Body

A research team led by Dr Rosario Delgado from the UAB Department of Mathematics, in collaboration with the Hospital de Mataró, developed a new machine learning-based model that predicts the risk of mortality of intensive care unit patients according to their characteristics. The research was published in the latest edition of the journal Artificial Intelligence in Medicine, with a special mention as a "Position paper".

Under the framework of Artificial Intelligence, machine learning allows a model to gain knowledge based on the information provided by available historical data, and automatically modifies its information when new information appears. One of the current challenges is the creation of models with which to make personalised medical predictions, and one of the areas in which artificial intelligence can be of great help is in deciding how to proceed with intensive care unit (ICU) patients. This process is complex and comes at a high cost, and depends on the inherent variability of the opinion of specialists, based on their experience and instinct. Therefore, to improve the quality of care in the ICUs, it is important to set down protocols based on objective data and on an accurate prediction of a patient's risk of mortality according to their characteristics. In this sense, machine learning tools may be of great help to medical experts.

A group of researchers led by Dr Rosario Delgado from the Department of Mathematics of the UAB, in collaboration with Head of the ICU at Hospital de Mataró Dr Juan Carlos Yébenes, UAB associate lecturer Àngel Lavado from the Information Management Unit of the Maresme Health Consortium, and José David Núñez-González, PhD student of the UAB Department of Mathematics, used machine learning tools to create a model capable of predicting the risk of mortality of ICU patients, based on a real database which also served to validate the model. The model will aid in the decision-making process of healthcare workers by improving the prediction of premature deaths, making medical decisions about high-risk patients more efficient, evaluating the effectiveness of new treatments and detecting changes in clinical practices.

The use of this model represents a clear improvement in traditional approaches, consistent with predicting the risk of mortality based on the Acute Physiology And Chronic Health Evaluation (APACHE) score - a questionnaire widely used to assess a person's state of health with the help of different indicators. The new model makes use of an estimated logistical regression that was validated in previous groups of patients. Researchers were able to demonstrate experimentally that the new model they created overcomes the weak points of traditional approaches, offering good results and presenting itself as a better alternative.

The predictive self-learning prognosis model created by researchers consists in a set of Bayesian classifiers used by assigning a life prognosis label (live or die) to each individual, according to traits such as demography, gender and age; the Charlson comorbidity index; their place of origin; the cause of admission; the presence or lack of sepsis; severity reached in the first 24 hours after aadmission; and the APACHE II score.

Researchers improved the model's prediction through a combination of individual predictions of each classifier designed in a way that the faults of some predictions could be compensated with other correct predictions, and taking into account the imbalance represented by a low proportion of patients dying in the ICUs. The model predicts the cause of death of patients at a high risk, as well as the outcome of patients at a low risk of dying. This type of model is known as a hierarchical predictive model, given that there are two stages of prediction.

"The hierarchical predictive prognosis model we have introduced has a good predictive behaviour, and it also allows studying which of the patient's traits are the most decisive, which can become risk factors, in assessing their risk of death. It also can be extrapolated to compare different ICUs, or in a longitudinal study to analyse improvements through the timing of protocols in specific ICUs", explains Dr Rosario Delgado. "This is a useful and promising methodology, and has important clinical applicability from the moment in which it can help physicians make patient-tailored medical decisions, and also for health authorities in their management of available resources", she concludes.

MUSC Hollings Cancer Center was one of 28 clinical sites around the world that participated in the LOTIS-2 trial to test the efficacy of Loncastuximab tesirine, a promising new treatment for aggressive B-cell lymphoma. The results of the single-arm, phase 2 trial were published online in May 2021 in Lancet Oncology.

Brian Hess, M.D., a Hollings researcher and lymphoma specialist at MUSC Health, was instrumental in bringing the phase 2 trial to Hollings. The manufacturer of Loncastuximab tesirine, ADC Therapeutics S.A., sponsored the trial.

B-cell non-Hodgkin lymphoma (NHL) is a blood cancer that begins in the lymph nodes, spleen or bone marrow. Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive NHL. New treatment options are vital for patients with DLBCL. While nearly two-thirds of patients have a durable response to frontline therapy, the remaining one-third of patients relapse or are refractory to frontline treatment and typically have a poor prognosis.

The trial was open label, which means the clinician and patient were aware of the treatment that was given, and it was available to patients 18 years or older with relapsed or refractory DLBCL after two or more lines of treatment. This trial is significant because it includes a difficult-to-treat patient population, said Hess.

"Traditional chemotherapy is very unlikely to lead to a sustained response in this patient population. CD19 CAR-T cell therapy is now approved and provides hope for durable response and cure for the majority of these patients; however, not everyone is a candidate for CAR-T cell therapy. In addition, the majority of patients that receive CD19 CAR-T cell therapy eventually relapse and are in need of novel therapies such as loncastuximab," said Hess.

The LOTIS-2 trial tested the efficacy of Loncastuximab tesirine, an antibody-drug complex that targets CD19 - the same molecule targeted on the lymphoma B-cells by CAR-T therapy. The drug complex works by attaching to CD19, widely expressed on lymphoma B cells, and delivering the drug payload into the cell, thereby minimizing systemic toxicity. Once internalized, the drug damages the DNA of the lymphoma cells, leading to cell death.

"This is a novel mechanism of action that provides potential benefit for patients who otherwise do not have a lot of options," said Hess. "For patients who are not candidates for, not interested in, or relapse after CAR-T, this is could be a promising therapy option. Additionally, the drug is delivered intravenously every three weeks, so patient proximity to treatment centers is less critical for this therapy."

The overall response rate in this clinical trial was 48% (70 out of 145 patients). This means that nearly 50% of relapsed DLBCL patients who had already tried two or more treatments had a complete or partial response to this new therapy.

The phase 2 trial result led to Food and Drug Administration (FDA) approval of Loncastuximab tesirine as a single agent. The next step will be to combine it with other agents to see if this improves efficacy and durability of response. This new trial is expected to be open for enrollment at MUSC in the next six months.

"I am excited that this therapy can now be given to patients who may live two to three hours away from Charleston, South Carolina, and not want or be able to travel to MUSC for treatment. We look forward to providing education on the potential efficacy and toxicity of this agent to oncology practitioners throughout the state of South Carolina so that patients can receive this therapy locally," said Hess.

July 23, 2021 - Last year, the American Cancer Society (ACS) issued an updated set of guidelines for cervical cancer screening - emphasizing the shift toward screening with primary human papillomavirus (HPV) testing. While the ACS recommendation accounts for a transition period to implement primary HPV screening, additional factors should be considered to operationalize these guidelines, according to a special white paper in the July issue of the Journal of Lower Genital Tract Disease (JLGTD), official journal of ASCCP. The journal is published in the Lippincott portfolio by Wolters Kluwer.

