Body

By Karina Toledo | Agência FAPESP – Can a high dose of vitamin D administered on admission to hospital improve the condition of patients with moderate or severe COVID-19? The answer is no, according to a Brazilian study published in the Journal of the American Medical Association (JAMA).

The article reports a randomized, double-blind, placebo-controlled clinical trial, the kind of study considered the gold standard to evaluate drug efficacy. It was conducted with FAPESP’s support by researchers at the University of São Paulo’s Medical School (FM-USP), who recruited 240 patients treated at Hospital das Clínicas (HC), the hospital complex run by FM-USP, and the Ibirapuera field hospital in São Paulo City in June-August 2020.

“In vitro studies or trials with animals had previously shown that in certain situations vitamin D and its metabolites can have anti-inflammatory and anti-microbial effects, as well as modulating the immune response. We decided to investigate whether a high dose of the substance could have a protective effect in the context of an acute viral infection, reducing either the inflammation or the viral load,” Rosa Pereira, principal investigator for the project, told Agência FAPESP.

The volunteers were randomly divided into two groups, one of which was given vitamin D3 in a single dose of 200,000 units (IU) dissolved in a peanut oil solution. The other group was given only the peanut oil solution. All participants were treated according to the standard protocol for hospital treatment of the disease, which includes administration of antibiotics and anti-inflammatory drugs.

The main purpose was to see if acute supplementation would affect the length of hospital stay for these patients, but the researchers also wanted to find out whether it would mitigate the risks of admission to the intensive care unit (ICU), intubation and death.

No significant difference between the groups was observed for any of these clinical outcomes. According to Pereira, the study was designed above all to assess the impact on hospital stay and a larger number of volunteers would be needed to achieve a scientifically acceptable estimate of the effect on mortality.

“So far we can say there’s no indication to administer vitamin D to patients who come to the hospital with severe COVID-19,” she said.

For Bruno Gualano, a researcher at FM-USP and penultimate author of the article, the findings show that at least for now there is no “silver bullet” for the treatment of COVID-19. “But that doesn’t mean continuous use of vitamin D can’t have beneficial effects of some kind,” he said.

Ideal dose

Pereira is currently leading a study at FM-USP to find out whether subjects with sufficient circulating levels of vitamin D combat infection by SARS-CoV-2 better than those with insufficient levels of the nutrient.

The ideal level of vitamin D in the blood and the daily supplementation dose vary according to age and overall health, she explained. Older people and patients with chronic diseases including osteoporosis should have more than 30 nanograms per milliliter of blood (ng/mL). For healthy adults, 20 ng/mL is an acceptable threshold.

“The ideal approach is case-by-case analysis, if necessary dosing the substance periodically by means of blood work, with supplementation if a deficiency is detected,” Pereira said.

The article “Effect of a single high dose of vitamin D3 on hospital length of stay in patients with moderate to severe COVID-19” can be read at: jamanetwork.com/journals/jama/fullarticle/2776738.

Journal

JAMA

DOI

10.1001/jama.2020.26848

(Boston)-- Being a parent of a Neonatal Intensive Care Unit (NICU) infant does not come with its own playbook of instructions. Preparing to care for a medically needy infant requires the mastery of technical skills, knowledge, emotional comfort and confidence. After confirming that an infant is medically ready for discharge, the quality of NICU discharge training/teaching is the strongest predictor of discharge readiness. A new study reinforces the importance of discharge preparation and transition to home planning.

NICU discharge readiness is defined as the "masterful attainment of technical skills and knowledge, emotional comfort, and confidence with infant care by the primary caregivers at the time of discharge. NICU discharge preparation is "the process of facilitating discharge readiness to successfully make the transition from the NICU to home," optimally through a standardized family-centered education program. Discharge readiness is the desired outcome, and discharge preparation is the process.

To compare the assessment of parental NICU discharge preparedness with parental satisfaction with the NICU discharge preparation, researchers from Boston University School of Medicine (BUSM) surveyed families four to six weeks after NICU discharge on whether they were "satisfied" with their discharge preparation. On discharge day, families were considered "prepared" for discharge based on their overall level of preparedness and their nurse's rating of them on a discharge readiness assessment tool.

In total, 1104 families (60 percent) reported being both "satisfied" and "prepared"; 293 families (16 percent) were "satisfied" but not "prepared"; 297 families (16 percent) were not "satisfied" but were "prepared"; and 134 families (seven percent) were neither "satisfied" nor "prepared." Compared with families that were both "satisfied" and "prepared," families that were neither "satisfied" nor "prepared" were more likely to be raising the infant as a single parent, of Black race and to have sicker infants.

"Some families are at a higher risk and need more consideration during NICU discharge planning," explained corresponding author Vincent C. Smith, MD, associate professor of pediatrics at BUSM. Smith stresses that assessing the discharge readiness of all families prior to discharge is crucial. "Those at an increased risk may benefit from more discharge education and training, specifically for single mothers, those with limited resources, or others considered at high risk," adds Smith who also is division chief of Newborn Medicine at Boston Medical Center.

According to the researchers, the discharge planning process has long-term implications because part of the life course of adults who were born preterm is positively and negatively influenced early on by parenting practice and appropriate care.

