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NEW YORK, May 11, 2020 -- JDRF, the American Diabetes Association (ADA), and The Leona M. and Harry B. Helmsley Charitable Trust, announce the results of a study examining the consistency and potency of insulin purchased at U.S. retail pharmacies. The study, led by University of Florida researcher Timothy Garrett and published in Diabetes Care, found all human and analog insulins measured contained the expected quantity of active insulin.

Insulin is a life-saving drug for people with diabetes that can be dangerous and potentially fatal when incorrectly dosed. Variation in insulin activity or insufficient insulin activity would pose significant challenges and safety risks for people with diabetes attempting to manage their blood glucose levels.

"During such an unprecedented time it's more important than ever for people with T1D to feel safe. This study reaffirms our confidence in the safety and effectiveness of insulin products," said Aaron Kowalski, Ph.D., president and CEO of JDRF. "As JDRF, our partners, and the type 1 diabetes community pursue cures and support the development of better insulins, we must also work together to make these safe and effective insulin products affordable and accessible to everyone who needs them."

"People living with type 1 diabetes make a life or death decision each time they decide how much insulin to dose, which happens many times a day. Having confidence in insulin quality is paramount," said David Panzirer, a Trustee at the Helmsley Charitable Trust, and a parent of two children with type 1 diabetes. "Helmsley is committed to easing the burden of living with type 1 diabetes, and this study brings welcomed good news to our community and should alleviate any lingering concern around the quality of our insulin supply."

In April 2018, JDRF, ADA, and Helmsley issued a request for proposals (RFP) to study insulin potency and consistency, which was prompted by a small study published in 2017 that found variation in the level of active insulin in products available commercially in the United States. Notably, this 2017 study did not use a research method approved by the U.S. Pharmacopeia (USP) and was inconsistent with data from previous regulatory audits. To research the issue further, JDRF, ADA, and Helmsley supported a team that devised an unbiased, well-powered, and independent assessment of insulin products from major manufacturers using approved USP methods.

USP and the U.S. Food and Drug Administration require insulin vials and cartridges to contain 100 U/mL (± 5 U/mL).

This single year of research will be expanded during a second study phase to measure any potential seasonal variations in reported insulin activity.

New Rochelle, NY, May 11, 2020--A new study has shown that initiating screening for gestational diabetes in high-risk women in the first trimester of pregnancy instead of the second trimester, allowing for treatment to start earlier, can help optimize gestational weight gain. The timing of gestational diabetes diagnosis reduced gestational weight gain in the first trimester and in the pregnancy overall, according to the study published in Journal of Women's Health, a peer-reviewed publication from Mary Ann Liebert, Inc., publishers. Click here to read the full-text article on the Journal of Women's Health website through June 11, 2020.

Screening for gestational diabetes is usually performed during the second trimester at 24-28 weeks. In this study, high-risk women -- those who were obese or had a history of gestational diabetes -- were screened during the first trimester, at about 10 weeks. Women diagnosed early with gestational diabetes had significantly less gestational weight gain (2.4 kg less) than women diagnosed during the second trimester. Furthermore, among obese women, only those diagnosed with early gestational diabetes were, on average, able to meet the Institute of Medicine guidelines for overall gestational weight gain of less than 9.0 kg (mean 8.1 kg). Obese women diagnosed with gestational diabetes were less likely to exceed these guidelines if they were diagnosed earlier rather than later in pregnancy.

Treatment guidelines for hypertension in pregnancy suggest that more women should be on medication to control their blood pressure. However, new research led by the Centre for Health Evaluation and Outcome Sciences (CHÉOS) suggests that a one-size-fits-all approach doesn't work when it comes to women's treatment decisions during pregnancy.

The findings, published recently in the Canadian Journal of Cardiology, are important for health-care providers to help women better understand the risks and benefits of hypertension treatment during pregnancy, and to better determine how their patients' values align with those treatments.

"Pregnancy is a unique period in a woman's life," says Rebecca Metcalfe, the study's lead author and a PhD candidate in the School of Population and Public Health at UBC. "Decisions are being made for two people at once and, historically, the emphasis has often not been on what the woman wants."

"But we know that treatment adherence and effectiveness is improved when treatments align with patients' values," Metcalfe says. "Our results show that there are diverse preferences and values among patients, and different levels of need when it comes to shared decision making."

Hypertension and related disorders during pregnancy are the leading cause of pregnancy-related health complications worldwide. In Canada, one in 10 women may have high blood pressure during pregnancy.

While women in Canada are fortunate to have relatively good access to health care so we are able to avoid most infant and maternal deaths due to hypertension, Metcalfe says these unfortunate events do still happen here, even with proper management of blood pressure.

