Body

DALLAS, May 27, 2020 -- Women and minorities, particularly African Americans, continue to be inadequately represented in clinical trials for novel cardiometabolic medications, with no evidence of improvement in enrollment numbers over the past decade, according to new research published last week in the Journal of the American Heart Association, an open access journal of the American Heart Association.

Cardiovascular and cardiometabolic (the combination of both cardiovascular and metabolic) diseases are the leading cause of mortality around the world, and Type 2 diabetes increases the risk of cardiovascular disease by about four times in women. A lack of gender and racial diversity in clinical trials evaluating safety and efficacy of medications for cardiovascular and cardiometabolic diseases has been a point of concern for researchers. In 1993, the U.S. Food and Drug Administration (FDA) established guidelines to increase the diversity of participants in clinical trials.

In this study, researchers investigated the 10-year participation trends of women and racial and ethnic minorities in pivotal trials supporting approval of new cardiometabolic medicines. Researchers examined the gender and racial/ethnic enrollment data from nearly 300,000 trial participants to assess the proportion of women and minorities. About 6,000 people participated in each medication trial, on average. The FDA approved 35 new medications during the study period (24 cardiovascular medications and 11 for diabetes from 2008 to 2017).

"Demographic characteristics, such as race and gender, may have contrasting effects on medication response, which may inadvertently lead to variation in treatment outcomes and survival," said Muhammad Shahzeb Khan, M.D., resident in internal medicine at the John H. Stroger, Jr., Hospital of Cook County in Chicago. "It is important that individuals who participate in these trials are representative of the patients who will be treated with these medicines in clinical practice."

"Unfortunately, we found that the enrollment of women and racial minorities has remained disproportionately low," Khan added. "The disparities in gender, race and ethnicity of participants in major clinical trials may have significant implications in determining the effects of these therapies in these groups and may impair generalizability of trial results to routine clinical practice."

The analysis showed that the proportion of women and minorities in clinical trials for FDA approval remained low over time. Researchers found that from 2008-2017:

Women accounted for only 36% of trial participants;

Only 4% of trial participants were black/African American;

Only 12% of trial participants were Asian; and

Only 11% of trial participants were Hispanic/Latino.

Furthermore, women were underrepresented in research trials for coronary heart disease, heart failure and acute coronary syndrome compared to the proportion of women in the population who had those diseases. The study results reinforce the need to increase representation of all demographic subgroups to ensure variations in outcomes of both benefits and safety are reported. This information is critical so that treatments can be tailored.

"While we examined representation of women and minorities in trials specifically for cardiometabolic medicines, the same principles apply for the ongoing trials of COVID-19 therapies - we need to know which medications work and are safe in all demographic subgroups," said Khan. "Therefore, all treatment modalities currently being investigated as potential treatment options for novel coronavirus should be investigated equally among all demographic subgroups, so that any differences in safety and efficacy can be accounted for in advance. Inclusion of diverse participants is essential to holistic understanding of gender and racial differences in treatment response."

Through its signature women's initiative, Go Red for Women®, the American Heart Association has advocated for increased representation of women in cardiovascular research studies for nearly two decades. Go Red for Women's Research Goes Red empowers women to contribute to health research. The initiative has built a community of women scientists, researchers, and medical and health professionals to further raise awareness around women's heart health by closing gender disparity gaps in research and clinical trials. In light of the COVID-19 pandemic, Research Goes Red expanded their reach and impact through a COVID-19 survey, which launched in May. This survey assesses the top concerns women have related to the health, social, economic and emotional impact COVID-19 has had on their lives.

ANN ARBOR, Mich. - If your preschooler often pushes their dinner plate away or wages battles against taking another bite of a vegetable they don't like, they may not grow out of it anytime soon.

By age four, children could be established picky eaters, a new study suggests. And the more parents try to control and restrict children's diets, the more finicky they may become, according to findings published in Pediatrics.

"Picky eating is common during childhood and parents often hear that their children will eventually 'grow out of it.' But that's not always the case," says senior author Megan Pesch, M.D., a developmental behavioral pediatrician at Michigan Medicine C.S. Mott Children's Hospital.

But there's a silver lining for worried parents - while fussy eaters have a lower body mass index, most are still in the healthy range and not underweight, researchers found. They may also be less likely to be overweight or experience obesity than peers.

"We still want parents to encourage varied diets at young ages, but our study suggests that they can take a less controlling approach," Pesch says. That being said "we need more research to better understand how children's limited food choices impact healthy weight gain and growth long term."

The study followed 317 mother-child pairs from low-income homes over a four-year period. Families reported on children's eating habits and mothers' behaviors and attitudes about feeding when children were four, five, six, eight and nine.

Picky eating was stable from preschool to school-age, indicating that any attempts to expand food preferences may need to occur in toddler or preschool years to be most effective. High picky eating was associated with lower BMIs and low picky eating was associated with higher BMIs.

The pickiest eaters also were often associated with increased pressure to eat and restriction on certain types of foods. This reinforces previous Mott-led research suggesting that pressuring children to eat foods they dislike won't lead to a well-rounded diet later in life or encourage better health or development.

Certain child characteristics, including sex, birth order, and socioeconomic status, also have been associated with persistence of picky eating.

"We found that children who were pickier had mothers who reported more restriction of unhealthy foods and sweets," Pesch says. "These mothers of picky eaters may be trying to shape their children's preferences for more palatable and selective diets to be more healthful. But it may not always have the desired effect."