The researchers believe this study illustrates the need for a prospective study that surveys?families just prior to discharge, at two and four weeks and again six months after discharge to help explain which families have problems, when the family first experienced the challenges and how long the benefits of discharge preparation persist.

It's been hailed as a wonder drug and it's certainly creating wonder profits. By some estimates, the Cannabidiol (or CBD) market could be worth $20 billion dollars by 2024. While users tout its effectiveness in pain relief, up until now there's been limited experimental human research on the actual effectiveness of the drug. However, a new study led by researchers at Syracuse University sheds light on the ability of CBD to reduce pain along with the impact that the so-called placebo effect may have on pain outcomes.

"For science and the public at large the question remained, is the pain relief that CBD users claim to experience due to pharmacological effects or placebo effects," asked Martin De Vita, a researcher in the psychology department at Syracuse University's College of Arts and Sciences. "That's a fair question because we know that simply telling someone that a substance has the ability to relieve their pain can actually cause robust changes in their pain sensitivity. These are called expectancy effects." De Vita, along with Syracuse Emeritus Psychology Professor Stephen Maisto, were uniquely prepared to answer that exact question. The pair, along with fellow lab member and doctoral candidate Dezarie Moskal, previously conducted the first systematic review and meta-analysis of experimental research examining the effects cannabinoid drugs on pain. As the first experimental pain trial to examine CBD, their study yielded consistent and noteworthy results. Among other findings, the data showed that CBD and expectancies for receiving CBD do not appear to reduce experimental pain intensity, but do make the pain feel less unpleasant.

De Vita and Maisto used sophisticated equipment that safely induces experimental heat pain, allowing them to measure how the recipient's nervous system reacts and responds to it. "Then we administer a drug, like pure CBD, or a placebo and then re-assess their pain responses and see how they change based on which substance was administered," said De Vita. Researchers then took it a step farther by manipulating the information given to participants about which substances they received. In some cases, participants were told that they got CBD when they actually received a placebo, or told they would be getting a placebo when they actually got CBD. "That way we could parse out whether it was the drug that relieved the pain, or whether it was the expectation that they had received the drug that reduced their pain," according to De Vita. "We hypothesized that we would primarily detect expectancy-induced placebo analgesia (pain relief). What we found though after measuring several different pain outcomes is that it's actually a little bit of both. That is, we found improvements in pain measures caused by the pharmacological effects of CBD and the psychological effects of just expecting that they had gotten CBD. It was pretty remarkable and surprising."

"The data is exciting but pretty complex in that different pain measures responded differently to the drug effect, to the expectancy, or both the drug and expectancy combined--so we're still trying to figure out what is behind the differential data with different kinds of pain measures," said Maisto. "The next step is studying the mechanisms underlying these findings and figuring out why giving instructions or CBD itself causes certain reactions to a pain stimulus."

Most people think of pain as an on and off switch, you either have it or you don't. But pain, as De Vita describes it, is a complex phenomenon with several dimensions influenced by psychological and biological factors. For example, whereas pain intensity reflects a "sensory" dimension of pain, unpleasantness represents an "affective," or emotional, aspect of pain. "If you think of pain as the noxious noise coming from a radio the volume can represent the intensity of the pain, while the station can represent the quality," said De Vita. Results from his previous study showed that while cannabinoid drugs weren't reducing the volume of pain, they were "changing the channel making it a little less unpleasant." According to De Vita, "It's not sunshine and rainbows pleasant, but something slightly less bothersome. We replicated that in this study and found that CBD and expectancies didn't significantly reduce the volume of the pain, but they did make it less unpleasant--it didn't bother them as much." As part of the study De Vita and Maisto developed advanced experimental pain measurement protocols "to pop the hood and start looking at some of these other mechanistic pain processes," said De Vita. "It's not just pain, yes or no, but there are these other dimensions of pain, and it would be interesting to see which ones are being targeted. We found that sometimes pharmacological effects of CBD brought down some of those, but the expectancies did not. Sometimes they both did it. Sometimes it was just the expectancy. And so, we were going into this thinking we were going to primarily detect the expectancy-induced pain relief but what we found out was way more complex than that and that's exciting."

One important note to also consider is the source of the CBD. "What we used in our study was pure CBD isolate oil," said De Vita. "Commercially available CBD products differ in their content and purity, so results might be different for different CBD products, depending on what other compounds they may or may not contain."

LEBANON, NH - Researchers at Dartmouth's and Dartmouth-Hitchcock's Norris Cotton Cancer Center (NCCC) hope to make estrogen therapy a more accessible treatment option for breast cancer patients who could benefit from it. Anti-estrogen treatments, which block growth signals from estrogen receptors (ER) in tumors, are effective treatments for ER+ breast cancer. But it is common for breast tumors to become resistant to anti-estrogen treatments over time. The research team, led by molecular biologist Todd Miller, PhD, and Nicole Traphagen, a PhD candidate in the Miller Laboratory, found that in mice, cycling between estrogen treatment and anti-estrogen treatment at a specific point in time can dramatically increase the duration of tumor regression.

