Body

Individual choices in medicine carry a certain amount of uncertainty.

An innovative partnership at The University of Texas at Austin takes aim at medicine down to the individual level by applying state-of-the-art computation to medical care.

"Medicine in its essence is decision-making under uncertainty, decisions about tests and treatments," said Radek Bukowski, MD, PhD, professor and associate chair of Investigation and Discovery in the Department of Women's Health at Dell Medical School at UT Austin.

"The human body and the healthcare system are complex systems made of a vast number of intensely interacting elements," he said. "In such complex systems, there are many different pathways along which an outcome can occur. Our bodies are robust, but this also makes us very individualized, and the practice of medicine challenging. Everyone is made of different combinations of risk factors and protective characteristics. This is why precision medicine is paramount going forward."

To that effect, in the January 2021 edition of the American Journal of Obstetrics Gynecology, experts at Dell Med, Oden Institute for Computational and Engineering Sciences (Oden Institute), and Texas Advanced Computing Center (TACC), along with stakeholders across healthcare, industry, and government, stated that the emergence of computational medicine will revolutionize the future of medicine and health care. Craig Cordola of Ascension and Christopher Zarins of HeartFlow co-authored this editorial review with Bukowski and others.

According to Bukowski, this interdisciplinary group provides a unique combination of resources that are poised to make Texas a leader in providing computational solutions to today's and tomorrow's health care issues.

"At UT Austin we're fortunate to have found ourselves at a very opportune point in time for computational medical research," Bukowski said. "The Oden Institute has world-class expertise in mathematical modeling, applied math, and computational medicine; TACC is home to the world's largest supercomputer for open science, and also committed to improving medical care, including outcomes for women and babies."

Powered by such collaborations, the emerging discipline of computational medicine focuses on developing quantitative approaches to understanding the mechanisms, diagnosis, and treatment of human disease through applications, more commonly found in mathematics, engineering, and computational science. These computational approaches are well-suited to modeling complex systems such as the human body.

An On-Point area of Study for Obstetrics

While computation is pivotal to all domains in medicine, it is especially promising in obstetrics because it concerns at least two patients -- mother and baby, who frequently have conflicting interests, making medical decision-making particularly difficult and the stakes exceptionally high.

According to state Rep. Donna Howard, D-Austin, a co-author of the editorial review, Texas legislators should be concerned about the unacceptably high rate of maternal morbidity and mortality in the state.

"When I became aware of the efforts to bring computational medical approaches to addressing maternal morbidity and mortality, I was immediately intrigued," Howard said. "And when I learned of the interdisciplinary expertise that has found itself conveniently positioned to create this new frontier of medicine, I was sold."

Individualized medicine is happening now because of advancements in computing power and mathematical modeling that can solve the problems which were unsolvable until now.

Case in point: in 2018 the National Science Foundation awarded UT Austin a $1.2 million grant to support research using computational medicine and smartphones to monitor the activity and behavior of 1,000 pregnant women in the Austin area.

In particular, the growing array of data sources including health records, administrative databases, randomized controlled trials, and internet-connected sensors provides a wealth of information at multiple timescales for which to develop sophisticated data-driven models and inform theoretical formulations.

"When combined with analysis platforms via high performance computing, we now have the capability to provide patients and medical providers analysis of outcomes and risk assessment on a per-individual basis to improve the shared decision making process," Bukowski concluded.

New Rochelle, NY, February 10, 2021--It may be safe for COVID-infected mothers to maintain contact with their babies. Keeping them apart can cause maternal distress and have a negative effect on exclusive breastfeeding later in infancy, according to The COVID Mothers Study published in the peer-reviewed journal Breastfeeding Medicine. Click here to read the article now.

In this worldwide study, infants who did not directly breastfeed, experience skin-to-skin care, or who did not room-in within arms' reach of their mothers were less likely to be exclusively breastfed in the first 3 months of life. Nearly 60% of mothers who experienced separation reported feeling very distressed, and 78% reported at least moderate distress. Nearly 1/3 of separated mothers (29%) were unable to breastfeed once reunited with their infants, despite trying.

"Our research contributes to the emerging evidence that skin-to-skin care, rooming-in within arms' reach, and direct breastfeeding may be safe for mothers infected with SARS-CoV-2," said Melissa Bartick, MD, Mount Auburn Hospital, and coauthors.

Arthur I. Eidelman, MD, Editor-in-Chief of Breastfeeding Medicine, states: "This report strengthens the recommendation that breastfeeding should be continued to be encouraged and supported in this era of the COVID-19 pandemic and that direct breastfeeding is indicated for mothers infected with SARS-CoV-2."

DALLAS, Feb. 10, 2021 — Reducing the prevalence of obesity may prevent up to half of new Type 2 diabetes cases in the United States, according to new research published today in the Journal of the American Heart Association, an open access journal of the American Heart Association. Obesity is a major contributor to diabetes, and the new study suggests more tailored efforts are needed to reduce the incidence of obesity-related diabetes.

Type 2 diabetes is the most common form of diabetes, affecting more than 31 million Americans, according to the U.S. Centers for Disease Control and Prevention[1]. The risk factors for Type 2 diabetes include being overweight or having obesity; being over the age of 45; having an immediate family member diagnosed with Type 2 diabetes; being physically active less than 3 times per week; or a history of gestational diabetes (diabetes during pregnancy). Type 2 diabetes is more common among people who are Black, Hispanic or Latino, American Indian, Alaska Native, Pacific Islander or Asian American.

The number of deaths due to Type 2 diabetes in people younger than 65 is increasing along with serious complications of the condition, including amputations and hospitalizations. In addition, Type 2 diabetes impacts heart disease and stroke risk: adults with Type 2 diabetes are twice as likely to have a heart attack or stroke than people without diabetes.