It is unknown if children who are picky eaters would have become even more selective if they did not receive higher levels of controlling feeding behaviors, Pesch says. She says future studies should investigate interventions around maternal feeding and child picky eating.

Vaping is most heavily concentrated in U.S. schools with a higher proportion of white students, schools in the South and West, and schools where more students smoke cigarettes, a new University of Michigan study shows.

Overall, more than one in 10 American middle and high school students report having used e-cigarettes within the last month. In certain schools, as many as 60% of students said they vaped during that time.

It's useful to look at vaping prevalence at both the individual and school levels, because each uses different variables, said study author Sean Esteban McCabe, professor at the U-M School of Nursing and co-director of the Center for the Study of Drugs, Alcohol, Smoking and Health. School-level prevalence does not suggest that more students are vaping overall, but rather that vaping is more popular in certain schools.

Most e-cigarette studies examine individual-level use, but school-level use trends matter because during adolescence, peers are a major influence, McCabe said.

"Imagine how different a school environment would be to a teenager if none of their peers were vaping, compared to three out of every five of their peers," he said. "These would feel like two different worlds to a teenager."

Also, the more a teenager's peers have e-cigarettes or vaping devices, the greater the opportunity to access these products, said co-author Philip Veliz, U-M research assistant professor of nursing.

"Greater availability of these products puts others at greater risk of using these products," he said.

If schools know what's driving e-cigarette use in their district, policymakers can tweak that school's environment to change student behavior and reduce e-cigarette use, Veliz said.

The wide range of vaping prevalence across schools surprised Veliz, McCabe and their study colleagues, and suggests that in high-risk schools, one-size-fits-all interventions to reduce vaping should be replaced by tailored programs specific to that environment, they said.

The study, published online ahead of print in the Journal of Adolescent Health, revealed other surprises as well.

"The finding that current e-cigarette use was significantly higher at schools with a higher proportion of white students was a powerful reminder about the association race can have both at the individual and school level when it comes to substance use behaviors," McCabe said.

The researchers also expected the prevalence of other substance use at the school level to influence individual e-cigarette use, but only past-month cigarette smoking predicted e-cigarette use.

Vaping among teens has skyrocketed in recent years, and McCabe and Veliz said that sheltering in place can be a good opportunity for families to discuss vaping with their kids. Centering talk on vaping activity in school is less threatening than focusing on the child's individual behavior, they said.

"It's important to find the right time and context to have a discussion with your teenager about vaping," McCabe said. "Parents and guardians can have nonjudgmental conversations about vaping by talking with their kids in middle and high school about what vaping is like in their schools. Based on the prevalence of vaping, all students are exposed either directly or indirectly to vaping in school."

The study used 2015 and 2016 Monitoring the Future survey data from 8th, 10th, and 12th graders in 580 public and private schools. More recent data was not available, but McCabe said variation among schools is probably even greater now, with the rise of Juul and other popular e-cigarette products

Individual-level differences in vaping prevalence include age, race and sex, and school-level differences include public versus private, urban versus rural, racial composition and prevalence of cigarette smoking.

McCabe, Veliz and colleagues did not look at what drives vaping in high-risk schools, but other studies have suggested that availability plays a major role in e-cigarette use prevalence. Their future studies will examine what factors drive this wide variation among schools, and if high-risk schools are likely to remain high risk.

Berkeley -- Hospitalized COVID-19 patients in the U.S. are enduring longer hospital stays and facing higher rates of intensive care unit (ICU) admission than patients in China, finds a new study led by researchers at the University of California, Berkeley, and Kaiser Permanente.

The results suggest that hospitals in the U.S. may be harder hit by the coronavirus pandemic than initially thought, as many forecasts of disease burden -- particularly the number of hospital beds and ICU units needed at the peak of infection -- are based on data out of China.

"The hospital resources needed to meet the needs of severely ill patients are substantial," said Joseph Lewnard, an assistant professor of epidemiology at UC Berkeley and lead author of the paper. "We found that observations from China may not provide a sufficient basis for anticipating the U.S. health care demand."

The team analyzed the anonymized medical records of the nearly 9.6 million Kaiser Permanente members in Southern California, Northern California and Washington state.

The study focused on 1,277 Kaiser Permanente members who were hospitalized with clinically- or laboratory-confirmed cases of COVID-19 between the start of the year and early April.

"Because Kaiser Permanente members receive comprehensive health care from a single provider network, we overcome many of the difficulties that arise in studies of diseases within the fragmented U.S. health care delivery system," said Lewnard.

Despite the grim forecast for hospitals, the report does offer a glimmer of hope: Estimates of transmission intensity, based on extrapolations of infection rates from hospitalization data, indicate that the social distancing measures in the region are succeeding at "flattening the curve" of contagion.

"When people engaged in protecting themselves and their communities through social distancing, their efforts translated into a substantial reduction in the transmissibility of the disease," said Vincent Liu, a research scientist at the Kaiser Permanente Division of Research in Northern California and co-author of the paper. "Those efforts are going to be critical for this next phase, in which social distancing measures are gradually relaxed. We need our communities to stay really engaged, because these data show that even the actions of individuals and small groups can really impact the spread of the virus."

The results appeared online May 22 in the The BMJ.