Results of the Control of Hypertension in Pregnancy Study (CHIPS) trial convinced many health care providers to promote "tight" control of blood pressure for mothers compared to less-tight control. Tight control meant that treatments are aimed to get diastolic blood pressure down to 85 mmHg, whereas less-tight control is aimed for 100 mmHg. The recommendation for tight control was added to the Hypertension Canada clinical guidelines in 2018.

However, the margin of benefit between tight and less-tight control in the CHIPS trial was small. Tight control also tends to require more medication, which women often feel nervous about taking. This means it's important to consider patient preferences and values in this treatment decision.

To better understand patient priorities and preferences, Metcalfe interviewed pregnant women to understand what characteristics of a treatment they considered to be most important. For example, participants identified that the three per cent increase in risk of early delivery with less-tight control seen in the trial was very important to them, even though this finding was not considered statistically significant.

Based on those interactions, the research team developed a survey to determine women's preferences for blood pressure control, their priorities in choosing a treatment, and how they factored risk of adverse outcomes into their decision-making. The survey was administered online to 183 women across Canada.

Survey results showed that half of the women preferred tight control and half preferred less tight. The characteristics associated with preferring tight control were Caucasian ethnicity, a university education, and a higher score for knowledge about hypertension and pregnancy.

These characteristics, explains Metcalfe, are also factors that predict better experiences with the health care system meaning that these women may be more inclined to accept treatment compared to women who have not had positive experiences.

Unexpectedly, respondents with a current or past experience of hypertension in pregnancy had a significantly lower knowledge score than those without experience.

"This result shows that we can't expect women to have all the information they need just because they've been through this experience before," says Metcalfe.

The research team also observed three distinct groups of people; the majority participants gave equal priority to all aspects of a treatment, while 25 per cent prioritized avoiding the risk of an early delivery and 15 per cent prioritized avoiding medications during pregnancy. Half of the women in the study wanted to make the final decision about treatment on their own, after talking to their doctor.

Since very few randomized controlled trials have been done for treatments in pregnancy and, historically, some dangerous treatments have been approved without proper evidence, like thalidomide, having a group of women who aim to avoid all medications during pregnancy is not surprising, says Metcalfe

The team is now working on a decision aid to help women better understand the risks and benefits of treatment and how their values align with those treatments.

"This next step is about supporting women in their discussions with their doctor so they can spend the time discussing what matters to them and ultimately choose and receive a treatment that aligns with their values," says Metcalfe.

The study was co-authored by CHÉOS scientists Drs. Nick Bansback, Mark Harrison and Joel Singer, as well as Dr. Laura Magee, who is also the principal investigator of the CHIPS trial. Metcalfe is supervised by Dr. Nick Bansback.

The role of diets in the pathogenesis of cardiac dysfunction is controversial. However, it is well known that Western diet causes oxidative stress and has pro-inflammatory effects, whereas Mediterranean style diets are anti-inflammatory. Recently, cohort studies and case control studies, have demonstrated that western style diets rich in sugar and physical inactivity with obesity are important behavioural risk factors of heart failure. Pre-heart failure may be defined as a state of myocardial dysfunction, which is at high risk for developing complete heart failure. It is similar to pre-diabetes or pre-hypertension for developing diabetes mellitus and hypertension, respectively. Pre-heart failure is characterised with changes in cardiac muscles that are known as remodelling which may help to keep the blood pumping, but the ventricular walls may eventually weaken and are not able to pump adequate blood to the circulatory system resulting in to chronic heart failure. The heart may have high filling pressure with symptoms of dyspnoea and other congestive symptoms. In this process, aldosterone and cortisol predict medium-term left ventricular remodelling in an attempt to prevent cardiac failure. In the pathophysiology of cardiomyocyte dysfunction as well as in the conversion of physiological remodelling to pathological remodelling and pre-heart failure to complete heart failure, behavioural risk factors have important role. In previous studies, Dhalla et al. have observed subcellular remodelling and alterations in sarcoplasmic reticulum to be important which could be identified early by speckle tracking echocardiography. In view of the rapid increase in the burden of heart failure in the developed and developing countries, and unmet needs in the early diagnosis and treatment, it is important to find out new risk factors and methods for identification of heart failure in early stage of pre-heart failure. This analysis, re-examines, the role of nutritional factors as unmet needs in the pathogenesis and management of heart failure. This meta-analysis included data from three randomized, controlled single blind trials, published earlier, The intervention and control groups were compared for behavioural risk factors, food intakes, fatty acid intake and on ratio of polyunsaturated fatty acid(PUFA)/flavonoid intake respectively in the two groups (n = 1446 vs 1320).The criteria for the diagnosis of pre-heart failure and heart failure were electrocardiographic and radiological increase in size of the heart. Effects of Indo-Mediterranean style foods on parameters of pre-heart failure and heart failure and arrhythmias were significantly lower in the intervention group compared to control group. At baseline all the parameters of heart failure showed no significant differences, between intervention and control group. However, after a follow up of two years, left ventricular strain (Odds Ratio 0.57 (P

This article is open access and can be obtained from the following link: https://benthamopen.com/ABSTRACT/TOINFJ-8-1

New Haven, Conn. -- A new study by Yale researchers looking at nearly 400 clinicians at four urban academic emergency departments found that, despite scientific evidence supporting the benefits of buprenorphine for opioid use disorder, just 21% of emergency department clinicians indicated readiness to offer it to patients in need.

