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In May 2019, the U.S. Food and Drug Administration (FDA) approved a gene replacement therapy for the inherited, progressive neuromuscular disease 5q-linked spinal muscular atrophy (SMA). Approval included all children with SMA under the age of two years; however, the gene therapy had only been studied in children aged up to 8 months.

Now, a new study discusses safety and early outcomes in a large cohort of SMA patients under the age of two years who were treated with gene therapy. The report is published in the journal Pediatrics.

SMA is caused by the absence of the SMN1 gene and subsequent insufficient survival motor protein, which is critical for the maintenance and function of motor neurons. It causes afflicted babies to progressively lose muscle control. Those with the most common form of the disease die within the first two years of life without treatment.

One of three FDA-approved treatments for SMA is a gene replacement therapy called onasemnogene abeparvovec-xioi. The treatment involves a one-time intravenous injection of an adeno-associated virus vector that delivers a fully functional copy of the missing SMN1 gene into motor neuron cells.

Jerry Mendell, MD, a neurologist with Nationwide Children's Center for Gene Therapy, was pivotally involved in the preclinical work and human trial that demonstrated the safety and efficacy of onasemnogene abeparvovec-xioi. The treatment was approved by the FDA for children diagnosed with any type of SMA under two years of age without end-stage disease. However, the 15 patients treated by Dr. Mendell and his colleagues were all children with type 1 SMA under 8 months of age.

In the new study, Dr. Mendell and colleagues from Nationwide Children's and three other Ohio children's hospitals report safety and early outcome data from 21 children (age 1-23 months) treated with onasemnogene abeparvovec-xioi in Ohio.

Megan Waldrop, MD, a pediatric neurologist at Nationwide Children's and the study's first author, says their data show the treatment is safe and effective through age 2 years with genotypes predicted to be SMA1, 2 and 3, if proper screening and monitoring is conducted.

"If the children are older and heavier, there is a potential for more liver injury and those patients require closer monitoring and may require longer corticosteroid treatment," says Dr. Waldrop. "But if they are monitored appropriately, they tolerate the treatment well."

In addition to close monitoring in the weeks to months post-treatment, Dr. Waldrop and her colleagues emphasize the need for a thorough screening process prior to treatment and social isolation afterwards to minimize the risk of illness.

Overall, the results of the study were promising; all symptomatic patients experienced subjective and objective functional improvements in motor function, while the five children treated prior to symptom onset developed none of the signs of weakness characteristic of SMA.

"We think this is a good treatment for SMA that can make a dramatic clinical impact in the lives of children," says Dr. Waldrop, who is also assistant professor of Pediatrics and Neurology at The Ohio State University College of Medicine.

"Gene therapy is a remarkable treatment paradigm for certain diseases," Dr. Waldrop continues. "At the moment, we are able to design gene therapies for some conditions that are recessive, loss-of-function, and involve small genes.

"I suspect that as the field continues to move forward, we will make progress and find ways to broaden the conditions we can treat using gene therapy."

UNIVERSITY PARK, Pa. - Chronic pain affects the majority of older adults in the U.S., and getting enough exercise plays a key role in pain management. New research suggests that how people think about their pain can have a significant effect on whether they get enough physical activity - or if they spend more time sedentary.

In a study, a team led by Penn State researchers found that when people with knee osteoarthritis "catastrophized" -- feeling an exaggerated helplessness or hopelessness -- about their pain more than usual, they were less likely to be physically active later in the day, contributing to a domino effect of sedentary behavior followed by even more pain catastrophizing.

According to the researchers, the results -- recently published in the journal PAIN -- have potential implications for pain management and wellness in older adults, and suggest that pain catastrophizing could be an important therapeutic target for interventions and pain treatment.

"Reducing daily pain catastrophizing may help older patients to be more active and less sedentary on a daily basis," said Ruixue Zhaoyang, assistant research professor. "This could help improve their chronic pain condition, physical function, and overall health, and reduce the possibility of hospitalization, institutionalization, and healthcare costs in the long term."

According to the researchers, chronic or persistent pain affects between 60 and 75 percent of older adults in the U.S., making pain management strategies like engaging in enough physical activity an important part of many older adults' lives.

Zhaoyang said that catastrophizing about pain -- thought patterns like "the pain is terrible and is never going to get any better" or "I can't stand the pain anymore" -- may lead some older adults to avoid exercise in an effort to also avoid pain. But if exercise is put off for too long, it can lead to spirals of depression and even worse pain.

"Staying physically active is one of the most important self-management strategies for chronic pain patients," said Lynn Martire, professor of human development and family studies. "However, many chronic pain patients avoid physical activities that they are actually capable of doing. Our study focused on one critical psychological factor that may explain why patients avoid physical activity despite its importance for pain management: their catastrophic thinking about their pain."

For the study, the researchers used data from 143 older adults with knee osteoarthritis. The participants kept daily diaries and wore accelerometers -- a wearable device for measuring physical activity -- for 22 days. Each morning, the participants would report how they felt about their pain that day and the accelerometer would gather information on physical activity and sedentary behavior.