Type 2 diabetes can be prevented or delayed with healthy lifestyle changes, such as losing weight, eating healthy food and being physically active. According to the National Diabetes Prevention Program, behavior changes have been shown to help people with prediabetes lose 5% - 7% of their body weight and reduce their risk of developing type 2 diabetes by 58% (71% for people older than age 60). Researchers examined the prevalence and excess risk of Type 2 diabetes associated with obesity.

“Our study highlights the meaningful impact that reducing obesity could have on Type 2 diabetes prevention in the United States. Decreasing obesity needs to be a priority. Public health efforts that support healthy lifestyles, such as increasing access to nutritious foods, promoting physical activity and developing community programs to prevent obesity, could substantially reduce new cases of Type 2 diabetes,” says the study’s first author Natalie A. Cameron, M.D., a resident physician of internal medicine at the McGaw Medical Center of Northwestern University in Chicago.

Researchers used information from the Multi-Ethnic Study of Atherosclerosis (MESA) and four pooled cycles (2001-2016) of the National Health and Nutrition Examination Survey (NHANES). MESA is an ongoing, longitudinal study of 45 to 84-year-olds who did not have cardiovascular disease upon recruitment. MESA data included in this study was collected during five visits from 2000 to 2017 at six centers across the U.S. NHANES is a cross-sectional study of the American population that takes place every other year using patient questionnaires and examination data.

For this analysis, authors limited data to participants ages 45 to 79-years old. They included only those who were non-Hispanic white, non-Hispanic Black or Mexican American and who did not have either Type 1 or Type 2 diabetes at the beginning of the study. Researchers calculated both the prevalence of obesity and the excess risk of Type 2 diabetes associated with obesity.

The study’s findings include:

Among NHANES participants, the overall prevalence of obesity increased from 34% to 41% and was consistently higher among adults with Type 2 diabetes.
Among MESA participants

about 1 in 10 (11.6%) developed Type 2 diabetes after nine years.
People with obesity were nearly three times as likely to develop Type 2 diabetes compared to those without obesity (20% vs. 7.3%, respectively).

In both the MESA and NHANES groups:

Obesity was linked to the development of Type 2 diabetes in 30 – 53% of cases.
a greater proportion of participants with obesity had an annual family income of less than $50,000, and they were more likely to be non-Hispanic Black or Mexican American.
Obesity prevalence was the lowest among non-Hispanic white females, however, this group experienced the highest obesity-related Type 2 diabetes.

“Our study confirms there is a higher prevalence of obesity among non-Hispanic Black adults and Mexican-American adults compared to non-Hispanic white adults. We suspect these differences may point to important social determinants of health that contribute to new cases of Type 2 diabetes in addition to obesity,” says Cameron.

“Additionally, the obesity epidemic has collided with the COVID-19 pandemic,” says Sadiya S. Khan, M.D., M.Sc., the study’s senior author and an assistant professor of medicine and preventive medicine at Northwestern University’s Feinberg School of Medicine. “The greater severity of COVID-19 infection in individuals with obesity is concerning because of the growing burden of adverse health consequences they could experience in the coming years; therefore, further efforts are needed to help more adults adopt healthier lifestyles and hopefully reduce the prevalence of obesity.”

This analysis included only middle-aged to older adults without cardiovascular disease who were non-Hispanic white, non-Hispanic Black or Mexican-American, so results may not be generalizable to the entire U.S. population. Future research is required to assess the burden of obesity on new cases of Type 2 diabetes in other age groups and racial and ethnic groups.

Increased level of plasma cells linked to improved cancer survival

1,300 prostate tumor samples studied

Immunotherapy-based precision medicine clinical trials being developed

CHICAGO--- Black men die more often of prostate cancer yet, paradoxically, have greater survival benefits from immunotherapy treatment. A new Northwestern Medicine study discovered the reason appears to be an increase of a surprising type of immune cell in the tumor. The findings could lead to immune-based precision medicine treatment for men of all races with localized aggressive and advanced prostate cancer.

In the new study, Northwestern scientists showed tumors from Black men and men of African ancestry have an increased proportion of a special immune cell called plasma cells compared to the tumors of white men. A research team lead by Dr. Edward Schaeffer, chair of urology at Northwestern University Feinberg School of Medicine and Northwestern Medicine, found this increase in plasma cells correlated with improved cancer survival following surgery and identify plasma cells as potential drivers of prostate cancer immune-responsiveness.

The study will be published on Feb. 10 in Nature Communications.

"If a man's prostate cancer has numerous plasma cells, we found he had improved cancer survival," Schaeffer said. "Our study suggests plasma cells are important in the body's response to cancer."

Although recent research suggests Black men with advanced prostate cancer have improved survival outcomes with immunotherapy, there has been no way to predict which individual patients -- Black or white -- with prostate cancer may respond best to immunotherapy drugs.

Schaeffer's team explored this by analyzing the genomics of 1,300 tumor samples annotated with self-identified race or genetic ancestry. They found, on average, more plasma cells in Black men's tumors than white men's.

The finding was not unique to Black men, and the work showed that in all men with elevated plasma cell levels there was improved cancer-free survival following surgery.

"The finding comes at a time as researchers are discovering plasma cells may play a greater role in cancer immunotherapy than previously thought," said first author Dr. Adam Weiner, a Northwestern Medicine urology resident. "Testing for plasma cells in prostate cancer may help identify men who will benefit from immune-based treatments."

