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Disability rights advocates are concerned that crisis triage protocols aimed at allocating scarce health care resources to save the most lives could be biased against people with disabilities. These concerns have prompted an investigation by the Office of Civil Rights at the Department of Health and Human Services and appeals to Congress to prohibit crisis triage based on "anticipated or demonstrated resource-intensity needs, the relative survival probabilities of patients deemed likely to benefit from medical treatment, and assessments of pre- or post-treatment quality of life."

An article published in the New England Journal of Medicine on May 19 gives policy recommendations that aim to meet the goals of allocating scarce resources primarily to save the most lives, but doing so in a way that explicitly protects core values. such as the equal moral worth of all people. The article, "Covid-19 Crisis Triage--Optimizing Health Outcomes and Disability Rights," was written by Mildred Z. Solomon, EdD, president of The Hastings Center; Matthew K. Wynia, MD, MPH, a professor at the Colorado School of Medicine and the Colorado School of Public Health and director of the Center for Bioethics and Humanities at the University of Colorado Anschutz Medical Campus; and Lawrence O. Gostin, JD, director of the O'Neill Institute for National and Global Health Law at Georgetown Law School.

"Allocation of ventilators has become symbolic of the difficult ethical choices we face, but the criteria and processes we recommend apply to any scarce medical resource," the authors write.

Crisis triage arises when not everyone can receive essential care. Some disability rights advocates argue that triage based on assessing patients' likelihood of benefit is fundamentally incompatible with respect for human dignity. Instead, these advocates call for allocating ventilators and other resources on a first-come, first served basis. But this approach would result in more deaths overall and would leave many people with disabilities worse off, especially if they face barriers in accessing care, such as difficulty with transportation and communication, write Solomon, Wynia, and Gostin.

"We believe that crisis triage protocols should focus on identifying the patients who are most likely to die without a ventilator yet most likely to survive with one, using the best available clinical survivability scores, not broad categorical exclusions," they write.

The authors recommend focusing on near-term survivability--living 1 year after hospital discharge--rather than on long-term survival because near-term survivability can be assessed more accurately, whereas long-term survival is hard to predict and, therefore, subject to bias.

The most controversial triage protocols, the authors state, are those that aim to maximize the number of life-years saved, either by prioritizing young people over older ones or by giving lower priority to people with severe life-limiting illnesses. "Both kinds of life-year considerations are ethically acceptable, though only as tiebreakers," they write. "Privileging younger patients is justifiable because it's based not on stereotyping or bias against older patients but on equal opportunity and minimizing harm: the younger persons have had less opportunity to experience a full life and therefore would suffer greater harm if they were to die."

With regard to advanced illness, if two patients have the same likelihood of near-term survival, but one patient has advanced cancer and a low likelihood of 5-year survival, the authors say that it would be ethical to choose the person with the greater prospect of living longer. "It would not be acceptable, however, to assume that all patients with a given disability have shorter life expectancies than other patients and decide that therefore none should receive scarce resources," they write.

Solomon summed up the rationale for writing the paper. "Discrimination against the disabled in health care is well documented, so it behooves us to ensure that triage protocols do all they can to avoid bias," she said. "Responsible health systems and health care leaders are doing the nation a service by anticipating the potential, tragic need for these protocols and working to design them as responsibly as possible."

Given that the science and epidemiology of Covid-19 are rapidly changing, the authors recommend that health care organizations consider current triage protocols provisional. "To ensure the trustworthiness of the health system," they write, "disability rights advocates and health care leaders should work together to finalize crisis triage plans that save the most lives, protect the equal worth of all persons, and enhance communities' capacity to heal in the wake of a once-in-a-century pandemic."

OAK BROOK, Ill. - Women with mammographically detected breast lesions that are probably benign should have follow-up surveillance imaging at six months due to the small but not insignificant risk that the lesions are malignant, according to a new study published in the journal Radiology.

The Breast Imaging and Reporting System (BI-RADS) was established by the American College of Radiology to help classify findings on mammography. Findings are classified based on the risk of breast cancer, with a BI-RADS 2 lesion being benign, or not cancerous, and BI-RADS 6 representing a lesion that is biopsy-proven to be malignant.

BI-RADS 3, a probably benign finding, is a particularly challenging category that can cause confusion for physicians and anxiety for patients. This assessment means that the lesion is one of a few specific findings that has been shown to have less than a 2 percent chance of being cancer and that any cancer present is not likely to spread in the time frame recommended for follow-up imaging.

The interval for follow-up imaging has been a point of contention in the breast imaging community. Some earlier research suggested that malignancies were so rare in the BI-RADS 3 group that follow-up could be safely pushed back from six months to a year. However, much of that research was done before the advent of the National Mammography Database (NMD).

"I thought that we should really look at this again now that we've got this large database we can work with and try to find out what happened with these patients," said study lead author Wendie A. Berg, M.D., Ph.D., a renowned breast cancer researcher at the University of Pittsburgh School of Medicine and professor of radiology at UPMC Magee-Womens Hospital in Pittsburgh.

Dr. Berg and colleagues assessed outcomes from six-, 12-, and 24-month follow-up of probably benign findings first identified on recall from screening mammography in the NMD. The study group included women recalled from screening mammography with BI-RADS 3 assessment at additional evaluation over a period of almost 10 years. The women in the study group had no personal history of breast cancer and underwent either biopsy or two-year imaging follow-up.

Out of 43,628 women given BI-RADS 3 assessment after screening mammography recall, 810 (1.9%) were diagnosed with cancer. About a third had ductal carcinoma in situ (DCIS), an early-stage, noninvasive form of breast cancer. However, 12% of the invasive cancers diagnosed within six months with node staging had spread to the lymph nodes.

"The majority of cancers were diagnosed at or right after the six-month follow-up, so it actually is important to get these patients back in that six-month time frame," Dr. Berg said.