In the article, the ASCCP Cervical Cancer Screening Task Force voices its support for the ACS's 2020 cervical cancer screening guidelines, which include "a strong recommendation to screen with primary HPV testing." Meanwhile, the ASCCP Task Force reserves its full endorsement for the 2018 US Preventive Services Task Force (USPSTF) recommendations, which provide greater flexibility as the US healthcare system shifts to more widespread use of primary HPV screening. Jenna Z. Marcus, MD, of Rutgers New Jersey Medical School and Cancer Institute of New Jersey, Newark, is lead author of the ASCCP Task Force white paper.

During shift to primary HPV testing, ASCCP task force 'endorses any cervical cancer screening'

Coauthor Patty Cason, MS, FNP-BC notes, "Since HPV causes the vast majority of cervical cancers, testing for HPV as the primary screening test is a more effective approach to screening than cervical cytology (Pap testing)." With this approach, a cervical swab is used to test for the presence of high-risk HPV strains responsible for virtually all cervical cancers. In its 2020 guideline update, the ACS recommends the HPV test alone (primary HPV screening), for people with a cervix, beginning at age 25 and continuing through age 65.

At the current time, many patients receive care at sites where FDA-approved tests for primary HPV screening are not yet available, so this screening approach is not yet accessible to all patients. The ACS states that when FDA-approved tests for primary HPV screening are not available at a given health center, other options - co-testing with both HPV testing and cervical cytology, and cervical cytology alone - are "acceptable" alternative strategies. The ACS also suggests that these methods may be excluded from future guideline updates.

The Task Force acknowledges the benefits of primary HPV screening. "The ASCCP recognizes the need to transition to primary HPV screening and acknowledges that logistical considerations surrounding implementation, the impact of limited HPV vaccination in the United States, and inclusion of populations who may be marginalized are necessary and must be prioritized."

However, during this transition period, a flexible approach is needed to ensure maximum availability of screening. For that reason, the ASCCP Task Force endorses the 2018 USPSTF cervical cancer screening recommendations, which include "all screening modalities." The USPSTF statement provides "flexibility that may benefit those who are marginalized, underinsured, or experiencing inequity and health disparities." Through its endorsement of the 2018 USPSTF guidelines, that document is considered official ASCCP clinical guidance.

ASCCP assesses guidance from other organizations according to its Guidelines Endorsement Policy, which has three levels: endorsement, support, and comment. Endorsement indicates endorsement of a peer organization's clinical document and denotes that ASCCP fully supports the clinical guidance. Support of a peer organization's clinical document denotes that ASCCP deems the document to be of educational value to its members, although ASCCP may not agree with every recommendation or statement in the document. Comments to a peer organization's clinical document denotes that ASCCP does not agree with the recommendation, and feels the need to formally voice that opinion through public comment. In announcing its support for the 2020 ACS guidelines, The ASCCP recognizes the need to transition to primary HPV screening and acknowledges that logistical considerations surrounding implementation, the impact of limited HPV vaccination in the United States, and inclusion of populations who may be marginalized are necessary and must be prioritized.

The Task Force emphasizes the need for "sound and conservative clinical judgment" when applying the guidelines to the individual patient's situation. The authors conclude: "Most importantly, the ASCCP endorses any cervical cancer screening for secondary prevention of cervical cancer and recommends interventions that improve screening for those who are underscreened or unscreened."

A study by researchers at the Texas A&M University School of Public Health shows that inexpensive and convenient devices such as silicone wristbands can be used to yield quantitative air quality data, which is particularly appealing for periods of susceptibility such as pregnancy.

The research team found that the wristbands, when used as passive samplers, have the ability to bind smaller molecular weight semi-volatile polycyclic aromatic hydrocarbons (PAHs) -- a class of chemicals that occur naturally in coal, crude oil and gasoline and are produced when coal, oil, gas, wood, garbage and tobacco are burned -- in a similar pattern as active sampling.

Published recently in Nature's Journal of Exposure Science & Environmental Epidemiology, the study focused on pregnant women in Hidalgo County in South Texas. This particular area of Texas was selected because of the heightened prevalence of childhood asthma in the region, as well as a higher prematurity rate (14.8 percent) compared to the rest of the state (12.9 percent).

The study was aimed at quantifying maternal PAH exposure in pregnant women residing in McAllen. To gather the data, participants carried backpacks containing air-sampling equipment. A silicone wristband was also attached to each backpack. After three nonconsecutive 24-hour periods, the air-sampling equipment and wristbands were analyzed for PAHs. Prenatal exposure to PAHs has been shown to lead to adverse health effects in children.

When the researchers analyzed and compared the data from the air sampling equipment and the wristbands, they found that the wristbands yielded similar results to the more traditional testing methods. The researchers suggest that the use of the silicone wristbands as a passive sampler could be useful in studies of semi-volatile PAHs.

"The use of wristbands is appealing because it is inexpensive and easy to wear," said co-author Itza Mendoza-Sanchez, assistant professor in the Department of Environmental and Occupational Health (EOH). "Wristbands have been used to detect a number of pollutant, but qualification of those pollutants remains a challenge. Our goal was to evaluate to what extent we can use wristbands as passive samplers to quantify PAHs in air.

"We found that patterns of detection are similar for low-molecular weight compounds and that attaching the wristbands to the backpack's strap is a good sampling design for evaluating conditions under which wristbands could be used for quantifying PAHs in air."

Mendoza-Sanchez co-authored the study with Inyang Uwak, a recent Doctor of Public Health graduate. It was part of a larger maternal environmental health study led by Associate Professor Natalie Johnson and Associate Professor Dr. Genny Carrillo. Former EOH students Louise Myatt, Kristal A. Rychlik, Jairus C. Pulczinski, and Allison Van Cleve also took part in the research.

"Maternal exposure to PAHs during pregnancy is particularly harmful to children's health since this is a phase of rapid human growth and development," Johnson said. "Thus, easy methods to quantify PAH exposure are of critical need in order to evaluate risk and develop effective intervention strategies."

Johnson said the results of the study support that wristbands used as passive samplers may be helpful in future studies evaluating adverse health outcomes from prenatal PAH exposure.

The first clinical trial of a new dietary treatment for children and adults with severe forms of epilepsy, co-developed by UCL researchers and based on the ketogenic diet, has been successfully completed.

For the study, published in Brain Communications, clinicians evaluated the use of K.Vita®, (also known as Betashot), an oral liquid dietary supplement developed by UCL in collaboration with Royal Holloway, University of London, and Vitaflo International Ltd.

The ketogenic diet (KD) consists of high-fat, low-carbohydrate and adequate protein consumption and mimics the fasting state, altering the metabolism to use body fat as the primary fuel source. This switch from carbohydrates to fat for body fuel is known as ketosis.

