Body

DOCTORS and nurses on the COVID-19 frontline are spending many hours a day wearing face masks, and many members of the general public are doing the same. But although the devices offer invaluable protection, they can be the cause of significant skin damage through sweating and the rubbing of the masks against the nose.

Skincare experts at the University of Huddersfield are warning about the risks and are suggesting remedies.

Professor Karen Ousey is the University's Director of the Institute of Skin Integrity and Infection Prevention and was part of a team that conducted detailed research into the pressure damage caused by a wide range of medical devices, including face masks. The findings and recommendations were published in February.

Now, the current emergency emphasises the problems that can arise with face masks, being worn for long periods by healthcare professionals.

"The wearers are sweating underneath the masks and this causes friction, leading to pressure damage on the nose and cheeks," said Professor Ousey. "There can be tears to the skin as a result and these can lead to potential infection," she added.

"The masks the healthcare professionals are wearing have to be fitted to the face - so if healthcare professionals add dressings to the skin under the mask after being fitted there is a chance the mask will no longer fit correctly," continued Professor Ousey.

She suggests that people wearing masks keep their skin clean, well-hydrated and moisturised and that barrier creams should be applied at least half an hour before masks are put on.

"And we are suggesting that pressure from the mask is relieved every two hours. So you come away from the patient, relieve the pressure in a safe place and clean the skin again."

Professor Ousey advises members of the general public - such as shop workers - who are wearing masks to keep their skin clean, dry and free of sweat.

"And if they do feel their masks rubbing, take them off as soon as they safely can."

The COVID-19 pandemic has presented challenges to many health care systems across the globe. With limited science to guide staff and structure surge response, authors Matteo Paganini, Andrea Conti, Eric Weinstein, Francesco della Corte and Luca Ragazzoni from the Research Center in Emergency and Disaster Medicine (CRIMEDIM), Università del Piemonte Orientale in Novara, Italy reviewed the available surge literature and using a translational science approach posed the question "How does the concept of sudden onset mass casualty incident (MCI) surge capability apply to the process to expand COVID-19 response?

After reviewing the on-line ahead of print and print COVID-19 scientific publications, as well as grey literature, a checklist was created to guide the Emergency Department team's COVID-19 surge structural response in the Novara hospital.

According to Dr Paganini "Preparedness is crucial for the resilience of healthcare systems. This pandemic has found us unprepared. We have to translate disaster medicine theory into practice, reconfiguring our Emergency Departments to meet the surge of patients. These guidelines can help the hospital team meet this demand."

As some consider treating coronavirus patients with a combination of the malaria drug hydroxychloroquine and the antibiotic azithromycin, cardiologists are advising caution because both medications can increase the risk for dangerous abnormal heart rhythms.

In guidance published in the American College of Cardiology publication Cardiology Magazine, cardiologists from Oregon Health & Science University and Indiana University recommend clinicians who treat COVID-19 patients with the malaria-antibiotic drug combination also consider monitoring those patients for ventricular arrhythmia, which involves the lower heart chambers beating quickly and irregularly and can lead to cardiac arrest.

There are hundreds of drugs that can increase the risk for cardiac arrest, but using two together in patients who are already at risk or critically ill could increase that risk further, the paper notes.

"While there is yet very little data regarding hydroxychloroquine and azithromycin's effectiveness as a treatment for COVID-19, some clinicians are considering combining them during this global pandemic," said the paper's lead author, Eric Stecker, M.D., M.P.H., an associate professor of medicine (cardiovascular medicine) in the OHSU School of Medicine and OHSU Knight Cardiovascular Institute. "If physicians use their best medical judgement and order this drug combination for coronavirus patients, we want them to be aware of potential adverse side effects."

Stecker and colleagues recommend clinicians who treat COVID-19 patients with the drug combination also monitor patients for dangerous arrhythmias. However, they acknowledge limited resources could make monitoring a challenge.

"Until we have clinical outcome data supporting the benefit or harm of these medications, I would advocate for a cautious approach in using the combination of hydroxychloroquine and azithromycin," Stecker said. "Any medications that increase the risk of cardiac risk require consideration of both risks and benefits, and right now we do not have evidence that benefits outweigh risks for use of hydroxychloroquine or chloroquine. Until we have more information, patients should be monitored for arrhythmias during any use of these medications, alone or in combination, unless risk of infection for health care workers or limitations in use of personal protective equipment are prohibitive."

Two new studies from the Boston University School of Public Health (BUSPH) shed light on the relationship between obesity and the use of prescription opioids in the United States.