After analyzing the data, the researchers found that on mornings when participants catastrophized about their pain more than usual, they ended up engaging in less moderate to vigorous physical activity later that day.

Additionally, the researchers found that catastrophizing about pain in the morning lead to more time in sedentary behavior the same and the following day, as well. In turn, more time spent sedentary lead to increased pain catastrophizing on the following day.

"One particularly interesting finding is that the detrimental influence of catastrophizing thinking about pain is independent of the pain experience itself," Zhaoyang said. "In other words, how patients think about their pain, rather than the level of experienced pain, had a more powerful impact on their daily physical activity."

Martire said the results suggest that pain catastrophizing can kick-start a potentially harmful cycle -- greater pain catastrophizing in the morning leads to avoid of physical activity, which in turn worsens catastrophizing about pain on the following day.

The researchers added that these findings suggest that pain catastrophizing could be a good target for interventions aimed at managing chronic pain and increasing physical activity.

"Our study demonstrated that patients' catastrophizing thinking can change from day to day and can be modified by their everyday activity behavior," Martire said. "Future interventions may get better results from using mobile technology to monitor patients' activity levels in everyday life and provide just-in-time adaptive interventions targeting patients' pain catastrophizing to reduce their sedentary behavior."

The researchers added that while their study looked specifically at people with knee osteoarthritis, catastrophizing can happen with any type of pain. They said the implications of their findings could potentially apply to pain management in patients with other types of chronic pain.

New Rochelle, NY, August 25, 2020--Those over age 65 who self-reported as socially isolated were more likely to have a future hospital admission or emergency room visit. The study is published in the peer-reviewed journal Population Health Management. Click here to read the article now.

"These results are novel for 2 reasons," states David Mosen, PhD, MPH, Kaiser Permanente Center for Health Research, and coauthors. "It is the first study to find that social isolation was predictive of future hospital admission and ED utilization among a population of Medicare Advantage members ages 65 and older. Second, the relationship between social isolation and utilization remained significant, even after adjusting for a comprehensive set of demographic and clinical measures."

"The work of Mosen and colleagues, from one of the most respected health plans in the nation, confirms what was always a hunch --that lonely older folks end up utilizing more health care resources, of all types, as their social situation worsens. So, let's go upstream to shut off the faucet--provide them with support services--instead of mopping up the floor with more unnecessary emergency room visits and the like. We now have the data to prove just how important this strategy is!" says David Nash, MD, MBA, Editor-in-Chief of Population Health Management and Founding Dean Emeritus and Dr. Raymond C. and Doris N. Grandon Professor, Jefferson College of Population Health, Philadelphia, PA.

Sophia Antipolis, France - 25 Aug 2020: Today scientists report that 58% of "sudden" cardiac arrest sufferers sought medical help during the two weeks before the event. The research is presented today at ESC Congress 2020.1

Out-of-hospital cardiac arrest is the third leading cause of death worldwide. Cardiac arrest is lethal within minutes if left untreated and it is estimated that, on average, less than 10% of victims survive.

"The high mortality from cardiac arrest in the community emphasises the need to identify those at risk," said study author Dr. Nertila Zylyftari of Copenhagen University Hospital Herlev and Gentofte, Hellerup, Denmark. "This is very challenging since these are considered sudden and unexpected events. But our study indicates that patients felt unwell in the days leading up to the cardiac arrest."

Previous studies have reported that some patients had symptoms such as shortness of breath, chest discomfort and palpitations in advance of a cardiac arrest and contacted the healthcare system. But there is little information on when and where these contacts occurred.

This study investigated contacts with GPs and hospitals in the year before a cardiac arrest. To get a picture of whether there was any variation throughout the year, the researchers examined each week separately. In other words, what proportion of patients contacted a GP or hospital 52 weeks before the arrest, 51 weeks before, and so on, up to one week before.

The researchers used the Danish Cardiac Arrest Registry to identify all residents who suffered a cardiac arrest outside of hospital in Denmark between 2001 and 2014. Using the unique civil registration number assigned to all Danish citizens, the researchers linked information from several national administrative registries, including dates of GP and hospital contacts.

A total of 28,955 people had an out-of-hospital cardiac arrest during the 14-year study period. The median age of victims was 72 years and 67% were men. To compare the results in cardiac arrest patients with the overall population in Denmark, each patient was matched by age and sex to nine people from the general public.

Each week during the year before the cardiac arrest, the percentage of patients in contact with their GP was relatively constant (26%), until two weeks before when it rose to 54%. Every week during that same year, just 14% of people in the matched population contacted their GP.

As for hospital contacts in the year before the arrest, these were relatively constant for the first six months. Each week during that six months, around 3% of patients contacted a hospital. Weekly contacts then gradually increased during the next six months, peaking at two weeks before the arrest, when 6.8% of patients contacted a hospital. Every week during that same year, just 2% of people in the matched population contacted a hospital.

Dr. Zylyftari said: "To our knowledge this was the first study to assess cardiac arrest victims' attempts to get help from both GPs and hospitals throughout the year before the event and compare them with the general population. We show that the proportion of patients who contacted GPs and hospitals were higher every week throughout the year before their event compared to the matched population in the same year."