It is widely used to treat drug resistant epilepsies. However, the highly restrictive diet, which can cause constipation, low blood sugar, and stomach problems, can have poor compliance and is not suitable for everyone. Some KD supplements are also known to be unappetising.

K.Vita is based on novel findings by UCL researchers*, who discovered a different underlying mechanism to explain why the KD is effective against epilepsy; in developing a new treatment, researchers also sought to reduce the adverse side effects caused by KD.

Corresponding author Professor Matthew Walker (UCL Queen Square Institute of Neurology) said: "The ketogenic diet has been used for 100 years to treat epilepsy, helping reduce seizures in both children and adults.

"It has long been thought the diet was effective due to its production of ketones**, however we now believe the increase in levels of the fatty acid, decanoic acid, also produced by the diet, may provide the powerful antiseizure effects.

"In this study we evaluated a newly developed medium chain triglyceride (type of dietary fat) supplement, designed to increase levels of decanoic acid, while also reducing the adverse side effects, and to be more palatable."

For the feasibility trial, researchers wanted to establish participants' tolerance (side effects such as bloating or cramps) to the treatment, acceptability (flavour, texture, taste) and compliance (how easy it is to use K.Vita at the advised quantity, as part of their daily diet).

As secondary outcomes, they also monitored the frequency of epileptic seizures or paroxysmal events (fits, attacks, convulsions) and whether ketone production was decreased.

In total, 35 children (aged 3 to 18) with genetically caused epilepsy and known to be unresponsive to drugs, and 26 adults with drug-resistant epilepsy*** (DRE), were given K.Vita liquid supplements (a drink), to be taken with meals. They were also asked to limit high-refined sugary food and beverages from their diets.

The trial lasted 12 weeks with K.Vita treatments increasing incrementally over time, taking into account individuals' tolerance to the treatment.

In total, 23/35 (66%) children and 18/26 (69%) adults completed the trial i.e they were continuing to take K.Vita at 12 weeks. Gastrointestinal disturbances were the primary reason for discontinuation, and their incidence decreased over time

Over three-quarters of participants/caregivers reported favourably on sensory attributes, such as taste, texture and appearance, and ease of use.

In regards to the secondary outcomes, there was a mean 50% reduction in seizures or paroxysmal events, and fewer than 10% of people on the diet produced significant ketones.

Commenting on the findings, Professor Walker, who is also a consultant neurologist at the National Hospital for Neurology and Neurosurgery, said: "Our study provides early evidence of the tolerability and effectiveness of a new dietary supplement in severe drug-resistant epilepsies in adults and children and provides a further treatment option in these devastating conditions.

"It also offers an alternative, more liberal, diet for those who cannot tolerate or do not have access to ketogenic diets."

He added: "While this study was not designed to include enough patients to fully assess the supplement's effects on seizures, it is exciting to report that there was a statistically significant reduction in the number of seizures in the group overall after three months of treatment.

"Furthermore, high ketone levels were not observed in over 90% of the participants. This indicates that the effect of the diet was independent from ketosis; this is important because high ketone levels in the ketogenic diets contribute to both short- and longer-term side effects."

First author, Dr Natasha Schoeler, Research Dietitian at UCL Great Ormond Street Institute of Child Health, commented: "This novel dietary approach for epilepsy management involves following the principles of a healthy balanced diet alongside use of K.Vita, allowing greater dietary freedom compared to ketogenic diets. Our approach also requires much less input from a specialist dietician than is required by traditional ketogenic diets, and so may allow more widespread access to people with drug-resistant epilepsy."

Researchers say larger, controlled studies of K.Vita are now needed to determine the precise epilepsies and conditions in which the supplement is most effective.

Gene therapy in mouse models showed promise in preventing vision loss or blindness from serious retinal injury including optic nerve damage, and from retinal disease including diabetic retinopathy and glaucoma, Mount Sinai researchers report. Their study, published in the July 22 online publication of Cell, could transform treatment for those at risk of major vision loss from retinal degenerative diseases, which currently have no cure.

The researchers focused on retinal ganglion cells, which process visual information by sending images to the brain. These cells can degenerate as a result of retinal injury and retinal disease. The team of researchers demonstrated how reactivation of a key enzyme known as CaMKII and its downstream signaling in retinal ganglion cells through a gene therapy approach provided robust protection against further vision loss or impairment in multiple disease and injury models.

"Neuroprotective strategies to save vulnerable retinal ganglion cells are desperately needed for vision preservation," says senior author Bo Chen, PhD, Associate Professor of Ophthalmology and Neuroscience, and Director of the Ocular Stem Cell Program at the Icahn School of Medicine at Mount Sinai. "We uncovered evidence for the first time that CaMKII is a key regulator of the survival of retinal ganglion cells in both normal and diseased retinas, and could be a desirable therapeutic target for vision preservation in conditions that damage the axons and somas of retinal ganglion cells."

Glaucoma is the leading cause of irreversible visual impairment worldwide, affecting 76 million people, some of whom will progress to blindness despite aggressive treatment to reduce the pressure in their eyes. The major barrier to restoring vision loss from glaucoma and other retinal diseases and injuries is that the long nerve fibers known as axons, which allow retinal ganglion cells to process visual information by converting light that enters the eye into a signal transmitted to the brain, do not regenerate. For that reason, neuroprotective strategies to preserve the RGC's axons and somas (the main body of the nerve cell from which axons branch off along the optic nerve to the brain) and thereby prevent further vision loss are urgently needed.

Mount Sinai researchers investigated whether CaMKII could play such a therapeutic role. They tested the enzyme across a wide range of injury and disease animal models, including optic nerve damage, excitotoxicity (where nerve cells are destroyed by the overactivation of glutamate receptors that result in damage to the cell structure), and two glaucoma models that mimicked the pathophysiology of human disease with both high and normal intraocular pressure. The team learned that CaMKII regulated the survival of retinal ganglion cells across many of these pathologies, and that in the small-animal excitotoxicity model, insults to the retinal ganglion cell's somas or optic nerve injury to its axons led to inactivation of CaMKII and its downstream signaling target CREB (or cAMP response element binding protein). "Intriguingly, we found that reactivation of CaMKII and CREB provided robust protection for retinal ganglion cells," notes Dr. Chen, who is also the McGraw Family Vision Researcher at Icahn Mount Sinai, "and that CaMKII-mediated protection slowed down the disease progression in both glaucoma models."

That reactivation was made possible by a gene therapy approach deployed by the researchers to introduce a more active type of CaMKII into the original retinal ganglion cells to boost their activity. The modified version of CaMKII, with a mutated amino acid, was transferred to the targeted cells through an adeno-associated viral vector, a Food and Drug Administration-approved gene delivery system common to the growing field of gene therapy.