The team's unconventional approach has exciting implications for breast cancer patients by suggesting that treating short-term with estrogen before anti-estrogen therapy resistance occurs, and then switching back to a more standard anti-estrogen therapy can better control tumor growth long-term. Traphagen and Miller have newly published their findings, entitled "High estrogen receptor alpha activation confers resistance to estrogen deprivation and is required for therapeutic response to estrogen in breast cancer," in Oncogene.

"Although we typically think of estrogens as feeding breast cancer growth, treatment with estrogens can actually induce tumor regression in some patients with anti-estrogen resistant breast tumors," says Miller. Despite the fact that estrogen treatment is effective in some patients, estrogen therapy is rarely used. An ongoing clinical trial at NCCC (POLLY; NCT0218875) will determine whether the strategy of cycling between estrogen therapy and anti-estrogen therapies is effective in human patients with advanced breast cancer.

"Tumors that initially respond to estrogen therapy eventually develop resistance to it by decreasing the amount of estrogen receptors in the tumor cells. Once these tumors become resistant to estrogen therapy, they can be successfully treated with anti-estrogen therapies," says Traphagen. "This finding suggests that treatment with estrogen can re-sensitize patients' tumors to anti-estrogen therapies, even if those tumors had previously acquired resistance to anti-estrogen treatments."

Miller and Traphagen will also study the molecular characteristics of breast cells that respond to estrogen therapy. The goal is to use this information to predict and improve selection of patients who may respond to estrogen therapy and inform development of new drug combinations to optimize the anti-cancer effects of estrogen therapy.

A patient arrives at hospital with chest pain. Doctors suspect heart attack and rapid diagnosis is important, but the tests to confirm it can be invasive and it could easily be something else. Could a simple blood test help to non-invasively rule heart attack in or out? A new study in open access journal Frontiers in Cardiovascular Medicine certainly suggests so. The study identified telltale markers in the blood of heart attack patients that distinguished them from patients suffering chest pain with other causes. The researchers hope that the results will lead to new diagnostic tests for heart attacks.

If you have ever suffered chest pain, the possibility of a heart attack may have popped into your head. While chest pain is an important symptom for heart attacks, there are a variety of other conditions that can cause similar symptoms, and many of them are not serious. If a patient presents with chest pain at hospital, doctors need to quickly determine if a heart attack is the culprit. Early treatment is important in limiting the damage that occurs.

At present, this may involve coronary angiography, where a catheter is placed into the blood vessels of the heart. While effective, angiography is invasive, and not something you would like to undergo if unnecessary. In addition, in busy or poorly resourced hospitals, angiography may not always be available in time. Another test involves taking a blood sample to check for proteins that indicate damage to the heart muscle. However, these markers are sometimes unreliable, and can be elevated by other conditions.

These issues inspired these researchers to look for new markers in the blood that form a unique fingerprint for a heart attack. They turned to small molecules called metabolites that are produced during biochemical processes within our bodies.

"We analyzed circulating metabolites in blood plasma samples from cardiac chest pain patients, including heart attack cases and other cardiac chest pain cases, to identify potential markers for heart attack diagnosis and early warning," explained Dr Xiangqing Kong of the First Affiliated Hospital of Nanjing Medical University, corresponding author on the paper. "Such markers could be helpful in confirming heart attack in a timely manner when angiography is unavailable."

The researchers collected blood samples from 146 patients who presented at hospital with chest pain and 84 healthy volunteers. Of the 146 chest pain patients, 85 were later confirmed to have suffered a heart attack and the remainder had chest pain from other causes.

Strikingly, on analyzing the samples, the researchers found an array of metabolites that were present in different amounts, and the differences were significant enough that they could successfully distinguish between the samples from heart attack patients, those with non-heart attack-related chest pain and the healthy volunteers. Three metabolites showed particular promise as diagnostic markers.

"Even after accounting for other cardiac risk factors such as hypertension, smoking and diabetes history, the metabolites deoxyuridine, homoserine and methionine scored highly as potential diagnostic and risk markers of heart attack," explained Dr Jiye Aa of the China Pharmaceutical University, another author on the paper.

In reality, a suspected heart attack patient will likely undergo various tests before a heart attack is confirmed, but expanding the available arsenal of reliable tests will be useful for doctors in narrowing things down quickly. The researchers plan to conduct further research to assess why and how these biomarkers are involved in heart attacks.

Now that teens and young adults across the country account for an increasing share of COVID-19 cases, and many have become eligible for vaccination, several recently published studies based on polls of this age group provide insights into the kinds of messaging that might work best for both preventing transmission and vaccine uptake.

Using data from text-message polls of people between the ages of 14 and 24 taken at several points in 2020, researchers from the University of Michigan find a clear theme: that most young people are taking COVID-19 seriously and trying to follow public health guidance, and that many of them they are motivated by the desire to protect others.

The latest paper, in the Journal of Adolescent Health's May issue, finds that 86% of young people are moderately or very concerned about spreading COVID-19. The data come from the MyVoice poll, which allows open-ended answers to questions texted to a national sample of young people.

At the time the poll was taken, 89% said they wear masks or other face coverings all or most of the time - and the most common reason they gave was to prevent themselves from spreading the coronavirus.

But nearly 20% said that they made exceptions when they were near people they considered close contacts or part of their "pod," and 16% said they based their mask-wearing behavior on social cues, such as whether they felt they could trust that the people they were with had been cautious about potential sources of exposure.

