Body

ATLANTA -- New research shows that adults with systemic lupus erythematosus, who receive trimethoprim-sulfamethoxazole (TMP-SMX), a prophylactic therapy to help prevent pneumocystis pneumonia, are at high risk for adverse reactions to the drug, particularly if they are also positive for anti-Smith (anti-Sm) antibodies. Details of the study was presented at ACR Convergence, the American College of Rheumatology's annual meeting (ABSTRACT #1830).

Systemic lupus erythematosus, referred to as SLE or lupus, is a chronic (long-term) disease that causes systemic inflammation which affects multiple organs. In addition to affecting the skin and joints, it can affect other organs in the body such as the kidneys, the pleura tissue lining the lungs, or the heart and brain. Many patients with lupus experience fatigue, weight loss and fever.

Pneumocystis pneumonia, is an infection that can be life-threatening for people whose immune systems are suppressed by medications for autoimmune diseases, including connective tissue diseases. These patients may be treated with drugs like steroids or other immunosuppressants. One way to help prevent pneumocystis pneumonia infection is prophylactic treatment with the drug TMP-SMX, which is an antibiotic used to treat a variety of bacterial infections. It is effective but can cause adverse drug reactions in people with connective tissue diseases, and past research shows that people with SLE are at especially high risk for these serious reactions to the drug.

"Patients with moderate to severe SLE usually require a high dose of corticosteroid and various types of immunosuppressants, creating a risk of developing pneumocystis pneumonia," says the study's co-author, Shinji Izuka, MD, a rheumatologist and researcher at the National Centre for Global Health and Medicine in Tokyo. "Unlike patients with HIV, who are also at high risk of pneumocystis pneumonia, patients with connective tissue diseases such as SLE are at risk for fatality when developing this infection so prophylaxis is important. Moreover, due to the COVID-19 pandemic, it is important to prevent pneumocystis pneumonia for patients on immunosuppressants, because the symptoms and image findings are similar to COVID-19. Fortunately, TMP-SMX can prevent pneumocystis pneumonia effectively."

Because past studies suggested that lupus patients were at higher risk of adverse reactions to the drug, Dr. Izuka's group launched this study to confirm the risk and discover any specific risk factors. among people with SLE and other connective tissue diseases.

The researchers examined their hospital's in-patient database for records of patients with connective tissue diseases who were administered TMP-SMX as a prophylactic agent against pneumocystis pneumonia between January 2009 and April 2020. The baseline data was obtained at the time that TMP-SMX was started. They excluded patients with HIV and anyone who did not suffer adverse drug reactions within one month. They compared adverse reaction prevalence between people with lupus and those with other connective tissue diseases and also analyzed the data for any specific risk factors in lupus patients.

The 427 patients in the study included 164 with lupus, while the rest had another connective tissue disease, such as polymyositis or dermatomyositis, Sjögren's syndrome, systemic sclerosis, mixed connective tissue disease and different forms of vasculitis. Forty, or 9.4%, of patients developed an adverse drug reaction to TMP-SMX, including 10 with thrombocytopenia, nine with skin rash, seven with a liver function test abnormality, seven with fever, and 12 with other reactions.

People with lupus were more likely to have an adverse drug reaction: 13.4% compared to 6.9% in the control group patients. Their odds ratio of developing an adverse drug reaction was 2.12. When the researchers performed univariate analysis to look for risk factors, they found that lupus patients with anti-Sm, anti-RNP and anti-Ro/SS-A antibodies were significantly associated with higher risk of an adverse drug reaction. Then, they performed multivariate analysis and found that only anti-Sm antibodies was significantly associated with higher risk in people with lupus.

Due to these increased risks, patients with SLE who receive prophylactic TMP-SMX should be carefully monitored for any adverse reaction to the drug, especially those with anti-Sm antibodies, the researchers concluded.

"In these cases, it might be better to choose other options," says Dr. Izuka. "The important thing is, however, that there were no patients in our study who developed severe conditions, such as Stevens-Johnson syndrome, due to adverse drug reactions to TMP-SMX. We should not hesitate to initiate TMP-SMX for those who require it. The mechanisms of the association between adverse drug reactions and anti-Sm antibody remains unclear. Further study to identify them and other unrevealed factors is needed. Also, we should clarify the best way to prevent pneumocystis pneumonia for SLE patients with anti-Sm antibody and other autoantibodies for safety and efficacy."

A joint study by the National Neuroscience Institute (NNI) and Singapore General Hospital (SGH) revealed that patients who have been diagnosed with Parkinson's disease might actually have NIID instead.

NIID is a disabling neurodegenerative condition due to a gene mutation and has no effective treatment. Symptoms of NIID include dementia, Parkinsonism, poor balance, as well as numbness and weakness in the limbs. A patient with NIID may or may not experience symptoms, depending on age and stage of disease. The severe form of NIID is usually seen in older patients, where the disease has progressed to an advanced stage.

