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DALLAS, May 20, 2020 -- Women receiving treatment in primary care received some cardiovascular medication prescriptions at a lower rate than men, according to new research published today in the Journal of the American Heart Association, an open access journal of the American Heart Association.

"Additional efforts need to be taken to ensure that everyone, women and men, who should receive cardiovascular medications are actually prescribed these medications," said lead study author Sanne Peters, Ph.D., research fellow in epidemiology at the George Institute for Global Health at the University of Oxford in the United Kingdom and associate professor at the University Medical Center Utrecht in the Netherlands. "We also need to reduce the persistent treatment gaps between women and men."

Cardiovascular disease (CVD) is the leading cause of death worldwide. Lifestyle changes, including maintaining a healthy weight, quitting smoking, being physically active, eating a healthy diet, controlling high blood pressure and cholesterol, and reducing high blood sugar, can lower heart disease risk. "For some people, however, medication also may be necessary to reduce risk," Peters noted.

Previous research among heart attack survivors found that women were less likely to receive recommended medications in a hospital setting. In this study, researchers wanted to understand whether this occurs even earlier, in primary care and among patients at high risk or with existing cardiovascular disease.

A systematic review of two large medical databases was conducted to find studies with data showing the number of cardiovascular-disease prescriptions among men and women. Researchers looked specifically for studies with data on statin prescriptions, which lower cholesterol; aspirin, which decreases the risk of blood clots; and blood-pressure lowering medications, including ACE-inhibitors and diuretics.

A total of 43 international studies with data on primary-care prescriptions among more than 2.2 million patients (28% women; average age 51-76 years) who were at risk for heart attack were evaluated. Among the findings, the analysis indicates women received:

19% fewer aspirin prescriptions than men;

10% fewer statin prescriptions than men; and

15% fewer ACE-inhibitor prescriptions than men.

However, women were 27% more likely than men to be prescribed diuretics.

"Patients should talk with their physicians about the benefits of using heart disease medications and weigh them against the potential risks," Peters said.

This analysis had limitations. For example, it could not control for differences in the 43 separate studies, and there was limited information about combined medications or other health conditions in addition to heart disease. Finally, the researchers examined sex differences in prescriptions only, not the effects of these differences on cardiovascular risk and events.

(Boston)--Higher blood pressure during exercise and delayed blood pressure recovery after exercise are associated with a higher risk of hypertension, preclinical and clinical cardiovascular disease and death among middle-aged to older adults.
Blood pressure responses to exercise are significant markers of cardiovascular disease and mortality risk in young to middle-aged adults. However, few studies have examined the associations of midlife blood pressure responses to submaximal (less than the maximum of which an individual is capable) exercise with the risk of cardiovascular outcomes and mortality in later life.

Researchers from Boston University School of Medicine (BUSM) evaluated the association of blood pressure changes and recovery with indicators of preclinical disease among participants from the Framingham Heart Study (average age 58 years, 53 percent women). They then followed these participants to assess whether these blood pressure changes were associated with the risk of developing hypertension, cardiovascular disease or dying.

They observed that both higher exercise systolic blood pressure (SBP) and exercise diastolic blood pressure (DBP) were associated with a greater risk of developing hypertension. Additionally, both delayed SBP and DBP recovery after exercise were associated with higher risk of cardiovascular disease and death.

"The way our blood pressure changes during and after exercise provides important information on whether we will develop disease in the future; this may help investigators evaluate whether this information can be used to better identify people who are at higher risk of developing hypertension and CVD, or dying later in life," explained corresponding author Vanessa Xanthakis, PhD, assistant professor of medicine and biostatistics at BUSM and an Investigator for the Framingham Heart Study.

Xanthakis recommends that people know their blood pressure numbers, speak to their physician regarding changes during and after exercise and follow a healthy lifestyle (including a regular physical activity schedule) to help lower risk of disease later in life.

These findings appear online in the Journal of the American Heart Association.

ARLINGTON, Va., May 20, 2020 - Despite facing challenges such as limited access to personal protective equipment (PPE) following the COVID-19 outbreak, radiation oncology clinics quickly implemented safety and process enhancements that allowed them to continue caring for cancer patients, according to a new national survey from the American Society for Radiation Oncology (ASTRO). All 222 physician leaders in the survey, which was in the field April 16-30, said their practices continued to provide radiation therapy services during the early weeks of the pandemic, yet 85% also reported declines in the number of patients seen, by an average of one-third.

Once the COVID-19 threat was apparent, radiation oncology clinics adapted their safety protocols so they could continue to care for patients and protect their staff, although 69% experienced limited access to or shortages of PPE. Protective measures included, for example, requiring masks for staff (99%) and patients (83%), screening patients at the clinic door (98%), social distancing (98%) and not allowing visitors (90%).

"Safety has always been at the forefront of radiation oncology, and when the COVID-19 threat emerged, clinics quickly updated their safety protocols to minimize exposure risk and protect their patients and staff. The rapid adoption of masking, social distancing and other protective measures meant that radiation oncologists largely have been able to be resilient and provide care without compromise throughout the initial months of this pandemic," said ASTRO Board Chair Theodore L. DeWeese, MD, FASTRO.

Telehealth patient consultations also emerged as an important aspect of continuing care. Radiation oncology clinics quickly adopted telemedicine consultations, with nearly all respondents saying this was a new offering for their patients. In the survey, 89% of respondents said their clinics offered patients telemedicine options for consultations and follow-up visits.

Despite these changes, patient volume declined substantially at most radiation therapy clinics. On average, physicians said they were seeing two-thirds of their typical number of patients. These decreases were due mostly to delayed/deferred treatment (82%) and fewer patients being referred for radiation therapy (81%) by other physicians.

