary embolisms, or a chance of the cells being rejected.

"This all has led to the questions of whether MSC-derived EVs might serve as a surrogate for stem cell therapy in cases of severe IVH and, if so, whether the neuroprotection is related to protein transfer from EVs to the damaged host brain tissue," said the current study's corresponding author, Won Soon Park, M.D., Ph.D.

To find the answers, they applied either MSCs, MSC-derived EVs with or without BDNF knockdown, or fibroblast-derived EVs in vitro to rat neuronal cells that had first been exposed to thrombin to induce cell death. They repeated the process in vivo by injecting 4-day-old rats with 200 μL of blood to induce severe IVH, and then two days later treating them with a transplantation of either MSCs or one of the EV groups. (A non-treated group of newborn rats was used as a control.) The results were assessed via MRIs and functional behavioral tests.

"We learned that the MSCs and MSC-derived EVs - but not the EVs derived from BDNF-knockdown MSCs or fibroblasts - significantly reduced both the thrombin-induced neuronal cell death in vitro and the severe IVH-induced brain injuries and inflammatory responses in vivo," Dr. Park said. "As such, our data indicate that MSC-derived EVs are as effective as parental MSCs in attenuating severe IVH-induced brain injuries, and this neuroprotection is primarily mediated by BDNF transfer via EVs. We hope now to move on to establishing the optimal timing, route and dosage of the MSC-derived EVs."

"The promising potential of mesenchymal stem cell derivatives are highlighted in this early study for a treatment for bleeding in the brain, a common occurrence in premature babies," said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. "This approach offers hope someday of a treatment to prevent or reduce the devastating effects of brain hemorrhage that can cause seizures, developmental delay and death in these vulnerable babies."

Even before the pandemic, older Americans had concerns about seeking emergency care because of the costs they might face, the amount of time they might spend in the waiting room and the worry that they might end up hospitalized.

But the risk of catching the novel coronavirus in the emergency department and developing COVID-19 added to those worries, according to a national poll of people ages 50 to 80 taken in June.

Eighty-six percent of those polled cited risk of COVID-19 as something they'd take into account when deciding whether to seek emergency care, compared with 91% who mentioned wait times, 79% who said they worried about what they'd have to pay and 77% who were concerned about hospitalization.

Such concerns may be affecting many older Americans; the poll finds that nearly one in four adults in their 50s and early 60s, and one in three in their late 60s up to age 80, have have been to an emergency department in the last two years.

Those who say they're in fair or poor physical or mental health were almost twice as likely to have been to an ED.

Examining the poll's full findings could help hospitals and health providers improve the way they advise older adults on seeking emergency care, treat them once they arrive at the ED, and help them with follow-up care, say the University of Michigan emergency physicians who worked on the poll with the team from the National Poll on Healthy Aging, based at U-M's Institute for Healthcare Policy and Innovation.

The poll receives support from AARP and Michigan Medicine, U-M's academic medical center, and draws from the answers of a national sample of more than 2,000 adults aged 50 to 80.

"These findings highlight important opportunities and a clear need for health care providers, insurers and health systems to better support older adults during and after medical emergencies to achieve higher-value, patient-centered acute care," says Christina Cutter, M.D., M.Sc., M.S., an emergency physician at Michigan Medicine and National Clinician Scholar at IHPI.

Emergency care cost worries

Cost concerns were more common among those in their pre-Medicare years of 50 to 64, with nearly half of this group saying they were very concerned compared with just over a third of those aged 65 to 80.

In fact, 7% of poll respondents said that in the past two years, worries about cost had kept them from going to the ED when they thought they needed to go. The percentage was higher among women and those in the younger age group, as well as those with lower incomes and worse self-reported health.

And 26% of the people in the younger age group who had visited an emergency department in the last two years said they had received a larger-than-expected bill for their care. And more than a third of people with incomes under $30,000 and a quarter of those with incomes between $30,000 and $59,999 said they were not confident they could afford the out-of-pocket costs of an ED visit.

"Health insurers and policymakers are increasingly shifting costs to patients to deter over-use of care including the emergency department, but these policies may be putting our most vulnerable patients at risk of avoiding care even when they have urgent concerns," says Rachel Solnick, M.D., M.Sc., an IHPI National Clinical Scholar and emergency medicine physician who worked on the poll.

Before and after the ED visit

The poll also looks at the role of other types of health care providers in older adults' decisions to seek emergency care. In fact, 13% of those who said they had been to an ED in the past two years reported they went because they couldn't get a timely primary care or specialty appointment.

More than 60% of those polled said they would consult their existing health care provider, most often their primary care provider, before going to an emergency department.

"Access to appointments, or to timely advice, is critical to this age group," says Preeti Malani, M.D., the poll director and a Michigan Medicine physician specializing in geriatrics and infectious diseases. "This is especially true in the time of COVID-19, when early recognition of symptoms that require advanced care may make a sizable difference in outcomes."

More than 70% of the older adults who had had an emergency visit in the last two years had gone home from the ED, rather than being admitted to the hospital.

Few respondents reported issues with getting the follow-up primary care and prescriptions recommended by their emergency department care team, but one-third said they had trouble getting follow-up tests and specialty care, and three-quarters said they didn't get the recommended in-home care services.

"Delaying emergency care can be dangerous, particularly for older adults who are at higher risk of complications and long-term health problems by putting off their treatment," says Alison Bryant, Ph.D., senior vice president of research for AARP. "These findings come at a critical time as coronavirus cases and deaths continue rising across the country, making individuals more reluctant to go to the emergency room."

