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WHAT:

COVID-19 treatments for people with early infection are needed urgently, according to a JAMA Viewpoint article by National Institute of Allergy and Infectious Diseases (NIAID) Director Anthony S. Fauci, M.D., and colleagues. Treating people early in the course of infection with SARS-CoV-2, the virus that causes COVID-19, would speed their recovery, reduce the likelihood that they develop severe outcomes and reduce demand on the healthcare system, they write.

Despite experiencing only mild symptoms early in infection, many COVID-19 patients progress to severe disease that leads to hospitalization. Some also will experience lengthy recoveries and develop long-lasting fatigue, mental impairment and problems with heart and lung function.

While several treatments such as remdesivir and dexamethasone are either available or in development for severe COVID-19, interventions that can be administered early during the course of infection to prevent disease progression and longer-term complications are urgently needed.

Studies are underway to assess whether existing antivirals can be repurposed for early treatment. Scientists also are exploring the effectiveness of early treatment with therapies that specifically target SARS-CoV-2, such as convalescent plasma and monoclonal antibodies. Investigators also are exploring strategies to deliver therapies by alternative routes than by intravenous infusion, such as by inhalation or intramuscular injection.

Continued research is needed to refine current treatment candidates and develop new drugs, and treatments will need to be administered easily and made available widely at low cost, according to the authors.

The article also highlights the need to design novel antiviral treatment approaches akin to successful efforts for hepatitis C virus and HIV. Such approaches could be helpful against future emergent viruses as well.

EAST LANSING, Mich. - Michigan State University researchers have identified a potential genetic target for treating an especially painful and invasive form of endometriosis.

Their study published in Cell Reports, a scientific journal, could lead to better treatments for women suffering from severe forms of endometriosis, said Mike Wilson, a postdoctoral fellow in the MSU College of Human Medicine. Wilson and Jake Reske, a graduate student in the MSU Genetics and Genome Sciences Program, are first authors of the study.

Their research focused on a type of endometriosis that occurs in women who have a mutation in a gene called ARID1A, which is linked to the more invasive and painful form of the disease. When ARID1A is mutated, so-called "super-enhancers," a part of the DNA that determines the function of cells, run wild, Reske said. This allows the cells that normally line the uterus to form deep implants outside the uterus and cause severe pelvic pain.

"There haven't been many successful nonhormonal therapies for this form of endometriosis that have made it to the bedside yet," Reske said.

In laboratory experiments, he and Wilson tested a drug that appeared to target the super-enhancers and stop the spread of endometriosis. Such a drug -- part of a new type of treatment called "epigenetic therapy" that controls how genes are expressed -- could be far more effective than current treatments, including surgery, hormone therapy and pain management.

Endometriosis, particularly the kind associated with the ARID1A mutation, can be debilitating for many women, often leading to infertility.

"It can seriously impact women's quality of life and their ability to have a family and work," said Ronald Chandler, an assistant professor of obstetrics, gynecology and reproductive biology, who supervised the study. "It's not easy to treat, and it can become resistant to hormone therapy. The most clinically impactful thing we found is that targeting super-enhancers might be a new treatment for this deeply invasive form of the disease."

The drug they studied targeted a protein in cells called P300, suppressing the super-enhancers and offsetting the effects of the ARID1A mutation, Wilson said. The same type of treatment could be used to treat other forms on endometriosis, he said.

The researchers already are planning follow-up studies to find other drugs that could target P300, Wilson and Reske said.

The MSU team collaborated with Van Andel Institute researchers, providing them with tissue samples for VAI scientists to analyze with a machine called a next-generation sequencer.

Spain's annual life expectancy at birth dropped by 0.9 years between 2019 and the annual period up until July 2020 due to the COVID-19 pandemic, according to a new study published this week in the open-access journal PLOS ONE by Sergi Trias-Llimos of the Center for Demographic Studies, Spain, and colleagues.

The COVID-19 pandemic is causing substantial increases in mortality in populations worldwide, and Spain was one of the most affected countries in the spring of 2020. Life expectancy is an easy to interpret, standard indicator in mortality patterns. However, few studies assessing the impact of the pandemic on mortality to date have reported life expectancy estimates.

In the new study, researchers used daily death count data from the Spanish Daily Mortality Monitoring System (MoMo) as well as information on death, population and demographic information from the Spanish National Statistics Institute. The team estimated weekly and annual life expectancies at birth for 2019 and the annual period up until July 2020.

The weekly life expectancies at birth in Spain were lower in weeks 11 through 20 of 2020--spanning early March through early May--compared to the same weeks in 2019. This drop was particularly significant in weeks 13 and 14--March 23 through April 5--with national declines in weekly life expectancy ranging from 6.1 to 7.6 years and regional weekly declines of up to 15 years in Madrid.

Likewise, the annual life expectancy for the country as a whole declined by 0.9 years between 2019 and the annual period up until July 2020, for both men and women. Regionally, this decline in life expectancy was as high as 2.8 years (95% CI 2.6-2.9) among men in Madrid. The authors state that these findings provide an intuitive measure of the health impact of the pandemic throughout Spain.