Longer hospital stays, lower transmission rates

Of the 1,277 Kaiser Permanente members who were hospitalized with COVID-19, 42% required care in the ICU, and 18% died from the disease. Modeling estimates based on observations in China usually assume that only about 30% of hospitalized patients will require ICU care.

Similarly, the data showed that hospital stays lasted an average of 10.7 days for survivors and 13.7 days for non-survivors, compared to an average of 7.5 days among non-survivors in China. Troublingly, 25% of patients were hospitalized for 16 days or more. In comparison, a widely-used modeling study from Imperial College London projecting health care needs assumes an average stay of eight days.

While the underlying reasons for these discrepancies remain unclear, the authors stress the need to collect data in different regions and under different health care settings and caution against heavy reliance on models based on data from other countries.

"The spread of COVID-19 and its impact on local health care systems show differences across the world," Liu said. "Health care systems differ, and their capabilities and structure have an effect on the local response and the impact of the surge. So, it's really important to understand how our own data agree with, or in some cases differ, from the experience we've seen in other countries."

Not surprisingly, the analysis also revealed that the virus tends to hit older people the hardest. Approximately 50% of hospitalizations were among adults aged 60 and older, and 25% were among adults aged 73 and older. Similarly, hospitalized men seemed to be hit harder than women: Hospitalized males over the age of 80 faced a 58% risk of death, and hospitalized females of the same age faced only a 32% risk of death.

Estimates of transmission intensity over time yielded promising results. The team found that the transmission rate of the virus has decreased significantly, and the drop began slightly before statewide shelter-in-place orders went into effect in late March. This effect is likely due to the implementation of smaller-scale social distancing measures, such as local restrictions on gatherings and individuals' compliance with safety recommendations, in the weeks prior to the statewide orders, the authors said.

However, while the data indicate that social distancing is succeeding, the authors warn that we shouldn't expect to return to normal anytime soon.

"These data suggest that if we were to release all of our mitigation measures at one time, the disease would start rapidly spreading again," Liu said. "We have to be really strategic and vigilant about how and when we roll back our social distancing measures. It's going to require coordination between health care systems, community partners, government and public health agencies, academic institutions and industry."

"We also need to be mindful of just how severe the disease is," Lewnard added. "We see an 18% overall fatality rate among all people who are getting hospitalized, and 42% end up in the ICU, so the impact of transmission in terms of severe disease and hospital burden is quite high."

Malignant tumors consume nutrients and oxygen faster than healthy cells. To do so, they recruit blood vessels in their environment. Depending on tumor type and genetic profile, there are differences on how tumors look internally. Typically, tumors present different patterns across their volume. The role of this spatial heterogeneity is not well understood or studied in living tumors. Typically used to understand biological functions in tumors, optical microscopy, for example, gives limited insights into the spatial heterogeneity of tumors as it only accesses volumes of less than a cubic millimeter.

High resolution with new imaging method

A new technique developed by Munich researchers, known as multi-spectral optoacoustic mesoscopy (MSOM), has now been shown capable of resolving optical contrast through tumor volumes that are at least 1,000 times larger than those possible with optical microscopy, enabling high-resolution visualization of tumor heterogeneity patterns. With this imaging method, the tumor is first excited from all sides with pulses of infrared laser light. "Tumor and tissue components that absorb this excitation light undergo a tiny, transient temperature increase, which leads to a small local volume expansion, followed by a contraction. This expansion and contraction process generates a weak ultrasound signal, which we collect with a detector," says guest researcher Dr. Jiao Li.

The data collected is mathematically processed to form light absorption images which indicate different tumor patterns reflecting tumor oxygenation and vascularization. "For the first time, MSOM offers optical images that reach inside tumors to depths of ten millimeters and more with a resolution of less than 50 micrometers," says Dr. Li.

Understanding functional variety in tumors

"MSOM imaging of solid tumors allowed us to see tumors in a new light," says Prof. Vasilis Ntziachristos, holder of the Chair of Biological Imaging at TUM and Director of the Institute for Biological and Medical Imaging at Helmholtz Zentrum München. "MSOM allows us to understand how tumor functionality varies across the tumor, clearly moving the reach of optical observations well beyond the depth penetration limitations of optical microscopy".

In the pictures taken from mamma carcinomas of mice, researchers can see patterns indicating the presence or absence of blood vessels, and thus study blood supply patterns. MSOM can also resolve hemoglobin levels, and indicate whether oxygen is bound to hemoglobin or not. Furthermore, MSOM images were used to determine permeability of the vessel walls relative to nanoparticles. Using the mouse model, the scientists were already able to track how tiny gold particles were transported.

3D tumor pictures without surgical biopsy

In contrast to conventional histology, where tissue has to be removed, cut up and examined under the microscope by a pathologist, MSOM allows a three-dimensional analysis of entire living tumors without the need for surgical biopsies. This further supports longitudinal studies so that tumor growth or recession under different drugs can be studied with greater accuracy. All of which paves the way for an improved understanding of biological function and drug efficacy during drug development for humans.

In women with a history of miscarriage, higher levels of physical activity were associated with a greater risk of subclinical, or very early, pregnancy loss, according to new research at the University of Massachusetts Amherst. Among women with confirmed pregnancy, physical activity and miscarriage risk were unrelated.

"Risk related to physical activity is different for pregnancy failure close to the time of implantation compared with that for later, clinical pregnancy loss," writes lead author Lindsey Russo, a Ph.D. student working with senior author Brian Whitcomb, associate professor of epidemiology in the School of Public Health and Health Sciences. Their study, which sheds new light on the question of physical activity and very early pregnancy, was recently published in the journal Fertility and Sterility.