"Very often, our ability to send patients home from the emergency department depends on a carefully crafted plan for follow-up care. Our findings show that as older patients' care gets more complicated, we must make a commensurate effort to make care more coordinated across all domains," says Kathleen Li, M.D., M.S., an IHPI clinician scholar and emergency medicine physician.

Southampton-led research has shown that implementing point-of-care testing in hospitals to diagnose influenza can lead to better treatment and faster recovery for patients. The researchers are now calling for routine use of these tests to become standard for patients admitted with acute respiratory symptoms during the influenza season.

The influenza virus causes seasonal epidemics of acute illnesses every winter. Adults who are admitted to hospitals are often taken to critical care wards and between 3% to 15% die in hospital. Diagnosis of influenza in hospitals takes time due to the turnaround time of the standard PCR test, which requires samples to be sent to a laboratory, leading to later antiviral treatment and isolation facility use.

Molecular Point-of-care tests are highly accurate and can provide results in less than one hour but there has been limited assessment of their effectiveness in terms of improving recovery for patients in clinical settings.

In this new study, a team of researchers from University of Southampton and University Hospital Southampton randomised patients admitted with acute respiratory symptoms to receive point-of-care testing using the FilmArray Respiratory Panel 2 or routine clinical care - where testing was at the discretion of the clinical teams and used stranded laboratory testing.

Over two concurrent influenza seasons 600 patients were enrolled in total with just over 300 in each group. Patients in point-of-care group had a nose and throat swab performed and immediately tested on the FilmArray instrument located in the acute area, with the results communicated to clinical teams as soon as available.

The findings, published in the journal Lancet Respiratory Medicine, showed that patients tested routinely with the point-of-care test received their result much more rapidly and were much more likely to be correctly diagnosed with influenza. 100% of the patients who had influenza in this group were correctly diagnosed compared to just 62% of patients with influenza who received routine care. Those that remained undiagnosed in the routine care group did not receive antivirals and were not nursed in single room accommodation, meaning that they were much more likely to pass influenza on to other patients.

The results for the patients in the point-of-care group were available within one hour, meaning those with confirmed influenza received the necessary antiviral treatment faster than those in the routine care group whose results took almost a day to come back. In addition, those in the point-of-care testing group recovered faster and were less likely to deteriorate, compared to those in the standard care arm.

The trial was led by Dr Tristan Clark, Associate Professor and Honorary Consultant in Infectious Diseases at the University of Southampton and University Hospital Southampton. He said, "Our trial has shown that Routine molecular POCT for influenza in hospitals leads to improvements in influenza detection, antiviral use, isolation facility use and recovery compared with the current standard of care.

"We feel that this is practice changing and that guidelines should change as a result. Obviously the current COVID-19 pandemic makes the current situation more complex but the broad principles of needing to test at the point-of-care are applicable to both conditions."

LOS ANGELES -- Scientists have long known that therapies that target the cancer-driving MAPK pathway are only effective in a handful of cancers with specific mutations in a cancer gene called BRAF, and these cancers that initially respond to the therapy often end up developing resistance to the treatment, resulting in relapse for many patients.

Now, scientists at the UCLA Jonsson Comprehensive Cancer Center describe a new combination therapy that suppresses the MAPK pathway by holding cancer-driving proteins in a death grip. This combination of two small molecules has the potential to treat not only BRAF mutated melanoma but also additional aggressive subtypes of cancers, including melanoma, lung, pancreatic and colon cancers that harbor common mutations in cancer genes called RAS or NF1.

The preclinical study, published today in Cancer Discovery, a journal of the American Association for Cancer Research, found that a second-generation RAF inhibitor (type II RAFi) in combination with a standard MEK inhibitor (MEKi) could be effective in treating cancers with these mutations and could also help overcome acquired resistance to the current standard-of-care treatment targeting specific BRAF mutations.

"The idea behind this study was to develop a combination treatment that helps people with common lethal cancers by eliciting durable anti-tumor responses," said senior author Roger Lo, MD, PhD, a professor of medicine at the David Geffen School of Medicine at UCLA and member of the UCLA Jonsson Comprehensive Cancer Center. "Right now, MEK inhibitors by themselves provide limited clinical benefits, and the current MAPK pathway-targeted, combination therapy can help only certain patients with cancers harboring specific BRAF mutations."

To test the effectiveness of the experimental combination, researchers used patient-derived models of melanoma, non-small cell lung cancer, pancreatic cancer and colon cancer as well as mouse tumors that mimic these human cancers. The team evaluated how the combination of type II RAFi plus MEKi impacts the MAPK pathway inside the cancer cells and the body's cancer-fighting immune or T-cells over time in order to achieve long-term response by suppressing drug-resistant clones.

The next-generation combination works by two unique mechanisms that can suppress drug-resistant clones. First, the two small molecules lock RAF and MEK proteins in the MAPK signaling pathway into a tight complex, which is unusual. Normally, molecules in this pathway touch and go in order to fire off growth-promoting signals. Keeping these molecules stuck together allows the drugs to effectively and durably block the MAPK pathway.

"It is quite remarkable that two drugs were able to bind to each of two proteins and sequester them from further propagating signals inside the cancer cells," said co-senior author Gatien Moriceau, PhD, assistant adjunct professor at the David Geffen School of Medicine at UCLA.

Second, the combination prevented an attrition of killer T-cells inside the tumor and promoted T-cell clonal expansion, which is an important immune mechanism that will allow immunotherapies, such as anti-PD-1/L1, to effectively attack the tumors when combined with a MAPK-targeted therapy.

