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A combination of reduced-dose radiotherapy using intensity-modulated radiotherapy (IMRT) combined with concurrent cisplatin met the threshold for disease control and quality of life compared to the standard of care for good-risk patients with HPV-associated oropharyngeal squamous cell carcinoma on the NRG Oncology clinical trial NRG-HN002. The outcomes from this data justify the advancement of the reduced radiotherapy dose with cisplatin to a Phase III clinical trial setting in this population. These results were recently published in the Journal of Clinical Oncology.

"Currently, patients with HPV-associated oropharyngeal cancer are treated with 70 Gy of radiotherapy with concurrent platinum chemotherapy, but this treatment is typically associated with severe short-and long-term toxicities. NRG-HN002 was designed as a Phase II trial assessing a treatment approach using a reduced radiotherapy dose with or without cisplatin based on preclinical data and data from single-arm studies to see if this produced good outcomes for this patient population," stated Sue S. Yom, MD, of the University of California, San Francisco, and the lead author of the NRG-HN002 manuscript.

NRG-HN002 randomly assigned 306 eligible patients to either the experimental arm of 60 Gy of IMRT for 6 weeks with concurrent weekly cisplatin (IMRT+C) or the control arm of 60 Gy of IMRT for five weeks. In order to establish acceptability as compared to the standard of care, at least one arm had to achieve a 2-year progression-free survival (PFS) rate above the historical control rate of 85% as well as a 1-year mean composite score of 60 or greater based on the MD Anderson Dysphagia Inventory (MDADI).

Data indicated that the IMRT+C arm yielded a 2-year PFS rate of 90.5% (p=0.04, rejecting the null hypothesis of 2-year PFS ? 85%) compared to 87.3% (p=0.23) in the IMRT alone arm. 1-year mean MDADI scores were 85.30 for the IMRT+C arm versus 81.76 for the IMRT alone arm. 2-year overall survival rates were 96.7% and 97.3% for the IMRT+C and the IMRT alone arms, respectively. While more grade 3-4 acute toxicities were discovered for the IMRT+C arm (79.6% vs. 52.4%; p

"Our next step is a Phase II-III trial in which we intend to compare disease control rates using reduced-dose radiation with cisplatin or nivolumab against the standard of care," added Dr. Yom.

Coronary artery calcification -- the buildup of calcified plaque in the walls of the heart's arteries -- is an important predictor of adverse cardiovascular events like heart attacks. Coronary calcium can be detected by computed tomography (CT) scans, but quantifying the amount of plaque requires radiological expertise, time and specialized equipment. In practice, even though chest CT scans are fairly common, calcium score CTs are not. Investigators from Brigham and Women's Hospital's Artificial Intelligence in Medicine (AIM) Program and the Massachusetts General Hospital's Cardiovascular Imaging Research Center (CIRC) teamed up to develop and evaluate a deep learning system that may help change this. The system automatically measures coronary artery calcium from CT scans to help physicians and patients make more informed decisions about cardiovascular prevention. The team validated the system using data from more than 20,000 individuals with promising results. Their findings are published in Nature Communications.

"Coronary artery calcium information could be available for almost every patient who gets a chest CT scan, but it isn't quantified simply because it takes too much time to do this for every patient," said corresponding author Hugo Aerts, PhD, director of the Artificial Intelligence in Medicine (AIM) Program at the Brigham and Harvard Medical School. "We've developed an algorithm that can identify high-risk individuals in an automated manner."

Working with colleagues, lead author Roman Zeleznik, MSc, a data scientist in AIM, developed the deep learning system described in the paper to automatically and accurately predict cardiovascular events by scoring coronary calcium. While the tool is currently only for research purposes, Zeleznik and co-authors have made it open source and freely available for anyone to use.

"In theory, the deep learning system does a lot of what a human would do to quantify calcium," said Zeleznik. "Our paper shows that it may be possible to do this in an automated fashion."

The team began by training the deep learning system on data from the Framingham Heart Study (FHS), a long-term asymptomatic community cohort study. Framingham participants received dedicated calcium scoring CT scans, which were manually scored by expert human readers and used to train the deep learning system. The deep learning system was then applied to three additional study cohorts, which included heavy smokers having lung cancer screening CT (NLST: National Lung Screening Trial), patients with stable chest pain having cardiac CT (PROMISE: the Prospective Multicenter Imaging Study for Evaluation of Chest Pain), and patients with acute chest pain having cardiac CT (ROMICAT-II: the Rule Out Myocardial Infarction using Computer Assisted Tomography trial). All told, the team validated the deep learning system in over 20,000 individuals.

Udo Hoffmann, MD, director of CIRC@MGH who is the principal investigator of CT imaging in the FHS, PROMISE and ROMICAT, emphasized that one of the unique aspects of this study is the inclusion of three National Heart, Lung, and Blood Institute-funded high-quality image and outcome trials that strengthen the generalizability of these results to clinical settings.

The automated calcium scores from the deep learning system highly correlated with the manual calcium scores from human experts. The automated scores also independently predicted who would go on to have a major adverse cardiovascular event like a heart attack.

The coronary artery calcium score plays an important role in current guidelines for who should take a statin to prevent heart attacks. "This is an opportunity for us to get additional value from these chest CTs using AI," said co-author Michael Lu, MD, MPH, director of artificial intelligence at MGH's Cardiovascular Imaging Research Center. "The coronary artery calcium score can help patients and physicians make informed, personalized decisions about whether to take a statin. From a clinical perspective, our long-term goal is to implement this deep learning system in electronic health records, to automatically identify the patients at high risk."

A new report combining forecasting and expert prediction data, predicts that 125,000 lives could be saved by the end of 2021 if 50% or more of the U.S. population initiated COVID vaccination by March 1, 2021.