One of the studies, published in the American Journal of Preventive Medicine, finds that patients with higher body mass indices (BMIs) were up to 158% more likely to use prescription opioids long-term, and that 27% of long-term opioid prescriptions from 2000 to 2015 were attributable to higher BMIs.

The other study, published in JAMA Open Network, examines the pain conditions underlying this increased likelihood of opioid prescriptions for people with higher BMIs. This study finds that osteoarthritis and other joint disorders were the two reasons for an opioid prescription most strongly associated with obesity. Together, osteoarthritis, other joint disorders, and back disorders accounted for more than half of the difference in opioid prescriptions by obesity.

"Research on the opioid crisis to date has focused heavily on the supply-side factors that increased access to opioids," says Dr. Andrew Stokes, assistant professor of global health at BUSPH, who led both studies. "Our studies offer new evidence for policymakers to consider how addressing the roots of this crisis will require attention to the underlying sources of demand for pain relief, including obesity through its association with pain."

The JAMA Open Network study is the first in a collaboration between BUSPH and athenahealth, supported by the Robert Wood Johnson Foundation, with Stokes and colleagues drawing from the multipayer electronic health record data in athenahealth's network of over 60 million patients receiving care from more than 120,000 health professionals across the United States.

For this study, the researchers used anonymized data from 565,930 patients who were between 34 and 64 years old in 2016 and had a BMI measurement recorded during that year. They then identified any opioid prescriptions for these patients in the year before or after their BMI measurement, as well as any related pain diagnoses.

After adjusting for age, sex, race/ethnicity, urbanicity, and other factors, the researchers found that patients with BMIs considered "overweight" or "obese" were more likely to be prescribed opioids than patients with BMIs in the "normal" range. The associations were particularly strong for opioid prescriptions related to joint and back pain, suggesting that these conditions play a significant role in increasing demand for pain management among patients with obesity.

In their other study, Stokes and colleagues used data from the Medical Expenditure Panel Survey to report on 89,629 adults between the ages of 30 and 84 years old who had never been prescribed opioids when first surveyed. They then analyzed the incidence of long-term (approximately 10 months or longer) use of prescription opioids. The team found that patients with higher BMIs were more likely to use opioids long-term, ranging from a 24% increased likelihood for those with BMIs considered "overweight" to a 158% increased likelihood for those with BMIs in the "obese III" range. Joint pain, back pain, injury, and muscle/nerve pain were commonly identified as reasons for opioid prescriptions.

"Policy efforts are urgently needed to regulate the obesogenic environment in this country," says Dielle Lundberg, a research fellow in the Department of Global Health at BUSPH and co-author of both studies. "When people are denied access to affordable, healthy food and to the sort of built environments that promote physical activity and health across the life course, obesity is more likely to occur. The results of both studies suggest that through obesity, such environments can also increase pain and create future demand for prescription opioids."

"These data also highlight the urgent need for better pain management approaches and options for millions of Americans," says Dr. Tuhina Neogi, professor of epidemiology at BUSPH, professor of rheumatology at the Boston University School of Medicine, chief of rheumatology at Boston Medical Center, and senior author of the JAMA Open Network study. "The lack of sufficient medication options, woeful underutilization of physical therapy (which is well-supported by high-quality evidence for these conditions), and challenges in supporting weight loss efforts have led to prescription of opioids in management of painful musculoskeletal conditions where little evidence exists to support their use."

In elective surgery, does the likelihood of treatment success depend on how often the hospital or the medical team performs the intervention? This is the question addressed in eight commissions on minimum volumes awarded in Germany by the Federal Joint Committee (G-BA) to the Institute for Quality and Efficiency in Health Care (IQWiG). The IQWiG report is now available for the third indication investigated, the surgical treatment of lung carcinoma. According to the findings, in this indication a largely positive correlation exists between the volume of services provided and the quality of treatment results: In hospitals with a larger case volume, the survival probabilities for patients who underwent this type of surgery are higher overall.

The most common malignant tumour in men, the second most common in women

In 2014, 53,840 patients in Germany were diagnosed with lung cancer, with more men being affected (64%). In the same year, 45,084 people died of lung cancer in Germany. The 5-year survival rate of patients is less than 20%, which is, among other things, due to the fact that lung cancer causes clinical symptoms only later on in the disease and is therefore often detected only at an advanced stage. For instance, approximately 50% of all lung cancer patients have distant metastases at the time of diagnosis. Lung cancer is thus the most common fatal malignant tumour in men and the second most common after breast cancer in women.