Schaeffer's research team at the Polsky Urologic Cancer Institute at the Robert H. Lurie Comprehensive Center of Northwestern University is now developing immunotherapy-based precision medicine clinical trials to investigate whether increased levels of plasma cells in prostate cancers from men of all races and ancestry can enhance the efficacy of immunotherapy and improved survival.

Prostate cancer is the second most common cancer in American men with an estimated 175,000 new cases every year and about 32,000 deaths. The severity and resulting mortality from prostate cancer are about two times greater in patients of African American origin.

Identification and characterization of effective therapeutic targets is a significant and unmet need to improve clinical outcomes and reduce mortality from lethal prostate cancer among African American men.

ANN ARBOR, Mich. and VANCOUVER, B.C. (February 10, 2021) - After screening more than 1,100 independently assessed, point-of-care COVID-19 tests, researchers at NSF International and Novateur Ventures have identified 5 direct (antigen/RNA) tests for detection of acute infection and 6 indirect (antibody) tests for detection of prior infection that meet the recently published World Health Organization (WHO) "desirable" Target Product Profile (TPP) criteria. The researchers hope their work will help communities and healthcare systems make more informed decisions when choosing rapid, point-of-care COVID-19 tests.

TPPs outline the desired characteristics of a product aimed at a specific disease. The WHO TPPs can be used to compare key features of COVID-19 tests and select products that best respond to the public health needs of each region.

"As communities around the world consider expanding existing COVID-19 testing strategies to include large-scale, rapid point-of-care tests, it's essential for them to understand which tests work best in different situations," said study co-author Robyn Meurant, Executive Director of Health Sciences at NSF International. "Our previous research found significant variability in performance and features of commercially available point-of-care tests, which makes it difficult to select and procure an appropriate test for a specific use case."

The study, COVID-19 Point-of-Care Diagnostics That Satisfy Global Target Product Profiles, appears in the January 2021 issue of the journal Diagnostics, an international peer-reviewed, open-access journal published monthly by the Multidisciplinary Publishing Institute (MDPI).

"The COVID-19 pandemic will continue to pose a major public health threat until vaccination mediated herd immunity is achieved," said study co-author Ali Ardakani, Founder & Managing Director at Novateur Ventures. "Most projections predict vaccines will reach a large subset of the population in late 2021 or early 2022. Until then, there will continue to be a need for fast and accurate COVID-19 testing."

The researchers screened more than 300 COVID-19 diagnostic tests that have obtained U.S. Food and Drug Administration (FDA) Emergency Use Authorization (EUA), and more than 850 tests¬ listed on the Switzerland-based Foundation for Innovative New Diagnostics (FIND) database. From those tests, they analyzed two types of COVID-19 point-of-care (POC) tests: direct (antigen/RNA) tests to detect acute infection and indirect (antibody) tests to detect past infection.

Top Performing COVID-19 POC Tests

According to the study, the following COVID-19 POCTs met the WHO TPP "desirable" criteria for clinical sensitivity/specificity, limit of detection, and time to results:

Direct (Antigen/RNA) POC Tests:

DetectaChem MobileDetect Bio BCC19 Test (RT-LAMP)

Mammoth Biosciences SARS-CoV-2 Detectr Test (RT-LAMP/CRISPR)

Quidel Sofia-2 Flu+SARS Antigen Test

Seasun Biomaterials AQ?TOP Plus COVID-19 Rapid Test (RT-LAMP)

Shenzhen Bioeasy Biotechnology Bioeasy Diagnostic Kit COVID-19 Antigen Test

Indirect (Antibody) POC Tests:

Guangzhou Wondfo Biotech Wondfo SARS-CoV-2 Ab Test 1

Hangzhou Biotest Biotech RightSign COVID-19 IgG/IgM Rapid Test

Hangzhou AllTest Biotech AllTest COVID-19 IgG/IgM Rapid Test 1

NG Biotech NG IgG/IgM Rapid Test

Sugentech SGTi-flex COVID-19 IgG

VivaChek Biotech COVID-19 IgM/IgG Rapid Test

"A few weeks has passed since we conducted our research in December 2020, so it is likely that additional tests have undergone independent assessment and can meet the WHO criteria now," Robyn Meurant said. "The most important takeaway from this study is that purchasers of point-of-care COVID tests should do their research and make sure they are selecting a test that meets the WHO TPP criteria for their specific use case."

A new paper in Oxford Open Immunology, published by Oxford University Press, examines prior findings in the field of neuroimmunology that suggest potential treatment strategies for patients suffering long-term symptoms from COVID-19.

Though COVID-19 was initially believed to be a short-term illness, lasting between one and three weeks, it's clear that a substantial number of patients will experience symptoms beyond that, with some patients suffering from health problems for more 12 weeks. In fact, for patients who were initially hospitalized, more than 80% reported at least one symptom that persisted beyond the first month.

The symptoms of long-COVID can vary widely, including cough, low grade fever, fatigue, chest pain, shortness of breath, headaches, cognitive difficulties, muscle pain and weaknesses, gastrointestinal distress, rashes, metabolic disruption, depression and other mental health conditions. In the context of other disorders and syndromes, these symptoms appear to have a strong link with a challenge to the immune system. Even mild infections and low-grade inflammation can cause depression or persistent fatigue.

As a number of causes have been proposed to explain the persistence of these long-term COVID symptoms - from the presence of persistent low viral load and reinfection, to changes in immune cell activity and tissue damage caused by the initial infection - researchers here explored insights gained in recent decades from several large-scale studies of chronic fatigue syndrome, fibromyalgia, depression and other mental health disorders that show immune abnormalities.