The survey also pointed to financial challenges caused by COVID-19. All respondents estimated their clinics would lose revenue, most commonly in the range of 21-30%. Freestanding radiation oncology clinics are expected to face disproportionately higher financial difficulty, with one in five predicted to lose more than half of its annual revenue due to the pandemic.

"The emergency relief funding and flexibilities from the Congress and the Trump Administration provided a lifeline for radiation oncology clinics. It will not be enough to sustain hard-hit practices that will continue to experience decreased treatments, however, as patient volumes likely decline further due to recent drops in cancer screenings, biopsies and surgeries. ASTRO continues to ask Congress and the Administration for more resources and direct financial assistance to support radiation therapy practices and the patients they serve," said Dr. DeWeese.

The majority of practices experienced staff reductions, due mainly to declines in patient volume (49%) and increased family care responsibilities (28%). Very few had reductions due to COVID-19 illness among staff members (11%).

This is the initial report of a longitudinal survey, and future reports will examine changes over time. Survey details are available in the Executive Summary.

In response to the COVID-19 outbreak, a workgroup convened by ASTRO leadership issued clinical guidance for radiation oncology practices in mid-March. Resources include FAQs that address common questions and a summary of the recommendations. ASTRO also collaborated with the European Society for Radiotherapy and Oncology (ESTRO) to publish guidelines for lung cancer radiotherapy and head and neck cancer radiotherapy during the pandemic.

Radiation oncologists shared their experiences and advice for patients and fellow providers via case reports and research in ASTRO's peer-reviewed journals, blog posts with provider stories, and webcasts including an update on radiation oncology care with the National Coalition for Cancer Survivorship and a discussion of cancer patient safety with the Infectious Disease Society of America.

"Although COVID-19 has presented us with unprecedented challenges and forced us to think anew, our goals as radiation oncologists remain unaltered," said Dr. DeWeese. "We stand resilient and ready to care for our patients, today and always."

Pregnant women who take the thrush treatment fluconazole orally appear to have a higher risk of giving birth to a baby with muscle and bone malformations, suggests research published by The BMJ today.

However, the absolute risk is small and there is no association between taking the treatment and babies having heart defects or oral clefts, as previously feared, US researchers found.

Vulvovaginal candidiasis, commonly known as thrush, is common in pregnant women and the recommended treatment is usually a short course of topical antifungal agents or one dose of oral fluconazole (150mg).

Although the topical antifungal treatment is available over the counter in many countries, oral fluconazole is often preferred by patients because of the convenience of taking one oral dose.

Previous studies have suggested that high doses of fluconazole can be harmful and cause cleft palate and skeletal abnormalities, while use of the treatment carries an additional potential risk of congenital malformations in babies of women who take them during the first trimester of their pregnancy.

However, findings from these studies have been inconsistent.

US researchers, therefore, set out to examine the risk of congenital malformations associated with exposure to oral fluconazole from commonly used doses in women taking it during the first trimester of pregnancy to treat thrush.

They carried out a study using data from the nationwide Medicaid Analytic eXtract (MAX) database between the years 2000 and 2014.

The MAX includes a set of patient level files with information on patients' Medicaid enrollment, demographics, diagnoses, and procedures at all outpatient and inpatient settings, as well as dispensing records for outpatient prescription drugs for reimbursement.

For their study, the researchers identified pregnant women aged 12 to 55 who were continuously enrolled in Medicaid from three or more months before the last menstrual period to one month after delivery, and infants enrolled for three or more months after birth.

The study group of 1,969,954 pregnancies included 37,650 (1.9%) pregnancies exposed to oral fluconazole and 82,090 (4.2%) pregnancies exposed to topical antifungal treatment during the first trimester.

Results showed that the risk of musculoskeletal malformations was 52.1 per 10,000 pregnancies exposed to fluconazole compared with 37.3 per 10,000 pregnancies exposed to topical treatment.

Using oral fluconazole in the first trimester was not found to be associated with oral clefts or heart defects (conotruncal malformations).

However, the risk of musculoskeletal malformations was double in women taking the highest dose in early pregnancy (above 450mg), but absolute risks were still small (12 incidents per 10,000 exposed pregnancies overall).

There was also a 30% increased risk amongst women who had taken a smaller cumulative dose of 150mg of oral fluconazole.

The study had some limitations such as the fact that the number of outcomes for the least common malformations was relatively low, the researchers were unable to determine if the women consumed the dispensed drug, and there were unmeasured or poorly measured variables such as obesity or overweight which could account for the increased risk.

Nevertheless, the study had a large sample size, it used pharmacy prescriptions to calculate exposure, and generated evidence more applicable to clinical decision making, with careful control for a broad range of potential confounding variables and sensitivity analyses to address the concerns about unmeasured confounding.

The researchers conclude: "Our study confirmed an increase in the risk of musculoskeletal malformations if fluconazole is used during the first trimester, and refuted large increased risks of conotruncal malformations, oral clefts, and other specific types of malformations.

"Oral fluconazole during the first trimester, especially prolonged treatment at higher than commonly used doses, should be prescribed with caution, and topical azoles should be considered as an alternative treatment."

MINNEAPOLIS - A blood test may help predict which people with multiple sclerosis (MS) will get worse during the following year, according to a study published in the May 20, 2020, online issue of Neurology®, the medical journal of the American Academy of Neurology.

"In a disease like MS that is so unpredictable and varies so much from one person to the next, having a noninvasive blood test like this could be very valuable, especially since treatments are most effective in the earliest stages of the disease," said study author Ali Manouchehrinia, PhD, of the Karolinska Institutet in Stockholm, Sweden.