The malignancy rates in the BI-RADS 3 group substantially exceeded those of women downgraded to BI-RADS 1 or 2 at each follow-up, further supporting short-interval follow-up imaging surveillance.

"The important thing about this paper is that these data come from a wide number of facilities across the United States, so it really brings to bear that, yes, this is the appropriate practice and yes, you still need to see these patients in six months," Dr. Berg said.

Dr. Berg has also been studying how a personal history of breast cancer affects malignancy rates in women with BI-RADS 3 findings. Preliminary findings she reported at the 2019 RSNA annual meeting indicate that the malignancy rate could be as high as 15%.

"That suggests that we should probably be much more cautious about BI-RADS 3 findings in those patients," she said.

While it's too soon to use COVID-19 antibody testing to issue "immunity passports", antibody tests that are available today are good enough to inform decisions about public health and relaxing social distancing interventions, says an international group of infectious disease and public health experts in Science Immunology today.

"We don't need to wait for the perfect test to monitor populations. We can use what we have if we go in with our eyes open," says University of Utah Health infectious disease physician-researcher Daniel Leung, M.D. He is corresponding author on the editorial together with specialists from seven different countries and leading public health institutions in the U.S., including Johns Hopkins Bloomberg School of Public Health, Harvard School of Public Health, University of California, San Francisco and Pennsylvania State University.

Today's Tests are Ready for Populations, Not People

Some have suggested that detecting antibodies to SARS-CoV-2 -- the coronavirus that causes COVID-19 -- become the basis of "immunity passports" that enable people to return to work or school, or to travel. Yet, facts indicate that it is premature to take that step. For one, scientists have yet to determine whether the antibodies, or perhaps a threshold level of antibodies, protect a person from being re-infected. For another, there are multiple antibody tests, none with the levels of specificity needed to declare someone immune.

In short, we are far from being at a place where a positive antibody test guarantees that a person cannot get COVID-19 nor spread it to someone else, the authors say. And the stakes are too high to risk getting it wrong.

Regardless, these same tests are good enough to monitor the spread of COVID-19 in populations. "There is no need to throw out the baby with the bathwater," says Leung. "We can use serological testing at the population level to get valuable information about transmission and the impact of interventions, and we don't need a perfect serology test to do it."

Understanding trends such as where outbreaks are occurring and which regions are quiet, and the characteristics of who is getting ill and who is protected, can provide information to guide policy. Is a specific county ready to ease restrictions? Are students safe to go back to school? Do certain populations need extra protection?

Fine-Tuning Existing Tests to Meet Different Needs

One reason many of today's tests can work for public-level decisions is that they do not just give black and white answers. Instead, their parameters can be adjusted to fit different needs. One of these characteristics is specificity -- how well a test detects antibodies to SARS-CoV-2 and not to antibodies against other coronaviruses. The other is sensitivity -- the minimum level of antibodies someone must have in their blood in order to test positive.

In general, there is a tradeoff between the two. Adjusting a test to prioritize sensitivity makes it not as specific, and making a test more specific makes it less sensitive. But it's ok to sacrifice one for the other in order to answer certain questions, the editorial says.

Take the situation in a rural countryside where relatively few people have had COVID-19 per capita. In that setting, a test with high sensitivity and low specificity would not be optimal. These characteristics could easily result in the same number of people testing positive who never had COVID-19 as the number of people who really are positive. In this situation, the results would be practically meaningless.

However, the same test can be used if it is tuned for that situation. This can be done by designating a higher cutoff and saying that a test does not count as positive unless it has a stronger signal. Doing so lowers the false positive rate by increasing specificity. In this scenario, positive tests are more likely to be truly positive and that data can be safely used to monitor that population.

On the other hand, an urban setting where higher proportions of the population have been infected would do better with a test prioritized for higher sensitivity. That would give a better snapshot of the spread of COVID-19 by capturing a greater segment of the population.

Additional studies will only make the results of antibody testing more informative. The editorial specifies that we still need to understand whether antibodies remain in the body for months or years, what levels of antibodies provide immunity, and how responses might differ in people who had various severity of infection, or who have other medical conditions.

The authors say that equally as important as leveraging the technologies at hand is building an infrastructure that allows states and countries to share protocols, standardize methods, share results and coordinate activities. This would not only improve the response to the current pandemic but could build a foundation for monitoring other infectious diseases including influenza, cholera, malaria and future pandemics.

The editorial sums up the advantages that stand to be gained. "The current crisis presents an opportunity to rethink how health systems generate and use surveillance data and how to harness the power of serological tests and seroepidemiology."

Singapore, 19 May 2020 -- Very young children exposed to antibiotics at an early age (from birth to 12 months) are associated with higher risks of childhood obesity and increased adiposity in early to mid-childhood. The findings by a team of researchers from Singapore's NUS Yong Loo Lin School of Medicine (NUS Medicine), Agency for Science, Technology and Research's (A*STAR) Singapore Institute for Clinical Sciences (SICS), and KK Women's and Children's Hospital (KKH) were published in the scientific journal International Journal of Obesity in April 2020.

Animal studies using mice have documented that early life antibiotic exposure causes metabolic abnormalities including obesity through gut microbiota disruption although there is limited evidence from human studies.

There is also accumulating evidence that suggests colonization of the gut microbiota at an early age plays a pivotal role in the weight gain and development of obesity in the later life (between ages 12-14).

In a sub-study of the Growing up in Singapore Towards healthy Outcome (GUSTO) birth cohort, led by Professor Lee Yung Seng, Head of Paediatrics at NUS Medicine and Group Director, Paediatrics, National University Health System (NUHS) and Principal investigator at SICS, and Dr Neerja Karnani, Adjunct Assistant Professor at NUS Medicine's Department of Biochemistry and Senior Principal Investigator, SICS, the team examined the implication of gut microbiota in the relationship between infant antibiotic exposure and childhood obesity. Other lead researchers for this study are Dr Ling-Wei Chen and Dr Jia Xu from SICS, A*STAR. Very few human studies to date have examined this association.

