Body

A new approach to predicting which babies will develop type 1 diabetes moves a step closer to routine testing for newborns which could avoid life-threatening complications.

Scientists at seven international sites have followed 7,798 children at high risk of developing type 1 diabetes from birth, over nine years, in The Environmental Determinants of Diabetes in the Young (TEDDY) Study. The TEDDY Study is a large international study funded primarily by the US National Institutes of Health and U.S. Centers for Disease Control, as well as by the charity JDRF.

In research published in Nature Medicine, scientists at the University of Exeter and the Pacific Northwest Research Institute in Seattle used the TEDDY data to develop a method of combining multiple factors that could influence whether a child is likely to develop type 1 diabetes. The combined risk score approach incorporates genetics, clinical factors such as family history of diabetes, and their count of islet autoantibodies - biomarkers known to be implicated in type 1 diabetes.

The research team found that the new combined approach dramatically improved prediction of which children would develop type 1 diabetes, potentially allowing better diabetes risk counselling of families. Most importantly, the new approach doubled the efficiency of programmes to screen newborns to prevent the potentially deadly condition of ketoacidosis, a consequence of type 1 diabetes in which insulin deficiency causes the blood to become too acidic. Identifying which children are at highest risk will also benefit clinical trials on drugs that are showing promise in preventing the condition.

Dr Lauric Ferrat at the University of Exeter Medical School, said: "At the moment, 40 per cent of children who are diagnosed with type 1 diabetes have the severe complication of ketoacidosis. For the very young this is life-threatening, resulting in long intensive hospitalizations and in some cases even paralysis or death. Using our new combined approach to identify which babies will develop diabetes can prevent these tragedies, and ensure children are on the right treatment pathway earlier in life, meaning better health."

Professor William Hagopian of the Pacific Northwest Research Institute, said: "We're really excited by these findings. They suggest that the routine heel prick testing of babies done at birth, could go a long way towards preventing early sickness as well as predicting which children will get type 1 diabetes years later. We're now putting this to the test in a trial in Washington State. We hope it will ultimately be used internationally to identify the condition as early as possible, and to power efforts to prevent the disease."

Researchers believe the combined approach can also be rolled out to predict the onset of other diseases with a strong genetic component that are identifiable in childhood, such as celiac disease.

Sanjoy Dutta, JDRF Vice President of Research, said:" We know that while genetics have a strong correlation as a risk factor for family members to develop T1D, most newly diagnosed individuals do not have a known family history. JDRF has been exploring the non-genetic, environmental risk factors that trigger T1D to help develop treatments to forestall or prevent disease onset."

New Haven, Conn. -- Researchers at the Yale Liver Center found that patients with COVID-19 presented with abnormal liver tests at much higher rates than suggested by earlier studies. They also discovered that higher levels of liver enzymes -- proteins released when the liver is damaged -- were associated with poorer outcomes for these patients, including ICU admission, mechanical ventilation, and death.

The study appeared online on July 29 in Hepatology.

Previous studies in China found that approximately 15% of patients with COVID-19 had abnormal liver tests. The Yale study, which looked retrospectively at 1,827 COVID-19 patients who were hospitalized in the Yale New Haven Health system between March and April, found that the incidence of abnormal liver tests was much higher -- between 41.6% and 83.4% of patients, depending on the specific test.

In all, the Yale researchers examined five liver tests, looking at factors such as elevations in aspartate aminotransferase (AST) and alanine transaminase (ALT), which indicate liver cell inflammation; an increase in bilirubin, which indicates liver dysfunction; and increased levels of alkaline phosphatase (ALP), which may indicate inflammation of bile ducts.

Although the researchers do not know why the incidence of abnormal liver tests was so much higher than in previous studies from China, senior author Dr. Joseph Lim, professor of medicine and director of the Yale Viral Hepatitis Program, said other health differences between the Chinese and U.S. populations could account for it.

"We can speculate that U.S. patients may have an increased rate of other risk factors such as alcoholic or non-alcoholic fatty liver disease," he said.

Liver disease is widespread in the U.S. population. Dr. Michael Nathanson, the Gladys Phillips Crofoot Professor of Medicine (digestive diseases), professor of cell biology, director of the Yale Liver Center, and a co-author of the study, said: "In the U.S., close to one-third of people have fatty liver disease, and several million people have chronic hepatitis B or C."

Because the Yale researchers had access to patients' health records, they were also able to look at their liver tests prior to being diagnosed with COVID-19. Approximately one-quarter of patients in the study had abnormal liver tests prior to being admitted for the virus. But regardless of whether patients came to the hospital with existing liver problems or developed them during their COVID-19-related hospitalization, a strong association was observed between abnormal liver tests and the severity of the COVID-19 cases, the researchers said.