Researchers at King's College London here argue that several possible pathways could be relevant to understanding the persistence of long-COVID, like the involvement of glial cells and the permeability of the blood brain barrier. They also propose strategies to manage symptoms. Some of the symptoms of long-COVID, depression and other mental health problems, are related to chronic, low-grade inflammation. As such, current treatment strategies for patients with depression include anti-inflammatory medications. Psychosocial factors are also very important in regulating our immune activation. It's clear that strategies tackling a patient's level of stress with increased social support, physical exercise, and an adjusted diet could also be useful in managing long term symptoms related to COVID-19.

"We are suggesting taking advantage of what we have learnt over the years about how the brain and the immune system communicate and about the contribution of the immune system to the development of symptoms of long-COVID in other medical conditions," said the paper's lead author, Valeria Mondelli. "This is likely to accelerate our understanding of the mechanisms underlying long-COVID and the identification of effective treatments."

Washington, DC - February 9, 2021 - A team of investigators from the Republic of China has discovered that 6 drugs previously approved by the US Food and Drug Administration (FDA) for other indications could be repurposed to treat or prevent COVID-19. The research is published in Antimicrobial Agents and Chemotherapy, a journal of the American Society for Microbiology.

Using FDA-approved drugs saves time -- the drugs don't need to go through the FDA approval process again -- making them available quickly to treat patients who need them.

The research shows that the investigators screened 2 large drug libraries cumulatively containing 3,769 FDA-approved drugs and found drugs that can inhibit 2 protein-cutting enzymes, called proteases, that are essential to the replication of SARS-CoV-2.

The assays for testing the drugs involved growing the virus in petri dishes, applying each drug to different petri dishes containing the virus, and then conducting plaque reduction assays to determine each drug's effectiveness. The original outbreak strain, clade S, was used in the assays. ("Clade" is a technical term for a familial group.)

The researchers, led by corresponding author Po-Huang Liang, PhD, also plan to test the drugs against the dominant GR strain, which was the first variant to emerge, in late January or February, 2020, and the recent, highly contagious United Kingdom strain. Dr. Liang is research fellow and professor at the Institute of Biological Chemistry, Academia Sinica, Taiwan, Republic of China.

Their research also enables the investigators to better understand how coronavirus proteases recognize their substrates during replication. That will help them tweak the drugs they identified to be more effective inhibitors against the protease.

"Despite the variations of the virus strains emerging over the years, considering the significance of the 3CL protease in the viral replication, and the relatively low likelihood for this protein target to mutate, we aim to develop a broad spectrum of antiviral drugs using our platform, helping to prevent the emergence of future pathogenic SARS-CoV strains," said Dr. Liang.

Dr. Liang's group began working on one of the proteases, known as 3CLpro, 18 years ago, during the outbreak of the original SARS virus. At that time, Coauthor Chih-Jung Kuo was Dr. Liang's PhD student, and the research was the subject of his PhD dissertation. Dr. Kuo is now Associate Professor at the Department of Veterinary Medicine, National Chung Hsing University, Taiwan, Republic of China.

Researchers at the Garvan Institute of Medical Research have developed a computational model to calculate 'skeletal age', a personalised estimate of an individual's risk of bone fracture and premature death.

The skeletal age calculator, which will be accessible to doctors and health professionals, aims to better identify those at risk of a first bone fracture and subsequent fractures, and also estimates how fractures impact life expectancy.

Osteoporosis, a disease which reduces bone strength and increases bone fracture risk, is a major national health issue and estimated to affect over 900,000 Australians. The cost of osteoporosis and fracture in Australia is $3.4 billion annually.

"A fracture shortens life expectancy, even more so in men than in women. But there is a lot of complacency in the community when it comes to bone health - only 20% of those with fragility fractures are taking approved treatments for osteoporosis, which could significantly reduce their risk of further fractures," says Professor Tuan Nguyen, Head of the Genetic Epidemiology of Osteoporosis Lab at Garvan, Professor of Predictive Medicine at the University of Technology Sydney and senior author of the research published in eLife.

"We hope that calculating a person's skeletal age, which may be much higher than their actual age, will identify those who are at higher risk of fractures and encourage them to speak to their doctor about how to better manage their condition."

Predicting fracture risk

From age 50, bone fractures affect one in two women and one in three men. For women, the lifetime risk of a hip fracture is equal to or higher than the risk of developing an invasive breast cancer.

With each fracture, the risk of future fracture increases two-fold and studies have shown that pre-existing fractures increase the risk of premature death by about 50% in both men and women. One in three adults over 50 dies within 12 months of sustaining a hip fracture.

"There are existing models to predict the risk of an initial fracture, such as the Garvan Fracture Risk Calculator that is already available to doctors. But it remains unclear why some individuals do well after an initial fracture, while others go on to sustain further fractures and have a higher risk of mortality," says first author Dr Thao Ho-Le.

"We set out to develop a model to complement existing tools, which could simultaneously predict an individual's risk of subsequent fractures and consequently, their chance of premature death."

To develop their sophisticated computational model, the team led by Professor Nguyen used data from Garvan's Dubbo Osteoporosis Epidemiology Study, which was started in 1989 and is the world's longest-running large-scale study of osteoporosis in men and women.

Their model incorporates an individual's age, bone density, history of previous fractures and other health conditions to calculate a personalised estimate of 'skeletal age'.

"In our new model, we quantified the intricate transitions between fracture, re-fracture and mortality. We define skeletal age as the age of an individual's skeleton that results from their risk factors for fracture," explains Professor Nguyen.

"Using this definition, we for instance estimated that a typical 70 year old man who had sustained a fracture had a skeletal age of 75 years. But when the man had a second fracture his skeletal age rose to 87 years. This means the individual now has the same fracture risk profile as an 87 year old man who has a healthy risk profile."