The authors say: "Annual life expectancy differences between 2019 and 2020* (annual window that closes out on 5 July 2020) reflected an overall drop in life expectancy of 0.9 years for both men and women. These drops ranged between 0 years in several regions (e.g. Canary and Balearic Islands) to 2.8 years among men in Madrid. Weekly life expectancy dropped by up to 15 years in Madrid during the worst weeks of the first wave." The authors go on to add: "Weekly and annual life expectancy are sensitive and useful indicators for understanding disparities and communicating the gravity of the situation because differences are expressed in intuitive year units...The recently observed mortality excess in the second wave suggests the drops in life expectancy by the end of the year to be larger than what currently estimated in this paper (only accounting for the first wave)."

BOSTON - There are several different types of heart attacks, which occur when blood flow to the heart is blocked or reduced. New research by investigators at Massachusetts General Hospital (MGH) reveals considerable uncertainty in how to care for patients with one type. The findings, which were published in Circulation: Cardiovascular Quality and Outcomes to coincide with the American Heart Association's Scientific Sessions 2020, point to the need for clinical trials to provide more guidance to physicians.

The cause of type 2 myocardial infarction is not from rupture of a plaque in the blood vessels but rather from medical conditions that contribute to an imbalance between oxygen supply and demand in the heart. "Initial management typically focuses on treating the medical illness that precipitated the heart attack; however, we now have evidence that patients with this type of heart attack have high rates of recurrent cardiovascular events and may need tailored follow-up care," says investigator and lead author Cian P. McCarthy, a cardiology fellow at MGH.

To investigate how these patients are treated during their hospital admission and afterwards, McCarthy and his colleagues examined the electronic health records of patients with type 2 myocardial infarction at MGH between October 2017 and May 2018. "We sought to investigate how frequently patients with this type of heart attack are evaluated by a cardiologist during their admission, and whether this is associated with differences in cardiac testing and treatment," McCarthy says. "In addition, we wanted to explore: How often do patients receive follow-up care with a cardiologist after discharge, given their cardiovascular risk?"

Among 359 patients identified, 207 (57.7%) were evaluated by cardiologists, 120 (33.4%) received cardiology consultation requests, and 87 (24.2%) were admitted or transferred to the cardiology department. Patients evaluated by cardiologists more commonly underwent stress tests and heart imaging exams during their hospital admission, and they were more likely to be discharged on a statin and a beta blocker. There were no differences in death rates among those who were or were not evaluated by cardiologists.

Among patients who were discharged, 38.4% had an outpatient cardiology follow-up visit within six months, and patients who were evaluated by cardiologists during their hospital admission were more likely to have such follow-up visits.

The analysis raises the possibility of gaps in care for patients with type 2 myocardial infarction. "These data highlight the uncertainty among clinicians on how to best manage patients with this type of heart attack," says McCarthy. He notes that because no clinical trials have addressed this specific patient population, the roles of cardiologists, traditional heart attack medications, and stenting or bypass surgery are unknown. "As these patients have high rates of recurrent cardiovascular events, my personal opinion is that they should be seen by a cardiologist either during their admission or as an outpatient after discharge; however, we need clinical trials to investigate this."

Senior author Jason H. Wasfy, MD, director of Quality and Analytics at MGH's Corrigan Minehan Heart Center, notes that the wide variation in care provided to patients with type 2 myocardial infarction might point to different treatment strategies that could be tested prospectively in randomized trials. "We need to develop validated treatment strategies because the prognosis for these patients is sobering," he says.

HOUSTON — Promising clinical results with combination treatments for patients with melanoma and lung cancer highlight immunotherapy advances being presented by researchers from The University of Texas MD Anderson Cancer Center at The Society for Immunotherapy of Cancer (SITC) 35th Anniversary Annual Meeting & Pre-Conference Programs (SITC 2020) .

"The SITC Annual Meeting provides us the opportunity to learn about and share groundbreaking new discoveries in tumor immunology and clinical advances for treating patients," said Giulio Draetta, M.D., Ph.D., chief scientific officer. "As we strive to expand the use of immunotherapy for more patients, we look forward to seeing these results presented at this year's meeting."

Combination immunotherapy shows activity in metastatic melanoma (Abstract 420)

First-line treatment with a combination of nivolumab and interleukin-2 agonist bempegaldesleukin (BEMPEG) resulted in encouraging clinical activity for patients with metastatic melanoma in the Phase I/II PIVOT-02 trial. Results from the ongoing trial will be presented by Adi Diab, M.D., associate professor of Melanoma Medical Oncology.

Forty-one patients with previously untreated stage IV melanoma were enrolled on the trial, 38 of whom were able to be evaluated on the study. The treatment was well tolerated, as described in previous studies with this combination.

Twenty of the 38 efficacy evaluable patients (53%) had an overall response, or tumor shrinkage, and 13 (34%) had a complete response. Sixteen patients (80%) had ongoing responses and the median duration of response had not been reached at a follow-up of 29 months.

Median progression-free survival was 30.9 months, and median overall survival had not yet been reached.