"The combination unexpectedly preserves killer T-cells inside the tumors, which allows them to hunt down drug-resistant tumor clones," said Moriceau. "This favorable impact on T-cells paves the way to combine MAPK-targeted therapies with anti-PD-1/L1 immune checkpoint therapy."

The combination of type II RAFi plus MEKi is currently being tested in clinical trials in both melanoma and other solid cancers such as non-small cell lung cancer.

DALLAS - Dec. 14, 2020 - Recently published UT Southwestern research reveals new insights about risk factors for depression based on data from a landmark longitudinal study focused on heart disease.

One study, published in the Journal of Clinical Psychiatry, shows a link between an inflammatory molecule in the blood and a person's likelihood of depressive symptoms. The other study, in the journal Maturitas, indicates which symptoms of menopause are most predictive of depression.

Both studies are based on data from the Dallas Heart Study (DHS), which since 2000 has tracked the health of thousands of participants with the goal of improving the diagnosis, prevention, and treatment of heart disease.

"The DHS dataset is an extraordinary resource at UT Southwestern," says Sherwood Brown, M.D., Ph.D., senior author of both papers and professor of psychiatry and vice chair for clinical research at UTSW.

The first two years of the study, more than 6,000 residents of Dallas County completed a detailed medical survey; 3,500 of them, aged 30 to 65, provided blood samples and underwent imaging studies. The DHS put particular emphasis on recruiting a diverse group; more than half of all participants were African American and 17 percent were Hispanic.

In the process of collecting information, data useful for studying other medical conditions was amassed. Brown immediately saw the utility for the DHS data in his own work on depression.

Inflammation and depression

Depression is estimated to affect 4.4 percent of the world's population, making it one of the leading causes of disability. Researchers have struggled to understand all the molecular changes in the body that accompany major depressive disorder. More than 20 years ago, clinicians found that a pro-inflammatory drug used to treat some diseases could cause depression. Since that time, researchers including Brown have wondered about the link between inflammatory molecules and depression.

To that end, Brown and Samara Huckvale - an undergraduate at Columbia University who as a high school student worked in Brown's lab in 2019 through UT Southwestern's STARS (Science Teacher Access to Resources at Southwestern) Summer Research Program - analyzed data on 3,033 adults who had provided blood samples and completed a depression screening questionnaire as part of the DHS. The STARS Program, begun in 1991, provides summer research opportunities to high school students.

They discovered that levels of GlycA, an inflammatory molecule that's not routinely tested for in patients, correlated with the severity of depressive symptoms. Even after controlling for factors such as sex, ethnicity, antidepressant use, education, and body mass index, GlycA levels remained associated with depression severity.

"This study suggests that maybe we could predict or diagnose depression based on inflammatory scores," says Huckvale, who aspires to be a chemist. "Or maybe eventually we'll be able to design therapies that actually target this inflammation to treat depression."

Brown, who holds the Lou and Ellen McGinley Distinguished Chair in Psychiatric Research and the Aradine S. Ard Chair in Brain Science, adds that he'd like to study whether GlycA levels can predict how well a treatment for depression works or help guide the best antidepressants for particular patients. He'd also like to follow patients over time to gauge whether GlycA levels rise before or after the onset of depression symptoms.

Menopause and depression

In the Maturitas paper, Brown and his colleagues used DHS data to study menopausal women, a group known to have an increased risk of depression.

Previous studies have found a correlation between the most common symptoms of menopause - hot flashes, night sweats, and sleep disturbances - and the onset of depression. Menopause also causes sexual symptoms, including vaginal dryness and low libido, but few studies have looked at the association between these symptoms and depression.

In the study, Brown and colleagues analyzed DHS data on 384 women aged 37 to 73 years old who self-reported being in menopause. Sixty-four percent of the women were non-Hispanic Black, 26.8 percent were non-Hispanic white, and 9.11 percent were Hispanic.

"There are very different cultural and ethnic experiences around menopause, so it was important to us to look at a very diverse sample of women," says Michael Xincheng Ji, co-first author of the study and a fourth-year UTSW medical student.

As part of the Dallas Heart Study, the women reported whether they had symptoms classically associated with menopause, which the researchers grouped into vasomotor, psychosocial, physical, or sexual symptoms. In addition, each woman completed the Quick Inventory of Depressive Symptomatology-Self Report survey (QIDS-SR), which gauged the presence of depression symptoms.

The prevalence of sexual symptoms of menopause was positively associated with a higher score on the QIDS-SR. This association remained even after excluding women who were taking antidepressants, and there was also an association between psychosocial symptoms of menopause and the QIDS-SR score. No association was found between vasomotor or physical symptoms and the QIDS-SR score, and ethnicity was not a strong predictor of the depression symptoms.

"Recognizing patterns in who is most likely to develop depression is really important to help guide our screening efforts," says Sydney Singleterry, co-first author of the new work and a fourth-year UTSW medical student.

"What we hope is that these findings make clinicians think about the possibility of depression when they hear a woman reporting these symptoms," says Brown, also a member of the Peter O'Donnell Jr. Brain Institute.

PHILADELPHIA (December 14, 2020) - National efforts to develop a coronavirus disease 2019 (COVID-19) vaccine at "warp speed" will likely yield a safe and effective vaccine by early 2021. However, this important milestone is only the first step in an equally important challenge: getting a majority of the U.S. public vaccinated.