Surgical treatment of lung carcinoma

The histological tumour type is decisive in the choice of therapy. In particular, the distinction between non-small-cell and small-cell lung carcinoma (NSCLC and SCLC) is important.

For NSCLC, surgery alone is recommended in early-stage disease; surgery with supportive chemotherapy is recommended in the later stage.

In contrast to NSCLC, SCLC grows very rapidly and often soon forms metastases in other organs. Surgery is only a treatment option in early-stage disease.

In Germany, there is currently no binding minimum volume for hospitals with regard to lung cancer surgery.

Positive correlation between volume and quality

On the basis of 19 observational studies included in the assessment, IQWiG sees a positive correlation between the volume of services provided and the quality of treatment results for the surgical treatment of lung carcinoma. In particular, the more frequent performance of such interventions increases the survival probabilities of patients. However, the certainty of this conclusion is impaired by the rather low analytical quality and occasionally inadequate reporting of study results.

The study results on the outcomes "overall survival", "treatment-related mortality" and "death in hospital" are decisive for IQWiG's assessment. According to these results, with a lower volume of services a higher mortality rate can be assumed in patients who underwent lung cancer surgery.

No usable results were available on the outcome category "morbidity" with the outcomes "disease-free survival", "serious, life-threatening or fatal infections", and "further serious treatment-related complications"). The same applied to the outcome "health-related quality of life". Accordingly, for these outcomes no conclusion can be drawn on the correlation between the number of interventions performed for the surgical treatment of lung carcinoma and the quality of treatment results.

With regard to other malignant lung tumours, IQWiG's search for meaningful studies on the correlation between the volume of services and the quality of treatment results was inconclusive. The IQWiG researchers are unable to answer the question as to the effects on the quality of treatment results if specific minimum volume thresholds were to be introduced into health care for the surgical treatment of lung carcinoma, as no suitable publications are available.

Process of report production

In December 2018, the Federal Joint Committee (G-BA) commissioned IQWiG to prepare the report on the correlation between the volume of services and the quality of treatment results in lung carcinoma in an accelerated procedure as a so-called rapid report. Interim products were therefore not published or made available for a hearing. This rapid report was sent to the contracting agency, the G-BA, in October 2019.

COPD, short for chronic obstructive pulmonary disease, is linked to a heightened risk of lung cancer in people who have never smoked, indicates research published online in the journal Thorax.

The risk is on a par with that of smokers without chronic lung disease, the findings indicate.

COPD is an umbrella term for respiratory conditions that narrow the airways, such as bronchitis and emphysema. Smoking is the main risk factor for COPD, which itself is associated with a heightened risk of developing lung cancer.

But up to 39% of people who develop COPD have never smoked, and it's not clear what their risk of lung cancer is, because most of the studies looking at this have included too few participants.

To explore this further, the researchers drew on data from the National Health Insurance Service (NHIS) National Sample Cohort study, involving a representative sample of Korean citizens.

For the purposes of the current study, the researchers included 338,548 men (146,996) and women (191,552) between the ages of 40 and 84, with no history of lung cancer, who had had at least one health check provided by NHIS between 2002 and 2013.

Their health was tracked for an average of 7 years, based on inpatient and outpatient treatment and prescriptions issued.

During this monitoring period, 1834 participants developed lung cancer. In 290 cases, the person had COPD, but in 1544 cases, the person didn't.

Among current and former smokers, those without COPD were around twice as likely to develop lung cancer while those with COPD were 6 times as likely to do so, compared with people who had never smoked and didn't have COPD.

But after taking account of potentially influential factors, among those who had never smoked, people with COPD were more than 2.5 times as likely to develop lung cancer as those without COPD, the data analysis showed.

What's more, the risk of lung cancer in those with COPD, but who had never smoked, was on a par with that of smokers without COPD, the findings indicate.

"Given that poor lung function in COPD is often a barrier to optimal lung cancer treatment due to increased risk of treatment related morbidities, our study suggests that early detection of lung cancer in COPD patients may reduce the risk of treatment complications," write the researchers.

They acknowledge that the severity of COPD wasn't assessed, nor were they able to glean information on environmental and occupational exposures, all of which may have influenced the development of lung cancer.

Nevertheless, they suggest their findings indicate that COPD is a strong independent risk factor for lung cancer.

"Future studies should evaluate whether COPD patients are candidates for lung cancer screening, irrespective of smoking status," they conclude.

Many patients previously diagnosed with a penicillin allergy can have their allergy label removed after testing and safely undergo treatment with penicillin medications, according to a study published in American Journal of Respiratory and Critical Care Medicine.