"Despite the tremendous successes we have seen with immunotherapy in treating patients with advanced melanoma, current therapies are not effective for all patients. We have an unmet clinical need for new therapies that can provide prolonged benefit to more patients," said Diab. "We are encouraged by the safety profile and durable responses seen with this combination therapy, and we look forward to continued evaluation in Phase III studies, which are enrolling now."

Based on these results, the combination of BEMPEG and nivolumab was awarded Breakthrough Therapy designation by the U.S. Food and Drug Administration.

The study was supported by Nektar Therapeutics. A complete list of collaborating authors can be found within the abstract here.

Diab reports research support and consulting fees from both Nektar and Bristol Myers Squibb.

BEMPEG plus targeted therapy stimulates anti-tumor immune activation in advanced cancers (Abstract 368)

In the Phase I REVEAL trial for patients with advanced refractory solid tumors, combination treatment with BEMPEG and NKTR-262, a small-molecule agonist of Toll-like receptors (TLR) 7/8, led to activation of immune pathways associated with antitumor response. Results from the dose-escalation study will be presented by Diab.

NKTR-262 is designed to promote stimulation of an immune response in the tumor microenvironment, which can lead to antitumor activity when combined with BEMPEG in preclinical studies, explained Diab.

In 36 enrolled patients, the most frequent side effects were flu-like symptoms, fatigue, nausea and itching, all of which are consistent with the known safety profile of BEMPEG. One dose-limiting toxicity of elevated transaminase levels was observed at the highest dosage.

Two patients experienced partial responses, and seven patients had disease control (partial response or stable disease). Analysis of the immune response revealed increased activation of both T cells and natural killer (NK) cells in patients as well as of cytokines and interferon genes.

Based on these results, this combination will be evaluated in a Phase Ib dose-expansion with or without nivolumab for patients with advanced melanoma.

The study was supported by Nektar Therapeutics. A complete list of collaborating authors can be found within the abstract here.

Presurgical nivolumab and chemotherapy achieves high rates of tumor downstaging in patients with resectable lung cancer (Abstract 277)

Combining platinum-based doublet chemotherapy with nivolumab as a neoadjuvant, or presurgical, therapy for patients with stage I-IIIA non-small cell lung cancer (NSCLC) resulted in the highest rates of tumor downstaging at surgery, relative to other neoadjuvant regimens. Results of the study will be presented by Boris Sepesi, M.D., associate professor of Thoracic and Cardiovascular Surgery.

Patient cohorts on the study included 302 MD Anderson lung cancer patients treated with neoadjuvant platinum doublet chemotherapy and patients treated on the Phase II NEOSTAR study, led by Tina Cascone, M.D., Ph.D., assistant professor of Thoracic/Head & Neck Medical Oncology. NEOSTAR participants include 21 patients receiving nivolumab only, 16 patients receiving nivolumab plus ipilimumab and 22 patients receiving nivolumab with platinum doublet chemotherapy.

Among all cohorts, the combination of chemotherapy with nivolumab achieved the highest rates of clinical downstaging at 68%, compared to 38% in each additional cohort, a statistically significant difference.

"Maximizing the effectiveness of neoadjuvant therapy will help us to prevent relapse after surgery and improve outcomes for our patients," said Sepesi. "The robust clinical downstaging rates seen after platinum doublet chemotherapy in combination with nivolumab are encouraging in patients with operable non-small cell lung cancer, and we look forward to learning if there are survival benefits in long-term follow-up data."

This study was supported by Bristol Myers Squibb and MD Anderson's Lung Cancer Moon Shot®, part of the institution's Moon Shots Program®. A complete list of collaborating authors can be found within the abstract here.

Sepesi reports consulting fees from Bristol Myers Squibb and research support from Rexanna's Foundation for Fighting Lung Cancer. Cascone reports consulting fees from MedImmune/AstraZeneca and Bristol Myers Squibb, and advisory role fees from EMD Serono and Bristol Myers Squibb and clinical research funding to MD Anderson Cancer Center from Boehringer Ingelheim, MedImmune/AstraZeneca, EMD Serono, and Bristol Myers Squibb.

A team of researchers has discovered that a protein found in the nervous system can predict the severity of brain damage and long-term outcomes in patients who have suffered a stroke. Their analysis of data from 464 patients who experienced different types of strokes may provide clinicians with a reliable marker to assess damage to brain tissue, which could facilitate rehabilitation strategies and streamline the testing of new therapeutics in trials. Strokes are a major cause of death and disability worldwide, but patients can show a wide range of outcomes: some have only temporary and mild symptoms while others die or develop permanent disabilities. Current clinical scoring systems such as the National Institutes of Health Stroke Scale correlate poorly with the actual extent of tissue and neuron damage in patients, which has hampered clinicians' ability to predict outcomes and tailor treatment protocols. However, Tania Gendron and colleagues discovered that the levels of neurofilament light protein (NFL) in blood consistently correlated with more severe brain damage and poorer survival rates after stroke, according to data from 314 patients with three different types of stroke. The researchers confirmed this link using plasma samples from two additional groups of patients with stroke (150 total) and 48 healthy controls; they also showed that patients with lower NFL levels recovered day-to-day function better 6 months after stroke. Gendron et al. say one key step to clinical translation will be to determine exactly when blood NFL levels begin to correlate with long-term outcomes in the aftermath of stroke.