The blood test looks for a biomarker called neurofilament light chain, a nerve protein that can be detected in the blood when nerve cells die.

The study involved 4,385 people with MS and 1,026 people matched for age and sex who did not have MS. The level of the biomarker in the blood was tested in all of the participants. The participants were followed to see which people with MS got worse during the following year and then which reached continued, increased levels of disability over a total of five years. They also looked at whether people with high levels of the protein were more likely to develop worsening of disability during the following years, and later a more serious stage of the disease, called secondary progressive MS.

The people with MS had an average of 11.4 picograms per milliliter (pg/ml) of the nerve protein in their blood compared to an average of 7.5 pg/ml for the people who did not have MS.

The people with MS with high levels of the protein were 40% to 70% more likely to have worsening disability during the next year than those with low levels of the protein. These results took into account other factors that could affect their risk of worsening disability, such as how long they had the disease and how often they were having relapses at the start of the study.

The people with high protein levels were also 50% more likely to reach either a level of moderate disability that affected daily activities but not walking ability, or significant disability that impaired walking but still meant people were able to walk without help or rest for 500 meters. A total of 525 people reached the moderate level of disability, or 16%, and 352 people, or 9% reached significant disability.

The researchers found that high protein levels were not consistently associated with a greater risk of more significant disability, defined as needing a cane or crutch to walk 100 meters, or with the risk of developing secondary progressive MS.

"These results suggest that elevated levels of these proteins measured early on in the course of the disease may help us to predict how the disease will develop and monitor how treatment is working," Manouchehrinia said. "More research is needed before a blood test could be used routinely in the clinical setting, but our results are encouraging."

He said that a limitation of the study was that the level of the nerve protein varied significantly and overlapped between the people with MS and the people without the disease, and it is likely that the levels are influenced by other factors, such as other medical conditions, that were not analyzed in the study.

HAMILTON, ON (May 20, 2020) -A huge study of more than 160,000 people in 21 countries has found that women are less likely to have cardiovascular disease, and die of it, than men.

It didn't matter if women had, or didn't have, a previous heart attack or stroke. It also didn't matter where they lived around the world, nor their economic status.

The study from the Population Health Research Institute (PHRI) of McMaster University and Hamilton Health Sciences was published in The Lancet today. The information came from the Prospective Urban Rural Epidemiological (PURE) study which followed the participants an average of 10 years.

It is the first global study to document the risk factors, use of treatment, incidence of heart attacks and strokes and mortality in people from the community, rather than just hospital patients.

The study found that women with no history of cardiovascular disease (CVD) were more likely to use preventative medicines, control hypertension and to have quit smoking, compared to men.

"There have been concerns that women with CVD are managed less aggressively than men which could lead to women having poorer prognoses. Some have attributed this to a treatment bias against women," said Marjan Walli-Attaei, the first author and a research fellow at the PHRI.

"In our global study we observed that while prevention strategies were used more often by women, invasive strategies such as percutaneous coronary intervention and coronary artery bypass surgery was used more often for men.

"But, overall, outcomes such as death or a new heart attack or stroke in women were lower than in men. This suggests there may be factors other than a treatment bias against women that contribute to the treatment differences."

Co-author Annika Rosengren, a professor of the University of Gothenburg in Sweden, said that the lower rates of invasive cardiac treatments of women with CVD could be partly explained by the fact that fewer women than men have the type of extensive atherosclerosis that requires medical interventions.

"Other studies have reported that the sex differences in invasive cardiac procedures are not seen once we consider the extent and severity of the coronary artery disease. This suggests that the lower rates of coronary interventions in women is appropriate as they have less extensive disease," she said.

There is, however, substantial concern about the differences in treatment between poorer and richer countries, said Salim Yusuf, professor of medicine at McMaster University and the principal investigator of the PURE study.

"The differences in outcomes in both women and men in low-income countries, where approximately 40% die within 30 days of a heart attack or stroke compared to the less than 10% in high-income countries, is matter of substantial concern. This deserves major attention," he said.

The COVID-19 pandemic is stressful enough, but for children and adults with autism spectrum disorder (ASD) and their families, the crisis can be especially difficult.

Adrien A. Eshraghi, M.D., M.Sc., professor of Otolaryngology, Neurological Surgery and Biomedical Engineering, has dedicated much of his career to caring for individuals with various disabilities including individuals with autism, who are very dear to him.

Dr. Eshraghi and Miller School coauthors published a new correspondence titled COVID-19: overcoming the challenges faced by individuals with autism and their families in The Lancet Psychiatry*. In this commentary, the authors address specific challenges patients with autism and their families might encounter during the pandemic, as well as what healthcare providers should know and do to ensure optimal and safe care.

Chances are good that providers caring for COVID-19 patients in all settings, including the emergency room (ER) and inpatient settings, will encounter adults and children with autism.

"Autism spectrum disorder prevalence has increased significantly in the last 20 years. In 2004, the prevalence of autism was 1 in 166. Today the Centers for Disease Control (CDC) estimates that 1 in 54 children are on the autism spectrum", according to Dr. Eshraghi, who also is the director of the University of Miami Hearing Research and Communication Disorders Laboratory and co-director of the University of Miami Ear Institute.

The goal of this paper is to define the challenges these patients face in a pandemic like this, so physicians, caregivers, and the overall health system can better anticipate and meet the needs of these particular patients. At a time when everyone is stressed about contracting COVID-19, becoming better educated about how to manage patients with autism will increase patient and provider safely, while appropriately helping these patients and their families."

People with autism are at higher risk for COVID-19 complications, according to the CDC. This is because they tend to have immune disorders and other comorbidities.