Around 8-15% of the U.S. population is labeled with a penicillin allergy, but and many of these allergies are the result of viral rashes, drug-viral interactions, or non-allergic side effects. Even patients who experience a severe anaphylactic reaction appear to lose their sensitivity at a rate of 10% or more every year.

"To date, our team has removed more than 90 low-risk penicillin allergies without any patients reporting a symptomatic challenge," said lead author Cosby A. Stone, Jr., MD, instructor in Allergy/Immunology at Vanderbilt University Medical Center.

"Around one-third of the patients whose penicillin allergies were removed have already gone on to safely use penicillin treatments in their subsequent health care when they were needed," he said.

A false penicillin label can prohibit appropriate patient treatment through limitations that force doctors to use broader spectrum and second line antibiotics, increasing the chances of surgical site infections, greater health care utilization, treatment failure for common infections, drug resistant infections, and longer lengths of stay.

Data collected from the outpatient Drug Allergy Clinic at Vanderbilt University Medical Center was used to develop a risk-stratification tool that could identify patients with low-risk penicillin allergies in the Medical Intensive Care Unit (MICU).

Over a seven-month period, patients who were screened and identified as low-risk received an oral dose of 250mg of amoxicillin and remained under observation for an hour and a half following this challenge, without a preceding allergy skin test.

The team's results showed that none of the low-risk patients who underwent a direct oral challenge during the study period had any symptoms of an allergic reaction when challenged, enabling their penicillin allergy label to be removed.

Directly challenging low-risk penicillin allergies with a dose of amoxicillin is expected to be a strategy that can remove up to 60% of all penicillin allergies and improve a patient's future health care by expanding possible treatment options.

Few novel or emerging infectious diseases have posed such vital ethical challenges so quickly and dramatically as the novel coronavirus. An early-view essay in the March-April 2020 Hastings Center Report offers guidance at a time when health care institutions and governments are desperately confronting these challenges.

The authors are Prof. Lawrence O. Gostin, director of the O'Neill Institute for National and Global Health Law at Georgetown University, director of the WHO Center on Global Health Law, and a Hastings Center fellow; Eric A. Friedman, the Global Health Justice Scholar at the O'Neill Institute; and Sarah A. Wetter, a law fellow with the O'Neill Institute.

Their essay addresses these vital questions as the United States responds to the Covid-19 pandemic:

When the health system becomes stretched beyond capacity, how can we ethically allocate scarce health goods and services?

How can we ensure that marginalized populations can access the care they need?

What ethical duties do we owe to vulnerable people separated from their families and communities?

How do we ethically and legally balance public health with civil liberties?

The full text of the essay, "Responding to Covid-19: How to Navigate a Public Health Emergency Legally and Ethically," is available for free.

"How we respond to this pandemic, whether we act ethically and safeguard the most vulnerable among us, will be a test of our humanity," Gostin said. "Everyone will suffer, and many will die, in the coming months, but those who are unemployed, uninsured, poor, or disabled will suffer most. As a society, we have an ethical duty to do all we can to meet the needs of the most disadvantaged among us."

To ethically allocate scarce goods and services, the authors point to a "World War II-style mobilization" and call on the president "to exercise his full authority under the Defense Production Act to mobilize industry to project urgently needed resources."

The authors discuss steps that should be taken to ensure that marginalized populations, like people with disabilities and people of color, receive a fair distribution of scarce resources. "In addition to identifying specific groups that need special care, ethical distribution requires a fair process in deciding," they write. That process should include the public and must be transparent and grounded in scientific evidence. Fair distribution is not only a national issue but also a global one. "Globally, lower?income countries will face much more scarcity than wealthier states and, if Covid?19 takes hold, a higher burden of disease," they write. "The United States is ethically obligated to assist--even if this means reducing American stockpiles--to maximally protect and equally value all human life."

The essay offers several recommendations for protecting vulnerable populations, including under- and uninsured persons and immigrants, and assuring that they have access to care. Among the recommendations is this: "Governments must assure that Covid?19 testing and care, and vaccines and treatment once available, are free so that cost does not cause anyone to delay or avoid care."

The authors address the economic and social disruption that results from physical distancing, quarantine, and other measures to control the spread of infections. To balance public health and civil liberties, they write, "a basic rule is that governments should employ the least restrictive means necessary to protect public health." That standard should "be based on rigorous scientific assessment of risk and effectiveness." Further, "containment measures must not be a subterfuge for discrimination."