"It was surprising to see that in the two weeks prior to the cardiac arrest there was an increase in contacts especially with their own doctor," she added.

In a separate analysis, the researchers examined all contacts made to the healthcare system (either GP, hospital or both) during the two-week period prior to the cardiac arrest. This showed that 58% of cardiac arrest patients had contacted the healthcare system compared to 26% of the matched population.

Information was not collected on the reasons why cardiac arrest patients sought medical advice. But the data show that of those who communicated with their GP during the two-week period before the event, 72% did so by phone or email and 43% had a face-to-face consultation. (Some did both, which is why the total exceeds 100%.) Meanwhile, 25% of the cardiac arrest patients who visited hospital during the two-week period before the event had cardiovascular disease.

Dr. Zylyftari said: "More data and research are needed on the reasons for these interactions - for example symptoms - to identify warning signs of those at imminent danger so that future cardiac arrests can be prevented."

Sophia Antipolis, France - 25 Aug 2020: Scientists today urged people with atrial fibrillation - the most common heart rhythm disorder - to kick the habit and cut their stroke risk. The research is presented today at ESC Congress 2020.1

One in four middle-aged adults in Europe and the US will develop atrial fibrillation, a condition set to affect up to 17 million people in the EU by 2030.2 People with atrial fibrillation are five times more likely to have a stroke than those without the arrhythmia. The risk of death is also elevated with atrial fibrillation, by two-fold in women and 1.5-fold in men. Stroke is the most common cause of death in patients with atrial fibrillation.

Previous studies have shown that smokers are more likely to develop atrial fibrillation and subsequent stroke. While many strokes are prevented with oral anticoagulant drugs, there are limited data on the impact of smoking cessation after atrial fibrillation diagnosis.

This study examined the association between smoking cessation after newly diagnosed atrial fibrillation and the risks of stroke and all-cause death. The researchers used the Korean National Health Insurance Service database and the National Health Screening database. Koreans aged 40 and older are advised to have a national health check-up every two years. Take-up rates are high: for example, 75% were screened in 2014.

The researchers identified 523,174 patients with newly diagnosed atrial fibrillation in 2010 to 2016. Patients with prior strokes were excluded. The study included the 97,637 patients who had a national health check-up less than two years before being diagnosed with atrial fibrillation, and a second check-up within two years afterwards. Patients were followed-up after the second check-up until the end of 2017 for the occurrence of stroke or death.

The average age was 61 years and 62% were men. Participants were classified according to smoking status before and after atrial fibrillation diagnosis: never-smoker, ex-smoker (stopped smoking before diagnosis), quitter (stopped smoking after diagnosis), current smoker (includes those who persistently smoked before and after diagnosis; and new smokers who started after the diagnosis). The proportions of never smokers, ex-smokers, quitters, and current smokers were 51.2%, 27.3%, 6.9%, and 14.6%, respectively.

During a median three-year follow-up, there were 3,109 strokes and 4,882 all-cause deaths (10.0 per 1,000 person-years and 15.4 per 1,000 person-years, respectively).

Compared to current smokers, quitters had a 30% lower probability of stroke and 16% reduced likelihood of all-cause death, after accounting for other factors that could influence the relationships such as age, sex, high blood pressure, body mass index, and physical activity.

Quitters remained at higher risk compared with never-smokers. The risks of stroke and all-cause death were raised by 19% and 46%, respectively, but these associations were consistently observed only in men. New and persistent smokers had even greater risks of stroke compared to those who had never smoked. For new smokers, the probability was raised by 84% and for persistent smokers it was elevated by 66%.

Study author Dr. So-Ryoung Lee of Seoul National University Hospital, Korea, said: "Smoking precipitates blood clots that could lead to a stroke, which may be why giving up lowers risk. The remaining stroke risk after quitting might be through the damage already caused to the arteries - called atherosclerosis."

She noted that the benefits of quitting were less pronounced in those who had been heavy smokers before their atrial fibrillation diagnosis. Heavy smokers were defined as those who had smoked 20 cigarettes every day for at least 30 years. "This may be related to longer-term damage to the blood vessels which increases susceptibility to having a stroke," said Dr. Lee.

Dr. Lee said: "If you don't smoke, don't start. If you do, it's never too late to quit. Regardless of how much you smoke, kicking the habit is good for health."

CLEVELAND - Published in Nature Physics, findings from a new study co-led by Cleveland Clinic and Case Western Reserve University teams show for the first time how ideas from quantum physics can help develop novel drug interventions for bacterial infections and cancer.

The research team demonstrated that principles of quantum control, a field of quantum physics used in computing applications, can be translated and applied to biological problems. They constructed a mathematical algorithm that can be used to design and speed-up specific interventions to prevent or overturn drug resistance.

Typically cells in the presence of drugs evolve according to Darwinian natural selection: mutants that are resistant to the drug can outcompete their susceptible neighbors, dominating the population. Counterintuitively, one can also co-opt this process to achieve the opposite result, ultimately defeating drug resistance. For example, a mutation that causes resistance to one drug may cause extreme susceptibility to another, a phenomenon known as collateral sensitivity.

