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The COVID-19 pandemic has placed unprecedented pressure on societies worldwide, given the pandemic's rapid, often deadly spread. In health care, the pandemic has raised the pressing question of how society should allocate scarce resources during a crisis. This is the question experts addressed today in a new position statement published by the American Geriatrics Society (AGS) in the Journal of the American Geriatrics Society (DOI: 10.1111/jgs.16537). The statement focuses primarily on whether age should be considered when making decisions to allocate scarce resources.

"A just society strives to treat all people equally, so there's something particularly unjust about characteristics beyond our control--like age--determining whether we receive care," explains Timothy W. Farrell, MD, AGSF, who led the writing group responsible for the statement. "The AGS believes we must focus on the most relevant clinical factors for each person and case when considering how to distribute resources fairly without placing arbitrary weight on age."

COVID-19 continues to impact older adults disproportionately when it comes to serious consequences, from severe illness and hospitalization to increased risk for death. Concerns about potential shortages of ventilators, hospital beds, and other supplies to address these shortages have focused attention on decision-making about who gets access to these resources.

"Unfortunately, some strategies use age as an arbitrary criterion, which disfavors older adults regardless of their function and health relative to COVID-19," said AGS President Annie Medina-Walpole, MD, AGSF. "With this statement, we hope to support hospitals, health systems, and policymakers as they develop resource allocation strategies for use in emergent situations that do not rely on age as a criterion."

After reviewing existing frameworks, recommendations, and research, an expert panel of interprofessional experts, AGS leaders and members of the AGS Ethics Committee devised seven principles aimed at helping develop strategies to allocate resources equitably when they remain in short supply:

1. Age should never be used as a means for categorically excluding someone from what is ordinarily the standard of care, nor should age "cut-offs" be used in allocation strategies.

2. When assessing comorbidities (the medical term for multiple health concerns we live with concurrently), decision-makers should carefully consider the impact of race, ethnicity, and other "social determinants," especially since these often are beyond a person's control.

3. Strategies for making allocation decisions should primarily--and equally--weigh how severe comorbidities and survival in hospital might contribute to the short-term risk for death. This means that health professionals should focus primarily on what is most within their control: Potential outcomes over the next 6 months (and not beyond, which could disproportionately impact care for older people).

4. In order to avoid bias in decision making, health professionals also should avoid criteria that might disadvantage us all as we age. These include characteristics such as:

"Life years saved" (how many years could be added to someone's life by treatment).

"Long-term predicted life expectancy" (the long-term view of length of life from this point in time).

5. Committees and officers tasked with triage (the technical term for organizing and prioritizing a health system's response, especially in times of crisis) also need to be chosen carefully. Ideally, these individuals not only have expertise in medical ethics and geriatrics (the healthcare specialty dedicated to our needs as we age) but also work outside "day-to-day" care so triage officers can maintain impartiality.

6. Institutions should develop resource allocation strategies that are transparent, and applied uniformly. Ideally, that means leveraging advanced planning and input from multiple disciplines, including ethics, law, medicine, and nursing. To make the work of an officer or committee transparent, institutions also should develop consistent strategies available to all for review. "Clinicians at the front lines should be applying--not selecting--emergency rationing criteria when resources are limited," the AGS position statement explained.

7. The COVID-19 pandemic highlights the critical importance of appropriate advance care planning (ACP)--the technical term for working with a health professional and anyone else you choose to document preferences for possible care situations, such as whether you'd want to be placed on a ventilator if you weren't able to breathe on your own. While engaging in these conversations early and often remains critical, they also never should be viewed as a form of rationing, nor should someone be compelled into documenting care preferences primarily because of a broader health crisis. ACP is most effective when it lives up to its name: A conversation in advance, planned with personal preferences at heart.

To help with the urgent need to put in place policies and approaches within the context of the COVID-19 pandemic, the AGS also suggested frameworks to aid health leaders and health systems. They include:

Developing a multi-factor allocation strategy based on AGS insights;

Establishing triage committees and identifying triage officers;

Clearly communicating about available resources;

Ensuring access to important treatment options (like hospice and palliative care); and

Working to develop individual care plans for patients.

Long-term, the AGS also advocated for post-pandemic reviews of COVID-19 rationing strategies, with the goal of removing discriminatory provisions--including age-based cutoffs--which disfavor older adults.

"Health care is unlike other 'goods' or services in that it's a prerequisite for pursuing virtually every other opportunity that makes life meaningful," summarized Dr. Farrell. "Our position statement is aimed at recognizing resource allocation shouldn't be a question of 'if' but rather how we can make decisions safely and smartly, making good on our societal commitment to treat all people fairly."