The team studied more than 2,000 study participants, comprising healthy individuals and those with Parkinson's disease (PD), over more than a decade. They were surprised to find NIID-causing mutations in those diagnosed with PD. Dr Ma Dongrui, Senior Medical Laboratory Scientist, Department of Neurology, SGH, and first author of the study explains, "To our knowledge, this is the first study reporting PD patients with NOTCH2NLC gene mutations as seen in NIID patients. Thankfully, they responded to PD medications better than most PD patients do. This suggests that there must be factors that can influence why some develop PD while many others develop the more severe form of NIID.

While analysing the NIID gene, the team found a group of healthy participants who had a "milder" form of mutation. Such mutation in the NIID gene could indicate that they are at risk of developing NIID or PD.

Since NIID can go undetected, a high index of suspicion may be needed even in PD patients. "With what we know now, it might be beneficial for clinicians to be watchful of early cognitive impairment or imaging evidence that may suggest NIID in patientsdiagnosed with PD. As NIID is caused by a genetic mutation, it also may be worth looking out for family members of PD patients who may show signs of NIID," suggests Professor Tan Eng King, Deputy Medical Director and Director of Research, NNI.

"Our findings suggest that many neurodegenerative diseases overlap and may share a common etiology. Finding a common link and uncovering the reason why a similar gene mutation leads to both mild PD and a severe form of NIID can help identify new drugs for these conditions," continues Prof Tan, who is also the senior author of the study and a Senior Consultant at NNI's Department of Neurology on SGH Campus.

Following this study, the team plans to conduct more studies to better understand the mechanism behind NIID and identify new drugs for this condition. More research is needed to understand if the broad clinical phenotype of NIID is related to the subtle genetic differences at the NOTCH2NLC gene locus, race or other factors. Long-term follow-up of carriers of the gene mutation with PD phenotype may provide additional clues.

The study findings were published online in JAMA Neurology on 24 August 2020.

ATLANTA -- The American College of Rheumatology (ACR) will preview the 2021 Guideline for the Treatment of Juvenile Idiopathic Arthritis at ACR Convergence, the ACR's annual meeting. The new recommendations address pharmacologic and non-pharmacologic treatments and are the culmination of a two-part update of the ACR's JIA guidelines published in 2011 and 2013. It includes treatments for systemic JIA, oligoarthritis, TMJ arthritis, and recommendations for medication monitoring and immunizations.

JIA includes several types of arthritis affecting children and teenagers, all involving chronic (long-term) joint inflammation. This inflammation begins before patients reach the age of 16, and symptoms must last more than 6 weeks to be called chronic. JIA may involve one or many joints, may also affect the eyes, and cause other symptoms, such as fevers or rash.

"Our overarching goal with the update project, including part one in 2019 and this current project, was to cover as many of the important topics as possible that affect care given to children with juvenile arthritis," says Karen Onel, MD, chief of the Division of Pediatric Rheumatology at the Hospital for Special Surgery in New York City, and the lead investigator of the guideline's Core Team. "We have estimated that half of our patients are cared for by adult rheumatologists, not pediatric rheumatologists, so these recommendations will be helpful for those physicians who may not be as familiar with all the currently available treatments for children with JIA. Also, as we developed these recommendations, we kept in mind that children with JIA represent a broad age range--from infants to teenagers." Onel will discuss the recommendations at a press conference on Monday, Nov. 9 at 8:30 a.m. (ET).

Since the last JIA guideline was published, new medications have been approved for JIA, making the update a high priority for the ACR. More importantly, rheumatologists' treatment paradigms for JIA have shifted. These new approaches are reflected throughout the guideline, which include reduced use of steroids to treat acute inflammation and increased emphasis on biologic drugs now available for JIA that modify disease activity and target the sources of inflammation. The new guideline also strongly recommends that most children with JIA get regular immunizations for infectious diseases, an update from the last published guideline.

"Pediatric rheumatologists now more rapidly escalate disease-modifying treatment in JIA patients, and are much less likely to use oral or intravenous steroids. This is especially true for children with systemic JIA. In addition, and this is very timely, the evidence strongly shows that children with JIA should receive and will respond to vaccines without a risk of flare. We are strongly encouraging children to follow the immunization schedule when safe and to receive annual flu shots. Immunosuppressed children should still refrain from live virus immunizations, as per the Centers for Disease Control and Prevention guidelines," says Dr. Onel.

Another treatment paradigm shift reflected in the new recommendations is how nonsteroidal anti-inflammatory drugs (NSAIDs) should be used to alleviate acute joint pain in JIA patients.

"In the past, we thought of NSAIDs as a treatment to be used in benign disease, but we have moved away from this approach and now shorten the period of NSAID use based on input from parents and patients. NSAIDs don't really fix the problem of underlying inflammation and have serious side effects, especially gastritis," says Dr. Onel.

"There is a difference between what scientific evidence would support in a treatment recommendation, and how the recommended treatment might affect the quality of life of patients. We can make all the recommendations in the world, but if they don't consider all of the patient's values and preferences, and all of their needs, then we will not be achieving the level of patient care that we should attain. These recommendations reflect our goal of shared decision making," she adds. "One mother told us that having a child with arthritis affects every aspect of a family's life: finances, children missing school, parents missing work to care for their children, families having to travel long distances for pediatric rheumatology care or treatment at a hospital. This disease has an incredibly broad range of effects on families. These experiences are so important and also, so common."