Through the study, the team showed that use of antibiotics in infancy can raise the risk of obesity in early childhood, with the boys being slightly more vulnerable. Recurrent administration of antibiotics can disrupt the development of infant gut microbiota and serve as a potential mechanism for linking antibiotic exposure with later adiposity.

"Childhood obesity is a growing concern for the many adverse health effects it brings in adulthood such as Type 2 diabetes. The infancy period (1st year) represents part of a critical window of development which can have a lasting effect on subsequent health and disease later in life," explained Prof Lee.

The human gut relies on its microbial inhabitants to provide certain essential nutrients, aid digestion, and support their immune system. Acquisition of these friendly microbes starts immediately after birth and this process is highly sensitive to infant exposures. Antibiotics use is one such exposure. Although it helps eliminate the pathogenic bacteria, it may also eliminate some good bacteria during the course of its action.

"Acquisition of gut microbes in infancy is a highly dynamic and vulnerable process. Use of antibiotics during this process can disrupt the normal colonization and development of infant gut microbiota, and this may consequently influence a child's weight gain and obesity risk," added Dr Karnani.

The associated alterations in the gut microbiota through the use of antibiotics and their link with child adiposity has important implications on the role of gut microbiota in the development of body fat and risk of obesity, and the mechanism through which antibiotics exposure can lay the foundation for bad metabolic outcomes in the future. The findings of this study amplify the need for the careful consideration of the benefits vs the risks of administrating antibiotics and the frequency of their use in early life.

The data from the study was based on interviewer-administered questionnaires with parents, body composition measurements, and laboratory analysis of stool samples in children from the GUSTO mother-offspring cohort study.

Eager to ramp up your fitness while stuck at home? A new generation of virtual reality (VR) exergames nudges home-based cyclists to perform a lot better by immersing them in a crowd of cyclists. And as all cyclists participating in the race are versions of the flesh-and-blood player, the Covid-19 norms of social distancing are maintained even in the parallel universe of VR.

The discovery that exergamers get fit twice as fast when they race against multiple versions of themselves rather than pedalling alone was made by researchers at the REal and Virtual Environments Augmentation Labs (REVEAL), based at the University of Bath. The studies were conducted by Computer Science student Alex Michael and the paper was published by this year's CHI Conference on Human Factors in Computing Systems.

Self-competition is a known feature in the world of racing exergames. It involves a player going head-to-head with an opponent who is a replay (or 'ghost') from a past performance. The researchers at Bath are the first to create a VR bicycle-racing game where players compete against an entire crowd of ghosts - including a ghost of the future.

Dr Christof Lutteroth from the Department of Computer Science, who led the research, said: "People get a richer racing experience by playing against both their performance history and a model of their future performance. They are motivated to push themselves harder in order to beat all of their ghosts. It becomes obvious when you're getting fitter because you stay ahead of the pack."

The Bath study ran over four weeks and implemented a five-minute High-Intensity Interval Training (HIIT) protocol, with participants alternating between periods of low intensity cycling and high-intensity sprints. Participants increased their power output twice as much when compared to solitary racers and also hit higher heartrates.

Competing against a single ghost already yields better results than solitary racing. However, a multi-ghost race is better still, as exercisers put in even more effort, enjoy themselves more and perceive themselves as more capable.

"In other words, participants exert themselves more intensely and have more fun," said Dr Lutteroth. "We think this offers exciting possibilities for motivating rapid performance improvement in exergames and may also apply to other types of activities."

The rise of self-competition VR exergames

Full-immersion VR exercise games are proving popular among people who consider themselves neither fit nor competitive in sport.

"Not enjoying exercise is one of the biggest barriers to doing exercise long-term," explained Dr Lutteroth. "By making exercise intrinsically more fun and motivating, we're taking an important step towards tackling the global epidemic of sedentary behaviour."

He added: "Ghost racing highlights the importance of competing against opponents with similar abilities to you. When you're well matched with the people you're racing against, you have a realistic chance of winning, which motivates you and lets you avoid the stigma of losing."

Dr Lutteroth says the main aim of his research is to find fast, fun antidotes to people being inactive. Moving too little is a leading cause of obesity, mental health problems and preventable death.

"And of course, a sedentary lifestyle is particularly prevalent when we're in lockdown," he said.

He hopes his findings will spark interest both from individuals keen to get fit, and from the wider world of sport and fitness. "It would be amazing if this research could have a wider impact on society," he said. "In an ideal world, the benefits of ghost racing would reach gyms, sports clubs, and charities involved in physical and youth activities - in fact, any organisation that aims to improve physical and mental health."

"Regular endurance training and good fitness seem to protect against serious cardiovascular events and early mortality for people diagnosed with atrial fibrillation," says exercise physiologist Lars Elnan Garnvik.

Garnvik recently completed his doctorate at the Norwegian University of Science and Technology. His latest article was recently published in the prestigious European Heart Journal.

Garnvik and his colleagues in the Cardiac Exercise Research Group (CERG) have investigated how physical activity and good fitness levels are linked to future health risks for men and women who have been diagnosed with atrial fibrillation.

"The results show that people with atrial fibrillation who meet the authorities' recommendations for physical activity generally live longer than patients who exercise less. They also have almost half the risk of dying from cardiovascular disease," says Garnvik.

The minimum recommendation is to be physically active for 150 minutes of moderate intensity or 75 minutes of high intensity exercise each week. Moderate intensity means getting out of breath and sweaty, but still able to carry on a conversation. At high intensity you are so out of breath that you can't speak in longer sentences.

"We found that both moderate and high intensity training are associated with significantly reduced risk," says Garnvik.

People with atrial fibrillation have a higher health risk than same-aged individuals who do not have the disease. The new NTNU study also shows that inactive men and women with atrial fibrillation generally die earlier than inactive men and women without the condition.