"At a time of vast inequities, we are all only as safe as the most vulnerable among us--both in the United States and globally . . . . ," the essay concludes. "We are in uncharted territory, where vital human connections and economic activity are disrupted in ways not seen in generations. If we want to safeguard the public's health while being faithful to our most fundamental values, then we must ensure that our response is effective, ethical, and equitable."

Sophia Antipolis, 2 April 2020: The effects of exercise on metabolism are even greater than scientists believed. That's the finding of a unique study published today in Cardiovascular Research, a journal of the European Society of Cardiology (ESC).1

The study is the first to examine the metabolic effects of exercise while carefully controlling for differences between participants in diet, stress, sleep patterns, and work environment.

"These results show that metabolic adaptation to exercise is far more profound than previously reported," said senior author Dr. John F. O'Sullivan of the University of Sydney, Australia. "The results increase our knowledge of the widespread benefits of exercise on metabolism and reveal for the first time the true magnitude of these effects. This reinforces the mandate for exercise as a critical part of programmes to prevent cardiovascular disease."

One of the major challenges when studying the effects of exercise is controlling for factors that differ between participants and could influence the results. For example: age, gender, weight, baseline fitness, diet (some healthy, some very unhealthy), sleep patterns, jobs (physical work versus a desk job), alcohol, and smoking.

"Our motivation for this study was to overcome this limitation by studying exercise under controlled conditions, thereby revealing the true extent of effects on the body," said Dr. O'Sullivan. "Therefore, we used a cohort of newly-enlisted healthy male soldiers of similar age and baseline fitness who lived in the same domicile, had the same sleep patterns, ate the same food, and underwent the same exercise regimen."

One of the major benefits of exercise is on metabolism, which is how the body converts food into energy and eliminates waste. Substances produced during metabolism are called metabolites. "Metabolites are the intermediates of the metabolic machinery in the body and can signal how metabolic health is changing in response to exercise," explained Dr. O'Sullivan.

The researchers measured approximately 200 metabolites in the blood of 52 soldiers before and after an 80-day aerobic and strength exercise programme and related these to changes in fitness.

Compared to previous studies, the researchers found dramatic changes in many metabolites. Trained, energy-efficient muscle used far more fuel - for example fat - than shown ever before. The researchers also captured heretofore unseen, in terms of scale and scope, changes in levels of factors derived from the gut, factors involved in blood clotting, breakdown products of protein, and factors involved in opening up blood vessels to increase blood flow.

Participants who did not experience these metabolic benefits of exercise had higher levels of a metabolite called DMGV. "This is intriguing because a recent study also found that this metabolite predicted who did not benefit from exercise," said Dr. O'Sullivan. "DMGV levels are influenced by genetics and diet, rising with sugary drinks and falling with vegetables and fibre. Measuring DMGV may identify people who need strategies other than exercise to reduce their cardiovascular risk."

He concluded: "The power of exercise to boost metabolism is on top of its positive effects on blood pressure, heart rate, fitness, body fat, and body weight. Our findings cement the central role of exercise in preventing cardiovascular disease."

HOUSTON-(April 1, 2020)-We've all been warned about the dangers of triglycerides, the fat stored in your blood. But what if that unhealthy fat could effectively transport oral medication to your body and eliminate the need for some injections or IV treatment?

Houston Methodist nanomedicine researchers are studying this new drug delivery system for a diabetes drug that resulted in approximately 25% absorption in mice models, which is considered to be very high for an oral drug.

The research published in Science Advances may pave the way for oral delivery of more biological drugs, like those used to treat rheumatoid arthritis and other autoimmune diseases.

"We know the human body can absorb fatty acids, so we decided to chemically link biological drug molecules to fatty acids to see how well these drugs are absorbed into the gastrointestinal system. It turns out that our 'transporter approach' was effective," said Haifa Shen, M.D., Ph.D., professor of nanomedicine, Houston Methodist Research Institute, who began this work more than five years ago when a family member diagnosed with diabetes needed insulin injections three times a day.

After designing a platform where a peptide-based drug used to treat diabetes mellitus was chemically linked to fatty acids, Shen and team packaged the resulting combination in a nanoparticle that was resistant to gastric acids in the stomach. Once inside the small intestine, the drug molecules were released from the nanoparticle and the mice absorbed 24.8% of the drug dosage.

The majority of small molecule drugs are prepared in tablets and given orally. But biological drugs, like those to treat diabetes, cannot sustain the harsh environment in the GI tract, which includes gastric fluids and digestive enzymes in the stomach. The only option has been intravenous infusion or injections, which are more costly than oral drugs and pose compliance challenges for many patients who struggle with inconvenient appointments and the high cost of treatment.