"If that mutant is initially only a small fraction of the population, we can use the first drug to encourage its dominance, and then apply the second drug to rapidly wipe out the infection," said physician-scientist Jacob Scott, MD, DPhil, a practicing radiation oncologist at Cleveland Clinic and co-senior author on the study, referencing findings from a study his group published earlier this year. "But we also know that the first stage can be slow: mutations occur at random times, and waiting long enough until the mutant fully takes over could compromise treatment effectiveness and patient outcomes. The time it takes to ensure these interventions are successful has been a significant limitation to adopting evolutionary medicine into clinical practice."

Speeding up this process is where quantum physics can provide inspiration. "The randomness of mutations in evolution has intriguing mathematical parallels to the randomness of quantum phenomena," according to Prof. Michael Hinczewski, a theoretical biophysicist at Case Western Reserve University and co-senior author. "This randomness makes it challenging to reliably and quickly drive a quantum system from one state to another. Solving this driving problem is an essential ingredient in certain kinds of quantum computing. Our new study exploits these parallels, translating a particular quantum technique known as counterdiabatic driving into the language of evolutionary biology."

"Imagine trying to get a system to follow a desired path from an initial to a final state over a short time--whether this path is a sequence of quantum states or varying proportions of mutants in an evolving population," said Prof. Hinczewski. "Counterdiabatic driving is a form of dynamic correction, providing just enough external intervention to keep the system on the path at every instant no matter how fast the protocol."

The researchers created a mathematical algorithm to calculate this intervention in evolutionary medicine applications. The algorithm's output is a prescription for dynamically altering the drug dosages or types to stay on the target path. The team demonstrated their technique by using it to manipulate evolution in simulations of living cells. These simulations were based on experimental data from an earlier study on a set of mutants showing varying degrees of resistance to anti-malarial drugs.

Counterdiabatic driving changed the proportion of mutants, affecting the population's overall drug sensitivity, faster and with better control than could be expected using current experimental methods in evolutionary medicine.

Given the team's promising findings, the next phase of their research will be to conduct direct experimental testing of the approach. As the first example of counterdiabatic driving in a biological context, the researchers are hopeful that their work could provide a foundation for a novel area of study: quantum-inspired biological control. The researchers plan to apply these ideas to other biological systems that share similarities with evolution, such as stem cell development and ecology.

Melbourne researchers have identified mechanisms leading to the functional deterioration of the immune system in response to severe viral infections, such as HIV or COVID-19.

It is widely known that severe viral infections and cancer cause impairments to the immune system, including to T cells, a process called immune 'exhaustion'.

Overcoming immune exhaustion is a major goal for the development of new therapies for cancer or severe viral infections.

A team from the Peter Doherty Institute of Infection and Immunity (Doherty Institute) led by University of Melbourne's Dr Daniel Utzschneider, Dr Sarah Gabriel and Professor Axel Kallies has focused on the question of when and how T cells lose their function and become 'exhausted'.

It was previously thought that during severe infections, T cells lost their function slowly and over long periods of time.

This research published today in Nature Immunology, however, shows that T cells can be impaired within just a few days.

It also identifies several new mediators of immune exhaustion that maybe targeted in new therapies.

"This is an exciting finding, particularly in the context of COVID-19 as one of the big questions is why some people get severely sick, while others experience mild disease," Dr Utzschneider said.

"We looked at both mild and overwhelming Lymphocytic Choriomeningitis Virus infections in mice, which serves as a model for severe viral infections in humans, early after onset of disease, and identified striking differences at the molecular and functional level."

Dr Gabriel explained: "In response to overwhelming infections that are difficult to eliminate and may become chronic, we were able to show that T cells down-regulate their function within days, while T cells responding to a weaker infection remained highly functional."

T cells are at the heart of immunotherapy for cancer. Therefore, understanding how T cell function is impaired is central to improving these therapeutic approaches and applying them to other diseases, such
as viral infections.

"These findings are extremely exciting. Our data show that T cells could be manipulated during early stages of severe viral infection to improve their activity," Professor Kallies said.

When cancer metastasizes and spreads throughout the body, it can severely change the prognosis of the disease. It is estimated that metastasis is responsible for 90 percent of cancer deaths.

University of Chicago Medicine investigators have found a new way to slow the metastasis of colon cancer: by treating it with a small molecule that essentially locks up cancer cells' ability to change shape and move throughout the body.

In a mouse model, the molecule cut the rate of cancer metastasis in half. Though more research is needed, the result could ultimately become a new therapy that, when combined with radiation and chemotherapy, could help provide better outcomes for several types of cancer.

"It's a very promising approach," said Ronald Rock, PhD, Associate Professor in the Department of Biochemistry and Molecular Biology at the University of Chicago and co-author of the paper. "It appears to be broadly applicable. If you can improve outcomes by 5 or 10 percent, that will help a lot of people."

The results are published in the journal Proceedings of the National Academy of Sciences. Rock co-authored the paper with Ralph Weichselbaum, MD, Daniel K. Ludwig Distinguished Service Professor of Radiation and Cellular Oncology and Chair of the Department of Radiation and Cellular Oncology at UChicago.