"The implantation period may represent a time of vulnerability, when high-strain activity could pose a risk for subclinical, or very early pregnancy loss," Russo adds, though the researchers say larger studies are needed to further examine the issue. "There was roughly a two-fold higher risk of very early pregnancy loss for women who were highly active compared to those who were less active."

Subclinical pregnancy loss can be difficult to detect because they may occur before a woman is even aware that she's pregnant. "We were able to address an interesting gap in the literature, where there has been conflicting evidence of whether physical activity can have a negative, beneficial or no effect on pregnancy," Whitcomb says. "Determination of these very early pregnancy failures requires lab tests and daily specimen collection to identify pregnancies and losses. Few studies are able to do this."

The researchers analyzed data from the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial. Whitcomb, then working at the National Institutes of Health, was involved in the original four-year trial, which recruited women between 18 and 40 years old with one or two pregnancy losses who were trying to conceive from 2007 to 2011.

The study participants used home pregnancy tests that were combined with information from laboratory tests for pregnancy confirmed by a rise in the hormone hCG, which is one of the earliest indicators of pregnancy. Among 785 women who became pregnant, 188 (23.9%) experienced pregnancy loss, including 55 subclinical losses detected only from hCG testing in biospecimens.

"Physical activity is a complicated measure," Whitcomb explains. "It represents a combination of being health conscious, as well as the physiological effects of physical activity, which is generally good for physical health but can also be a stress."

Physical activity was defined in terms of time spent and intensity level to calculate an overall exercise score. "We're trying to provide good, evidence-based information for women who are pregnant and want to know what to do and also for clinicians who are giving guidance and advice to their patients," Whitcomb says.

Russo notes that according to recommendations from the American College of Obstetricians and Gynecologists, "women with uncomplicated pregnancies should be encouraged to engage in aerobic and strength-conditioning exercises before, during and after pregnancy."

The researchers say their study suggests that women who have lost a pregnancy may want to avoid high-strain activity in the earliest stage of a subsequent pregnancy, or around the time of trying to become pregnant.

"For women who are experiencing difficulty conceiving, our results are consistent with prior work that has also shown that high exercise strain during the implantation period may be related to increased risk of loss," Whitcomb says.

A new study by Johns Hopkins researchers found that it may take between seven and 16 months for surgeons to complete the backlog of elective orthopaedic surgeries that have been suspended during the COVID-19 pandemic. This accounts for more than a million surgeries in the U.S. for spinal fusion and knee and hip replacements.

The study was published online May 12 in The Journal of Bone and Joint Surgery.

Lead author Amit Jain, M.D., chief of minimally invasive and outpatient spine surgery and associate professor of orthopaedic surgery and neurosurgery at the Johns Hopkins University School of Medicine, says that in fields such as orthopaedic surgery, where procedures are frequently performed in an inpatient setting, the ramp-up may be slower than surgeries typically done in outpatient facilities. "We will keep adding to the backlog as long as we are not operating at 100% capacity," states Jain.

Jain and his colleagues used the Agency for Healthcare Research and Quality National Inpatient Sample, a national database that contains hospital inpatient data, to model the number of current and forecasted spinal fusion and hip and knee replacement surgeries in the United States. The researchers found that, in an optimistic scenario where most elective surgeries are back to full capacity in June, it would take approximately seven months to get through the backlog. Delays to the ramp-up to full capacity could extend the backlog to 16 months.

To help ease the backlog, Jain proposes several strategies to increase surgical throughput, including more use of telemedicine. At Johns Hopkins, telemedicine use has skyrocketed. He also suggests making more timeslots available in operating rooms for orthopaedic surgeries, increasing care coordination resources and shifting care to ambulatory surgery centers as much as possible.

A new landmark study by researchers at the University of Maryland School of Medicine (UMSOM) found that patients with a vascular condition, called abdominal aortic aneurysm, received no benefits from taking a common antibiotic drug to reduce inflammation. Patients who took the antibiotic doxycycline experienced no reduction in the growth of their aneurysm over two years compared to those who took a placebo, according to the study published today in the Journal of the American Medical Association (JAMA).

The finding could lead doctors to stop prescribing the drug as a way to prevent small aneurysms from growing larger and bursting.

"This study provides strong evidence that doxycycline is of no benefit for patients with small abdominal aortic aneurysms in terms of preventing their growth. Health care providers should take note of the finding and stop using this as a prophylactic treatment," said corresponding author Michael Terrin, MDCM, MPH, Professor of Epidemiology and Public Health at UMSOM. Researchers from the University of Nebraska Medical Center, the University of Wisconsin School of Medicine and Public Health and Vanderbilt University School of Medicine also had leadership roles in the study.

Abdominal aortic aneurysm is a swelling or ballooning that occurs in the major blood vessel (aorta) that supplies blood from the heart to the lower half of the body. It affects about 3 percent of older Americans, most commonly men and smokers. The condition can cause fatal internal bleeding if the aneurysm grows large enough to burst. Small aneurysms frequently cause no symptoms and are often detected when an abdominal ultrasound or CT scan is performed for other reasons.

Doctors usually monitor the growth of the aneurysm and sometimes opt to prescribe doxycycline in an effort to forestall surgery in higher-risk patients. This practice was based on earlier research suggesting that certain antibiotics reduce inflammation that contributes to aneurysm growth.

