Culture

Young survivors of acute myeloid leukemia have long-term complications from treatment

Adolescent and young adult (AYA) patients treated for acute myeloid leukemia (AML) have a high risk of developing several long-term health complications, a study led by UC Davis Comprehensive Cancer Center researchers has found.

The most common complications among AYA survivors (ages 15–39) were cardiovascular, endocrine and respiratory diseases. The complications - known as late effects - were more present among non-white AYA patients and those living in more deprived neighborhoods.

“Our study shed light on the high burden of late effects among young survivors of AML,” said Renata Abrahão, the study’s lead author. Abrahão is a postdoctoral fellow at the UC Davis Comprehensive Cancer Center and the Center for Healthcare Policy and Research.

According to the American Cancer Society, around 20,000 cases of AML will be diagnosed in 2020 in the U.S. alone. With AML, the myeloid cells produced inside the bone marrow grow abnormally. The main treatment for most types of AML is chemotherapy. In some cases, it might be followed by a stem cell transplant.

Late effects of AML linked to health disparities

The study used comprehensive information from 1168 AYA patients with AML. These patient cases were reported to the California Cancer Registry from all non-federal hospitals in California between 1996 and 2012.

The researchers found that after 10 years of AML diagnosis, some patients developed an endocrine disease (26%), a cardiovascular disease (19%) and a respiratory disease (7%). Other late effects were less frequent but included serious illnesses such as another cancer. The study found that AYA survivors who underwent bone marrow transplant were at least twice as likely to experience most of the late effects.

Hispanic, Black and Asian/Pacific Islander survivors were at a higher risk of many of the late effect diseases. The study showed that AYA survivors who lived in poorer neighborhoods at the time of AML diagnosis had more of these late effects.

According to the researchers, many factors can lead to the disparities in disease burden. These include differences in therapeutic management, patient’s response to treatment, AML with high-risk mutations, coexisting diseases and socioeconomic factors.

“This higher risk may relate to the financial hardship that patients with cancer often experience. As a result of cancer, AYA survivors and their families may miss work, experience income loss and incur substantial out-of-pocket expenses,” said Theresa Keegan. Keegan is an associate professor at the UC Davis Comprehensive Cancer Center and the study’s senior author.

AYA patients suffer a higher financial burden compared to younger or older cancer survivors. They may forgo treatment and long-term follow-up visits that could mitigate the impact of late effects. Their risk of late effects may be compounded by unhealthy lifestyle habits such as smoking, excessive alcohol consumption, lack of exercise, non-protected sun exposure and poor diet.

“Our findings can help clinicians and policymakers develop better survivorship care plans to reduce suffering and death among AYA survivors of AML,” Abrahão said.

The study was published Nov. 9 in the International Journal of Epidemiology.

This study was supported by the Rich and Weissman Family Lymphoma and Survivorship Fund, St. Baldrick’s Research Grant, the National Research Service Award (NRSA) for Primary Medical Care, from the Health Resources and Services Administration (HRSA) [T32HP300370401].

The co-authors on this work are Jasmine C. Huynh and Qian W. Li from the UC Davis Comprehensive Cancer Center; David J. Benjamin of University of California, Irvine; Lena E. Winestone of University of California, San Francisco; and Lori Muffly of Stanford University.

Article: Abrahão et al. (2020) Chronic medical conditions and late effects after acute myeloid leukemia in adolescents and young adults: a population-based study. International Journal of Epidemiology. Doi: 10.1093/ije/dyaa184

Journal

International Journal of Epidemiology

DOI

10.1093/ije/dyaa184

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University of California - Davis Health

Study confirms spit testing may help doctors diagnose concussions

HERSHEY, Pa. -- Doctors may soon be able to more accurately diagnose concussions by measuring the number of certain molecules in a person's saliva, according to Penn State College of Medicine researchers. The results of a recent clinical study confirmed that a patient's spit may be used to aid concussion diagnosis in a non-invasive, non-biased fashion.

Researchers analyzed the saliva of more than 500 study participants for tiny strands of genetic material called micro ribonucleic acid (microRNA). These molecules play an important role in cellular processes and exist in high amounts in the brain. The investigators hypothesized that due to the presence of cranial nerves in the mouth, altered microRNA levels could indicate whether a patient is experiencing a concussion.

Concussions occur as a result of physical injury to the head and may result in short-lived symptoms including headaches, dizziness and confusion. Physicians currently use symptom scales and neurocognitive tests to assess patients and diagnose concussions. Researchers say these methods may not be reliable because they can be subject to patient and physician bias. For example, athletes may underreport a symptom's severity to return to the field.

"Current methods rely on accurate symptom reporting and honest performance on neurocognitive testing," said Dr. Steve Hicks, associate professor of pediatrics and principal investigator. "Analyzing microRNA profiles in saliva following a head trauma is a non-invasive way to test for concussion that can't be influenced by a patient's feelings or motives."

To develop the diagnostic approach, researchers recruited 538 participants across 11 clinical sites. Approximately half the participants had a concussion reported within two weeks of starting the study, while the other half of participants did not, but had conditions that might mimic concussion symptoms including anxiety, depression, attention deficit hyperactivity disorder, exercise-related fatigue or chronic headaches.

The researchers used RNA sequencing to evaluate saliva samples from half of the participants, then used statistical modeling and machine learning to identify noticeable differences between the RNA profiles of participants with concussions and those without. Once they knew what RNA changes to look for, they tested more than 200 additional participants and were able to successfully identify which patients had concussions. The accuracy of the saliva approach performed favorably when compared with currently available tests involving balance and reaction time. The results were published in the journal Clinical and Translational Medicine.

"This method has lots of promising applications," Hicks said. "A rapid, reliable diagnostic means that early, appropriate action can be taken to alleviate the symptoms of patients with concussions."

Hicks said the work expands upon a smaller pilot study that showed microRNA could be used to predict the duration of concussion symptoms and that further effort is needed to develop the test into a portable technology that can be used field-side by athletic trainers immediately after an injury occurs, by emergency responders at the scene of an accident, or by army medics on a battlefield. He is working with Quadrant Biosciences, who recently received a grant to do a larger clinical study to validate the method and further develop the technology.

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Penn State

Study finds surprising diversity in early child care

COLUMBUS, Ohio - A new study of kindergarteners in one Midwestern state identified seven different pathways the children took in their early education and care before arriving at school.