"Our research showed that CaMKII could indeed be a valuable therapeutic target to save retinal ganglion cells and preserve vision in treating potentially blinding diseases like glaucoma," says Dr. Chen, a winner of the Pew Scholars in the Biomedical Sciences award given to young investigators showing outstanding promise. "The fact that manipulation of CaMKII would involve a one-time transfer of a single-gene adds to its vast potential to treat serious retinal conditions in humans. The next step is testing this in larger animal models, which may pave the way for starting clinical trials."

Mount Sinai has filed patent applications for this technology through Mount Sinai Innovation Partners (MSIP), the commercialization arm of the health system. MSIP is in active discussions with multiple companies to help advance this treatment to the clinic.

A form of gene therapy protects optic nerve cells and preserves vision in mouse models of glaucoma, according to research supported by NIH's National Eye Institute. The findings suggest a way forward for developing neuroprotective therapies for glaucoma, a leading cause of visual impairment and blindness. The report was published in Cell.

Glaucoma results from irreversible neurodegeneration of the optic nerve, the bundle of axons from retinal ganglion cells that transmits signals from the eye to the brain to produce vision. Available therapies slow vision loss by lowering elevated eye pressure, however some glaucoma progresses to blindness despite normal eye pressure. Neuroprotective therapies would be a leap forward, meeting the needs of patients who lack treatment options.

"Our study is the first to show that activating the CaMKII pathway helps protect retinal ganglion cells from a variety of injuries and in multiple glaucoma models," said the study's lead investigator, Bo Chen, Ph.D., associate professor of ophthalmology and neuroscience at the Icahn School of Medicine at Mount Sinai in New York City.

The CaMKII (calcium/calmodulin-dependent protein kinase II) pathway regulates key cellular processes and functions throughout the body, including retinal ganglion cells in the eye. Yet the precise role of CaMKII in retinal ganglion cell health is not well understood. Inhibition of CaMKII activity, for example, has been shown to be either protective or detrimental to retinal ganglion cells, depending on the conditions.

Using an antibody marker of CaMKII activity, Chen's team discovered that CaMKII pathway signaling was compromised whenever retinal ganglion cells were exposed to toxins or trauma from a crush injury to the optic nerve, suggesting a correlation between CaMKII activity and retinal ganglion cell survival.

Searching for ways to intervene, they found that activating the CaMKII pathway with gene therapy proved protective to the retinal ganglion cells. Administering the gene therapy to mice just prior to the toxic insult (which initiates rapid damage to the cells), and just after optic nerve crush (which causes slower damage), increased CaMKII activity and robustly protected retinal ganglion cells.

Among gene therapy-treated mice, 77% of retinal ganglion cells survived 12 months after the toxic insult compared with 8% in control mice. Six months following optic nerve crush, 77% of retinal ganglion cells had survived versus 7% in controls.

Similarly, boosting CaMKII activity via gene therapy proved protective of retinal ganglion cells in glaucoma models based on elevated eye pressure or genetic deficiencies.

Increasing retinal ganglion cell survival rates translated into greater likelihood of preserved visual function, according to cell activity measured by electroretinogram and patterns of activity in the visual cortex.

Three vision-based behavioral tests also confirmed sustained visual function among the treated mice. In a visual water task, the mice were trained to swim toward a submerged platform on the basis of visual stimuli on a computer monitor. Depth perception was confirmed by a visual cliff test based on the mouse's innate tendency to step to the shallow side of a cliff. Lastly, a looming test determined that treated mice were more apt to respond defensively (by hiding, freezing or tail rattling) when shown an overhead stimulus designed to simulate a threat, compared with untreated mice.

"If we make retinal ganglion cells more resistant and tolerant to the insults that cause cell death in glaucoma, they might be able to survive longer and maintain their function," Chen concluded.

What The Study Did: This study included 647 patients with untreated nonmetastatic prostate cancer (269 patients during the pandemic and 378 from before the pandemic). During the initial COVID-19 lockdown, only 1% of Black men underwent prostatectomy, while 26% of white patients did. Prior to the pandemic, there was no difference in the rate of prostatectomy between the two races (18% of Black men and 19% of white men). The lessons from this study suggest systemic inequities within health care and are likely applicable across medical specialties. Public health efforts are needed to fully recognize the unintended consequence of diversion of cancer resources to the COVID-19 pandemic to develop balanced mitigation strategies as viral rates continue to fluctuate.

Authors: Andres Correa, M.D., of the Fox Chase Cancer Center in Philadelphia, 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/jamaoncol.2021.2755)

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.

Around 50,000 people suffer sudden cardiac arrest in Germany every year. When occurring outside a hospital, the chances of survival are only ten percent. Survivors often suffer from severe permanent neurological damage. On July 21st, 2021, researchers from the Faculty of Medicine - University of Freiburg, Germany, published together with German and US colleagues a review article in the journal Nature Reviews Neuroscience. They describe the most important therapeutic factors for successful resuscitation. The scientists name the therapy concept based on these factors CARL (Controlled Automated Reperfusion of the whoLe body). In recent years, the Freiburg physicians and perfusionists have already developed a special and mobile heart-lung machine for resuscitation that allows a CARL therapy for the first time. One of the first persons treated with CARL therapy successfully survived a cardiac arrest after about 120 minutes of resuscitation. The affected person suffered no brain damage.

„After decades of research, we were able to develop a new treatment method to reduce the physical damage that would otherwise occur after cardiac arrest and resuscitation. Our findings and the device we developed could be of great importance for emergency medicine," said Prof. Dr. Friedhelm Beyersdorf, Medical Director of the Department of Cardiovascular Surgery at Medical Center - University of Freiburg. „The CARL method incorporates the latest basic research and state-of-the-art cardiac surgical techniques. Through innovative medical technology developments of our own, we now have the opportunity to apply this new treatment principle inside and outside the hospital. This raises the prospect of people surviving much longer and better after cardiac arrest than was previously thought," Beyersdorf said.

Success factors for resuscitation

As a result of cardiac arrest, blood vessels in the brain swell, making them less permeable to gas exchange. „By maintaining a high, pulse-like blood pressure during controlled whole-body reperfusion (CARL therapy), we can resuscitate the brain most quickly," Beyersdorf says. Oxygen levels must be low and increased only slowly. Otherwise, free radicals are generated in the tissues. These very aggressive molecules can then attack, among other things, the mitochondria, the power plants of the cells. A reduced calcium concentration in the blood also helps to protect the mitochondria. „It is very important to lower the body temperature of the patients as quickly as possible in order to slow down metabolic processes," explains the Freiburg cardiac surgeon, who published the study together with colleagues from Yale University, USA, and Max Planck Institute for Metabolic Research, Germany.

CARL - For the first time, resuscitation therapy in its complexity is possible

Some of the aspects were known in principle, but not in the depth of detail. In addition, various aspects of therapy were not technically feasible until now. That is why scientists at the Medical Center - University of Freiburg founded the startup Resuscitec a few years ago, where they developed a device that specifically meets the complex requirements of resuscitation: the CARL system.

