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New Rochelle, NY, April 20, 2020--A group of researchers with experience in treating high altitude pulmonary edema (HAPE) have written to correct the misconception in medical social media forums and elsewhere that the lung injury seen in COVID-19 is not like typical acute respiratory distress syndrome (ARDS) and is instead like HAPE. COVID-19 lung injury is not like HAPE, and treating it like HAPE could have adverse effects on patient outcomes, according to an article published in High Altitude Medicine & Biology, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Click here to read the full-text article free on the High Altitude Medicine & Biology website through May 20, 2020.

The article entitled "COVID-19 Lung Injury Is Not High Altitude Pulmonary Edema" is coauthored by Andrew M. Luks, MD, University of Washington, Seattle, and colleagues from Himalayan Rescue Association, Intermountain Medical Center (Salt Lake City, UT), University of Utah, Salt Lake City, St. Mary's Medical Center, San Francisco (CA), VA Puget Sound Health Care System, Seattle, and University of Colorado Anschutz Medical Campus (Aurora).

The researchers discuss the similarities between HAPE and ARDS, and also highlight the differences between them. ARDS in COVID-19 occurs as a result of an inflammatory response to the presence of the virus, whereas HAPE does not occur as a result of underlying inflammation, but rather as a result of excessive and uneven hypoxic pulmonary vasoconstriction. Understanding the different mechanisms of HAPE and ARDS is critical for patient management because the treatment for each will be quite different. Long-term supportive care including mechanical ventilation may be needed to overcome the underlying inflammation in COVID-19.

"It is vitally important to not equate these two diseases simply because they share some similarities in their radiologic appearance and cause hypoxemia (low blood oxygen content). This can be said for many other acute lung injuries. Any perceived link of HAPE to COVID-19 lung injury could have deleterious consequences if the same medications useful in HAPE were tried in those with COVID-19 related respiratory failure," says Erik R. Swenson, MD, Editor-in-Chief of High Altitude Medicine & Biology and Professor of Medicine, University of Washington and Division of Pulmonary and Critical Care Medicine, Veterans Administration Puget Sound Healthcare System.

New evidence published in the Cochrane Library today finds MMR, MMRV and MMR+V vaccines are effective and that they are not associated with increased risk of autism.

Measles, mumps, rubella and varicella (also known as chickenpox) are infectious diseases caused by viruses. They are most common in children and young adults, and can lead to potentially fatal illnesses, disabilities and death. Measles remains one of the leading causes of childhood death around the globe. Rubella is also dangerous for pregnant women, as it can cause miscarriage or harm to unborn babies.

The MMR (measles, mumps, rubella) is a combined vaccine that protects against all three infections. Clinicians can vaccinate against varicella (chickenpox) by a combined MMR and varicella vaccine (MMRV) or giving it separately at the same time (MMR+V).

"We wanted to assess the effectiveness, safety, and long- and short-term harms of the MMR vaccines in this updated review which was last updated in 2012," explains lead author, Dr Carlo Di Pietrantonj of Italy's Regional Epidemiology Unit SeREMI. "From the 138 randomised and non-randomised studies included in the review, 51 studies (10 million children) assessed how effective the vaccines were at preventing the diseases, and 87 studies (13 million children) assessed harms."

In terms of effectiveness the review found:

Measles: one dose of vaccine was 95% effective in preventing measles. Based on the data analysed in the review, the number of cases would fall from 7% in unvaccinated children to under 0.5% in children who receive one dose of the vaccine. After two doses, effectiveness was similar at around 96%.

Mumps: one dose of vaccine was 72% effective in preventing mumps. This rose to 86% after two doses. From data analysed in the review. the number of cases would fall from 7.4% in unvaccinated children to 1% in children were vaccinated with two doses.

The results for rubella and chickenpox also showed that that vaccines are effective. After one dose of vaccine was 89% effective in preventing rubella, and one study found that after 10 years the MMRV vaccine was 95% effective at preventing chickenpox infection. If exposed to chickenpox, 5 out of 100 vaccinated children would catch it.

"In terms of safety, we know from previous studies all around the world that the risks posed by these diseases far outweigh those of the vaccines administered to prevent them," says Dr Di Pietrantonj. "In this review, we wanted to look at evidence for specific harms that have been linked with these vaccines in public debate - often without rigorous scientific evidence as a basis."

In relation to the controversy arising from false claims linking vaccination and autism, the review summarises evidence from two studies with 1,194,764 children. Diagnosed cases of autism were similar in vaccinated and unvaccinated children (1.)

Two further studies with 1,071,088 children find no evidence for any association between the MMR vaccines and encephalitis, inflammatory bowel disease, Crohn's disease, cognitive delay, type 1 diabetes, asthma, dermatitis/eczema, hay fever, leukaemia, multiple sclerosis, gait disturbance and bacterial or viral infections.

"We judged the certainty of the evidence for the effectiveness of the MMR vaccine to be moderate. Although the studies that provide these data are not randomised the effects are very large. The certainty of the evidence for the varicella vaccine, based on an RCT, was judged to be high." says Di Pietrantonj.

"Overall we think that existing evidence on the safety and effectiveness of MMR/MMRV/MMR+V vaccines supports their use for mass immunisation. Campaigns aimed at global eradication should assess epidemiological and socioeconomic situations of the countries as well as the capacity to achieve high vaccination coverage. More evidence is needed to assess whether the protective effect of MMR/MMRV could wane with time since immunisation."