The researchers were surprised by the diverse experiences that kids brought with them to kindergarten: While some received care only in their home or mainly in a child care center, others switched back and forth between different types of care, or had other arrangements.

This study is one of the few that has looked at kids' child care experiences all the way from birth to kindergarten, which allowed the researchers to capture the broad range of pathways, said Nathan Helsabeck, lead author of the study and a graduate research associate in educational studies at The Ohio State University.

"There are more nuanced differences in children's experiences before kindergarten than we originally thought," said Helsabeck, who is also an associate of Ohio State's Crane Center for Early Childhood Education and Policy.

"Looking at how children get to kindergarten could help us better consider what they need when they are entering school."

The study was published online in the journal Early Education and Development.

The study is part of a larger federally funded project designed to improve understanding of what happens in classrooms from pre-school to third grade. Data was collected from two large, suburban school districts including 25 schools, 152 classrooms and 3,472 students. A subsample of 568 students was used in this study.

One part of the study involved having parents complete questionnaires about their children's education and care from birth to 5 years old.

The researchers found that the largest group of children - 44% - received care only in the home over the first five years of life.

About 10% spent their first two years at home and in the third year became increasingly likely to be in center-based care. Another 7% spent these early years mostly in center-based care.

Those were the three pathways that the researchers had hypothesized would occur before they conducted the study, said Kelly Purtell, co-author of the study and associate professor of human sciences at Ohio State and faculty associate at the Crane Center.

But they found four other pathways as well: The second-largest group, 21%, were at home most of the early years, but were enrolled in a preschool or pre-kindergarten program in the last year before kindergarten. Other groups included children mostly cared for in informal settings (5%); those who went between home and informal care (8%); and those had both home and center care through the whole 5 years (5%).

Why were there so many different pathways?

"It reflects the patchwork availability of child care in this country," Purtell said.

"Child care for infants and young kids is expensive, so there are not a lot of affordable options for parents. Parents have to find different ways to take care of their kids while they work."

Helsabeck said he was particularly struck by the children whose care shifted from year to year, often from home to informal care, as their parents' situations changed.

"There was more than I expected in this category," he said.

"We need to realize that some kids face a lot of instability and their child care situations may change a lot. That may affect how they do in school."

The study also looked at how children who took different pathways did in kindergarten.

Findings did not show differences in test scores between children from different pathways. That was surprising, because most studies show an advantage to kids who spent more time in center-based care, Helsabeck said.

But he cautioned against making too much of that finding. It could be that there were not enough children in each of the seven groups to reveal differences in this study.

Results confirmed other studies that found children who spent most of their time in center-based care during their first five years had more teacher-reported social and behavioral problems in kindergarten.

That may be because these kids are already comfortable in school-like settings and are not as shy about acting out, Purtell said. They may also be more easily bored because for them, the experience is not novel.

"This is a real challenge for kindergarten teachers to navigate children who are brand new to this setting with those kids who are already familiar with the classroom setting," she said.

The researchers said that the seven pathways to kindergarten found in this study may not be the same everywhere.

"We looked at only two school districts in one state. That's not going to represent the whole country," Helsabeck said.

"But what we can take away from this is the wide range of experiences kids bring to kindergarten. It is going to affect how they do in school."

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Ohio State University

New discovery may change how dexamethasone is prescribed for some COVID-19 patients

Research has shown that dexamethasone, a widely available steroid, can significantly reduce the chance of death from COVID-19. However, because of the way dexamethasone is transmitted throughout the body, it may be less effective in patients with diabetes, according to new research performed at the Advanced Photon Source (APS), a U.S. Department of Energy (DOE) Office of Science User Facility at DOE’s Argonne National Laboratory.

A research team led by scientists at the University of Virginia studied the way a blood protein, called serum albumin, picks up and transports dexamethasone throughout the body. The team used powerful X-rays from the APS to get a full picture of the structure of serum albumin combined with dexamethasone. Their work was published in the Journal of the International Union of Crystallography.

Low levels of albumin may already make it more difficult for some patients to get the benefits of dexamethasone. This research shows that patients with diabetes may experience the same difficulty, since high blood sugar changes the way albumin binds with dexamethasone. These findings, researchers say, may lead to physicians rethinking how they prescribe the drug for certain patients.

The X-ray macromolecular crystallography work was performed at Life Sciences Cooperative Access Team (LS-CAT) beamline 21-ID-F at the APS. The research team made use of remote access technology to control the APS beam without visiting the site.

“Gaining new insight into the mechanisms of this drug will help doctors design more effective treatments,” said Argonne’s Bob Fischetti, life sciences advisor to the APS director. “Since the start of this pandemic, the APS has been a powerful tool for gaining insights into the virus itself, and into methods for combating it.”

This research is the latest of many contributions the APS has made to the battle against COVID-19. Since January the APS has devoted more than 8,000 hours of experimental time across multiple X-ray beamlines to research on the SARS-CoV-2 virus. As of October 2020, more than 70 groups of researchers have used the APS to learn more about the virus, and lay the groundwork for treatments and vaccines.

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DOE/Argonne National Laboratory

Study finds patients prefer doctors who share their same race/ethnicity

PHILADELPHIA - Patients who shared the same racial or ethnic background as their physician were more likely to give the maximum patient rating score, according to a new analysis of 117,589 patient surveys from 2014 to 2017. The findings, from a team of Penn Medicine researchers, were published today in JAMA Network Open.

"What it comes down to is that patients who see physicians of their own race or ethnicity are more likely to rate their physicians higher than patients who see physicians of a different race or ethnicity," said the study's corresponding author Junko Takeshita, MD, PhD, MSCE, an assistant professor of Dermatology and Epidemiology in the Perelman School of Medicine at the University of Pennsylvania.

The study's findings underscore the need for health systems to address issues of implicit biases and to diversify the physician workforce, she added. "In a healthcare setting, racial and ethnic biases can affect health care delivery and ultimately, lead to health disparities."

In order to improve patient-centered care, health systems have made strides to both measure and publicly share patient ratings for individual physicians, sometimes linking these ratings to promotion and compensation decisions. The Press Ganey Outpatient Medical Practice Survey is one such tool used by many practices to evaluate the patient experience. Despite its wide use, the relationships between the patient experience and patient, physician, and clinical encounter characteristics are not completely understood, particularly when it comes to whether racial/ethnic concordance leads to higher Press Ganey scores.