„To our knowledge, CARL is the first device that was developed specifically for resuscitation and can take over the complete cardiopulmonary function of the patient. With CARL we can treat the damage caused by cardiac arrest and the associated lack of oxygen. This is possible because we can immediately measure and control all the important parameters, such as blood values, that are necessary for successful resuscitation," says Prof. Dr. Christoph Benk, Head of Perfusion at the Department of Cardiovascular Surgery at Medical Center - University of Freiburg.

A unique dual-pump control system enables the necessary high pulsatile blood flow and realizes a high blood pressure, oxygen levels can be precisely controlled, and a mobile cooling unit allows the patient's body to be cooled down quickly and safely. „The device is designed relatively small and light so that it can fit in the ambulance and be carried directly to the patients," explains Benk.

First CARL deployments give great hope

In an initial pilot study, the doctors were able to save many of the patients treated with CARL therapy even though resuscitation time was very long, ranging from 50 to 120 minutes. „In the case of a 43-year-old patient, resuscitation was successful after 70 minutes. The patient has fully recovered and is back to working as a teacher," says Prof. Dr. Georg Trummer, Head of cardiovascular surgical Intensive Care Unit in the Department of Cardiovascular Surgery at Medical Center - University of Freiburg. In another case, a patient suffered cardiac arrest at home and was brought to the Medical Center - University of Freiburg by helicopter after first responder resuscitation. „Here, the patient was immediately connected to the CARL device and - after 120 minutes - successfully resuscitated," Trummer said. The patient suffered no brain damage and was able to return to her job. To back up these initial promising results, a study is now planned at three European universities as part of the European Commission's Horizon 2020 program.

Key Takeaways

A survey of American College of Surgeons members found almost two-thirds treat firearm injuries and more than 85 percent support the organization advocating for policies to reduce firearm-related injuries.
Forty-two percent of ACS members keep firearms in their homes and nearly one-third (32 percent) of surgeon firearm owners store firearms unlocked and loaded.
Survey findings will enable the ACS to identify ways to engage all members, including gun owners, and advocate for initiatives that prevent firearm-related injuries.

CHICAGO (July 22, 2021): In what may be the largest survey of physician attitudes about firearms and how firearm-owning surgeons store guns in their homes, U.S. members of the American College of Surgeons (ACS) said they support the organization taking an active role in advocating for policies and programs designed to lower the risk of firearm-related injuries and deaths. The advocacy initiatives they support include preventing people with serious mental illness from buying firearms and cracking down on illegal firearms sales.

Results from the survey of 54,761 U.S. ACS members, of whom 11,147 responded, have been published as two articles on the website of the Journal of the American College of Surgeons (JACS) in advance of print.
One article reported broad support among members, ranging from medical students to retired surgeons, for a number of initiatives to reduce firearm injuries. More than 60 percent of surveyed members said they treat firearms injuries, and almost three-quarters "support the ACS being right at the frontline of solving this issue," said lead study author Deborah A. Kuhls, MD, FACS, interim assistant dean for research and professor of surgery at the Kirk Kerkorian School of Medicine at the University of Nevada Las Vegas. That is, survey respondents said it's very or extremely important for the organization to support policies to lower the incidence of firearm injury.
The second article analyzed survey data on the subset of ACS members who own firearms (42 percent), their reasons for firearm ownership, and how they store their guns (61 percent of whom lock them up) and ammunition. Those habits compare favorably to what smaller surveys have found about storage habits of gun owners in the broader population. A 2015 survey of 3,949 adults in households with children found that only 30 percent store firearms unloaded and locked.1 A more recent online survey of 1,444 firearm owners found that only 46 percent safely store all of their firearms.2
"What's really important about the work that came out of this survey is that it provided data that speak for most of the membership of the ACS," said Brendan T. Campbell, MD, MPH, FACS, lead author of the study on firearm storage habits and a pediatric surgeon at Connecticut Children's in Hartford. "It really helps the ACS speak with a unified voice on this sometimes contentious issue."
The ACS Committee on Trauma (COT) commissioned the survey to get a clearer idea of members' attitudes and behaviors about firearms and preventing firearm injuries. More than 20 percent of the ACS membership completed the survey. The authors stated this is the largest survey of American physicians related to firearms ownership and storage practices.
Dr. Kuhls noted that the publication of the articles is timely because firearm deaths in the U.S. have continued to increase since the survey was conducted in 2018. The nonprofit Gun Violence Archive reported 43,558 firearm deaths in 2020, 19,379 from gun violence and 24,090 from suicides where a firearm was used, compared with 39,537 firearm deaths in 2019.3 Firearm deaths in the first six months of this year are already exceeding last year's pace, with an estimated 22,804 all-cause firearm deaths through July 7.4
"The objective of this study was not to say firearms are good, firearms are bad, or this is exactly what the ACS should do, but rather to understand clearly what ACS members think can and should be done to make firearm ownership as safe as possible," Dr. Campbell added.
Firearm ownership findings
Among ACS members who own firearms, 82 percent own long guns, 82 percent own handguns, and 32 percent own high-capacity magazine-fed semi-automatic rifles (totals exceed 100 percent because many respondents own more than one type of firearm). Study results also ascertained why they own firearms: 75 percent say for self-defense and 73 percent for target practice.
Reasons for gun ownership varied by gender. Women were more likely to own a gun for self-defense, while men were more likely to do so for target shooting and hunting. Urban respondents were more likely to own handguns; rural respondents more likely to own long guns. Nineteen percent said they had taken a concealed carry course. While 42 percent of ACS members keep firearms in their home, nearly two-thirds (63 percent) of ACS members have had some type of firearm training.
"There's a real opportunity for surgeons to promote safe firearm storage and responsible firearm ownership," said Dr. Campbell, who is a firearm owner and Chair of the Injury Prevention and Control Committee of the ACS COT. He credited Ronald M. Stewart, MD, FACS, Medical Director of ACS Trauma Programs, and ACS COT Chair Eileen M. Bulger, MD, FACS, with wanting to engage firearm owners in this effort. "Who better than the surgeons who care for the victims of gun violence in this country to be the leaders in its prevention?" Dr. Campbell said.
Firearm injury prevention analysis and consensus
The injury prevention analysis included three questions about respondents' attitudes toward gun ownership. Answers were just about even on whether gun ownership is beneficial or harmful, with 22.8 percent saying it's beneficial, 21.6 percent saying it's harmful, and 49.2 percent saying it's both. Rural respondents viewed firearm ownership most favorably, with 32.3 percent saying it's beneficial vs. 17.9 percent for respondents from large cities.
Regarding firearm ownership and personal liberty, 41.7 percent indicated that it protects personal liberty vs. 8.5 percent who said it limits personal liberty and 44.8 percent saying it did neither. Further, 73.7 percent of respondents indicated that firearm ownership is a constitutionally protected right.
Respondents were also asked to rate their support on a scale of 1 to 5 for 25 possible advocacy/policy initiatives, with 85.5 percent indicating that it's important to support policy initiatives to reduce firearm injuries and deaths. Receiving the highest scores--4.4 or higher--were preventing people with mental illness from purchasing firearms; increasing penalties for dealers who sell guns illegally or bypass background checks and for straw purchasers (people who give guns to others illegally); enhancing the National Instant Criminal Background Check System (NICS); and using NICS for mandatory background for all gun purchases from authorized dealers.
"The results were really overwhelmingly in support that the ACS should play a role in decreasing firearm injuries and deaths," Dr. Kuhls said. "There was broad support that this is a public health problem and that the ACS should be leading and joining other organizations in addressing this very unfortunate cause of injuries and death in the United States."
Sixteen suggested initiatives carried a score of 4 or above, which was considered very important. But there wasn't such strong consensus on the other nine initiatives, such as increasing interstate reciprocity on concealed carry permits and allowing teachers and staff to carry concealed weapons in schools scored at the bottom. Nor was there strong consensus on limiting firearm ownership to people age 21 and over.
"There is uniformity that this is a huge public health problem, we need to do something about it, and we need to be sure that the people who own firearms can be responsible owners," Dr. Kuhls said. "It's even stronger in certain ethnic backgrounds for which we didn't have an adequate sample in our previous work."
Dr. Kuhls added, "Some of the results really speak for all members regardless of age and regardless of where they practice, whether they own firearms or not, regardless of what demographic group they represent. I think that's part of the real power of this study."