Improving bone health

The team is now developing an online calculator, which doctors will be able to use to calculate their patients' skeletal age.

The researchers hope it will be a valuable tool for initiating discussions between health professionals and their patients on how to improve bone health, which may involve medication, exercise, increasing dietary calcium and getting enough vitamin D.

"The key message of this study is that it's never too early to think about your bone health," says Professor Nguyen. "Do not wait until a fracture has occurred to take preventive action. If your skeletal age is higher than your actual age, you should seek medical advice from your doctor on how to manage the higher risk."

A global survey of healthcare providers by the International Osteoporosis Foundation (IOF), the National Osteoporosis Foundation (NOF) and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) has revealed unprecedented effects of the Covid-19 pandemic on worldwide healthcare delivery for osteoporosis.

Osteoporosis is a chronic, age-related disease which is associated with life-changing fragility fractures. Approximately 740,000 people lose their lives following hip fractures every year.

The survey report is based on online questionnaires completed from April to June 2020 by 209 healthcare providers in 53 countries: 28% from Europe, 24% from North America, and 19%, 17% and 12% from the Asia-Pacific, Middle East and Latin America, respectively. The majority of the respondents (85%) were physicians, mainly representing the specialties of rheumatology (40%), endocrinology (22%), orthopaedics (15%) and internal medicine (11%).

The report provides an insight into how healthcare delivery for osteoporosis has been affected by the pandemic:

Clinic/hospital closures: 21% of institutions were only open for emergency visits; 23% for non-acute/routine visits; 57% for both emergency and routine appointments; and 7% closed for all visit types.

Form of consultations: 33% performed telephone consultations; 21% video consultations; 26% face-to-face appointments; 18% urgent in-person visits; and 3% other modalities (including instant messaging).

Telemedicine: Lock-downs and self-isolation saw a necessary move toward telemedicine, which was found very useful for 20% of the respondents, who scheduled approximately more than 20 online appointments per week. In contrast, 20% only scheduled 1-5 appointments per week and 20 % did not schedule any appointments at all. Issues included unavailability of telemedicine, its non-reimbursement, or uncertainties about reimbursement.

Risk Assessment: 29% scheduled a Dual-energy X-ray Absorptiometry (DXA) scan as soon as possible in order to inform treatment decisions; 11% assessed patients based on a clinical risk calculator alone (for e.g. FRAX®); 29% assessed patients based on a risk calculator with a planned DXA at a later date; 33% postponed a DXA; 5% indicated that their DXA unit was currently closed or that they were referring patients to a fracture clinic service.

Delivery of medication: Almost half (43%) reported difficulty arranging osteoporosis medications, including limited supply or difficult in acquiring medications, delay in administration of infusions and injections, reluctance on the part of patients to attend, or travel restrictions/self-isolation resulting in patients being unable to attend office visits.

Prescriptions: 28% prescribed refills only; 63% prescribed both refills and new prescriptions; 3% issued new prescriptions only; and 4% did not prescribe any medication unless for an acute indication.

Professionally administered treatment: 60% of clinicians had systems in place to identify patients receiving parenteral medication so that plans of care could be arranged; 46% were able to administer injections or infusions with safeguards in place to minimize patient risk; 3% moved treatments to an alternate clinical location; 21% suggested delaying treatment until Covid-19 risk had abated; 13% recommended switch to an oral medication; and 8% considered arranging in-home administration of treatment.

Time needed for patient charts/electronic health records: 93% of the respondents reported that it took as much or more time than prior to the pandemic to complete documentation. Reasons included technical and work-flow related issues, among others.

Patient follow-up: The time taken to follow-up patients was reported as greater by 39% of respondents, less by 9%, no change by 45%, and 7% of respondents were unsure. More time was often required to provide explanations or results over the phone, among other reasons.

IOF President Professor Cyrus Cooper, corresponding author, noted:

"The survey indicates that the identification and management of osteoporosis in patients has been profoundly affected by the pandemic, by delays in obtaining a DXA scan or in providing medication. There is a concern that the traditional gold standard assessment and management of osteoporosis patients was not performed in the majority of cases during the pandemic, leaving many patients without assessment and treatment."

Professor Susan L. Greenspan, President of NOF and senior author, stated:

"There appears to be a substantial impact on reimbursement, which may have implications for the ability to sustain and offer various osteoporosis clinical services and tests such as DXA. In the USA, despite Medicare allowing greater flexibility for home administration of injectable medication, some 39% of survey respondents were either not sure about the new arrangement or would not consider using this option. This could potentially lead to a reduction in resources, and corresponding decrease in the assessment and treatment of patients with osteoporosis and related fracture."

On a positive note almost one in three healthcare providers performed telephone consultations and one in five performed video consultations. Telemedicine has potential benefits for patients and can result in savings and efficiencies for healthcare systems. In some countries, temporary adjustments made to telemedicine reimbursement rates during the pandemic are being evaluated for implications and opportunities in the future when societies return to the new 'normal'.

FOLSOM, Calif., February 9, 2021 - A new animal study, published in the Journal of Clinical Biochemistry and Nutrition, suggests regular walnut consumption may be a promising intervention for reducing negative outcomes associated with Helicobacter pylori (H. pylori) infection, a widespread bacterial infection that affects more than half of the world's population.

Using mice models, researchers from the CHA Cancer Prevention Research Center in Korea found preliminary evidence that eating a diet rich in walnuts may help protect against negative outcomes associated with H. pylori infection. Specifically, the research found that walnut extracts, formed from whole walnuts, may help create protective proteins and anti-inflammatory actions in the gut that may safeguard against H. pylori infection and resulting cancer in mice. The study was supported by the California Walnut Commission.