"It's a new area of cancer treatment, and we're really excited to see how far this can go," Weichselbaum said.

For cancer cells to disseminate from a tumor throughout the body, they must remodel their structure and increase their deformability to essentially crawl through tissue and worm their way into the bloodstream.

But Weichselbaum, whose research focuses on metastasis, wanted to find a way to stop that process in its tracks. He and Rock began to study a small molecule called 4-hydroxyacetophenone (4-HAP), which activates a protein in the cancer cell called nonmuscle myosin-2C (NM2C). That protein is one of the machines that allows the cell to deform and travel. When activated, it becomes locked in place, ensuring that the cancer cell cannot travel.

The investigators studied this process at both the molecular level and using human colon cancer tumors in a mouse model, and found that it significantly limited the cancer's ability to metastasize to other parts of the body, while leaving healthy cells alone. The rate of metastasis was cut in half, compared to non-treated colon cancer.

The team envisions using this molecule in tandem with chemotherapy and radiation to create a more effective cancer-killing treatment.

"Using this molecule means there are fewer cancer cells traveling in the body, so they would be easier to kill with radiation or chemotherapy," Weichselbaum said. "It we can decrease the spread, we have a better chance of curing the patient."

The molecule could be an improvement over other treatments for metastasis, like kinase inhibitors, which are the basis of many chemotherapies. Those treatments work by targeting the enzymes that allow cancer to proliferate, but many times, cancer cells just find a workaround.

"With our approach, we're essentially pouring sand right into the machine," Rock said. "There's no way for the cell to get around it. The engine is not going to run."

Though the experiment was conducted on colon cancer, these preliminary results show that the molecule could work on several types of cancer that metastasize. Next the team hopes to find other molecules that could also inhibit NM2C to create a multi-layer approach for hindering metastasis. That's important for up-and-coming physicians like Darren Bryan, MD, a former UChicago Medicine surgery resident and first author on the paper.

"In the future, drugs like 4-HAP will be used in patients who are at high risk for developing metastases," he said. "I was always struck by the connections I developed with patients going through difficult new cancer diagnoses. We often have good, curative surgical therapy for localized tumors that have not metastasized. I learned early on, however, that patients with more advanced tumors that had metastasized could rarely be cured with surgery alone. Targeting the motor proteins of cells is a new approach, and with 4-HAP, we will be able to help patients to have better outcomes."

Inflammatory bowel disease (IBD) is a group of intestinal disorders affecting an estimated six to eight million people worldwide. Although there are many treatments for IBD, a number of patients fail to respond long-term, leaving those afflicted with a host of chronic issues, from abdominal pain and cramping to frequent, bloody stools.

In a new study, published August 21, 2020 in Science Immunology, an international team of researchers, led by scientists at University of California San Diego School of Medicine, report that the lasting nature of IBD may be due to a type of long-lived immune cell that can provoke persistent, damaging inflammation in the intestinal tract.

Led by co-senior authors John T. Chang, MD, professor of medicine, and Gene W. Yeo, PhD, professor of cellular and molecular medicine, the research team performed mRNA and antigen receptor sequencing from immune cells isolated from samples taken from rectal biopsies or blood of IBD patients and healthy controls.

"We took advantage of a state-of-the-art approach allowing us to generate mRNA and antigen receptor sequencing data from the same single-cells," said Yeo, "and analyzed thousands of individual cells, which is quite exciting."

It has long been believed that immune system dysfunction, in concert with genetic susceptibility and changes in the gut microbiome, plays a significant role in IBD. However, the types of immune cells involved and their specific contributions to IBD have remained unclear. CD8+ T cells are one component of the immune system that identify and kill cells infected by microbial pathogens.

When an infection has been conquered, the immune system leaves behind long-lasting cells called memory T cells, which reside in tissues or circulate through the body remembering past pathogens, ever ready to sound the alarm should specific invaders reappear.

Chang and Yeo, along with co-first authors Brigid S. Boland, MD, Zhaoren He, PhD, Matthew S. Tsai, MD PhD, and colleagues, discovered that there appear to be several subtypes of CD8+ tissue-resident memory T (TRM) cells, a specific class of memory cell that resides in organs once formed.

One of these TRM cell subtypes was distinguished by high levels of the transcription factor Eomesodermin and programmed to produce large amounts of cytokines and other molecules to kill newly detected infected cells. The downside is that excessive, persistently high levels of some cytokines can cause inflammation and tissue damage.

"We found that this inflammatory TRMcell subtype seemed to be enriched in the intestinal tissues of patients with ulcerative colitis, a form of IBD that affects the colon," said Chang. "Long-lived memory cells are a goal of vaccines, but this finding suggests that these same cells, coveted in the fight against infectious diseases, may actually be harmful in the context of IBD."

The researchers also found evidence that this inflammatory TRM cell subtype might not remain confined to intestinal tissue, but may also escape into the bloodstream.

"This may explain why IBD can affect not just the intestines, but many other parts of the body as well," said Boland, a gastroenterologist at UC San Diego Health and assistant adjunct professor of medicine.