Clinicians from two hospitals in Boston report that the majority of even the sickest patients with COVID-19--those who require ventilators in intensive care units--get better when they receive existing guideline-supported treatment for respiratory failure. The clinicians, who are from Massachusetts General Hospital (MGH) and Beth Israel Deaconess Medical Center, published their findings in the American Journal of Respiratory and Critical Care Medicine.

During the COVID-19 pandemic, hospitals around the world have shared anecdotal experiences to help inform the care of affected patients, but such anecdotes do not always reveal the best treatment strategies, and they can even lead to harm. To provide more reliable information, a team led by C. Corey Hardin, MD, PhD, an Assistant Professor of Medicine at MGH and Harvard Medical School, carefully examined the records of 66 critically ill patients with COVID-19 who experienced respiratory failure and were put on ventilators, making note of their responses to the care they received.

The investigators found that the most severe cases of COVID-19 result in a syndrome called Acute Respiratory Distress Syndrome (ARDS), a life-threatening lung condition that can be caused by a wide range of pathogens. "The good news is we have been studying ARDS for over 50 years and we have a number of effective evidenced-based therapies with which to treat it," said Dr. Hardin. "We applied these treatments--such as prone ventilation where patients are turned onto their stomachs--to patients in our study and they responded to them as we would expect patients with ARDS to respond."

Importantly, the death rate among critically ill patients with COVID-19 treated this way--16.7%--was not nearly as high as has been reported by other hospitals. Also, over a median follow-up of 34 days, 75.8% of patients who were on ventilators were discharged from the intensive care unit. "Based on this, we recommend that clinicians provide evidence-based ARDS treatments to patients with respiratory failure due to COVID-19 and await standardized clinical trials before contemplating novel therapies," said co-lead author Jehan Alladina, MD, an Instructor in Medicine at Mass General.

An international research team has identified the mechanism behind one of science's most enduring mysteries: what makes the 100-year-old tuberculosis (TB) vaccine so effective at preventing newborn deaths from diseases other than TB?

The ability of Bacillus Calmette-Guérin (BCG)--one of the oldest, safest and cheapest vaccines available--to provide protection to newborns beyond its intended purpose of fighting off TB has been known since at least the 1940s, but until now no one has been able to explain why or show how it works.

In a new study, published today in Science Translational Medicine, researchers reveal how they identified a dramatic and rapid increase in neutrophils -- white blood cells that patrol the body and destroy invading bacterial pathogens - in mice and babies within three days of BCG vaccination.

The five-year study is the first to demonstrate the beneficial mechanism triggered by administration of BCG in newborns. It involved researchers from around the world, including senior co-authors Dr. Tobias Kollmann, an affiliate professor in the UBC department of paediatrics, and Dr. Nelly Amenyogbe, a graduate of UBC's experimental medicine program. The study's lead author Byron Brook, a UBC PhD candidate in experimental medicine, is based at the Kollmann Lab at BC Children's Hospital Research Institute in Vancouver.

"It's been known for a very long time that neutrophils play a very important role in managing sepsis, but until now nobody understood the role of BCG in initiating this critical process," said Amenyogbe. "It was actually thought to be biologically implausible, however we've not only shown how BCG is involved, but that it kicks off this process almost instantly following vaccination -- far more quickly than anticipated."

The researchers first witnessed the phenomenon--known as emergency granulopoiesis (EG)--in mice, with the team later validating it in blood samples from newborn babies in West Africa and Papua New Guinea.

Kollmann, who also heads up the Systems Vaccinology team at Telethon Kids Institute (TKI) in Australia in partnership with the Perth Children's Hospital Foundation, said the findings reinforce how critical it is for newborns in low-resource settings to receive BCG immediately after birth. Kollmann was previously the head of the paediatric division of infectious diseases at UBC before relocating to Australia.

"Less than half the babies who should get this vaccine right after birth actually get it then, partly because of logistics and partly because TB is not seen as a huge risk in those first few weeks. Administration is often delayed to four to six weeks, but by then it's too late for many newborns," said Kollmann, also an affiliate investigator at BC Children's Hospital in Vancouver. "Around half of all newborn deaths from infection happen in the first week of life, with about 75 per cent of those deaths caused by sepsis. Given BCG's clear role in helping newborns to fight off sepsis, we could save the lives of close to a million newborns every year if they were given this vaccine within days of birth instead of weeks later."

Brook, the study's lead author, added: "If every newborn was vaccinated with BCG, the greatest impact would be in regions of highest newborn mortality, specifically low- and middle-income countries. It could also help save newborns here in Canada, and represents a new strategy of how to get more benefit from existing vaccines."

The researchers cautioned that while the effect was rapid and offered robust protection against newborn sepsis, it was relatively short-lived and did not occur in adult mice.

Kollmann and Amenyogbe are also involved in Australia's BRACE trial, which is testing BCG's potential to fight off COVID-19. Kollmann said whether BCG may or may not be protective against COVID-19 remains to be seen, but in the meantime, its real and proven potential to save the lives of vulnerable newborns had to be maximized.