Researchers at the University of São Paulo (USP) in Brazil investigated the effects of regular exercise on the physical and mental health of 344 volunteers during the pandemic. The study compared the effectiveness of three techniques: sessions led in person by a fitness instructor, sessions featuring an online instructor but no supervision, and sessions supervised remotely by an instructor via video call.

The two kinds of session with professional supervision had the strongest effects on physical and mental health. According to the researchers, this was due to the possibility of increasing the intensity of the exercises over time. To their surprise, remotely supervised sessions were more effective than face-to-face sessions. Sedentary subjects served as controls.

“The findings underscore the benefits of either approach, with the instructor online or physically present, compared with being sedentary. However, the physical and mental benefits have much to do with a secure and progressive increase in the intensity of the exercises, which occurred only when they were supervised by a professional. What’s interesting is that remote supervision by video call was more efficient. The difference was small but statistically significant,” Carla da Silva Batista, last author of the study published in Psychiatry Research, told Agência FAPESP. Batista is a researcher at the University of São Paulo’s School of Physical Education and Sports (EEFE-USP).

The study was supported by FAPESP. Volunteers were selected in different age and income groups and came from different parts of Brazil. Some had symptoms of depression.

The remotely supervised participants, who worked out using Pilates, Crossfit, yoga, dance and aerobics, exercised more intensely than those who lacked supervision.

“Increasing intensity in supervised online sessions was of paramount importance during the pandemic,” Batista said. “Around half the participants, or 55%, performed high-intensity exercises before the pandemic, but the proportion fell to 30% once lockdown began.”

Other research shows intense exercise increases longevity, reduces the risk of developing Parkinson’s disease, and is associated with a reduced risk of 26 types of cancer.

“We don’t know exactly why working out with remote supervision by video call gets better results than when the instructor is physically present,” Batista said. “It’s probably that the participants felt the discomfort of wearing a mask hindered their performance during the pandemic.”

Other reasons could include the possibility that remotely supervised participants were more motivated. “They were doing exercises in safety and at home, but with supervision and without having to wear a mask. They didn’t have to worry about spreading the virus, so the instructor may have felt free to increase the intensity of the exercises safely, without risking injury or discomfort,” Batista said.

To evaluate the participants’ physical and mental health, in July-August 2020 the researchers applied validated online questionnaires known as the International Physical Activity Questionnaire – Short Form (IPAQ-SF) and the Montgomery-Asberg Depression Rating Scale – Self-Rated (MADRS-S). The latter covers nine items: apparent and reported sadness, inner tension, reduced sleep and appetite, concentration difficulties, lassitude, inability to feel, and pessimistic and suicidal thoughts.

The researchers also checked the exercise routines of the participants, who worked out for at least 30 minutes and at most 180 minutes per day, giving a total of between 150 and 900 minutes per week.

“About half were depressed before the pandemic. Our results showed that even these people improved their mental health score,” Batista said.

Previous studies had shown that people who exercised moderately or vigorously for more than 30 minutes every day during lockdown ran less risk of depression and avoided the problems arising from a sedentary lifestyle, such as stress, lack of sleep and obesity, all of which may be associated with metabolic alterations.

“We already knew about the physiological benefits of getting exercise while being forced to stay at home, but our study innovated by evidencing the effectiveness of remotely supervised exercise classes. This wasn’t clear to us before we did the study. The approach proved beneficial, especially for the period we’re living in,” Batista said.

July 22, 2021 - Early in the COVID-19 pandemic, more than 40 percent of nurses and other health care workers had risks associated with an increased likelihood of burnout, reports a survey study in the August issue of the American Journal of Nursing (AJN). The journal is published in the Lippincott portfolio by Wolters Kluwer.

The study identifies risk factors for poor well-being as well as factors associated with greater resilience - which may reduce the risk of burnout for hands-on care providers, according to the new research by Lindsay Thompson Munn, RN, PhD, and colleagues of a North Carolina healthcare system. They write, "The insights gained from this study can help health care leaders to target these risk factors and develop strategies that allow organizations to better support well-being and resilience among clinicians."

New evidence of pandemic's impact on well-being in health care workers

The researchers conducted an online survey of nurses and other non-physician health care workers (HCWs), and received responses from 2,459 participants who provided direct patient care. The survey focused on risk factors for decreased well-being: a key contributor to the epidemic of burnout among health care professionals.

The survey also evaluated aspects of resilience. Defined as the ability to cope with and adapt positively to adversity, resilience is an important contributor to well-being. Data were collected in June and July 2020, providing a snapshot of well-being and resilience among HCWs a few months into the pandemic.