DALLAS, April 20, 2020 --Hypertensive pregnancy disorders, especially preeclampsia, a form of high blood pressure during pregnancy, may lead to adverse mental health conditions in children, according to new research published today in Hypertension, an American Heart Association journal.

A Finnish study of 4,743 mother-child pairs found associations between hypertensive pregnancy disorders - including chronic hypertension (high blood pressure), gestational hypertension, preeclampsia and eclampsia - and childhood mental disorders. Preeclampsia is a common pregnancy complication often characterized by high blood pressure and protein in the urine, which indicates damage to other organs including the liver and kidneys. Eclampsia is a severe complication of preeclampsia in which high blood pressure during pregnancy results in seizures.

Maternal preeclampsia and its severity were associated with an increase in the risk of any childhood mental disorder and psychological development and behavioral and emotional disorders in the offspring.

Researchers found:

a 66% higher risk of mental disorders among children whose mothers had preeclampsia; and

a two-fold higher risk of childhood mental issues among children whose mothers had severe preeclampsia.

"While previous studies have shown significant effects of preeclampsia on ADHD, autism spectrum disorder and schizophrenia in the offspring, a novel aspect of our findings was that the predisposing effects of maternal preeclampsia extended to any childhood mental disorder in the offspring," said Marius Lahti-Pulkkinen, one of the senior researchers of the study, Ph.D. a docent at the University of Helsinki in Helsinki, Finland.

Researchers also noted that the combination of maternal hypertensive disorders, overweight/obesity and diabetes disorders in pregnancy increase the cumulative incidence of childhood mental disorders from 6.6% among offspring of mothers with none of those conditions to 22.2% in offspring exposed to all of these three adverse maternal conditions.

The associations of maternal preeclampsia with offspring childhood mental disorders are not explained by maternal mental disorders, age, substance use, number of previous pregnancies, education, overweight/obesity or diabetes disorders or paternal mental or hypertensive disorders.

"The findings emphasize the need for preventive interventions and treatments for maternal hypertensive disorders, since such interventions have the potential to benefit both the well-being of the expectant mother and her offspring," he said. "The findings also shed important new light on the etiology of childhood mental disorders. This information may help in targeting preventive interventions and support for families at risk, and aid clinicians in understanding issues and the underlying causes of childhood mental disorders."

Hypertensive pregnancy disorders are key risk factors for maternal mortality, stillbirth, preterm birth and intrauterine growth restriction and they predict cardiovascular morbidity in the mother and her offspring.

Sexual health interventions are effective at increasing both abstinence and condom use in Black adolescents, according to research from North Carolina State University evaluating dozens of studies on interventions and outcomes in Black youth.

The new paper, published in JAMA Pediatrics, draws on data from 29 studies that reported on a total of 11,918 Black adolescents. Sexual health interventions range from school-based health classes to programs offered by community organizations.

"We focused on Black adolescents because they face greater health disparities when it comes to the risk of unplanned pregnancy and contracting sexually-transmitted infections (STIs) compared to other adolescents," says Reina Evans, first author of the paper and a Ph.D. student at NC State. "This disparity stems, in large part, from the context in which Black teens make decisions about their health. For example, stress from racism and discrimination, as well as unequal access to health care can impact the health of Black teens. We wanted to see whether sexual health interventions can be a valuable tool in addressing this disparity."

The researchers found that young people were slightly more likely to abstain from sex if they took part in one of these programs - particularly if the intervention occurred at school. The researchers also found a modest increase in condom use for adolescents who took part in an intervention.

"When we considered if youth who completed these programs had lower rates of unintended pregnancy or STIs, we did not see any effect - positive or negative - from the programs," Evans says. "However, only 4 of the 29 studies investigated these important outcomes, so these findings should be considered preliminary. It is likely that offering a sexual health program to youth could be one component of the puzzle of preventing teen pregnancy and STIs, and other components are also needed - like increasing access to contraception and STI testing and addressing racism in healthcare in the United States."

The study also showed that interventions made Black adolescents more knowledgeable about sexual health and more confident that they could and would make safe sexual decisions in the future.

In addition, researchers found that the effects were similar regardless of whether interventions were coeducational or aimed at a specific gender, and regardless of the target age range for an intervention.

"These findings highlight that sexual health interventions make a positive difference for many Black adolescents," Evans says. "Important next steps include finding ways to disseminate interventions more broadly to teens, ensuring the interventions are accessible, and encouraging participation and engagement.

"What's more, there's an urgent need to address disparities in access to long-term, high-quality reproductive healthcare, which could have a significant effect on health outcomes for Black teens."

PHILADELPHIA (April 20, 2020) - Sitting a baby in front of a tablet or television, as well as less parent-child play time, are associated with developing greater autism spectrum disorder (ASD)-like symptoms later in childhood. These findings, from the first prospective study on the subject, are published today in JAMA Pediatrics from researchers at Drexel University's College of Medicine and Dornsife School of Public Health.

The authors suggest that these findings come at a critical time during this coronavirus pandemic with many children at home all day and parents juggling working from home or other new responsibilities while watching their children.

"The literature is rich with studies showing the benefits of parent-infant interaction on later child development, as well as the association of greater screen viewing with developmental delays," said lead author Karen F. Heffler, MD, a researcher in the College of Medicine. Our study expands on this previous research by associating early social and screen media experiences with later ASD-like symptoms."