"Meta and consensus forecast of COVID-19 targets," developed by Thomas McAndrew, a computational scientist and faculty member at Lehigh University's College of Health, and colleagues, incorporates data from experts and trained forecasters, combining their predictions into a single consensus forecast. In addition McAndrew and his team produce a metaforecast, which is a combination of an ensemble of computational models and their consensus forecast.

In addition to predictions related to the impact of vaccinations, the report includes forecasting analyses on a variety of U.S. COVID-related issues, including number of cases, hospitalizations and deaths and the prevalence of the B.1.1.7 variant, which first emerged in the United Kingdom but is believed to be spreading rapidly in the U.S.

From the report:

125,000 fewer deaths predicted by end of 2021 if greater than or equal to 50% of U.S. population initiates vaccination by March 1, 2021: McAndrew finds that if greater than or equal to 50% of the U.S. population initiates vaccination by March 1, 2021 the consensus median prediction of the cumulative number of deaths by Dec. 31, 2021 is 520,000. In contrast, if less than 50% of the U.S. population initiates vaccination the consensus median prediction is 645,000. A consensus of subject matter experts and trained forecasters predict 125,000 (difference between two medians above) fewer deaths due to COVID-19 if at least 50% of the population was vaccinated by March 1. 2021 and highlights the importance of increasing the rate of vaccinations throughout the U.S.

Predicted increases in hospitalizations, cases and deaths: The team finds that a consensus of experts and trained forecasters predicts, for the week beginning Jan 24th and ending Jan 30th, an increase in the number of pediatric and adult hospital admissions (median = 132,500), increase in the number of new confirmed cases of COVID-19 (median = 1,700,000), and an increase in the number of new deaths due to COVID-19 (median = 22,400).

Predicted increase in B.1.1.7 variant prevalence: The report shows that a consensus of subject matter experts and trained forecasters predict 87% of US samples sent for genomic sequencing in the first two weeks of Feb. that have an S-gene dropout (present in all B.1.1.7 samples) will be identified as the B.1.1.7 variant. Currently, according to McAndrew, approximately 22% of samples are being identified as the B.1.1.7 variant.

McAndrew's approach to forecasting is different from the traditional approach, he says. Rather than build a computational model to predict cases, deaths, and hospitalizations due to COVID, he asks experts and trained forecasters to predict these targets and combines their predictions into a single consensus forecast.

In addition he produces a metaforecast: a combination of an ensemble of computational models and the consensus forecast.

"The idea is to combine computational models with human judgment to make more accurate predictions of the US outbreak," says McAndrew.

More fully appreciating family and engaging in more conflict are among the heightened experiences during the coronavirus pandemic, according to a new UC Riverside study.

The study from David Funder's psychology lab looked at how people experience everyday life and its situations and how those experiences change because of an extraordinary event - the global pandemic.

Undergraduate students took part in the study, which first collected responses from 544 of them in 2017, and then from 123 students during the pandemic in spring 2020, when most of the participants were sheltering at home.

The before-and-during comparison isn't all roses for pandemic living. Some everyday experiences suffer, such as conversation, finding new relationships and romantic partners, and playing by the rules.

"These differences appear to reflect how being at home with one's family is a situation with simple, well-learned expectations but also how living in close quarters with others can be a source of tension," wrote the authors of the paper, "The Experience of Situations Before and During a COVID-19 Shelter-at-Home Period," published in the journal Social Psychological and Personality Science.

For the study, participants visited a website that assessed how they experience situations pre- and post-pandemic, along with demographic and personality variables.

For some situations measured, it was difficult to assign a good-or-bad value. For instance, respondents said there is less expectation for talking - "something some would consider good, and some bad," the study authors wrote.

Overall, though, study authors were surprised to find that respondents positive feelings remained about the same before and during the pandemic.

"Even in the midst of events as extreme as being forced to give up normal social activities and shelter at home, the degree to which one experiences daily life as a positive experience is largely determined by one's personality," said Funder, a distinguished professor of psychology and the study's lead author.

(Singapore--16:45 p.m. SPT/3:45 EST January 29, 2021)--Two presentations from the ADAURA clinical trial advanced previous research that demonstrated improved disease-fee survival (DFS) outcomes for patients with surgically resected non-small cell lung cancer (NSCLC) receiving osimertinib. The data were reported today at the International Association for the Study of Lung Cancer's 2020 World Conference on Lung Cancer (WCLC) Singapore.

Osimertinib is a third-generation, irreversible, central nervous system-active, epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor. ADAURA is a randomized Phase III trial comparing adjuvant osimertinib with placebo in patients with surgically resected stage IB to IIIA (AJCC 7th edition; pathologic stage) NSCLC that harbors an activating EGFR mutation with either an exon 19 deletion or exon 21 L858R substitution. Postoperative chemotherapy was allowed, per physician and patient choice. Adult patients were randomized 1:1 and treated with osimertinib 80 mg once-daily oral tablets or placebo for three years or until disease recurrence.

In one analysis (Abstract 3505), presented by Dr. Margarita Majem, Department of Medical Oncology at the Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, adjuvant osimertinib, with or without prior adjuvant chemotherapy, provided a significant DFS benefit without affecting health-related quality of life (HRQoL), a secondary endpoint of the study, in completely resected and disease-free patients with stage IB-IIIA EGFRm NSCLC.

HRQoL was assessed with the short form-36 (SF-36) health survey, which consisted of eight domains and two aggregated summary scores, physical [PCS] and mental [MCS] component summary, and was completed by patients at randomization, 12 and 24 weeks, then every 24 weeks until treatment completion or discontinuation.

The SF-36 T-scoring system assesses different physical and mental health parameters. Higher T?scores indicate better health. Survey compliance was high, at ?85% among both treatment and placebo arms.

