Author Interviews, Cancer Research, Immunotherapy / 05.12.2020

MedicalResearch.com Interview with: Dr. Corina Dutcus MD Vice President of Clinical Research Oncology Business Group Eisai MedicalResearch.com: What is the background for this study? Would you briefly explain how lenvatinib works? Is it used for any other malignancies, ex. thyroid cancer? Dr. Corina Dutcus Response: LENVIMA (lenvatinib), discovered and developed by Eisai, is an orally available multiple receptor tyrosine kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4, the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. LENVIMA is approved in combination with everolimus for the treatment of patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy. The approved starting dose for LENVIMA is 18 mg daily. The objective of Study 218, a randomized, open-label, Phase 2 trial, was to assess whether the lower starting dose of LENVIMA (14 mg daily) in combination with everolimus (5 mg daily) would provide similar efficacy with an improved safety profile compared to the FDA-approved starting dose of LENVIMA (18 mg daily) plus everolimus (5 mg daily) in patients with advanced renal cell carcinoma (RCC) following prior treatment with an antiangiogenic therapy. In the US, LENVIMA is also indicated for:
  • the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC);
  • for the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC);
  • and in combination with pembrolizumab, for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy, and are not candidates for curative surgery or radiation. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial.
Please see Prescribing Information for LENVIMA (lenvatinib) at http://www.lenvima.com/pdfs/prescribing-information.pdf.
Author Interviews, Dermatology, Environmental Risks / 04.12.2020

MedicalResearch.com Interview with: [caption id="attachment_56138" align="alignleft" width="142"]Jeremy M. Gernand, PhD, CSP, CRE Associate Professor Environmental Health and Safety Engineering Department of Energy and Mineral Engineering Dr. Gernand[/caption] Jeremy M. Gernand, PhD, CSP, CRE Associate Professor Environmental Health and Safety Engineering Department of Energy and Mineral Engineering MedicalResearch.com: What is the background for this study? Response: Given concern in the public about exposure to nanoparticles in cosmetics, we decided to investigate the exposure potential for inhaling nanoparticles during the application of aerosol mineral-based sunscreens that are typically marketed as safer for children. We choose three commercially available sunscreens to test in the lab in a manner intended to capture the amount of inhaled particles that would typically occur during application of sunscreen to the mid-point of one’s own arm. 
Allergies, Author Interviews, Immunotherapy, Pediatrics / 04.12.2020

MedicalResearch.com Interview with: [caption id="attachment_56134" align="alignleft" width="200"]Lianne Soller, PhD Allergy Research Manager, BC Children’s Hospital Allergy Clinic Vancouver, BC, Canada Dr. Soller[/caption] Lianne Soller, PhD Allergy Research Manager BC Children’s Hospital Allergy Clinic Vancouver, BC, Canada MedicalResearch.com: What is the background for this study? Response: Peanut oral immunotherapy (also known as OIT) has been studied for many years in clinical trials and has been found to be safe and effective in preschoolers. However, we know that clinical trials do not always reflect what happens in the real world. We wanted to see study whether peanut OIT would work as well in the real world. This is a follow up of our preschool peanut OIT safety study published in April 2019 which noted only 0.4% severe reactions and 4% epinephrine use during build-up.
Aging, Author Interviews, Cognitive Issues / 03.12.2020

MedicalResearch.com Interview with: [caption id="attachment_56112" align="alignleft" width="150"]Susanna Rosi, Ph.D.  Lewis and Ruth Cozen Chair II Professor, Brain and Spinal Injury Center Weill Institute for Neuroscience Kavli Institute of Fundamental Neuroscience Departments of Physical Therapy Rehabilitation Science, Neurological Surgery University of California San Francisco Dr. Rosi[/caption] Susanna Rosi, Ph.D.  Lewis and Ruth Cozen Chair II Professor, Brain and Spinal Injury Center Weill Institute for Neuroscience Kavli Institute of Fundamental Neuroscience Departments of Physical Therapy Rehabilitation Science, Neurological Surgery University of California San Francisco MedicalResearch.com: What is the background for this study? Response: Everybody has experienced a “senior moment” forgetting where the car keys are, or where you put your glasses. These forgetful moments are not always indicative of a disease, but rather can be a consequence of normal aging. Normal aging is associated with decline of cognitive abilities, such as memory, spatial orientation, problem solving and executive functioning. Investigating what changes happen in the brain with age, can help us to understand why these ‘senior moments’ occur. When we understand what causes these moments, we can design therapeutics with the hopes of preventing or reversing them.  With increased life expectancy age-associatedmemory decline becomes a growing concern. We wanted to investigate (i) What causes memory decline with age? (ii) Are there ways to reverse it? 