Rather than the liver itself driving poorer outcomes in COVID-19 patients, the organ is more likely "a bystander" affected by the hyperinflammation associated with COVID-19 and by the side effects of related treatments, Nathanson said.

The study noted a relationship between drugs used to treat severe COVID-19 and liver damage, most significantly the drug tocilizumab.

"We observed a strong association between the use of COVID-19 medications and abnormal liver tests," said Lim, but added that they could not confidently tease out that the abnormal tests were due to "drug-induced liver injury" as opposed to the disease.

The researchers have additional clinical and lab-based studies underway to further understand COVID-19's impact on liver pathology. Nathanson noted that as one of only four National Institutes of Health-sponsored liver centers in the country, the Yale Liver Center is uniquely positioned to advance this research.

By applying the renewal theory in probability to reduce recall bias in initial case reports, scientists have come up with a new estimate for the incubation period of COVID-19. Their mean estimate of 7.76 days, longer than previous estimates of 4 to 5 days, involves the largest amount of patient samples to date in such an analysis. By providing health authorities with a potentially more accurate figure for the incubation period, the results could inform guidelines for containment efforts such as quarantines and studies investigating the disease's transmission. Countries and health authorities have implemented various containment measures such as quarantines to slow the spread of COVID-19. To work effectively, these strategies depend on understanding the disease's incubation period, or the time between someone becoming infected and showing the first symptoms of disease, and how much it varies from individual to individual. However, researchers lack a reliable estimate of the incubation period of COVID-19. The few existing estimates of 4 to 5 days were based on small samples sizes, limited data, and self-reports that could be biased by the memory or judgement of the patient or interviewer. Here, Jing Qin and colleagues developed a low-cost approach to estimate incubation periods and applied it to 1,084 confirmed cases of COVID-19 that had known histories of travel or residency in Wuhan, China. Their approach improves accuracy by relying on a public database of dates of infection, and uses the renewal theory in probability to reduce recall bias - the inaccurate recollection of past events. Ultimately, the team calculated that the median incubation period was 7.75 days, with 10% of patients showing an incubation period of 14.28 days. The authors note that this last finding may concern health authorities relying on the standard 14-day quarantine, but caution that their approach relies on several assumptions and may not apply to later cases where the virus may have mutated.

Discovering antiviral and anticancer drugs will soon be faster and cheaper thanks to new research from Simon Fraser University chemist Robert Britton and his international team.

For the past 50 years, scientists have used manmade, synthetic and nucleoside analogues to create drug therapies for diseases that involve the cellular division and/or the viral reproduction of infected cells. These diseases include hepatitis, herpes simplex, HIV and cancer.

But, says Britton, "That process has been intensive and challenging, limiting and preventing the discovery of new drug therapies."

Now, using the new process, scientists can create new nucleoside analogues months earlier than with the previous method, paving the way for quicker drug discoveries. A paper on this research was published today in the journal Science.

"The reduction in time and cost of synthesis will vary, depending on the individual nucleoside analogue, but we have examples where we cut a 20-plus step synthesis, which takes several months to complete at the very least, down to three or four steps, which would only take a week or so," says Britton.

"This is clearly a critical factor when it comes to treating newly evolved viruses like SARS-CoV-2 (COVID-19)."

The team shortened the process by replacing naturally occurring carbohydrates typically used for synthesising these types of drugs.

"This entirely new approach builds in opportunities to diversify these drug scaffolds and should inspire new and unusual nucleoside analogue drug discoveries," says Britton.

The team also replaced naturally derived chiral materials with achiral materials since they are generally cheaper and more versatile.

L.-C. Campeau, Merck's head of process chemistry and discovery process chemistry says, "One of our priorities is identifying problems limiting the speed of drug discovery and development, especially regarding synthesizing custom nucleoside analogues. We are very excited to collaborate with Professor Britton in establishing new methods to access this therapeutically important class of molecules."

A test designed by UCLA researchers can pinpoint which people with gonorrhea will respond successfully to the inexpensive oral antibiotic ciprofloxacin, which had previously been sidelined over concerns the bacterium that causes the infection was becoming resistant to it.

In research published in the peer-reviewed journal Clinical Infectious Diseases, a UCLA-led team found that of 106 subjects the test identified as having a strain of gonorrhea called wild-type gyrA serine, all were cured with a single dose of oral ciprofloxacin. Though the test has been available for three years, this is the first time it has been systematically studied in humans.

The new test gives doctors more choices to treat the sexually transmitted infection and could help slow down the spread of drug-resistant gonorrhea, said Dr. Jeffrey Klausner, the study's lead author and a professor of medicine in the division of infectious diseases at the David Geffen School of Medicine at UCLA.

"Gonorrhea is one of the most common drug-resistant infections worldwide and is becoming harder to treat. Current treatment methods require an antibiotic injection, which is expensive and painful," said Klausner, who is also an adjunct professor of epidemiology at the UCLA Fielding School of Public Health. "This new test could make it easier and safer to treat gonorrhea with different antibiotics, including one pill given by mouth.