To explore the relationships between race/ethnicity, as well as gender, and patient experience, the research team examined 117,589 Press Ganey surveys collected following adult outpatient visits across various medical specialties within the University of Pennsylvania Health System between July 2014 and May 2017. The patients were predominantly white (81.6 percent), followed by Black (12.8 percent), Asian (3.4 percent), and Hispanic (2.3 percent).

The surveys query patients on six domains: access, moving through your visit, nurse/assistant, care provider, personal issues, and overall assessment. Patients can rate their experience in each domain, ranging from one (very poor) to five (very good). For their study, the researchers focused on the responses for the "likelihood of your recommending this care provider to others" in the care provider domain of the survey.

They found that 87.6 percent of physicians from racially/ethnically concordant patient-physician pairs received the maximum score for this question, while only 82.1 percent of physicians from discordant pairs received the maximum score.

At the level of specific patient-physician racial/ethnic pairs, among Black patients, for example, the average ratings for white physicians were 0.03 points lower than those for Black physicians. According to Takeshita, these seemingly small differences are significant.

"Even a 0.02 difference in the mean score for the Press Ganey survey could take a physician from the 100th percentile down to the 70th percentile in terms of rankings," Takeshita said.

Along with examining racial/ethnic concordance, the authors also investigated gender concordance as a factor that might affect the patient experience. However, unlike the racial/ethnic concordance data, analyses incorporating gender did not reveal statistically significant differences in ratings.

While a valuable tool and reflection of the patient experience, there are limitations to the Press Ganey survey, said study senior author Deirdre Sawinski, MD, an associate professor of Renal-Electrolyte and Hypertension in the Perelman School of Medicine. In particular, it was not meant to be used to evaluate and compare individual physicians to one another, she said.

"Misapplication of these evaluations on an individual level can disadvantage some physicians in terms of survey data being used for promotions or bonuses," Sawinski said. "Misinterpreting the data can contribute to physician burnout or job dissatisfaction and not get at the heart of what's important for the patient experience. This study is an important step towards understanding how different factors contribute to create the patient experience, but clearly there is still more work to do. Most of all, we do not want our findings to discourage physicians from caring for a diverse patient population."

Even so, the study's findings suggest that racial/ethnic concordance does in fact play a role in patient-physician interactions, and the team hopes this will generate discussion and action to improve cultural competency among all physicians, so that they are prepared to care for a diverse patient population.

"Our data highlights why it's more important than ever to have a diverse physician workforce who looks like all the different types of patients we take care of, including different genders and different races," Sawinski said.

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University of Pennsylvania School of Medicine

Cleveland Clinic researchers identify melatonin as possible COVID-19 treatment

CLEVELAND - Results from a new Cleveland Clinic-led study suggest that melatonin, a hormone that regulates the sleep-wake cycle and is commonly used as an over-the-counter sleep aid, may be a viable treatment option for COVID-19.

As COVID-19 continues to spread throughout the world, particularly with cases rising during what some have termed the "fall surge," repurposing drugs already approved by the U.S. Food and Drug Administration for new therapeutic purposes continues to be the most efficient and cost-effective approach to treat or prevent the disease.
According to the findings published today in PLOS Biology, a novel artificial intelligence platform developed by Lerner Research Institute researchers to identify possible drugs for COVID-19 repurposing has revealed melatonin as a promising candidate.

Analysis of patient data from Cleveland Clinic's COVID-19 registry also revealed that melatonin usage was associated with a nearly 30 percent reduced likelihood of testing positive for SARS-CoV-2 (the virus that causes COVID-19) after adjusting for age, race, smoking history and various disease comorbidities. Notably, the reduced likelihood of testing positive for the virus increased from 30 to 52 percent for African Americans when adjusted for the same variables.

"It is very important to note these findings do not suggest people should start to take melatonin without consulting their physician," said Feixiong Cheng, Ph.D., assistant staff in Cleveland Clinic's Genomic Medicine Institute and lead author on the study. "Large-scale observational studies and randomized controlled trials are critical to validate the clinical benefit of melatonin for patients with COVID-19, but we are excited about the associations put forth in this study and the opportunity to further explore them."

Here, the researchers harnessed network medicine methodologies and large-scale electronic health records from Cleveland Clinic patients to identify clinical manifestations and pathologies common between COVID-19 and other diseases. Specifically, they measured the proximity between host genes/proteins and those well-associated with 64 other diseases across several disease categories (malignant cancer and autoimmune, cardiovascular, metabolic, neurological and pulmonary diseases), where closer proximity indicates a higher likelihood of pathological associations between the diseases.

They found, for example, that proteins associated with respiratory distress syndrome and sepsis, two main causes of death in patients with severe COVID-19, were highly connected with multiple SARS-CoV-2 proteins. "This signals to us, then," explained Dr. Cheng, "that a drug already approved to treat these respiratory conditions may have some utility in also treating COVID-19 by acting on those shared biological targets."

Overall, they determined that autoimmune (e.g., inflammatory bowel disease), pulmonary (e.g., chronic obstructive pulmonary disease and pulmonary fibrosis) and neurological (e.g., depression and attention-deficit hyperactivity disorder) diseases showed significant network proximity to SARS-CoV-2 genes/proteins and identified 34 drugs as repurposing candidates, melatonin chief among them.

"Recent studies suggest that COVID-19 is a systematic disease impacting multiple cell types, tissues and organs, so knowledge of the complex interplays between the virus and other diseases is key to understanding COVID-19-related complications and identifying repurposable drugs," said Dr. Cheng. "Our study provides a powerful, integrative network medicine strategy to predict disease manifestations associated with COVID-19 and facilitate the search for an effective treatment."

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Cleveland Clinic

Putting stock into Twitter: Social media can influence returns, WVU finance professor says

image: Alexander Kurov has studied Twitter's effect on the stock market.

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Brian Persinger/West Virginia University

Twitter's impact is not limited to news, sports and political opinions.

Posts on the social media platform can influence stock returns, according to research led by a West Virginia University financial expert.

Alexander Kurov, Fred T. Tattersall Research Chair and Professor of Finance in the John Chambers College of Business and Economics, found that firm-level Twitter content has information useful for predicting next-day stock returns, and that it is a stronger predictor of returns for firms with less analyst coverage.