Analysis of the survey data showed that patients treated with adjuvant osimertinib maintained their quality of life, with no clinically meaningful differences in the physical or mental health scores between the osimertinib and placebo arms (PCS -1.18 [95% CI: -2.02, -0.34]; MCS -1.34 [95% CI: ?2.40, ?0.28]. There were no differences in time to deterioration (TTD) of PCS (HR: 1.17) or MCS (HR: 0.98).

"The effect of adjuvant treatment on health-related quality of life is an important clinical consideration for patients who, following surgery with curative intent, are disease-free and require long-term treatment to reduce the risk of disease recurrence," Dr. Majem said.

In the next trial (Abstract 3464), Dr. Yi-Long Wu, one of the WCLC co-chairs and of Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Guangzhou/China, presented data that adjuvant osimertinib demonstrated a highly statistically significant improvement in DFS vs placebo in patients with resected stage IB-IIIA EGFRm NSCLC. Quality of life was maintained during osimertinib treatment, with no clinically meaningful differences observed between arms.

Dr. Wu and colleagues randomly assigned patients with resected stage IB-IIIA (AJCC 7th edition; pathologic stage) EGFR-mutated NSCLC to receive 80 mg of daily osimertinib or to placebo for three years (study completion) or until disease recurrence. Disease staging was based on electronic case report forms for baseline characteristics data, and interactive voice response system (IVRS) for efficacy data (per statistical analysis plan).

In ADAURA, 60% (410/682) of all patients randomly assigned received adjuvant chemotherapy for a median duration of 4.0 (Q1: 4.0, Q3: 4.0) cycles, balanced across treatment arms. Overall, 409 patients received platinum-based chemotherapy, most with stage IIIIIA (II: 71% [165/231]; IIIA: 80% [187/235]), and fewer with stage IB (26% [57/216]), disease. Across disease stages, the overall proportion of patients who received chemotherapy was 66% in patients aged younger than 70 (338/509), compared with 42% (72/173) in patients aged 70 or older, reducing to 27% (21/78) in patients aged 75 or older.

The group that received chemotherapy (n = 230) experienced 22 DFS events (11%), and the placebo group (n = 207) experienced 103 DFS events (50%). The treatment arm that received osimertinib without chemotherapy (n = 136) experienced 15 DFS events or 11% while the placebo group that did not receive chemotherapy experienced 56 DFS events or 40% rate.

Dr. Wu reported that DFS benefit with osimertinib vs placebo for patients who received prior chemotherapy was similar to that for patients who had not received prior chemotherapy, regardless of disease stage.

"These data further support adjuvant osimertinib as a new treatment strategy in this setting, with significant DFS benefit and maintained quality of life," said Dr. Wu.

Four million UK patients could benefit annually from genetic testing before being prescribed common medicines, according to new research from the University of East Anglia (UEA) in collaboration with Boots UK and Leiden University (Netherlands).

Researchers looked through 2019 NHS dispensing data across the UK to see how many patients are started on new prescriptions each year that could be potentially optimised by genetic testing.

They studied 56 medicines, including antidepressants, antibiotics, stomach ulcer treatments and painkillers where there are known drug-gene interactions.

And they found that in more than one in five occasions (21.1 per cent) there was the potential for a doctor or pharmacist to take action under international pharmacogenetic guidelines.

If this screening was applied to all new prescriptions, an estimated one in 11 (9.1 per cent) would lead to a change of drug or dose, affecting over five million dispensed items.

Depending on the results of individual pharmacogenetic tests, they might either get a higher or lower starting dose than normal or be more closely monitored during the early stages of treatment.

Pharmacogenomic testing services already working in the Netherlands show that specially-trained GPs and pharmacists can carry out pre-prescribing tests and use the results to give advice on safer and more effective prescribing, delivering better patient outcomes.

Essra Youssef, a research pharmacist at UEA's School of Pharmacy, said: "We know over 95 per cent of the population carry a genetic marker that predicts an atypical response to at least one medicine.

"Our study looked at nine of these genetic markers, affecting 56 medicines that are commonly dispensed by community pharmacies in the UK. The most common of these are weak opioids, antidepressants and proton-pump inhibitors, which are prescribed to reduce stomach acid.

"We wanted to see how pharmacogenetic testing, before being prescribed common medicines, could benefit patients.

"We found that around four million patients annually in the UK could benefit from having this new technology.

"Better selection of medicines based on a patient's genetic information could mean less side-effects and better treatment outcomes. This not only benefits the patient but also the NHS, as patients may not need to return to their GP so often to change their medication.

"It could also reduce hospital visits related to side effects of medicines. The testing process is quite simple in most cases, with a cheek swab sample collected and DNA analysed for genes related to medicines. As the cost of this testing continues to drop, the technology is more likely to represent good value for the NHS."

Marc Donovan, Chief Pharmacist at Boots UK, said: "We strongly believe that pharmacy has a key role to play supporting the wider accessibility and use of pharmacogenomics.

"Our work shows the benefits that patients and the NHS could get from rolling out a national screening programme as part of their plans to embed pharmacogenomics in clinical practice by 2025, and that this testing could be effectively delivered by community pharmacists.

"Last year, around four million people could have had a change in their prescribing, according to our figures. This would have reduced their risk of side effects and could have led to better clinical outcomes."

New research from the University of Iowa and University Hospitals Cleveland Medical Center demonstrates that offspring can be protected from the effects of prenatal stress by administering a neuroprotective compound during pregnancy.

Working in a mouse model, Rachel Schroeder, a student in the UI Interdisciplinary Graduate Program in Neuroscience, drew a connection between the work of her two mentors, Hanna Stevens, MD, PhD, UI associate professor of psychiatry and Ida P. Haller Chair of Child and Adolescent Psychiatry, and Andrew A. Pieper, MD, PhD, a former UI faculty member, now Morley-Mather Chair of Neuropsychiatry at Case Western Reserve University and Investigator and Director of the Neurotherapeutics Center at the Harrington Discovery Institute, University Hospitals Cleveland Medical Center.