"Using a pill instead of a shot would also make it easier and faster to treat sex partners of patients with gonorrhea," he added.

The ability of bacteria to change over time in ways that limit or eliminate the effectiveness of drugs designed to kill them has created a global problem. Gonorrhea is particularly skilled in this regard and has developed increasing resistance to all current antibiotics. Due to the spread of multidrug-resistant gonorrhea, public health authorities have declared it one of the top five urgent threats to public health.

Ciprofloxacin was used to treat gonorrhea until 2007, when the Centers for Disease Control and Prevention stopped recommending its use after gonococcal infections developed resistance to the drug.

Nevertheless, about 70% to 80% percent of gonorrhea infections in the United States could still be treated with ciprofloxacin. Scientists have been trying to determine how to better identify cases for targeted use of ciprofloxacin therapy, reducing the need to use the injectable antibiotic ceftriaxone and decreasing the risk of resistance to that drug. Gonorrhea's resistance rate to ceftriaxone is currently less than 1%.

The DNA test the researchers developed detects a particular genetic mutation in the gonorrhea bacterium that makes it resistant to ciprofloxacin. Ciprofloxacin is highly effective against infections without that mutation.

The researchers note that the findings are limited by the relatively small number of people studied and the fact that participation was limited to asymptomatic individuals. In addition, several people who were initially diagnosed with the wild-type strain through the test were subsequently found to be infected with other strain types.

WINSTON-SALEM, NC - Aug. 10, 2020, - A patient-specific tumor organoid model is being used to identify the most effective chemotherapy protocol to treat appendix and colon tumors, a personalized medicine approach that is showing promise. The organoids were created by researchers at the Wake Forest Organoid Research Center (WFORCE), a joint effort by the Wake Forest Institute for Regenerative Medicine (WFIRM) and the Wake Forest Comprehensive Cancer Center.

Treatment for advanced stages of colon and appendiceal cancer with spread in the abdomen consists of cytoreductive surgery which removes tumors from the organs in the abdominal area which is then followed by hyperthermic intraperitoneal chemotherapy (HIPEC). As its name suggests, HIPEC is a cancer treatment that involves filling the abdominal cavity with chemotherapy drugs that have been heated at a specific temperature. Paired together, the two treatments increase life expectancy for patients that in the past were deemed candidates only for palliative approaches.

With the patient-specific tumor organoid model, doctors can test the effect of HIPEC on individual tumors to tailor the conditions needed for optimal effect, thus providing a personalized medicine approach for each patient. Appendix cancer is a rare disease and affects only 1 in 100,000 people while as many as 200,000 people in the U.S. are diagnosed each year with colon cancer.

"Patients undergoing the combination of cytoreductive surgery and HIPEC endure a long surgery that lasts for many hours," said Konstantinos Votanopoulos, MD, PhD, professor of surgery and senior author of the study published recently in the journal Annals of Surgical Oncology.

The effect of intraperitoneal chemotherapy on the viability of the tumor of every individual patient is largely unknown, Votanopoulos said. "With this organoid platform we can quantify the impact of each drug in killing cancer cells. We can select the correct drug for the correct patient at the correct concentration and temperature, or even spare the patient from a procedure that will not substantially improve his or her outcomes."

An important finding of this work is that every tumor responds to heat differently with some tumors having showing dramatic response while others showing minimal or no meaningful response at all. The authors conclude this is probably related to genetically determined biologic machinery built in the cancer cells to counteract the impact of hyperthermia. Votanopoulos said a future hope would be to perform an image guided biopsy and grow organoids that will determine the optimal approach for each patient.

Shay Soker, PhD, a co-author and professor of regenerative medicine at WFIRM, said the study suggests that "the organoid model can accurately represent what occurs inside a patient's body. The research continues to show that organoids are promising candidates for drug screening to assist in clinical decision making as well as in the study of how environmental factors, viruses or toxins impact cellular function of both normal and tumor cells."

Organoids are tiny, 3D tissue-like structures created in the laboratory that mimic the function of human tissues and organs such as the heart, liver, lung, blood vessels, as well as cancerous tumors. The organoids are used as a testing and predicting platform to model diseases, evaluate efficacy and/or toxicity of new and existing drugs, and can also be used to test environmental hazards.

"Using a patient-specific tumor organoid model will eventually allow patients to be treated with the best available chemotherapy, while sparing the toxicity of drugs that are not effective for their specific tumor," said Steven Forsythe, MS, first author of the study.