The new guideline reflects the ACR's commitment to producing regular updates on clinical practice recommendations to allow rheumatologists to stay up to date on rapidly expanding treatment options for their patients with rheumatic diseases. A 16-member panel of patients and parents of children with JIA greatly contributed to the guideline's creation, along with a core team of leading pediatric rheumatologists and methodologists. Recommendations were developed by panelists using GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology to assess available evidence from current scientific literature. In 2019, the ACR published the first half of this new guideline, with recommendations on treatment of polyarthritis, uveitis, sacroiliitis and enthesitis.

The manuscripts containing the full list of recommendations and supporting evidence are currently under review and are anticipated to be simultaneously published in two of the ACR's journals, Arthritis Care & Research and Arthritis & Rheumatology, in early 2021, pending peer review.

ATLANTA -- The American College of Rheumatology (ACR) will preview its 2020 Guideline for the Management of Rheumatoid Arthritis (RA) at ACR Convergence, the ACR's annual meeting. The comprehensive, clinical recommendations for pharmacologic treatment of RA includes important updates to the previous guideline released in 2015.

Rheumatoid arthritis (RA) is the most common type of chronic inflammatory arthritis. In RA, the immune system, the body's defense system against disease and injury, is not working properly. RA commonly causes pain and swelling in the wrist and small joints of the hand and feet but can affect almost all joints. Treatments for RA can stop joint pain and swelling and may also prevent joint damage. Early treatment will give patients with RA better long-term results.

While these recommendations focus solely on drug treatments for RA, future ACR guidelines will include non-drug therapies and vaccines. The new guideline was developed by a broad range of stakeholders in RA treatment, including rheumatologists, methodologists, and patients living with the disease.

"Patients with RA were involved at every step of the process and these recommendations truly reflect their perspectives. By including their personal experiences with different therapies, including their effectiveness, ease of use and side effects, the recommendations reflect the ACR's goal of shared decision making between the rheumatologist and patient," says Principal Investigator Liana Fraenkel, MD, MPH, professor adjunct in the Division of Rheumatology, Allergy and Immunology at Yale University School of Medicine. Fraenkel will discuss the recommendations at a press conference on Monday, Nov. 9 at 8:30 a.m. (ET).

Recommendations emphasize:

Starting patients on methotrexate and continuing with the treatment instead of rapidly switching to another disease-modifying anti-rheumatic drug (DMARD). "We offer rheumatologists guidance on the nuances of how to really maximize the use of methotrexate in these patients," says Dr. Fraenkel.

New recommendations include:

Minimizing the use of glucocorticoids, or steroids, to treat RA inflammation, due to the serious side effects associated with these drugs. "This conditional recommendation was based on the significant side effects of steroids."

A change from past recommendations to escalate to triple therapy before starting a biologic. "Now, we recommend that rheumatologists add a biologic or a targeted synthetic DMARD instead of switching patients to triple therapy."

New, specific recommendations on drug tapering and treatment of patient populations not covered in previous guidelines, including those with subcutaneous nodules, pulmonary disease, non-alcoholic fatty liver disease, persistent hypogammaglobulinemia and non-tuberculous mycobacterial lung disease. Because patients with RA may develop complications affecting their livers, eyes, lungs and just about every organ system, physicians from other specialties were invited to review clinical questions and provide input to the voting panel.

RA is a complex disease that may affect patients in different ways, so rheumatologists often need to individualize management approaches and decision making. Also, new pharmacologic agents are being approved for RA at a rapid pace, expanding the treatment options for this disease.

"Despite the many treatment recommendations included in this guideline, there are a number of remaining questions to address in more frequent, future updates. This guideline is a living document. As more therapies for RA emerge, we will modify what we recommend now," she says.

Recommendations were developed by panelists using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology to assess available evidence from current scientific literature.

The manuscript, containing the full list of recommendations and supporting evidence, is currently under review and is anticipated to be simultaneously published in Arthritis Care & Research and Arthritis & Rheumatology by fall 2020, pending completion of peer review.

Leesburg, VA, November 6, 2020--According to an open-access article in ARRS' American Journal of Roentgenology (AJR), ultrasound (US)-guided percutaneous pleural needle biopsy (PCPNB) has excellent diagnostic accuracy for small pleural lesions.

"US-guided PCPNB is highly likely to be diagnostic for small pleural lesions with nodular morphology on CT or US, or with pleural thickness - 4.5 mm," explained Jongmin Park and colleagues from South Korea's Kyungpook National University.

To determine the diagnostic yield of US-guided PCPNB for small (? 2 cm) pleural lesions and the impact of CT and US morphologic and technical factors, Park's team retrospectively studied 103 patients (73 men, 30 women; mean age, 60.8) who underwent US-guided PCPNB of a small pleural lesion by a single experienced operator from July 2013 to December 2019. Histopathological results established final diagnosis, including from repeat US-guided and CT-guided biopsies, as well as imaging and clinical follow-up. CT and US assessed pleural morphology and thickness, while US measured needle pathway length throughout the pleura.

Summarizing their results, Park et al. noted: "[US-guided PCPNB] of small pleural lesions had a diagnostic accuracy of 85.4%. The yield was 96.4% for nodular CT lesions, 95.0% for diffuse CT lesions with thickness ?4.5 mm, 55.6% for diffuse CT lesions with thickness."