During babies' 12- and 18-months well visits, their caregivers were asked about how often their baby is exposed to screens or books, and how often they play with their child. Following this group of 2,152 children from the National Children's Study the team examined how watching television or videos, as well as social play time and reading together, were associated with ASD risk and ASD-like symptoms at two years of age as measured by the Modified Checklist for Autism in Toddlers (M-CHAT). While toddlers generally are interested in interacting with others, those with ASD-like symptoms are less likely to show these social behaviors.

Controlling for gender, race, maternal age, and prematurity, the team found that viewing screens at 12 months of age was associated with four percent greater ASD-like symptoms, and daily play time with a parent compared to less than daily play time was associated with nine percent less ASD-like symptoms. The findings back recommendations from the American Academy of Pediatrics which discourages screen time in children younger than 18 months, unless it is used for video chatting.

One in 54 children has ASD, a condition four times more prevalent in boys than in girls, according to the Centers for Disease Control and Prevention. Previous studies report that about 50 to 80 percent of overall autism risk is genetic, yet non-genetic contributors are poorly understood.

"These findings strengthen our understanding of the importance of play time between parents and children relative to screen time," said senior author David S. Bennett, PhD, a professor of Psychiatry in the College of Medicine. "There is a great opportunity for public health campaigns and pediatricians to educate and empower parents to possibly minimize their child's risk of ASD symptoms, which may include increasing social interaction and limiting screens at an early age."

The authors note that their study did not find an association with ASD risk, but rather with ASD-like symptoms. Future studies should explore whether this relationship is determined by children predisposed to ASD being drawn to the screens or screens contributing to ASD-like symptoms. In the meantime, the authors suggest that parents adhere to the American Academy of Pediatrics recommendation to avoid screen time in children younger than 18 months and limit screens to one hour daily through age 5 years, co-viewed to help children understand what they are seeing.

The paper also provides additional evidence associating prematurity, minority race or ethnicity, as well as lower income with higher risk of ASD and ASD-like symptoms.

LA JOLLA--A new study co-led by scientists at the La Jolla Institute for Immunology (LJI) adds increasing evidence that Parkinson's disease is partly an autoimmune disease. In fact, the researchers report that signs of autoimmunity can appear in Parkinson's disease patients years before their official diagnosis.

The research could make it possible to someday detect Parkinson's disease before the onset of debilitating motor symptoms--and potentially intervene with therapies to slow the disease progression.

The study, published in the April 20, 2020, issue of Nature Communications, was co-led by LJI professor Alessandro Sette, Dr. Biol. Sci, and Professor David Sulzer, Ph.D., of the Columbia University Medical Center.

Scientists have long known that clumps of a damaged protein called alpha-synuclein build up in the dopamine-producing brain cells of patients with Parkinson's disease. These clumps eventually lead to cell death, causing motor symptoms and cognitive decline.

"Once these cells are gone, they're gone. So if you are able to diagnose the disease as early as possible, it could make a huge difference," says LJI research assistant professor Cecilia Lindestam Arlehamn, Ph.D., who served as first author of the new study.

A 2017 study led by Sette and Sulzer was the first to show that alpha-synuclein can act as a beacon for certain T cells, causing them to mistakenly attack brain cells and potentially contribute to the progression of Parkinson's. This was the first direct evidence that autoimmunity could play a role in Parkinson's disease.

The new findings shed light on the timeline of T cell reactivity and disease progression. The researchers looked at blood samples from a large group of Parkinson's disease patients and compared their T cells to a healthy, age-matched control group. They found that the T cells that react to alpha-synuclein are most abundant when patients are first diagnosed with the disease. These T cells tend to disappear as the disease progresses, and few patients still have them ten years after diagnosis.

The researchers also did an in-depth analysis of one Parkinson's disease patient who happened to have blood samples preserved going back long before his diagnosis. This case study showed that the patient had a strong T cell response to alpha-synuclein ten years before he was diagnosed with Parkinson's disease. Again, these T cells faded away in the years following diagnosis.

"This tells us that detection of T cell responses could help in the diagnosis of people at risk or in early stages of disease development, when many of the symptoms have not been detected yet," says Sette. "Importantly, we could dream of a scenario where early interference with T cell responses could prevent the disease from manifesting itself or progressing."

Sulzer added, "One of the most important findings is that the flavor of the T cells changes during the course of the disease, starting with more aggressive cells, moving to less aggressive cells that may inhibit the immune response, and after about 10 years, disappearing altogether. It is almost as if immune responses in Parkinson's disease are like those that occur during seasonal flu, except that the changes take place over ten years instead of a week."

In fact, already therapies exist to treat inflammation from autoreactive T cells, and these TNF therapies are associated with lower incidence of Parkinson's disease. Going forward, the researchers are especially interested in using a tool called a T cell-based assay to monitor patients already at risk for Parkinson's to see if they could benefit from TNF therapies. These patients include people with REM sleep disorders and certain genetic mutations.

The researchers hope to study more Parkinson's patients and follow them over longer time periods to better understand how T cell reactivity changes as the disease progresses.

TAMPA, Fla. (April 17, 2020) – The short-term acute inflammatory response triggered to mend injured cardiac tissue following a heart attack can lead to weakening of the heart’s pumping function if the inflammation remains active over the long-term. Heart failure associated with this unresolved chronic cardiac inflammation has become a leading cause of death in the U.S. and worldwide, yet little is known about the differences in cardiac repair and safe clearance of inflammation between men and women.

Ganesh Halade, PhD, an associate professor of cardiovascular sciences at the University of South Florida Health (USF Health) Morsani College of Medicine and Heart Institute, looks for ways to delay or prevent heart failure — including targeted therapies that may account for potential physiological sex differences.