Chang said the findings may help to explain why IBD is chronic and life-long, and point to the possibility of a remedy in the future: Targeting this inflammatory TRM cell subtype for elimination, thus ending the cycle of inflammation and tissue damage.

The researchers noted that much more work is needed to gain a deeper understanding of the role of tissue-resident memory T cells in IBD and to determine whether they can be targeted therapeutically.

August 24, 2020 - Automated patient monitoring systems (PMSs) have been designed to reduce delays in diagnosis of sepsis in hospitalized patients. But so far, studies evaluating these systems have shown inconsistent effects on mortality rates and other patient outcomes, according to an evidence review in a special September supplement to the Journal of Patient Safety, which was funded by the Agency for Healthcare Research and Quality (AHRQ). The journal is published in the Lippincott portfolio by Wolters Kluwer.

"AHRQ funded this special supplement to help the field better understand and apply the latest research on safety issues related to eight important patient safety harm areas, including infections, sepsis, adverse drug events, inappropriate opioid use, and failures in teamwork and communication," said Jeff Brady, MD, MPH, Director of AHRQ's Center for Quality Improvement and Patient Safety.

The new supplement presents a cross-section of reviews from AHRQ's long-awaited Making Healthcare Safer III (MHS) report: an ongoing series dedicated to providing reliable information for improving the safety and quality of patient care.

Automated Monitoring Improves Sepsis Outcomes in Some Studies

Sepsis is a common and serious condition, estimated to occur in six percent of all hospital admissions in the United States. It has one of the highest mortality rates of any hospital condition, estimated at 15 to 30 percent. Delayed diagnosis and recognition of sepsis - leading to delays in starting treatment - are a key contributor to the high mortality from sepsis. "Automated sepsis PMSs have the potential to improve sepsis recognition and outcomes, but current evidence is mixed on their effectiveness," according to the report by Bryan M. Gale, MA, and Kendall K. Hall, MD, MS, of IMPAQ International in Columbia, Md.

Many hospitals are now using automated electronic PMSs, which continuously analyze data from patient monitoring devices and/or electronic health records and send clinical alerts when criteria for sepsis are met. In their systematic review, Mr. Gale and Dr. Hall gathered and analyzed evidence on how these monitoring systems affect mortality and other important outcomes. The analysis included data from 19 papers, including four previous systematic reviews.

Twelve studies provided data on patient outcomes - in eight of these, PMSs led to improvement in at least one outcome. Six studies provided evidence of reduced mortality: in one study, risk of death was nearly 50 percent lower in patients screened using the PMS.

Several studies also reported improvements in key processes of care with the use of PMSs - in eight out of nine studies, time to starting antibiotic treatment was significantly reduced. "[M]ore high-quality studies are needed to help to understand the effects of sepsis PMS on important process and outcome measures in different hospital units," Mr. Gale and Dr. Hall conclude.

New Haven, Conn. -- Less is sometimes more when treating heart patients who go into shock after a heart attack.

A new study found that more than 30 percent of hospital patients who have a heart attack complicated by low blood pressure undergo an aggressive treatment in which coronary stents are placed in cardiac blood vessels showing any restriction of blood flow to the heart. This is happening despite the existence of a less aggressive approach, called a "culprit-only" strategy, that places stents only in the blocked blood vessels that caused the heart attack.

The study, led by Yale and Beth Israel Deaconess Medical Center, looked at patients undergoing either of the two procedures at hospitals in the United States from 2009 to 2018. The study's aim was to evaluate patterns in the use of the aggressive, multivessel procedure.

In 2017, an unrelated study found that the more aggressive procedure may lead to a higher death rate than the more conservative treatment. But until now, no research has examined patterns in the use of the two treatments such as relative frequency and its variation among hospitals.

"Our work emphasizes the need for optimization of care practices for a group of patients who experience really bad outcomes," said Dr. Rohan Khera, an assistant professor of cardiovascular medicine at Yale and first author of the study. "In this case, less is more."

The senior author of the study is Dr. Robert Yeh of Beth Israel Deaconess Medical Center.

Overall, more than one-third of all heart attack patients who go into shock die during their initial hospital presentation. About half of them die within one year. By contrast, the mortality rate for heart attack patients who do not go into shock is less than 5%.

Despite concerns about the aggressive stenting of multiple blood vessels raised in the 2017 research, Khera said, his team found no early signals that its revelations have affected the proportion of patients undergoing aggressive versus more conservative stenting approaches.

But, he said, the team found wide variation among hospitals as to the approach they use -- and that "those hospitals using multi-vessel treatments more frequently had worse patient outcomes."

ROCHESTER, Minn. - A study of search engine queries addressed the question of whether online searches for chest pain symptoms correlated to reports of fewer people going to the emergency department with acute heart problems during the COVID-19 pandemic.