Stevens's lab studies the long-lasting impact of stress during pregnancy, which can lead to neuropsychiatric impairment in offspring during early life and in adulthood. Pieper's lab focuses on discovery of neuroprotective treatments, exemplified by the pharmacologic agent used here, known as P7C3-A20, which has previously been shown to protect the adult brain from injury.

Schroeder spent time in both labs early in her graduate school career and was inspired to bring the two lines of research together in her own work, investigating the potential impact that P7C3-A20 might have in protecting the embryonic brain during adverse events in pregnancy. Her work is the first to explore the therapeutic potential of prenatal exposure to P7C3 compounds.

"Prenatal stress increases the risk for offspring to have neurodevelopmental problems," Schroeder said. "We wanted to know whether the P7C3-A20 compound protected the embryonic brain from damage. Our results show that offspring are protected from the negative effects of stress when the mothers are treated with P7C3-A20 during the same time."

The research was published online this week in the journal Antioxidants & Redox Signaling.

Previous work by Pieper's lab has shown that P7C3-A20 enables nerve cells to maintain normal levels of an energy molecule known as nicotinamide adenine dinucleotide (NAD+), under toxic or injury conditions that are otherwise overwhelming and energy-depleting for the cell.

Schroeder's research showed that chronic prenatal stress in mice disrupted the embryonic brain's NAD+-synthesis machinery, which led to degeneration of nerve cell axons, learning deficits, and depression-like behavior when the offspring reached adulthood. Schroeder demonstrated that when prenatally-stressed pregnant mice were simultaneously treated with P7C3-A20, their offspring were protected from these negative effects.

"By stabilizing critical NAD+-producing mechanisms, we enabled the developing embryonic brain to continue developing normally despite the stress," Schroeder said.

"Though there are many challenges associated with administering medicines during pregnancy, Rachel Schroeder's discovery represents an exciting move forward in understanding how prenatal stress harms the brain, and strategies for protecting the developing embryo," said Pieper, who is also a psychiatrist at the Louis Stokes VA Medical Center in Cleveland.

This study represents an important proof of concept for a new approach to early prevention of neuropsychiatric problems, Stevens said. "Neuropsychiatric problems are the most common chronic illnesses of young people, which means we need many more ways to protect the brain as it develops. Our lab is focused on mechanisms of brain development prenatally, a critical time when we could make a difference."

A research team from HSE University and SkolTech, together with experts from the Smorodintsev Research Institute of Influenza in St. Petersburg and the RAS Kharkevich Institute for Information Transmission Problems (IITP), discovered that the SARS-CoV-2 virus independently entered Russia at least 67 times, mostly at the end of February and beginning of March 2020. The vast majority of introductions came from European countries. No cases of introduction from China were registered, which is likely due to the timely closure of borders with the country. Currently, nine local virus lineages are circulating in Russia, which are not present elsewhere in the world. Given that Russia was actively 'importing' the virus from abroad, the researchers have not detected any cases of 'exporting' any SARS-CoV-2 lineages in other countries.

The article 'Genomic epidemiology of the early stages of the SARS-CoV-2 outbreak in Russia' was published in Nature Communications.

To analyse and build phylogenetic trees, the researchers used 211 virus genomes, which were sequenced at Smorodintsev Research Institute of Influenza. All the genomes had been obtained from patients from 25 Russian regions (including the Republic of Crimea) during the period from March 11 to April 23, 2020. The resulting dataset reflected the situation at the early stages of the epidemic in Russia.

In addition, to establish the full scope of phylogenetic links, the scholars used a dataset of 19,623 SARS-CoV-2 genomes from the rest of the world available on May 26, 2020. The analysis also extensively used data about people's transit across Russian borders and inside the country.

The phylogenetic trees built by the researchers demonstrated that in the early stages of the epidemic, almost all lineages of SARS-CoV-2 that evolved by that time circulated in Russia. Meanwhile, a vast majority of genomes belonged to the lineages prevailing in Europe. It turned out that only 2% of them were Asian ones, while they comprised about 50% of the lineages in China at the moment. This means that the main channel of coronavirus 'import' was the passenger traffic from European countries. Probably, the Chinese lineages also came from Europe, since the borders with China had already been closed long before that.

The researchers believe that such a high diversity of the virus was achieved due to at least 67 independent virus introductions in different Russian cities in the end of February - beginning of March. Out of these, nine introductions led to the appearance of local virus lineages, which circulate only in Russia.

'The study demonstrates a way to objectively investigate the paths and character of a virus spreading in a population. Today is a unique situation for researchers: we are getting data, including genomic data, almost in real time. 'Thanks' to the pandemic, we are learning a lot about epidemics more broadly, which will help in predicting and controlling them in future,' says Vladimir Shchur, Head of International Laboratory of Statistical and Computational Genomics

One of the most interesting results is that the virus that launched the epidemic appeared in Russia quite late. Most of the people who brought the novel coronavirus to Russia arrived in late February - early March. There were no traces of earlier evolution of specific lineages in the country.

SARS-CoV-2 came to Russia to stay. There are no signs of 'exporting' the Russian variations of the virus abroad (at least to the countries with data available). This sets the country apart from such global super-spreaders as Italy and Spain, which laid the foundation for the European epidemic, or Great Britain. Inside Russia, the virus started spreading almost immediately after it was imported. The first in-Russia transmission happened as early as March 11.

The researchers paid particular attention at the virus outbreak at one of non-infectious hospitals in St. Petersburg - the Vreden Hospital, where over 700 people were locked down in a quarantine for a month, and over 400 of them were infected. According to the city governor Alexander Beglov, the virus was brought there by an employee who came back from a vacation in Turkey. However, the analysis of several dozen genomes from the institution demonstrated that the virus was introduced there from two to three times. And each time, this led to a specific outbreak, which merged and looked like one big outbreak.