The study, which appears in the May 11 issue of JAMA Network Open, involved emergency departments at Mt. Sinai Hospital in Manhattan, the Johns Hopkins Hospital in Baltimore, Harborview Medical Center in Seattle, and University of Cincinnati Medial Center.

The study is the first installment in Project ED Health, an implementation study funded by the National Institute on Drug Abuse Clinical Trials Network to support strategies for increasing buprenorphine prescriptions in emergency departments. Buprenorphine, a partial opioid agonist -- a drug that activates opioid receptors in the brain to a lesser degree than oxycodone and morphine -- is safe to administer, relieves withdrawal symptoms, and can prevent overdose, according to years of established medical research. An implementation study reveals barriers to adopting research findings.

Project ED Health is led by two Yale physician-researchers, Dr. Gail D'Onofrio, professor and chair of the department of emergency medicine and Dr. David Fiellin, professor of internal medicine and director of the Yale Program in Addiction Medicine.

"This study provides a baseline evaluation of what care emergency departments are providing to patients with opioid use disorder," said lead author Dr. Kathryn Hawk, assistant professor in emergency medicine and attending physician in the Yale New Haven Hospital Emergency Department.

Despite barriers, clinicians are willing to give buprenorphine to patients in the emergency department, provided that they receive sufficient support and training, the study found.

"The willingness of emergency department providers to take on a new treatment is changing drastically," said Hawk.

Researchers conducted the study between April 2018 and January 2019. A team of addiction medicine physicians met with providers at the hospitals, including doctors, advance practice providers (APPs), and emergency medicine residents. Providers participated in a web-based anonymous survey that collected data about their demographics, training, experiences with ED-initiated buprenorphine, and readiness to administer buprenorphine for opioid use disorder on a scale of one to 10. Providers then rated their work culture, clinical experience, and perceived patient needs. Later, the study team ran focus groups to better understand factors impacting buprenorphine prescribing in the ED.

The researchers found that barriers to providing buprenorphine included lack of formal training, limitations on time, limited knowledge of local treatment resources, absence of local protocols and referral networks, and perceptions that initiating buprenorphine therapy falls outside the scope and practice of emergency medicine.

One resident physician quoted in the study said: "Trying to suss out which of those patients might be appropriate for initiating some therapy and which aren't is a skill that I don't have. I don't think that it's a skill that we're necessarily being trained for right now."

There was also confusion about required waivers. Just 3% of providers interviewed had DATA 2000 (x-waiver) training for buprenorphine. Providers need the waiver, which requires eight hours of approved training for physicians and 24 hours for APPs, to write a prescription for buprenorphine to be filed at a pharmacy. Emergency providers can give buprenorphine in the ED without the special waiver, said Hawk, but added that they "needed clarification around what they can and can't do."

Historically, emergency departments have not been thought of as places where patients are treated for opioid use disorder, she said. Typically, those patients were referred to outpatient clinics for treatment.

"The opioid epidemic has really changed that," Hawk said.

In 2015, Yale researchers published a landmark study in JAMA that found that patients admitted to emergency departments for opioid use disorder who were treated with buprenorphine along with medical management in primary care were twice as likely than patients not given buprenorphine to remain in addiction treatment one month later.

"The big message of that study was that initiating treatment in the ED setting was very effective," said D'Onofrio, "but true adoption lagged. So now we're trying to understand why that is, and how we can improve implementation of this best practice."

This latest study found that in order to improve adoption of ED-initiated buprenorphine there needs to be more education and training, established protocols, and enhanced communication across different stakeholder groups.

"We believe these findings will be valuable for other EDs working to enhance delivery of buprenorphine, a life-saving medication that should be available as a treatment option for all patients with untreated opioid use disorder walking into an ED," said Dr. Jennifer Edelman, associate professor of internal medicine and senior author on the study.

Despite our better knowledge, we often make choices that aren't good for us - and feel bad about it later. But it's possible to strengthen our self-control by making simple changes to our environment. Researchers from the University of Helsinki and the Max Planck Institute for Human Development describe how that can be achieved in a new article published in Behavioural Public Policy.