Authors of a viewpoint article in the Journal of the American Medical Association share five strategies and implementation considerations, informed by insights from behavioral science, for a national COVID-19 vaccine promotion program. Alison M. Buttenheim, PhD, MBA, the Patricia Bleznak Silverstein and the Howard A. Silverstein Term Endowed Professorship in Global Women's Health at the University of Pennsylvania School of Nursing (Penn Nursing), is senior author of the article.

"The U.S. needs a national strategy for the promotion of COVID-19 vaccines that unites the urgency and commitment of Operation Warp Speed with innovative behavioral science and social marketing approaches to increase COVID-19 vaccine confidence and acceptance in diverse populations," she says.

The recommended strategies are:

Make the vaccine free and easily accessible.

Make access to valued settings conditional on getting vaccinated.

Use public endorsements from trusted leaders to increase uptake.

Provide priority access to people who sign up to get vaccinated before vaccines are widely available.

Transform individual vaccination decisions into a public act.

The researchers also recommend the formation of a national entity similar to Operation Warp Speed to steer federal COVID-19 vaccine promotion efforts. "This entity should include scientists from multiple disciplines (epidemiology, vaccine science, behavioral science, social marketing, communications) as well as vaccine program delivery experts," says Buttenheim. "The team should represent a spectrum of political views to depoliticize pandemic response."

RICHMOND, Va. (Dec. 14, 2020) -- The first COVID-19 vaccine has received emergency use authorization. Yet a key question remains: Will U.S. adults be willing to get it?

A new study led by a Virginia Commonwealth University professor is among the first to examine the psychological and social predictors of U.S. adults' willingness to get a future COVID-19 vaccine and whether these predictors differ under an emergency use authorization release of the vaccine.

The study, "Willingness to Get the COVID-19 Vaccine with and without Emergency Use Authorization," will be published in the American Journal of Infection Control. It involved a survey of 788 U.S. adults, and found that 59.9% of respondents were definitely or probably planning to receive a future coronavirus vaccine, while 18.8% were neutral and 21.3% were probably or definitely not planning to get it.

When asked if they would get the vaccine under an emergency use authorization, 46.9% of respondents said they were definitely, likely, or somewhat willing to do so; while 53.1% said they were definitely, likely, or somewhat unwilling to do so.

"The biggest issue coming out of this study is that participants seemed worried about receiving the COVID-19 vaccine under emergency use authorization," said lead author Jeanine Guidry, Ph.D., an assistant professor in the Richard T. Robertson School of Media and Culture in the College of Humanities and Sciences and director of the Media+Health Lab at VCU.

The study found that concerns about side effects were a significant barrier, Guidry noted.

"[Such concerns are] not unusual," she said, "but we now also know that two of the vaccines -- Pfizer and Moderna -- may have some expected side effects ... [and that] may make people hesitate to get the vaccine."

The study also found troubling disparities among demographic groups. For example, younger respondents were more likely than older respondents to express a willingness to get the vaccine. And it found that white respondents were more likely than Black respondents to be willing to get the vaccine, either under emergency use authorization or regular Food and Drug Administration approval.

"That is something researchers have found in other previous vaccine studies as well, but it is more worrying with COVID-19 because we know that Black Americans are infected with COVID-19 significantly more frequently than white Americans, and they are also more likely to die from the virus," Guidry said.

"Unfortunately, there is history of medical mistreatment of African Americans and individuals from low-income communities in the U.S.," said co-author Bernard Fuemmeler, Ph.D., a professor in the Department of Health Behavior and Policy in the VCU School of Medicine.

"Against this backdrop it is understandable that mistrust among certain communities will be an issue to contend with as we hope to make progress in delivering the vaccine to those most in need," Fuemmeler said. "It starts with recognizing this history and providing people with the information they desire to alleviate their justifiable wariness about the vaccine."

The researchers found that significant predictors of a willingness to get the coronavirus vaccine included education level and having health insurance, as well as a high-perceived susceptibility to COVID-19. Predictors of a willingness to get the vaccine under an emergency use authorization included age and race/ethnicity.

The study's findings could help shape health communications and messaging as distribution of the vaccines begin across the country. It suggests that messages should address concerns about the COVID-19 vaccine and its development and reinforce its benefits. It also suggests that these efforts may need to go beyond just communications campaigns correcting misinformation about a vaccine to focusing on re-establishing public trust in government agencies and medicine.

"A vaccine is only effective if people are vaccinated, and so it is really crucial that people trust the vaccine, and are willing to get it," Guidry said. "We will only reach community-level immunity if about 70% of the population has gotten the vaccine. So knowing what some of the barriers are to getting this vaccine is really important, because we may be able to better communicate and address these concerns."

Guidry added that the study reflects significant concerns and misunderstandings that must be addressed in the months ahead.

"[It is] a reminder that there are some real fears among the public about the vaccine being developed too quickly," she said. "In reality, while this particular vaccine was developed rather quickly, the science that has allowed for this to occur has been progressing for the past 10 years. I think we need to make sure people better understand the vaccine development process, and what exactly it means when a vaccine becomes available under emergency use authorization."

DALLAS - Dec. 15, 2020 - A study of patients resuscitated from out-of-hospital cardiac arrest shows that women have a lower likelihood of survival compared with men and are less likely to receive procedures commonly administered following cardiac arrest.

The multicenter study, led by UT Southwestern researchers, was published online today in Circulation. The percentage of patients who survived to hospital discharge was significantly lower among women (22.5 percent) than men (36.3 percent). About 300,000 people suffer cardiac arrests outside of a hospital setting each year in the U.S.