The JAMA study involved 254 patients with small aneurysms who were randomly assigned to take either 100 milligrams of doxycycline twice daily or a placebo for two years; CT scans performed at the beginning of the study and on follow-up found no differences in aneurysm growth between those who took the drug and those who took the placebo. Study participants were mostly white and male with an average age of 71 years.

"Randomized clinical trials are essential when it comes to answering important clinical questions," said Dean E. Albert Reece, MD, PhD, MBA, who is also Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor, University of Maryland School of Medicine. "This finding will help guide doctors to avoid an unnecessary treatment for a common condition associated with aging."

Giving beneficial bacteria to stressed mothers during the equivalent of the third trimester of pregnancy prevents an autism-like disorder in their offspring, according to a new animal study by University of Colorado Boulder researchers.

The study, published in the journal Brain, Behavior, and Immunity, marks the latest in a series of studies in animals and humans suggesting that exposure to certain immune-modulating microbes can dampen inflammation, positively impacting the brain and central nervous system.

It's among the first studies to suggest that such exposures during pregnancy influence neurodevelopment of a fetus and, while far more research is necessary, could open the door to new prenatal interventions.

"It suggests that you could develop microbial interventions that lower the risk of neurodevelopmental syndromes like autism," said co-author Christopher Lowry, an associate professor in the Department of Integrative Physiology.

In humans, research has long shown that maternal stress during pregnancy prompts systemic inflammation in both the mother and fetus and is a risk factor for autism, said senior author Daniel Barth, a professor of psychology and neuroscience.

In a previous study, Barth found that when rats were stressed and given a drug called terbutaline, which is often administered to women to delay preterm labor, their offspring demonstrated an autism-like syndrome - including the two hallmark features of social deficits and repetitive behavior. They also developed an epilepsy-like seizure disorder.

"Our fundamental question with this new study was whether we could use an immunoregulatory microbe to prevent the long-term consequences of environmental stressors during pregnancy," said first author Zachariah Smith, a post-doctoral researcher in Barth's lab.

For the study, the researchers exposed rats to mild stressors and gave them terbutaline during what would be the equivalent of the third trimester of pregnancy in humans.

Half were also given a series of injections of a heat-killed preparation of a friendly bacterium known as Mycobacterium vaccae (M. vaccae), shown in previous studies to have lasting anti-inflammatory effects on the brain. A third control group of rats got no treatments.

At two and four months, the pups were given a series of tests assessing, among other things, their degree of social interaction and whether they exhibited repetitive behaviors.

As in the previous study, those whose mothers had been stressed and given terbutaline showed autism-like behaviors. But those who had been immunized with M. vaccae did not.

"Immunization with M. vaccae appears to provide some protection against the negative effects of environmental stressors during development, specifically against Autism Spectrum Disorder (ASD)-like behavior," said Smith.

The inoculation did not appear to protect against development of seizure disorders. But because epilepsy tends to develop later in life, the researchers intend to repeat the experiment with a larger sample size and longer treatment period.

Autism and epilepsy often manifest together in humans, with about 30% of autistic individuals exhibiting epileptic symptoms, such as seizures. Stress-induced inflammation likely plays a role in both, the researchers suspect.

"It could be that if we continue the treatment for longer we could also prevent the development of some cases of epilepsy, but much more research is necessary," said Lowry.

The researchers caution that they are not developing an "autism vaccine" and they are not suggesting that microbial interventions could reverse the disorder in children who already have it. But their study does reinforce the idea that exposure to beneficial microorganisms, sometimes referred to as "old friends," can play a critical role in brain development in utero.

Ultimately, Lowry envisions a day when stressed moms deemed particularly high risk of having a child with a neurodevelopmental disorder could be given a specially formulated probiotic or inoculation to support healthy brain development of their child.

"This is the first maternal intervention that I know of that has been able to prevent an autism-like syndrome, including the behavioral and social aspects," Lowry said. "If this could be replicated in humans, that would be pretty profound."

Meantime, they say, mothers should be cognizant of the potential risks of emotional and environmental stressors, including the drug terbutaline, during pregnancy.

And they should try to expose themselves to beneficial bacteria, through fermented foods like yogurt and sauerkraut and even time spent in nature.

WHAT:

The investigational antiviral remdesivir is superior to the standard of care for the treatment of COVID-19, according to a report published today in The New England Journal of Medicine. The preliminary analysis is based on data from the Adaptive COVID-19 Treatment Trial (ACTT), sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The randomized, controlled trial enrolled hospitalized adults with COVID-19 with evidence of lower respiratory tract involvement (generally moderate to severe disease). Investigators found that remdesivir was most beneficial for hospitalized patients with severe disease who required supplemental oxygen. Findings about benefits in other patient subgroups were less conclusive in this preliminary analysis.

The study began on Feb. 21, 2020 and enrolled 1,063 participants in 10 countries in 58 days. Patients provided informed consent to participate in the trial and were randomly assigned to receive local standard care and a 10-day course of the antiviral remdesivir intravenously, developed by Gilead Sciences, Inc., or local standard care and a placebo. The trial was double-blind, meaning neither investigators nor participants knew who was receiving remdesivir or placebo.