Mayo Clinic researchers looked at Google Trends data for Italy, Spain, the U.K. and the U.S., reviewing search terms such as "chest pain" and "myocardial infarction" (heart attack). The study spanned June 1, 2019 to May 31. Prior to the pandemic, those searches had relatively similar volumes to each other. The expectation would be that the frequency of heart attacks would stay the same or even rise in this setting. However, at the onset of the COVID-19 pandemic, searches for "myocardial infarction" dropped, while searches for "chest pain" rose at least 34%.

Conor Senecal, M.D., a Mayo Clinic cardiology fellow in Rochester, is first author on the study, which is published in JMIR Cardio.

"Interestingly, searches for 'heart attack' dropped during the same period of reported reduced heart attack admissions, but surprisingly, searches for 'chest pain' rose," says Dr. Senecal. "This raises concern that people may have either misconstrued chest pain as an infectious symptom or actively avoided getting care due to COVID-19 concerns."

To differentiate between Google searches for general COVID-19 symptoms, the study also tracked queries for "cough" and "fever." Initially, these searches were numerous, but then dropped off. The searches related to "chest pain," however, stayed at a high volume through May.

"Some of the rising searches, such as 'home remedies for chest pain' and 'natural remedies for chest pain' - both of which had a greater than 41 times increase - were surprising and provide insight into patients' possible avoidance of health care contact during the pandemic," says Dr. Senecal.

He adds that while concern over COVID-19 infection is warranted, if people are experiencing chest pain, they need to seek medical evaluation. This can be done in a safe manner that will help them avoid the consequences of delayed cardiovascular care.

The study underscores the need to find additional ways to educate patients that emergency conditions such as a heart attack and stroke can be safely cared for, even during the COVID-19 pandemic. People can be prepared by learning the common symptoms of a heart attack and being aware that some symptoms can vary between men and women.

A new study conducted by a team of researchers, including University of Colorado Denver Business School associate professor Jiban Khuntia, PhD, found while social distancing is an effective preventative measure in the fight against COVID-19, there are significant variations being observed in how and why individuals follow the restrictions. The reasons ascribed in the study are: (1) citizen's perception that government is doing good by responding to COVID situation, (2) citizen's perception of government business reopening efforts are good, (3) messages sent to citizens through different information sources, (4) specific social media use and (5) levels of knowledge around COVID.

Looking at three different countries--the United States, Kuwait, and South Korea--researchers found government response efforts to COVID-19 heavily influenced self-adherence to social distancing measures. According to data collected, overall, people believe they are following social distancing recommendations, but when asked if others adhering, the numbers decrease, as shown in the table below.

According to researchers, governments who instilled fear instead of providing important, knowledgeable information, are less likely to be trusted. This fear can lead to panic and limited adherence to policies implemented later. For example, in the United States, some citizens are hesitant to follow masks orders because they believe it will take away their freedom. Khuntia believes governments should have stated early-on that mask-wearing does not infringe on your freedom, but rather saves lives.

"The sole argument of this research is that the government should have given citizens a much better informative story, channelized through 'more personal' broadcasting and media sources than it was handled," says Khuntia. "Rather than focus on political ramifications, and media-driven 'sensational breaking stories', a positive, well put-together message should have been formed."

When comparing the different countries' responses to government mandates, the United States and Kuwait expect the government to provide enough information and rationale as to why they are taking away certain freedoms (staying inside, limiting gatherings, etc.). On the other hand, looking at South Korea, respondents are more willing to give up individual freedoms during a national crisis, regardless of the in-depth rationale provided by government officials.

"Countries have different institutional and cultural patterns involving trust, belief, and convictions on governance," says Khuntia.

When it comes to shaping decisions based on knowledge, Khuntia notes that higher knowledge level is influential in shaping the decisions on self-adherence for the US, whereas it raises a skepticism on others' adherence decisions for Kuwait.

"A possible reason may be due to differences in the cultural norm as well as the information surrounding the culture or community--i.e., health promotion behavior across cultures," says Khuntia.

After looking at all data and findings, researchers suggest policymakers explore four ideas to better COVID-19 social distancing adherence:

Tell citizens more precisely and directly what individuals need to do for themselves

Express what individuals should expect from others and what others need to do when dealing with other individuals

Messages from policymakers to citizens must be done through social media and similar channels, and not only through press and TV

With no current cure for COVID-19 and with no vaccine available, governments will have to continue to implement social distancing measures. They must keep in mind that there is a feeling of uneasiness and frustration with the economic downturn and loss of certain freedoms.

Researchers from this study conclude that public opinions must be considered while implementing new d to provide knowledge about the disease along with information that should calm the citizens, and messages should nudge citizens on what others in their community are doing in terms of health-prom COVID policies, in addition to medical research.

[Vienna, 24 August 2020] With the first COVID-19 epidemic peak behind them, many countries explained the decrease of infection numbers through non-pharmaceutical interventions. Phrases like "social distancing" and "flatten the curve" have become part of common vocabulary. Yet some explanations fell short: How could one explain the linear rise of infection curves, which many countries display after the first peak, in contrast to the S-shaped curves, expected from epidemiological models?

In a new paper published in PNAS (Proceedings of the National Academy of Sciences of the United States of America), scientists at the Complexity Science Hub Vienna (CSH) are the first ones to offer an explanation for the linear growth of the infection curve.