Adapting to life in self-isolation during the coronavirus pandemic is a challenge, and we are all figuring out how to restructure our lives. We are spending more time at home, cooking for ourselves rather than eating in the canteen, meeting with friends and family online instead of in person, and we can't go to the gym. All that makes it difficult to resist certain temptations - even when we know they aren't good for us. We reach for sugary snacks rather than crunching on vegetable sticks, scroll through our social media feeds for hours on end, and lie around on the couch binge-watching one series after another instead of getting up and going out for a run. In short, we often decide on the option that's more comfortable, enjoyable, or attractive in the short term, rather than the one that's better for us in the long term. Companies often take advantage of precisely these biological, psychological, and social weak spots when shaping advertising campaigns or designing apps and products.

Self-nudging is a behavioral science technique that we can all use to improve our self-control. Researchers Ralph Hertwig, Director of the Center for Adaptive Rationality at the Max Planck Institute for Human Development, and Samuli Reijula, philosopher at the University of Helsinki, describe how it works in an article published in Behavioural Public Policy.

The idea behind self-nudging is that people can design and structure their own environments in ways that make it easier for them to make the right choices - and ultimately to reach their long-term goals. The first step is to understand how the environment in which we make our choices - also known as the choice architecture - influences our decisions. The second step is to change that architecture - whether it be the constant notifications from our smartphone or the positioning of the foods in our fridge - in ways that enable us to make choices that are in our own interests. In other words, to nudge ourselves in the direction we want to go.

Four tools for self-nudging

The researchers describe four categories of self-nudging tools: (1) We can use reminders and prompts. For instance, a car driver can tape a note to their car door handle as a reminder to always use the 'Dutch reach' method when getting out - in other words, to use the hand furthest from the handle to open the door, as it forces them to check over their shoulder for approaching cyclists. (2) We can choose a different framing. We can frame the decision between jogging and not jogging as a decision between health and sickness in old age, for example, or we can welcome every flight of stairs as an opportunity to increase our life expectancy by a small amount. (3) We can reduce the accessibility of things that can harm us by making them less convenient or, conversely, we can make it easier to do the things we want to do - for example, by changing the default settings of our devices and disabling notifications from social media apps. (4) We can use social pressure and self-commitments to increase accountability. For example, someone might make a public commitment to a friend that they will donate a given sum to a political party they abhor if they don't meet a work deadline.

"Various needs and desires are always competing for attention in our minds and bodies. Self-nudging can help us to negotiate these internal conflicts. It is a practical tool that can enhance self-understanding," says Samuli Reijula, philosopher at the University of Helsinki.

Self-nudging applies insights from research on nudging, which has gained increasing popularity among psychologists, behavioral economists, and politicians in recent years. The idea is to help people make more rational and healthier decisions without the need for bans or financial incentives, by steering their behavior in a certain direction. But nudging has had a mixed reception among researchers.

The government's task is to inform citizens and not to nudge them

"Nudging always involves an information gap. For example, a government that uses nudging determines its citizens' behavior by deciding on what's good for them and introducing measures to nudge them in that direction. Citizens sometimes don't even know that they're being nudged, or how. This raises concerns about paternalism and manipulation," says Ralph Hertwig, Director of the Center for Adaptive Rationality at the Max Planck Institute for Human Development. What's more, policy makers can only make changes in the public sphere - but many of our choices are made in the private sphere. Self-nudging avoids the problem of the information gap and extends the reach of nudging to the private domain.

A typical example of a nudge in a cafeteria or school canteen would be to position fruit at eye level while hiding cakes and puddings away in a less accessible back corner. Policy makers who are aware of the harmful long-term health effects of people's inborn craving for sugar can influence their choices by changing the layout of the options available in public canteens. But once we get home, those nudges no longer apply. Self-nudgers, on the other hand, learn to understand the environmental factors that challenge their self-control and are able to apply the same evidence-based principles that nudging uses in the public sphere to their own immediate environments. For example, they could decide to keep the biscuit tin at the very back of the top shelf in their own kitchen.

"In this way, it's no longer policy makers who are nudging us, we're nudging ourselves - if we choose to do so. A government that gives its citizens targeted and easily understandable information on ways of using self-nudging in formats such as fact boxes, apps, or brochures can pursue socially accepted goals such as promoting healthier eating habits by enabling its citizens to make more informed and self-determined decisions. Of course, self-nudges do not replace regulations and other measures but they extend the policy makers' toolkit," says Ralph Hertwig.

Can a very common allergy medicine improve survival among patients suffering from the serious skin cancer, malignant melanoma? A new study from Lund University in Sweden indicates that this may be the case.

"Previous studies have shown that the same antihistamines have survival benefits in breast cancer. Now we see the same thing concerning malignant melanoma. However, more research is required to confirm the results", emphasises Professor Håkan Olsson. He is one of the researchers behind the study, which was recently published in the research journal, Allergy.

In the study, the researchers examined the use of six antihistamines in patients diagnosed with malignant melanoma; desloratadine, cetirizine, loratadine, clemastine, ebastine and fexofenadine.