Author Interviews, Heart Disease, JAMA, Lifestyle & Health, USPSTF / 03.12.2020

MedicalResearch.com Interview with: [caption id="attachment_56105" align="alignleft" width="133"]Dr. John Epling, M.D., M.S.Ed Professor of family and community medicine Virginia Tech Carilion School of Medicine in Roanoke, VA. Medical director of research for family and community medicine Medical director of employee health and wellness for the Carilion Clinic Dr. Epling[/caption] Dr. John Epling, M.D., M.S.Ed Professor of family and community medicine Virginia Tech Carilion School of Medicine in Roanoke, VA. Medical director of research for family and community medicine Medical director of employee health and wellness for the Carilion Clinic Dr. Epling joined the U.S. Preventive Services Task Force in January 2016. MedicalResearch.com: What is the background for this study? What are the main findings? Response: Cardiovascular disease, which includes heart disease and stroke, is one of the leading causes of death in the United States. Nearly half of all adults have at least one risk factor for cardiovascular disease. Evidence shows that counseling aimed at helping people improve their diet and increase their physical activity can help prevent cardiovascular disease. This typically involves a trained counselor who provides education, helps people set goals, shares strategies, and stays in regular contact.  The Task Force recommends behavioral counseling interventions that promote a healthy diet and physical activity to help people at risk for cardiovascular disease stay healthy.
Author Interviews / 01.12.2020

MedicalResearch.com Interview with: Daniel Maloney, Ph.D Farrar Lab Smurfit Institute of Genetics Trinity College Dublin MedicalResearch.com: What is the background for this study? Would you briefly describe the condition of Dominant optic atrophy? Response: Dominant Optic Atrophy (DOA) is a progressive blinding disorder that affects roughly 1:10,000 to 1:30,000 people. It is primarily caused by mutations in the OPA1 gene, which plays a pivotal role in the maintenance of the mitochondrial network. There is currently no way to prevent or cure DOA. We sought to build upon previous work to test if OPA1 could be delivered as a potential gene therapy intervention. 
Author Interviews, Cancer Research, Genetic Research / 01.12.2020

MedicalResearch.com Interview with: [caption id="attachment_56006" align="alignleft" width="130"]Dr-Nina Bhardwaj Dr. Bhardwaj[/caption] Nina Bhardwaj MD PhD Director of Immunotherapy Tisch Cancer Institute Icahn School of Medicine at Mt Sinai Ward-Coleman Chair in Cancer Research Professor of Hematology and Oncology MedicalResearch.com: What is the background for this study? Response: Neoantigens are novel antigens expressed by tumors as a result of somatic mutations or frame shift mutations. They can be very immunogenic and consequently they are being incorporated into cancer vaccine platforms. In most cases it is necessary to determine each patient’s individual mutations and customize their vaccine antigens accordingly. We sought to identify shared mutations in cancer antigens which are deficient in DNA repair mechanisms namely microsatellite unstable tumors. These tumors have mutations in genes that normally are responsible for ensuring that DNA is properly replicated. Because these genes encode proteins that ensure proper repair around micro-satellite areas (which contain short repeated sequences of DNA and are present in similar regions from one person’s genome to the next), when they are mutated, these regions may not be repaired. Consequently due to nucleotide deletions and insertions one gets frame shift mutations which result in new protein expression which can be shared across tumors, as has been observed for a few regions. We therefore did a comprehensive study of a subset of tumors to determine the breadth of shared frame shift mutations.