Repeating their assessments on both CT and US 2 weeks later yielded the following representative measurements:

82-Year-Old Man Diagnosed With Tuberculous Pleurisy on US-Guided PCPNB (see image)

84-Year-Old Man Diagnosed with Pleural Metastasis From Lung Adenocarcinoma on US-Guided PCPNB (see image)

"In multivariable analysis," the authors of this AJR article concluded, "pleural morphology on US and needle pathway length through the pleura independently predicted diagnostic yield," adding that if the pleura is nodular or thicker than 4.5 mm on CT, US-guided PCPNB is justifiable as an initial or repeat diagnostic test.

A new study has shown pregnant women with obesity could reduce the health risks for their infants through improved diet and more physical activity.

Research published today in the journal PLosMed investigates the impact of high glucose in mothers with gestational diabetes mellitus (GDM) and changes to infants DNA.

GDM is becoming more frequent around the world alongside a rise in obesity and can increase the risk of complications during pregnancy and childbirth as well as increasing the risk of metabolic disease in the child in later life. High levels of glucose in mothers with GDM have been suggested to trigger epigenetic changes in the developing fetus (chemical modifications to the genetic blueprint of the fetus that function of genes activity) resulting in adverse health outcomes for the child.

Researchers from the University of Southampton and King's College London studied data from over 550 pregnant women with obesity and their children, from the UK Pregnancies Better Eating and Activity Trial (UPBEAT).
The trial aims to improve the diet and physical activity of obese pregnant women across the UK. Compared to women in a control group, who made no changes to their lifestyle during pregnancy, women who were supported in changing their diet to lower glycemic index foods that are broken down less quickly by the body, a reduced fat intake and increasing their physical activity put on less weight and were metabolically healthier.

In this new study, researchers compared the level and pattern of DNA methylation, a major epigenetic mechanism which controls gene activity, in the newborn infants from mothers who developed GDM with those that did not. They then looked at whether a dietary and physical activity intervention during pregnancy altered these modifications in infants born to mothers who developed GDM.

The results showed that GDM and high glucose levels in mothers were linked to changes in the level and pattern of functional modification to the infants DNA. Moreover, they found that the dietary and exercise intervention significantly reduced these methylation changes in the infant associated with GDM in the mothers.

Karen Lillycrop, Professor of Epigenetics at the University of Southampton said, "These findings suggest that improvements to diet and physical activity can have an impact on the development of their children.

"These are very encouraging finding and further studies are now needed to establish whether reducing these epigenetic changes through a healthier lifestyle during pregnancy are accompanied by improved health outcomes for the children in later life."

Professor Lucilla Poston, Tommy's Chair of Maternal & Fetal Health and lead investigator of the UPBEAT trial at King's College London, said: "we have known for some time that children of mothers who had gestational diabetes are a greater risk of obesity and poor control of glucose; this new research implies that epigenetic pathways could be involved."

Tommy's chief executive Jane Brewin said: "Obesity during pregnancy can have lifelong negative impacts on mother and baby - so one of the best things mums can do is to improve their health, including their weight, before embarking on a pregnancy. However, this study shows that mums who are overweight and their babies can still benefit from adopting a healthy diet while pregnant. All mums-to-be need access to healthy eating advice, and those who are overweight should be given non-judgemental practical support and encouragement to eat healthily during pregnancy."

November 6, 2020 - Cosmetic surgery is not just another way of saying plastic surgery. Doctors who advertise themselves as certified by the American Board of Cosmetic Surgery (ABCS) don't measure up to meet the criteria required for board-certified plastic surgeons.

In a study published in the November issue of Plastic and Reconstructive Surgery®, the official medical journal of the American Society of Plastic Surgeons (ASPS), Brian C. Drolet, MD, of Vanderbilt University Medical Center, Nashville, Tenn., and colleagues reviewed online information to assess residency training history and advertised scope of practice for 342 ABCS-certified physicians. "Our review of ABCS diplomate training backgrounds revealed nearly ten percent of ABCS members were not even trained in a surgical discipline," the researchers write.

According to the study, over half (62.6%) of ABCS diplomates advertised surgical operations beyond the scope of their ACGME or CODA residency training. Specialties with the highest prevalence of practicing beyond scope of training were internal medicine (n=2, 100%), general surgery (n=69, 95.8%), obstetrics and gynecology (n=17, 85%), otolaryngology (n=65, 59.1%), dermatology (n=16, 51.6%), and oral and maxillofacial surgery (n=30, 50%).

The most commonly offered out of training scope procedures were liposuction (59.6%), abdominoplasty (50.0%), breast augmentation (49.7%) and buttock augmentation (36.5%).