The process of isolating can be especially hard on children with autism and their families. The pandemic disrupts routine, which is problematic for these patients and caregivers. Patients might have difficulty comprehending the situation and expressing themselves.

Depending on where they are on the spectrum--from extremely high to low functioning --patients might have challenges with communicating, hyperactivity, and behavioral issues. Some individuals on the spectrum are extremely sensitive to sound or bright light.

Because of all these multiple challenges which may be experienced at the same time in some instances, people with autism and their caregivers are likely experiencing heightened stress during this time.

If patients need medical care during the pandemic, the situation for patients and their families often becomes even more overwhelming, according to Dr. Eshraghi.

"The healthcare environment, especially in the emergency room, can be difficult and overstimulating for people with autism spectrum disorder possibly due of the crowd, sounds and lights," Dr. Eshraghi said. "It's important to reduce that stress. For example, caregivers are not allowed into many ER exam and hospital rooms during the pandemic. But in the case of autism, patients need their caregivers to help keep them be calm and facilitate communication with providers."

Dr. Eshraghi recommends that ERs train staff to recognize the signs of autism and understand how to best manage these patients. Often, that means thinking out of the box.

If the patient is running around the ER waiting room, for example, it is not because the parents don't know how to discipline the child, but rather the child is overwhelmed because of the environment.

"Another issue with people on the spectrum is that some don't have a concept of having to wait for their turn, so they're impatient when they have to wait," Dr. Eshraghi said.

At a time when it is important to wear masks, children with autism might refuse or take off their masks because of sensory issues.

Potential solutions include bringing the child and caregiver to wait in an exam room, rather than keeping them in the waiting room. If the patient keeps taking off his or her mask, provide parents with additional masks to keep the child, parents, and providers safe.

Telehealth can also be a viable and promising solution, but research is needed to develop telehealth services geared specifically toward people with autism, he said. It might actually be even an opportunity for many kids on the spectrum to use these online services, even post COVID-19.

"It's important that providers and hospital staffs not judge those parents and avoid unintentional discrimination, simply because they don't understand the behaviors of a person on the autism spectrum," Dr. Eshraghi said.

A pandemic presents a perfect storm of challenges for patients with autism and their family.

"We need policies to help those people who are more vulnerable during a pandemic," Dr. Eshraghi said. "Hopefully, this paper will bring these patients' needs and potential solutions to light."

"Those with autism spectrum disorder are not just another vulnerable population in the context of COVID-19. While they may share similar needs with other vulnerable groups, some are in fact quite unique. We hope our commentary begins to provide a framework for strategic enhancement and investment in healthcare, therapy, education, and family support during future crises" said co-author Michael Alessandri, Ph.D., executive director of the University of Miami-Nova Southeastern University Center for Autism and Related Disabilities (CARD).

"The care required by individuals with ASD and their families during this pandemic is the care we all desire for ourselves and our families" said co-author Daniel S. Messinger, Ph.D., professor and coordinator of the Developmental Psychology Program.

"It is imperative to understand the challenges encountered by individuals with ASD and their families in this era of COVID-19 to develop solutions for ameliorating or mitigating these challenges" said co-author Rahul Mittal, Ph.D., researcher in Dr. Eshraghi's Hearing Research and Communication Disorders Laboratory at the University of Miami Miller School of Medicine.

A team of scientists from Hollings Cancer Center at the Medical University of South Carolina (MUSC) has developed a novel flow cytometry technique that can, for the first-time, quantify protein production in T-cells. T cells are immune cells that surveil the body and can effectively target and kill cancer cells. However, when T cells are in the vicinity of a tumor, cancer cells sap their energy, leading to a decrease in their protein production. This change leads to T cells losing their tumor-killing ability.

The new technique, developed by the MUSC team, can be used to monitor protein production in T cells and understand how it becomes depressed in the tumor microenvironment. Interventions could then be developed to restore T cells' protein production and ability to control tumor growth. The team, led by Jessica E. Thaxton, Ph.D., recently reported its findings in a priority brief in Cancer Immunology Research. Thaxton is an assistant professor in the departments of Orthopaedics and Physical Medicine and Microbiology and Immunology at MUSC and a member of Hollings Cancer Center, a National Cancer Institute designated cancer center.

"This study reveals our first attempt at trying to understand how T cells undergo the process of making proteins," explained Thaxton. "Before this paper or before this technology, scientists had very little idea how much protein T cells make. It was a shot in the dark. But now we have quantitative data that shows how much protein T cells make, and we can begin to ask questions like, 'Which proteins?' and 'How are they made?'"

In the past four years, the team observed more than 50 human tumors, and in most tumors, they noticed the existence of T cells that made very little protein. This finding led them to surmise that there are T cells unable to make proteins residing in tumors. According to Thaxton, the new technology will help them to monitor these T cells and reawaken their protein production machinery and cancer-fighting ability.

"This paper establishes that T cells that are able to make protein in tumors have phenomenal ability to control tumor growth," explained Thaxton. "We ultimately want to remodel the existing T cell population in tumors, and that is really where our laboratory is headed."

To understand more fully protein production in T cells in tumors, the scientists used two different types of signaling molecules (cytokines) called IL-15 and IL-2. It has been established in other studies that T cells treated with IL-15 control tumor growth very well, but those conditioned with IL-2 do so poorly. The team found that T cells conditioned with IL-15 were able to make proteins in the tumor microenvironment and in tumors, whereas IL-2 conditioned T cells experienced diminished protein production in tumors.

These results will help scientists to understand how they can reawaken tumor T-cells and increase their protein production, thereby enhancing their ability to control tumor growth. Thaxton believes that a simple strategy of combining a modulator that changes the way that T cells generate energy will allow T cells to experience sustained protein production in tumors and produce more effective immunotherapy treatments for patients.