They have matched information from three large registers (the prescribed drug register, cancer register and cause of death register) for everyone in Sweden between 2006 and 2014 who received their first diagnosis of skin cancer, a total of 24 562 individuals. Of these individuals, 1 253 were antihistamine users. Most used desloratadine (395) cetirizine (324), loratadine (251) or clemastine (192). The other antihistamines were used by considerably fewer individuals. The follow-up of individuals was carried out on 31 December 2018.

"We observed improved survival among those who used desloratadine and to a certain extent also loratadine, particularly in the age group 65 and older, when we compared with those who had not used antihistamines. The use of the other antihistamines showed no significant survival effect. The use of desloratadine and loratadine also seemed to reduce the risk of getting a new malignant melanoma", says Håkan Olsson.

"The finding is interesting for a future drug against melanoma and may also help in advanced stages of the disease. In addition, the medicines have virtually no side effects."

The research team is now planning animal experiments and randomised studies in order to understand the mechanisms behind the effect, the appropriate dose and optimum treatment period.

"We are collaborating with researchers in Barcelona and Stockholm. In Lund, we are underway with studies in both animal and human subjects, in which doses of antihistamines will be compared with the patients who do not take antihistamines, in order to measure the treatment effect", concludes Håkan Olsson.

Individuals who used drugs occasionally reported less use six months after a motivational interview with a health professional, while individuals who did not receive the intervention reported more use.

A new pilot randomized trial by researchers from the Boston University School of Public Health (BUSPH) and School of Medicine (BUSM) and Boston Medical Center (BMC) finds that a brief intervention for people with lower-risk drug use may help prevent increased and riskier use, as well as other health issues.

The study, published in the journal Drug and Alcohol Dependence, found that participants, who were identified by screening and then assigned to have a motivational interview with a health professional, reported reduced drug use six months later, while those who were not part of the intervention reported increased drug use.

"Among those with lower risk drug use--that is, infrequent use but use nonetheless--a brief conversation with a health professional could prevent it from increasing. This finding is important because it is among the first hints that we might be able to prevent some substance use disorder and other medical consequences through a brief intervention," says study lead author Dr. Nicolas Bertholet, a physician-researcher and senior lecturer at Lausanne University Hospital in Switzerland. Bertholet was a fellow with the BUSM/Boston Medical Center Clinical Addiction Research and Education (CARE) Unit when the study was being developed.

"Based on other high-quality studies, we know that brief interventions do not work for risky drug use and drug use disorder in people identified by screening. Our focus in this study on a lower-risk group suggests that this kind of low intensity intervention may work as prevention, as distinct from treatment. Brief intervention-as-prevention for people using drugs fills a gap, and could reduce not only the harms of infrequent use, but also progression to more frequent and uncontrollable use," says Dr. Richard Saitz, professor and chair of community health sciences at BUSPH, professor of general internal medicine at BUSM, and former director of CARE.

The pilot trial ran from June 2009 to January 2012 and included 57 participants from a Boston primary care clinic who reported occasional drug use. Most of the participants used cannabis (which was not yet legal for recreational use in Massachusetts), but some reported cocaine, prescription opioids, and other drugs as the main drug that they used. Some received no intervention, some received an adaptation of a method called motivational interviewing from trained health educators, and some received a longer but less structured version of a motivational interview from master-level counselors. Six months later, the participants reported their levels of drug use again, and the researchers took hair samples to test for evidence of drug use.

At the beginning of the trial, the participants reported a mean of 3.4 days in the last month that they had used their main drug. After six months, the participants who did not receive any intervention reported a mean of 6.4 days of using their main drug in the past month, while those who received the more structured intervention reported 2.1 days and those who received the less structured intervention reported 2.3 days. Hair analysis supported the finding that those who had received the intervention had used their main drugs less frequently and/or recently than those who had not received either intervention.

A diversity of vaccine approaches, not a single SARS-CoV-2 vaccine or vaccine platform, must be pursued to meet the global need to protect from the continued threat of the SARS-CoV-2 virus, write Lawrence Corey, John R. Mascola, Anthony S. Fauci, and Francis S. Collins in this Policy Forum. As part of this approach, industry, government and academia must collaborate in unprecedented ways, each adding their individual strengths, Corey and colleagues say. At present, even though a number of biotechnology and pharmaceutical companies are bringing forward vaccine approaches for the SARS-CoV-2 virus, these "encouraging efforts are tempered" by questions that remain about what constitutes a protective immune response. Only a diversity of vaccine approaches, managed by collaborative approaches from different sectors, can help explore the many questions that remain, say Corey and colleagues. Such a collaborative program has recently emerged with the founding of the ACTIV (Accelerating COVID19 Therapeutic Interventions and Vaccines) public-private partnership, wherein NIH has partnered with its sister agencies, other U.S. government departments, representatives from academia, philanthropic organizations, and more than 15 biopharmaceutical companies, to bring together the strengths of all sectors. The authors involved with the ACTIV public-private partnership call for harmonizing each step of the coordinated vaccine development process, from creating a common oversight body and shared set of criteria to evaluate the vaccine studies underway, to transparency and data sharing, to marshalling the full resources of private, public and philanthropic sectors to scale up eventual manufacturing capacity and distribution chains for COVID-19 vaccines.