Procedures considered "out of scope" by specialty:

Otolaryngology - Aesthetic surgery below the neck (e.g. breast augmentation, abdominal liposuction, abdominoplasty, buttock augmentation)

Ophthalmology - Aesthetic surgery outside of periorbital region (e.g. rhinoplasty, full face lift, neck lift)

OB/GYN - Any aesthetic surgery

General Surgery - Any aesthetic surgery

Dermatology - Surgical procedures not including Mohs surgery or skin lesion

OMFS - Any aesthetic surgery below the neck

Internal Medicine - Any surgical procedure

"When selecting an aesthetic surgeon, many patients place trust in knowing their surgeon is a 'board-certified' plastic surgeon," Dr. Drolet and coauthors write. "Many patients falsely assume all surgeons must be board-certified in plastic surgery in order to perform cosmetic procedures."

As the authors write, the unregulated growth of the aesthetic marketplace may make it difficult for patients to find a qualified cosmetic surgeon. Misleading marketing and overtly false advertising are widespread in many large markets. One metric commonly used to select a qualified surgeon is board-certification; however, that distinction has become obfuscated, blurring the lines for patients.

A board-certified plastic surgeon must have at least six years of surgical training, including completion of an accredited plastic surgery training program. They must perform thousands of cosmetic and reconstructive surgery procedures of different types, pass rigorous written and oral examinations, and commit to continuing education and assessment throughout their careers.

However, an ABCS-diplomat is asked to complete only one year of surgical training, experience 300 procedures, and one written and oral examination completed during a single weekend, with no continuing medical education requirements.

These differences are so pronounced that in 2018 the Medical Board of California concluded ABCS certification is not equivalent to ABMS Board Certification, and that ABCS diplomates cannot advertise themselves as "board-certified."

The high demand for cosmetic surgery - 1.8 million procedures performed in 2019, according to ASPS statistics - underscores the need for regulation and education to help patients make informed decisions. ASPS offers patients tips on how to select a board-certified plastic surgeon.

Click here to read "Board Certification in Cosmetic Surgery: An Evaluation of Training Backgrounds and Scope of Practice."
DOI: 10.1097/PRS.0000000000007242

Implementing social distancing, business closures, and other non-pharmaceutical interventions (NPIs) in the U.S. two weeks sooner, during the earliest stages of the COVID-19 pandemic, may have prevented more than a million cases and saved more than 59,000 lives prior to May 3, 2020, when many state and local governments began relaxing restrictions, according to a new metapopulation modeling study. The results highlight the importance of quick and aggressive NPI implementation to counter transmission of the SARS-CoV-2 virus and could help inform efforts to control new surges in the U.S. and elsewhere in the world. Seeking to understand the impact of timing when implementing NPIs, Sen Pei and colleagues first built a metapopulation model of COVID-19 transmission in all 3,142 U.S. counties during the period spanning February 21 through May 3, 2020. They built the model using county-level data of confirmed cases and deaths compiled by USAFacts.org and commuter mobility data from the U.S. Census, adjusting the latter for reductions in mobility due to NPIs implemented beginning around March 15. The model revealed notable yet asynchronous reductions in disease transmission rates, reflected in changes to the estimated effective basic reproduction number (Re) in most counties during this time period. They then performed counterfactual simulations with the same model, moving the timing of NPI implementation either one week or two weeks sooner. In the first model, advancing NPIs by a week, to March 8, resulted in 601,667 fewer confirmed cases and 32,335 fewer deaths nationwide as of May 3. In the second model, implementing NPIs a full two weeks earlier, on March 1, resulted in 1,041,261 fewer confirmed cases and 59,351 fewer deaths. Pei et al. acknowledge that their modeling simplifies some assumptions related to general uncertainty, economic concerns, administrative decision-making, and public adherence to social distancing rules. However, they also point to continuing successes in countries such as South Korea, New Zealand, Vietnam, and Iceland that did implement NPIs in early March, suggesting that tens of thousands of cases and deaths in the U.S. "could have been averted, not merely postponed."

New research reveals that tinnitus, a common condition that causes the perception of noise in the ear and head, is being exacerbated by COVID-19 - as well as the measures helping to keep us safe.

The study of 3,103 people with tinnitus was led by Anglia Ruskin University (ARU), with support from the British Tinnitus Association and the American Tinnitus Association. The study involved participants from 48 countries, with the vast majority coming from the UK and the US.

Published in the journal Frontiers in Public Health, the research found that 40% of those displaying symptoms of COVID-19 simultaneously experience a worsening of their tinnitus.

Although the study focused on people with pre-existing tinnitus, a small number of participants also reported that their condition was initially triggered by developing COVID-19 symptoms, suggesting that tinnitus could be a 'long COVID' symptom in some cases.

Tinnitus affects an estimated one in eight adults in the UK and is associated with reduced emotional wellbeing, depression, and anxiety.

The new study also found that a large proportion of people believe their tinnitus is being made worse by social distancing measures introduced to help control the spread of the virus. These measures have led to significant changes to work and lifestyle routines.

UK respondents reported this to be a greater issue compared to people from other countries, with 46% of UK respondents saying that lifestyle changes had negatively impacted their tinnitus compared to 29% in North America.

Internal worries such as fear of catching COVID-19, financial concerns, loneliness and trouble sleeping have contributed to making tinnitus more bothersome for 32% of people overall, with external factors such as increased videocalls, noisier home environments, home schooling and increased coffee and alcohol consumption also cited by respondents. Females and the under-50s found tinnitus significantly more bothersome during the pandemic.