Kurov co-authored the study, "Informational role of social media: Evidence from Twitter sentiment," with Chen Gu, a 2018 graduate of the WVU finance doctoral program. Their findings are being published in the Journal of Banking and Finance.

In reaching their conclusions, Kurov and Gu obtained data from Bloomberg, which classifies individual tweets about a given company, aggregates them and calls the resulting variable "Twitter sentiment."

"Academic research in finance generally shows that investor sentiment tends to be driven by investor beliefs or feelings not justified by fundamentals, such as facts and rational expectations that should determine the value of a stock," Kurov said. "Our results show, however, that Twitter sentiment contains relevant information not yet reflected in stock prices.

"In particular, we show that Twitter sentiment contains information about upcoming analyst recommendation changes, analyst target price changes, quarterly earnings surprises and opening prices of stock initial public offerings."

Since 2013, the Securities and Exchange Commission has allowed public firms to distribute news, such as quarterly earnings, to the public via Twitter. The increased use of Twitter by firms and investors - including famous names like Warren Buffett - spurred Kurov and Gu to research the matter and determine how social media can be employed as part of an investment strategy.

Kurov also pointed to events in which information was prematurely revealed on Twitter, leading to large moves in stock prices.

For example, at a 2016 conference of the American Diabetes Association, the results of a clinical trial of Victoza, a new diabetes drug produced by Novo Nordisk, were announced during a presentation. While the ADA asked attendees to keep that information confidential, pictures of presentation slides showing those results popped up on several Twitter accounts within minutes.

Novo's stock price fell by 5.6 percent the following day because the new drug appeared less effective than expected.

"On the one hand, it is possible that tweets mentioning companies have little new relevant information," Kurov said. "In that case, Twitter content is just random noise that should have no permanent effect on stock prices. On the other hand, Twitter may aggregate bits and pieces of relevant information from diverse sources. We wanted to see which of these two plausible stories has more support in the data. Some previous studies have looked at information content of Twitter messages, but we were the first to test systematically if these messages contain useful information about thousands of individual stocks."

These findings have important implications for market participants, Kurov added. Traders should now analyze social media content carefully, and entities should continue to improve transparency and market efficiency by utilizing social media, he said.

And despite the evidence that tweets can influence stock prices, Kurov said it is unlikely that firms or investors can systematically manipulate stocks through Twitter activity.

"If a Twitter feed consistently disseminates information that is not factual, investors will quickly figure this out," he said. "Furthermore, spreading false information with intent to manipulate security prices is illegal and could make the person doing that a target of an investigation by the Securities and Exchange Commission."

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West Virginia University

COVID Misinformation a Roadblock to Curbing Pandemic

image: HDFS Professor Valerie Earnshaw's new research confirms that stigma around COVID-19 may lead people to avoid testing and that people who believe COVID conspiracies will be less likely to support public health policies to slow the pandemic's spread.

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Photo by Elizabeth Adams

The World Health Organization calls the spread of false information about the coronavirus (COVID-19) an "infodemic," and the results are broadly visible across society. The refusal of some people to wear a mask or socially distance, or self-quarantine when exposed to the virus, is often motivated by false information or conspiracy theories that are popular on social media.

So what are public health officials to do?

In a pair of newly published studies, University of Delaware researchers shed new light on the stigma, stereotypes and conspiracy theories that have spread alongside the novel coronavirus.

Understanding the impact of misinformation "is important for identifying potential barriers to public health efforts" to combat the virus, said Valerie Earnshaw, associate professor in UD's Department of Human Development and Family Sciences and lead author on both studies.

"Evidence suggests that people are more likely to believe conspiracy theories when they feel anxious, powerless, and unable to control their outcomes, as well as in times of crisis and when faced with large-scale events with serious consequences," she said. "Pandemics such as COVID-19 are powerful contexts wherein individuals may turn to conspiracy theories in an attempt to restore feelings of safety and control."

Ultimately, the more prominent the misinformation, the more difficult it will be for communities to bring the pandemic under control.

The first study, "Anticipated Stigma, Stereotypes, and COVID-19 Testing," which appeared in the journal Stigma and Health, suggests that stereotypes and anticipated stigma may be barriers to COVID-19 testing efforts. The results, Earnshaw said, are very similar to previous studies about HIV and Ebola stigma.

"We know from studies on mental illness and HIV that stigma will keep people from getting tested," said Earnshaw. "And stereotypes are one way that people experience stigma. Stereotypes are how stigma gets into our heads and shapes our views. Stereotypes help people feel safe. Stereotypes help people believe that those who get COVID, or HIV, are unlike them or doing the wrong thing. Stereotypes can sometimes give people a false security blanket."

Participants who anticipated more stigma, and those who endorsed more harmful stereotypes, reported that they would be less likely to get tested for COVID-19. By contrast, participants who demonstrated greater knowledge of COVID-19 reported that they would be more likely to get tested.

The second study, "COVID-19 conspiracy beliefs, health behaviors, and policy support," which appeared in the journal Translational Behavioral Medicine, found that one-third of participants believed in one or more conspiracies about COVID-19, and the results suggest that belief in conspiracy theories makes a person less likely to support public health policies designed to slow the spread of the virus. Participants who believed in conspiracy theories said that they were less likely to get vaccinated and trusted public health experts less.

The results of both studies were derived from an online survey of 845 U.S. adults that was conducted in April 2020. The survey was posted to Amazon Mechanical Turk, a crowdsourcing marketplace that researchers use to "collect rapid, high-quality data for psychological studies," said Earnshaw.

Despite the prevalence of misinformation, both studies suggest that people trust their personal doctor, regardless of their conspiracy beliefs. In the first study, most participants agreed that they would get tested if ordered by their doctor. In the second study, over 90% said they trusted information about COVID-19 from their doctor.

"Medical doctors are highly trusted sources of medical information," said Earnshaw. "Doctors can play a leading role in combating misinformation because even people who believe conspiracy theories still believe information about COVID from their doctors."

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University of Delaware

New insight into a placental gene pathway and its association with vitamin D

image: Illustration showing the relationship between preeclampsia and an axis of genes that includes NKX2-5, also known as the tinman gene. Angiogenesis is the development of new blood vessels. VEGFR1 = vascular endothelial growth factor receptor 1.