"Our work points to new directions in how we can work to improve survival in women," says Ahamed Idris, M.D., a professor of emergency medicine and internal medicine at UT Southwestern who practices at Parkland Memorial Hospital. "Why are emergency interventions different with women than with men?"

This study draws upon data from two clinical trials and a cardiac arrest registry conducted by the Resuscitation Outcomes Consortium (ROC), an initiative of the National Institutes of Health and the U.S. Department of Defense. The trials included patients at 10 sites in the U.S. and Canada during 2010-2015.

Among 4,875 successfully resuscitated patients in the study, 37.4 percent were women and 62.6 percent were men. The men were slightly younger, with an average age of 65 versus 67 for the women.

According to Idris, there are two treatments available for cardiac arrest following a successful resuscitation: therapeutic hypothermia (cooling a person's body to a temperature that is lower than normal) and coronary angiography, which is used to examine arteries to the heart and open them to blood flow. The study documents that women receive hypothermia 35 percent of the time compared with 44 percent for men. With coronary angiography, women receive this treatment 14 percent of the time compared with 30 percent for men. Further study is needed to find out why this disparity exists.

Also, women were 6 percent less likely to receive cardiopulmonary resuscitation (CPR) from a bystander. Other data showed fewer of them had cardiac arrests that were witnessed or had shockable rhythm versus the men.

Idris says that men are more likely to suffer cardiac arrest in public, resulting in a quicker call to 911 from a companion or bystander and therefore doubling their chance of survival to hospital discharge. However, once resuscitated, both women and men begin recovery from similar starting points.

"This is one of few studies looking at what happens to people post-resuscitation," says cardiologist Ambarish Pandey, M.D., assistant professor of internal medicine at UTSW. "Now we need insight into whether these outcomes may be driven by what happens in the hospital. We have a long way to go in providing gender equity in treatment."

Dallas-Fort Worth was the largest U.S. site in the ROC, with 36 hospitals and 22 emergency medicine agencies involved across Dallas, Collin, and Tarrant counties, including both UT Southwestern and Parkland Memorial Hospital. While the original Resuscitation Outcomes Consortium was discontinued in 2016, the Dallas-Fort Worth branch, the Center for Resuscitation Research, continues to be maintained with studies ongoing by Idris, who is director of emergency medicine research in the department of emergency medicine at UT Southwestern.

"Were the women sicker or was there a difference in care?" asks Purav Mody, M.D., a cardiologist and assistant professor of internal medicine at UT Southwestern. "Our study demonstrates the existence of gender disparities in post-resuscitation care and highlights the need for future research focused on decision-making and care being provided in the post-resuscitation phase in order to narrow gender-based differences in cardiac arrest outcomes."

Idris was part of the team that launched the study 15 years ago. "We followed these patients into the hospital and tracked what they received: every chest compression, every shock treatment, every ventilation (forcing air into the patient's lungs to start the breathing process). We studied the CPR features used out-of-hospital to see which worked best."

When he first started working in emergency medicine in 1979, heart attack patients usually were placed in intensive care for observation. If the patient went into cardiac arrest, the person was given shock treatment. Treatment options today, such as aspirin, beta blockers, or anti-coagulants, were not available at the time. Similarly, for patients resuscitated from cardiac arrest, once they reach the hospital they can receive therapeutic hypothermia and coronary angiography, both of which improve outcomes, but were not available in 1979.

"Today, if a patient makes it to the hospital early enough, they should not walk away with permanent heart damage," Idris says.

Using a large nationwide registry of patients receiving maintenance hemodialysis, this study published in the American Journal of Kidney Diseases found that higher frequency of low blood pressure episodes during hemodialysis was associated with a higher incidence of diagnosed peripheral arterial disease.

Peripheral artery disease (PAD) is a condition characterized by progressive atherosclerotic narrowing or occlusion of the arteries, particularly to the lower extremities. PAD often goes undiagnosed in patients with kidney failure who may not experience traditional symptoms of claudication. It is plausible that sudden reductions in blood pressure as occurs during intradialytic hypotension (IDH) could reduce limb perfusion and lead to more PAD events or exacerbate PAD symptoms. Using a large nationwide registry of hemodialysis patients and the electronic health records of a large dialysis provider, researchers found that more frequent IDH was associated with a higher incidence of recognized PAD. These results suggest that patients with more frequent IDH warrant careful examination for PAD such as foot examinations or other diagnostic evaluations.

PITTSBURGH, Dec. 11, 2020 - In a paper published today in the American Journal of Human Genetics, a group of international collaborators led by researchers from the University of Pittsburgh School of Medicine identified new genetic associations that can predict individual susceptibility to a rare inflammatory disease called Takayasu arteritis.

The study, conceived by Amr Sawalha, M.D., professor of pediatrics and medicine at Pitt, and chief, Division of Pediatric Rheumatology, UPMC Children's Hospital of Pittsburgh, accumulated samples from 1,226 individuals with Takayasu arteritis across five different populations around the globe, making it the largest collection of these samples in the world.

In Takayasu arteritis, inflammation damages the aorta and other large vessels, which can lead to rupture of major blood vessels or decreased blood supply to the limbs, brain and other vital organs and puts patients at risk of a heart attack, stroke or major blood loss and organ damage.

"Many of us who treat patients with Takayasu arteritis are frustrated because we don't really know how the disease works," said Sawalha. "We don't have good tools to predict a disease flare-up. Some patients have very active disease without clear symptoms or an increase in inflammatory markers."