"On the other hand, the risk for physically active participants with atrial fibrillation wasn't higher than for physically inactive healthy people in the same age group," Garnvik says.

The study includes a total of 1117 people who participated in the Trøndelag Health Study (HUNT Study) between 2006 and 2008. All had a confirmed atrial fibrillation diagnosis, and their average age was over 70. Garnvik used national health records to find out who died or was impacted by cardiovascular disease in the years leading up to and including 2015.

"It's worth noting that this is an observational study, so the results cannot be used to establish definite causal relationships. However, we've tried to isolate the relationship between exercise and health risk as much as possible by adjusting the analyses for all other known differences between people who exercise a lot and a little," he says.

In the study, the researchers calculated the condition of atrial fibrillation patients with CERG's widely used Fitness Calculator. It was found that the participants with the lowest calculated fitness levels had the highest mortality risk during the follow-up period.

"For every 3.5 point increase in fitness score, the risk of dying dropped by 12 per cent over the next eight to nine years. In the case of cardiovascular-related deaths, this risk reduction was 15 per cent," Garnvik says.

The fact that fitness is important is not new information.

"Both our research and other research suggests that staying in shape can be even more crucial to health than the level of physical activity. Our genes determine some of our fitness, but the vast majority of people can improve on their gene pool by exercising properly. This is also the case for individuals with atrial fibrillation," he says.

Training in a way that actually influences your fitness level is especially important.

"Our research team has repeatedly shown that high-intensity interval training is more effective than moderate exercise for improving fitness. This is true for both healthy individuals and people with different types of lifestyle diseases," says Garnvik.

No specific training recommendations for people with atrial fibrillation have been published yet. Last year, however, another CERG researcher completed his doctorate on the same topic. Cardiologist Vegard Malmo's studies show that interval training using the 4 × 4 method is very effective for this group as well.

"The findings suggest that aerobic interval training has the same beneficial effect on risk factors in people with atrial fibrillation as in patients with other cardiovascular illnesses," says Malmo.

Four months of regular interval training reduced both the recorded flutter length and the symptoms of the disease. In addition, the exercise provided better quality of life and heart function. And last but not least: the training resulted in a marked increase in fitness.

"Lifestyle changes, including exercise, should be key for treating atrial fibrillation," Malmo says.

Biathlete Ole Einar Bjørndalen had to end his sports career due to atrial fibrillation. Cross-country ski racer Marit Bjørgen has experienced flutter episodes, and the same goes for several other high-level Norwegian and international endurance athletes.

"We know that very high levels of exercise over many years can increase the risk of developing atrial fibrillation. However, this is not something most of us need to worry about. Too little physical activity is a much greater cause of atrial fibrillation in the population than people exercising too much," says Garnvik.

The people who exercise the most probably don't tend to be the first to get scared and stop exercising if they have a flutter episode. A study of older people who participated in the Birkebeinerrennet - an annual long-distance cross-country ski marathon held in Norway - shows that two-thirds of these super-exercisers continue to train actively even after being diagnosed.

And they can do that with good conscience. Recently, Vegard Malmo and other Norwegian experts published an overview article on exercise and atrial fibrillation and concluded by saying:

"We believe that most athletes with non-permanent atrial fibri

May 19, 2020-- A new paper published online in the Annals of the American Thoracic Society describes a nimble, pragmatic and rigorous multicenter clinical trial design to meet urgent community needs in the face of the COVID-19 pandemic.

In "Hydroxychloroquine vs. Azithromycin for Hospitalized Patients With Suspected or Confirmed COVID-19 (HAHPS): Protocol for a Pragmatic, Open Label, Active Comparator Trial," Samuel Brown, MD, MS, and co-authors report on the design of a clinical trial, now underway, that they were able to quickly establish and adopt in community and academic hospitals throughout Utah comparing hydroxychloroquine and azithromycin as potential COVID-19 treatments.

"We developed the trial in response to local pressures for widespread, off-label use of these medications," said Dr. Brown, director of pulmonary and critical care research at Intermountain Healthcare in Salt Lake City, who oversees the Center for Humanizing Critical Care at Intermountain Medical Center. "This, and past experience with Ebola, underscored the need for nimble, timely, rigorous controlled trials in a pandemic setting."

The researchers hope to recruit up to 300 study participants with varying degrees of COVID-19 severity from within the Intermountain Healthcare and University of Utah health systems.

The study design differs from that of other randomized, controlled trials in that it does not have a placebo arm.
"Placebos can take weeks or months to manufacture and distribute and generally require a research pharmacy to manage," Dr. Brown explained. "We were able to launch quickly because we didn't have to wait for the placebo manufacture. We were also able to start the trial at hospitals that don't have research pharmacies, including many community hospitals. It's really been an all-hands-on-deck effort."

In place of a placebo, the investigators chose to use a comparator drug - the antibiotic azithromycin. Because the drug showed anti-inflammatory pulmonary effects and other potential benefits in some previous trials, they felt it might have efficacy, and have a very low likelihood of harm due to its established safety profile.

The study is a prospective, randomized, open-label, active comparator trial of hydroxychloroquine versus azithromycin among hospitalized patients with confirmed or suspected COVID-19. Study participants in the hydroxychloroquine arm receive 400mg twice a day for one day, followed by 200mg twice daily for four days.

Participants in the azithromycin study arm receive 500mg on the first day, plus 250mg daily on days two through five.
These patients are monitored remotely on a daily basis while receiving the study medication for adverse events and possible introduction of other medications that may result in cardiac problems.

Study participants are observed for 14 days, at which point their progress or decline are assessed (primary endpoint) based on the WHO COVID Ordinal Outcomes Scale. Secondary endpoints are calculated at 28 days based on whether they are hospital-free, ventilator-free and ICU-free.

A formal statistical analysis plan will be written prior to the initial formal interim analysis. New information may come to light that makes it necessary to modify the study protocol and analyses, due to the rapidly evolving state of knowledge about the COVID-19 pandemic.