Summary:

A nanomedicine-based strategy for chemo-immunotherapy (CIT) of glioblastoma (GBM), which has the worst prognosis among brain tumors, was successfully developed. In vivo experiments demonstrated that the combined use of epirubicin-encapsulating nano-micelles (Epi/m) with immune checkpoint inhibitors (ICI) eradicated PTEN-negative GBM, which is highly resistant to ICI alone. Due to the synergistic effects of Epi/m plus ICI combination, the number of tumor-infiltrating T cells (TIL) and other antitumor immune cells significantly increased to kill cancer cells effectively. On the other hand, intratumoral bone marrow-derived immunosuppressive cells (MDSC), which interfere with the immune response, were significantly reduced. The CIT also provided robust immunological memory effects against the tumors, which effectively rejected newly implanted PTEN-negative GBM cells in the brain. While free epirubicin can cause damage to organs, including hematopoietic organs especially, our nanomedicine strategy significantly reduced these side effects, improving the immune response. Epi/m has already advanced into clinical trials for other cancer types, and this CIT strategy could be expected to be translated to clinical evaluation in the future. These results has been published in ACS Nano (Impact Factor = 14.588 in 2019) issued on August 6 by the American Chemical Society.

The Innovation Center of Nanomedicine ((Director: Prof. Kazunori Kataoka, Location: Kawasaki-City, Abbreviation: iCONM) announced that a new therapeutic option for glioblastoma (GBM) was demonstrated in mice, in a collaboration study with the Department of Bioengineering, Graduate School of Engineering, The University of Tokyo. GBM is a brain tumor with extremely rapid progression and poor prognosis (5-year survival rate: 10.1%). Although several compounds are being evaluated in clinical studies, there is no therapeutic option to significantly improve the survival period. In particular, patients with abnormalities in the PTEN gene (Note 1), one of the cancer suppressor genes, are highly resistant to currently available therapies and have high medical needs. In general, immune checkpoint inhibitors (ICIs) (Note 2) are considered to ineffective against GBM, as GBM is immunosuppressive with low T cell infiltration. In the method presented in this paper, iCONM's nano-drug delivery technology allows selective tumor accumulation of epirubicin, which causes immunogenic cell death (ICD) (Note 3), to tumor tissues, thereby, causing ICD locally for synergizing with ICI. As a result, this nanomedicine-based chemo-immunotherapy (CIT) (Note 4) was effective in mice transplanted with GBM in the brain (hereinafter referred to as mouse GBM model), and succeeded in significantly prolonging mice survival. The combination of the epirubicin-loaded nano-micelles treated mice showed high infiltration of cytotoxic T cells (TIL) (Note 5) and decreased bone marrow-derived immunosuppressive cells (MDSC) (Note 6). Eventually suppression of the immune checkpoint function was observed.

Mutations in the PTEN gene occur frequently in GBM, resulting in immunosuppressive pathways that promote the resistance to ICIs. Thus, while ICIs eradicated 40% of tumors in a mouse GBM model in which the PTEN gene is normal, in a model in which the PTEN gene was knocked-out, ICIs were unable to extend mice survival. At the cellular level, it was found that PTEN-deficient cells (CT2A-luc) expressed approximately 5-fold more PDL1 than that of normal cells, which is probably connected to the therapeutic resistance with ICI. As epirubicin have shown the ability to suppress PDL1 expression in tumors, such as breast cancer (Note 7), it would be possible to decrease PDL1 levels of GBM if sufficient amount of epirubicin can be delivered into GBM lesions. Thus, CIT using nanomicelles containing epirubicin (Epi/m) in combination of ICI (Note 8) were used for enhancing the antitumor efficacy against GBM.

In a GBM model with normal PTEN expression (GL261-luc), Epi/m (5 mg/kg on Epi basis) plus anti-PD1 antibodies (5 mg/kg) resulted in the survival of all mice for more than 70 days, with a remarkable extension of survival time. In this model, PBS-treated mice died within 30 days, mice treated with anti-PD1 antibodies alone (5 mg/kg) allowed 40% of mice to survive for at least 70 days, and Epi/m (5 mg/kg of Epi basis) resulted 80% of mice survival for more than 70 days. In contrast, in the PTEN-deficient model (CT2A-luc), Epi/m (5 mg/kg on Epi basis) plus anti-PD1 antibodies (5 mg/kg) resulted in only 30% of mice survival for more than 70 days, and no clear survival effect could be confirmed for the other control groups. When the dose was increased to 15 mg/kg of Epi/m (in Epi basis) and combined with anti-PD1 antibodies (5 mg/kg), 90% of mice were able to survive for more than 70 days, remarkably prolonging mice survival.

FINDINGS

UCLA researchers have found that chemotherapy is not commonly used when treating adults with localized sarcoma, a rare type of cancer of the soft tissues or bone. In a nationwide analysis of nearly 20,000 patients whose cancer had not yet spread to other organs, the scientists learned that only 22% were treated with some form of chemotherapy.