Unlike many current immunotherapies, which can be quite expensive, this approach would be cost-effective and thus a more realistic strategy for treating cancer patients from all walks of life.

Thaxton believes that the current study is the very first set of experiments that begins to delineate the role of protein production in anti-tumor immunity.

"There is a lot more in store that we are now uncovering from this basic first set of experiments," explained Thaxton. "This paper is a model of our first insight into how protein production is regulated in T cells, and we are working on which parts of the regulation are the most important for tumor control."

The coronavirus pandemic's life-altering effects are likely to result in lasting physical and mental health consequences for many people--particularly those from vulnerable populations--a new study led by the Yale School of Public Health finds.

Assistant Professor Sarah Lowe and colleagues studied low-income women from New Orleans who were surveyed the year prior to, and at intervals after Hurricane Katrina struck in 2005. The women reported a range of traumatic experiences during Katrina, many of which are similar to those now occurring during the pandemic, including bereavement, lack of access to medical care and scarcity of medications.

The research showed that at one, four and 12 years after the hurricane, the exposures most strongly associated with posttraumatic stress, psychological distress, general health and physical health symptoms were those most common to the current pandemic. The pandemic continues to cause widespread death and sickness, as well as job loss and severe economic hardship for many.

"This pandemic is likely to have profound short- and long-term consequences for physical and mental health," said Lowe. "These impacts are likely to be even larger than what we have seen in previous disasters like Hurricane Katrina, given the distinctive qualities of the pandemic as a disaster."

The study did not include other exposures that are taking place during the pandemic, such as financial losses and unemployment, which are also likely to have additional and significant impacts on public health.

The study is published in the journal Proceedings of the National Academy of Sciences.

The study results suggest that, in addition to promoting actions to reduce COVID-19 transmission and addressing longstanding health disparities contributing to COVID-19 morbidity and mortality, public health measures should also prevent and mitigate exposures that will have indirect effects on mental and physical health. This includes preventing lapses in medical care and medication access.

Additionally, another key exposure in the study was fear for one's own safety and the safety of others. As such, public health messaging should provide tips for managing anxiety and fear, in addition to promoting efforts to increase safety from COVID-19 transmission. Supplemental health services should be provided to those who are bereaved or are experiencing clinically significant fear and anxiety related the pandemic, Lowe said.

Although a large body of previous research has shown that greater exposure during a disaster is associated with adverse mental and physical health outcomes, most studies have relied on counts of different disaster-related exposures rather than separately examining specific trauma and stressors upon which policymakers and practitioners can intervene, Lowe said. Moreover, few studies have adjusted for preexisting health conditions or socioeconomic vulnerabilities.

"This study represents a step toward disentangling the health consequences of disasters, while also recognizing more longstanding factors that contribute to health disparities," she said.

Soon after coronavirus appeared, an all-encompassing quarantine put into effect by the Chinese government slowed the spread of the disease and saved lives, but the quarantine also produced another unanticipated health benefit.

A new study led by researchers at the Yale School of Public Health and published in the journal Lancet Planetary Health, finds that China's countrywide ban on traffic mobility from February 10 to March 14 greatly limited automobile emissions and sharply reduced the country's often severe air pollution.

The improved air quality, in turn, prevented thousands of pollution-related deaths. More premature deaths were avoided by cleaner air--an estimated 12,125--than lives lost from the pandemic--4,633 as of May 4, the study finds.

"This is a very surprising result. The pandemic continues to be a terrible thing for China and the rest of the world, but the decrease in emissions that accompanied it has actually conferred some positive health results," said Kai Chen, assistant professor at the Yale School of Public Health and the study's first author. "The question is, how can we have one without the other?"

Although the findings cannot be directly applied to other countries due to different severity of and responses to COVID-19, as well as differing air pollution levels and population characteristics, reduced air pollution levels have been detected in other Asian and European countries and the U.S. after their own lockdowns, Chen said. He notes that this reduction in pollution has likely conferred similar health benefits.

The study found that ground-level air pollution levels dropped remarkably throughout China, with nitrogen dioxide (NO2) dropping by 12.9 μg/m3 (or 37% compared with before the quarantine period) and fine particulate matter (PM2.5) dropping by 18.9 μg/m3 (30%) across 367 Chinese cities. The decline in NO2 across China during the quarantine period was so dramatic that it was detected by satellite measurements.

NO2 is a gaseous air pollutant, which is mainly produced from fuel burning in vehicles and power plants. NO2 level before the quarantine (January 5 to 20) was as high as 40.5 μg/m3 in Wuhan, where the outbreak began in China. During the quarantine (February 10 to March 14), those levels had fallen to 18.8 μg/m3 (micrograms per cubic meter).

Particulate matter includes all solid and liquid particles suspended in air, many of which are hazardous when inhaled. This mixture includes both organic and inorganic particles, such as dust, pollen, soot, smoke, and liquid droplets. Before the quarantine, PM 2.5 (fine inhalable particles with diameters of 2.5 micrometers or smaller) levels were measured at 62.5 μg/m3 in many Chinese cities. During the quarantine, the fine particulate matter reading has been 36.5 μg/m3 in those same locations.

The authors then calculated the number of avoided deaths attributable to these decreases in NO2 and PM2.5 across China based on the short-term association between these pollutants and daily mortality using data from a previous epidemiological study of 272 Chinese cities, and mortality data from the China Health and Family Planning Statistical Yearbook 2018. The authors found that among the more than 12,000 avoided deaths, about two-thirds were from avoided cardiovascular diseases (hypertensive disease, coronary heart disease and stroke) and chronic obstructive pulmonary disease.