"BCG is very, very safe, costs only a few cents per dose, and reduces infectious causes of mortality - not just tuberculosis - in newborns by almost 50 per cent," Kollmann said. "There's nothing that we have in our entire current medical arsenal that is as effective, cheap, safe, feasible and affordable as this vaccine. All we have to do is ensure all newborns at risk get it right away at birth."

Lower extremity artery disease (LEAD) is a leading cause of morbidity and mortality worldwide, affecting hundreds of millions of people. On top of that, LEAD also represents a prominent marker of associated coronary artery disease (CAD), as demonstrated by ?70% prevalence of significant CAD in patients with symptomatic LEAD. Accordingly, in the last decades increasing attention has been devoted to the management of LEAD, including antithrombotic strategies in asymptomatic patients, symptomatic patients and following surgical or endovascular revascularization.

The large randomised COMPASS (Cardiovascular Outcomes for People Using Anti-coagulation Strategies) trial recently demonstrated that an intensified antithrombotic regimen comprising rivaroxaban 2.5 mg twice daily on top of aspirin is associated with an impressive 46% reduction in major adverse limb events (acute and chronic limb ischaemia including major amputation) as compared to aspirin alone; importantly, this therapeutic strategy can be cost-effective in patients with peripheral artery disease.

However, while attention has been given to the definition of the best long-term antithrombotic strategy for the secondary prevention of patients with LEAD, the same is not true regarding the treatment of patients undergoing peripheral vascular interventions (PVIs), whose medical management has been largely extrapolated from the coronary field. This aspect is of particular relevance considering the high number of patients in whom lower limb revascularization is currently indicated, such as both those at risk of limb amputation or with lifestyle-limiting claudication. Over recent years, the number of PVIs has soared worldwide, driven by a consistent improvement of endovascular techniques and devices. While this growth has been accompanied by many clinical trials aimed at assessing the safety and efficacy of the various revascularisation strategies, very little evidence was collected regarding the best antithrombotic treatment in patients undergoing PVI.

With these considerations in mind, we aimed at outlining the "state-of-the-art" of antithrombotic therapy for peripheral revascularisation, hopefully contributing to a better management of LEAD patients in clinical practice, which is actually the mission of the Working Group on Aorta and Peripheral Vascular Diseases of the European Society of Cardiology, which I recently had to honour to chair.

Our review, published in the last Special Issue of Current Vascular Pharmacology, provides an overview of the indications and techniques of lower extremity revascularisation, and an in-depth analysis of the available evidence regarding type and duration of antiplatelet and anticoagulant treatment following endovascular and surgical revascularisation. A specific focus was dedicated to endovascular revascularisation, whose growth in number has not been accompanied by a parallel growth in high-quality scientific evidence regarding antithrombotic therapy. In the lack of dedicated randomised trials, we pragmatically analysed and compared the antithrombotic strategies recommended in the randomised trials dedicated to endovascular devices and techniques.

Of notice, during the ACC congress in March 2020, shortly after the publication of our review, the results of the VOYAGER PAD study ("Vascular Outcomes Study of ASA Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD") were presented. This trial demonstrated that, in patients undergoing lower limb revascularization (65% endovascular), the combination of a low-dose anticoagulation with rivaroxaban (2.5 mg bid) on top of aspirin is associated with significantly lower limb-related and major vascular events than aspirin ± clopidogrel (17.3% vs 19.9% at 3 years, respectively), with a limited increase in major bleedings (5.9% vs 4.1%). However, despite rivaroxaban 2.5 mg bid + aspirin has the potential to become the reference treatment strategy in patients undergoing lower limb revascularization, in the absence of favourable cost-effective analysis and waiting for the approval of regulatory agencies, a rapid worldwide implementation of the results of the VOYAGER PAD study in clinical practice is unlikely. Therefore, our review provides a useful guidance on antithrombotic treatment for both endovascular and surgical revascularisation procedures in current clinical practice.

Amsterdam, NL, May 6, 2020 - Despite 30 years of research, not a single therapy has been found to successfully delay or stop the progression of Parkinson's disease (PD). In the Journal of Parkinson's Disease scientists report on the possibility of using a multi-arm, multi-stage (MAMS) trial platform to evaluate several potential therapies at once, using lessons learned from other diseases.

Many potential disease-modifying therapies have been identified as suitable for clinical evaluation in PD. Each potential cure for PD has to go through three clinical trial phases to test its safety, whether it shows signs of improving PD, and whether there is any meaningful benefit to people with PD. Running a clinical trial is a huge logistical, costly, and time-consuming undertaking. For a single new therapy this process can take the best part of a decade. Currently, phase II and phase III clinical trials in PD are set up in isolation from each other, a process that is lengthy, costly, and inefficient.