Melissa DeJonckheere, Ph.D., the first author of the paper and an assistant professor in U-M's Department of Family Medicine, says, "By and large, youth thought they were doing the right thing and following face covering guidelines, even when making exceptions. At the time our data were collected, youth were engaged and concerned about their impact on others, and overall wanted to do their part."

Kao-Ping Chua, M.D., Ph.D., senior author and an assistant professor of pediatrics, says that the findings have implications for improving messaging to young people around COVID-19 vaccination, as well as mask use. "Public health campaigns should leverage youths' desire to protect others and not be the cause of spread. Youth may not be very strongly motivated to get a vaccine to protect themselves. A message like "Get a vaccine to protect your grandparents" might be more effective."

Two other recent MyVoice papers found similarly high percentages of youth reported following rules about social distancing for the most part, but making exceptions for close contacts including situations where young people seemed to be misinterpreting public health guidance. Protecting others was cited as the most common motivation for distancing and following other guidance.

Etrasimod 2 mg treatment group achieved statistical significance in the percentage change in weekly peak pruritis (PP-NRS), in the change in Dermatology Life Quality Index (DLQI), and in the change in Patient-Oriented Eczema Measure (POEM)

Etrasimod 2 mg was generally well tolerated, consistent with data in previous trials

Park City, Utah, April 23, 2021 - Arena Pharmaceuticals, Inc. (Nasdaq: ARNA) today announced data at a late-breaking session at the American Academy of Dermatology VMX Experience. Etrasimod, a novel investigational drug candidate to treat moderate-to-severe atopic dermatitis (AD), demonstrated statistical significance in both clinician and patient reported outcomes in the ADVISE Phase 2b clinical trial. Etrasimod is a highly selective, once-daily, oral sphingosine 1-phosphate (S1P) receptor modulator. Today's results are presented by Emma Guttman-Yassky, MD, PhD, Waldman Professor and Chairwoman, The Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai.

"Etrasimod demonstrated clinically meaningful improvements in both clinical signs of atopic dermatitis and patient reported outcomes," Dr Guttman said. "Additionally, patient reported outcomes were improved as early as 2 weeks after etrasimod treatment was initiated. Combined with a favorable safety profile, these results are promising for this new mechanism of action for the treatment of atopic dermatitis."

In the ADVISE trial, Arena Pharmaceuticals evaluated the safety and efficacy of etrasimod in participants with moderate to severe eczema as well as to gain insight into design parameters for a potential pivotal Phase 3 program. Additionally, Arena quantified participants' assessments of etrasimod's efficacy using the peak pruritis numeric rating scale (PP-NRS), Dermatology Life Quality Index (DLQI) and Patient-Oriented Eczema Measure (POEM). Given the statistically significant and clinically meaningful improvements in PROs coupled with the statistically significant improvements shown on the clinician-observed vIGA scale, Arena Pharmaceuticals expects to advance etrasimod into a pivotal registrational Phase 3 program for atopic dermatitis.

"The results reported today by Dr. Guttman-Yassky from the ADVISE trial have demonstrated impressive clinical benefit for patients living with moderate to severe atopic dermatitis," said Paul D. Streck, MD, Senior Vice President, Clinical Development, and Chief Medical Officer. "Together with a favorable safety profile, both the clinician-based assessments and the patient reported outcomes provide a strong basis to advance etrasimod to a global Phase 3 program as a potential treatment for atopic dermatitis. If approved, etrasimod has the potential to bring a novel, easily dosed oral therapy to patients who currently face limited treatment options for this chronic and debilitating disease."

Discussion of Trial

In the trial, 140 participants with chronic, moderate to severe eczema for at least a year were randomized into three equal cohorts for etrasimod 1 mg, etrasimod 2 mg, and placebo, treated once daily for 12 weeks. At the start of the trial, participants showed an Eczema Area and Severity Index (EASI) equal to or greater than 16, a vIGA score equal to 3 or more, and were affected by AD over 10% or more of their body surface. Of the etrasimod 2 mg participants, 29.8% successfully reduced their clinician-reported vIGA at 12 weeks to 0 or 1 (representing "clear" or "almost clear" skin) and improved by at least 2 points, compared to 13% for placebo (p=0.0450).

ADVISE also included three dermatology-specific patient reported outcomes. Participants gave regular evaluations of their peak pruritis numeric rating scale (PP-NRS), Dermatology Life Quality Index (DLQI) and Patient-Oriented Eczema Measure (POEM).

For the PP-NRS, individuals in the etrasimod 2 mg cohort showed a statistically significant improvement as early as Week 2, compared to placebo, in their PP-NRS percentage score from baseline at the start of the trial; the etrasimod 2 mg cohort reported peak pruritis dropped 15.3% compared to a drop for placebo of only 1.0% (p=0.0380) at Week 4. This early dramatic drop suggests a rapid onset of action for etrasimod. The PP-NRS also dropped numerically a greater amount at Week 12 for the etrasimod 2 mg cohort (34.1%) than for the placebo cohort (23.9%) (p=0.1549).