"This was just the first drug we tested. Our approach could be used to deliver many other biological drugs, such as human growth hormone and therapeutic antibodies," said Shen.

Now that the nanomedicine researchers have proven the drug platform works in animal models, the next step is to perform toxicity studies, produce the drugs in a larger quantity and, eventually, move to clinical trial in patients. Although fatty acids may one day be key to fighting diabetes, the technology still has a ways to go before people can derive benefit from consuming fatty acids.

A new paper in The American Journal of Hypertension, published by Oxford University Press, finds that mat Pilates may be an effective strategy to improve cardiovascular health for young obese women, a population that is at risk for hypertension and early vascular complications.

With an estimated 9 million participants in 2018 and a series of celebrity endorsements, including Beyoncé and Emma Stone, mat Pilates training has seen a recent resurgence in popularity. It has become one of the most widely known wellness routines in the United States. The program emphasizes core strength, flexibility, body posture, and controlled breathing.

At the same time, the prevalence of obesity in young adults has become a major public health issue. Though it is well-documented that exercise is a key factor in preventing and managing cardiovascular health problems, obese women tend not to maintain traditional workout routines. Despite sources in the media reporting on the cardiovascular benefits of Pilates, the existing scientific literature is scarce.

Researchers here studied young obese women (age 19-27) with elevated blood pressure and a body mass index between 30-40kg/m2 through 12 weeks of mat Pilates. The participants were free of chronic diseases, were non-smokers and performed less than 90 minutes of regular exercise per week. There were three one-hour training sessions per week, which were divided into the following stages: initial warm up and stretch (10min), general mat Pilates exercises (40 min), and a cool down (10 min). The training increased over the 12 weeks, with the repetition of each exercise steadily increasing. A certified mat Pilates instructor supervised all sessions.

This is the first study to find that mat Pilates routines significantly reduced arterial stiffness and blood pressure, including central (aortic) pressure.

"We hypothesized that Mat Pilates might decrease the risk of hypertension in young obese women. Our findings provide evidence that Mat Pilates benefit cardiovascular health by decreasing blood pressure, arterial stiffness, and body fatness in young obese women with elevated blood pressure. Because adherence to traditional exercise (both aerobic and resistance) is low in obese individuals, Mat Pilates Training might prove an effective exercise alternative for the prevention of hypertension and cardiovascular events in young obese adults."

Investigators at St. Jude Children's Research Hospital, the European Molecular Biology Laboratory, and the German Cancer Research Center have identified ELP1 as a novel predisposition gene in the SHH subgroup of pediatric medulloblastoma. The work appears as an advance online publication today in Nature.

Medulloblastoma is the most common malignant pediatric brain tumor. The SHH subgroup accounts for about 30% of all pediatric medulloblastoma cases. Previous research suggested that this subgroup is affected by genetic predisposition from abnormalities in the germline (inherited) DNA of patients. However, this prior work was restricted to known cancer predisposition genes.

"The scientific evidence and the experiences of patients and families suggested to us that inherited mutations might play a bigger role than previously thought," said co-senior author Paul Northcott, Ph.D., of the St. Jude Department of Developmental Neurobiology. "By searching for genes beyond the usual suspects, we showed that a significant portion of SHH medulloblastoma with inherited mutations wasn't being recognized."

The team looked at all protein-coding genes (the exome) in more than 1,000 patients with medulloblastoma. The researchers compared their medulloblastoma findings to more than 118,000 exomes from several databases of individuals without cancer. Results showed that the gene ELP1 is abnormally mutated in the germline DNA of 14-15% of children with SHH medulloblastoma.

With the addition of ELP1 to the list of known cancer predisposition genes, the researchers showed that at least 40% of pediatric SHH medulloblastoma is driven by an inherited abnormality. ELP1 mutations occur at more than double the rate of any other previously acknowledged cancer predisposition gene in SHH medulloblastoma.

A better understanding of predisposition

ELP1 normally functions as part of a multi-subunit complex called elongator. Elongator plays a role in regulating translation, the process of translating genetic information into proteins. This finding supports investigations into how dysregulation of translation contributes to medulloblastoma.

"When multiple members of a family have the same kind of medulloblastoma, but don't have mutations in any of the recognizable predisposition genes, there has to be more to the story," said co-first author Giles Robinson, M.D., of the St. Jude Department of Oncology. "ELP1 has not been part of routine genetic testing offered to patients and families, but this work suggests that it should be included for medulloblastoma."