The researchers found that even among patients with the largest and most aggressive tumors, less than half (45%) received chemotherapy. The team also found that patients were more likely to be treated with chemotherapy at facilities that perform at least 55 surgeries for sarcoma each year, versus people who received care at facilities that perform fewer such surgeries.

BACKGROUND

Although experts have debated the benefit of chemotherapy for people with localized sarcoma, several studies, including a recent randomized clinical trial, have demonstrated that chemotherapy can prolong the survival of patients with larger, more aggressive sarcomas. Because chemotherapy targets the cancer cells that have started escaping from the tumor and moving on to other places, such as the lungs or liver, it's often the only way to prevent or reduce the risk of the cancer spreading. Although it can cause side effects, like nausea and hair loss, chemotherapy can help prolong survival or even help cure patients of the disease.

Other studies, however, have not found a clear benefit to chemotherapy for treating localized sarcoma, so there is a lack of clear guidelines on the role, number of agents or timing of chemotherapy for managing high-risk sarcoma in adults.

METHOD

Using the National Cancer Database, researchers analyzed patterns of care for 19,969 adults who underwent surgery for primary high-grade soft tissue sarcoma from 2004 to 2016.

IMPACT

The study highlights the infrequent use of chemotherapy for people with sarcoma, especially at medical centers that treat fewer people with sarcoma, and it paves the way for future study on which patients might benefit most from chemotherapy as part of their treatment for sarcoma.

Four months ago, Michigan glowed red on COVID-19 maps. Hundreds of patients packed hospital intensive care units in the southern part of the state, and hospitals statewide rapidly put strict new visitor policies in place to slow the spread of the new coronavirus. ICU teams had to scramble to connect with the families of critically ill and dying patients in new ways.

Now, a new study documents how 49 of those hospitals reacted, and how those efforts varied. It finds that virtually all hospitals put in place a "no visitors" blanket policy. But 59% of hospitals did allow some exceptions to this rule, most often for end-of-life visits, even at the pandemic's regional peak in April and early May.

Meanwhile, ICU teams that had spent years increasing the involvement of family members in care decisions and patient support turned to telephones and video chats, including on newly purchased tablets and critically ill patients' own smartphones.

The new findings may hold lessons for hospitals in current and future COVID-19 hotspots, as they try to strike a balance between safety and human connection. The study, performed by a University of Michigan team, appears in the American Journal of Respiratory and Critical Care Medicine.

The authors say that as the pandemic continues, more studies are needed on how visitation and communication changes affect patients, families and care team members -- especially when patients can't communicate by themselves. They also point to the potential for restrictive visitor policies and virtual presence options to widen already stark health disparities.

Looking back

Lead author Thomas Valley, M.D., M.Sc., remembers all too well what those intense weeks of Michigan's peak were like, when the state had the fifth-highest ICU occupancy in the nation and hospitals stopped providing all but the most essential care.

He's an intensive care physician who was one of the first to work in a special COVID-19 ICU opened by Michigan Medicine, U-M's academic medical center.

On his first day, he took care of a patient who was clearly about to die, and whose daughter might have been able to come visit under Michigan Medicine's policy. But the daughter didn't want to risk exposure, so Valley found himself holding the patient's smartphone so the daughter could see her parent. She didn't want the patient to be without a family presence, even a virtual one, as they died.

"Talking with her was one of the most difficult things I've ever had to do as a physician, and I can't imagine what her family and so many others affected by this situation are going through," he says. "Conversations with families about critical care and the end of life are never easy, but it's so much harder to have them over the phone. For instance, I never thought about how important nonverbal cues are to these discussions."

This experience is what prompted him and colleagues, including U-M medical sociologist Katie Hauschildt, Ph.D., to perform the study by surveying ICU leaders in hospitals in urban, suburban and rural areas across the state by phone and computer in April and May.

More findings

While one hospital maintained a policy of allowing one visitor per ICU patient throughout, the rest of the state's hospitals cracked down hard on visitation. Nineteen of the hospitals surveyed were not allowing any visitors, without exception, at the time of the survey.

Of the 29 hospitals that allowed exceptions, 15 let visitors in to see patients at the end of life only. In another 13 hospitals, there were a few other exceptions besides end-of-life, including births, surgery and pediatric patients. One hospital considered each case individually.

Nine of the hospitals that allowed visitors only allowed one per patient, while 20 hospitals allowed more, often within a certain limit. A few hospitals required visitors to wear PPE or test negative for COVID-19 before coming to see their loved one.

More than 80% of the hospitals changed the way that ICU clinicians communicated with family members of critically ill patients. For the 17 hospitals that provided information about exactly what had changed, most said they were focusing on telephone - but 6 had started using video conferencing.

In addition, ICU leaders from two-thirds of all surveyed hospitals said they were encouraging video communication between patients and their family members using the patient's own tablets or smartphones.