The authors concluded: "Faced with the prospect of massive statewide expansion of clinical use of untested therapies with unknown risk/benefit profiles in COVID-19 and operating within the context of global placebo-controlled trials being launched in parallel, we initiated a pragmatic trial intended to both provide treatment options in a structured environment, with informed consent and formal safety monitoring, and to contribute to knowledge about which treatment strategies may be of use in subsequent waves of COVID-19 activity."

New Rochelle, NY, May 18, 2020--Pregnant and breastfeeding women have been excluded from clinical trials of drugs to treat COVID-19, and as result, there is no safety data to inform clinical decisions. Such drugs include remdesivir according to a new article in the peer-reviewed journal Breastfeeding Medicine. Click here to read the article.

Since pregnant and lactating women are not included in clinical trials, little is known about whether the drug transfers into breast milk and reaches the infant's circulation.

The lack of such data complicates a decision between giving lactating women a potentially life-saving drug and having them stop breastfeeding or risking any potential adverse effects of the drug on the infant, writes Alison Stuebe, MD, University of North Carolina School of Medicine and President of the Academy of Breastfeeding Medicine.

Suspending breastfeeding in mothers infected with COVID-19 could be detrimental because the infant is missing out on critical nutrients in human milk. Additionally, antibodies acquired from the mother may protect the infant against acquiring COVID-19.

"This quandary illustrates the consequences of longstanding policies to exclude pregnant and lactating women from clinical trials," Stuebe says. "Rather than excluding pregnant and lactating women from research, we must protect them through research."

Arthur I. Eidelman, MD, Editor-in-Chief of Breastfeeding Medicine, states: "Pregnant and breastfeeding women and their fetuses and infants cannot continue to be administrative orphans regarding new drug trials, and this situation warrants immediate correction."

Climate change threatens prospects for further progress in cancer prevention and control, increasing exposure to cancer risk factors and impacting access to cancer care, according to a new commentary by scientists from the American Cancer Society and Harvard T. H. Chan School of Public Health.

The commentary, appearing in CA: A Cancer Journal for Clinicians, says that progress in the fight against cancer has been achieved through the identification and control of cancer risk factors and access to and receipt of care. And both these factors are impacted by climate change.

The authors say climate change creates conditions favorable to greater production of and exposure to known carcinogens. Climate change has been linked to an increase in extreme weather events, like hurricanes and wildfires, which can impact cancer. Hurricane Harvey for example inundated chemical plants, oil refineries, and Superfund sites that contained vast amounts of carcinogens that were released into the Houston community. Wildfires release immense amounts of air pollutants known to cause cancer. Both events can affect patients' exposure to carcinogens and ability to seek preventive care and treatment; they threaten the laboratory and clinic infrastructure dedicated to cancer care in the United States.

The authors also propose ways to diminish the impact of climate change on cancer, because climate change mitigation efforts also have health benefits, especially to cancer prevention and outcomes. For example, air pollutants directly harmful to health are emitted by combustion processes that also contribute to greenhouse gas emissions. Some dietary patterns are also detrimental to both health and the environment. The agricultural sector contributes to approximately 30% of anthropogenic greenhouse gas emissions worldwide. Meat from ruminants have the highest environmental impact, while plant-based foods cause fewer adverse environmental effects per unit weight, per serving, per unit of energy, or per protein weight. Replacing animal source foods with plant-based foods, through guidelines provided to patients and changes made in the food services provided at cancer treatment facilities, would confer both environmental and health benefits.

"While some may view these issues as beyond the scope of responsibility of the nation's cancer treatment facilities, one need look no further than their mission statements, all of which speak to eradicating cancer," write the authors. "Climate change and continued reliance on fossil fuels push that noble goal further from reach. However, if all those whose life work is to care for those with cancer made clear to the communities they serve that actions to combat climate change and lessen our use of fossil fuels could prevent cancers and improve cancer outcomes, we might see actions that address climate change flourish, and the attainment of our missions to reduce suffering from cancer grow nearer."

What The Study Did: Following an outbreak of electronic cigarette or vaping product use-associated lung injury (EVALI) linked to hospitalizations and deaths, this  study used data reported to the Centers for Disease Control and Prevention to compare demographic and clinical characteristics, along with substance use behaviors, between adolescents and adults with EVALI.

Authors: Susan H. Adkins, M.D., of the Centers for Disease Control and Prevention in Atlanta, is the corresponding author.

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

(doi:10.1001/jamapediatrics.2020.0756)

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

Understanding people's short- and long-distance travel patterns can inform economic development, urban planning, and responses to natural disasters, wars and conflicts, disease outbreaks like the COVID-19 pandemic, and more. A new global mapping method, developed by scientists from Boston Children's Hospital and the University of Oxford, provides global estimates of human mobility at much greater resolution than was possible before. It is described in a paper published May 18 in Nature Human Behaviour.

Data scientists led by Moritz Kraemer, DPhil, of Boston Children's and the University of Oxford, and John Brownstein, PhD, head of the Computational Epidemiology Lab at Boston Children's, aggregated weekly human movement data from Google Location data in 2016. This captured the movements of 300 million mobile phone users from almost all countries of the world. The scientists estimate that their work captured 65 percent of inhabited land surface representing about 2.9 billion people, a greater reach than previous mobility studies.

"This dataset from Google provides an amazing leap forward in our ability to understand population mobility," says Brownstein, who is also chief innovation officer at Boston Children's. "As evidenced by the emergency of COVID-19, being able to quantify movement can fuel our ability to track outbreaks, predict populations at risk and help us evaluate the effectiveness of interventions."

Incorporating statistical machine learning techniques, the results were fine-grained enough to allow comparisons of movement patterns country by country and based on factors like local geography, infrastructure, degree of urbanization, and income, which may affect people's capacity to respond to societal and economic changes.