TORONTO, May 11, 2020 - How is your sense of smell? Do you find yourself frequently dozing off during the day or thrashing about during dreams? Often, early stage Parkinson's disease does not present with typical motor disturbance symptoms, making diagnosis problematic. Now, neuroscientists at York University have found five different models that use these types of non-motor clinical as well as biological variables to more accurately predict early-stage Parkinson's disease.

Their five-model analysis is one of the first utilizing only non-motor clinical and biologic variables. Some models performed better than others but all distinguished early stage (preclinical) Parkinson's disease from healthy, age-matched controls, with better than 80 per cent accuracy. The models may assist in more timely administration of future treatments as they become available, according to the study published in Frontiers in Neurology today.

Using the multiple model method as a first pass for diagnosis would also be a less invasive alternative to using the traditional radioactive tracer scan (DaTscan) usually used to assess patients.

The study's lead author, PhD candidate Charles Leger, and his lab supervisor Joseph DeSouza, associate professor Department of Psychology at York University, say the goal was to develop models that could be used to predict, with greater than 80 per cent efficiency, those with early-stage Parkinson's pathology versus those without apparent disease.

In the study, two separate analyses were conducted: one for the classification of early Parkinson's disease versus controls, and the other for classification of early Parkinson's versus SWEDD (scans without evidence of dopamine deficit). The term SWEDD refers to the absence, rather than the presence, of an imaging abnormality in patients clinically presumed to have Parkinson's disease.

"Right now, there's no cure for Parkinson's disease. All we know now are the signs and symptoms and we can only treat the symptoms," says DeSouza. "These models could be very useful in differentiating patients who may present with Parkinson's-like symptoms not related to Parkinson's pathology from patients who actually have the disease."

Facilitated and more accurate prediction of early-stage, de novo Parkinson's can allow those positively diagnosed to adopt lifestyle changes such as regular physical exercise early on that can improve mobility and balance, says DeSouza.

Researchers used cross-sectional, baseline data from the Parkinson's Progressive Markers Initiative (PPMI). The PPMI data used was confined to non-motor clinical variables (e.g. sense of smell, daytime sleepiness, presence of rapid eye movement behaviour disorder, age, etc.) and biologic variables (e.g. cerebral spinal fluid alpha-synuclein, tau protein, beta-amyloid-142, etc.) Five different model types were "trained" models that could prove useful in helping to differentiate early stage Parkinson's pathology.

"What's unique about this study is that it provides a dual analysis, which hasn't been done before for early Parkinson's disease," says Leger.

The dual analysis included: (a) prediction of early, preclinical Parkinson's vs. controls, then in a separate analysis, (b) early Parkinson's vs. SWEDD (the Parkinson's lookalike condition). The trained models attempted to predict early Parkinson's from controls (a); and early Parkinson's from SWEDD (b).

"Every feature used was first proven relevant in the literature. Of those, we allowed each model to pick out which predictors were most important. No model is guaranteed to provide the best fit," says Leger. "With five models, if you get the same feature that stands out, then you know that particular variable is very important in distinguishing disease. Neurologists could apply one or more of the models to their own data to assist distinguish Parkinson's pathology from pathology masquerading as Parkinson's. Two of the models may be useful in helping to screen those in the SWEDD category with Parkinson's type pathology from those whose pathology is not Parkinson's related."

In both early Parkinson's/control and early Parkinson's/SWEDD analyses, and across all models, hyposmia - a reduced ability to smell and to detect odours - was the single most important feature to distinguish early-onset Parkinson's, followed by rapid eye movement behaviour disorder.

Children, teens and young adults are at greater risk for severe complications from COVID-19 than previously thought and those with underlying health conditions are at even greater risk, according to a study coauthored by a Rutgers researcher.

The study, published in JAMA Pediatrics, is the first to describe the characteristics of seriously ill pediatric COVID-19 patients in North America.

"The idea that COVID-19 is sparing of young people is just false," said study coauthor Lawrence C. Kleinman, professor and vice chair for academic development and chief of the Department of Pediatrics' Division of Population Health, Quality and Implementation Science at Rutgers Robert Wood Johnson Medical School. "While children are more likely to get very sick if they have other chronic conditions, including obesity, it is important to note that children without chronic illness are also at risk. Parents need to continue to take the virus seriously."