(Los Angeles - Nov 11, 2020) According to the National Institutes of Health, opioid misuse and addiction in the United States is a national crisis, with an economic burden upwards of $78 billion. Opioids are useful for pain management following surgery and other major procedures, but until now there have been no recommendations guiding safe use of opioids in children. Pediatric Surgeon Lorraine Kelley-Quon, MD, MSHS, led a diverse team of health care providers and advocates to establish the first such guidance. Published in JAMA Surgery, Dr. Kelley-Quon and her colleagues outline 20 guidelines for safer pain management in children and adolescents.

"Many people are aware that there's an opioid epidemic," says Dr. Kelley-Quon, "but when I talk about my work, people are surprised to hear that it impacts children."

One of the primary concerns is the use of opioids among teens and adolescents. Dr. Kelley-Quon cites a CDC report revealing that approximately 9 percent of teens aged 15-19 report receiving an opioid prescription in 2018. This age group is of concern because prescription medications can be used recreationally and shared with friends. In addition, research shows that death due to opioid overdose is on the rise for all age groups.

"Opioids can be very effective in pain management following pediatric procedures," she says, "but we need to work with the medical community to ensure they are used safely and judiciously."

As a member of the American Pediatric Surgical Association's Outcomes and Evidence-Based Practice Committee, Dr. Kelley-Quon led an effort to develop evidence-based guidelines for best practice in opioid prescribing. Her team did an extensive review of scientific and medical publications, but the effort went far beyond a literature search. Dr. Kelley-Quon created a multidisciplinary group that included specialists in pediatric surgery, pediatric anesthesia, and addiction science, and included other key stakeholders representing nursing, physician assistants, surgery trainees, and family advocates. After pooling data from published studies, the entire group met and constructed the guidelines together.

"Opioid prescribing doesn't just impact what a pediatric surgeon does," says Dr. Kelley-Quon. "Nurses and other medical care providers are involved in pain management discussions with patients and their families, so we wanted their input as well."

The team came up with three basic tenets, into which all the guidelines fall. First is simply a recognition that misuse of prescription opioids is a problem to be taken seriously when caring for children and adolescents. Second is to acknowledge there are many non-opioid medications that have excellent data supporting their use for children who require surgery. The team reviewed and presented those options. Finally, health care providers must educate patients and families before and after surgery about what an opioid is, what the risks are, and how they should be safely stored and disposed of.

"With these guidelines, we didn't want to suggest that opioids should never be used," says Dr. Kelley-Quon. "Instead, we wanted to impart the idea that they need to be used in a thoughtful way." Just as health care providers and patients have come together around the idea of antibiotic stewardship--using an antibiotic only when medically necessary to prevent development of antibiotic-resistant bacteria--she says we should practice opioid stewardship.

The publication, endorsed by the American Pediatric Surgical Association, sets the stage to begin shaping policies around prescribing opioids in pediatric medicine, but Dr. Kelley-Quon says we are not there yet.

"We are laying the groundwork," she says. "It is our hope that this work will change paradigms in pain management for children and teens by increasing surgeon awareness and facilitating family engagement."

Surviving a case of COVID-19 that's bad enough to land you in the hospital is hard enough. But life after the hospital stay - and especially after an intensive care stay - is no bed of roses, either, according to a new study.

Within two months of leaving the hospital, nearly 7% of the patients had died, including more than 10% of the patients treated in an ICU. Fifteen percent had ended up back in the hospital. The data come from more than 1,250 patients treated in 38 hospitals across Michigan this spring and summer, when the state was one of the earliest to experience a peak in cases.

When researchers interviewed 488 of the surviving patients by phone around 60 days after their hospitalization, they heard a litany of health and life woes. They've published their findings in the Annals of Internal Medicine.

"These data suggest that the burden of COVID-19 extends far beyond the hospital and far beyond health," says Vineet Chopra, M.D., M.Sc., lead author of the study and chief of hospital medicine at Michigan Medicine, the University of Michigan's academic medical center. "The mental, financial and physical tolls of this disease among survivors appear substantial."

Lasting effects

More than 39% of the patients interviewed said they hadn't gotten back to normal activities yet, two months after leaving the hospital. Twelve percent of the patients said they couldn't carry out basic care for themselves anymore, or as well as before.

Nearly 23% said they became short of breath just climbing a flight of stairs. One-third had ongoing COVID-like symptoms, including many who still had problems with taste or smell.

Of those who had jobs before their bout with COVID-19, 40% said they couldn't return to work, most because of their health and some because they'd lost their job. And 26% of those who had gone back to work said they had to work fewer hours or have reduced duties because of their health.

Nearly half of those interviewed said they'd been emotionally affected by their experience with COVID-19 - including a minority who said they'd sought mental health care.

More than a third - 37% -- of those interviewed said their experience with COVID-19 had left them with at least a minor financial impact. Nearly 10% said they'd used up most or all of their savings, and 7% said they were rationing food, heat, housing or medications because of cost.

"The sheer number of people struggling after COVID brings new urgency to developing programs to better promote and support recovery after acute illness," says Hallie Prescott, M.D., M.Sc., senior author and pulmonary/critical care physician at University of Michigan and the VA Ann Arbor Healthcare System.