At that time, 44 percent of HCWs surveyed had "at risk" well-being, which is associated with increased risk of burnout, fatigue, and patient care errors. Analysis of the responses identified several factors associated with increased odds of poor well-being, including:

Having low scores on a measure of resilience
Believing that supplies of personal protective equipment (PPE) were insufficient
Feeling that the organization did not understand health care workers' emotional support needs during the pandemic
Believing that workload had increased
Believing that staffing was inadequate to safely care for patients
Having a lower degree of psychological safety (feeling that the work environment was conducive to vulnerability and interpersonal risk-taking)

In contrast, opposite levels of some of the same factors were associated with higher scores for resilience:

Feeling that the organization did understand emotional support needs
Believing that staff were being redeployed to areas of critical need
Having a higher degree of psychological safety

Less than one-fourth of health care workers had used available resources to support their well-being and resilience (such as meditation apps, employee assistance programs, and counseling). Perhaps reflecting high levels of stress early in the COVID-19 pandemic, those who used such resources were more likely to have "at risk" well-being.

Dr. Munn and coauthors believe their study has practical implications for health care leaders to promote well-being and resilience among health care workers, during the COVID-19 pandemic and beyond.

"While it may seem obvious that nurses and other HCWs would sustain burnout and poor well-being after dealing with providing care under arduous circumstances, it's important to establish the contributing factors and to learn how some were able to mitigate the effects of the stressors," notes Maureen Shawn Kennedy, MA, RN, FAAN, Editor in Chief of AJN. "We're in serious need of successful strategies to support frontline caregivers."

The researchers discuss steps that may help to support resilience while addressing modifiable factors that negatively affect well-being in the health care work environment. "[L]eaders can take crucial steps toward optimizing workers' well-being by paying careful attention to workload and staffing, creating a culture of psychological safety within teams and units, and recognizing and actively addressing the unique challenges posed by the pandemic," Dr. Munn and colleagues conclude.

Click here to read "Well-Being and Resilience Among Health Care Workers During the COVID-19 Pandemic: A Cross-Sectional Study."

DOI: 10.1097/01.NAJ.0000767352.47699.0c

Participation in elite adult rugby may be associated with changes in brain structure.

This is the finding of a study of 44 elite rugby players, almost half of whom had recently sustained a mild head injury while playing.

The study, part of the Drake Rugby Biomarker Study, was led by Imperial College London and published in the journal Brain Communications.

The research found a significant proportion of the rugby players had signs of abnormalities to the white matter, in addition to abnormal changes in white matter volume over time.

White matter is the 'wiring' of the brain, and helps brain cells communicate with each other. The research team say more work is now needed to investigate the long-term effects of professional rugby on brain health.

Professor David Sharp, senior author from Imperial's Department of Brain Sciences, said: "Despite relatively high rates of head injury and an increasing focus on prevention, there has been relatively little research investigating the long-term effects of rugby participation. More objective measures of the effects of sporting head injuries on the brain are needed to assist with the assessment and management of individual players.

"Our research using advanced magnetic resonance imaging suggests that professional rugby participation can be associated with structural changes in the brain that may be missed using conventional brain scans. What is not clear at this stage is the long-term clinical impact of these changes. Further research is needed to understand the long-term implications of repeated head injuries experienced during a rugby career and to provide more accurate ways to assess risk for an individual."

The work, in collaboration with University College London, was funded and instigated by The Drake Foundation, who brought together academia and sport for this pioneering study, and was additionally supported by the National Institute for Health Imperial Biomedical Research Centre, the UK Dementia Research Institute and the Rugby Football Union.

Lauren Pulling, The Drake Foundation's CEO, said: "The Drake Foundation would like to thank the RFU, rugby clubs and research team for their support in this vital study. At present, the long-term consequences of these brain structure abnormalities are unknown and require further research. However, taken together with existing evidence across different sports, as well as recent cases of rugby players being diagnosed with brain diseases in their 40s, they are painting a concerning picture when it comes to players' long-term brain health."

The study, which took place between July 2017 and September 2019, assessed 41 male players, and three female.

All underwent a type of brain scan called an MRI, and around half then had a second MRI scan a year later. The study used two advanced types of MRI called susceptibility weighted imaging and diffusion tensor imaging. This allowed them to look at the structure of blood vessels and the white matter. The study is the first to assess long-term changes in MRI images of professional rugby players.

The rugby players were compared to athletes in non-collision sports, as well as individuals who were not athletes.

Among the group of rugby players, 21 were assessed shortly after sustaining a mild head injury, called a mild traumatic brain injury. In professional rugby union in England, these types of head injuries, which often cause concussions, are the most common reported match injury - accounting for one in five injuries.

The scientists analysed the brain scans for changes in the white matter of the brain, and compared these to the athletes in non-collision sports, and the non-athletes.

The results revealed that 23 percent of all of the rugby players showed abnormalities to their cell axons (the 'wires' of brain cells), or small tears in blood vessels. These tears cause small leaks in the brain, called microbleeds.

These changes were seen in both players with and without a recent head injury.

In addition, the scans provide evidence for unexpected changes in white matter volume across the whole group of rugby players. These could indicate a longer-term effect of these abnormalities to connections in the brain. However, further research is needed to understand the significance of these changes in brain structure.

The research team also asked the players to complete assessments, such as memory tests, to analyse their brain function. The results revealed players with abnormalities in their brain structures did not perform worse than players without abnormalities.

The study team add that long-term studies are needed to investigate the long-term effects on brain health. They add that other health benefits of sports participation must also be taken into account when assessing impact on the brain health.

Mr Karl Zimmerman, lead author of the research, from Imperial's Department of Brain Sciences, said: "The implications on an individual level of the brain changes associated with elite rugby participation are unclear, although obviously it is concerning to see these changes in some of the players' brains. It is important to note that our results in adult professional rugby union and league players are not directly comparable to those who play at local or youth levels. The overall health benefit of participating in sports and physical exercise have been well established including the reduction in mortality and chronic diseases such as dementia. Long-term studies are now needed of both active and retired rugby players to investigate the effect of participation on long-term brain health."

Dr Simon Kemp, Medical Services Director at the Rugby Football Union (RFU) added: "The RFU is fully committed to advancing our understanding of the short, medium and long term consequences of head impacts and concussions so that we can ensure we can make continued improvements in player welfare. We welcome any research that helps to advance our knowledge which is why we actively collaborated with the academic institutions on the Drake Foundation Rugby Biomarker Study from its inception, particularly to promote the recruitment of players. While it is unclear from that research what the individual long-term implications are regarding the brain changes seen in these advanced imaging techniques, it is clearly a priority to investigate this further. To further develop our understanding the RFU, in partnership with Premiership Rugby and independent experts, will be providing a specialist clinical service for the assessment and management of retired elite male and female rugby players between the ages of 30-55 to individually assess their brain health. An integrated research programme will review the risk, causes, assessment and management of brain problems for those who have participated in elite rugby."

The study was carried out in collaboration with UCL researchers Dr Etienne Laverse and Professor Huw Morris from the Department of Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology.