The study followed 48 children and young adults - from newborns to 21 years old -- who were admitted to pediatric intensive care units (PICUs) in the United States and Canada for COVID-19 in March and April. More than 80 percent had chronic underlying conditions, such as immune suppression, obesity, diabetes, seizures or chronic lung disease. Of those, 40 percent depended on technological support due to developmental delays or genetic anomalies.

More than 20 percent experienced failure of two or more organ systems due to COVID-19, and nearly 40 percent required a breathing tube and ventilator. At the end of the follow-up period, nearly 33 percent of the children were still hospitalized due to COVID-19, with three still requiring ventilator support and one on life support. Two of the children admitted during the three-week study period died.

"This study provides a baseline understanding of the early disease burden of COVID-19 in pediatric patients," said Hariprem Rajasekhar, a pediatric intensivist involved in conducting the study at Robert Wood Johnson Medical School's Department of Pediatrics. "The findings confirm that this emerging disease was already widespread in March and that it is not universally benign among children."

The researchers said they were "cautiously encouraged" by hospital outcomes for the children studied, citing the 4.2 percent mortality rate for PICU patients compared with published mortality rates of up to 62 percent among adults admitted to ICUs, as well as lower incidences of respiratory failure.

Kleinman noted that doctors in the New York metropolitan area are seeing what appears to be a new COVID-related syndrome in children.

"Although our data collection for this study has ended, we continue to develop collaborations with colleagues in our region and across the country to try to understand these more severe complications," he said, citing concerns such as heart failure and the Kawasaki disease-like condition termed pediatric multi-system inflammatory syndrome as examples.

WHAT:
A harmonized and collaborative approach to the clinical testing, scale-up and distribution of candidate vaccines to prevent COVID-19 is essential, scientific leaders write in a perspective published today in Science. As the COVID-19 pandemic continues, government, industry and academia have introduced a variety of vaccine candidates. The authors note that more than one effective vaccine approach likely will be required to successfully protect the global community from SARS-CoV-2, the virus that causes COVID-19. They describe a strategic approach to research and development that would generate essential data for multiple vaccine candidates in parallel.

National Institutes of Health Director Francis S. Collins, M.D., Ph.D., National Institute of Allergy and Infectious Diseases (NIAID) Director Anthony S. Fauci, M.D., Lawrence Corey, M.D., professor in the Vaccine and Infectious Disease Division at the Fred Hutchinson Cancer Research Center in Seattle, and John R. Mascola, M.D., director of NIAID's Vaccine Research Center are the co-authors of the commentary.

The perspective discusses diverse vaccine candidates and key considerations for development, including the characteristics of various vaccine platforms in terms of prior commercial experience, scalability, and the types of immune responses generated. It also emphasizes that no single vaccine or vaccine platform is likely to meet the global need, highlighting the need for a coordinated strategic approach to vaccine development.

The authors stress that researchers need to learn more about what constitutes a durable protective immune response against COVID-19. They review considerations for vaccine efficacy trials, explaining how trials for several candidate vaccines can be conducted in parallel to generate essential safety and efficacy data and accelerate the licensure and distribution of COVID-19 vaccines. The authors propose specific approaches to harmonizing the clinical testing of multiple vaccine products, including using common clinical trials designs, clinical endpoints, standardized immune assays and a common Data Safety and Monitoring Board.

The authors emphasize that developing COVID-19 vaccines will require unprecedented cooperation from governments, academic institutions, industry, and global philanthropic partners. The ACTIV (Accelerating COVID-19 Therapeutic Interventions and Vaccines) public-private partnership spearheaded by NIH aims to facilitate such collaboration with discussions and collaborations on trial designs and data sharing.

Protecting the entire global community from COVID-19 through vaccination will require significant manufacturing capacity, according to the authors. They emphasize the need to fund the necessary biomanufacturing infrastructure and note possible hurdles in the eventual delivery of vaccines, including cost, distribution systems and cold chain requirements. The authors conclude that strategic collaboration among public and private sectors to effectively accelerate COVID-19 vaccine development is essential.

OAK BROOK, Ill. (May 11, 2020) - Patients with COVID-19 can have bowel abnormalities, including ischemia, according to a new study published today in the journal Radiology.

Several studies have evaluated the chest imaging findings in COVID-19, which helped improve understanding of how the disease affects the lungs. More recently, reports have documented that gastrointestinal symptoms, liver injury, and vascular findings are common in these patients. However, abdominal imaging findings have not yet been widely reported. Imaging findings may help physicians understand abdominal manifestations in patients with the infection. Therefore, the authors of this study set out to explore abdominal imaging findings in patients with COVID-19.

The retrospective study included 412 patients consecutively admitted to a single quaternary care center from March 27 to April 10, 2020, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The cohort included 241 men (58.5%) and 171 women (41.5%), with an average age of 57 years.