More about the study

The study used date from the MI-COVID19 initiative, which rapidly evolved in April as a way for Michigan hospitals to pool and analyze data on their COVID-19 patients.

It grew out of existing multi-hospital quality improvement efforts funded by Blue Cross Blue Shield of Michigan, and drew on existing staff who are experienced at analyzing medical records and interviewing patients. That gave researchers a head start on studying COVID-19 patients treated in most of the hospitals that received such patients in the early-peak state of Michigan.

Details obtained from patient medical records, and in-depth interviews conducted after attempting to contact patients by phone multiple times, give a picture of what life is like for post-COVID patients.

Nearly 52% of the patients in the study are Black, and 4% are Hispanic. The average age is 62, and 83% lived at home before being hospitalized for COVID-19.

More than 14% had no chronic conditions before COVID-19 landed them in the hospital, and for many others the only condition they had was high blood pressure. The well-known risk factors of diabetes, cardiovascular disease and kidney disease were present in about a quarter of patients.

While hospital care for COVID-19 patients has improved since the early months of the pandemic, the study shows that the 63% of patients who were ever treated in an ICU had died during their hospital stay or within two months of leaving the hospital. That's more than twice the rate for patients hospitalized but not admitted to an ICU.

Patients with advanced chronic kidney disease (CKD) suffer from impaired bone quality and quantity, with a non-vertebral fracture risk which is 4-to 6-fold higher than the fracture risk of matched controls. However, due to the complexity and many challenges involved in diagnosing and treating osteoporosis in advanced stage CKD, there is an exceptionally high care gap, leaving these high-risk patients unprotected against potentially life-threatening fragility fractures.

In an effort to foster a paradigm shift with regard to osteoporosis care in CKD, the European Renal Osteodystrophy (EUROD) Working Group, bringing together expertise from the European Renal Association-European Dialysis and Transplant Association and International Osteoporosis Foundation (IOF) Committees of Scientific Advisors and National Societies, has published the 'European Consensus Statement on the diagnosis and management of osteoporosis in chronic kidney disease stages G4-G5D'.[1] The Consensus provides a succinct review of current clinical practice and outlines practical recommendations for diagnosis, assessment of fracture risk, intervention thresholds, non-pharmacological and pharmacological intervention strategies, monitoring, and secondary fracture prevention through coordinator-based fracture liaison services.

Lead author, Dr Pieter Evenepoel, Department of Nephrology of the University Hospitals Leuven, Leuven, Belgium stated:

"Disturbances in mineral and bone metabolism occur early in the course of CKD and become almost universal in patients with advanced disease. Nevertheless, despite their very high risk of sustaining osteoporosis-related fractures, there is a vast osteoporosis care gap in these patients. Many clinicians are uncertain about the optimal diagnostic and therapeutic strategy and this may be fuelling inertia and a 'wait-and-see' approach in regard to osteoporosis care."

The Consensus recommendations are timely and important given that chronic kidney disease is a rapidly growing problem worldwide. It is estimated that as much as 10-15% of the adult population is affected. In 2010, 284 individuals per million population were estimated to be undergoing maintenance dialysis (CKD G5D) globally, and this is on the increase given the rapid increase in chronic cardiometabolic diseases worldwide.

Professor Serge Ferrari, co-author and Vice-Chair of the IOF Committee of Scientific Advisors, added:

"Recent studies suggest a similar efficacy of common osteoporosis drugs in patients with CKD G4-G5D as in the general patient population. We hope that the pragmatic consensus recommendations resulting from this successful collaboration between European societies, covering assessment, treatment and monitoring of bone health in renal disease, will serve to stimulate a proactive and cohesive approach to the management of osteoporosis in these high-risk patients."

The recommendations also highlight the importance of coordinator-based fracture liaison services in systematically identifying and guiding CKD patients with fragility fractures, in close collaboration with nephrologists as part of the multidisciplinary team.

People with neurological conditions, such as stroke and head injury, often have problems with swallowing food and drinking safely, which is called "neurogenic dysphagia".

Unfortunately there are few effective treatments and many people subsequently develop pneumonia, which leads to extended stays in hospital and many even die.

In response to this, a group of experts carried out PHADER - the largest-ever study testing whether electrical stimulation of the back of the throat (pharynx), using a treatment catheter, would improve swallowing in people with a recent stroke or head injury, or who had been in an intensive care unit and needed ventilation.

The study was a collaborative project between experts at the Universities of Nottingham and Manchester and the University of Münster in Germany, and was funded by Phagenesis - a company dedicated to the treatment of dysphagia.

The observational study recruited 255 patients from 14 different centres in Austria, Germany and the UK, with five different neurological conditions. Electrical stimulation was administered once daily for three days, and the outcome was then measured on the severity of the dysphagia at three months.

The findings of the research, published today in EClinicalMedicine, showed that most people's swallowing problems improved, and so allowing feeding tubes to be removed and for patients to be discharged from hospital.

The treatment catheters were easy to insert into the back of the throat and no serious complications attributable to the treatment occurred.