The researchers also found that ELP1 may help guide prognosis. Patients with this mutation tend to do well on currently available therapies. Researchers are continuing to study ELP1 in the laboratory to determine if the identified mutations could be used to tailor medulloblastoma therapy in the future.

(Boston)--People living with human immunodeficiency virus (HIV) infection are at higher risk of cardiovascular disease (CVD) compared to people without HIV. Data linking HIV and CVD, CVD risk factors and CVD risk assessment come predominantly from North America and Europe. However, of the estimated 37.9 million people living with HIV worldwide, two-thirds (25.6 million) live in sub-Saharan Africa, where less is known about rates of incident CVD and the burden of risk factors driving CVD risk.

Using published, peer-reviewed studies, a multidisciplinary research team reports that while similar mechanisms increasing risk CVD among people with HIV, the distribution of CVD risk factors varies by geography: in sub-Saharan Africa where the HIV epidemic is concentrated populations are younger, prevalence of elevated blood pressure is higher, but prevalence of tobacco smoking and elevated cholesterol is lower than in North America and Western Europe. "These variations mean the profile of CVD risk differs in lower compared to higher income countries," said corresponding author Kaku So-Armah, PhD, assistant professor of medicine at BUSM.

These findings appear as a Review in the journal Lancet HIV.

In addition to describing current approaches to reducing CVD risk in HIV and potential gaps where additional research is needed, the researchers explore the biological mechanisms that could explain why people with HIV have higher risk for specific cardiovascular diseases, highlighting important potential differences in higher and lower income countries.

According to the researchers, reducing CVD risk among people with HIV globally calls for a concerted, thoughtful balancing of public and individual health approaches, evidence-informed strategies and expert healthcare provider and patient opinions, as well as basic, translational and implementation research in areas with the highest HIV burden.

The researchers hope this review will contribute to awareness about increased heart disease risk in HIV globally and allow for continued research on integrating heart disease prevention into HIV care in a manner most appropriate for the target population.

BUFFALO, N.Y. - Activity from phony Twitter accounts established by the Russian Internet Research Agency (IRA) between 2015 and 2017 may have contributed to politicizing Americans' position on the nature and efficacy of vaccines, a health care topic which has not historically fallen along party lines, according to new research published in the American Journal of Public Health.

The findings, based on machine learning analysis of nearly 3 million tweets from fake accounts, expose a general threat made startlingly more relevant in the face of the pandemic caused by the novel coronavirus, according to Yotam Ophir, an assistant professor of communication in the University at Buffalo College of Arts and Sciences, who co-authored the study.

"There is a real danger of health topics being politicized and used as propaganda tools. If that happens for topics such as coronavirus, people would be inclined to evaluate the importance and veracity of health messages - from either health experts, politicians, or trusted media outlets -- based on how it reflects their political leanings," says Ophir, an expert in computational modeling, media effects and persuasion.

"If people perceive health topics as being aligned with a political agenda, whether it's left or right, then they will consequently begin to lose trust in health organizations and question their objectivity."

To understand why this might only be the beginning of more intense polarization is to understand that the threat posed by polarizing health care topics may be an unintended side effect of Russian attempts to influence other political discussions, including topics tied closely to the 2016 U.S. presidential election.

"I don't believe the Russians wanted to sow discord around vaccines specifically, but rather chose to harness social tensions around vaccines in order to make the Republican characters they created appear more Republican and the Democratic characters they created to appear more Democratic. This intensifies a recently emerging divide where one previously did not exist."

The Russians' intentions in this particular case, however, don't matter when considering the implications for public health, according to Ophir. What is pertinent is that the IRA used a public health topic to serve its own strategic and political needs that targeted Republicans and Democrats with different messages. If that proves effective, the Russians will ramp up their misinformation campaign, moving from what might be an unplanned outcome to a more persistent and focused effort.

"In recent years, we see the change already with Republicans starting to lose trust in vaccines while Democrats seem unmoved," Ophir says. "Again, I don't think the Russians care about vaccines, but along the way they created and intensified this emerging divide.

"Now they can target each party with different messages, spreading misinformation unequally, targeting susceptible groups with lower trust in government and science."

Ophir's paper with Dror Walter, an assistant professor of communication at Georgia State University, and Kathleen Hall Jamieson, director of the Annenberg Public Policy Center at the University of Pennsylvania, began as a conversation at a 2018 conference, after it was first discovered that Twitter troll accounts were discussing non-political topics such as vaccines.