In this review, scientists introduce the concept of a multi-arm, multi-stage (MAMS) PD trial platform. MAMS trials test many potential therapies in parallel (multi-arm), transitioning seamlessly through various phases (multi-stage), i.e., from a phase II safety and efficacy study to a phase III trial. Early analyses allow unsuccessful therapies to be replaced. At the interim checkpoint, ineffective arms can be dropped and replaced by new treatment arms, thereby allowing for the continuous evaluation of interventions.

MAMS trial platforms already exist for prostate, renal, and oropharyngeal cancer and are currently being developed within the UK for other neurogenerative disorders such as progressive multiple sclerosis (PMS) and motor neuron disease (MND).

"The current way we do trials in Parkinson's is too slow and inefficient," explained lead author Camille Buchholz Carroll, MD, PhD, Applied Parkinson's Research Group, University of Plymouth, Faculty of Health, Plymouth, UK. "We need to develop new ways of doing trials such as the MAMS trial platform, which will speed up the process and bring us closer to finding a cure, faster. We have the opportunity to learn from the experience in these other conditions and design a new trial that will work for people with Parkinson's."

Because a MAMS trial for PD would evaluate many potential treatments, it is critical that a widely endorsed core protocol is developed that will investigate outcomes and objectives meaningful to patients. Dr. Carroll and colleagues describe the challenges of drug selection, trial design, stratification and outcome measures, type and stage of PD to be tested, and how to best measure PD. They explore how these challenges have been met in promising MAMS trials instituted to address other diseases including the STAMPEDE trial; Motor Neuron Disease Systematic Multi-Arm Adaptive Randomized Trial (MND SMART]; and UK MS Society's 2018-2022 Research Strategy.

"I was personally very excited to read about this new development," noted Prof. Bas Bloem, Co-Editor-in-Chief of the journal. "There are many promising drugs in the pipeline that have potential to slow down the progression of PD but taking that hypothesis to the test is still a long and cumbersome process. The new approach described here holds great promise for facilitating this complex procedure, so that we can gather the necessary evidence for new treatments much quicker than before. Patients will certainly applaud this development as well!"

The authors stress that to maximize the potential of a MAMS platform trial running over many years and interrogating many research questions, it is crucial that there is a pipeline in place that will continuously identify and evaluate suitable drug candidates. Furthermore, outcome measures have to be chosen that are sensitive enough to changes in disease progression over interim stages as well as the full duration of the trial.

"We believe a MAMS trial for PD is possible and could dramatically speed up the search for a cure," concluded Dr. Carroll. "Over the coming 12-18 months we will be working with the Cure Parkinson's Trust and other organizations, nationally and internationally, to achieve this."

PD is a slowly progressive disorder that affects movement, muscle control, and balance. It is the second most common age-related neurodegenerative disorder affecting about 3% of the population by the age of 65 and up to 5% of individuals over 85 years of age.

University of Virginia researchers are pioneering the use of focused ultrasound to defy the brain's protective barrier so that doctors could, at last, deliver many treatments directly into the brain to battle neurological diseases. The approach, the researchers hope, could revolutionize treatment for conditions from Alzheimer's to epilepsy to brain tumors - and even help repair the devastating damage caused by stroke.

Richard J. Price, PhD, of UVA's School of Medicine and School of Engineering, is using focused soundwaves to overcome the natural "blood-brain barrier," which protects the brain from harmful pathogens. His approach aims to breach the barrier only where needed, and only when needed, and then deliver treatments in exquisitely precise fashion.

"The blood-brain barrier is one of the greatest, if not the greatest, challenge to drug delivery for the central nervous system," Price explained. "Evolution gave us this barrier because the central nervous system needs to be protected. The problem is now we want to deliver something to those cells and evolution has had millions and millions of years to optimize a solution to stop it. ... So I'm attempting to circumvent biology with physics."

Focused Ultrasound's Great Potential

Focused ultrasound focuses sound waves inside the brain much like a magnifying glass can focus light, letting doctors manipulate tissue without cutting into the skull. Magnetic resonance imaging (MRI), meanwhile, lets them watch what's happening inside the brain in real time. While Price, a biomedical engineer, is developing his techniques in the lab, doctors are already using the technology to treat conditions such as Parkinson's tremor.

Price marvels at the approach's specificity. "With MRI, we can look at the target, whether it's a brain tumor or maybe it's a part of the brain we want to do gene therapy on, and we can select it - we can actually make a treatment plan and say, We only want to open the [blood-brain] barrier there. The other 95% of the brain, we don't even touch," said Price, the research director at UVA's Focused Ultrasound Center. "Then, when we apply the focused ultrasound, it opens the barrier there for a few hours. It lets us get the gene therapy across, and then it closes naturally."