Professor Philip Bath from the School of Medicine at the University of Nottingham, and co-lead investigator on the study, said: "PHADER is the largest-ever study of electrical stimulation, and our findings show that most people's swallowing problems improved after receiving the treatment, which is a potential game changer for patients with severe swallowing problems who previously were at risk of complications including pneumonia. It will also mean quicker discharge from hospital for these patients."

Professor Shaheen Hamdy from The University of Manchester and co-lead Investigator said: "This study shows conclusively that electrical stimulation of the throats of these patients can help improve their ability to swallow safely and that is tremendously exciting. We clearly show the device is easy to use, safe and most critically, impacts on swallowing recovery in a range of disorders, which could make a major difference to patients' quality of life. We feel this constitutes a new avenue for treatment in this sometimes life-threatening condition and are looking forward to seeing this technology go from strength to strength".

Professor Rainer Dziewas from the University of Münster and co-lead Investigator said: "These results are fascinating since most patients were treated in a chronic state of the illness, where it is usually extremely difficult to achieve any treatment success. PHADER clearly suggests that electrical stimulation may help even in this notoriously difficult situation. However, it is important to mention that patients with dysphagia should be treated as early as possible for best outcomes."

Reinhard Krickl, CEO Phagenesis, said: "PHADER not only confirms the very encouraging outcomes of previous studies in stroke patients, but also demonstrates that patients suffering from dysphagia after brain injury, or who had been in an intensive care unit and needed long periods of ventilation, will benefit from electrical stimulation using our treatment system, Phagenyx®. We have even just recently learned that our treatment can improve swallowing in critically-ill COVID-19 patients after weeks of mechanical ventilation. In times of crisis like in the current global pandemic, this could be incredibly important in helping patients with life-threatening dysphagia recover faster allowing medical teams to make ICU resources available for other patients much faster."

Six Ways Primary Care "Medical Homes" Are Lowering Health Care Spending

New analysis of 394 U.S. primary care practices identifies the aspects of care delivery that are associated with lower health care spending and lower utilization of emergency care and hospital admissions. Researchers from the Urban Institute and RTI International analyzed health care cost data from a large group of Medicare patients and their primary care practices. Each practice previously took part in a 2011-2014 Centers for Medicare and Medicaid Services initiative to establish advanced primary care "medical homes," with improved and centralized care coordination.

What worked to reduce overall health care cost and utilization? At the top of the list: primary care practices that used patient clinical data to identify and remind patients due for preventive services saved, on average, about $70 per patient per month, lowered acute care hospital spending, and reduced hospitalizations and emergency department visits in their patient population.. Additionally, using their patient clinical records to initiate pre-visit planning, clinician reminders, targeted patient outreach, and population health monitoring were also linked to lower total Medicare spending. In short, practices that were able to leverage their patient data registry to anticipate need and target effective preventive services saved money.

Additional activities that were associated with fewer emergency department visits, reduced acute care spending and/or reduced hospital admissions include: offering targeted consultations for patients with chronic conditions to set health goals; following patients during hospital stays and supporting other specialists in patient care; establishing a protocol for sharing information in medical referrals; and adopting systematic approaches to quality improvement. Surprisingly, expanding access to care, such as expanded night and weekend hours, was not associated with lowered health care spending, utilization of emergency departments, nor reduced hospital readmissions.

Patient-Centered Medical Home Activities Associated With Low Medicare Spending and Utilization
Rachel A. Burton, MPP, et al
The Urban Institute, Washington, D.C.
https://www.annfammed.org/content/18/6/503

Older Americans Who Are Black, Hispanic, or Medicaid-Eligible Are More Likely to Experience Preventable Hospitalizations

When complications due to diabetes, asthma, urinary tract infections, high blood pressure and other common conditions lead patients to visit the ER, researchers and health care quality administrators may label these visits as "potentially preventable hospitalizations." That is, with good outpatient care, these visits could have been potentially avoided. Potentially preventable hospitalizations are costly and can negatively impact the health and well-being of individuals, particularly if they are older. Researchers examined national trends in PPH to see differences across racial and socioeconomic subpopulations, as well as county-level differences, using 2010-2014 Medicare claims data. Overall, PPH rates consistently declined across all subpopulations. However, they found that Black and Hispanic Americans had higher PPH rates compared to Whites. Additionally, those who also had Medicaid insurance had higher rates than those with only Medicare coverage.

This examination of county-level potentially preventable hospitalization trends can inform health and social policies to support groups identified to be at-risk of PPH. The primary care system needs to be accessible and affordable, particularly for populations who are at higher risk of PPH. Policies with financial incentives to increase the number of primary care physicians, especially in rural and low-income areas, can potentially improve health care access and reduce PPH among vulnerable populations.

Potentially Preventable Hospitalizations Among Older Adults: 2010-2014
Elham Mahmoudi, PhD, et al
University of Michigan, School of Medicine, Ann Arbor, Michigan
https://www.annfammed.org/content/18/6/511

NEW YORK, NY (Nov. 10, 2020)--Researchers have identified a genetic signature in localized prostate cancer that can predict whether the cancer is likely to spread, or metastasize, early in the course of the disease and whether it will respond to anti-androgen therapy, a common treatment for advanced disease. The new gene signature may also be useful for evaluating responses to treatment and for developing new therapies to prevent or treat advanced prostate cancer.