Dr. Halade’s team delves into the details of metabolic and leukocyte responsive signaling that facilitate cardiac repair during acute inflammation after injury (like a heart attack) and the resolution thereafter. In particular, he studies how unresolved inflammation driven by a deficiency in fatt acid-derived signaling molecules influences heart failure. Known as specialized proresolving mediators (SPMs), these molecules are naturally made by the body (endogenous).

Now, a new study led by Dr. Halade has investigated the molecular and cellular processes underlying cardiac repair in male and female mice after a severe heart attack. The USF Health study, conducted with collaborator Charles N Serhan, PhD, DSc, at Harvard Medical School, reports that females showed improved heart failure survival characterized by differences in cardiac functional recovery and structure, more reparative immune cells and higher levels of epoxyeicosatrienoic acids (EETs), signaling molecules with anti-inflammatory effects.

The findings were published April 16 in the Journal of the American Heart Association.

“We discovered heart repair happens faster in the female mice than the males after heart attack, that improves survival and delays cardiac failure,” said Dr. Halade, the paper’s senior author.

His ongoing translational work may have applications for the development of sex-specific and other more precise heart failure therapies with fewer side effects due to endogenous nature of bioactive signaling molecules. Currently, men and women receive the same standard first-line medications (angiotensin converting enzyme/receptor inhibitors, diuretics, and beta-blockers) to manage mild-to-severe forms of heart failure.

For this study appearing in JAHA, the researchers used “risk-free” young, healthy mice to control for variable cardiovascular risk factors — such as obesity, insulin resistance, diabetes, hypertension and aging, — common in a clinical setting. They compared the risk-free male and female mice who underwent a procedure to induce severe heart attack with those that did not.

To frame the study, it helps to know that physiological inflammation after tissue injury has two steps — an acute response, where white blood cells rush to the heart to remove dead cardiac tissue, and a resolving phase, where inflammation is cleared with the help of macrophages that arrive to repair the damage, and form stable scar. Both responses are governed by ‘get in’ and ‘get out’ signals to leukocytes (a type of immune cell) infiltrating at the site of the heart muscle injured by the heart attack.

Among the key USF Health research findings:

Following a heart attack, leukocyte infiltration to clear diseased cardiac muscle cells is coordinated by the production of SPMs that resolve inflammation and promote timely cardiac repair.
Female mice showed better recovery of the heart’s capacity to pump blood compared to males. “Improvement in heart functional recovery is believed to be enabling the female mice to ‘bounce back’ and survive at a significantly higher rate than male mice after myocardial infarction (heart attack),” the authors wrote.
Less post-MI scarring and adverse structural remodeling of heart muscle in female mice helps explain their improved recovery of cardiac function and survival in acute and chronic heart failure.
While both male and female mice equally produced SPMs in response to massive heart attacks, the females generated higher levels of a particular lipid signaling molecule known as epoxyeicosatrienoic acid (EET) to facilitate healing after a heart attack.

“The beauty of these SPM and EET molecules is that they are endogenously biosynthesized and can be useful for clearing harmful inflammation in asthma and other diseases, not just heart failure,” Dr. Halade said.

The USF Health researchers plan to study these bioactive lipid signaling molecules after heart attack in men and women, and consider human-related variable factors absent in mice, such as race.

The study was supported by grants from the NIH’s National Institute of Heart Lung and Blood Institute (Dr. Halade) and the National Institute of General Medical Sciences (Dr. Serhan).

Journal

Journal of the American Heart Association

DOI

10.1161/JAHA.119.015672

Decision scientists have developed models to help governments and policymakers allocate limited healthcare resources. The decision model developed by Aalto researchers accounts for differences between population segments and shows that segment-specific strategies for tests and treatments are crucial for attaining positive health outcomes, especially when there is limited capacity for treatments. 'When we were revising the paper just a few months ago, we never thought how soon the framework would become so relevant' says Professor Ahti Salo Director of the Systems Analysis Laboratory at Aalto University.

All health outcomes benefit from stopping the disease spreading

The paper, published in the journal Decision Sciences, shows how healthcare resources can be spent to achieve different population-level objectives, such as the "utilitarian" objective (which focuses on maximizing the aggregate health of the whole population) and the "egalitarian" objective (which gives priority to the neediest while limiting differences between segments). The decision model helps policymakers balance these two objectives, and shows how they can be attained by allocating resources accordingly.

The research was carried out before the Covid19 outbreak and the data for illustrating the model is actually about coronary heart disease. As a result, the model is not directly adapted to contagious diseases, although the group will consider this in their future work. However, contagiousness does not alter the relevance of the model regarding testing. 'Adding contagion into our model most likely increases the value of all forms of testing, as all health outcomes benefit from stopping the disease spreading' said Professor Salo.

Multi-disciplinary work led by researchers from Trinity College Dublin has pinpointed a potential new therapeutic target for treating retinal degeneration. The work has discovered that a protein (SARM1) involved in neuronal cell injury may also have a role in the progression of retinal degeneration.

The research, involving experts from Trinity's Schools of Medicine, Biochemisty and Immunology, Genetics and Microbiology, and Engineering, has just been published in the journal Life Science Alliance.

Retinal degenerative diseases are prevalent in Ireland, and across the globe

Millions of people worldwide suffer varying degrees of vision-loss due to irreversible retinal degenerative diseases. In Ireland alone, approximately 5,000 people are affected by inherited retinal degenerations, while another 80,000 are known to live with age-related macular degeneration (AMD).