The trial closed to enrollment on April 19, 2020. On April 27, 2020 (while participant follow-up was still ongoing), an independent data and safety monitoring board overseeing the trial reviewed data and shared their preliminary analysis with NIAID. NIAID quickly made the primary results of the study public due to the implications for both patients currently in the study and for public health. The report published today in The New England Journal of Medicine describes the preliminary results of the trial.

The report notes that patients who received remdesivir had a shorter time to recovery than those who received placebo. The study defined recovery as being discharged from the hospital or being medically stable enough to be discharged from the hospital. The median time to recovery was 11 days for patients treated with remdesivir compared with 15 days for those who received placebo. The findings are statistically significant and are based on an analysis of 1059 participants (538 who received remdesivir and 521 who received placebo). Clinicians tracked patients' clinical status daily using an eight-point ordinal scale ranging from fully recovered to death. Investigators also compared clinical status between the study arms on day 15 and found that the odds of improvement in the ordinal scale were higher in the remdesivir arm than in the placebo arm. Trial results also suggested a survival benefit, with a 14-day mortality rate of 7.1% for the group receiving remdesivir versus 11.9% for the placebo group; however, the difference in mortality was not statistically significant.

Ultimately, the findings support remdesivir as the standard therapy for patients hospitalized with COVID-19 and requiring supplemental oxygen therapy, according to the authors. However, they note that the mortality rate of 7.1% at 14 days in the remdesivir arm indicates the need to evaluate antivirals with other therapeutic agents to continue to improve clinical outcomes for patients with COVID-19. On May 8, 2020, NIAID began a clinical trial (known as ACTT 2) evaluating remdesivir in combination with the anti-inflammatory drug baricitinib compared with remdesivir alone.

Proteins are found throughout our cells and regulate a lot of biological processes that are important forour survival. But some of them also regulate processes that can make us sick. Now, an international research team, with researchers from the University of Copenhagen at the forefront, has achieved a much better understanding of one such protein.

In a new study, the researchers discovered how the protein PP2A works at the molecular level, and how it inhibits the development of tumours in mice. The new results have been published in the scientific journal, the EMBO Journal.

'We call PP2A a household protein because it is found almost everywhere. In everything living - from simple yeast cells to complex cells in humans. PP2A removes phosphate groups on other proteins, and now we have found these proteins and how PP2A, via one of these proteins, inhibits cancer development', says Jakob Nilsson, Professor at the Novo Nordisk Foundation Center for Protein Research.

Turned-Off Enzyme

According to the researchers, there is a great deal of interest from both the academic research community and from the pharmaceutical industry for the protein PP2A because it is well-known that PP2A is a so-called tumour suppressor that suppresses tumours. But precisely which proteins PP2A regulates in order to inhibit cancer have so far not been known. Now, the researchers have gained detailed insight into this.

'The new thing about our study is that we show how PP2A selects the phosphate groups that shall be removed from other proteins. And then at the same time, we show that PP2A turns off an enzyme named ADAM17. This shutdown of ADAM17 results in inhibition of tumour growth in mice', explains Associate Professor Marie Kveiborg from the Biotech Research and Innovation Centre.

The researchers have used advanced methods to show that PP2A can turn off the activity of ADAM17 on the outside of the cell by removing phosphate groups from the part of ADAM17 that is located inside the cell.

The Function is Inhibited

Normally, ADAM17 sits as a pair of molecular scissors in the cell's outer membrane and cleaves other proteins from the cell surface - for example, growth factors that will then stimulate cell growth. But that function ceases when PP2A removes the phosphate groups from ADAM17.

The researchers already knew from previous studies that ADAM17 stimulates a variety of cancers, including breast and bowel cancer. But this is the first time that PP2A has been shown to actively turn off ADAM17 activity.

Going forward, the researchers hope that their new cancer discovery will also apply to human tumoursFor now, the next step for the researchers is to clarify whether substances that activate PP2A can be used to regulate ADAM17 activity. In addition, the researchers also want to look at how PP2A regulates other proteins that may be important for the understanding of its tumour suppressor function.

New research indicates that only four in 10 UK adults have been sexually active during the COVID-19 lockdown - a finding that could have important physical and mental health implications.

The study, published in The Journal of Sexual Medicine and led by Dr Lee Smith of Anglia Ruskin University (ARU) and Professor Mark Tully of Ulster University, is the first to investigate levels of sexual activity during social distancing and self-isolation.

Only 39.9% of the 868 British adults surveyed for the research had taken part in any form of sexual activity during the previous seven days. The study found that being younger, male, married and a consumer of alcohol was associated with greater sexual activity.

Previous research has shown an association between sexual activity and physical health, including helping to protect older adults against cardiovascular events. Frequent sexual activity has also been associated with various mental health benefits and improved cognitive function.

The findings of this new study suggest that the UK Government's public health messaging around COVID-19 self-isolation and social distancing could include promoting sexual activity as a way of maintaining physical and mental health.

Dr Lee Smith, Reader in Physical Activity and Public Health at Anglia Ruskin University (ARU), said: "When starting this research we expected there to be a high level of sexual activity while social isolating at home, but interestingly we found a very low level.

"This low level of sexual activity could be explained by people currently feeling anxious and stressed owing to the pandemic and not being in the mood to engage in the act. Moreover, those who are not married or cohabiting may not currently be able to meet up with their sexual partners and similarly those who use online apps to facilitate casual sex will currently not be able to do this.

"A lot of my previous research has shown that a frequent and trouble-free sex life is important for higher levels of enjoyment of life and general mental health, and this is particularly true for older adults. However, this study showed that older adults were less likely than younger adults to engage in sexual activity."