The DLQI measures overall impairment due to a dermatologic condition on a scale of 0 to 30, with 30 representing an extremely large effect on a patient's life. In assessing their overall DLQI, participants in the etrasimod 2 mg cohort saw statistically significant declines in their degree of impairment, dropping 7.6 points at Week 12 versus a drop of 4.2 points for placebo (p=0.0122).

The POEM patient-reported measure of etrasimod's efficacy also validated the investigational drug as a potential treatment for AD. The indexing of POEM indicates that as disease severity is reduced, the patient's life improves. In ADVISE, the etrasimod 2 mg cohort experienced an 8.4 point reduction versus 4 points for placebo (p=0.0045), results that are both clinically and statistically significant.

Etrasimod showed a favorable safety profile in ADVISE. During the trial there were no serious adverse events or opportunistic or serious infections observed. The most common adverse events for participants of >5% and greater than placebo were nausea, constipation, back pain and dizziness.

Arena plans to submit data from the ADVISE trial for publication in a peer-reviewed journal.

Dr. Guttman-Yassky is a paid consultant and researcher for Arena Pharmaceuticals.

Researchers from the University of Oxford and their partners have today reported findings from a Phase IIb trial of a candidate malaria vaccine, R21/Matrix-M, which demonstrated high-level efficacy of 77% over 12-months of follow-up. In their findings (posted on SSRN/Preprints with The Lancet) they note that they are the first to meet the World Health Organization's Malaria Vaccine Technology Roadmap goal of a vaccine with at least 75% efficacy.

The authors report (in findings in press with The Lancet) from a Phase IIb randomised, controlled, double-blind trial conducted at the Clinical Research Unit of Nanoro (CRUN) / Institut de Recherche en Sciences de la Santé (IRSS), Burkina Faso. 450 participants, aged 5-17 months, were recruited from the catchment area of Nanoro, covering 24 villages and an approximate population of 65,000 people.

The participants were split into three groups, with the first two groups receiving the R21/Matrix-M (with either a low dose or high dose of the Matrix-M adjuvant) and the third, a rabies vaccine as the control group. Doses were administered from early May 2019 to early August 2019, largely prior to the peak malaria season.

The researchers report a vaccine efficacy of 77% in the higher-dose adjuvant group, and 71% in the lower dose adjuvant group, over 12 months of follow-up, with no serious adverse events related to the vaccine noted.

Following these results, the Phase IIb trial, which was funded by the EDCTP2 programme supported by the European Union (grant number RIA2016V-1649-MMVC), was extended with a booster vaccination administered prior to the next malaria season one year later.

The researchers, in collaboration with Serum Institute of India Private Ltd., and Novavax Inc., have now started recruitment for a Phase III licensure trial to assess large-scale safety and efficacy in 4,800 children, aged 5-36 months, across four African countries.

Halidou Tinto, Professor in Parasitology, Regional Director of IRSS in Nanoro, and the trial Principal Investigator said:
'These are very exciting results showing unprecedented efficacy levels from a vaccine that has been well tolerated in our trial programme. We look forward to the upcoming phase III trial to demonstrate large-scale safety and efficacy data for a vaccine that is greatly needed in this region.'

Adrian Hill, Director of the Jenner Institute and Lakshmi Mittal and Family Professor of Vaccinology at the University of Oxford, and co-author of the paper, said:

'These new results support our high expectations for the potential of this vaccine, which we believe is the first to reach the WHO's goal of a vaccine for malaria with at least 75% efficacy.

'With the commitment by our commercial partner, the Serum Institute of India, to manufacture at least 200 million doses annually in the coming years, the vaccine has the potential to have major public health impact if licensure is achieved.'

Professor Charlemagne Ouédraogo, Minister of Health, in Burkina Faso said:

'Malaria is one of the leading causes of childhood mortality in Africa. We have been supporting trials of a range of new vaccine candidates in Burkina Faso and these new data show that licensure of a very useful new malaria vaccine could well happen in the coming years. That would be an extremely important new tool for controlling malaria and saving many lives.'

Professor Alkassoum Maiga Ministry of Higher Education, Scientific Research and Innovation in Burkina Faso, said:

'I am proud of Burkina Faso researchers who made a great contribution to reach this important milestone. Hope that the upcoming phase III trial will confirm these exciting findings and that this vaccine could have a real impact on this disease affecting millions of children every year.'

Dr Cyrus Poonawalla and Mr Adar Poonawalla, Chairman and CEO of the Serum Institute of India said:

'We are highly excited to see these results on a safe and highly effective malaria vaccine which will be available to the whole world through an excellent collaborative effort between Serum Institute, the University of Oxford and Novavax Inc.. Serum Institute is committed to global disease burden reduction and disease elimination strategies by providing high volume, affordable vaccines. We are highly confident that we will be able to deliver more than 200 million doses annually in line with the above strategy as soon as regulatory approvals are available.'

Dr Michael Makanga, EDCTP Executive Director, said:

'We congratulate the Multi-stage Malaria Vaccine Consortium on these highly promising results from the Burkina Faso trial of R21. This study represents a key advance in the clinical development of the R21 malaria vaccine towards licensure, and an important step closer to malaria control and elimination.'