The study noted that as well as increasing the severity of tinnitus symptoms, the COVID-19 pandemic has also made it more difficult for people to access healthcare support for the condition. This could further increase emotional distress and worsen tinnitus symptoms, creating a vicious cycle. Before COVID-19, more than eight out of 10 UK patients were already unhappy with the treatment options available from their health professional.

Lead author Dr Eldre Beukes, a Research Fellow at Anglia Ruskin University (ARU) in Cambridge, England, and Lamar University in Texas, said: "The findings of this study highlight the complexities associated with experiencing tinnitus and how both internal factors, such as increased anxiety and feelings of loneliness, and external factors, such as changes to daily routines, can have a significant effect on the condition.

"Some of the changes brought about by COVID-19 appear to have had a negative impact on the lives of people with tinnitus and participants in this study reported that COVID-19 symptoms are worsening or, in some cases, even initiating tinnitus and hearing loss. This is something that needs to be closely examined by both clinical and support services."

David Stockdale, Chief Executive of the British Tinnitus Association and a co-author of the study, said: "With the second wave of COVID-19 and the resulting national lockdown likely to increase feelings of stress and isolation, it's vital that we don't see the same mistakes as before when it comes to community health provision for people with tinnitus.

"Poor treatment of tinnitus in the early stages often leads to much worse cases and severe tinnitus can have a huge impact on mental health. With this in mind, as the COVID-19 second wave takes hold, the healthcare system needs to ensure that anyone who develops tinnitus or experiences a worsening of their condition can access the professional healthcare support they need as quickly as possible."

What The Study Did: The implementation of swab screening program for COVID-19 cancer patients prior to each cycle of anticancer therapy at a hospital in the United Arab Emirates was assessed in this study.

Authors: Humaid O. Al-Shamsi, M.D., of the Burjeel Oncology-Burjeel Medical City in Abu Dhabi, United Arab Emirates, is the corresponding author.

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

(doi:10.1001/jamaoncol.2020.5745)

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

What The Study Did: Researchers compared the rate of death for patients diagnosed with breast, colorectal or lung cancer and living in states that expanded Medicaid under the Patient Protection and Affordable Care Act with states that didn't.

Authors: Miranda B. Lam, M.D., M.B.A., of the Harvard T.H. Chan School of Public Health in Boston, is the corresponding author.

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

(doi:10.1001/jamanetworkopen.2020.24366)

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

SAN DIEGO - Nov. 5, 2020-- A vast majority of doctors and parents of babies in intensive care, with diseases of unknown origin, believe genomic sequencing is beneficial in managing care, according to two new papers published by Rady Children's Institute for Genomic Medicine.

The study examined the attitudes of parents and physicians of infants admitted to neonatal intensive care at Rady Children's Hospital-San Diego about their perceptions of the usefulness of applying genomic testing in search of a diagnosis.

"In the case of babies who received genomic sequencing, we surveyed their physicians and parents and found that both groups overwhelmingly felt that genetic testing was beneficial," said Stephen Kingsmore, MD, DSc, President & CEO of Rady Children's Institute for Genomic Medicine (RCIGM). "When results are positive, sequencing reveals the genetic variation responsible for the child's disease. But what astounded us was the high proportion of both doctors and parents who perceived that this testing had life-changing utility, even in cases when results were negative for genetic disease."

Doctors reported genomic sequencing was medically useful 93% of the time in the 23% of cases where the test was positive and 72% of the time when the test was negative. Physicians reported the genome wide sequencing improved the outcomes of 32 infants in this study. The likelihood of changes in management increased when test results were returned faster.

Similarly 97% of parents whose children were tested reported that genomic sequencing was useful. Only 2 parents reported that having testing performed in the ICU setting increased stress or confusion.

"These studies clearly show that genomic sequencing can be done safely in the NICU, leading to improved communication between families and their healthcare teams," said David Dimmock, MD, Senior Medical Director for RCIGM. "These results underscore the importance of rapid test results in changing care"

The research was done as part of an NIH initiative called the second Newborn Sequencing in Genomic Medicine and Public Health (NSIGHT). The specific study was called NSIGHT2, a randomized controlled trial comparing two different methods of genomic sequencing as a means for diagnosing the cause of rare disease in babies admitted to intensive care (ClinicalTrials.gov Identifier: NCT03211039).

A total of 213 infants were offered a genome wide sequencing test within four days of being admitted to intensive care. Two dozen of those babies were too seriously ill to be randomized and instead received ultra-rapid whole genome sequencing to return results to attending physicians as soon as possible - a median of 2.3 days. The rest of the infants, who were more stable, were randomized for rapid whole exome sequencing or rapid whole genome sequencing with results returned in an average of 12 days.

The current work produced two papers published Nov. 5 in The American Journal of Human Genetics. The first, "An RCT of Rapid Whole Genome and Exome Sequencing in exome sequencing among seriously ill infants results in high clinical utility, changes in management, and low perceived harm." (https://doi.org/10.1016/j.ajhg.2020.10.003) was written by RCIGM investigators led by Dr. Dimmock.

The second paper, "A prospective study of parental perceptions of rapid whole genome and exome sequencing among seriously ill infants" was led by RCIGM and UC San Diego investigators Julie Cakici and Cinnamon Bloss with co-authors from RCIGM.