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Medical University of South Carolina

According to the World Health Organization, preeclampsia affects between 2% to 8% of pregnancies. It can cause serious, sometimes fatal, complications in the mother and child. Among other risk factors, such as obesity and diabetes, vitamin D deficiency during pregnancy has been associated with an increased risk of preeclampsia.

In an article in Pregnancy Hypertension, a team of researchers at the Medical University of South Carolina (MUSC) found that expression of a set of genes previously studied in the setting of early onset and severe preeclampsia is significantly affected by vitamin D status during late-stage pregnancy.

Exactly how preeclampsia develops is unclear. Recent evidence points to poor development of blood vessels in the placenta - the organ that nourishes the fetus throughout pregnancy. This leads to hypertension and several other complications in the mother. The only cure for preeclampsia is to deliver the fetus, which can be dangerous if done too early.

In a previous study that was supported by pilot funding from the South Carolina Clinical & Translational Research Institute (SCTR), the research team led by Kyu-Ho Lee, M.D., Ph.D., assistant professor in the departments of Pediatrics and Obstetrics and Gynecology at MUSC found that the expression of three genes - NKX2-5, SAM68, and sFLT1 - are highly correlated in the setting of early-onset and severe preeclampsia (EOSPE), with sFLT1 being an identified marker for preeclampsia risk. In the current study, which also received SCTR support, the authors examined the expression of these genes in healthy pregnant women.

"Having observed the correlated expression of these genes in preeclampsia, we wanted to see the pattern of expression of these genes in normal pregnancy," said Lee. "We had a secondary goal of seeing whether vitamin D status affected the expression of these genes."

The sFLT1 protein interferes with the activity of vascular endothelial growth factor (VEGF), which is an important regulator of blood vessel development. This reduces vascular growth in the placenta. The amount of sFLT1 in the placenta is regulated in part by SAM68 and NKX2-5, also known as the tinman gene. This hypothesized NKX2-5/SAM68/sFLT1 gene "axis" may contribute to the development of preeclampsia.

"NKX2-5 might be controlling the regulation of sFLT1 and SAM68 in such a way that in preeclampsia, the expression levels of those genes go awry and tilt the vascular development in a direction that might trigger preeclampsia," said Lee.

Vitamin D affects many aspects of the mother's health during pregnancy. To investigate how the gene axis is affected by maternal vitamin D status, Lee's team studied placental samples from 43 pregnant women enrolled in a clinical trial at MUSC organized by their collaborator, MUSC Health neonatologist Carol L. Wagner, M.D., a professor in the Department of Pediatrics. Half of the women received a high dose of vitamin D3 (4,000 IU/day), and the other half received a placebo. The study group included African American, Hispanic American and Caucasian American women.

In contrast to their previous study, the team did not detect significant levels of NKX2-5 in placental tissue samples before a healthy delivery. This finding suggests that NKX2-5 expression is important in early at-risk pregnancies but not healthy pregnancies. However, the team did observe a strong positive correlation between SAM68 and sFLT1 in all study participants.

"The tight correlation between SAM68 and sFLT1 makes us think that there's a functional relationship between these genes," said Lee.

Interestingly, when assessed at the last visit before delivery, women who were vitamin D deficient (

This study provides novel insight into the activity of the NKX2-5/SAM68/sFLT1 gene axis during healthy pregnancies in a diverse group of women and how it may be affected by the vitamin D status of the mother.

"These results raise the possibility that vitamin D somehow directly regulates sFLT1 and/or SAM68 expression at some level," said Lee. "However, at this point, we haven't addressed the exact molecular relationship."

Future studies might investigate the relationship between vitamin D status and the expression of sFLT1 and SAM68 in mothers diagnosed with preeclampsia.

"Ideally, you would want a study with an equal number of diseased versus control pregnancies that had differential levels of vitamin D," said Lee. "Then we could look at the incidence of disease in correlation to the levels of vitamin D they achieved and the amount of gene expression that we had observed."

The team's current findings contribute to a basic biological understanding of the development of pregnancy and preeclampsia. Lee believes that this understanding will improve the standard of care for treating preeclampsia.

"We can begin to develop clinical markers that would help us gauge the health of a pregnancy during its course," said Lee. "This could provide warning signs for an increasing risk of pregnancy complication."

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Medical University of South Carolina

Why do bats fly into walls?

Bats excel in acoustic perception and detect objects as tiny as mosquitoes using sound waves. Echolocation permits them to calculate the three-dimensional location of both small and large objects, perceiving their shape, size and texture. To this end, a bat's brain processes various acoustic dimensions from the echoes returning from the object such as frequency, spectrum and intensity.

But sometimes bats collide with large walls even though they detect these walls with their sonar system. Researchers from Tel Aviv University (TAU) have concluded that these collisions do not result from a sensory limitation but rather from an error in acoustic perception.

The study was led by Dr. Sasha Danilovich, a former PhD student in the lab of Prof. Yossi Yovel, Head of the Sagol School for Neuroscience and faculty member at the School of Zoology at the George S. Wise Faculty of Life Sciences. Other participants included Dr. Arian Bonman and students Gal Shalev and Aya Goldstein of the Sensory Perception and Cognition Laboratory at the School of Zoology and the Sagol School of Neuroscience. The paper was published on October 26, 2020, in PNAS.

The TAU researchers released dozens of bats in a corridor blocked by objects of different sizes and made of different materials. To their surprise, the researchers discovered that the bats collided with large sponge walls that produce a weak echo as if they did not exist. The bats' behavior suggested that they did this even though they had detected the wall with their sonar system, indicating that the collision did not result from a sensory limitation, but rather from an acoustic misperception.

The researchers hypothesize that the unnatural combination of a large object and a weak echo disrupts the bats' sensory perception and causes them to ignore the obstacle, much like people who bump into transparent walls.

The researchers then methodically changed the features of the objects along the corridor, varying their size, texture and echo intensity. They concluded that the bats' acoustic perception depends on a coherent, typical correlation of the dimensions with objects in nature -- that a large object should produce a strong echo and a small object a weak echo.

"By presenting the bats with objects whose acoustic dimensions are not coherent, we were able to mislead them, creating a misconception that caused them to repeatedly try to fly into a wall even though they had identified it with their sonar," Danilovich explains. "The experiment gives us a peek into how the world is perceived by these creatures, whose senses are so unique and different from ours."