Delivering Gene Therapy

Gene therapy introduced via focused ultrasound would essentially reprogram faulty cells.

For brain tumors, Price is exploring the potential of using focused ultrasound to deliver gene therapy via "deep-penetrating nanoparticles." The nanoparticles, designed by Price's collaborators at Johns Hopkins University, "are specifically engineered to penetrate the tissue extremely well," he said. The problem has been transporting them where they're needed, often deep inside the brain, and Price says focused ultrasound holds the answer.

His solution is to use the focused soundwaves to open spaces between cells in the tissue. "It doesn't help us if you can't get to the neuron that's 50 microns away," he said. "So that becomes an engineering transport problem."

In addition to delivering the therapy, focused ultrasound can "precondition" targeted tissue to enhance the effectiveness of the gene delivery up to five-fold, Price has found. The preconditioning represents a "simple and effective strategy" to boost the benefits of the nanoparticles, he and his colleagues report in a scientific paper.

Improving Stroke Outcomes

For stroke, a condition that is often debilitating when it's not deadly, Price aims to help the brain heal itself. He would do this by using focused ultrasound to put "homing molecules" inside damaged areas to recruit neural stem cells to do repairs. For this, his team has developed an innovative technique called "sonoselective transfection" that avoids opening the blood-brain barriers in brains that are already compromised.

"With stroke, there's a lot of effort to try to salvage as much neural tissue as possible by doing things like gene therapy," he said. "In our lab, we thought, well, maybe we can deliver treatment right to the cells that need it, without breaching the blood-brain barrier. And my students basically figured out how to do that."

That notion of helping the body heal itself, of using focused ultrasound to activate an immune response, could be useful in cancer treatments as well. "We would love to be able to put something into those [tumor] cells that will then allow them to start recruiting immune cells into the tumor," he said. "We have a lot of evidence that we can we can do some interesting things with focused ultrasound with respect to the internal landscape of those tumors."

Price, of UVA's Department of Biomedical Engineering, emphasizes that his work is still early, but he is excited to be creating new techniques that could change how many major diseases are treated in the not-too-distant future.

"We've had good results [with the research] so far. But what I, as an engineer, get excited about are all these tools we have made," he said. "You can use these tools for all these different applications. We think there are a lot of really exciting possibilities."

Men and women aged 40-79 are at significantly lower (25-27%) risk of long or frequent hospital admissions if they do some form of physical activity, a new study suggests.

Inactive participants in the study spent just over 4 days more in hospital over the next ten years than those who did at least some physical activity, whether for work or leisure. And similar results were observed 10 years later when the same participants were 50-90 years old.

The study, by researchers at the University of Cambridge's Department of Public Health and Primary Care and MRC Epidemiology Unit, calculates that for every inactive person who started to take at least some exercise, the NHS could save around £247 per year. This would equate to around 7% of the UK's per capita health expenditure.

The findings, published today (6 May) in BMC Geriatrics, are based on a general British population cohort study of 25,639 men and women aged 40-79 living in Norfolk and recruited from general practices between 1993 and 1997.*

The researchers found that in the first ten years active participants were 25-27% less likely than inactive participants to have more than 20 hospital days or more than 7 admissions per year with similar results over the subsequent ten years. They also reported that in 9,827 study participants with repeated measurements, those who remained physically active or increased their activity were 34% less likely to spend 20 days in hospital.

Lead author Robert Luben from the Institute of Public Health says:

"Our study provides some of the clearest evidence yet that small, feasible increases in usual physical activity substantially reduce the future hospital usage of middle-aged and older people, and would significantly ease pressure on the NHS."

The study is one of relatively few to examine the physical activity (both occupational and leisure-time) of middle-aged and older men and women - validated against heart rate monitoring with individual calibration - and their subsequent healthcare use. As well as studying a large cohort over a long follow-up period, the researchers used record linkage to hospital data and took a range of demographic and lifestyle factors into account.

When recruited, participants completed a lifestyle questionnaire where they were asked about their physical activity. Occupational activity was assessed using a four category question ("sedentary", "standing", "moderate physical work" and "heavy manual work") with examples such as office worker, shop assistant, plumber and construction worker respectively.

Leisure activity in both summer and winter was assessed from the number of hours per week spent cycling, attending keep fit classes or aerobics and swimming or jogging. Estimated average hours of leisure activity was calculated as the mean of summer and winter activities. Based on a score (validated using heart rate monitoring with individual calibration) combining leisure and occupational elements, individuals were categorised as "inactive", "moderately inactive", "moderately active" and "active".

The study found that those with a physical activity score of at least "moderately inactive" had fewer hospital admissions and fewer days in hospital, than those who were "inactive".