Author Interviews, COVID -19 Coronavirus, Inflammation, JAMA, Pediatrics, Race/Ethnic Diversity / 30.11.2020

MedicalResearch.com Interview with: Ellen H. Lee, MD Incident Command System Surveillance and Epidemiology Section New York City Department of Health and Mental Hygiene Long Island City, New York  MedicalResearch.com: What is the background for this study? Response: Published reports of the COVID-19-associated multisystem inflammatory syndrome in children (MIS-C) have described higher proportions of cases among Black and Hispanic children. However, case series are limited by the lack of population-level data, which could help provide context for the racial/ethnic distribution of cases described in these reports. The New York City (NYC) Department of Health and Mental Hygiene required reporting of all possible cases of MIS-C among NYC residents, and for cases meeting MIS-C criteria, applied population denominators to calculate MIS-C incidence rates stratified by race/ethnicity. To help characterize the burden of severe COVID-19 disease in NYC, we also calculated COVID-19 hospitalization rates stratified by race/ethnicity.
AHA Journals, Author Interviews, Heart Disease, Women's Heart Health / 30.11.2020

MedicalResearch.com Interview with: [caption id="attachment_56073" align="alignleft" width="200"]Justin A. Ezekowitz, MBBCh, MSc Professor, Department of Medicine Co-Director, Canadian VIGOUR Centre Director, Cardiovascular Research, University of Alberta Cardiologist, Mazankowski Alberta Heart Institute Dr. Ezekowitz[/caption] Justin A. Ezekowitz, MBBCh, MSc Professor, Department of Medicine Co-Director, Canadian VIGOUR Centre Director, Cardiovascular Research, University of Alberta Cardiologist, Mazankowski Alberta Heart Institute MedicalResearch.com: What is the background for this study? What are the main findings? Are women older, sicker when they experience heart disease? Response: Previous research looking at sex-differences in heart health has often focused on recurrent heart attack or death, however, the vulnerability to heart failure between men and women after heart attack remains unclear. Our study includes all patients from an entire health system of over 4 million people and includes information not usually available in other analyses. Women were nearly a decade older and more often had a greater number of other medical conditions when they presented to hospital for their first heart attack, and were at greater risk for heart failure after the more severe type of heart attack (also known as a ST-elevation MI). This gap between men and women has started to narrow over time.
Author Interviews, Infections, OBGYNE, Pediatrics / 26.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55957" align="alignleft" width="200"]Jessica Miller PhD Postdoc Fellow Murdoch Childrens Research Institute Dr. Miller[/caption] Jessica Miller PhD Postdoc Fellow Murdoch Childrens Research Institute  MedicalResearch.com: What is the background for this study? Response: Cesarean section (CS) may be a lifesaving intervention for women and babies. However, the global proportion of CS births is rapidly increasing and may not be medically justified. As CS has implications for both mother and child, the increasing rates warrant population-level analyses of potential risks. Many suggested long-term outcomes in CS-born children relate to altered immune development. It is possible that differences in the newborn microbiome by mode of birth contribute to the development of early immune responses which may influence the risk of immune-related outcomes, including infection. CS has been associated with an increased risk for specific infection-related hospitalisations, mainly lower respiratory tract and gastrointestinal infections, but it remains unclear whether CS is associated with increased risk of overall infection-related hospitalisation or only certain infection types, and whether risk differs for emergency versus elective/pre-labour CS.
Accidents & Violence, Author Interviews, Pediatrics, Race/Ethnic Diversity / 26.11.2020

MedicalResearch.com Interview with: [caption id="attachment_56050" align="alignleft" width="200"]Dr. Monika K. Goyal, Dr. Goyal[/caption] Dr. Monika K. Goyal, MD Associate Division Chief, Emergency Medicine Children’s National Hospital Department of Pediatrics, School of Medicine and Health Sciences The George Washington University Washington, District of Columbia MedicalResearch.com: What is the background for this study? Response: There has been growing attention to the disproportionate use of police force in communities of color. Therefore, we sought to investigate whether Black and Hispanic teenagers have higher rates of death due to police shootings when compared to white youth.