Photoreceptor cells are specialised neurons found in the back of our eyes that convert light into electrical signals that allow us to see. It is the death of these cells, and the cells that nourish them, that is termed retinal degeneration and is characteristic of blinding diseases such as AMD and retinitis pigmentosa.

Dr Ema Ozaki, research fellow in clinical medicine at Trinity, said:

"Lots of different factors can initiate retinal degeneration and lead to severe visual impairment and eventual blindness, but ultimately the end-point is photoreceptor cell death. Although it seems unlikely the process of cell-death is - in fact - a programmed or organised event that directs proteins in our cells to take on 'executioner' roles."

In this research, the team led by Dr Sarah Doyle, assistant professor in immunology at Trinity, investigated the role of one such "executioner protein" called SARM1.

SARM1 has come to the fore recently in the study of brain and spinal injury, as it is highly efficient at triggering the degeneration of neuronal cells. While the retina is an extension of the brain, this report is the first to describe a role for SARM1 in photoreceptor cell biology.

Explaining the significance, Dr Sarah Doyle, said:

"Our research indicates that SARM1 is likely to be a key executioner in the process of retinal degeneration, because if we remove it from our experimental model system this has the effect of delaying the photoreceptor cells from dying."

"This is an important finding because the first steps involved in processing 'light into sight' take place in the photoreceptors. As a result, losing photoreceptors ultimately equates to losing vision. For this reason, interventions that prevent or delay photoreceptor cell death are critical to preserve sight for as long as possible in people with degenerative retinal diseases."

The research team was also able to show that the protected and surviving photoreceptors maintained their function and continued to transmit electrical signals to the optic nerve. This research has therefore provided a new therapeutic target to slow the progression of blinding diseases.

Dr Sarah Doyle added:

"This is particularly exciting for the future because others have recently shown that a gene therapy approach for inhibiting SARM1 is effective in protecting against neuronal degeneration. We know that gene therapy is well suited as a treatment for retinal disease, so such an approach for inhibiting SARM1 activity may offer an option for protecting vision across multiple retinal degenerative diseases."

The introduction of policies that restrict healthcare access for visitors and migrants not entitled to free NHS care may be associated with delays in diagnosis and treatment for patients with tuberculosis (TB) who were not born in the UK, according to a study published in the open access journal BMC Public Health. Delays in diagnosis and treatment of an infectious disease like TB may increase morbidity and mortality for infected individuals, as well as transmission in the community.

In 2014, the UK government launched the NHS Visitor and Migrant Cost Recovery Programme (CRP) to recoup costs from 'chargeable' (largely non-UK born) patients not entitled to free NHS care. Researchers at Queen Mary University of London, UK investigated a possible association between the introduction of the CRP and diagnostic and treatment delays in subsequent years.

Jessica Potter, the corresponding author said: "This study provides novel data showing an association with delayed diagnosis and treatment of an infectious disease - tuberculosis - among people not born in the UK with the roll out of government policy designed to restrict healthcare access for some migrants. These findings are despite the fact that infectious diseases are exempt from charging."

The authors analysed data on 2,237 TB cases notified between 2011 and 2016 on the London TB Register across Barts Health NHS trust, which serves three East London boroughs and treats over 500 patients with TB each year, representing about 10% of cases in England.

They found that among non-UK born patients, median time to treatment - the average number of days between the date of symptom onset and the date of starting treatment - increased from 69 to 89 days following the introduction of CRP. Non-UK born patients were also more likely to experience a delay in diagnosis after introduction of the CRP. The number of years migrants had been living in the UK before diagnosis was found to increase from 10 years before to 14.8 years after the CRP was introduced.

A number of mechanisms may underlie the association between treatment and diagnostic delays and health policies, such as the CRP, which aim to restrict access to care based on migration status, according to the authors. Previous research has suggested that migrants in the UK are often not aware of their entitlement to care and patients' concerns about being charged for care may delay them seeking health advice, even before diagnosis.

The authors suggest that while the study area is small geographically, the findings may be applicable to other areas within England which have similar migrant populations and have been subject to similar policies as the East London boroughs examined in this study. They caution that the observational nature of the study does not allow for conclusions about cause and effect. Nevertheless, the findings show an important association that warrants further investigation.

Jessica Potter said: "Whilst we have demonstrated an association and not proven causality, we provide a convincing argument for more research in this area and contribute to the growing body of evidence that restricting healthcare access to some has public health implications for us all."

PLYMOUTH MEETING, PA [April 20, 2020] -- A recently-published study from researchers in Australia and South Africa found the NCCN Guidelines for Patients to be among the most trustworthy resources for patients and caregivers seeking information online about prostate cancer. The independent, peer-reviewed international study published in Current Urology examined the top 90 English-language Google results for medical information on prostate cancer, and measured reliability and transparency according to Journal of American Medical Association (JAMA) benchmarks and DISCERN criteria from the Division of Public Health and Primary Care at Oxford University. The NCCN Guidelines for Patients received highest rankings in both.

"We publish the NCCN Guidelines for Patients so people with cancer and their caregivers have access to the same information as their doctors, including the latest evidence and expert consensus on the best ways to manage their cancer," said Robert W. Carlson, MD, Chief Executive Officer, NCCN. "This knowledge is intended to empower people with cancer to take an active role in shared decision-making, ensuring their treatment plan is truly patient-centered."