By performing a genome-wide association study in healthy people and Takayasu arteritis patients, the researchers identified variations in several regions of the genome suggestive of the role of certain immune cells in this disease. They also identified novel molecules and pathways that can be targeted for therapy.

The team went on to compare the genetics of Takayasu arteritis with genetic predisposition to hundreds of other traits, assessing shared genetics between Takayasu arteritis and other immune-mediated diseases.

"We found that, genetically speaking, Takayasu arteritis was closest to Crohn's disease," said Sawalha. "This suggests that we can try developing treatments based on what we know works for inflammatory bowel disease, which is a much more common condition."

Until this report, knowledge about the genetic predisposition to Takayasu arteritis was extremely limited, due to difficulty collecting a large enough number of samples to represent the genetic architecture of ancestrally diverse populations.

This study was made possible only because of international collaborations, said Sawalha. His group gathered samples and data from patients in Turkey, Canada, China, Italy, the United Kingdom and across the U.S., and included patients from populations under-represented in genetic studies.

In the future, scientists hope to use their data to find genetic determinants of how the disease manifests itself--which individuals are more likely to develop severe disease, which arteries might be affected and which patients are more likely to carry the disease silently without presenting easy-to-identify molecular markers.

"This study opens a lot of possibilities," said Sawalha. "Expanded knowledge of the genetic component of Takayasu arteritis will help us develop more effective therapies moving forward."

There have been over 280,000 deaths in the United States due to COVID-19, with the infectious nature of the disease preventing many patients from receiving end-of-life care at home. Researchers from Brigham and Women's Hospital and collaborators found that 95.5 percent of individuals who died with a diagnosis of COVID-19 in the Mass General Brigham health system between February 18 and May 18, 2020 did so in the hospital. To better characterize the intensity of end-of-life care and promote discussions about at-home care, the researchers analyzed specific death settings, determining that roughly 40 percent of hospital deaths occurred in the intensive care unit. Findings were published as a letter to the editor in the Journal of Palliative Medicine.

"Surveys have shown that most patients prefer to die at home, but there is also an ongoing debate about whether that is the best option for patients when resources for at-home care are limited," said corresponding author Isaac Chua, MD, MPH, of the Division of General Internal Medicine and Primary Care at the Brigham. "The purpose of this study was to open up a larger conversation about whether we need to provide more advanced care at home, so that if patients want to die at home, they would have that option."

The researchers state that the large percentage of patients that died in the intensive care unit (ICU) suggests that end-of-life care was intense for the plurality of those who died in the hospital. Roughly a third of the other deaths occurred in the general ward, and less than one fifth (17.8 percent) occurred in an inpatient palliative care unit. Based on the overwhelming number of patients who died in the hospital and ICU, it is likely that most patients who expressed a desire to die at home were unable to do so.

While the study population only included 16 patients who died outside of the hospital, making observations about this group hard to generalize, two patterns emerged. First, more than 93 percent of the patients who died outside of the hospital were white, whereas white individuals accounted for only about 61 percent of those who died in the hospital. Secondly, the population was on average older, with a median age of 91.2, compared to 77.8 among those who died in hospital.

Chua hypothesizes that the higher median age among those who died outside the hospital possibly reflects that older adults may have been more prepared to make end-of-life decisions, facilitating earlier plans for a safe discharge to the home while minimizing risk of infecting other household members. In contrast, a younger patient may have been more likely to continue to pursue hospital-based care.

"Most COVID-19 patients likely have not been thinking about their own mortality, and so they may be undecided about what they want," Chua said. "There's a lot of uncertainty and a lot of stress."

Clinicians face uncertainty as well. "Especially at the beginning of the pandemic, the prognostic factors for good and bad outcomes were unknown," Chua said. "It's hard to create a pathway for sound end-of-life care because of how novel this virus is, how little we know about it, and how hard it is to plan ahead."

Notably, 61 percent of the COVID-19 patients received a form of sub-specialty palliative care, which Chua says is a positive finding reflective of MGB institutions' commitment to implement palliative care services amidst the COVID-19 crisis. Still, patient preferences surrounding end-of-life care for COVID-19 remain understudied, and hospital systems are still exploring ways to provide patient-centered care at home for acute and subacute illnesses.

"Our health care system needs to be thoughtful about different patient trajectories, and patients should really think through what they would want, too," Chua said. "Even if one isn't anticipating a poor outcome, being able to have these difficult conversations early on in a hospitalization enables the hospital team to figure out what it can do to plan ahead and be as patient-centered as possible, coordinating resources to align care with patient priorities."

Breast cancer affects 1/8 women in the USA, and rates of breast cancer are increasing.

Humans are good at spotting cancer by looking at patterns in cells. But a new AI tool, ReceptorNet, can supplement human theragnosis by identifying the subtle differences in those patterns to inform better treatment decisions.

ReceptorNet was developed in collaboration between Salesforce and Dr. David Agus at the Lawrence J. Ellison Institute for Transformative Medicine of USC.

ReceptorNet could make treatment less expensive and more readily available, particularly in developing countries.

Imagine being a doctor and having a precocious resident permanently by your side, giving you brilliant insight into disease and helping you to identify the best treatment path for your patients.

A team at Salesforce Research believes this scenario is closer to reality than you might think, as a result of a series of exciting developments in AI vision technology and machine learning.

Breast cancer rates on the rise

Breast cancer affects more than two million women worldwide each year, with around one in eight women in the United States developing breast cancer over the course of their lifetime. There were also 2,550 new cases of breast cancer in men in the U.S. in 2018. Alarmingly, rates of breast cancer are increasing in nearly every region globally.