At around the same time, Jamieson published "Cyber-War," a book about Russian interference in the 2016 presidential election that identified thematic personas among Twitter trolls. These personas are designated topical and linguistic roles played by each fake account.

Inspired by Jamieson's work, previous research and Ophir's focus on connecting health misinformation and politics, the team used computational methods to identify nine personas among nearly 2,700 accounts.

The pro-Trump personas were more likely to express anti-vaccine sentiment, while anti-Trump personas expressed support for vaccines. Accounts falling under the persona type mimicking African Americans and Black Lives Matter activists also expressed more anti-vaccine messages.

The researchers used their own method, the Analysis of Topic Model Networks, to identify patterns among the nearly 3 million tweets and network analysis that treats each topic as a node in a semantic network.

This form of unsupervised machine learning finds associations and clusters that are beyond human reach.

"I have reason to strongly believe, though we don't have the data, that Russia and other countries who try to interfere in our political discourse will use coronavirus to spread misinformation and rumors to solidify the relationships they're building with new troll accounts that replace the ones removed by Twitter," says Ophir.

"The virus is not political, but when any health topic becomes a political matter at the expense of fact, the result is to base conclusions and make decisions, such as whether to social distance or not, on party loyalty, not science.

"That's extremely dangerous," Ophir says.

WASHINGTON--Liraglutide 3.0 mg, approved by the United States Food and Drug Administration (FDA) as an adjunct to a reduced-calorie diet and increased physical activity to help adults with obesity manage their weight, appears to help adolescents too, according to an industry-sponsored randomized controlled trial. The study was accepted for presentation at ENDO 2020, the Endocrine Society's annual meeting, and will be published in a supplemental issue of the Journal of the Endocrine Society.

The research also will be published in The New England Journal of Medicine Tuesday.

"The results of this clinical trial suggest that liraglutide 3.0 mg given once daily along with lifestyle therapy improves body-mass index (BMI) standard deviation score (BMI SDS) and other measures of BMI and body weight among adolescents with obesity who have had difficulties in managing their weight with lifestyle therapy alone," said study author Aaron S. Kelly, Ph.D., a professor in the Department of Pediatrics and a co-director of the Center for Pediatric Obesity Medicine at the University of Minnesota Medical School in Minneapolis.

Kelly and his colleagues studied adolescents between 12 and 17 years of age with obesity who did not respond to lifestyle therapy. The trial took place at 33 sites in the United States, Mexico, Belgium, Sweden, and the Russian Federation. They investigated changes over time in BMI SDS, which reflects the relative weight to height ratio adjusted for age and sex, and they examined changes from baseline in other weight-related outcomes.

During the 12-week run-in period, all 251 participants received lifestyle therapy that involved counseling in healthy nutrition and physical activity for weight management. Afterwards, 125 participants received subcutaneous liraglutide 3.0 mg (or the highest dose tolerated) once daily and 126 participants received placebo once daily. Participants in both groups continued with lifestyle therapy throughout the 56-week treatment period and the 26-week off-treatment follow-up. In the treatment group, 101 participants remained through week 56 and 99 completed through week 82; in the placebo group, 100 remained through week 56 and 99 completed at week 82.

At week 56, participants who received liraglutide showed significantly reduced BMI SDS and greater improvements in body weight, BMI, waist circumference and other weight-related outcomes compared with those who received placebo.

At week 56, the authors found no significant differences in blood pressure, fasting lipids, fasting plasma glucose or hemoglobin A1c (HbA1c). At week 82, after 26 weeks of drug discontinuation but continued lifestyle therapy, participants who had received liraglutide during the 56-week treatment period had a greater increase in BMI SDS than those in the placebo group. The safety profile of liraglutide was similar to that of adults, with no reported unexpected safety concerns or severe hypoglycemia. The adolescents taking liraglutide reported more gastrointestinal side effects (64.8%) than those taking placebo (36.5%) and few serious adverse events (three versus five events, respectively). Mental health questionnaire results at 52 weeks were similar in both groups, and the authors found no apparent effects on growth or pubertal development.

"Obesity is a serious, chronic, progressive disease affecting around 107.7 million children and adolescents worldwide and is associated with an increased risk of developing other health problems," Kelly said. "Over 70% of children with obesity before puberty maintain obesity as adults. Effective treatment options for adolescents with obesity are limited, and lifestyle therapy, the typical first treatment, often yields suboptimal responses. In adolescents with obesity, we need additional treatment options that we can use along with lifestyle therapy."