The NCCN Guidelines for Patients are based on the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), which are the recognized standard for clinical direction and policy in cancer management and the most thorough and frequently-updated clinical practice guidelines available in any area of medicine. The patient guidelines are written in an easy-to-learn format and include a glossary of medical terms and suggested questions to ask during appointments. The books are available for free digital download at NCCN.org/patients or via the NCCN Patient Guides for Cancer App, with printed versions available for a nominal fee at Amazon.com. Funding for the NCCN Guidelines for Patients comes from the NCCN Foundation and its generous donors. The NCCN Foundation also collaborates with more than 100 patient advocacy groups to help deliver this vital information to patients and families.

"The NCCN Guidelines for Patients: Prostate Cancer outlines essential information about diagnosis and treatment in a comprehensible format. It serves as a foundation of knowledge as patients and families begin to discuss options with their health care provider," according to the Prostate Cancer Foundation (PCF), one of ten organizations to endorse the book, along with California Prostate Cancer Coalition (CPCC), Malecare Cancer Support, National Alliance of State Prostate Cancer Coalitions (NASPCC), National Prostate Cancer Awareness Foundation (PCaAware), Prostate Health Education Network (PHEN), Urology Care Foundation, Us TOO International Prostate Cancer Education and Support Network, Veterans Prostate Cancer Awareness, and ZERO - The End of Prostate Cancer.

In the Current Urology study, the researchers found NCCN's patient information site met all four criteria for validating the quality of information it contained according to the JAMA benchmarks--one of only 15 websites to do so. Additionally, the evaluation based on the DISCERN criteria gave NCCN a score of 76 out of 80, making it the highest ranked site of the first 90 Google search results.

"These patient guidelines are intended to augment, but not replace the information patients get from their physician," said Marcie Reeder, MPH, Executive Director, NCCN Foundation. "It can be difficult to understand complicated medical details at any time, and especially when your mind is reeling after getting a cancer diagnosis. These books give people the opportunity to absorb what's happening to them and mentally prepare at their own pace. With so many people relying on the internet for health information, we're proud to offer something that's been independently validated as reliable and trustworthy. No matter where people receive their care, they can advocate for the latest and best options currently available."

In response to the ongoing Coronavirus Disease 2019 (COVID-19) pandemic, NCCN is also helping to share essential information from NCCN Member Institutions on how to continue providing safe, optimal cancer care under current conditions. Visit NCCN.org/covid-19 for a growing list of free, downloadable resources for patients, providers, and caregivers, including a factsheet for cancer patients and tips for self-care and stress management.

The patient guidelines site had approximately 900,000 unique visitors from all over the world in 2019. Visit NCCN.org/patients to learn more or make a donation to the NCCN Foundation to support essential resources for people with cancer.

Study suggests testing and contact tracing and population behavioural changes--measures which have far less disruptive social and economic impact than total lockdown--can meaningfully control COVID-19

Hong Kong appears to have averted a major COVID-19 outbreak up to March 31, 2020, by adopting far less drastic control measures than most other countries, with a combination of border entry restrictions, quarantine and isolation of cases and contacts, together with some degree of social distancing, according to a new observational study published in The Lancet Public Health journal.

The study estimates that the rate at which the virus is transmitted--known as the effective reproductive number, or the average number of people each individual with the virus is likely to infect at a given moment--has remained at approximately 1 in the 8 weeks since early February, after public health measures were implemented from late January onwards, indicating that the epidemic in Hong Kong is holding steady [1].

As of March 31, 2020, Hong Kong had 715 confirmed COVID-19 cases including 94 asymptomatic infections, and 4 deaths in a population of about 7.5 million.

The public health measures implemented to suppress local transmission in Hong Kong are probably feasible in many locations worldwide, and could be rolled out in other countries with sufficient resources, researchers say. However, they caution that because a variety of measures were used simultaneously, it is not possible to disentangle the individual effects of each one.

"By quickly implementing public health measures, Hong Kong has demonstrated that COVID-19 transmission can be effectively contained without resorting to the highly disruptive complete lockdown adopted by China, the USA, and Western European countries," says Professor Benjamin Cowling from the University of Hong Kong who led the research. "Other governments can learn from the success of Hong Kong. If these measures and population responses can be sustained, while avoiding fatigue among the general population, they could substantially lessen the impact of a local COVID-19 epidemic." [2]

The control measures implemented in Hong Kong in late January included intense surveillance for infections, not only for incoming travellers, but also in the local community, with around 400 outpatients and 600 inpatients tested every day in early March. Extensive efforts were also made to track down and quarantine all close contacts an infected person had seen two days before becoming ill, and holiday camps and newly built housing estates were repurposed into quarantine facilities. Additionally, anyone crossing the border from mainland China, as well as travellers from infected countries, were required to undergo 14 days of quarantine at home or in designated facilities. The government also deployed measures to encourage social distancing including flexible working arrangements and school closures, and many large-scale events were cancelled (figure 1).

In the study, researchers analysed data on laboratory-confirmed COVID-19 cases in Hong Kong between late January and 31 March, 2020, to estimate the daily effective reproductive number (Rt) for COVID-19, and changes in transmissibility over time. To examine whether control measures have been associated with reducing silent transmission of COVID-19 (ie, transmission in the community from people never diagnosed), researchers also analysed influenza surveillance data in outpatients of all ages and influenza hospitalisations in children, as a proxy for changes in COVID-19 transmission--assuming a similar mode and efficiency of spread between influenza and COVID-19.

The researchers also conducted three cross-sectional telephone surveys among the general adult population (aged 18 and older) of Hong Kong to assess attitudes to COVID-19 and changes in behaviours on January 20-23 (1,008 respondents), February 11-14 (1,000), and March 10-13 (1,005).