The specific features of the Vreden Hospital case - its isolated community - make it look like the notorious infection at Diamond Princess cruise ship in the beginning of the pandemic. Such closed populations really get infected by one introduction. There had been no reason to believe that the situation in St. Petersburg was different. And only genome analysis helped reveal the real dynamics of infection in the hospital, with multiple repeated virus introductions.

Genomic epidemiology is only able to dispel the rumours and myths about the 'early epidemic' in Russia in November 2019 - January 2020, which are persistently discussed on social media. It also demonstrates the effectiveness of the state restrictive policies. For example, the timely closure of borders with China did not allow the novel coronavirus to be introduced from there into Russia in January and February 2020.

At the same time, the measures to control passenger traffic from Europe and other countries in February and March 2020 turned out to be insufficient. This is where SARS-CoV-2 came from, which provoked several local outbreaks that led to a full-scale epidemic.

In addition, genomic epidemiology is a good practical tool for epidemiologists, doctors and developers of vaccines. The more time that passes since the beginning of the pandemic, the more there are sequenced genomes of viruses from all parts of the planet. Different lineages will depart further, which will help us understand the general evolutionary vector of SARS-CoV-2, how it adapts to humanity and whether it demonstrates the signs of attenuation (decreasing the harmful effect on the human body and virulence).

ROCHESTER, Minn. -- In a new study published in Circulation, Mayo Clinic researchers provide the first preclinical, proof-of-concept study for hybrid gene therapy in long QT syndrome, a potentially lethal heart rhythm condition.

Researchers demonstrated its potential therapeutic efficacy in two in vitro model systems using beating heart cells reengineered from the blood samples of patients with 1 long QT syndrome. They targeted the whole KCNQ1 gene rather than specific LQT1-causative mutations, making this study applicable to all patients with long QT syndrome 1, regardless of their specific disease-causing variant.

The team consisted of Mayo Clinic researchers from Mayo Clinic's:

Department of Cardiovascular Medicine.

Department of Molecular Pharmacology and Experimental Therapeutics.

Department of Pediatric and Adolescent Medicine.

Center for Individualized Medicine.

Center for Regenerative Medicine.

The prevalence of long QT syndrome is about 1 in 2,000. When untreated, high-risk patients have an estimated 10-year mortality of 50%.

Long QT syndrome is a genetic heart rhythm condition that can potentially cause fast, chaotic heartbeats. These rapid heartbeats might trigger people to suddenly faint. Some people with the condition have seizures. In some severe cases, long QT syndrome can cause sudden cardiac death. The most common subtype, type 1 long QT syndrome, or LQT1, is caused by pathogenic variants in the KCNQ1 gene.

"Gene therapy is an emerging area of interest for treating a variety of genetic heart diseases in general and long QT syndrome in particular," says Michael Ackerman, M.D. Ph.D., a Mayo Clinic genetic cardiologist and director of Mayo Clinic's Windland Smith Rice Comprehensive Sudden Cardiac Death Program. "We designed and developed the first suppression and replacement KCNQ1gene therapy approach for the potential treatment of patients with type 1 long QT syndrome." Dr. Ackerman is senior author of this study.

According to Dr. Ackerman, over the past two decades, substantial improvements have been made to manage long QT syndrome, but current therapies, such as beta blockers and defibrillators, a more invasive therapy, still have limitations, risks and an array of unwanted side effects.

Gene therapy is a technique that treats diseases caused by defective genes by altering genes in a patient's cells rather than using drugs or surgery. Genes contain DNA -- the code that controls the body's form and function. Gene therapy replaces faulty genes or adds a new gene to try to treat a disease.

According to Dr. Ackerman in this case, this is the first time that hybrid gene therapy (simultaneous out with the old, in with the new) has been created for any form of genetic heart disease.

"If the therapeutic efficacy of this 'disease-in-the-dish' gene therapy trial with KCNQ1 can be replicated in a nonhuman, animal model of long QT syndrome, then suppression-replacement (hybrid) gene therapy may be a promising strategy for long QT syndrome in general and in theory almost any sudden death-predisposing autosomal dominant genetic heart disease," says Dr. Ackerman. "Of course, we still have a long way to go from nearly curing a patient's heart cells in the dish to effectively treating the whole person. Nevertheless, we are excited by this first critical milestone and look forward to the next step."

In addition to heart disease, researchers at Mayo Clinic's Center for Individualized Medicine are investigating an approach to replace and fix mutated genes in a wide range of genetic disorders.

Results of study by Children's Hospital Colorado, presented at the Society for Maternal Fetal Medicine's Annual Meeting, show a third of patients not needing narcotic pain pills after c-section

Aurora, Colo. (Jan. 28, 2021) In a retrospective analysis of cesarean deliveries from 2015 through 2020, a team of doctors from the Colorado Fetal Care Center at Children's Hospital Colorado (Children's Colorado) found that using a wound infusion pump in combination with enhanced recovery efforts such as removing urinary catheters earlier and walking around the same day of surgery can reduce opioid use by more than 80%. Also notable, the researchers found that a third of patients never took a single narcotic pain pill after the cesarean delivery.

"In line with our work to reduce opioid usage with the wound infusion pump, we wanted to see if enhanced recovery efforts in combination with the pump would further reduce the need for narcotic pain medicine," said Cristina Wood, MD, co-research lead and obstetric anesthesiologist with the Colorado Fetal Care Center at Children's Colorado. "These are moms who are going through so much already. We want to do everything we can to help them care for and interact with their baby, while providing optimum pain control."

Cesarean delivery is one of the most common surgical procedures in the U.S., accounting for 32% of all deliveries, according to the CDC's National Center for Health Statistics. Historically, most care providers, including those at the Colorado Fetal Care Center at Children's Colorado, which performs a large number of cesarean deliveries for high-risk pregnancies, would use a multimodal pain management regimen including opioids.