As the pandemic continues, Valley and his colleagues continue to do research, even as Michigan's hospitalized COVID-19 cases remain much lower than in spring.

"These rules were put in place for good reasons, to keep patients, family and health care workers safe in the face of a new virus," he says. "But now we have the opportunity to reexamine and see if these restrictions really kept us safe, to see how common infection is when family comes to visit, and to evaluate what the other impacts were."

If hospitals implement exceptions to their no-visitation rules, or set other conditions, it's also important to be transparent and even-handed about how they're applied to each patient. For instance, defining which patients are now at the 'end of life' is not clear cut. And implicit biases may affect how clinicians decide to offer or grant visitation options to some families over others.

As visitor restrictions continue, and hospitals ramp up care for patients who do not have COVID-19, the importance of virtual communications facilitated by hospital teams will continue, says Valley.

"In normal times, most of our serious conversations except the most time-sensitive ones would be in person, and we might wait for the visitors to arrive before initiating the communication," he says. "In our study, we found that many hospitals were proactively calling their ICU patients daily, just to give updates."

Valley notes that previous studies have shown that more than a third of family members of ICU patients experience depression, anxiety or post-traumatic stress symptoms - and the inability to be with their loved one in person may make that more likely, whether or not their loved one has COVID-19. The same may be true for care team members who are used to speaking with families in person, especially if they need to communicate to a family member they've never seen that their loved one is near the end of life and discuss their wishes.

Boston - Results of a new study find that providers participating in an intervention with education and resources to help manage chronic opioid therapy for patients with HIV and chronic pain are more likely to adhere to national chronic opioid therapy guidelines compared to providers who do not take part. The intervention resources include a nurse care manager to work with physicians and nurse practitioners who are the primary care providers for such patients, and access to addiction medicine specialists. Led by researchers at Boston Medical Center's Grayken Center for Addiction, in collaboration with Emory University School of Medicine, the Grady Health System Infectious Diseases Program and published in Clinical Infectious Diseases, the study shows that the intervention is a promising tool that can help providers better treat their HIV patients with chronic pain who are already receiving chronic opioid therapy.

Previous research points to chronic pain being common among individuals with HIV. While chronic opioid therapy can be used to manage chronic pain, numerous studies have shown that providers caring for HIV patients have a low confidence in their ability to treat pain, as well as low satisfaction about how they deliver pain management to their patients.

"It's important to make sure that all providers have access to the tools and resources necessary for them to confidently provide chronic opioid therapy when treating patients with HIV and chronic pain while also working to prevent opioid misuse," said Jeffrey Samet, MD, MPH, the study's corresponding author and chief of general internal medicine at Boston Medical Center. Samet also is the John Noble, MD professor in general internal medicine and professor of community health science at Boston University Schools of Medicine and Public Health.

Targeting Effective Analgesia in Clinics for HIV (TEACH) was developed based on another chronic care model for the management of long term opioid treatment for pain (TOPCARE). The randomized control trial included 41 providers and 187 of their patients from two safety-net hospital-based HIV clinics. The study was conducted between 2015 and 2018 with a follow up at 12 months on patients with HIV receiving chronic opioid therapy to manage their chronic pain. Using medical records, the researchers looked at whether providers taking part in the intervention performed two or more urine drug screenings and if there were any early chronic opioid therapy refills within the 12-month period. The TEACH interventions include providers having access to: a nurse care manager with an interactive electronic registry to help manage patient cases and monitor prescription usage; a 60 minute didactic session on chronic opioid therapy guidelines; two or three sessions tailored to examining the providers' prescribing data and assessing future courses of action; and facilitated processes to refer patients to addiction specialists when necessary.

The results showed that providers who took part in the intervention were more likely to follow chronic opioid therapy guidelines, which are the recommendations established by both the Centers for Disease Control and Prevention and the HIV Medicine Association, compared to providers who followed usual care. In addition, the added monitoring was not associated with any adverse outcomes as reported by those in the study.

"Managing pain in persons with HIV may be challenging and the nurse care manager proved to be an effective way to support providers," Carlos del Rio, MD, executive associate dean of Emory University School of Medicine at Grady and co-principal investigator in this study with Samet.

CHAMPAIGN, Ill. -- Owners of electric multicookers may be able to add another use to its list of functions, a new study suggests: sanitization of N95 respirator masks.

The University of Illinois, Urbana-Champaign study found that 50 minutes of dry heat in an electric cooker, such as a rice cooker or Instant Pot, decontaminated N95 respirators inside and out while maintaining their filtration and fit. This could enable wearers to safely reuse limited supplies of the respirators, originally intended to be one-time-use items.

Led by civil and environmental engineering professors Thanh "Helen" Nguyen and Vishal Verma, the researchers published their findings in the journal Environmental Science and Technology Letters.