The data revealed many clear patterns. For example, human movements peaked around traditional vacation times and holidays such as Easter, the Hajj, and, in the U.S., Thanksgiving. Movements were greater in areas with higher populations and smartphone usage. Weather patterns (extreme cold, monsoons) clearly affected travel patterns. In certain countries, cross-border labor migrations could be detected, and large migration flows were detected from countries experiencing crises, such as Syria.

In low-income settings, movements tend to focus around individuals' home locations; long-distance movements were recorded much less frequently compared to people in high-income settings.

"We hope that our findings can help understand why diseases may spread faster in some regions than in others, and ultimately become the baseline for predicting disease propagation," says Kraemer, now in the Department of Zoology at Oxford.

The researchers acknowledge the limitations of their study. For example, they only had access to data from 2016, and while mobile phones are ubiquitous worldwide, subscriptions and service vary by income and geography. They are now expanding upon its work to map real-time shifts in human mobility during the COVID-19 pandemic.

"We anticipate that, by measuring these changes in real time, we will substantially improve our ability to forecast global phenomena, including infectious disease propagation," they write.

As the world focuses on finding a COVID-19 vaccine, research continues on other potentially catastrophic pandemic diseases, including Ebola and Marburg viruses.

The world cannot afford to take our eye of other threats, says Flinders University Professor Nikolai Petrovsky, who warns the highly lethal and infectious Ebola virus could appear in a more virulent form.

"While a live virus vaccine has recently been developed to protect against Ebola, it is not necessarily effective against all forms of Ebola and Marburg and is sensitive to heat which requires it to be stored frozen - a problem in poor tropical countries in Africa with erratic power supplies, which is where Ebola resides," he says.

In the latest collaboration with US partners, a vaccine turbocharger called Advax™ adjuvant, developed at Professor Petrovsky's Australian laboratory was combined with a synthetic protein against Ebola developed by the United States Army Medical Research Institute of Infectious Disease (USAMRIID).

The resulting vaccine appeared to be highly protective against a lethal Ebola virus infection in mice, including after just a single injection. As well, the protection generated by the vaccine was long-lasting and shown to be able to be transferred to naïve mice using antibodies taken from the immunised mice.

This work provides promise that a more convenient and heat stable version of the Ebola vaccine can be developed, which could then play a key role in preventing further Ebola outbreaks in Africa, Professor Petrovsky says.

"While developing a COVID-19 vaccine is a top priority including for our team, we must also continue developing vaccines against a wide range of other potentially catastrophic pandemic diseases including Ebola and Marburg viruses, as these continue to periodically jump from wild animals to people in Africa," he says.

The Petrovsky lab and Vaxine Pty Ltd is currently using the same Advax™ vaccine turbocharger approach to develop a recombinant protein vaccine against COVID-19, which is now in late stage animal testing ahead of human trials in Australia.

"Like coronaviruses, we must continue research into improving the world's vaccine pipeline for diseases, particularly rapidly changing viral infections believed to be transmitted to people from wild animals," he says.

The World Health Organisation notes Ebola virus disease (EVD) is a severe, generally fatal illness with an average case fatality of over 50%.

The 2014-2016 outbreak in West Africa was the largest and most complex Ebola outbreak with more cases and deaths than all others combined since the virus was discovered in 1976. It also spread between countries, starting in Guinea then moving across land borders to Sierra Leone and Liberia.

Infected patients travelled to many countries around the globe before the outbreak was stopped by quarantine measures.

Of all the hepatitis viruses, D is the most poorly known. This small virus, which can only infect people already infected with Hepatitis B, has so far been little studied. Hepatitis D is one of the most dangerous forms of chronic viral hepatitis because of its possible progression to irreversible liver diseases (cancer and cirrhosis, in particular). Scientists from the University of Geneva (UNIGE) and the Geneva University Hospitals (HUG) have studied the most serious consequence of chronic hepatitis: hepatocellular carcinoma, a particularly aggressive and often fatal liver cancer. By conducting a systematic review of the literature and a meta-analysis of all available data, they demonstrated that people infected with Hepatitis D have up to three times the risk of developing hepatocellular carcinoma compared to those infected only with Hepatitis B. These results, to be read in the Journal of Hepatology, plead for systematic screening of Hepatitis D in patients with Hepatitis B in order, on the one hand, to better manage patients and, on the other hand, to better understand the real prevalence of the disease.

There are five types of hepatitis viruses, with very different manifestations and consequences. Hepatitis A and E cause acute infections that can be severe but transient. Hepatitis B, C and D, however, can become chronic and cause liver dysfunction months or even years after infection. Although Hepatitis C is now well treated, Hepatitis B and especially D are still difficult to control. "The most serious consequence of Hepatitis B and D is hepatocellular carcinoma, explains Francesco Negro, Professor at the Department of Pathology and Immunology of UNIGE Faculty of Medicine and Head of the HUG Viropathology Unit. It was already known that co-infection of Hepatitis B and D accelerates the progression of cirrhosis. However, to what extent co-infection of Hepatitis B and D accelerates the progression towards this particularly aggressive liver cancer? This remained to be evaluated."

"To find out whether Hepatitis D is even more dangerous than B, we carried out a systematic review and meta-analysis of all epidemiological studies, explains Dulce Alfaiate, a researcher at the Department of Pathology and Immunology of UNIGE Faculty of Medicine and first author of this work. To do this, we re-examined the data presented in 93 studies, representing a total of more than 100,000 patients. Although not all these studies are of similar quality, the analysis of the best of them is very clear: patients with Hepatitis D have an almost threefold risk of developing hepatocellular carcinoma compared to those with Hepatitis B alone. That's huge!"

At least 15 million people infected worldwide

According to World Health Organization figures, hundreds of millions of people are infected with the Hepatitis B virus. In some regions, such as Polynesia and some African countries, more than 6% of the adult population is infected and the virus is largely transmitted from mother to child. Moreover, children infected at birth almost always develop the chronic form of the disease.