Genetic disease is a leading cause of death in the U.S. among infants admitted to intensive care hospital units. Disease in newborns can progress extremely rapidly making precise, fast diagnosis essential to guide medical intervention that can lessen suffering, reduce lasting disability or in some cases prevent death.

More than 14,000 genetic diseases have been identified with many new genetic variations or code errors discovered daily. The team at Rady Children's Institute of Genomic Medicine has optimized the use of rapid whole genome sequencing to speed answers to attending physicians in time to guide disease-specific intervention.

Governments should consider incentivising people to get a COVID-19 jab, when the vaccine becomes available, to achieve the required level of herd immunity--which could be up to 80%+ of the population--and stamp out the infection, argues a leading ethicist in an opinion piece accepted for publication in the Journal of Medical Ethics.

The incentive could be either financial or 'payment in kind', such as being allowed to forego the need to wear a facemask in public, he suggests.

Given the rising global death toll and the far reaching health and economic consequences of the pandemic, there have been calls, including in the UK, to mandate COVID-19 vaccination, if and when a jab is approved, points out the author, Professor Julian Savulescu, Oxford Uehiro Centre for Practical Ethics, University of Oxford.

In general, vaccination should be voluntary, he says. But there is a strong case for making any vaccination mandatory (or compulsory) if four conditions are met: a grave threat to public health; the vaccine is safe and effective; the pros outweigh the cons of any suitable alternative; and the level of coercion is proportionate.

Put simply, if voluntary schemes fail, we need to move to Vaccination Plan B, he suggests.

There are examples of coercion for the public good: conscription during wartime; taxes; the wearing of seat belts. And mandatory vaccination policies are already in place in different parts of the world, he says.

But there are ethical issues if a mandatory approach were to be adopted, he contends. So, if voluntary vaccination proves insufficient, incentivisation should be considered to address these issues while boosting vaccination uptake.

A certain level of uptake will be required to make any vaccination programme really effective and quell the relentless surge of the pandemic.

"To be maximally effective, particularly in protecting the most vulnerable in the population, vaccination would need to achieve herd immunity (the exact percentage of the population that would need to be immune for herd immunity to be reached depends on various factors, but current estimates range up to 82%)," he writes.

While there are obvious logistical issues to producing and administering a COVID-19 vaccine to the world's population, universal coverage also faces rising vaccine hesitancy--reluctance or refusal to be vaccinated because of safety concerns.

"Vaccines are some of the safest and most effective interventions we have, and have achieved incredible successes. We no longer face diseases that killed our ancestors," he says, "but vaccine hesitancy is on the rise even for well-established vaccinations.

"The problem is likely to be bigger for a new vaccine. For established vaccines, some countries have turned to mandatory vaccination schemes. In an ideal world, the vaccine would be proven to be 100% safe. But there will likely be some risk remaining, and there are risks that have not yet been identified.

"Any mandatory vaccination programme would therefore need to make a value judgement about what level of safety and what level of certainty are safe and certain enough. Of course, it would need to be very high, but a 0% risk option is very unlikely," he suggests.

"So we cannot say whether a mandatory policy of COVID-19 vaccination is ethically justified until we can assess the nature of the vaccine, the gravity of the problem and the likely costs/benefit of alternatives," he explains.

"However, another way of looking at this is that those at low risk are being asked to do a job which entails some risk, albeit a very low one. So they should be paid for the risk they are taking for the sake of providing a public good," Professor Savulescu suggests.

'Anti-vaxxers' may never be convinced to change their stance, but incentivising vaccination may persuade others who might not have done so to get the jab, he says.

"The advantage of payment for risk is that people are choosing voluntarily to take it on. As long as we are accurate in conveying the limitations in our confidence about the risks and benefits of a vaccine, then it is up to individuals to judge whether they are worth payment," he says.

Payment isn't about coercion, he insists. "If a person chooses that option, it is because they believe that, overall, their life will go better with it, in this case, with the vaccination and the payment.

"It is true that the value of the option might exercise force over our rational capacities, but that is no different from offering a lot of money to attract a favoured job applicant," he argues.

This is not about encouraging people to take unreasonable risks. Vaccine development and trials are in place to ensure that we are confident that there is very low risk, he emphasises.

"If a vaccine were deemed to be safe enough to offer on a voluntary basis without payment, it must be safe enough to incentivize with payment, because the risks are reasonable. It may be that those who are poorer may be more inclined to take the money and the risk, but this applies to all risky or unpleasant jobs in a market economy. It is not necessarily exploitation if there are protections in place such as a minimum wage or a fair price is paid to take on risk," he suggests.

"A payment model could also be very cheap, compared to the alternatives," he argues. "The cost of the UK's furlough scheme is estimated to reach £60 billion by its [original] planned end in October, and the economic shut down is likely to cost many billions more, as well as the estimated 200, 000 lives expected to be lost as a result.

"It would make economic sense to pay people quite a lot to incentivize them to vaccinate sooner rather than later--which, for example, would speed up their full return to work."

There are precedents for paying people to perform their civic duty: for example, blood donations are paid for in several countries, and while the UK doesn't pay donors directly, it does import blood from countries that do, he points out.