Prevalence of H. pylori is most common in developing countries as it is generally related to socioeconomic status and hygienic conditions and is thought to be spread through person to person contact or even through food and water. H. pylori infection is a major cause of ulcers in the stomach and small intestine as well as stomach cancer and peptic ulcer disease. While treatments are currently available, there are concerns about the bacteria's growing resistance to antibiotics.

Due to increasing challenges associated with antibiotic resistance, researchers have been investigating dietary and other non-bacterial approaches to improve impact from H. pylori infection, such as in this new study.

This is not the first time walnuts have been linked to a lower risk of gastrointestinal cancer development in mice. Two other animal studies published in Cancer Prevention Research and Nutrients found that walnuts in the diet may suppress colon tumor development by modifying gut bacteria as well as inhibit the progression of colorectal cancer by suppressing angiogenesis - the development of new blood vessels which facilitates the growth of cancer cells.

Animal studies are valuable for providing background information and can be used as a basis for future research in humans. Based on the existing body of evidence, including this study on walnuts, dietary approaches to reduce symptoms of H. pylori infection, such as inflammation, seem worthwhile to pursue in a well-designed clinical trial to confirm the findings.

While the World Health Organization (WHO) continues its mission to Wuhan investigating the origin and early transmission of SARS-CoV-2, a new study led by scientists from Duke-NUS Medical School, Singapore, and Chulalongkorn University, Thailand, shows that SARS-CoV-2-related coronaviruses (SC2r-CoVs) are circulating in animals as far away as Thailand. The study, published in Nature Communications today, reported that high levels of neutralising antibodies against the virus were present in both bats and pangolins found in the Southeast Asian country. The study further indicates that more SC2r-CoVs are likely to be discovered in the region. Southeast Asia with its large and diverse bat populations may be a more likely hotspot for such viruses.

"This is an important discovery in the search for the origin of SARS-CoV-2, which was made possible by rapid application of cutting-edge technology through transparent international collaboration," said Dr Supaporn Wacharapluesadee, from Thai Red Cross Emerging Infectious Diseases Health Science Centre, Faculty of Medicine, Chulalongkorn University, Bangkok Thailand.

In the study, the team examined Rhinolophus bats in a Thai cave. SARS-CoV-2 neutralising antibodies were detected in bats of the same colony and in a pangolin at a wildlife checkpoint in Southern Thailand.

"Our study extended the geographic distribution of genetically diverse SARS-CoV-2-related coronaviruses from Japan and China to Thailand over a 4,800-km range. Cross-border surveillance is urgently needed to find the immediate progenitor virus of SARS-CoV-2," said Dr Chee Wah Tan, Senior Research Fellow with Duke-NUS' Emerging Infectious Diseases (EID) programme and co-author of this study.

The team conducted serological investigations using the SARS-CoV-2 surrogate virus neutralisation test (sVNT) developed at Duke-NUS in early 2020.

"Our study demonstrates that our SARS-CoV-2 surrogate virus neutralisation test, developed mainly for determining neutralising antibodies in humans to monitor vaccine efficacy and detect past infections, can also be critical for tracing the animal origin and animal-human spillover events," said Professor Wang Linfa from Duke-NUS' EID programme and corresponding author of this study.

Prof Wang's team invented the sVNT assay, trade named cPass, which has been granted Emergency Use Authorisation by the US FDA to determine SARS-CoV-2-neutralising antibodies in human sera, due to its good performance concordance with live virus-based assays.

"Studies like this are crucial in furthering our understanding of the many SARS-CoV-2-related viruses that exist in the wild. This work is also timely as investigations into the origins of SARS-CoV-2 are ongoing and may provide further leads on the origin of this outbreak. Such studies also play a key role in helping us be better prepared against future pandemics as they provide a more detailed map of zoonotic threats, " said Prof Patrick Casey, Senior Vice Dean for Research at Duke-NUS.

Amsterdam, NL, February 9, 2021 - Globally, nearly 300,000 babies are born with neural tube defects including spina bifida (SB) each year. This openly available special issue of the Journal of Pediatric Rehabilitation Medicine (JPRM) provides 20 important evidence- and consensus-based updates to key sections of the 2018 "Guidelines for the Care of People with Spina Bifida" issued by the Spina Bifida Association (SBA). These reflect current recommendations for the care of patients with SB across the entire lifespan, from prenatal counseling to adult care.

As a result of research advancements and improved team-based patient care, approximately 80%-90% of children with SB now live to adulthood in the United States. The Guidelines were written with this idea in mind and present the best evidence for what care should be delivered, regardless of the model or types of practitioners available.

"Medical evidence and clinical practice continue to change, and so it was time to update the most recent set of Guidelines to provide the best, most up-to-date recommendations, focusing not only on pediatric care, but also on safely transitioning young adults with SB from pediatric to adult healthcare services," explained co-Guest Editors Jonathan Castillo, MD, MPH, and Heidi A. Castillo, MD, both from Developmental Pediatrics, Department of Pediatrics, Meyer Center, Texas Children's Hospital/Baylor College of Medicine, Houston, TX. "Guidelines needed to be included and/or revised to reflect the needs of adults with SB. The goal was to provide a more holistic approach to care. It is not just a condition that affects health but affects all of life."

Judy Thibadeau, RN, MN, Director of Research and Services, Spina Bifida Association, Arlington, VA, added, “Pediatric and adult providers need to embrace the fact that adult providers will be needed and are important to the lives of people with SB.”