Salesforce Research collaborated with the Ellison Institute to develop ReceptorNet, a deep-learning algorithm that can determine hormone-receptor status - a crucial biomarker for clinicians when deciding on the appropriate treatment path for breast cancer patients -- with excellent sensitivity and specificity numbers.

While using AI to try to improve outcomes for breast cancer patients is not new, efforts up until now - such as Google's AI breast cancer screening tool - have largely focused on diagnosing cancer.

What makes ReceptorNet unique is that it focuses on improving the way treatment decisions are made for breast cancer patients. Specifically, ReceptorNet predicts hormone-receptor status from an inexpensive and ubiquitous tissue image. That's in contrast to the current standard of care, which requires both a more expensive, less widely available type of tissue image -- and a trained pathologist to review those images.

Crucially, because it is a less expensive and quicker way of determining hormone-receptor status than the system used commonly today in countries like the U.S., it could potentially help make high-quality decision-making for breast cancer therapies more accessible - allowing patients globally to receive the best possible treatment path, regardless of the expertise available in their healthcare system.

How the ReceptorNet project began

The development of ReceptorNet originated in conversations between Salesforce researchers and Dr. David Agus, Founding Director and CEO of the Lawrence J. Ellison Institute for Transformative Medicine of USC.

Dr. Agus is a renowned oncologist and a professor of medicine and engineering. He explains that there has long been a belief among cancer doctors that tumor cells contain crucial information about cancer that the human brain can't quite extract.

"The human brain is very good at determining whether or not there is cancer based on looking at patterns in cells," says Dr. Agus, "but it can't determine the subtle differences in these patterns that correlate with the outcome of the cancer. In other words, what the molecular on/off switch is."

This means that a patient might be diagnosed with cancer but then have to wait weeks for the results of molecular studies to determine what treatment they should receive.

"Our team has been working on using AI to understand patterns of cells and help make treatment decisions for several years. We had this notion that maybe we could find the answer to those molecular questions instantaneously with AI and machine learning," Dr. Agus says.

That's where the Salesforce Research team came in. "We have a world-class AI research team," says Nikhil Naik, Lead Research Scientist at Salesforce Research and the first author on this study, adding that, "the collaboration also matched our philosophy of developing technology that doesn't just serve the purpose of the company, but also has a positive impact on people and on the world."

With a PhD in computer vision from MIT, Naik says he realized early on that Salesforce would be in an ideal position to help.

Finding clues to cancer that the eye can't see

The team developed an AI solution that is able to extract vital clues about breast cancer by learning to spot patterns in images of tumors, using a cheap and widely available imaging process. Naik gives a simple analogy.

Say you have an accident and you think you may have broken your arm. What if, instead of having to go to the hospital for an X-ray, you could just take a photo of your arm on your cell phone and an AI algorithm could determine whether or not you had a fracture?

"That is very similar to what we are doing. We are replacing an expensive, time-consuming process that requires specialized technology with a simpler, more widely available technology for imaging, using artificial intelligence."[MC(2]

So how does this work in practice? Typically, when a patient is diagnosed with breast cancer, a pathologist will analyze their tumor tissue under a microscope using a process called immunohistochemistry (IHC) staining, to look for the presence of hormone receptors that allow the cancer to grow. This helps them to decide on the best course of treatment, such as hormone therapy or chemotherapy.

The problem with IHC staining is that it is expensive, time-consuming, and not readily available in many parts of the world, particularly in developing countries.

ReceptorNet has learned to determine hormone receptor status by using a much less expensive and simpler imaging process - hematoxylin and eosin (H&E) staining - that analyzes the shape, size, and structure of cells.

ReceptorNet has been trained on several thousand H&E image slides, each containing billions of pixels, from cancer patients in dozens of hospitals across the world.

"The algorithm is able to look at individual pixels and determine subtle patterns that the human eye can't possibly perceive," says Andre Esteva, Head of Medical AI, and co-author on the study, explaining that patterns can yield vital clues about how to treat the cancer.

Exciting times for medical AI

Since early 2019, Naik and Esteva have been leading a team at Salesforce that focuses on delivering AI applications for social good, primarily in the areas of medicine and science. Recently, the team created search engines for COVID-19 to help researchers and clinicians find information faster.

"There's a significant benefit to doing this kind of AI research in industry, as opposed to academia. AI teams tend to flourish when provided with industrial scale compute capabilities - and industrial scale budgets - because those elements make it much easier to rapidly experiment," says Esteva.

"I think the most impactful applications of AI will be in healthcare," adds Research Scientist Ali Madani, who assisted on the computer vision algorithm that powers ReceptorNet.

Madani talks passionately about the transformative impact AI could have on people's lives. "There are direct applications that could improve society as a whole," he says. "That's the underlying motivation which has drawn me to AI and healthcare."

Eliminating bias, improving accessibility, transforming medicine

So, what could this mean for clinicians and patients? The ability to determine hormone-receptor status from H&E stains could make treatment less expensive and more readily available, particularly in developing countries.

It could also, says Dr. Agus, mean patients are spared an agonizing wait between diagnosis and the initiation of treatment.

Proposing a future use case of this new technology, Dr. Agus said to, "Imagine when a woman comes in for her diagnosis and we can tell her right there on the spot what her treatment should be. Or in a third-world country (where molecule tests aren't available), imagine potentially being able to, just by scanning a slide, tell a woman that she can get a pill that could put her breast cancer under control. All of a sudden there's a transformation in medicine."

In order for AI in medicine to deliver its full potential, clinicians must first have confidence in its accuracy.