Incentives could also take the form of 'payment in kind,' he suggests. "One attractive benefit would be the freedom to travel, to not wear a mask in public places if you carried a vaccination certificate, and not to socially distance," he suggests. "Moreover, it would help ameliorate the risks the unvaccinated would pose to others."

Angiogenesis is the process by which tumors create new blood vessels that will provide them the nutrients to continue growing. Antiangiogenic drugs specifically block this process. This type of therapy usually has good short-term results, reducing tumor growth. However, several studies suggest that these treatments increase the invasiveness of tumors, and promote more aggressive behavior, inducing a poor prognosis. Studies with animal models have attempted to decipher the molecular mechanisms involved in this discrepancy, but many questions remain unclear.

The team of Dr. Oriol Casanovas from the Bellvitge Biomedical Research Institute (IDIBELL) and the Catalan Institute of Oncology (ICO) has investigated the consequences of antiangiogenic treatment on the invasiveness and metastasis of kidney cancer to identify biomarkers that determine the aggressiveness of these tumors.

In the study published today in the journal EMBO Molecular Medicine, the Casanovas team in collaboration with clinicians from the Hospital de Bellvitge, the Hospital de la Vall d'Hebron, and the VHIO, shows that antiangiogenic drugs, in some cases, increase the aggressiveness of tumors, while in others it is not affected. "These results confirm the heterogeneous effects of antiangiogenic treatments, and how these can profoundly affect the natural progression of tumors and induce malignancy," explains Dr. Casanovas.

Once it had been confirmed the heterogeneity of the response, it was necessary to identify the molecular signals that determine it, and therefore, that would identify the patients who would benefit from the treatment. The study has used various bioinformatics tools for genetic and molecular analyses that have pointed to the involvement of a cell signaling pathway, specifically the ALDH1A3 gene, in the divergent response to antiangiogenic therapy.

Dr. Oriol Casanovas points out that "in this study, we have identified a new biomarker capable of predicting whether a patient may benefit from antiangiogenic treatment", and adds, "these findings may open the door to new targets and therapeutic strategies to suppress the malignancy of these treatments. "

Study tools

To study the tumor behavior with the antiangiogenic treatment, and determine the existing interpatient variation, the researchers created a battery of orthotropic mouse models. These models consist of the implantation of renal tumors biopsies from patients in the same mouse tissue, which reproduce the variability between patients and identifying key aspects of tumor evolution. It is a preclinical tool with great potential.
The study of the genes expressed by kidney tumors after treatment with antiangiogenics, and their correlation with the subsequent tumor response, has made it possible to identify the biomarker that can discriminate between invasive and non-invasive tumors.

SASKATOON - A new University of Saskatchewan (USask) study has found that exercise performance and blood and muscle oxygen levels are not affected for healthy individuals wearing a face mask during strenuous workouts.

Questions have been raised as to whether mask wearing during vigorous exercise might compromise oxygen uptake or increase the rebreathing of carbon dioxide, leading to a condition (hypercapnic hypoxia) whereby increased carbon dioxide displaces oxygen in the blood.

But the study, published Nov. 3 in the research journal International Journal of Environmental Research and Public Health, did not find evidence to support these concerns.

"Our findings are of importance because they indicate that people can wear face masks during intense exercise with no detrimental effects on performance and minimal impact on blood and muscle oxygenation," the researchers state.

"This is important when fitness centers open up during COVID-19 since respiratory droplets may be propelled further with heavy breathing during vigorous exercise and because of reports of COVID-19 clusters in crowded enclosed exercise facilities."

The study evaluated use of a three-layer cloth face mask--the type recommended recently by Dr. Theresa Tam, Canada's Chief Public Health Officer. "Results using a single-layer cloth mask may differ," the researchers note.

The study, involving 14 physically active and healthy men and women, controlled for the effects of diet, previous physical activity, and sleep during the 24 hours prior to the test.

"If people wear face masks during indoor exercise, it might make the sessions safer and allow gyms to stay open during COVID," said Phil Chilibeck, a professor in the USask College of Kinesiology, who was a co-author of the study. "It might also allow sports to continue, including hockey, where transmission of COVID-19 appears to be high."

Participants were required to do a brief warm-up on a stationary bike. The exercise test involved a progressive increase in the intensity on the bike while they maintained a required pedal rate. Once they could not sustain the pedal rate the test was over.

"Usually a participant reaches exhaustion on this test in six to 12 minutes depending on their fitness level," said Chilibeck.

The team assessed the participants, who did the test three times each, once wearing a surgical face mask, once wearing a cloth face mask and once with no face mask. The team recorded the participants' blood oxygen levels and muscle oxygen levels throughout the test using non-invasive measurement tools.

Chilibeck notes the study is timely, as Saskatchewan has recently issued new public health orders that go into effect this week making masks mandatory in indoor public spaces in Regina, Saskatoon and Prince Albert to help curb the spread of COVID-19.

While the new provincial mask rules state that persons working out in a gym, ice rink or other recreational space are exempt, Chilibeck recommends that people wear masks in these facilities to keep safe, especially in these areas where people may be breathing harder due to vigorous exercise.