While previous studies have suggested that pre-admission physical activity programmes may lower duration of hospital stay, these are short term, require funding and are targeted at a limited number of individuals. But these new findings indicate that usual physical activity patterns in the general population predict hospital usage over the next two decades.

The researchers acknowledge that participants may be physically inactive because of known or preclinical illness which may also predispose them to increased later hospitalisation. But sensitivity analyses excluding those with a self-reported chronic disease at baseline (heart attack, stroke or cancer), and excluding hospital admissions occurring in the first five years of follow-up, did not differ materially from the main findings.

DALLAS, May 6, 2020 -- Teenagers who have obesity, type 2 diabetes or high blood pressure may be more likely to have signs of premature blood vessel aging compared to teens without those health conditions, according to new research published today in the Journal of the American Heart Association, an open access journal of the American Heart Association.

Over five years, researchers evaluated 141 teens with normal weight; 156 who had obesity; and 151 who had type 2 diabetes, with an average age of 17.6 when the study began. At the end of five years, the teens with either obesity, type 2 diabetes or high systolic blood pressure - major risk factors for heart attacks and strokes later in life - were significantly more likely to have thicker and stiffer carotid arteries, the main blood vessel that leads to the brain.

"Our study demonstrates that the slow changes in blood vessels that lead to the development of atherosclerosis begins early in life," said lead study author Justin R. Ryder, Ph.D., assistant professor of pediatrics and associate director of research for the Center for Pediatric Obesity Medicine at the University of Minnesota Medical School in Minneapolis. Atherosclerosis is the slow narrowing of the arteries usually associated with natural aging, and it increases the risk of heart attacks, strokes and other cardiovascular events.

"Having obesity, type 2 diabetes or high systolic blood pressure were each independently associated with and equally predictive of having thicker and stiffer arteries among this group of young people. What surprised our team the most was that participants with higher systolic blood pressure compared to their peers in the study had a very similar risk as those with obesity or type 2 diabetes for thicker and stiffer blood vessels over time," said Ryder.

Carotid artery health was assessed by non-invasive ultrasound and pulse wave velocity. The ultrasound measured the thickness of the inner two layers of the blood vessel, known as carotid intima-media thickness. The pulse wave velocity gauges how fast blood flows through the vessels to determine arterial stiffness. Both measures were taken at the beginning of the study and five years later. The analysis concluded teens with obesity, type 2 diabetes or high systolic blood pressure had greater change in the thickness and stiffness of their arteries, compared to participants in the group with normal weight. This would suggest a greater risk of early heart attacks or strokes among the teens with obesity, type 2 diabetes or high systolic blood pressure.

"Although type 2 diabetes is treated aggressively in the U.S., obesity needs to be treated just as vigorously because it has the same increased risk for premature aging of the blood vessels, which is an early sign of cardiovascular dysfunction and a precursor to cardiovascular diseases in adulthood," according to Ryder.

Strengths of the study included its large study size of almost 150 teens in each group, for a total of 448 participants, and objective measurements of carotid artery health five years apart. A limitation of the research is that the teens will not be followed into adulthood to track if the premature aging of their blood vessels results in heart attacks, strokes and other cardiovascular conditions.

A condition involving excess fat buildup in the liver is grossly underdiagnosed in the United States, according to an analysis of Medicare claims data. The condition, called nonalcoholic fatty liver disease (NAFLD), is often associated with obesity and is not related to alcohol consumption.

In the Alimentary Pharmacology & Therapeutics analysis of information on 10,826,456 adults, the prevalence of NAFLD was 5.7%. NAFLD progressed to the more serious liver disease called cirrhosis in 39% of patients with NAFLD over 8 years of follow-up. Cardiovascular disease, kidney impairment, high cholesterol, and diabetes were linked with higher risks of disease progression.

"The study provides us with evidence regarding the real world natural history of NAFLD and long-term clinical outcomes," said lead author Rohit Loomba, MBBS, of the University of California, San Diego.

Use of emergency contraceptive pills (ECPs) is common among Scandinavian women, with one-third having used them at least once, according to a study published in Acta Obstetricia et Gynecologica Scandinavica.

For the study, women aged 18-45 years were randomly selected in 2011-2012 from national registers in Denmark, Norway, and Sweden. Of the 45,445 women, 33.9% had used ECPs at least once in their lifetime, and among users, 15.8% had used ECPs within the last year and 50.0% had used them more than once in their life.

Higher education, smoking, binge drinking, age at first intercourse, having new sexual partners, and not using condoms with the new partners were associated with ECP use.

"Since ECP use is not protective against sexually transmitted infections, our findings highlight the need to encourage awareness and regular use of condoms to prevent sexually transmitted diseases in women," said lead author Susanne K. Kjaer, MD, DMSc, of the Danish Cancer Society Research Center.