Credit: 
American Friends of Tel Aviv University

Researchers isolate and decode brain signal patterns for specific behaviors

image: Brain with its fibers showing its immense complexity. The new machine learning method can isolate patterns in brain signals that relate to a specific behavior and decode the behavior much better.

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Omid Sani & Maryam Shanechi, Shanechi Lab at the USC Viterbi School of Engineering

At any given moment in time, our brain is involved in various activities. For example, when typing on a keyboard, our brain not only dictates our finger movements but also how thirsty we feel at that time. As a result, brain signals contain dynamic neural patterns that reflect a combination of these activities simultaneously. A standing challenge has been isolating those patterns in brain signals that relate to a specific behavior, such as finger movements. Further, developing brain-machine interfaces (BMIs) that help people with neurological and mental disorders requires the translation of brain signals into a specific behavior, a problem called decoding. This decoding also depends on our ability to isolate neural patterns related to specific behaviors. These neural patterns can be masked by patterns related to other activities and can be missed by standard algorithms.

Led by Maryam Shanechi, Assistant Professor and Viterbi Early Career Chair in Electrical and Computer Engineering at the USC Viterbi School of Engineering, researchers have developed a machine learning algorithm that resolved the above challenge. The algorithm published in Nature Neuroscience uncovered neural patterns missed by other methods and enhanced the decoding of behaviors that originated from signals in the brain. This algorithm is a significant advance in modeling and decoding of complex brain activity which could both enable new neuroscience discoveries and enhance future brain-machine interfaces.

Standard algorithms, says Shanechi, can miss some neural patterns related to a given behavior that are masked by patterns related to other functions happening simultaneously. Shanechi and her PhD student Omid Sani developed a machine learning algorithm to resolve this challenge.

Shanechi, the paper's lead senior author says, "We have developed an algorithm that, for the first time, can dissociate the dynamic patterns in brain signals that relate to specific behaviors one is interested in. Our algorithm was also much better at decoding these behaviors from the brain signals."

The researchers showed that their machine learning algorithm can find neural patterns that are missed by other methods. This was because unlike prior methods which only consider brain signals when searching for neural patterns, the new algorithm has the ability to consider both brain signals and the behavioral signals such as the speed of arm movements. Doing so, says Sani, the study's first author, the algorithm discovered the common patterns between the brain and behavioral signals and was also much better able to decode the behavior represented by brain signals. More generally, he adds, the algorithm can model common dynamic patterns between any signals for example, between the signals from different brain regions or signals in other fields beyond neuroscience.

To test the new algorithm, the study's authors, which include Shanechi's PhD students Omid Sani and Hamidreza Abbaspourazad, as well as Bijan Pesaran, Professor of Neural Science at NYU and Yan Wong, a former Post-Doc at NYU, relied on four existing datasets collected in the Pesaran Lab. The datasets were based on recorded changes in the neural activity during the performance of different arm and eye movement tasks.

In the future, this new algorithm could be used to develop enhanced brain-machine interfaces that help paralyzed patients by significantly improving the decoding of movement or speech generated by brain signals and thus translating these signals into a specific, desired behavior such as body movements. This could allow a paralyzed patient to move a robotic arm by merely thinking about the movement or generate speech by just thinking about it. In addition, this algorithm could help patients with intractable mental health conditions such as major depression by separating brain signals related to mood symptoms and allowing for real-time tracking of these symptoms (which is outlined in previous studies Shanechi completed). The tracked symptom could then be used as feedback to tailor a therapy to a patient's needs.

Shanechi adds, "By isolating dynamic neural patterns relevant to different brain functions, this machine learning algorithm can help us investigate basic questions about brain's functions and develop enhanced brain-machine interfaces to restore lost function in neurological and mental disorders."

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University of Southern California

Don't be fooled by pretty food, USC research warns

image: USC researcher Linda Hagen found that food that is presented and styled expertly was often perceived as better or more natural.

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(Photo/iStock)

As the holiday season nears, thoughts of pumpkin pies, roasted chestnuts and turkey dinners fill our dreams and our grocery shopping lists. While visions of holiday food may be pleasing to the eyes and tantalizing to the palate, it would be a mistake to conclude that pretty food is healthier than other food.

Yet consumers often fail to make the distinction, a mistake that the food industry, advertisers and restaurants count on to promote products.

So says USC research recently published in the Journal of Marketing. The study employed social science and psychology to unravel the complexity of how perceptions of beauty drive our appetite and spending decisions. And the researcher suggested measures that industry and policymakers can take to protect public health.

"Marketers frequently style food to look pretty," said Linda Hagen, the study's lead author and an assistant professor of marketing at the USC Marshall School of Business. "In our minds, people associate aesthetic beauty with nature and natural things, which transfers to perceptions that pretty food is healthy food, but people are often misled by the prettiness of food that's not very good for you."

Consumers see almost 7,000 food and restaurant ads annually -- about 19 per day -- and nearly three-quarters of the messages promote fast food. Advertisers employ teams of food stylists and digital tools to render food irresistible. The images include the artful architecture of a hamburger, a perfect circumference of cheesy pizza or cascading colorful nachos or French fries.

Hagen examined how classical aesthetics used in food presentation skews perception. Features such as symmetry, patterns, order and balance are hallmarks of classical beauty because they mimic nature. Think spider webs or honeycombs, a starfish or sunsets, butterfly wings or fish scales. Food looks pretty when it copies naturelike features. Moreover, previous neuroscience research suggests viewing delectable food images activates the brain's gustatory cortex, essentially simulating the food's pleasurable taste.

USC research shows a perceived link between pretty and healthy food

This study goes a step further to determine if pretty aesthetics have other, less obvious effects on food choices, assessing if attractive food appears healthier to consumers and thus influences their decisions.

In a series of experiments involving 4,300 subjects, the researcher asked people to examine photos of food as well as actual samples of food, then evaluate the displays as healthy or unhealthy and processed or unprocessed.

In the first study, 800 people were asked to search the internet and pick out samples of pretty or ugly food. The subjects returned with images of ice cream, lasagna, omelets and sandwiches, among other items. Next, subjects were asked to determine if the food was nutritious and healthy or not. Overwhelmingly, both men and women reported that pretty food was healthier.

In another experiment, 400 subjects evaluated two renderings of avocado toast: one image that showed neatly sliced crescents of delicate avocado arrayed on the toast and the other that depicted the fruit as a chunky green glop smeared on the bread. The participants were asked to rate the images by healthiness, naturalness and tastiness.