"At the beginning of the pandemic, COVID-19 infection curves showed the expected exponential growth," says Stefan Thurner, CSH president and professor for Science of Complex Systems at the Medical University of Vienna. This can be well explained by a so-called snowball effect: An infected person would infect a few others, and in a chain reaction, those would pass the virus on to a few others as well. "With measures like social distancing, governments tried to push the growth rate below the recovery rate and therefore massively reduce the number of new infections. In this logic, however, individuals would have infected less than one other person, and the curve would have flattened, eventually reaching zero - something that did not happen," explains Thurner.

"What we saw instead was a constant level of infections with a similar number of new infections every day," adds co-author Peter Klimek (CSH & Medical Univ of Vienna). "To explain this with standard epidemiological models would basically be impossible."

The use of traditional epidemiological models would have required a lot of fine-tuning of parameters, making the model increasingly implausible. "If you want to balance measurements so that the effective reproduction number R stays exactly at 1 - something that would explain the linear growth -, you would have to reduce contacts by the same exact and constant percentage. In reality that is extremely unlikely," says Klimek.

In fact, the probability to observe linear growth in these standard compartmental models is practically zero, the CSH scientists point out. They were therefore inspired to extend the model and look for further explanations.

The complexity scientists explained the linear shape of the curves through a different form of spreading than initially expected: They assumed that the spreading dynamic continued in small and limited clusters. "Most people went to work, got infected and spread it to two or three people at home, and then those people went to work or school again. The infection was basically spreading from cluster to cluster," says Stefan Thurner. "The change of the infection curves from being S-shaped to a linear behavior is clearly a network effect - a dynamic very different from big superspreading events."

The scientists showed that there is a critical number of contacts, which they call degree of contact networks or Dc, below which linear growth and low infection prevalence must occur. They found Dc to equal 7.2, assuming that people circulate in a coronavirus-relevant network of about five people, which is even lower during an effective lockdown (household-size 2.5 people on average).

Instead of having to fine-tune parameters, their model allows for a wide range of possibilities that keep the infection curves linear. It explains why linear infection curves appear in so many countries, irrespective of the magnitude of the imposed non-pharmaceutical interventions.

In a further step the scientists compared Austria, a country which responded with a severe lockdown early on, and the United States, which initially did not impose severe measures. According to Peter Klimek, their model works for both scenarios: "Both types of countries showed linear curves, but in the case of the US and other countries like Sweden, these just happened on a much higher level."

The model not only explains the emergence of a linear growth regime, but also explains why the epidemic could halt below the levels of herd immunity by consequent social distancing. For the standard modelling procedure, the complexity scientists use a so-called compartmental model with SIR-models, extending it with the described cluster transmission.

But what will happen in the next months, with the potential of numbers rising again? With additional risk factors like people returning from vacation in other countries and more time spent inside, the spread of disease could change. "If infections rise again, there is the potential that linear curves turn to exponential growth again - something people described as a second wave," Klimek concludes.

Aerobic exercise clearly benefits young adults with major depression, and a Rutgers-led study suggests it may be possible to predict those who would benefit from behavioral therapy with exercise.

"Our study needs to be replicated, but the precision medicine approach of predicting who may or may not benefit from exercise as an antidepressant is provocative," said senior author Brandon L. Alderman, an associate professor in the Department of Kinesiology and Health in the School of Arts and Sciences at Rutgers University-New Brunswick. "We also need to know whether exercise has a similar antidepressant effect in younger adolescents and in adults with more treatment-resistant forms of depression who have not responded well to traditional treatments, including antidepressants and cognitive behavioral therapy."

Unique to this precision medicine study, published in the journal Psychological Medicine, is an assessment of cognitive control and reward-related brain activity, two facets of brain function that are impaired in people with depression. Like previous studies, this one showed that aerobic exercise helps young adults with major depression.

Cognitive control means processes that allow adjustments in behavior to help achieve goals and resist distractions. Reward processing (or reward-related brain activity) reflects the response to rewarding stimuli or outcomes and the ability to process and then modulate your response to positive and negative outcomes, such as loss. Deficits in reward processing have been linked to multiple psychiatric conditions, including major depression, and may reflect anhedonia - the loss of interest in or inability to experience pleasure in cases of depression.

Many people with major depression, a complex disease, do not respond favorably to evidence-based treatments. Depression symptoms include feelings of hopelessness, irritability, fatigue, difficulty concentrating and thoughts of suicide, according to the National Institute of Mental Health. People suffering from depression often seek effective treatment using a trial-and-error approach. They move in and out of various treatments, including antidepressants and cognitive behavioral therapies, according to Alderman.

The Rutgers-led team studied 66 young adults with major depression, focusing on aerobic exercise and its impact on depressive symptoms. Three times a week for eight weeks, some participants did moderate-intensity aerobic exercise and others did light-intensity stretching. Depression symptoms were reduced by 55 percent in the aerobic exercise group versus 31 percent in the light-intensity stretching group.

While aerobic exercise did not influence reward processing or cognitive control, people with better reward processing when the study began were more likely to successfully respond to exercise treatment.