Records showed that 17% of patients had cross-sectional abdominal imaging, including 44 ultrasounds, 42 CT scans, and 1 MRI. Bowel abnormalities were seen on 31% of CT scans (3.2% of all patients) and were more frequent in intensive care unit (ICU) patients than other inpatients. Bowel findings included thickening and findings of ischemia such as pneumatosis (gas in the bowel wall) and portal venous gas. Surgical correlation in four patients revealed unusual yellow discoloration of bowel in three of the patients, and bowel infarction (dead bowel) in two patients.

"We found bowel abnormalities on imaging in patients with COVID-19, more commonly in sicker patients who went to the ICU," said Rajesh Bhayana, M.D., FRCPC, abdominal imaging fellow in the Department of Radiology at Massachusetts General Hospital in Boston.

In two patients who had bowel resection, pathology demonstrated ischemia with patchy necrosis (injury due to reduced arterial flow with patchy areas of cell death). Both had fibrin thrombi (blood clots) in submucosal arterioles (small arteries in the bowel wall), suggesting bowel ischemia in these patients might be caused by these small blood clots. Lung base findings led to a diagnosis of COVID-19 in one patient who presented with abdominal symptoms only. Of right upper quadrant ultrasounds, 87% were performed for liver laboratory findings, and 54% demonstrated a dilated sludge-filled gallbladder suggestive of cholestasis, or a decrease in bile flow.

"Some findings were typical of bowel ischemia, or dying bowel, and in those who had surgery we saw small vessel clots beside areas of dead bowel," Dr. Bhayana said. "Patients in the ICU can have bowel ischemia for other reasons, but we know COVID-19 can lead to clotting and small vessel injury, so bowel might also be affected by this."

According to the researchers, possible explanations for the spectrum of bowel findings in patients with COVID-19 include direct viral infection, small vessel thrombosis, or nonocclusive mesenteric ischemia. "ACE2 expression is most abundant in lung alveolar epithelial cells, enterocytes of the small intestine, and vascular endothelium suggesting that small bowel and vasculature may be susceptible to SARS-CoV-2 infection," they wrote.

The authors added that further studies are required to clarify the cause of bowel findings in patients with COVID-19 and to determine whether SARS-CoV-2 plays a direct role in bowel or vascular injury.

"Our study is preliminary, and more work is needed to understand the cause of bowel findings in these patients," Dr. Bhayana said.

An analysis of more than half a million women in Sweden reveals that mammography screening reduces the rates of advanced and fatal breast cancers. The findings are published early online in CANCER, a peer-reviewed journal of the American Cancer Society (ACS).

For the analysis, László Tabár, MD, of Falun Central Hospital, Sweden, Stephen Duffy, MSc, of Queen Mary University of London, and their colleagues examined data on nearly one-third of the women in Sweden who were eligible for mammography screening. Among these 549,091 women, the investigators calculated the rates of advanced breast cancers and cancers that were fatal within 10 years of diagnosis, comparing the findings in women who participated in recommended mammography screening and those who did not.

The team found a 41 percent reduction in cancers that were fatal within 10 years after diagnosis and a 25 percent reduction in the incidence of advanced breast cancer in women who participated in screening.

"This study shows that participation in breast cancer screening substantially reduces the risk of having a fatal breast cancer. Because the comparison of participating with non-participating persons was contemporaneous--with mammography screening and breast cancer treatment belonging to the same time period--it is not affected by potential changes in treatment of breast cancer over time," said Dr. Duffy.

Dr. Tabár stressed that participating in breast cancer screening confers a reduced risk of dying from breast cancer above and beyond what is obtainable with current therapies in the absence of screening. "Some may believe that recent improvements in breast cancer treatment makes early detection less important," he said. "Our study shows that nothing can replace finding breast cancer early."

Given the rapid spread of COVID-19 and its relatively high mortality, filling the gap for coronavirus-specific drugs is urgent. It calls for repurposing existing drugs and developing trial plans to comprehensively test these drugs for use in COVID-19 patients much more quickly than researchers, ethics boards and regulators are accosted to, say R. Kiplin Guy and colleagues in this Perspective. They highlight several existing drugs that could be repurposed for COVID-19 patients that are being tested now. The key issue with any of these potential treatments, say the authors, is to balance the needs of making treatment decisions for individual patients during epidemic peaks on the basis of clinical studies that involve small number of patients with ensuring that well-designed, randomized clinical trials are carried out rapidly. Controlled, randomized trials are needed to continue to test the efficacy and safety of drugs like hydroxychloroquine, azithromycin and remdesivir, they say. As COVID-19 is expected to be active in several seasons of disease peaks, the difficulty is to coordinate rapid studies during this first peak to justify a smaller number of well-controlled large trials to be executed in later peaks. Guy and colleagues note that researchers, ethics boards and regulators are accustomed to developing trial plans over months, not weeks--a time frame not afforded now. "It is necessary for all involved to work faster and more efficiently and then position the well-justified drugs for registrant-enabling trials during the next peak," they say.