Gareth Jenkins, Director of Advocacy, Malaria No More UK, said:

'An effective and safe malaria vaccine would be a hugely significant extra weapon in the armoury needed to defeat malaria, which still kills over 270,000 children every year. For decades, British scientists have been at the forefront of developing new ways to detect, diagnose, test and treat malaria, and we must continue to back them.

'A world without malaria is a world safer both for the children who would otherwise be killed by this disease, and for us here at home. Countries freed from the malaria burden will be much better equipped to fight off new disease threats when they inevitably emerge in the future.'

What The Study Did: This review of 125 U.S.-based clinical trials that investigated the management of hearing loss assessed representation in the trials by race/ethnicity and sex.

Authors: Carrie Nieman M.D., M.P.H., of the Johns Hopkins University Bloomberg School of Public Health in Baltimore, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ 

(doi:10.1001/jamaoto.2021.0550)

Editor's Note: The article includes conflicts of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

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Media advisory: The full article is linked to this news release.

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/10.1001/jamaoto.2021.0550?guestAccessKey=4a6d3f17-01d3-4d8d-99c0-925e28e69efa&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=042221

What The Study Did: Researchers investigated racial/ethnic representation in clinical trials that led to U.S. Food and Drug Administration approval of ophthalmology drugs from 2000 to 2020.

Authors: Shriji Patel, M.D., of Vanderbilt University Medical Center in Nashville, Tennessee, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ 

(doi:10.1001/jamaophthalmol.2021.0857)

Editor's Note: The article includes conflicts of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

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Media advisory: The full article and commentary are linked to this news release.

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The unprecedented development of COVID-19 vaccines less than a year after discovery of this virus was enabled by more than $17 billion of research on vaccine technologies funded by the NIH prior to the pandemic, according to new research from Bentley University's Center for Integration of Science and Industry. The article, titled "NIH funding for vaccine readiness before the COVID-19 pandemic," demonstrates the critical role this broad foundation of government-funded research plays in ensuring vaccine readiness.

The report, published today in the journal Vaccine, examined the maturation of research and NIH funding for ten technologies that were applied in candidate COVID-19 vaccines as of July 2020. The maturation of these technologies was described in 51,530 published research papers from 2000-2019, of which 8,420 (16%) acknowledge NIH funding totaling $17.2 billion. Some of these technologies have been employed successfully in vaccines since the mid-20th century. Others, such as the viral vectors employed in the Johnson & Johnson and AstraZeneca vaccines, emerged from genetic engineering in the 1980s, and were found to be established prior to 2010. Still others, including the mRNA technologies employed by Pfizer/BioNTech and Moderna, only recently reached an established point.

"Rapid development of COVID vaccines was only possible because companies had access to a tool kit of established technologies," said Dr. Fred Ledley, Director of the Center for Integration of Science and Industry. "Some of the most recent technologies, including mRNA and viral vectors, proved to be particularly suitable for COVID-19 and the timelines required to combat this pandemic. The substantial public sector investments over the past 20 years that went into the maturation of these technologies needs to be considered in the pricing of these products and their availability to the public."

"This study also found surprisingly little NIH-funded, published research on vaccines for recognized pandemic threats, such as coronavirus, Zika, Ebola, or dengue virus," said Dr. Anthony Kiszewski, lead author of the study and Associate Professor of Natural & Applied Science at Bentley University. "Mechanisms need to be developed for funding research on vaccine technologies that accelerate vaccine development against emergent threats and preempt future pandemics."

Key takeaways

Tourniquet use has been consistently increasing in Los Angeles County since 2015 and is significantly associated with improved patient survival.
Tourniquet use is safe and does not lead to increased risk of amputation with proper surgical care after arriving at the hospital.
Findings are specific to Los Angeles County, where patients who had a tourniquet placed were able to be transported quickly to a trauma center for further life-saving care.

CHICAGO (April 22, 2021): Uncontrolled bleeding continues to be one of the most common causes of preventable death from a traumatic injury.1 However, patient survival from such injuries has improved in Los Angeles County due to an increased use of tourniquets to help stop severe bleeding before a patient arrives at a hospital. Findings appear in a Journal of the American College of Surgeons study published online in advance of print.

Researchers from the University of Southern California, Los Angeles set out to determine whether tourniquet use was increasing over time at the local level, specifically in Los Angeles County, and whether the use of tourniquets to control bleeding before a patient arrives at a hospital is associated with improved patient outcomes without complications. This study is believed to be the first of its kind, capturing tourniquet use data for an entire region, according to the authors.
"In Los Angeles County, the use of prehospital tourniquets for patients with extremity vascular injuries is increasing," the researchers concluded. "Its use is significantly associated with improved survival and a decreased blood transfusion requirement, without an increased risk of delayed amputation."
Tourniquets have previously been used more in the armed forces, but have become increasingly accepted in civilian life in recent years due to their effectiveness at reducing death after an injury. Although tourniquets had once fallen out of favor over concerns of complications, recent studies have shown they are largely safe with proper surgical care after arriving at the hospital.2
"What appears consistent across recent studies is that tourniquet use does not appear to be associated with an increased risk of delayed amputation, even with tourniquet times of over two hours," the authors note.
Study details
The researchers conducted a retrospective study from October 2015 to July 2019, including 944 patients in the study, 97 of which had a prehospital tourniquet placed before arriving at the hospital. Data on tourniquet placement by an EMS provider or a member of the public were not captured. Data were pulled from the Emergency Medical Services (EMS) provider registry and the trauma registry of the Los Angeles County Department of Health Services (LAC-DHS) EMS Agency. The patients included were trauma patients who were transported by EMS to one of the 15 Level I or Level II trauma centers in Los Angeles County.
The researchers compared two groups in the study, those with a prehospital tourniquet (PHTQ) placed with those who had no-tourniquet (no-PHTQ) placed. The average hospital length of stay, intensive care unit (ICU) length of stay, and delayed amputation rates were similar for both groups. Key differences include the following:

In-hospital mortality was significantly higher in the no-PHTQ group (1 percent for PHTQ vs 8.9 percent for no-PHTQ)
Prehospital tourniquet use was significantly associated with lower blood transfusion requirements at four hours and 24 hours (1 liter of blood needed at four hours and 2.5 liters at 24 hours for non-tourniquet patients and about a half-liter and one liter, respectively, for tourniquet patients)

"A higher number of tourniquets placed was associated with improved mortality and decreased requirements for transfusions and no difference in the rate of amputations," said lead study author Reynold Henry, MD, MPH, general surgery chief resident at LAC+USC Medical Center.
Importance of trauma center access
Although the researchers found a significant relationship between the use of tourniquets and an improvement in patient survival, they noted these findings are specific to Los Angeles County, where access to a trauma center is much more readily available than many rural areas in the U.S.
"The average transport time to a trauma center in Los Angeles County is around 10 to 15 minutes, which is quite short compared to other areas of the country, especially rural areas," said Kazuhide Matsushima, MD, FACS, assistant professor of surgery in the division of acute care surgery, LAC+USC Medical Center.
STOP THE BLEED® saves lives
One of the factors behind the increase in prehospital tourniquet use is STOP THE BLEED®, a public awareness campaign aimed at empowering the public by teaching bleeding control techniques--applying a tourniquet, applying pressure, or packing a wound--in communities across the U.S. and around the world. Dr. Henry and Dr. Matsushima stressed the importance of widespread tourniquet availability and public knowledge of bleeding control techniques. By knowing how to control bleeding, members of the public can become empowered to save a life.
"We'd like to encourage the public to think about this as a very simple intervention that anyone can do after a very simple training. Anyone can save a life," said Dr. Matsushima.
An important aspect of spreading this knowledge is governmental legislation that enhances the reach and lifesaving ability of STOP THE BLEED®.
"On a local, state, and federal level, policy needs to reflect that getting tourniquets into public spaces and mandatory STOP THE BLEED® training for certain types of jobs can go a long way. That is something we, as surgeons, should be advocating for," Dr. Henry said.

A phase 1 clinical trial led by investigators at the University of Chicago Medicine testing the effects of stereotactic body radiotherapy for treating multiple metastases has determined that treatments used for single tumors can also be safely used for treating patients with multiple metastases. The study was run through NRG Oncology and sponsored by the National Cancer Institute. The results were published on April 22 in JAMA Oncology.

Cancer is traditionally treated with a combined approach, with clinicians using surgery, chemotherapy and radiation therapy to kill and remove cancerous tumors. Systemic treatments such as chemotherapy often are not enough to stop the cancer's growth.

Stereotactic body radiation therapy (SBRT) is a type of radiation therapy that uses precisely targeted beams of very high doses of radiation to destroy tumors. The higher doses are more effective at killing cancer cells than traditional radiation therapy, while the careful targeting of tumors reduces damage to noncancerous tissue.

This approach has been used successfully to treat small, early stage tumors, but until now, it was not clear if such high doses of radiation would be safe in patients with multiple tumors due to metastatic cancer. Because SBRT uses multiple, high-intensity radiation beams, physicians have to be especially careful in locating tumors and targeting the radiation beams to maximize benefits and minimize risks -- a challenge that Steven Chmura, MD, PhD, likened to trying to "cross the beams" in the "Ghostbusters" movie.

"Part of the difficulty is working out the logistics for testing this approach in patients across multiple institutions," said Chmura, Professor of Radiation and Cellular Oncology at UChicago Medicine. "We've thought for a long time that you could treat three or four metastases at the same time, but it's very technically complicated to do so. But before we could test this in something like a large, phase 3 clinical trial, we had to prove that we could get multiple institutions together and come up with a 'cook book' for how to do this right, ensuring that treatment was the same across the board. This was really like seven phase 1 clinical trials rolled into one."

A phase 1 clinical trial, led by Chmura, set out to test the safety of such an approach. In a trial of 39 patients who had breast, prostate or non-small cell lung cancer with at least three metastases or two metastases in close proximity, the investigators determined that there were no treatment-related deaths and that the approach was safe enough to begin phase 2/3 clinical trials in a larger group of patients.

"At the end of the trial, the primary endpoint of six-month dose limiting toxicity was 0%," Chmura said. "This shows us that treating three or four sites of metastases throughout the body with these high-ablative doses of radiotherapy is safe."

Radiation therapy is not without risks. While the study found that no patients experienced side effects severe enough to call off the study, several adverse events were linked to the treatment, including gastric ulcers, broken bones and bone pain, and pneumonitis. In many cases during the four-year trial, these side effects appeared months to years following treatment, highlighting the importance of maintaining long-term follow-up contact with these patients. Overall, however, none of these treatments or side effects led to increased risk of death.