Aging, Author Interviews, Genetic Research, McGill / 22.11.2020

MedicalResearch.com Interview with: [caption id="attachment_56017" align="alignleft" width="111"]Richard C. Austin, PhD Professor and Career Investigator of the Heart and Stroke Foundation of Ontario Amgen Canada Research Chair in Nephrology McMaster University and St. Joseph’s Healthcare Hamilton, Ontario, Canada Dr. Austin[/caption] Richard C. Austin, PhD Professor and Career Investigator of the Heart and Stroke Foundation of Ontario Amgen Canada Research Chair in Nephrology McMaster University and St. Joseph’s Healthcare Hamilton, Ontario, Canada MedicalResearch.com: What is the background for this study? What are the main findings? Response: A previous study published in 2011 by my collaborator, Dr. Michel Chretien at the IRCM, identified a rare mutation in the PCSK9, termed Q152H. Individuals harboring this mutation demonstrated dramatic reductions in their LDL cholesterol levels and had a significantly lower risk of CVD. Furthermore, individuals harboring the Q152H mutation showed increases in longevity with no evidence of other diseases such as liver disease, cancer and chronic kidney disease. This Q152H mutation was unique with only 4 families in Quebec shown to harbor this genetic variant. In terms of its effect on PCSK9 expression/activity, the mutation at Q152H was precisely at the cleavage site in PCSK9 necessary for its activation. As a result, the Q152H mutation fails to be cleaved and activated, thereby blocking its secretion into the circulation. This is why the Q152H mutation is considered a loss-of-function PCSK9 mutant. Given our lab's interest in endoplasmic reticulum (ER) stress and ER storage diseases, we began to collaborate with Drs. Chretien and Seidah at the IRCM to investigate whether this Q152H mutant, when overexpressed in liver cells, would cause ER stress and liver cell injury. This was based on the findings that the Q152H mutant does not undergo autocatalytic cleavage and its subsequent secretion from liver cells. It is well known in the literature that the accumulation of misfolded or inactive proteins in the ER gives rise to ER stress and cell injury/dysfunction. As a result, we initially showed to our surprise that overexpression of the Q152H mutant in liver cells failed to cause ER stress BUT increased the protein levels of several important ER chaperones, GRP78 and GRP94, known to PROTECT against liver cell injury/dysfunction. As part of our JCI study, we furthered these studies to examine the effect of the Q152H mutant when overexpressed in the livers of mice. This is where we demonstrated that the Q152H mutation showed protection against ER stress-induced liver injury/dysfunction.
AHA Journals, Author Interviews, COVID -19 Coronavirus, Race/Ethnic Diversity, Stanford / 19.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55996" align="alignleft" width="200"]Fatima Rodriguez, MD, MPH, FACC, FAHA Assistant Professor, Cardiovascular Medicine Stanford University School of Medicine Palo Alto, CA 94304 Dr. Rodriguez[/caption] Fatima Rodriguez, MD, MPH, FACC, FAHA Assistant Professor, Cardiovascular Medicine Stanford University School of Medicine Palo Alto, CA 94304 MedicalResearch.com: What is the background for this study? Response: The COVID-19 pandemic has magnified existing racial/ethnic disparities in the United States. The goal of this study was to leverage new data collected from the American Heart Association’s COVID-19 Cardiovascular Disease Registry to understand racial/ethnic differences in presentation and outcomes for hospitalized patients.
Author Interviews, BMJ, Brigham & Women's - Harvard, Fertility, OBGYNE / 19.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55925" align="alignleft" width="200"]Jennifer Yland, MS Department of Epidemiology Boston University School of Public Health Jennifer Yland[/caption] Jennifer Yland Doctoral Student in Epidemiology Harvard T.H. Chan School of Public Health MedicalResearch.com: What is the background for this study? Response: Worldwide, about 22% of reproductive-aged women used hormonal contraception last year. Long-acting reversible contraceptive (LARC) methods, which include intrauterine devices (IUDs), implants, patches, and injectable contraceptives, have become increasingly popular. However, little is known about the return to fertility after use of different contraceptives, particularly LARC methods.
Alzheimer's - Dementia, Author Interviews, Lipids, Mental Health Research, Microbiome / 18.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55988" align="alignleft" width="200"]Moira Marizzoni, PhD Researcher, Fatebenefratelli Center in Brescia  Dr. Marizzoni[/caption] Moira Marizzoni, PhD Researcher, Fatebenefratelli Center in Brescia  MedicalResearch.com: What is the background for this study? Response: Alzheimer’s disease is the most common cause of dementia. Still incurable, it directly affects nearly one million people in Europe, and indirectly millions of family members as well as society as a whole. The gut microbiota could play a role in brain diseases including Alzheimer’s disease. Some gut bacteria components or products can reach the brain via the blood and might promote brain amyloidosis (one of the main pathological features in Alzheimer’s disease).   MedicalResearch.com: What are the main findings?  Response: This study evaluated a cohort of 89 people between 65 and 85 years of age composed of subjects suffering from Alzheimer’s disease or other neurodegenerative diseases causing similar memory problems, and of subjects with no memory problems. The study revealed that elevated levels of microbiota-products with known pro-inflammatory properties (i.e. lipopolysaccharides and the short chain fatty acids acetate and valerate) were associated with greater cerebral amyloid pathology while elevated levels of those with anti-inflammatory properties (i.e. the short chain fatty acid butyrate) were associated with lower amyloid pathology.