Professor Huw Morris said: "We have more to learn about the mechanisms and consequences of head injury, and the best approaches to player assessment. This Imperial/UCL collaborative study has brought together expertise from brain sciences across London. The Drake Foundation have pioneered work in this field in the UK and we are very grateful for the support of the foundation, players, medical teams, clubs and the RFU in carrying out this work. We hope that this work, and understanding the long-term implications will ultimately improve safety across contact sports."

In order to win the battle against COVID-19, studies to develop vaccines, drugs, devices and re-purposed drugs are urgently needed. Randomized clinical trials are used to provide evidence of safety and efficacy as well as to better understand this novel and evolving virus. As of July 15, more than 6,180 COVID-19 clinical trials have been registered through ClinicalTrials.gov, the national registry and database for privately and publicly funded clinical studies conducted around the world. Knowing which ones are likely to succeed is imperative.

Researchers from Florida Atlantic University's College of Engineering and Computer Science are the first to model COVID-19 completion versus cessation in clinical trials using machine learning algorithms and ensemble learning. The study, published in PLOS ONE, provides the most extensive set of features for clinical trial reports, including features to model trial administration, study information and design, eligibility, keywords, drugs and other features.

This research shows that computational methods can deliver effective models to understand the difference between completed vs. ceased COVID-19 trials. In addition, these models also can predict COVID-19 trial status with satisfactory accuracy.

Because COVID-19 is a relatively novel disease, very few trials have been formally terminated. Therefore, for the study, researchers considered three types of trials as cessation trials: terminated, withdrawn, and suspended. These trials represent research efforts that have been stopped/halted for particular reasons and represent research efforts and resources that were not successful.

"The main purpose of our research was to predict whether a COVID-19 clinical trial will be completed or terminated, withdrawn or suspended. Clinical trials involve a great deal of resources and time including planning and recruiting human subjects," said Xingquan "Hill" Zhu, Ph.D., senior author and a professor in the Department of Computer and Electrical Engineering and Computer Science, who conducted the research with first author Magdalyn "Maggie" Elkin, a second-year Ph.D. student in computer science who also works full-time. "If we can predict the likelihood of whether a trial might be terminated or not down the road, it will help stakeholders better plan their resources and procedures. Eventually, such computational approaches may help our society save time and sources to combat the global COVID-19 pandemic."

For the study, Zhu and Elkin collected 4,441 COVID-19 trials from ClinicalTrials.gov to build a testbed. They designed four types of features (statistics features, keyword features, drug features and embedding features) to characterize clinical trial administration, eligibility, study information, criteria, drug types, study keywords, as well as embedding features commonly used in state-of-the-art machine learning. In total, 693 dimensional features were created to represent each clinical trial. For comparison purposes, researchers used four models: Neural Network; Random Forest; XGBoost; and Logistic Regression.

Feature selection and ranking showed that keyword features derived from the MeSH (medical subject headings) terms of the clinical trial reports, were the most informative for COVID-19 trial prediction, followed by drug features, statistics features and embedding features. Although drug features and study keywords were the most informative features, all four types of features are essential for accurate trial prediction.

By using ensemble learning and sampling, the model used in this study achieved more than 0.87 areas under the curve (AUC) scores and more than 0.81 balanced accuracy for prediction, indicating high efficacy of using computational methods for COVID-19 clinical trial prediction. Results also showed single models with balanced accuracy as high as 70 percent and an F1-score of 50.49 percent, suggesting that modeling clinical trials is best when segregating research areas or diseases.

"Clinical trials that have stopped for various reasons are costly and often represent a tremendous loss of resources. As future outbreaks of COVID-19 are likely even after the current pandemic has declined, it is critical to optimize efficient research efforts," said Stella Batalama, Ph.D., dean, College of Engineering and Computer Science. "Machine learning and AI driven computational approaches have been developed for COVID-19 health care applications, and deep learning techniques have been applied to medical imaging processing in order to predict outbreak, track virus spread and for COVID-19 diagnosis and treatment. The new approach developed by professor Zhu and Maggie will be helpful to design computational approaches to predict whether or not a COVID-19 clinical trial will be completed so that stakeholders can leverage the predictions to plan resources, reduce costs, and minimize the time of the clinical study."

A new study by investigators from Brigham and Women's Hospital examined the relationship between active lifestyles and the risk of obstructive sleep apnea (OSA). The study followed around 130,000 men and women in the United States over a follow-up period of 10-to-18 years and found that higher levels of physical activity and lower levels of sedentary behavior were associated with a lower risk of OSA. Their results are published in the European Respiratory Journal.

"In our study, higher levels of physical activity and fewer hours of TV watching, and sitting either at work or away from home were associated with lower OSA incidence after accounting for potential confounders," said Tianyi Huang, MSc, ScD, an Associate Epidemiologist at the Brigham. "Our results suggest that promoting an active lifestyle may have substantial benefits for both prevention and treatment of OSA."

OSA is a type of sleep apnea in which some muscles relax during sleep, causing an airflow blockage. Severe OSA increases the risk of various heart issues, including abnormal heart rhythms and heart failure.

Using the Nurses' Health Study (NHS), Nurses' Health Study II (NHSII) and Health Professionals Follow-Up Study (HPFS), the research team used statistical modeling to compare physical activity and sedentary hours with diagnoses of OSA. Both moderate and vigorous physical activity were examined separately and both were strongly correlated with lower risk of OSA, showing no appreciable differences in the intensity of activity. Moreover, stronger associations were found for women, adults over the age of 65 and those with a BMI greater than or equal to 25 kg/m2.

"Most prior observational studies on the associations of physical activity and sedentary behavior with OSA were cross-sectional, with incomplete exposure assessment and inadequate control for confounding," said Huang. "This is the first prospective study that simultaneously evaluates physical activity and sedentary behavior in relation to OSA risk."

This study also differs from others because of its large sample size and detailed assessment pf physical activity and sedentary behaviors. The research team was able to take many associated factors into account, making the findings more credible.

The authors note that all collected data, both of OSA diagnosis and physical activity or sedentary behavior, were self-reported. While all study participants were health professionals, mild OSA is often difficult to detect and can remain clinically unrecognized. Furthermore, only recreational physical activity was taken into consideration, leaving out any physical activity in occupational settings. Sedentary behavior was only counted as sitting while watching TV and sitting away from home or at work.

According to Huang, the next research steps would be to collect data using actigraphy, home sleep apnea tests and polysomnography, rather than self-reports.

In light of the findings, investigators encourage physicians to highlight the benefits of physical activity to lower OSA risk.

"We found that physical activity and sedentary behavior are independently associated with OSA risk," said Huang. "That is, for people who spend long hours sitting every day, increasing physical activity in their leisure time can equally lower OSA risk. Similarly, for those who are not able to participate in a lot of physical activity due to physical restrictions, reducing sedentary hours by standing or doing some mild activities could also lower OSA risk. However, those who can lower sedentary time and increase physical activity would have the lowest risk."