In an analysis of randomized controlled trials, individuals who consumed green tea experienced a significant decline in body weight and body mass index. On the other hand, the analysis did not show any significant change in terms of waist circumference (a measure of abdominal fat) with green tea supplementation. The findings are published in Phytotherapy Research.

The analysis of 26 randomized controlled trials including 1,344 participants found that body weight and body mass index significantly changed after green tea was consumed for periods longer than 12 weeks and at a dosage of less than 800 mg/day.

In a study of adolescents who have used e-cigarettes in the past month, certain factors were associated with frequent use.

In the Public Health Nursing study of 1,556 adolescents in Korea, 55.1% reported that they had used e-cigarettes for 6 to 30 days in the past month and 44.9% used them from 1 to 5 days. Using e-cigarettes because of the belief they may be less harmful than cigarettes, they can be concealed, they're easy to purchase, and they have various added flavors were factors linked to more frequent use. Also, frequent users were more likely to have a higher weekly allowance, less likely to live with family, and more likely to be exposed to second-hand smoke at home.

"Due to the characteristics of e-cigarettes, such as ease of purchase and the addition of taste and flavoring, the risk of continued use in adolescents is particularly high," said corresponding author Hyunmi Son, PhD, RN, an associate professor at Pusan National University, in South Korea. "Regulation of e-cigarettes may prevent continued use among adolescents."

Health care professionals who provide contraceptive services outside of general practice are unlikely to discuss long-acting reversible contraception such as intrauterine devices (IUDs) or implants for young women without children - despite their proven safety, effectiveness and convenience.

A review published in the Journal of Clinical Nursing analysed the views of non-GP health practitioners who are often tasked with delivering contraceptive advice. It found a significant reluctance to recommend these superior contraception options arising from lack of knowledge, time constraints and the influence of inaccurate or outdated personal beliefs.

The practitioners studied included family planning counsellors, midwives, obstetricians and gynaecologists in developed countries (the UK, USA and Germany.)

"Global sexual health organisations have been recommending the use of long-acting reversible contraception such as IUDs and implants for several years, which are safe and carry a very high success rate of 99%," says Carri Welsby, a Flinders University Health Sciences (Honours) graduate and author of the paper.

"Research is strong in support of these efficient and cost-effective methods of preventing unwanted pregnancy, yet there remains low uptake compared to the oral contraceptive pill," Ms Welsby says.

"These findings highlight the need for a greater focus on education and training for non-GP health care professionals on contraception." Ms Welby says.

Her study identified incorrect views on long-acting reversible contraception centred on the risk of side effects, such as inconsistent bleeding, issues with future fertility, ectopic pregnancies and pelvic inflammatory disease.

"As such a wide range of professionals deliver contraceptive advice and services, addressing these knowledge gaps is essential if women are to receive accurate information to make informed decisions," she says.

"For example, the majority of health care practitioners in the literature would not discuss or suggest this form of contraception to women aged below 40 with no children, however a woman's age and gynaecological history should have no bearing on their suitability."

The review also highlights the significant role played by settings outside of general practice in delivering contraception services, and the need to ensure these are included in frameworks to improve clinical practice on modern and new contraceptive methods.

Researchers at the RIKEN Center for Biosystems Dynamics Research (BDR) in Japan have identified changes in the aging brain related to blood circulation. Published in the scientific journal Brain, the study found that natural age-related enlargement of the ventricles--a condition called ventriculomegaly--was associated with a lag in blood drainage from a specific deep region of the brain. The lag can be detected easily with MRI, making it a potential biomarker for predicting ventriculomegaly and the aging brain, which can then be treated quickly.

Ventriculomegaly is an abnormal condition in which fluid accumulates in the ventricles of the brain without properly draining, making them enlarged. Although ventricular enlargement within normal range is not itself considered a disease, when left unchecked it can lead to ventriculomegaly and dementia resulting from normal pressure hydrocephalus. In their study, the team found that ventriculomegaly was associated with changes in blood circulation of the brain. "We found an age-related perfusion timing shift in the brain's venous systems whose lifespan profile was very similar to, but slightly preceded that of ventricular enlargement," explains first author Toshihiko Aso.

After blood circulates through the brain providing necessary oxygen, the deoxygenated blood must return to the heart though our veins. This happens through two pathways, one draining blood from regions close to the surface of the brain, and the other from areas deep in the brain. By using MRI to measure changes in blood flow, the team at BDR recently found that as we age, the time it takes for blood to drain through these two pathways becomes out of sync. The result is a time lag between the deep drainage pathway and the surface pathway, which increases with age.

In the new study, the researchers found that in healthy aging, the time lag in circulation grows at almost the same rate as enlarging ventricles, but begins slightly earlier. A diagnostic MRI that measures an individual's lag between the two drainage pathways might be a good biomarker for the aging brain, and a possible predictor of ventriculomegaly.