The Hepatitis D virus in turn infects a significant proportion of Hepatitis B carriers, but the extent of the problem is unknown. "Some estimates suggest that at least 15 to 20 million people are infected with Hepatitis D, whereas other estimates may reach 60 million, almost double the number of people living with HIV worldwide, says Dulce Alfaiate. In the absence of systematic testing, however, it is extremely difficult to be precise." In Switzerland, an estimated 25,000 people live with Hepatitis B, among whom 1,500 with Hepatitis D. And this in spite of an available and effective Hepatitis B vaccine.

A call for research

Apart from interferon, an antiviral and an immuno-modulator with limited effectiveness but with deleterious side effects, there is currently no treatment for Hepatitis D. "In our view, the evolution towards liver cancer is grossly underestimated, Francesco Negro points out. And yet, this disease affects young patients who suffer from cirrhosis as early as the age of 25-30 years."
Several ways of controlling the disease are currently being explored: Francesco Negro's laboratory is studying the epigenetic changes induced by the virus and the mechanism of giving rise to liver tumours. The authors conclude: "Our work underlines the need to improve Hepatitis D screening in Hepatitis B patients and the urgent need for effective antiviral therapies, such as the one against Hepatitis C, which has saved the lives of millions of people since 2011."

PORTLAND, OR - Researchers from SWOG, a cancer clinical trials group funded by the National Cancer Institute (NCI), part of the National Institutes of Health, will make 31 presentations as part of the ASCO20 Virtual Scientific Program, the online annual meeting of the American Society of Clinical Oncology (ASCO), which runs May 29-31.

Due to the coronavirus pandemic, ASCO officials cancelled the annual Chicago meeting, the world's largest cancer research conference, and switched to an online format. About 2,215 abstracts will be presented over three days, and more than 3,400 abstracts were accepted for online publication. SWOG investigators will report on trials involving cancer treatment, prevention, and care strategies, as well as results of the first trial run through the NCI's National Clinical Trials Network (NCTN) to focus on financial toxicity - the severe financial and emotional toll exacted on patients by the costs of their cancer care.

Davendra Sohal, MD, MPH, an associate professor at the University of Cincinnati, will deliver an oral presentation on the primary findings from S1505, a randomized SWOG trial that compares two common chemotherapy regimens for early-stage pancreatic cancer, and tests chemotherapy prior to pancreatic cancer surgery.

In S1505, one group of pre-surgery patients received modified FOLFIRINOX, or mFOLFIRINOX, a combination of three chemotherapy drugs - fluorouracil, irinotecan, and oxaliplatin. The other group received a combination of gemcitabine and nab-paclitaxel. Sohal and his team found that chemotherapy treatment prior to surgery results in good outcomes - regardless of the drugs patients receive. Of the patients who received mFOLFIRINOX, 73 percent underwent surgery for their pancreatic cancer, while 70 percent of patients who received gemcitabine and nab-paclitaxel underwent surgery. Two years after treatment, 43 percent and 47 percent of all eligible patients who started treatment were alive in the mFOLFIRINOX and gemcitabine and nab-paclitaxel arms, respectively.

"We didn't find that one regimen was better than the other," Sohal said. "We did demonstrate that treating pancreatic cancer patients with chemotherapy before surgery can be done safely, and we established a benchmark with this approach, which can help us build future trials that can test other pancreatic cancer drugs and further refine pre-surgery chemotherapy treatment."

Here are other SWOG highlights of the ASCO20 Virtual Scientific Program:

Results from S1211 will be orally presented by Saad Usmani, MD, a hematologist with Atrium Health and co-vice chair of SWOG's myeloma committee. Usmani's phase II SWOG study is the first randomized trial comparing treatments for high-risk multiple myeloma, a difficult-to-treat version of this blood cancer for which there is no standard of care. Usmani and his team compared the effects of eight cycles of chemotherapy with lenalidomide, bortezomib, and dexamethasone induction with or without the addition of elotuzumab. Results were negative; The addition of elotuzumab didn't offer a significant benefit. However, patients on both arms of the trial appear to have better progression-free survival, and lived much longer, than high-risk multiple myeloma patients typically do. This finding casts a positive light on combination treatment for this disease, and sets a tangible benchmark for the next SWOG phase III trial.

Results from S1416 will be orally presented by Priyanka Sharma, MD, vice chair of SWOG's breast cancer research committee and professor of medicine at the University of Kansas Cancer Center. Eve Rodler, MD, of the University of California Davis Comprehensive Cancer Center, serves as co-leader of S1416. More than half of all cases of triple negative breast cancer (TNBC) demonstrate DNA repair deficiency, which can be due to an inherited, or germline mutation, in the BRCA gene, or due to other causes leading to tumors that appear "BRCA-like." In other words, they behave like tumors caused by a BRCA mutation but don't have an inherited gene abnormality. In germline BRCA mutation associated breast cancers, this DNA repair deficiency is successfully treated with PARP inhibitors, and Sharma and Rodler wanted to see if these drugs could also be effective for BRCA-like cancers. In S1416, patients were treated either with standard cisplatin chemotherapy and a placebo, or cisplatin plus veliparib, an investigational PARP inhibitor. Patients with germline BRCA normal but BRCA-like TNBC who got the investigational drug in addition to cisplatin had significantly improved progression-free survival and showed a trend towards improved overall survival. NCI funded the study with AbbVie Inc. providing veliparib to support the study through a Cooperative Research and Development Agreement with NCI.