"If we could know in advance which patients will develop metastases, we could start treatments earlier and treat the cancer more aggressively," says the study's senior author, Cory Abate-Shen, PhD, chair of the Department of Molecular Pharmacology and Therapeutics, the Michael and Stella Chernow Professor of Urologic Sciences (in Urology), and professor of pathology & cell biology (in the Herbert Irving Comprehensive Cancer Center) at Columbia University Vagelos College of Physicians and Surgeons.

"Conversely, patients whose disease is likely to remain confined to the prostate could be spared from getting unnecessary therapy."

The study was published online in Nature Cancer. 

Existing Tests Can't Identify Aggressive Cancers

Prostate cancer is the second-leading cause of cancer death among men in the United States; about 33,330 men are expected to die of the disease this year.

Most prostate cancers remain confined to the prostate and can be successfully managed by active surveillance or local therapy (mainly surgery or radiotherapy), with five-year survival rates above 99%. But once prostate cancer spreads, it is considered incurable, and five-year survival rates drop to approximately 30%. 

"The problem is that with existing tests, it's hard to know which cancers are which," says the study's lead author, Juan M. Arriaga, PhD, associate research scientist in molecular pharmacology and therapeutics at Columbia University Vagelos College of Physicians and Surgeons. 

"We miss a lot of aggressive cancers that should have been treated earlier, and we overtreat some slow-growing cancers that probably would not have spread." 

New Gene Signature First Identified in New Mouse Model

To identify a more accurate method of predicting advanced prostate cancer, the researchers first created a mouse model of prostate cancer that accurately reflects the human form of the disease, including how the cancer spreads to the bone, the tissue most often affected by prostate cancer metastases. 

Using this first-of-its-kind mouse model, the researchers discovered that bone metastases have a different molecular profile than that of primary tumors. "By focusing on those differences, we were able to identify 16 genes that drive localized prostate cancer to metastasize," Abate-Shen says. 

16 Genes Predict Metastasis in Patients

The genetic signature, called META-16, was then tested on biopsies from several hundred patients with localized prostate cancer. The outcomes of those patients were blinded to the researchers. 

The Columbia team found that META-16 was highly effective at predicting time to metastasis and response to anti-androgen therapy (which is used to suppress androgen, the male hormone, which promotes tumor progression).

The team is currently refining the test, which they then hope to evaluate in a prospective clinical trial.

In theory, META-16 could also be used to develop therapies against metastatic prostate cancer. 

"The genes in our signature are not only correlated with metastasis, they appear to be driving metastasis," Arriaga says. "That means that if that we can suppress the activity of those genes, we might be able prevent the cancer from spreading or at least improve outcomes."

Investigators from Brigham and Women's Hospital and Massachusetts Institute of Technology have been working to design a better, reusable respirator that could serve as an alternative to an N95 respirator. In the latest iteration of their work, they have introduced sensors to inform the user if the respirator is on properly and whether the filters are becoming saturated. The team tested the respirator, known as the transparent, elastomeric, adaptable, long-lasting (TEAL) respirator, at the Brigham and at Massachusetts General Hospital (MGH), and reports a 100 percent success rate for fit testing among 40 participants, with feedback demonstrating exceptional fit, breathability and filter exchange. Results are published in ACS Pharmacology & Translational Science.

"During the COVID-19 pandemic, the need for respirators and masks has been urgent. Our team has worked to develop a respirator platform that not only fits comfortably and snugly but can also be sterilized and re-sterilized," said corresponding author Giovanni Traverso, MB, BChir, PhD, a gastroenterologist and biomedical engineer in the Division of Gastroenterology at the Brigham and assistant professor in the Department of Mechanical Engineering at MIT. "In this study, we looked at up to 100 re-sterilization cycles and found that the TEAL respirator we've designed can withstand that."

The team evaluated 7 different methods for repeatedly sterilizing the TEAL respirator, including 100 cycles of autoclaving, 100 cycles of microwaving, prolonged exposure to UV treatment, high heat (200 °C), 100 percent isopropyl alcohol, and bleach. The researchers found minimal change to the respirator's elasticity after repeated sterilization.

The TEAL respirator is comprised of a transparent, stretchy shell that can be sterilized and filters that can be replaced by the user. The team found that all participants could successfully replace their filters and most participants (90 percent) reported an excellent or good fit for the respirator.

"TEAL is the first elastomeric respirator designed for use in a surgical setting, preserving the sterile field and providing the user a comfortable, reusable personal protective equipment solution," said co-author Adam Wentworth, MS, a senior research engineer in the Brigham's Division of Gastroenterology and the Traverso lab.

The respirator's sensors can help detect respiratory rate, exhalation temperature, and exhalation and inhalation pressures. The team also added a thermochromic coating to the respirator -- a coating that changes color from black to pink when the respirator is in direct contact with a person's face and therefore has a snug fit.