They also examined people with traumatic brain injury (TBI) because these individuals often suffer from enlarged ventricles and have brains that appear to have aged prematurely. Analysis showed a time lag in blood drainage that was related to the disease, but this effect depended on the age at injury, being large in people who suffered TBI when they were young, but much less for those who were injured later in life. "The timing asynchrony between deep and superficial venous drainage might therefore be a common mechanism that underlies both types of ventriculomegaly," says Aso. "This new biomarker might therefore be useful for diagnosing and monitoring normal-pressure hydrocephalus that is either age-related or that results from brain injury."

Because dementia resulting from hydrocephalus can be reversed by removing the fluid that builds up in the ventricles, early diagnosis is critical and the researchers at BDR are already developing non-invasive applications of this technology. "We hope that using this biomarker to monitor the aging brain becomes a part of the annual health checkup system for people in Japan."

The anti-cancer medicine venetoclax could improve the current therapy for estrogen receptor-positive (ER+) breast cancer - the most common form of breast cancer in Australia - according to preclinical studies led by Walter and Eliza Hall Institute researchers.

The research team showed that venetoclax could kill breast cancer cells that had been 'put to sleep' by a drug that blocks cell division (called a CDK4/6 inhibitor), which is currently used in combination with hormone therapies to treat ER+ breast cancer. The research, which used breast cancer cells taken from patients, was the first to show that venetoclax could kill sleeping, or 'senescent', cancer cells.

The promising preclinical results for this 'triple therapy' have underpinned a phase 1 clinical trial in Melbourne that is combining venetoclax with hormone therapy and CDK4/6 inhibitors in patients with ER+ breast cancer.

Dr James Whittle, Professor Geoff Lindeman and Professor Jane Visvader led the research, which was published in Clinical Cancer Research.

At a glance

ER+ breast cancers are currently treated with a combination of a hormone therapy plus a CDK4/6 inhibitor drug. These force the cancer cells into a 'sleeping' state but do not kill them, leading to a high risk of eventual cancer relapse.

Using hormone receptor-positive breast cancer samples taken from patients, our researchers showed that adding the anti-cancer drug venetoclax to the hormone therapy/CDK4/6 inhibitor combination could kill the 'sleeping cells' - potentially prolonging the cancer's response to therapy.

The potential new 'triple therapy' for hormone receptor-positive breast cancer is now being assessed in a phase 1 clinical trial in Melbourne.

Killing sleeping cells

Around 70 per cent of breast cancer cases in Australia are estrogen-receptor positive, meaning they will grow in response to the female hormone estrogen. The current 'gold standard' therapy for treating these breast cancers on relapse is a combination of anti-hormone therapy - which prevents estrogen signalling - plus a medicine called a CDK4/6 inhibitor that blocks cell division, said Dr James Whittle, a clinician PhD student at the Institute and a medical oncologist at the Peter MacCallum Cancer Centre.

"This current therapy works well in slowing cancer growth, but it does not actually kill the cancer cells - it just sends them into a sleeping or dormant state, called senescence," he said. "This unfortunately means cancer relapse is virtually inevitable. In fact, the majority of breast cancer deaths in Australia are from patients with ER+ breast cancer.

"If we could find a way to kill these sleeping cancer cells, we might be able to help patients live longer. To do this, we looked to medicines that directly block the proteins that help cancer cells to survive," he said.

The team examined whether ER+ breast cancer cells were sensitive to venetoclax, an anti-cancer medicine that inhibits the cell survival protein BCL-2. Venetoclax is in clinical use for treating certain types of blood cancers, and in clinical trials for a range of cancers including breast cancer.

"We discovered that venetoclax could indeed kill ER+ breast cancer cells that had been treated with a CDK4/6 inhibitor - even those that were senescent. This was an exciting result as it was the first time that venetoclax has been shown to kill senescent cells," Dr Whittle said.

Triple therapy threat for tumours

In several laboratory models, including those using ER+ breast cancer samples from patients, the researchers showed that adding venetoclax to the combination of hormone therapy and a CDK4/6 inhibitor led to a better and longer-term response of the tumour to the therapy, said Professor Lindeman, who is a clinician-scientist at the Institute and a medical oncologist at the Peter MacCallum Cancer Centre.

"These promising results provided a justification for starting clinical trials to look at a 'triple therapy' combining venetoclax, hormone therapy and a CDK4/6 inhibitor in patients with ER+ breast cancer," Professor Lindeman said.

"We have initiated the phase 1 PALVEN trial which will, in the first place, look at whether this triple therapy is safe for patients, and will also consider how patients' tumours respond to the triple therapy.

"It would be wonderful to see a new therapy that improves the outcomes of patients with ER+ breast cancer," Professor Lindeman said.

(Due to COVID-19, the PALVEN trial is currently not accepting new participants).