"As concerns about the use of opioids grew and literature on the effectiveness of wound infusion pumps was inconsistent, we saw an opportunity for improvement," said obstetrician Frank Chow, MD, co-research lead. "And the improvement was striking. Using enhanced recovery efforts such as scheduling non-narcotic medications postoperatively, limiting intraoperative IV fluids to reduce bowel swelling, implementing prophylactic anti-nausea medication, removing urinary catheters earlier and ambulating the same day of surgery in combination with the wound infusion pump resulted in a dramatic reduction in narcotic pain medication."

In 2019, the Colorado Fetal Care Center earned the Center of Excellence designation from the Society for Obstetric Anesthesia and Perinatology. With that designation came an increased focus on enhanced recovery after cesarean.

Philadelphia, January 28, 2021 - A collaborative study from the Center for Injury Research and Prevention (CIRP) and the Center for Autism Research (CAR) at Children's Hospital of Philadelphia (CHOP) found that compared with their non-autistic peers, young autistic drivers have lower rates of moving violations and license suspensions, as well as similar to lower crash rates.

The findings were recently published online by the Journal of the American Academy of Child and Adolescent Psychiatry.

Obtaining a driver's license is an important milestone for adolescents and young adults. One-third of autistic individuals without intellectual disability obtain their driver's license by the time they are 21 years old, increasing their mobility as they transition to adulthood.

Prior studies with driving simulators suggested that autistic drivers may be at higher risk for motor vehicle crashes, since autism spectrum disorder (ASD) can affect motor coordination and visual processing speed, both critical skills for safe driving. However, no previous research has objectively looked at the real-world risk of crashes and traffic violations among autistic adolescent and young adult drivers. This knowledge would help pinpoint specific skills instructors can build upon and inform tailored practice driving interventions and lessons to increase young autistic driver safety.

The researchers examined data from New Jersey residents born between 1987 and 2000 who were patients in the CHOP Care Network. Their electronic health records were linked with statewide driver licensing and crash databases. The data included 486 autistic and 70,990 non-autistic licensed drivers over their first four years of driving. The study team also examined the proportion of crashes that were attributed to specific driver actions and types of crashes.

"Our findings are noteworthy because they suggest newly-licensed autistic drivers may establish driving patterns that balance independent mobility and risk, bringing their crash risk in line with other young drivers," said Allison E. Curry, PhD, MPH, senior author of the study and a senior scientist and director of epidemiology at CIRP and an assistant professor of pediatrics at the Perelman School of Medicine at the University of Pennsylvania. "By learning more about their driving patterns and how their crashes differ from those of their peers, we can develop tailored training to help autistic adolescents and young adults develop the range of skills needed to become safe, independent drivers."

The study also found that young autistic drivers involved in crashes were substantially more likely to crash while making left- or U-turns and also more likely to crash due to not yielding for another vehicle or pedestrian.

The authors suggest that weaknesses in processing speed among young autistic drivers may make identifying, processing, or prioritizing potential hazards more difficult. Their motor speed and visual scanning skills may also be slower.

"Our study suggests that autistic adolescents and young adults may benefit from more on-road training than their non-autistic peers," said Benjamin E. Yerys, PhD, a co-author of the study, a psychologist in the Department of Child and Adolescent Psychiatry and Behavioral Sciences and director of the Data and Statistical Core at CAR. "They may need more tailored training in navigating turns and interacting safely with pedestrians and other vehicles."

Drawing on animal-foraging theory, a new model predicts psychological factors that may lead to panic buying during times of crisis. The model is largely supported by real-world data from the COVID-19 pandemic. Richard Bentall of the University of Sheffield, England, and colleagues presented these findings in the open-access journal PLOS ONE on January 27.

In the early stages of the pandemic, consumers in several countries around the world engaged in "panic buying" of household items, causing temporary shortages of toilet rolls and other products. Such behavior is typical during times of crisis, but few studies have examined the psychology of crisis-driven over-purchasing.

To better understand this phenomenon, Bentall and colleagues turned to animal-foraging theory, which considers tradeoffs between exploiting familiar local resources and traveling to seek resources of unknown abundance. They used this framework to develop a model that incorporates demographic, situational, and psychological factors to predict which factors lead to over-purchasing.

The researchers then tested the model using data from surveys conducted in 3,066 households in the U.K. and the Republic of Ireland shortly after strict physical distancing measures were first enacted. Participants self-reported their over-purchasing behaviors, as well as income, feelings of neighborhood belongingness, psychological distress, and other factors that might impact purchasing behaviors.

The survey showed that households that engaged in over-purchasing typically bought a wide range of products, rather than focusing on a single category. Over-purchasing was associated with higher income, the presence of children in the household, and a greater degree of psychological distress, threat sensitivity, and mistrust of others.

These findings were largely in line with the model's predictions. However, there were a few exceptions; for instance, greater neighborhood belongingness was unexpectedly associated with over-purchasing, perhaps because close neighbors talk amongst themselves about observed product shortages.

The researchers suggest that their model could help inform policies to mitigate panic-buying during future crises. Additional research could refine the model and examine it in the context of various types of crises.

The authors add: "Buying excessively and stockpiling is a natural response to a crisis, and can be adaptive if it does not lead to shortages. Governments who wish to avoid the shortages caused by panic buying need to pay attention to the psychology of this phenomenon and the cues that provoke this kind of behaviour."

People with sleep disorders commonly have a misperception about their actual sleep behaviour. A research group led by Karin Trimmel and Stefan Seidel from MedUni Vienna's Department of Neurology (Outpatient Clinic for Sleep Disorders and Sleep-Related Disorders) analysed polysomnography results to identify the types of sleep disorder that are associated with a discrepancy between self-reported and objective sleep parameters and whether there are any factors that influence this. The main finding: irrespective of age, gender or screening setting, insomnia patients are most likely to underestimate how long they sleep. The study has been published in the highly regarded Journal of Clinical Sleep Medicine.