Author Interviews, Brain Injury, Exercise - Fitness, JAMA / 17.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55977" align="alignleft" width="142"]Tara L Sharma DO Clinical Assistant Professor of Neurology at UWMC Seattle, WA 98133 Dr. Sharma[/caption] Tara L Sharma DO Clinical Assistant Professor of Neurology at UWMC Seattle, WA 98133 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Flying can lead to reduced oxygen partial pressures and cerebral blood flow causing worsening clinical outcome in cases of moderate to severe TBI; however, not much is known regarding the clinical consequences of flying in individuals with concussion or mild TBI. Because many athletes suffer concussions during games, it is necessary to know if flying afterward may potentially hinder their ability to return to play. Overall, we found no associated between air travel and increased symptom severity in both our entire cohort and the subset of football players.
AHA Journals, Author Interviews, Heart Disease, University of Michigan / 17.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55974" align="alignleft" width="125"]Sara Saberi, MD, MS Assistant Professor Inherited Cardiomyopathy Program Frankel Cardiovascular Center University of Michigan Hospital Michigan Medicine Dr. Saberi[/caption] Sara Saberi, MD, MS Assistant Professor Inherited Cardiomyopathy Program Frankel Cardiovascular Center University of Michigan Hospital Michigan Medicine MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by HCM? How common is it and whom does it affect? Response: HCM is short for hypertrophic cardiomyopathy, the most common genetic myocardial disorder. It occurs in 1:500 people worldwide and because it is inherited in an autosomal dominant fashion, it affects men and women equally. HCM is characterized by unexplained left ventricular (LV) hypertrophy, hypercontractility, myofibrillar disarray and myocardial fibrosis with associated abnormalities in LV compliance and diastolic function. In some patients, there is progressive adverse cardiac remodeling, associated with chronic heart failure and atrial fibrillation as a result of diastolic dysfunction, left ventricular outflow tract (LVOT) obstruction, or less commonly, LV systolic dysfunction. Current medical management of obstructive HCM (oHCM) is limited to the use of beta blockers and non-dihydropyridine calcium channel blockers, or disopyramide, none of which have been shown to modify disease expression or outcomes after onset. Mavacamten is a first-in-class, small molecule, selective inhibitor of cardiac myosin specifically developed to target the underlying pathophysiology of HCM by reducing actin–myosin cross-bridge formation. The phase 3 EXPLORER-HCM trial showed that mavacamten improved exercise capacity, LVOT gradients, symptoms, and health status compared with placebo in patients with symptomatic oHCM. At selected study sites, participants were enrolled in a cardiac magnetic resonance (CMR) imaging substudy. CMR is the gold standard for measurement of ventricular mass, volumes and noninvasive tissue characterization, making it an ideal imaging modality to assess the effect of mavacamten on cardiac structure and function in patients with HCM.
Author Interviews, Brigham & Women's - Harvard, Dermatology, JAMA, McGill, Mental Health Research / 17.11.2020

Editor's note: This piece discusses suicide. If you have experienced suicidal thoughts or have lost someone to suicide and want to seek help, you can contact the Crisis Text Line by texting "START" to 741-741 or call the Suicide Prevention Lifeline at 800-273-8255.  MedicalResearch.com Interview with: David-Dan Nguyen, MPH Research Fellow | Center for Surgery and Public Health, Brigham and Women's Hospital Medical Student | McGill University MedicalResearch.com: What is the background for this study? Response: There is ongoing concern about the side-effects of finasteride, a drug used for the management of alopecia and benign prostatic hyperplasia. These concerns have led to the coining of the “post-finasteride syndrome” which remains controversial. Indeed, there is conflicting evidence on the post-finasteride syndrome/adverse events associated with finasteride. We wanted to contribute to this conflicting body of evidence by examining suicidality, depression, and anxiety reports linked to finasteride use using the WHO’s pharmacovigilance database, VigiBase. Such pharmacovigilance databases are useful for the study of rare adverse events that are suspected to be associated with medication use.