For each criterion, the subjects reported the pretty version of avocado toast as healthier and more natural, but the foods were viewed as equally expensive and tasty, the study shows.

The same outcome occurred with another group of 800 study participants who viewed pictures of foods such as cupcakes, almond bread with bananas and a plate of spaghetti marinara -- but with a caveat. Before they saw the images, the researcher had advised the subjects that the image they were about to see was aesthetically either flawed or beautiful, even though the image was the exact same photo. Biased by their expectation, the subjects considered the "ugly" food less natural and nutritious than the "pretty" food, though there was no real difference.

And the pattern continued in another experiment at a curbside produce stand that Hagen set up during move-in day at USC several years ago. She gave students $1, led them to a booth and showed them one of two green bell peppers: either a cosmetically perfect one or a somewhat odd-shaped one. When asked how much money they would maximally pay to purchase the bell pepper, the subjects were willing to spend roughly 56% more for the flawless fruit, a boost that was explained by a simultaneous increase in perceived healthiness.

"Time and again, in each of these experiments, people perceived the same food as more natural when it looks prettier and believe that this naturalness implies healthiness," Hagen said. "Consumers expect food to be more nutritious, less fatty and contain fewer calories when it looks pretty based on classical aesthetic principles, and that bias can affect consumer choices and willingness to pay for food."

Advertisements for pleasing-looking food may have more influence than you realize

In daily life, the effect holds true at the grocery store, where people consider natural things -- organic food, natural remedies or garden crops -- to be healthier than unnatural things such as processed food or synthetic chemicals.

Given that stylized food advertisements can mislead consumers into making unhealthy choices, the study suggests that companies or regulators consider measures such as disclaimers on food images in ads to disclose that the product has been modified to enhance its healthy appearance.

"Many food advertisements and restaurant menus may be suggesting greater levels of healthiness in food than is true," Hagen said. "The use of aesthetics that misleads people warrants close consideration by policymakers. A statement that explicitly reminds people that pretty food was modified for depiction helped mitigate the effect in the lab, so disclaimers may be an effective way to protect consumers."

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University of Southern California

Researchers identify new Rickettsia species in dogs

Researchers at North Carolina State University have identified a new species of Rickettsia bacteria that may cause significant disease in dogs and humans. This new yet unnamed species, initially identified in three dogs, is part of the spotted-fever group Rickettsia which includes Rickettsia rickettsii, the bacteria that cause Rocky Mountain Spotted Fever (RMSF).

Rickettsia pathogens are categorized into four groups; of those, spotted-fever group Rickettsia (which are transmitted by ticks) is the most commonly known and contains the most identified species. There are more than 25 species of tick-borne, spotted-fever group Rickettsia species worldwide, with R. rickettsii being one of the most virulent and dangerous.

For dogs, R. rickettsii is the only known spotted fever group Rickettsia that causes clinical disease in North America. Symptoms of RMSF in dogs and people are similar, including fever, lethargy, weight loss and symptoms related to vascular inflammation, like swelling, rash and pain.

In 2018 and 2019, three dogs from three different states (Tennessee, Illinois and Oklahoma) with exposure to ticks and RMSF-associated symptoms had blood samples taken, to test them for R. rickettsii. While the samples reacted positively to antibody tests for R. rickettsii, when researchers at NC State utilized polymerase chain reaction (PCR) to amplify the pathogen's DNA from the samples, the DNA they retrieved was only 95% similar to R. rickettsii.

"Often, antibodies from other spotted fever group Rickettsia will cross-react in antibody tests for RMSF," says Barbara Qurollo, associate research professor at NC State and corresponding author of a paper describing the work. "So to be sure what we're dealing with, we also look at the genetic information via PCR and that's how we found that this is a new organism."

The initial PCR work led Qurollo and James Wilson, a PCR technician at NC State and first author of the study, to pursue the new bacteria further. They performed additional PCRs to amplify different genes and examined five different regions of the bacteria's DNA, comparing it to the sequenced DNA from other spotted fever group Rickettsia. They also performed a phylogenetic tree analysis, which allowed them to place the new Rickettsia firmly within the spotted fever group.

Before naming this new Rickettsia species, Qurollo and colleagues want to culture the organism, which would allow for better characterization of the new species. Culturing Rickettsia species from small amounts of a clinical sample has been difficult to do thus far.

"We're going to continue looking for this Rickettsia species, determine its geographical range and try to better characterize it - it's a slow process, but high on our radar," Qurollo says. "So far in 2020 we've detected this new Rickettsia species in four more dogs residing in the southeastern and midwestern U.S. We're also asking veterinarians to collect the ticks associated with dogs who show symptoms when possible, and we're collaborating with researchers in Oklahoma to collect ticks in the environment for testing. This will help us determine what tick species may be transmitting this particular bacteria.

"Another question we would like to answer is whether this new Rickettsia species also infects people. Dogs are great sentinels for tick-borne diseases - they have high rates of exposure to ticks and the ability to become infected with many of the same tick-borne pathogens that infect people. We hope to take a 'One Health' approach to this new pathogen and collaborate with scientists in human medicine as well."

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North Carolina State University

Large, delayed outbreaks of endemic diseases possible following COVID-19 controls

Measures to reduce the spread of COVID-19 through non-pharmaceutical interventions (NPIs) such as mask wearing and social distancing are a key tool in combatting the impact of the ongoing coronavirus pandemic. These actions also have greatly reduced incidence of many other diseases, including influenza and respiratory syncytial virus (RSV).

Current reductions in these common respiratory infections, however, may merely postpone the incidence of future outbreaks, according to a study by Princeton University researchers published Nov. 9 in the Proceedings of the National Academy of Sciences.

"Declines in case numbers of several respiratory pathogens have been observed recently in many global locations," said first author Rachel Baker, an associate research scholar at the High Meadows Environmental Institute (HMEI) at Princeton University.

"While this reduction in cases could be interpreted as a positive side effect of COVID-19 prevention, the reality is much more complex," Baker said. "Our results suggest that susceptibility to these other diseases, such as RSV and flu, could increase while NPIs are in place, resulting in large outbreaks when they begin circulating again."

Baker and her co-authors found that NPIs could lead to a future uptick in RSV -- an endemic viral infection in the United States and a leading cause of lower respiratory-tract infections in young infants -- but that the same effect was not as pronounced for influenza.