Results from S1417CD will be presented in a poster discussion session by Veena Shankaran, MD, MS, co-director of the Hutchinson Institute for Cancer Outcomes at Fred Hutchinson Cancer Research Center. Shankaran's SWOG trial, S1417CD, is the first prospective, multicenter study of financial toxicity. The primary goal was to determine how often patients with metastatic colorectal cancer experience financial hardship over the course of their treatment. Patients filled out questionnaires assessing assets, debt, spending, stress level, and quality of life when they enrolled in the trial, then subsequently three, six, nine and 12 months into their treatment. Dr. Shankaran and her team also pulled patients' credit reports at the trial's start and finish. Results are arresting. Three out of four patients experienced major financial hardship, defined as taking on credit card debt, taking out a loan, having a 20 percent or greater drop in income, or selling or refinancing a home. What's more, most patients enrolled in the trial were not considered financially vulnerable. Shankaran said the findings underscore the need for clinical and policy solutions, such as early financial navigation for patients and the elimination of cost sharing between patients and their insurance companies.

Results from one cohort of S1609 will be presented in a poster session by Sylvia Adams, MD, a SWOG and ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) investigator and professor of medicine at the Perlmutter Cancer Center at New York University Langone Health. Adams wanted to test immunotherapy drugs to treat metaplastic breast cancer, a concept she came up with through ECOG-ACRIN, which is also part of the NCTN. At the suggestion of the NCI, she found a home for her idea in DART, short for Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors, a unique SWOG trial testing the immunotherapy combination of ipilimumab plus nivolumab in a variety of rare cancers. Metaplastic breast cancer is a rare form of TNBC that's actually a hybrid, including cells from the breast and tissue such as muscle or bone. These unique features make this cancer very difficult to treat, and most patients die within nine months of developing metastatic disease. In this sub-set of DART, 17 eligible patients with metaplastic breast cancer received the immunotherapy combination. Three had positive, lasting responses; their tumors shrank significantly and all three remain alive and progression-free 23 to 27 months after treatment. While one patient died on the study, and some experienced side effects such as fatigue, Adams said results are promising, leading her team to study trial tissue samples to determine if there is a biological reason behind the positive responses. S1609 was sponsored by NCI and Bristol-Myers Squibb Company provided nivolumab to support the study through a Cooperative Research and Development Agreement with NCI.

"I'm particularly impressed with this year's ASCO presentations," said SWOG Chair Charles D. Blanke, MD. "They spotlight some of our most ground-breaking clinical trials in recent years, and are a testament to the creativity, ambition, and tenacity of SWOG researchers."

DALLAS, May 16, 2020 -- Although several artery-clogging diseases increase the risk of heart attack, prevention efforts are unequal, according to research presented today at the American Heart Association's Quality of Care & Outcomes Research Scientific Sessions 2020. The virtual conference, May 15-16, is a premier global exchange of the latest advances in quality of care and outcomes research in cardiovascular disease and stroke for researchers, health care professionals and policymakers.

Researchers found that patients with peripheral artery disease or stroke were less likely than those with coronary artery disease to receive recommended treatments to prevent heart attack. All three are types of atherosclerotic cardiovascular disease. 2016 AHA/ACC guidelines recommend aspirin for patients with symptomatic peripheral artery disease to prevent major adverse cardiovascular events, while 2018 guidelines from multiple organizations note that statin therapy reduces the risk of atherosclerotic events.

Worldwide, cardiovascular disease is the leading cause of death and a major contributor to cardiovascular disease is atherosclerosis, which occurs when cholesterol, fat and inflammatory cells build up and form plaque that blocks the arteries and impedes blood flow.

Depending on the location of the blockage, atherosclerosis increases the risk for three serious conditions: coronary artery disease, stroke and peripheral artery disease. Coronary artery disease results from damaged heart arteries and can cause a heart attack. A common type of stroke occurs when clogged arteries block blood flow to brain. Peripheral artery disease results from damaged arteries in the extremities, often the legs, and can lead to pain during walking and, in severe cases, amputation.

"Our study highlights the need for public health campaigns to direct equal attention to all three major forms of atherosclerotic cardiovascular disease," said senior study author Erin Michos, M.D., M.H.S., associate professor of medicine at the Ciccarone Center for the Prevention of Cardiovascular Disease at The Johns Hopkins University School of Medicine in Baltimore. "We need to generate awareness among both clinicians and patients that all of these diseases should be treated with aggressive secondary preventive medications, including aspirin and statins, regardless of whether people have heart disease or not."

Since atherosclerosis can affect arteries in more than one part of the body, medical guidelines are to treat coronary artery disease, stroke and peripheral artery disease similarly with lifestyle changes and medication, including statins to lower cholesterol levels and aspirin to prevent blood clots. Lifestyle changes include eating a healthy diet, being physically active, quitting smoking, controlling high cholesterol, controlling high blood pressure, treating high blood sugar and losing weight. What was unclear was if people with stroke and peripheral artery disease received the same treatments prescribed for those with coronary artery disease.

This study compared more than 14,000 U.S. adults enrolled in the 2006-2015 Medical Expenditure Panel Survey, a national survey of patient-reported health outcomes and conditions, and health care use and expenses. Slightly more than half of the patients were men, the average age was 65, and all had either coronary artery disease, stroke or peripheral artery disease. These individuals were representative of nearly 16 million U.S. adults living with one of the three forms of atherosclerotic cardiovascular disease.

Compared to participants with coronary artery disease:

participants with peripheral artery disease were twice more likely to report no statin use and three times more likely to report no aspirin use;

additionally, people with peripheral artery disease had the highest, annual, total out-of-pocket expenditures among the three atherosclerotic conditions;

participants with stroke were more than twice as likely to report no statin or aspirin use; and

moreover, those with stroke were more likely to report poor patient-provider communication, poor health care satisfaction and more emergency room visits.

"Our study highlights a missed opportunity for implementing life-saving preventive medications among these high-risk individuals," Michos said. "Peripheral artery disease and stroke should generally be treated with the same secondary prevention medications as coronary artery disease."

Limitations of the study include that it relied on medical diagnosis codes in health records, which could have been incorrectly coded, and did not include health information about people who live in nursing homes or who are incarcerated. Also, the study did not include information about medication changes over time or why people were not taking the recommended medication.