Author Interviews, COVID -19 Coronavirus, Occupational Health / 16.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55952" align="alignleft" width="200"]Emily Barrett, PhD  Associate Professor Department of Biostatistics and Epidemiology Rutgers School of Public Health Dr. Barrett[/caption] Emily Barrett, PhD Associate Professor Department of Biostatistics and Epidemiology Rutgers School of Public Health MedicalResearch.com: What is the background for this study? Response: We started this study in the very early stages of the pandemic to look at SARS-CoV-2 viral transmission and disease severity in health care workers as compared to non-health care workers.  There was a tremendous amount of fear and uncertainty about the virus and the early anecdotal reports coming out of China and Italy highlighted the plight of many frontline health care workers who had been infected on the job. We knew that our U.S. health care workers would soon be facing this tremendous challenge. We started this study to examine risks of infection in our vulnerable frontline health care workers and a comparison group of non-health care workers. Our results are from the early stages of the U.S. pandemic in March-April 2020.
Author Interviews, Genetic Research / 16.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55947" align="alignleft" width="130"]Philippe M Soriano, PhD Professor,  Cell, Developmental & Regenerative Biology and Oncological Sciences Icahn School of Medicine at Mount Sinai Dr. Soriano[/caption] Philippe M Soriano, PhD Professor,  Cell, Developmental & Regenerative Biology and Oncological Sciences Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? Response: The study was performed primarily to help understand how signals sent from growth factors to their receptors on the cell surface (see reply to the following question) initiate a cascade of events within the cells that lead to proliferation, survival, or other biological responses. This is important to know because deregulation of many of these pathways can lead to cancers. MedicalResearch.com: Would you explain what is meant by FGFs and their interaction with RTKs? Response: FGFs are cell signaling proteins that are also known as growth factors because they often lead to cell proliferation. They act by binding to receptors on the cell surface that are part of a family of receptor tyrosine kinases (RTKs). These RTKs are transmembrane proteins that have a domain outside of the cell that binds to the growth factor and a domain within the cell that has tyrosine kinase activity, hence the name “receptor tyrosine kinase (RTK).” This enzymatic activity adds a phosphate to a tyrosine residue of target proteins and starts a typical signal transduction pathway (referred to in the paper as “canonical”) leading to the usual biological responses (proliferation, survival, migration, etc.)
Author Interviews, Gout, Rheumatology / 12.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55936" align="alignleft" width="150"]MedicalResearch.com Interview with: Jeffrey D. Kent, M.D., FACG, FACP Executive Vice President, Medical Affairs and Outcomes Research Horizon MedicalResearch.com: What is the background for this study? What is the marker for reduced immunogenicity with Pegloticase? Response: Pegloticase is a recombinant, pegylated uricase that is used for treatment of chronic gout in patients who fail oral urate lowering therapy (uncontrolled gout) and has a demonstrated impact on the serum uric acid (sUA) level. As with other biologics, in some people the body’s immune system develops anti-drug antibodies and reduces the effectiveness of the biologic therapy. Recent case series and open-label trials have suggested that using an immunomodulator with pegloticase has the potential to increase the durability of response so patients can receive a full course of therapy. Researchers in the RECIPE trial sought to examine whether the co-administration of disease-modifying antirheumatic drugs (DMARDs), specifically mycophenolate mofetil, may mitigate this loss of efficacy and increase in response rates for people living with uncontrolled gout MedicalResearch.com: Are symptoms of gout improved as well as reduced infusion reactions? Response Results from this trial indicated that short-term concomitant use of mycophenolate mofetil with pegloticase was generally well tolerated. It was also associated with a statistically significant and clinically meaningful impact on the proportion of patients achieving and maintaining an sUA ≤6 mg/dL at 24 weeks. No infusion reactions were reported in the pegloticase/mycophenolate mofetil arm (0 or 22 patients) compared to 30 percent (3 of 10) of patients reporting infusion reactions in the pegloticase/placebo arm. It’s been well established that in patients receiving pegloticase with persistent urate lowering, they experience relatively rapid resolution of