Patients' misperceptions about the actual time that they sleep is a well-known phenomenon in sleep research. Their own impression of their sleep behaviour is often quite different from that demonstrated by clinical measurements. Nonetheless, until now there had been no scientific comparison between patients' actual total sleep time and their self-reported sleep time that also analysed the associated factors.

A research group led by neurologists Karin Trimmel and Stefan Seidel from MedUni Vienna's Outpatient Clinic for Sleep Disorders and Sleep-Related Disorders has now retrospectively analysed patient consultations from between 2012 and 2016 and polysomnograms (PSG) of a representative group of 303 sleep clinic patients, 49% of whom were women. 32% were suffering from the commonest sleep disorder, insomnia, 27% from sleep-related breathing disorders, 15% from sleep-related movement disorders, 14% from hypersomnia/narcolepsy and 12% from parasomnias. A PSG measures depth of sleep, muscle activity and breathing over the course of the night. It can be performed in the sleep lab or as ambulatory tests, where the patients sleep at home.

There was found to be a discrepancy between self-reported perception and objective readings in all sleep disorders, although it was largest in the case of insomnia, irrespective of age, sex or whether the monitored night was spent in the sleep lab or at home. Insomnia patients overestimate their sleep latency, that is to say the time it takes them to fall asleep, and significantly underestimate the amount of total sleep time. A constantly elevated level of background stress (hyperarousal) could be a factor in this, since this would result in disrupted sleep architecture (increased number of microarousals), as well as the fact that insomnia is often associated with psychiatric comorbidities. In contrast to insomnia patients, patients with other sleep disorders tended to underestimate their sleep latency and overestimate their total sleep time.

The study corroborates the clinical observation that sleep misperception occurs in all forms of sleep disorder but is most prevalent in insomnia. The treatment of choice in this instance is cognitive behavioural therapy. Karin Trimmel explains: "By incorporating this misperception into behavioural therapy, we can significantly improve treatment outcomes, so that polysomnography is highly recommended for patients with treatment-resistant insomnia."

-- Experts call for policy reform to improve ethnic equity of socioeconomic opportunity, service provision, and health outcomes. They also call for long-term studies to investigate how structural and institutional racism generate these ethnic inequalities in health.

In 15 out of 17 minority ethnic groups, health-related quality of life in older age (over 55 year-olds) was worse on average for either men, women, or both, than for White British people according to an observational study published in The Lancet Public Health journal.

In five of those groups - Bangladeshi, Pakistani, Arab, and Gypsy or Irish Traveller - the difference compared with the White British group is equivalent to, or greater than, the health impacts of being 20 years older.

The older population of England is becoming increasingly ethnically diverse. Although previous evidence suggests there are substantial health inequalities between ethnic groups, there is currently little detailed research available on this [1]. Using a large nationally representative survey asking participants how their daily life is impacted by their health, the new study provides the first detailed analysis of health inequalities among older adults in England from a broad range of ethnic groups.

Lead author on the study, Dr Ruth Watkinson, University of Manchester, UK, says "The disproportionate number of deaths due to COVID-19 in minority ethnic groups has highlighted ethnic inequalities in health among older adults in England. Our study adds detail to evidence of these inequities and their drivers before the pandemic. Now, we need decisive policy action to improve equity of socioeconomic opportunity and transformation of health and local services to ensure they meet the needs of all people in the multi-ethnic English population." [2]

The study used surveys taken by patients over 55-years-old registered at GP practices across England from July 2014 to April 2017. The authors analysed how ethnicity was associated with five self-reported aspects of daily life impacted by the health of participants: mobility (i.e. walking), self-care (i.e. washing and dressing), ability to engage in daily activities (i.e. working, studying, housework, spending time with family), pain or discomfort, and anxiety or depression. These five areas were combined to give an overall 'health-related quality of life' score for each ethnic group, which ranged from 1 (perfect health) to -5.94 (poorest health). Health-related quality of life was then compared across ethnic groups.

They did a further analysis to understand what the underlying causes of the ethnic disparities might be, estimating the association between ethnicity and five factors known to impact health. The survey asked if participants had one or more of 14 long-term health conditions, received high quality health care, received enough support from local services (such as social care and support groups) and were confident in managing their own health. The authors also considered level of deprivation in participants' residential area.

Out of the 1,394,361 survey respondents included in the analysis, 11% (152,710) self-identified as belonging to a minority ethnic group. The patterning of disadvantage observed between groups varied by sex.

Across most of the 15 ethnic groups that showed relative disadvantage compared with White British, the size of disadvantage was greater for women than men. Both men and women in Gypsy or Irish Traveller, Bangladeshi, Pakistani, and Arab ethnic groups showed substantial health disadvantage compared with the White British participants.

A 20-year increase in age was associated with an average change in health-related quality of life score of -0.065 for men and -0.094 in women. The average difference among people from each stated group compared to the White British group were: Gypsy or Irish Traveller (-0.192 in men; -0.264 in women), Bangladeshi (-0.111 in men; -0.209 in women), Pakistani (-0.084 in men; -0.206 in women), and Arab (-0.061 in men; -0.145 in women).

The two ethnic groups who were healthier than White British people were Chinese (men and women), and Black African (men only). However, this only applied across all age groups for Chinese men, whereas for Chinese women and Black African men further analyses suggested they were only healthier in the younger age groups (55-64 years for Black African men, and 55-74 years for Chinese women).

When looking at the association between ethnicity and factors that could cause poor health outcomes, the study suggested inequalities in health were accompanied by increased long-term health conditions (particularly diabetes), poor experiences of primary care, insufficient support from local services, low confidence in managing their own health, and high local social deprivation.