"Although the detailed trajectory of both RSV and influenza in the coming years will be complex, there are clear and overarching trends that emerge when one focuses on some essential effects of NPIs and seasonality on disease dynamics," said co-author Gabriel Vecchi, Princeton professor of geosciences and the High Meadows Environmental Institute.

The researchers used an epidemiological model based on historic RSV data and observations of the recent decline in RSV cases to examine the possible impact of COVID-19 NPIs on future RSV outbreaks in the United States and Mexico.

They found that even relatively short periods of NPI measures could lead to large future RSV outbreaks. These outbreaks were often delayed following the end of the NPI period, with peak cases projected to occur in many locations in winter 2021-22. "It is very important to prepare for this possible future outbreak risk and to pay attention to the full gamut of infections impacted by COVID-19 NPIs," Baker said.

The authors also considered the implications of COVID-19 NPIs for seasonal influenza outbreaks and found results qualitatively similar to RSV. The dynamics of influenza are much harder to project due to viral evolution, however, which drives uncertainty over future circulating strains and the efficacy of available vaccines.

"For influenza, vaccines could make a big difference," Baker said. "In addition, the impact of NPIs on influenza evolution is unclear but potentially very important."

"The decrease in cases of influenza and RSV -- as well as the possible future increase we project -- is arguably the broadest global impact of NPIs across a variety of human diseases that we've seen," said co-author Bryan Grenfell, the Kathryn Briger and Sarah Fenton Professor of Ecology and Evolutionary Biology and Public Affairs, who is associated faculty in HMEI.

"NPIs could have unintended longer-term impacts on the dynamics of other diseases that are similar to the impact on susceptibility we projected for RSV," he said.

A similar effect of pandemic-related NPIs on other pathogens was observed following the 1918 influenza pandemic. Historic measles data from London show a shift from annual cycles to biennial outbreaks following a period of control measures implemented at that time.

Co-author C. Jessica Metcalf, associate professor of ecology and evolutionary biology and public affairs and an associated faculty member in HMEI, said that directly evaluating the associated risks of NPIs by developing and deploying tools such as serology that would better measure susceptibility is an important public health and policy direction. "The future repercussions of NPIs revealed by this paper hinge on how these measures change the landscape of immunity and susceptibility," Metcalf said.

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Princeton University

Black patients less likely to receive added, higher dose meds to control blood pressure

DALLAS, Nov. 9, 2020 -- Nearly one-third of racial disparities in treating high blood pressure may stem from inequities in treatment intensification, according to preliminary research to be presented at the American Heart Association's Scientific Sessions 2020. The meeting will be held virtually, Friday, November 13 - Tuesday, November 17, 2020, and is a premier global exchange of the latest scientific advancements, research and evidence-based clinical practice updates in cardiovascular science for health care worldwide.

Treatment intensification is critical for optimal blood pressure control and includes either prescribing a new medication in a different class or increasing the dose of an existing medication when a patient's blood pressure is higher than the goal. In this study, the goal levels were 140 mm Hg for the top number (systolic) and 90 mm Hg for the bottom number (diastolic). According to the current American Heart Association/American College of Cardiology Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults, hypertension is defined as 130/80 mm Hg or higher.

"Missed opportunities for increasing therapy may be one of the most significant contributors to racial disparities in blood pressure outcomes that may, in turn, contribute to poor health for Black Americans," said Valy Fontil, M.D., M.A.S., assistant professor of medicine at the University of California San Francisco (UCSF) and first author of the study.

"Achieving blood pressure control in the U.S. still relies on decisions made by clinicians and patients during the clinical encounter," said Kirsten Bibbins-Domingo, Ph.D., M.D., M.A.S., chair of the department of epidemiology and biostatistics at UCSF and senior author of the study. "More research is necessary to explain why there are such variations in these decisions to intensify therapy."

Researchers examined data from 2015 to 2017 for more than 15,000 patients treated for hypertension at 12 San Francisco safety-net clinics, which typically provide care to low-income patients. Patients were diagnosed with hypertension and had at least one clinic visit with uncontrolled blood pressure. The average age of patients was 58; 50% were women; and included patients from diverse racial ethnic groups: 29% Asian, 23% Black, 24% Hispanic, and 17% white adults.

The study authors analyzed racial differences in achieving normal blood pressure control and whether those differences could be explained by increasing medication therapy for high blood pressure or patients missing clinic appointments. Missed visits were counted as the number of "no shows" in the four weeks following high blood pressure diagnosis.

The study found:

Black participants had more missed opportunities for treatment intensification and missed more clinic appointments, compared to other racial groups.

Lower treatment intensification accounted for 28% and missed clinic visits for 14% of the total effect of Black patients' blood pressure control, which surprised researchers.

Additional or intensified treatment for blood pressure control was lower in Black patients and higher in Asian Americans than in the other racial groups.

"Previous studies have shown that Black patients with hypertension are the least likely to achieve normal blood pressure and Asian Americans are the most likely to achieve normal blood pressure, and our results confirmed this. The most surprising finding is that this racial difference appears to be explained by whether patients received additional or intensified therapy for high blood pressure," said co-author Lucia Pacca, Ph.D., a research associate at UCSF.

"We were completely surprised that Asian Americans' higher performance in achieving normal blood pressure was almost entirely explained by prescribing behavior," said Fontil. "Although other investigators have shown that treatment decisions for some conditions such as pain can vary based on the patient's race and physician bias, this phenomenon has not been widely reported for hypertension treatment. So, we were surprised that doctors were less likely to increase treatment for Black patients, and even more surprised that Asian American patients' higher likelihood in achieving normal blood pressure was largely related to doctors providing treatment intensification to more patients."

In addition, the researchers used a statistical model to estimate the likelihood of blood pressure control (lower than 140/90 mm Hg) to compare Black and white patients with hypertension. After accounting for gender, age, first recorded blood pressure during the two years of the study, clinic visit frequency and diabetes diagnosis, Black patients remained 15% less likely than whites to achieve blood pressure control.

"Our findings should prompt further investigation to determine why Black patients are less likely to have blood pressure therapy increased and why Asian Americans are more likely to be receive more aggressive treatment," Fontil said. "These findings also reemphasize the call for adopting treatment protocols and clinical decision supports that can help standardize quality of care for hypertension and perhaps other chronic diseases."

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American Heart Association