Further analyses suggest that individual behaviours in the Hong Kong population have changed in response to COVID-19. In the most recent (March) survey, 85% of respondents reported avoiding crowded places, and 99% reported wearing face masks when leaving home--up from 75% and 61% respectively from the first survey in January. This compares to reported face mask use of around 79% in similar surveys during the SARS outbreak in 2003, and 10% during the influenza A (H1N1) pandemic in 2009. These changes in behaviour indicate the level of concern among the population about COVID-19, researchers say.

While unlinked COVID-19 cases--with no identified source of infection--have been detected in increasing numbers since early March, the Rt remains around 1 (figure 2). Increases in these cases could be the result of imported infections, highlighting the importance of border control measures including careful monitoring of arriving travellers, and testing and tracing efforts to maintain suppression--although these measures will be increasingly difficult to implement as case numbers increase, researchers say.

The analyses suggest that influenza transmission declined substantially after the implementation of physical distancing measures and changes in population behaviours in late January--with a 44% reduction in the influenza transmission rate in February, from an estimated average Rt of 1.28 in the two weeks before the start of school closures to 0.72 during the closure weeks (figure 3C). This is much greater than the 10-15% reduction in influenza transmission associated with school closures during the 2009 influenza (H1N1) pandemic, and the 16% decline in transmission of influenza B during the 2017-18 winter in Hong Kong.

Similarly, a 33% decline in influenza transmissibility was observed based on influenza hospitalisation rates among children, from an average Rt of 1.10 before the start of school closures to 0.73 following closures (figure 3D).

"The speed of decline in influenza activity in 2020 was quicker than in previous years when only school closures were implemented, suggesting that other social distancing measures and avoidance behaviours have had a substantial additional impact on influenza transmission," says co-author Dr Peng Wu from The University of Hong Kong. "As both influenza and COVID-19 are directly transmissible respiratory pathogens with similar viral shedding dynamics, it's likely that these control measures have also reduced COVID-19 transmission in the community." [2]

She adds, "As one of the most heavily affected epicentres during the SARS epidemic in 2003, Hong Kong is better equipped to contend with an outbreak of COVID-19 than many other countries. Improved testing and hospital capacity to handle novel respiratory pathogens, and a population acutely aware of the need to improve personal hygiene and maintain physical distancing, put them in good stead." [2]

The authors note some limitations in the study, including that while school closures can have considerable effects on influenza transmission, it is still not clear whether or how much children contract and spread COVID-19, so the role of school closures in reducing COVID-19 transmission is not known. The authors also note that the major impact of control measures and behavioural changes on influenza transmission might not have a similar impact on COVID-19. Finally, experience of avoidance behaviours was based on self-reported data and might have been affected by selection bias, away from adults who might have been working. However, surveys were also done in non-working hours to reduce this bias.

Bottom Line: Patients experienced a greater occurrence of infections in the years preceding a cancer diagnosis.

Journal in Which the Study was Published: Cancer Immunology Research, a journal of the American Association for Cancer Research

Author: Shinako Inaida, PhD, a visiting researcher at the Graduate School of Medicine at Kyoto University in Japan

Background: "Cancer can develop in an inflammatory environment caused by infections, immunity disruption, exposure to chemical carcinogens, or chronic or genetic conditions," said Inaida. "An individual's immunity is thought to be a factor in the development of cancer, but additional research is needed to understand the relationship among precancerous immunity, infections, and cancer development," added Inaida. "This information may contribute to efforts to prevent or detect cancer."

Studies have suggested an increase in infections prior to the development of non-solid tumors, such as lymphoma, chronic lymphocytic leukemia, and myeloma, explained Inaida. However, fewer studies have examined infection prior to the development of solid tumors.

How the Study was Conducted: In this retrospective case-control study, Inaida, along with Shigeo Matsuno, PhD, examined a medical claims database in Japan to determine the annual rate of infections in adults from 2005 to 2012. Individuals 30 years of age and older without any recorded immunodeficiencies were included in the study. The case group was composed of 2,354 individuals who were diagnosed with any malignant cancer between July 2010 and June 2011, and the control group was composed of 48,395 individuals who were not diagnosed with cancer between January 2005 and December 2012. The annual prevalence rates for influenza, gastroenteritis, hepatitis, and pneumonia infections were calculated for each group.

The case group included 1,843 men and 511 women; the control group had 37,779 men and 10,616 women. The average age of individuals in the case group was 45.1 years, while the average age of those in the control group was 43.9 years. The most common cancers diagnosed in the case group were digestive and gastrointestinal, head and neck, and stomach cancers. Other cancer types diagnosed in the case group fell into the following categories: respiratory and thoracic; germ cell; genitourinary; liver; female breast; hematologic, blood, bone, and bone marrow; endocrine; and unknown or other cancers.

Results: The authors found that individuals in the case group had experienced higher rates of infection over the six years prior to their cancer diagnoses than those in the control group over the same time period. The largest differences in annual infection prevalence rates occurred in the sixth year, which was one year prior to cancer diagnosis. During this year, the infection prevalence rates for the case group were higher than the control group by 18 percent for influenza, 46.1 percent for gastroenteritis, 232.1 percent for hepatitis, and 135.9 percent for pneumonia.

For individuals in the case group, the age-adjusted odds of infection increased each year. During the first year, those in the case group had a 16 percent higher likelihood of infection than the control group, compared with a 55 percent greater risk in the sixth year. During the sixth year, the highest age-adjusted odds ratio was observed for hepatitis infection, with those in the case group having had a 238 percent higher likelihood of hepatitis infection than those in the control group.