The findings illustrate the substantial human health benefits related to cardiovascular disease morbidity and mortality that can be achieved when aggressive air pollution control measures are put in place to reduce emissions from vehicles, such as through climate mitigation-related traffic restrictions or efforts to accelerate the transition to electric vehicles, the authors said.

"This unexpected health benefit suggests that if we were to address the climate crisis as aggressively as we are combating the COVID-19 pandemic with strong political will and urgent action, we could prevent the enormous health burdens associated with climate change," said co-author Paul T. Anastas, professor at the Yale School of Public Health and the Teresa and H. John Heinz III Chair of Chemistry for the Environment.

The authors said that they want to further identify whether climate or weather-related factors and air pollution could influence population susceptibility to COVID-19.

Reston, VA--Prostate cancer patients who do not respond well to PSMA-targeted therapy often have potentially treatable mutations in their DNA damage-repair genes, according to research published in the May issue of The Journal of Nuclear Medicine. In an exploratory study using a relatively new technique--targeted next-generation gene sequencing--researchers found mutations in six out of seven patients with metastatic castration-resistant prostate cancer who did not respond to prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical therapy despite sufficient PSMA expression in their tumors.

Prostate-specific membrane antigen-targeting α-radiation therapy (PSMA-TAT) with 225Ac-PSMA-617 is an emerging and promising approach to treating metastatic castration-resistant prostate cancer. However, a reported 37 percent of patients respond poorly to this therapy even though they have sufficient PSMA expression. Preclinical and early studies suggest that particular DNA damage-repair-associated gene mutations can either increase or decrease the radiosensitivity of prostate cancers and may influence a patient's response to radiopharmaceutical therapy.

"Given the important role of DNA damage-repair gene alterations, we sought to evaluate the frequency of these defects in patients with an insufficient response to 225Ac-PSMA-617 therapy with next-generation gene sequencing," said Clemens Kratochwil, MD, supervising physician for radionuclide therapy at Heidelberg University Hospital in Heidelberg, Germany. "A relatively new technique, targeted next-generation sequencing, allows rapid analysis of an individual tumor's genome. Theoretically, such information can be predictive as to whether a patient has an increased probability to benefit from one specific treatment or combination therapy."

From a group of 60 patients treated with 225Ac-PSMA-617 PSMA-TAT, researchers identified 10 patients with a poor therapy response despite sufficient PSMA expression. CT-guided biopsies were obtained from seven of the 10 patients and then validated with histopathology and immunostaining. Biopsy specimens were analyzed with two separate targeted next-generation-sequencing panels to detect mutations in 37 genes involved in DNA-damage recognition, checkpoint signaling or DNA-damage repair.

In the seven biopsy specimens, researchers found a total of 15 whole-gene deletions, deleterious mutations and presumably deleterious mutations. Loss of function alterations were found more than once in TP53, ATM and CHEK2, with one patient even having a co-mutation of TP53 and CHEK2. Further loss-of-function mutations or whole-gene deletions were detected once in the analyzed sample set for BRCA1, BRCA2, PMS1, NBN, MSH2, MSH6, PALB2 and FANCB, respectively. For some other alterations found in ATM, BRCA1, MSH2, SLX4, ERCC and various FANC genes, it was not clear whether they negatively affected its function or were non-pathological variants as part of the normal human diversity.

"Whether the efforts and costs of next-generation sequencing are warranted in a dedicated clinical situation will depend on several factors," noted Kratochwil. "First, the mutation must be druggable in order to be led to a change in therapeutic management. Second, if the mutations are very rare, then sophisticated testing would not be cost- or time-effective. Lastly, if many patients were found to have comparable mutations, individual testing could be avoided and a one-size-fits-all approach could be applied. The significance of this preliminary work is in guiding of further research, and our findings will likely lead to a change of research practice in the near future."

He continued, "Once it can be confirmed that a large number of patients receiving PSMA-TAT are simultaneously harboring potentially druggable mutations in genes that are causal related to radio-sensitivity, then clinical evaluation (and hopefully one day routine application) of combination therapies with the potential of over-additive efficacy will become available."

Cambridge, Mass., May 18, 2020 - In response to the COVID-19 pandemic, researchers from the Massachusetts Institute of Technology have published a pair of studies in a COVID-19 special issue of the Harvard Data Science Review, freely available via open access, describing new methods for accelerating drug approvals during pandemics and for providing more accurate measures of the probabilities of success for clinical trials of vaccines and other anti-infective therapies.

"Randomized clinical trials--where patients are assigned randomly to two groups, one receiving a new treatment and the other receiving a placebo or reference treatment--are the gold standard for determining the safety and effectiveness of a treatment," says Andrew Lo, Ph.D., the study's senior author and the Charles E. and Susan T. Harris Professor at the MIT Sloan School of Management. "Only when the treatment group shows significant improvement over the control group, will regulators approve the therapy." He adds, "the current process is designed to protect the public by minimizing the chances of "false positives" (approving ineffective and unsafe therapies), and by and large, it's been very successful."

But there is a trade-off between false positives and false negatives (not approving a safe and effective therapy), and Lo and his collaborators have developed a framework that uses an epidemiological model of COVID-19 to calculate the optimal statistical threshold for approving a drug during a pandemic. "In the midst of an outbreak, many lives are at stake so we need to be less concerned about false positives and more concerned about false negatives than during normal times," says Lo, "In response, we've developed an analytic framework that allows regulators to make this trade-off systematically, transparently, and rationally."