"People have been saying for years that if we used SBRT in patients with multiple, limited metastases, we could potentially cure more patients," said Chmura. "But we needed to conduct these large-scale, phase 2/3 clinical trials to prove that. And before we can do those large trials, we had to set up the infrastructure. The greatest challenge was having a whole team of people come together and figure out how we could define the doses and manage the real-time quality assurance to make sure every single patient had the best treatment possible."

With this collaborative infrastructure in place, the investigators have launched additional trials to test the efficacy of stereotactic body radiation therapy for treating patients with multiple metastases. The group is currently enrolling patients in a phase 2/3 trial for using SBRT for the treatment of metastatic breast cancer, with the goal of treating up to 450 people.

The 'stickiness', or viscosity, of microscopic liquids can now be measured thousands of times faster than ever before, potentially leading to better understanding of living cells, disease diagnostics and pharmaceutical testing.

University of Queensland's Professor Warwick Bowen and his colleagues at the Queensland Quantum Optics Lab developed the world-leading technology, technology that uses lasers to track microscale particles with world-record precision.

"The stickiness, or viscosity, of liquids is incredibly important in biology," Professor Bowen said.

"In living cells, viscosity fluctuations control shape and structure, modulate chemical reactions, and signal whether a cell is healthy or cancerous.

"However, current technologies to measure viscosity are too slow to monitor and track these important changes.

"Our innovative new technology overcomes this by achieving viscosity measurements a thousand times faster than ever before."

The technology may lead to a fundamental revision of scientists' understanding of cells.

"It's thought that fast viscosity fluctuations may occur in our cells - linked to their turbulent or chaotic activity - though they've never been observed," Professor Bowen said.

"Observing them would be re-calibrate our understanding of cells - it would force us to revise our basic models of cellular dynamics.

"These phenomena are predicted to occur on sub-millisecond timescales, far faster than can be measured with previous technology, but completely measurable with ours.

"Cells are the building blocks of life - we could be on the precipice of reimagining how they function."

Dr Lars Madsen said the discovery may spur advancements in pharmaceutical testing, allowing companies to quality control their drugs faster, and with greater accuracy.

"There are many moving parts when it comes to pharmaceutical manufacture - stirring, pumping, filling," Dr Madsen said.

"These processes need to be incredibly exact, and usually have to be controlled by performing regular viscosity checks with a viscometer.

"We've invented an alternative technology, with accuracy and selectivity far beyond existing viscometer technology.

"Faster, more accurate testing can create products that are not only be safer, but could offer better storage stability, reduce costs significantly by improving yield, reduce raw material variability and increase delivery reliability.

"We've all seen the impacts of pharmaceutical hold-ups this year - speed-to-market is critical in this industry."

Patients with chronic kidney dysfunction frequently develop thickening of the heart muscle, so-called left ventricular hypertrophy. This is particularly pronounced in patients who are in the late stage of renal dysfunction, that is to say those requiring renal replacement therapy such as haemodialysis. The danger of this cardiac hypertrophy lies in the considerable associated increase in risk of acute cardiovascular disease, such as sudden cardiac death, for example. Haemodialysis patients have a number of risk factors for developing this form of cardiac hypertrophy. One of those is elevated levels of the protein Fibroblast Growth Factor 23 (FGF23), and these levels increase as kidney function deteriorates. However, FGF23 can be influenced by drugs in various ways. That is the finding of a recent study led by Katharina Dörr from the Division of Nephrology and Dialysis at MedUni Vienna's Department of Medicine III.

In a randomised controlled trial, 62 patients from two dialysis centres in Vienna (Vienna General Hospital, Vienna Dialysis Center) received either etelcalcetide (from the group of calcimimetics) or alfacalcidol (Vitamin D) over a period of one year. Both drugs are primarily used to treat a bone disease that commonly occurs in patients with kidney disease (secondary hyperparathyroidism). The treatment was administered to the patients intravenously after each dialysis session. The thickness of the heart muscle was measured by means of an MRI scan at the start of the trial and again at the end.

The result: "We were able to show that the FGF23 values had fallen significantly in the group being treated with etelcalcetide and the left ventricular mass was unchanged after one year, while there had been an increase in FGF23 levels in the alfacalcidol group and a further increase in cardiac hypertrophy," summarises Katharina Dörr. "The reduction of FGF23 could slow the progression of pathological left ventricular hypertrophy by 6 to 8% within one year. An effective treatment for this disease could therefore reduce the risk of sudden cardiac death in this population, which already has a significantly elevated cardiovascular risk."

The trial was conducted at the Division of Nephrology and Dialysis of MedUni Vienna's Department of Medicine III between 2017 and 2019 by the working group led by Katharina Dörr and Divisional Head Rainer Oberbauer. Approximately 850 million people worldwide suffer from chronic kidney disease. In Western countries, around 10% of the adult population has chronic kidney damage, primarily caused by diabetes and hypertension. Globally, approximately 2.4 million people a year die from the sequelae of chronic kidney disease. Most causes of death are cardiological in nature.