The authors emphasise that social deprivation, although more common in ethnic minority groups, could not fully explain the health disparities they observed, and suggest that other factors are also at play, such as structural and institutional racism in health care and local service provision.

Dr Watkinson continues, "We must consider how social deprivation intersects with gender, ethnicity, and other personal characteristics, such as immigration status or religion, to affect poor health outcomes. Looking forward, we need much more long-term research to understand how structural and institutional racism creates health inequalities." [2]

The large sample size of the study allowed them to look at 17 ethnicities that are often grouped under just four categories (White, Asian, Black, and other). However, the authors found that health-related quality of life varied widely between ethnicities placed within these ethnic "meta-groups", raising questions about the usefulness of such categorizations.

Commenting on the importance of gathering more detailed data, co-author Dr Alex Turner, University of Manchester, UK, says, "Our study found large differences between ethnicities often grouped together in broad categories. For example, Bangladeshi, Pakistani and Chinese ethnicities are often all categorised as 'Asian'. In our study, people of Bangladeshi and Pakistani ethnicity had among the worst disadvantage in health, compared with White British, whereas people of Chinese ethnicity had a relative advantage. This emphasises the need for more nuanced research to understand the specific difficulties that older adults from particular minority ethnic groups experience." [2]

The authors note some limitations of their study. Although the large sample size and relatively high survey response rate among older adults allowed the authors to analyse outcomes for smaller ethnic groups, estimates for some ethnic groups were still imprecise owing to small numbers. They also note that some bias may have been introduced by those who chose not to respond to the survey and by the survey being taken from patients registered at a GP surgery (potentially excluding vulnerable adults or those without a fixed residence). In addition, the dataset used was recorded in 10-year age groups, so the authors were unable to ensure exact like-for-like age comparisons. This may have made some ethnic groups appear healthier, which the authors say are more likely to be minority ethnic groups than the White British group, due to younger overall age structures in the population.

Writing in a linked Comment, lead author Professor Seeromanie Harding (who was not involved in the study), from King's College London, UK, says, "Despite biases, such as the absence of data on ethnicity specific survey non-response rates and the social determinants of health, Watkinson and colleagues present strong evidence of ethnic inequalities in HRQoL [health-related quality of life], the presence of long-term conditions, and poor experiences of primary care. There seems to be inadequate support from local services to manage long-term conditions in ethnic minority groups. Although constrained by the availability of granular data, the report reinforces the need to consider the intersectional influences of sex and ethnicity on inequalities in healthy ageing."

Mason scientists employ a rapid-result, saliva-based test that significantly expands testing capacity, and an antibody test that can track vaccine response.

George Mason University announces it is introducing a rapid-result, saliva-based COVID-19 test that will greatly expand testing capabilities on its campuses this spring. The effort, led by Mason's faculty, is part of a comprehensive program to better track and control the virus on campus.

Mason scientists, who are pushing the boundaries of technologies that are keeping Mason's campuses safe, are also developing an antibody test that can track a body's response to the virus and vaccine. See more in this video.

The use of the saliva test with the recently acquired Fluidigm system, designed to analyze large numbers of test samples, will help Mason increase testing capacity from 1,000 tests per week to a goal of 10,000 by March, said Lance Liotta, co-director and co-founder of Mason's Center for Applied Proteomics and Molecular Medicine, who leads the CAP CLIA laboratory in which the COVID testing takes place.

CAP CLIA accreditation--from the College of American Pathologists (CAP) and the Centers for Medicare & Medicaid Services through the Clinical Laboratory Improvement Amendments (CLIA)--ensures laboratories provide precise test results and comply with professionally and scientifically sound laboratory operating standards.

"The more we test, the more we are able to identify people who are positive at the earliest stages of the infection and therefore stem the spread of infection," said Ali Andalibi, senior associate dean for the College of Science. "That's what we're striving toward."

Liotta leads the multidisciplinary team that is internationally recognized for its expertise in diagnostic testing. The team pivoted from its primary work in cancer research to take up the fight against COVID-19, following the start of the global pandemic last spring.

Mason was a model during the Fall semester for its efforts to combat the spread of the virus, with some of the lowest COVID-19 case numbers among Virginia's largest higher education institutions, and no known transmission in its classrooms.

"I've been very gratified to see the enormous amount of effort being put forth by Mason scientists in all the colleges toward the COVID crisis," Liotta said. "We collaborate with scientists in many different sectors of Mason, as we work together to develop these new strategies all the way from testing, to the methods, to how you collect samples, and how you care for patients."

The saliva test, which received an Emergency Use Authorization from the Food and Drug Administration, will help track symptomatic and asymptomatic cases on campus and will be available at five sites across Mason's three university campuses. The samples will be analyzed at Mason's Science and Technology Campus in Manassas, Virginia, in the CAP CLIA laboratories directed by research professor Virginia Espina. Turnaround time for results will be two days or less.

Julie Zobel, Mason's associate vice president for Safety, Emergency and Enterprise Risk Management, and her team led efforts to set up the campus infrastructure for testing. That entailed construction of five testing sites with card scanners, check-in counters and private saliva-collection booths. About 50 people, including 20 licensed medical professionals, were hired to staff the sites.

"It's been a challenge but we've had a large team of medical professionals, emergency and risk managers, researchers and lab personnel, and IT and finance professionals working tirelessly over the past five months to get us to this point," Zobel said. "I am proud to be part of such a high-performing and driven team all working towards keeping our community safe."

Liotta's team is also validating a novel test that measures a body's antibody response to the virus and COVID vaccine. The test will help researchers understand a person's post-vaccination response, how long individuals will remain resistant to the virus and how a person's immune system fights the virus.

"The antibody test is going to be the future because everyone wants to know, did the vaccine work for them?" Liotta said. "Somebody who has immunodeficiency syndromes gets the vaccine. Did the vaccine work for them? We can answer that question. We can also tell whether a patient should be donating their plasma to treat others."