"An algorithm that's only 80% accurate is not good enough for a critical application, like determining which cancer therapy to give to a patient," acknowledges Naik.

In the test phase of the ReceptorNet project, when the algorithm was tested on images it had never seen before, it achieved 92% accuracy for hormone receptor determinations, which indicates its potential for future clinical deployment.

Numerous small, incremental changes were made to ensure the algorithm was able to deliver accurate predictions, regardless of differences in the preparation of the tissue samples it was analyzing. Crucially, the algorithm has also been able to deliver reliable performance across different demographic groups.

There have long been concerns that healthcare and evidence-based medicine can be biased against certain groups, because they are often underrepresented in the evidence base. However, during the development of ReceptorNet, researchers were able to achieve accurate results across a variety of different groups, which could be vital in order to build confidence in the performance of the AI among healthcare professionals.

Naik says, "We analyzed this by splitting the data based on things like age, race, and location, and statistically there was no difference in the performance of the algorithm."

Importance of close collaboration

Throughout the design process, the Salesforce team worked closely with Dr. Agus, Dr. Dan Ruderman, and Dr. Michael F. Press at The Ellison Institute, to ensure they were aware of any possible biases that could exist in the data that was fed into the model. This close collaboration also helped to ensure that the objectives of the team were closely aligned with the clinical workflows and questions that clinicians, doctors, and nurses would be interested in.

Despite this, the team was aware that not every medical professional would be easily convinced that AI could be relied upon.

Naik says that the pathologists they spoke to were initially skeptical, explaining that this kind of prediction based on an H&E slide is not something pathologists could do on their own.

"However, when they saw that the algorithm was working so well, they were really impressed that it was able to make these predictions just by learning from thousands of images - and also that it was able to confirm their suspicions about what kinds of patterns could be predictive. That was very impressive and exciting for them."

Dr. Agus agrees. "When we first started looking at how we could answer molecular questions instantaneously with AI and machine learning, we achieved some good results. But when we teamed up with Salesforce, those results went from good to great."

Long-term and short-term implications

From a clinical perspective, this technology could eventually lead to a number of positive impacts. In a developed country such as the U.S., it could reduce the cost of care and the time it takes to initiate breast cancer treatment, because it uses much less expensive imaging technology and automated decision-making. It could also improve accuracy and deliver better outcomes for patients.

In developing countries where there is limited access to IHC staining, it could have a big impact in terms of broadening access to treatment.

The immediate effect of this work is to lay a foundation for future studies to compare the clinical workflow of a pathologist with and without this type of AI, in order to better understand its full potential.

Dr. Agus says that, "This is just the tip of the iceberg with what we're going to be able to do with AI in cancer care. It's just a pilot project to show what's doable. Now, we can get deeper and deeper, and I can envisage a day not too far away, when just by looking at a slide, I can tell, with the help of AI, tell somebody 'you're going to get Drug X and not Drug Y because of how the cells are arranged'."

For Esteva, one of the most exciting things about this project is that it has shown how AI can do more than just mimic the role of a doctor.

"What we're doing here is actually training AI to do something that the physician can't do, as an added capability to their repertoire. The AI can see patterns that are essentially invisible to the physician, and potentially critical for the patient."

AI could ultimately also have a positive impact on the doctor-patient relationship. With access to AI-powered insights, doctors could have more informed conversations with their patients at an early stage in their treatment path, giving them a fuller, data-driven picture of what may lie ahead in terms of treatment and therapy.

Moving into the future

Esteva is keen to stress that AI will help augment the role of a doctor, not replace it.

"What gets me really excited is thinking, 'where is this going to go in the next five or 10 years?' Unfortunately, many of us can relate to situations where someone we love was given the wrong therapy or misdiagnosed. You end up asking yourself how their lives could have been different if a slightly better decision was made. A single moment can have a ripple effect in a patient's life for years or decades."

"Physicians should be able to make the best possible decisions based on all available medical knowledge. If you can build AI that can help doctors make the right decisions, by harnessing the collective intelligence of physicians and medical data, that's incredibly powerful."

Dr. Agus adds, "AI and machine learning are going to herald a new era, with potential to be applied to diseases beyond cancer and ultimately create better outcomes for patients. It won't happen overnight, and it will be a slow, step-by-step process, but we're embarking on a journey over the next decade to improve every aspect of what we do, through data. That's really exciting."

According to many medical experts, reduced social mobility - defined here as social contact and travel within and among communities - is a necessary factor to contain the spread of COVID-19.

Joshua Clinton, professor of political science at Vanderbilt University, led a team of researchers to analyze data from more than one million US adults, determining that partisanship is a stronger determinant of social mobility behaviors than the relative prevalence of COVID-19 cases in the community. The research, "Partisan Pandemic: How Partisanship and Public HealthConcerns Affect Individuals' Social Mobility During COVID-19", will be published by the American Association for the Advancement of Science in Science Advances on Dec 12, 2020.

Between March and April 2020 - the first month of the pandemic - Democrats and Republicans both indicated increased concern about COVID-19 and a commitment to reduced social mobility. However, in April, the percentage of Republicans who indicated they were "very or somewhat worried about COVID-19" began to decline while remaining stable among Democrats. The reduced concern about the pandemic among Republicans correlated with a faster return to social activities, regardless of the rate of infections in their communities. By September, Republicans were engaged in nearly double the number of social activities per day than Democrats. Clinton asserts that stronger political leadership may help reduce social mobility among Republicans, considered by public health experts as a necessary step for reducing transmission and controlling the pandemic.