The authors also found that certain infections appeared to have a greater association with certain cancer types. The odds of influenza infection just before cancer detection, for example, were highest for those who developed male germ cell cancers. Additionally, the odds of pneumonia were highest in those who went on to develop stomach cancer, and the odds of hepatitis infection were highest in those who developed hematologic, blood, bone, or bone marrow cancers. "Interestingly, we found that infection afflicting a specific organ did not necessarily correlate with increased risk of cancer in the same organ," noted Inaida.

Study Limitations: A limitation of the study was the lack of information about environmental exposures, lifestyles, or underlying genetic or medical conditions, which could have contributed to increased infection in addition to causing cancer. Another limitation was that information regarding infection was based solely on diagnoses recorded in the database; thus, there may be variability in diagnoses across different clinicians, and some infections may not have been diagnosed or recorded. The small sample size for rare cancers was an additional limitation.

When physically fit women exercise during pregnancy they could be setting their children up for better fitness too.

That's according to a study published today in Science Advances led by Min Du, professor of animal sciences at Washington State University, and his PhD student Jun Seok Son.

They found exercise during pregnancy stimulates the production of brown adipose tissue, commonly known as brown fat, in a developing fetus. Brown fat's primary role in the body is to burn off heat. It is often called good fat. White adipose tissue or white fat, on the other hand, is responsible for obesity and harder to burn off. It is commonly known as bad fat.

Du and Son's results show the offspring of physically fit mice that exercised daily during pregnancy not only had a greater proportion of brown fat relative to body weight but also burned white fat off quicker than the offspring of a control group of pregnant mice that did not exercise. This helped prevent obesity and also improved metabolic health.

Their study is unique because up to now, the impacts of exercise during pregnancy on fetal development have only been examined in obese mothers.

"Previous research has shown that exercise among overweight women during pregnancy protects against metabolic dysfunction and obesity in their offspring," Du said. "This new study shows these benefits may also extend to the offspring of women who are healthy and in shape."

As exercise during pregnancy is becoming less common and obesity rates in children are increasing among mothers with various body mass indices, the researchers hope their findings will encourage healthy and fit women to continue living an active lifestyle during pregnancy.

"These findings suggest that physical activity during pregnancy for fit women is critical for a newborn's metabolic health," Son said. "We think this research could ultimately help address obesity in the United States and other countries."

In the study, healthy maternal mice were assigned either to a sedentary lifestyle or to exercise daily. Their offspring were then subjected to a high energy/caloric diet.

Notably, female and male offspring from the experimental group whose mothers had exercised consumed more feed than offspring from the control group. Nonetheless, the experimental group mice showed less weight gain.

Additionally, there was an improvement in glucose tolerance in the female and male offspring from the experimental group. Glucose intolerance is a precursor to developing diabetes and other obesity-related diseases later in life.

Exercise during pregnancy also stimulated the production of apelin, an exercise-induced hormone, in both mothers and their fetuses. Apelin stimulates brown fat development and improves metabolic health.

Du and Son also found administering apelin to the pregnant mice in the control group mimicked some of the beneficial effects of exercise on their offspring.

"This suggests that the apelinergic system could be a possible target for developing drugs that help prevent obesity," Du said.

Sophia Antipolis - 17 April 2020: Women are more likely to die after a heart attack than men because they are often not prescribed the drugs they need. That's the result of research presented today on ACVC Essentials 4U, a scientific platform of the European Society of Cardiology (ESC).

"Female heart attack patients may appear more fragile to physicians since they are often older than men, with smaller bodies and more co-existing conditions such as diabetes and kidney disease," said study author Dr. Claudio Montalto of the University of Pavia, Italy. "Therefore, I think doctors might avoid potent antiplatelets (a type of blood thinner) and aggressive blood pressure lowering."

The study prospectively enrolled 1,523 patients diagnosed with a heart attack between 2015 and 2017, including 471 (31%) women and 1,052 (69%) men. Prescribed medications were recorded, as were any medical reasons why a drug should not be prescribed (called contraindications).

Women were more likely to die after a heart attack than men. Rates of in-hospital death were similar between sexes but after an average 264-day follow-up, more women than men had died. "Previous studies have already established excess deaths in female heart attack patients, so we expected this result," said Dr. Montalto.

A significantly lower proportion of women received optimal medical therapy at discharge (55% of women versus 64% of men). Women were also less likely to undergo invasive procedures than men (71% of women versus 83% of men).

Dr. Montalto said: "It is well established that optimal medical therapy and invasive management are both associated with increased survival after myocardial infarction. Therefore, we then examined whether female patients had worse survival strictly due to their sex - which means genetic and hormonal status, and so on - or because of suboptimal treatment."

Using 'multivariable regression', a type of statistical analysis, it was observed that receiving optimal medical therapy after a heart attack was independently associated with a roughly 50% decrease in all-cause death, while female sex was not an independent predictor of death after a heart attack.

"Our study suggests that it is not being female that causes more deaths, but it is receiving fewer recommended drugs," said Dr. Montalto. "In fact, getting the right medication nearly halves the risk of dying."

Dr. Montalto noted that a strength the study was collecting data on contraindications. "This enabled us to discriminate whether non-prescription of a drug was due to a contraindication or not," he said.

Dr. Montalto concluded: "Appropriate drug prescription is easily improved with increased knowledge of guideline recommendations and closer attention to contraindications to drug therapy. Our study indicates that these actions could improve the outcome of female heart attack patients."