The researchers evaluated the respirator's performance in a clinical setting, enrolling 47 subjects from the Brigham and MGH (40 of the subjects underwent fit testing). Participants were asked to score the respirator on its fit, breathability and ease of filter exchange, and were also asked if they preferred the TEAL respirator to other options. Of those queried, 60 percent preferred the TEAL respirator compared to 5 percent who preferred standard hospital-supplied respirators. The remaining 35 percent had no preference.

"We were excited to receive the feedback from the trial participants that they would love to continue using and testing the respirator, given its comfort, transparency and ease of use," said co-author James Byrne, MD, PhD, a resident in the Department of Radiation Oncology at the Brigham and a postdoctoral fellow in the Traverso lab.

Byrne notes that in addition to its other features, the TEAL respirator's transparency may offer some advantages over more traditional respirators.

"One of the big benefits of the TEAL respirator is that it enables visualization of the lips," he said. "This can be immensely helpful in communication and expression, especially during this time when communication through N95 respirators and surgical masks makes it challenging to understand one another."

The sample size of the study was small, and the investigators acknowledge the importance of additional evaluation in a larger cohort of individuals and over a longer timeframe to further test the respirator's functionality. To use the respirator in a health care setting, additional testing according to National Institute for Occupational Safety and Health (NIOSH) criteria will be needed.

Wentworth, Byrne, Traverso and co-authors have filed multiple patents surrounding the respirator and sensors. In addition, Wentworth, Byrne and Traverso have a financial interest in TEAL Bio, a biotechnology company focused on developing the next generation of personal protective equipment. A co-author is on the board of directors for Analog Devices.

Funding for this work was provided by the Prostate Cancer Foundation (Prostate Cancer Foundation Young Investigator Award), the Department of Mechanical Engineering at MIT, Brigham and Women's Hospital, the Karl van Tassel Career Development Professorship, the National Institutes of Health (NIHK23DA044874, R44DA051106, 456 5T32DK007191-45), investigator-initiated research grants from e-ink corporation, Gilead Sciences, Philips Biosensing, and the Hans and Mavis Lopater Psychosocial Foundation.

Paper cited: Wentworth, A et al. "Prospective Evaluation of the Transparent, Elastomeric, Adaptable, Long-Lasting (TEAL) Respirator" ACS Pharmacology & Translational Science DOI: 10.1021/acsptsci.0c00157

TUCSON, Ariz. – A clinical trial at the University of Arizona Health Sciences designed to study the safety and effectiveness of a personalized cancer vaccine in combination with the immunotherapy drug Pembrolizumab will expand its cohort after promising preliminary data was presented at the annual meeting of the Society for the Immunotherapy of Cancer.

Julie E. Bauman, MD, MPH, deputy director of the University of Arizona Cancer Center and a professor of medicine and chief of the Division of Hematology and Oncology at the UArizona College of Medicine – Tucson, presented preliminary data on the first 10 patients with head and neck cancer, seven of which were treated at Banner – University Medicine, the clinical partner for the UArizona Cancer Center. Five of the 10 patients experienced a clinical response to the personalized cancer vaccine, and two patients had a complete response after the treatment (no detectable disease present).

The preliminary response rate of 50% is notable when compared to patients in clinical trials that receive Pembrolizumab immunotherapy alone without the personalized cancer vaccine. In those studies, the reported response rate is approximately 15%.

Watch an animated video describing the process of creating personalized cancer vaccines.

The UArizona Cancer Center is one of several sites where patients were recruited to participate in the phase I clinical trial sponsored by Moderna, Inc. The trial is studying the use of a personalized mRNA cancer vaccine in combination with Pembrolizumab for patients with multiple cancer types, including colorectal and head and neck cancers. No clinical responses were noted for the study’s cohort of 17 microsatellite stable (MSS) colorectal patients.

Dr. Bauman says the current study will now expand to 40 patients with head and neck cancer.

“The data are preliminary and the sample size is small, but it is promising,” Dr. Bauman said. “A phase I trial is about safety first and foremost, and we now know this treatment is safe and tolerable. But, we also have a strong signal to point us to further study this in head and neck cancer. That is why we are excited to expand this trial.”

Personalized cancer vaccines are an emerging treatment option that uses a patient’s own cancer cells to develop a vaccine intended to teach their immune system how to recognize and destroy their cancer. Cancer cells have DNA mutations that differ from the DNA in normal, healthy cells. These mutations are different from patient to patient, which is where the concept of a personalized vaccine is developed. Combining the personalized vaccine with Pembrolizumab, an immunotherapy medicine that works with the immune system to fight certain types of cancers, will hopefully allow further benefit to patients than pembrolizumab alone.

To identify the patient-specific mutations of the cancer, mutated DNA from the patient’s tumor is simultaneously sequenced with healthy DNA from the patient’s blood. Computers compare the two DNA samples to identify the unique cancer mutations. The results are used to develop a set of genetic instructions that are loaded onto a single molecule of messenger RNA (mRNA) and made into a vaccine. These instructions teach immune cells such as T-cells – white blood cells that help protect against infection – how to identify and attack the mutated cancer cells.

“Our goal is to understand how we can get better at applying this treatment to more patients to result in more successful outcomes,” Dr. Bauman said. “This preliminary data has generated exciting new hypotheses to investigate.”