The updated and expanded sections of the Guidelines presented in this issue move beyond more traditional issues of neurosurgical, urologic and orthopedic care, emphasize the continuum of care, health, wellbeing and quality of life, and include more background information about key topics and why they are important in the care of individuals with SB. They cover:

Bowel function and care

Central precocious puberty

Coordination of care

Family functioning in families with a child with SB

Health promotion and preventive healthcare service guidelines

Latex allergy

Mental health

Mobility

Neuropsychological care

Neurosurgical guidelines

Nutrition, metabolic syndrome, and obesity

Orthopedic guidelines

Prenatal counseling

Quality of life

Self-management and independence

Sexual health and education

Short stature and the effect of human growth hormone

Skin-related issues

Urologic guidelines

Women's health

"These Guidelines stress other issues that are important to successfully transition to adulthood including (but not limited to) family functioning, mental health, women's and men's health, and self-management skills in the broader societal and participation context," noted co-Guest Editor and SBA Medical Director Timothy John Brei, MD, Division of Developmental Medicine, Department of Pediatrics, Seattle Children's Hospital and the University of Washington School of Medicine, Seattle, WA. "These Guidelines acknowledge that one can have good medical health and still struggle in terms of independence and across the lifespan. So, they are not just about medical care across the lifespan, but 'life care.'"

Dr. Jonathan Castillo added, “Neural tube defects like SB have widespread global significance. Some countries manage the care of patients with SB better than others, particularly when it relates to the care of adults with SB. Therefore, global accessibility to the Guidelines and their updates is vital, as healthcare professionals embedded in local communities will seek to use this guidance to provide high-quality care with a view towards reducing healthcare disparities. Language differences, immigration, cultural beliefs, acculturation, local resources, and social determinants of health must be taken into account when Guidelines are implemented throughout the world.”

SBA's Collaborative Care Network, through a cooperative agreement with the National Center on Birth Defects and Developmental Disabilities (NCBDDD), part of the Centers for Disease Control and Prevention (CDC), supported the production of the "Guidelines for the Care of People with Spina Bifida." These Guidelines were the culmination of three years of planning and work involving over 100 international experts using evidence-based research and consensus methodologies. The text of the Guidelines is openly available on the SBA website and the position papers in this special issue have been published as open access through the support of the SBA.

"It is the hope of SBA that these and future Guidelines will promote and standardize best practice regardless of the characteristics of individuals with SB or where their care is received. It is through providing better care that we will ultimately achieve a better future for all those living with SB," remarked Brad E. Dicianno, Associate Medical Director, SBA, and Director, UPMC Adult Spina Bifida Clinic, Pittsburgh, PA.

"These open access Guidelines are paramount towards educating individuals with SB and their medical providers," commented Editor-in-Chief of JPRM Elaine L. Pico, MD, UCSF Benioff Children's Hospital Oakland, CA. "With better health and these Guidelines distributed worldwide we are looking at a robust aging population of those with SB that must be attended to by knowledgeable medical providers."

"We are so thankful to the journal for its continued focus on SB. Truly, it is a gift to our community, and we are grateful and excited to be part of what has happened thus far. We can't wait to see where this takes all of us," commented Sara Struwe, MPA, President & CEO, Spina Bifida Association, Arlington, VA. "From our community to yours, thank you!"

A study led by researchers at the University of Minnesota Medical School found a way to detect the presence of ovarian cancer in patients using Pap test samples, normally used to detect cervical cancer. Currently, no early warning system exists for ovarian cancer, which in 2021, is estimated to kill more than 13,700 women, according to the American Cancer Society.

"It is known as a 'silent killer' since women with early stages of ovarian cancer have symptoms that can often be confused with other ailments. Women are typically diagnosed when the cancer has progressed so far that other organs are involved, requiring major surgery and chemotherapy," said Amy Skubitz, PhD, senior author of the study and professor in the Department of Laboratory Medicine and Pathology. She is also the director of the Ovarian Cancer Early Detection Program at the U of M Medical School. "We set out to identify the proteins present in Pap test samples and cervical swabs to determine whether or not the same proteins are present in ovarian cancer tumor tissues."

This study, published in the journal Clinical Proteomics, found that:

The Pap test and swab samples contained proteins that were also found in the primary tumor of a woman with high-grade serous ovarian cancer;

More than 2,000 proteins were detected in all three sample types collected, suggesting potential biomarker candidates;

Pap test samples, which are already used to detect cervical cancer, may eventually be used to detect ovarian cancer.

"This study is proof of concept that these biospecimens, the Pap test and a swab of the cervix, could be developed for use in the detection of ovarian cancer biomarkers prior to surgery, but it does warrant further investigation," said Skubitz, who is also a member of the Masonic Cancer Center. "Our next step will be to use quantitative mass spectrometry to determine if these proteins or peptides are detected at higher levels in ovarian cancer Pap tests or swabs compared to controls. Their presence alone is not sufficient for diagnosis."

Skubitz also sees an opportunity for this method to be translated into a self-administered, at-home test, where swabs could be collected by women at home and sent to a central laboratory for analysis of proteins that would diagnose ovarian cancer.

CHICAGO: Elderly patients (70 years and over) with locally advanced esophageal (E) and esophagogastric junction (EGJ) cancer (located in the stomach and esophagus) should be considered for optimal therapy that has the potential to cure. This therapy regimen includes initial chemoradiotherapy (NACR) and surgical resection, an operation that removes the cancerous part of the organ.

According to researchers, this recommended therapy is often not offered to elderly patients out of concern that they will not tolerate such an intensive treatment regimen. In a new study, they found that older patients who received the therapy had outcomes comparable with those of younger patients (under 70 years old). The single-institution study from the Ochsner Clinic Foundation and The University of Queensland-Ochsner Clinical School, New Orleans, was selected for the 2020 Southern Surgical Association Program and published online as an "article in press" by the Journal of the American College of Surgeons in advance of print.