N95 respirator masks are the gold standard of personal protective equipment that protect the wearer against airborne droplets and particles, such as the coronavirus that causes COVID-19.

"A cloth mask or surgical mask protects others from droplets the wearer might expel, but a respirator mask protects the wearer by filtering out smaller particles that might carry the virus," Nguyen said.

High demand during the COVID-19 pandemic has created severe shortages for health care providers and other essential workers, prompting a search for creative approaches to sanitization.

"There are many different ways to sterilize something, but most of them will destroy the filtration or the fit of an N95 respirator," Verma said. "Any sanitation method would need to decontaminate all surfaces of the respirator, but equally important is maintaining the filtration efficacy and the fit of the respirator to the face of the wearer. Otherwise, it will not offer the right protection."

The researchers hypothesized that dry heat might be a method to meet all three criteria - decontamination, filtration and fit - without requiring special preparation or leaving any chemical residue. They also wanted to find a method that would be widely accessible for people at home. They decided to test an electric cooker, a type of device many people have in their pantries.

They verified that one cooking cycle, which maintains the contents of the cooker at around 100 degrees Celsius or 212 Fahrenheit for 50 minutes, decontaminated the masks, inside and out, from four different classes of virus, including a coronavirus - and did so more effectively than ultraviolet light. Then, they tested the filtration and fit.

"We built a chamber in my aerosol-testing lab specifically to look at the filtration of the N95 respirators, and measured particles going through it," Verma said. "The respirators maintained their filtration capacity of more than 95% and kept their fit, still properly seated on the wearer's face, even after 20 cycles of decontamination in the electric cooker."

The researchers created a video demonstrating the method. They note that the heat must be dry heat - no water added to the cooker, the temperature should be maintained at 100 degrees Celsius for 50 minutes and a small towel should cover the bottom of the cooker to keep any part of the respirator from coming into direct contact with the heating element. However, multiple masks can be stacked to fit inside the cooker at the same time, Nguyen said.

The researchers see potential for the electric-cooker method to be useful for health care workers and first responders, especially those in smaller clinics or hospitals that do not have access to large-scale heat sanitization equipment. In addition, it may be useful for others who may have an N95 respirator at home - for example, from a pre-pandemic home-improvement project - and wish to reuse it, Nguyen said.

What The Article Says: The COVID-19 pandemic has forced oncology clinicians and administrators in the United States to set priorities for cancer care because of resource constraints. As oncology practices adapt to a contracted health care system, expertise gained from partnerships in low-resource settings can be used for guidance. This article provides a primer on priority setting in oncology and ethical guidance based on lessons learned from experience with cancer care priority setting in low-resource settings.

Authors: Rebecca J. DeBoer, M.D., M.A., of the University of California, San Francisco, is the corresponding author.

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

(doi:10.1001/jamaoncol.2020.2976)

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

What The Study Did: A practical communication guide designed for oncologists to assuage the fear, anger and anxiety among patients with cancer during the COVID-19 pandemic is proposed in this qualitative study.

Authors: Reshma Jagsi, M.D., D.Phil., of the University of Michigan in Ann Arbor, is the corresponding author.

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

(doi:10.1001/jamaoncol.2020.2980)

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

The BCG vaccine, a vaccine originally made against tuberculosis, has a general stimulating effect on the immune system and is therefore effective against multiple infectious diseases - possibly also against COVID-19. This study compared groups of volunteers who have received a BCG vaccine (or not) in the past five years (before the corona pandemic), showing that the vaccine is safe and possibly influences COVID-19 symptoms.

The results of this research have now been published in Cell Reports Medicine.

The Bacille Calmette-Guérin or BCG vaccine is the most widely received vaccine in the world. Originally intended to treat tuberculosis, it later became apparent that it provides a long-lasting, general boost to the innate immune system. The vaccine was therefore also effective against other conditions. At Radboud university medical center, Professor of Experimental Internal Medicine Mihai Netea and his team conduct research into these effects, referred to as "trained immunity".

The 300BCG study is a result of his work, in which a group of healthy volunteers received the BCG vaccine and could thus be compared to a group of healthy volunteers who did not. Most volunteers received the vaccine between April 2017 and June 2018. The purpose of that study was to determine the difference in the immune response, but now that the corona pandemic is present, the same subjects were questioned to see if there is an effect of the vaccine on the symptoms attributable to infection with the SARS-CoV-2 virus.

It's safe, perhaps a positive effect

What the comparison between the groups shows is that those who received the vaccine did not have more symptoms, did not get sick more often or become more seriously ill, during the first wave of the COVID-19 pandemic in the Netherlands. The data show also a cautiously positive picture, with a lower number of sick people in the period March-May 2020 among the BCG-vaccinated group, and also lower incidence of extreme fatigue among the vaccinated individuals.