At the core of this new framework--which was jointly developed in collaboration with MIT students Qingyang Xu and Danying Xiao, and former MIT student Shomesh Chaudhuri, Ph.D. (now at QLS Advisors)--is an explicit optimization algorithm designed to minimize the expected loss of life across various scenarios generated by a statistical model of an infectious disease. This algorithm, says Xu, will lead to more drug approvals during outbreaks, not unlike the U.S. Food and Drug Administration's Emergency Use Authorizations (EUA) program. "Our framework complements the EUA, allowing regulators to incorporate loss-of-life considerations quantitatively during periods of extraordinary stress," explains Xu, the lead investigator of the study.

In a companion study authored by Lo and MIT Ph.D. students Kien Wei Siah and Chi Heem Wong, the MIT researchers estimated the probabilities of success (PoSs) of clinical trials for vaccines and other anti-infective therapies using the Citeline® dataset provided by Informa Pharma Intelligence, part of UK-based publishing company, Informa®. This dataset includes 43,414 unique triplets of clinical trial, drug, and disease over the past 20 years, yielding over 2,500 vaccine programs and more than 6,800 nonvaccine, anti-infective programs, the largest dataset of its kind.

"The PoS is a key input into each major decision of every biopharma company about which disease to tackle and how much resources to devote to it," observes Lo.

Because a successful clinical trial can mean billions of dollars in revenues, small changes in PoS can lead to very different business decisions. Therefore, having timely and accurate measures of PoS is critical--and often, these better measures of risk and reward allow investors to put more capital to work.

The overall estimated PoS for industry-sponsored vaccine programs is about 40%, which is the highest among all disease groups (by comparison, the PoS of cancer trials is, historically, less than 5%), and 16.3% for industry-sponsored nonvaccine, anti-infective programs. Viruses involved in recent outbreaks--Middle East respiratory syndrome (MERS), severe acute respiratory syndrome (SARS), Ebola, and Zika--have had 45 nonvaccine and 35 vaccine development programs initiated over the past two decades, and there have been only two approved vaccines to date (for Ebola). This points to a clear need for new policies to address this gap.

"As governments around the world begin to formulate a more systematic strategy for dealing with pandemics beyond COVID-19, these estimates can be used by policymakers to identify areas most likely to be underserved by private sector engagement and in need of public sector support," said Wong, the study's lead author. These results are part of Project ALPHA (Analytics for Life-sciences Professionals and Healthcare Advocates)--an ongoing initiative at the MIT Laboratory for Financial Engineering (LFE) where Lo is director--to help make the biomedical funding ecosystem more efficient. "We now provide this information on a regular basis, it's not just a one-shot deal," Lo says. Users can obtain the most current PoS estimates at https://projectalpha.mit.edu.

CAMBRIDGE, MA -- As more Covid-19 patients experience acute respiratory distress, there has been much debate over the idea of sharing ventilators, which involves splitting air tubes into multiple branches so that two or more patients can be connected to the same machine.

Several physicians' associations have issued a joint statement discouraging this practice. It poses risk to patients, they say, because of the difficulty in ensuring that each patient is receiving the right amount of air.

A team of researchers from MIT and Brigham and Women's Hospital has now come up with a new approach to splitting ventilators, which they believe could address many of these safety concerns. They have demonstrated its effectiveness in laboratory tests, but they still caution it should be used only as a last resort during an emergency, when a patient's life is at stake.

"We hope this approach, which requires off-the-shelf components, can ultimately help patients in extreme need of ventilator support," says Giovanni Traverso, an MIT assistant professor of mechanical engineering and a gastroenterologist at Brigham and Women's Hospital. "We recognize that ventilator sharing is not the standard of care, and interventions like this one would only be recommended as a last recourse."

The researchers are now working to engage with third parties for the purpose of seeking emergency use authorization from the U.S. Food and Drug Administration, which would grant temporary approval for using this approach on patients during the Covid-19 pandemic. Traverso is the senior author of a paper describing the new system today in Science Translational Medicine, and Shriya Srinivasan, a postdoc at MIT and BWH, is the lead author of the study.

Personalized flow

Ventilators are machines that help people breathe by delivering oxygen through a tube placed in the mouth or the nose. The Covid-19 outbreak has raised the possibility that the number of ventilators in the United States could be insufficient for the number of patients who will need them now or in potential future waves of the disease. Additionally, other nations around the world have struggled to obtain enough ventilators to handle the Covid-19 outbreak.

In late March, at least one hospital in New York City began sharing ventilators between patients by attaching a T-shaped connector that creates two branches, one that leads to each patient's breathing tube. When doctors do this, they have to match the patients very closely by size, age, and condition, because each patient receives the same volume of air (half of total produced by the ventilator).

This is considered risky, in part because there is no way to adjust the flow so that patients receive different amounts of air based on changes in their condition. For example, when one patient improves, his or her lungs become "stretchier" and can absorb more air, which could take air away from the other patient. Or, if one patient experiences a collapsed lung, a strong burst of air could be diverted to the other patient, causing damage to the lungs.

To overcome these challenges, the MIT team incorporated flow valves, one for each patient's branch, that allow them to control the amount of air that each receives.

"These flow valves allow you to personalize the flow to each patient based on their needs," Srinivasan says. "They also ensure that if one patient either improves or deteriorates, quickly or slowly, there's a way to adapt for that."

The setup also includes pressure release valves that can prevent too much air from going into one patient's lungs, as well as safety measures including alarms that go off when a patient's air intake changes.

To create their setup, the researchers used parts that are normally available in a hospital. The parts could also be obtained at hardware stores and sterilized, the researchers say. A typical ventilator produces enough air pressure to supply six to eight patients at a time, but the research team does not recommend using one ventilator for more than two people, as the setup becomes more complicated.