Below please find summaries of new articles that will be published in the next issue of Annals of Internal Medicine. The summaries are not intended to substitute for the full articles as a source of information. This information is under strict embargo and by taking it into possession, media representatives are committing to the terms of the embargo not only on their own behalf, but also on behalf of the organization they represent.

1. A single negative colonoscopy associated with long-lasting and significantly reduced cancer incidence and mortality
Study findings suggest that CRC screening interval might safely be extended

Abstract: https://www.acpjournals.org/doi/10.7326/M19-2477
URL goes live when the embargo lifts

Having a single negative high-quality screening colonoscopy was associated with reduced colorectal cancer (CRC) incidence and mortality (by 84 percent and 90 percent, respectively) for up to 17.4 years. These findings suggest that the currently recommended 10-year screening interval could safely be extended. Findings from an observational study are published in Annals of Internal Medicine.

Current guidelines recommend a 10-year interval between negative screening colonoscopies for average-risk adults. This recommendation is based on estimates of time between adenoma and carcinoma, as well as extrapolations from studies assessing colonoscopy sensitivity. A lack of long-term data makes it challenging to determine the optimal screening interval following a normal colonoscopy.

Researchers from The Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland studied a screening registry for 165,887 individuals to assess the long-term risk for CRC and death from CRC after high- and low-quality single negative screening colonoscopy. The researchers found that a single negative screening colonoscopy was associated with a significantly reduced CRC incidence and mortality over more than 17 years of follow-up, but only high-quality colonoscopy provided a profound and stable reduction in both CRC incidence and mortality throughout follow-up period. High quality was key for the profound long-term efficacy of screening colonoscopy in the proximal colon, and among women. The researchers point out that these findings are of paramount importance, because previous reports have questioned the efficacy of colonoscopy in the proximal colon and of screening sigmoidoscopy in women. These findings suggest that the currently recommended 10-year interval for screening colonoscopy is safe and could potentially be extended.

Media contacts: For an embargoed PDF please contact Lauren Evans at laevans@acponline.org. To speak with the lead author, Nastazja Dagny Pilonis, MD, nastazja@gmail.com.

2. Aldosterone production is a common and unrecognized cause of high blood pressure

Abstract: https://www.acpjournals.org/doi/10.7326/M20-0065
Editorial: https://www.acpjournals.org/doi/10.7326/M20-1758
URL goes live when the embargo lifts

Findings from a cross-sectional study published in Annals of Internal Medicine implicate the hormone aldosterone as a common and unrecognized contributor to hypertension.

Hypertension affects more than 1.5 billion people worldwide and is arguably the leading preventable cause of heart disease and stroke. Primary aldosteronism is a condition where the adrenal glands produce too much of the hormone aldosterone, which causes high blood pressure and cardiovascular disease. Primary aldosteronism has traditionally been considered to be an uncommon cause of hypertension, however, the findings of this study show that it is much more common than previously recognized.

Researchers from four academic medical centers (including Brigham and Women's Hospital, University of Alabama, University of Virginia, and University of Utah) studied patients with normotension (n = 289), stage 1 hypertension (n = 115), stage 2 hypertension (n = 203), and resistant hypertension (n = 408) to determine the prevalence of excess aldosterone production and primary aldosteronism. They found that there was a continuum of excess aldosterone production that paralleled the severity of blood pressure. Importantly, most of this excess aldosterone production would have not been recognized by currently recommended diagnostic approaches. According to the authors, this finding supports the need to redefine primary aldosteronism from a rare disease to, instead, a common syndrome that manifests across a broad severity spectrum and may be a primary cause of hypertension. Since generic medications that block the deleterious effects of aldosterone already exist and are easily available, these findings suggest that using these drugs more frequently to treat hypertension may be an effective way to lower the risk of cardiovascular disease.

The author of an accompanying editorial, Professor John Funder, who currently chairs the international guidelines for the diagnosis and management of primary aldosteronism, called the study a "game changer" and indicated that these findings should trigger a "radical reconstruction" of current clinical practice and guideline recommendations.

Media contacts: For an embargoed PDF please contact Lauren Evans at laevans@acponline.org. To speak with the lead author, Anand Vaidya, MD, MMSc, please contact Elaine St. Peter at estpeter@bwh.harvard.edu.

3. Liraglutide provides excellent glucose control in patients with type 2 diabetes and cirrhosis, but should we optimize the prevention of variceal bleeding?

Abstract: https://www.acpjournals.org/doi/10.7326/L20-0041
URL goes live when the embargo lifts

The glucagon-like peptide-1 (GLP-1) agonist drug, liraglutide, seems to provide excellent glucose control in patients with type 2 diabetes who are also taking a beta-blocker, specifically propranolol, to prevent bleeding from esophageal varices due to cirrhosis, but it seems to hamper the pharmacological effects of beta-blockers. A case report is published in Annals of Internal Medicine.

When using beta-blockers to prevent bleeding from esophageal varices, clinicians use the resting heart rate as a guide, as these therapies lower heart rate. GLP-1s are used to treat diabetes because they lower blood glucose levels and are especially useful when the patient is obese and has nonalcoholic fatty liver disease, but they are known to increase heart rate, although not significantly. No data are available on the concomitant treatment with GLP-1 analogues and β-blockers in patients with cirrhosis and diabetes.