Over the past three decades, incidence rates for cancers of the esophagus, the eighth most common cancer and sixth leading cause of cancer-related deaths worldwide, have risen in the U.S. and other developed countries.1,2,3,4 Recent evidence has shown that multimodal treatment consisting of NACR followed by surgical resection is considered the standard of care for stage II-III cancers.5,6,7,8

Although the toxicity of this optimal multimodality therapy has been low, older patients with potentially curable stage II/III disease are often not considered for this approach due to its perceived risks. Concerns prevail about frailty and co-morbidities that may accompany advanced age, patient and physician pre-conceived notions about cancer care in the elderly, patient choice in the context of life stage, and adaptability of the elderly to life-style changes brought about by cancer therapy.9

"Multiple studies have documented low utilization of esophagectomy in elderly patient populations with potentially curable esophageal or esophagogastric cancer despite current guidelines, which recommend curative-intent NACR followed by surgical resection," the authors wrote. (Esophagectomy is the surgical removal of some or all of the esophagus.)

In a previous study of more than 21,000 patients with a form of cancer known as esophageal adenocarcinoma, researchers analyzed 2004-2014 data from the Surveillance, Epidemiology, and End Results (SEER) Program database and found that older patients (over 70 years) were 50 percent less likely to undergo esophagectomy than were younger patients (under 70 years).10 Only 16.9 percent of patients over 70 underwent surgery. This approach was taken despite current National Comprehensive Cancer Network (NCCN) guidelines that recommend curative-intent NACR followed by surgery.11

In the current study, surgical oncologist John S. Bolton, MD, and colleagues analyzed 2004-2019 data from the 405 cancer patients who had esophagectomies with curative intent. Data collected included demographic information, tumor stage, preoperative co-morbidity scores, treatment variables, and short- and long-term outcomes. The patients were split into those who were over 70 years old ("older") and those who were under 70 ("younger").

After excluding 62 stage I cancer patients not receiving NACR, 343 patients remained. Of these, 282 patients received NACR prior to esophagectomy including 188 patients younger than age 70 and 94 patients 70 years or older, who serve as the basis for this study.

Although preoperative risk scoring and postoperative atrial arrythmias were higher among the older group, the rate of postoperative complication severity scores, perioperative mortality rates, and lengths of stay were similar. Long term age-adjusted survival was 44.8 percent at 5 years for the older group and 39 percent for the younger group.

These results suggest that optimal, curative-intent triple modality therapy can be used successfully in a sizeable segment of older patients with esophageal cancers. The researchers found evidence at their institution that, over time, older patients are increasingly getting triple modality therapy.

"Even though our results are not randomized, these findings provide a strong indication that declining to perform a surgical resection significantly reduces the likelihood of a cure for older patients who are deemed fit for the operation," said Dr. Bolton.

The authors note it's important to rule out patients for surgery who have unstable or chronic conditions of the heart, liver, or lungs. They further recommend that prospective patients regularly achieve certain metabolic physical fitness goals, undergo non-invasive cardiac stress testing, and encourage patients to perform a daily progressive exercise program prior to surgery.

A comprehensive prehabilitation program can potentially prepare more elderly patients for optimal triple modality therapy12 and "this is a current focus of our group for these patients," they write.

One such program is the American College of Surgeons Strong for Surgery, a public health campaign that engages patients and their surgeons to improve overall health and increase the likelihood of a positive surgical outcome. Preoperative checklists serve as a communication tool for patients and clinicians to consider common risk areas.

GRAND RAPIDS, Mich. (Feb. 9, 2021) -- Scientists have devised a new approach for detecting and potentially heading off the effects of two rare pediatric diseases before birth.

The study, performed in mouse models of the diseases and published today in Cell Reports, represents an important step toward much-needed early interventions for Beckwith-Wiedemann syndrome and Silver-Russell syndrome.

Both diseases result in growth-related symptoms in children and often lead to additional problems later in life, such as increased cancer risk from Beckwith-Wiedemann syndrome and increased metabolic disease risk from Silver-Russell syndrome.

"Both of these diseases have lifelong consequences," said Piroska Szabó, Ph.D., an associate professor at Van Andel Institute and the study's corresponding author. "Our findings provide a critical foundation for additional studies that we hope will translate into new, life-changing prenatal detection and treatment methods. Our goal is for children to be born healthy."

Fetuses with Beckwith-Wiedemann syndrome experience too much growth during development while fetuses with Silver-Russell experience too little growth. Likewise, about one-third of Beckwith-Wiedemann cases and two-thirds of Silver-Russell cases may arise from having either too much or too little of a protein called IGF2, which plays a critical role in fetal growth and development.

Using models of the diseases, Szabó and colleagues were able to detect and measure IGF2 in amniotic fluid and correlate variations in IGF2 levels with Beckwith-Wiedemann and Silver-Russell syndromes, opening up new opportunities for early detection.

The researchers also were able to correct IGF2 levels in a genetic experiment, essentially reversing the fetal growth problems associated with both disease models. They found that treatment before birth with an FDA-approved cancer medication that targets IGF2 signaling normalized fetal growth in the Beckwith-Wiedemann model.

More research and clinical studies are needed before it is known whether the findings hold true in humans, Szabó cautioned. She hopes to find a clinical collaborator with whom to partner for future studies.

"There's a big gap between an experiment in the lab and implementation in the clinic," Szabó said. "However, our results are a vital step toward finding ways to identify and treat these syndromes before birth."