Simulated scenarios

The researchers first tested their setup using a ventilator to split airflow between a pig and an artificial lung -- a machine that simulates the function of the lungs. By changing the properties of the artificial lung, they could model many of the changing conditions that might occur in patients; they also showed that the ventilator settings could be adjusted to compensate for them. They later showed that they could ventilate two animals on one ventilator and maintain the necessary airflow to both.

This system should make it easier for health care workers to change the settings as patients' conditions improve or deteriorate, the researchers say. The researchers also showed that if one patient experiences lung collapse, a pressure valve would automatically release the extra pressure that might flow toward the other patient.

The researchers are now working with pandemic response teams at Brigham and Women's and Massachusetts General Hospital to deploy this approach if it becomes necessary. They have also created a website with tutorials on how to set up the system and obtain the right parts.

Although they believe that this approach overcomes many of the challenges that usually make sharing ventilators too risky, the researchers caution that it still remains a last resort.

"In terms of the safety and personalization concerns that have been brought up, this system is definitely an improvement," Srinivasan says. "However, we don't recommend it unless it's a dire need."

NEW YORK (May 19, 2020) - While most children infected with the novel coronavirus have mild symptoms, a subset requires hospitalization and a small number require intensive care. A new report from pediatric anesthesiologists, infectious disease specialists and pediatricians at the Children's Hospital at Montefiore (CHAM) and Albert Einstein College of Medicine, describes the clinical characteristics and outcomes of children hospitalized with COVID-19, during the early days of the pandemic.

Published in the Journal of Pediatrics, the report compares 46 children between one month and 21 years old, who received care either on a general unit, or in the Pediatric Critical Care Unit (PCCU) at CHAM. This is the largest single-center study from the United States to date to describe in detail the full spectrum of COVID-19 disease in hospitalized children.

Researchers found that children requiring intensive care had higher levels of inflammation and needed additional breathing support, compared to those who were treated on a general unit. Of the children being cared for in the PCCU, almost 80% had Acute Respiratory Distress Syndrome (ARDS), which is more commonly associated with critically ill adult COVID-19 patients, and almost 50% of children with ARDS were placed on ventilators. On average, children in the PCCU stayed in the hospital four days longer than children on the general unit. Researchers at CHAM and Einstein also found that while obesity and/or asthma was highly prevalent in children in this study, these complications did not increase the likelihood that a child would need enhanced levels of care.

"We know that in adults, obesity is a risk factor for more severe disease, however, surprisingly, our study found that children admitted to the intensive care unit did not have a higher prevalence of obesity than those on the general unit," said lead author Jerry Y. Chao, M.D., M.Sc., pediatric anesthesiologist, CHAM, and assistant professor of anesthesiology, Einstein.

Researchers also found that more than half of the children had no known contact with a COVID-positive person. This may reflect the fact that the virus can be spread by asymptomatic people and COVID19 may be more prevalent in communities with a high population density.

"Thankfully most children with COVID-19 fare well, and some do not have any symptoms at all, but this research is a sobering reminder that children are not immune to this virus and some do require a higher level of care," said senior author Shivanand S. Medar, M.D., FAAP., attending physician, Cardiac Intensive Care, CHAM, and assistant professor of pediatrics, Einstein. "These preliminary findings contribute to our understanding of COVID-19 in pediatric patients, but more research is needed to determine how the virus truly impacts children."

A study by academics at the University of Bristol has found reductions in overall and individual antibiotic dispensing between 2013 and 2016 after evaluating, for the first time, national primary care prescribing policy on community antibiotic resistant infection.

The researchers investigated the relationship between primary care antibiotic dispensing and resistance in community-acquired urinary Escherichia coli infections from Bristol and the surrounding areas between 2013 and 2016.

This period was chosen because the NHS introduced an incentive scheme to reduce antibiotic dispensing from 2014 onwards. The work involved multilevel modelling analysis of data from 163 primary care practices (serving 1.5 million patients) and 152,704 urinary E. coli.

In keeping with national trends, the team, in a study published in PLOS ONE, found reductions in overall and individual antibiotic dispensing between 2013 and 2016.

Antibiotic dispensing reductions were associated with reduced resistance to ciprofloxacin, trimethoprim and amoxicillin. These reductions happened quickly - within three months - and persisted for a further three months for trimethoprim and amoxicillin. However, the study found despite reductions in the dispensing of two other antibiotics, cefalexin and co-amoxiclav, resistance to these antibiotics increased over time.

Dr Ashley Hammond, Senior Research Associate in the Centre for Academic Primary Care and lead author, said: "Our study suggests encouraging the first-line use of nitrofurantoin for uncomplicated lower UTI remains a reasonable approach. Whilst it is reassuring that reductions in antibiotic dispensing can result in reductions in resistance over a short timescale, this also suggests national prescribing guidelines will need to be reviewed and updated frequently."

More research is required to identify what else contributes to this increase in resistance. Reassuringly, despite nitrofurantoin - the go-to-first antibiotic for uncomplicated lower urinary tract infection (UTI) - dispensing increasing, there was no association with an increase in nitrofurantoin resistance, which remained very low.

Antibiotic resistance is considered one of the greatest threats to public health in the UK and worldwide. A major reason that antibiotic resistance is becoming more common is the inappropriate use of antibiotics, particularly in human medicine.

Primary care is responsible for over 75 per cent of all antibiotics dispensed in the UK and is therefore an important potential contributor to the rise of antibiotic resistant infections in the community. Numerous "antibiotic stewardship" strategies have been developed to encourage more appropriate use of antibiotics internationally in primary care. Recent Public Health England data suggests these strategies have been effective in reducing antibiotic dispensing, however, there has never been an investigation of the impact of these strategies on the amount of antibiotic resistance in the community.