Researchers from University of Bologna, Policlinico Sant'Orsola-Malpighi, Bologna, Italy studied 18 consecutive patients with cirrhosis who were receiving propranolol to prevent variceal bleeding while also receiving liraglutide for uncontrolled type 2 diabetes. Liraglutide provided optimal control of blood glucose, HbA1c and body weight, but the researchers observed a lack of optimal effect of beta-blockers on heart rate after starting a GLP-1 receptor agonist. However, in this small cohort no increase in bleeding rate was observed. The researchers propose a mechanistic molecular explanation of how a GLP-1 receptor agonist might prevent beta-adrenergic receptor blockade.

Media contacts: For an embargoed PDF please contact Lauren Evans at laevans@acponline.org. To speak with the lead author, Ranka Vukotic, MD, PhD, please email directly to ranka.vukotic2@unibo.it or ranka81@yahoo.it.

A new study by researchers from McGill University and the University of Toronto finds a cross-partisan consensus on battling COVID-19 in Canada. Unlike in the U.S., this consensus is fostering broad agreement on the threats posed by the pandemic and the actions necessary to contain it - all of which is crucial to efforts to fight the virus.

"We know that public opinion tends to become polarized on highly salient issues, except when political leaders are in consensus. In the United States, there appears to be political and public polarization on the severity of the pandemic," says co-author Aengus Bridgman, a PhD Candidate in Political Science at McGill University under the supervision of Dietlind Stolle. "Other evidence suggests that polarization is undermining compliance with social distancing."

In a study for the Canadian Journal of Political Science, the researchers evaluate Canadians' response to COVID-19 by analyzing data from the social media accounts of federal Members of Parliament (MPs), Google search trends, and public opinion surveys.

On social media, where platforms can often be sources of polarization, the researchers found no evidence of MPs from any party downplaying the pandemic. Surveying 2,500 Canadians between March 25 and 31, they also found no differences between partisan groups in terms of social distancing measures being taken. Conservative voters are just as likely to engage in social distancing as Liberal or NDP voters.

Similarly, there are no measurable differences across partisan lines in terms of how serious respondents believe the COVID-19 pandemic to be. The majority expressed some or a great deal of confidence in the federal government's response to date.

Yet there are still some differences. A third of Conservative respondents said they hold Justin Trudeau primarily responsible for the outbreak - twice as many as the share of Liberal partisans who assigned blame to the prime minister (15 per cent). Still, this is far less than the percentage of Conservatives who said the Chinese government was to blame for the outbreak (47 per cent).

According to the researchers, public unity is needed for coordinating society-wide measures to contain the pandemic, like social distancing or wearing masks. "During the COVID-19 pandemic individual citizens need to voluntarily sacrifice economic and social activity to protect others. Avoiding polarization is essential for an effective societal response to the pandemic," says co-author Taylor Owen, an Associate Professor at the Max Bell School of Public Policy at McGill University.

Hamilton, ON (May 22, 2020) - The evidence shows that cloth masks, particularly those with several layers of cotton cloth, block droplet and aerosol contamination of the environment, which may reduce transmission of COVID-19.

"The point is not that some particles can penetrate the mask, but that some particles are stopped, particularly outwardly, from the wearer," said first author Catherine Clase, associate professor of medicine at McMaster University and a nephrologist of St. Joseph's Healthcare Hamilton.

"Ideally, we would want a mask to work in both directions, protecting the wearer from the environment and reducing the contamination of the environment - air and surfaces - by the wearer."

Her international research team examined a century of evidence including recent data, and found strong evidence showing that cloth and cloth masks can reduce contamination of air and surfaces.

"Direct evidence about whether wearing a mask of any sort outside a health-care setting reduces actual transmission of COVID-19 is lacking. This is why public-health decisions about public mask wearing have been difficult to make, and why they differ around the world," said Clase. "Our review suggests that cloth can block particles, even aerosol-sized particles, and this supports Canadian public health policy on the issue."

The team's opinion was published in the Annals of Internal Medicine on May 22. It can be found at https://www.acpjournals.org/doi/10.7326/M20-2567.

Whether cloth masks protect others from the wearer was studied in the 1960s and 1970s. A mask made of three layers (muslin-flannel-muslin) reduced surface contamination by 99 per cent, total airborne microorganisms by 99 percent, and bacteria recovered from the smaller particles, aerosols, by 88 per cent to 99 per cent.

A commercial mask made of four-layer cotton muslin was shown to reduce all particles by 99 per cent, compared with 96 per cent to 99 per cent for contemporary disposable medical masks. Even for aerosols, the cloth mask was comparable with the medical masks of the day, the researchers say.

The filtration of cloth is quite variable and single layers of scarf, sweatshirt and t-shirt may be in the 10 to 40 per cent range. But multiple layers increase efficiency, and modern studies have confirmed that some combinations of cloth, for example, cotton-flannel, block more than 90 per cent of particles.

"Our work is just one part of a complex puzzle," said Clase. "In terms of making masks, it is important to realise that more layers will give more protection, both inward and outward, but will make it harder to breathe. For this reason, it is not recommended that children under two and people with breathing difficulties wear masks."

She added that more research is also needed into the best materials and design of cloth masks, to help the many people who are sewing masks to protect people in their community.

"Given the severity of this pandemic and the difficulty of control, we suggest that the possible benefit of a modest reduction in transmission likely outweighs the possibility of harm," said Clase.