The researchers underline that this was to be expected given the well-known effects of the BCG vaccine on healthy volunteers. However, the study also has limitations that prevent conclusions from being drawn regarding the benefit of the BCG vaccine against the novel coronavirus: "It is very important to confirm that someone who has been vaccinated with BCG does not experience any increased symptoms during the COVID-19 pandemic. Although we see less sickness in the people who have had the BCG vaccination, only the ongoing prospective BCG vaccination studies can determine whether this vaccination can help against COVID-19", says professor Mihai Netea of Radboudumc.

Various clinical randomized trials are already underway to answer this question, including several in the Netherlands.

A pre-clinical study led by scientists at Cincinnati Children's demonstrates that in mice the drug barasertib reverses the activation of fibroblasts that cause dangerous scar tissue to build up in the lungs of people with idiopathic pulmonary fibrosis (IPF).

Findings were posted online Aug. 8, 2020, in the journal EMBO Molecular Medicine. The study was led by Rajesh Kasam, PhD, Division of Pulmonary Medicine, and co-corresponding authors Satish Madala, PhD, Division of Pulmonary Medicine, and Anil Goud Jegga, DVM, MRes, Division of Biomedical Informatics.

The discovery suggests that a powerful treatment for a fatal disease that currently has no cure other than lung transplantation may be within a few years of launching human clinical trials.

"This study is the first to identify barasertib as an anti-fibrotic candidate," Madala says. "That's important because so far there are no treatments for IPF that appear to reverse the underlying process that causes the disease."

What is IPF?

Idiopathic pulmonary fibrosis is a chronic, progressive lung disease that usually affects people between the ages of 50 and 70, according to the National Institutes of Health. About 100,000 people in the US have IPF with 30,000 to 40,000 new cases diagnosed each year. Survival time varies, but most people live about 3 to 5 years after diagnosis.

Scientists believe a combination of genetic predisposition and environmental factors trigger IPF, but the exact causes and mechanisms remain unknown.

Currently, there are two approved drugs that can help slow the disease; Ofev (nintedanib) and Esbriet (pirfenidone). But both can cause have serious side effects. Doctors also use oxygen supplementation and other symptom management methods to prolong survival. Ultimately, however, people with IPF have needed lung transplantation, but the supply of donor organs is limited.

Scientists at Cincinnati Children's have been studying this disease because lung scarring also occurs in children.

"Pulmonary fibrosis is a major cause of death in both adult and pediatric chronic lung disease," Madala says. "Also, several genetic mutations have been identified in pediatric populations that have been shown to cause familial IPF. Identifying anti-fibrotic therapies will help to treat multiple chronic fibrotic lung diseases."

New clues emerge about how fibrosis occurs

In the new study, the co-authors reveal that a gene called aurora kinase B (AURKB) is expressed in high levels within the cells of lung scar tissue (also known as fibroblasts). This gene expression appears to be driven by multiple growth factors and a transcription factor called Wilms Tumor 1, the study states.

The team used several technologies to hunt through hundreds of possibilities to find this genetic connection, including gene expression data from IPF patients, transcriptional signatures from approved and investigational drug-treated cells, and a software tool developed at Cincinnati Children's called ToppFun. Once the team identified the involvement of barasertib, a known AURKB inhibitor, they explored the therapeutic relevance, underlying mechanistics and target pathways related to pulmonary fibrosis.

What is Barasertib?

Barasertib, made by AstraZeneca Pharmaceuticals, is a powerful aurora kinase inhibitor that has shown promise as a potential cancer treatment. In fact, the drug is being studied in Phase I/II clinical trials as a possible treatment for acute myeloid leukemia (AML).

The collaborators in this study used the drug to treat mice that were induced to develop lung disease that mimics human IPF. They found that inhibiting AURKB activity helped the mice in multiple ways.

Those treated with barasertib before developing lung fibrosis were less likely to do so once scar formation was induced. Once fibrosis had started, introducing the drug significantly slowed further disease progress, primarily by causing faster cell death among the fibroblasts. The results of treatment included less scar tissue, improved lung elasticity, and overall better lung function.

"These findings have therapeutic implications as they suggest targeting AURKB activity inhibits fibroblast activation, particularly when multiple pro-fibrotic growth factors promoting alternative fibroproliferative pathways are present," the co-authors state. "Together, our preclinical studies provide important proof-of-concept that demonstrate barasertib as a possible intervention therapy for IPF."

What's next?

"Since the current project was conducted in mouse models and human cells derived from lung biopsies of IPF patients, additional studies are needed to determine whether targeting AURKB would be effective and safe enough to test in human patients," Jegga says.

Also, barasertib is known to have systemic exposure-related side effects. Therefore, as part of ongoing and future work, the researchers are exploring alternative routes of administration to bypass systemic exposure and ensure targeted delivery.