tophi indicating significant reductions in their urate burden. MedicalResearch.com: What are the main findings? Response: This is the first randomized controlled trial evaluating pegloticase co-prescribed with an immunomodulator compared to pegloticase with placebo. Data showed that 86.4 percent of patients (19 of 22) receiving co-therapy of pegloticase with mycophenolate mofetil achieved an sUA ≤ 6 mg/dL through Month 3, the primary study endpoint, compared to 40.0 percent of patients (4 of 10) receiving pegloticase monotherapy. After Month 3, all patients received pegloticase only and at Month 6 a sustained response was shown in 68.2 percent (15 of 22) of patients who had received pegloticase with mycophenolate mofetil versus 30.0 percent (3 of 10) of patients who received pegloticase and placebo. This data adds to the growing body of evidence on the concomitant use of pegloticase with an immunomodulator to ultimately help more patients receive a full course of therapy and improve outcomes and may help shift the treatment paradigm in uncontrolled gout. MedicalResearch.com: What should readers take away from your report? Response: While rheumatologists are familiar with and may use DMARDs for other autoimmune conditions to minimize the development of anti-drug antibodies and increase response to therapies, data shows that the use of an immunomodulating therapy in patients with uncontrolled gout can improve response rates. MedicalResearch.com: What recommendations do you have for future research as a result of this work? Response: There is a consistent pattern demonstrating that the concomitant use of pegloticase and an immunomodulator can improve patient outcomes without introducing additional toxicities. As clinicians we understand the immense burden gout places on our patients. Future research should continue exploring options to maximize the benefit of effective treatments to improve patient outcomes. MedicalResearch.com: Is there anything else you would like to add? Response: Uncontrolled gout is a chronic, systemic inflammatory condition and we continue to see data linking it to many comorbid conditions. Horizon is evaluating the use of methotrexate to improve response rates for pegloticase. We are committed to exploring various immunotherapy co-treatment options to allow both patients and clinicians to address elevated sUA levels to minimize urate burden and avoid lasting damage to the body. RECIPE is an investigator-initiated trial led by Puja Khanna, M.D., M.P.H. and Kenneth Saag, M.D., M.Sc. Citation: Khanna P, Khanna D, Cutter G, Foster J, Melnick J, Jaafar S, Biggers S, Rahman A, Kuo H, Feese M, Saag K. Reducing Immunogenicity of Pegloticase (RECIPE) with Concomitant Use of Mycophenolate Mofetil in Patients with Refractory Gout—a Phase II Double Blind Randomized Controlled Trial [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/reducing-immunogenicity-of-pegloticase-recipe-with-concomitant-use-of-mycophenolate-mofetil-in-patients-with-refractory-gout-a-phase-ii-double-blind-randomized-controlled-trial/. Accessed November 12, 2020. [subscribe] Last Modified: [last-modified] The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website. Dr. Kent[/caption]Jeffrey D. Kent, M.D., FACG, FACP Executive Vice President, Medical Affairs and Outcomes Research Horizon MedicalResearch.com: What is the background for this study? What is the marker for reduced immunogenicity with Pegloticase?   Response: Pegloticase is a recombinant, pegylated uricase that is used for treatment of chronic gout in patients who fail oral urate lowering therapy (uncontrolled gout) and has a demonstrated impact on the serum uric acid (sUA) level. As with other biologics, in some people the body’s immune system develops anti-drug antibodies and reduces the effectiveness of the biologic therapy.  Recent case series and open-label trials have suggested that using an immunomodulator with pegloticase has the potential to increase the durability of response so patients can receive a full course of therapy. Researchers in the RECIPE trial sought to examine whether the co-administration of disease-modifying antirheumatic drugs (DMARDs), specifically mycophenolate mofetil, may mitigate this loss of efficacy and increase in response rates for people living with uncontrolled gout
Aging, Author Interviews, Geriatrics, Heart Disease, Lancet, Lipids / 11.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55907" align="alignleft" width="128"]Børge G. Nordestgaard, MD, DMSc Professor, University of Copenhagen Chief Physician, Dept. Clinical Biochemistry Herlev and Gentofte Hospital Copenhagen University Hospital Herlev, Denmark Dr. Nordestgaard[/caption] Børge G. Nordestgaard, MD, DMSc Professor, University of Copenhagen Chief Physician, Dept. Clinical Biochemistry Herlev and Gentofte Hospital Copenhagen University Hospital Herlev, Denmark  MedicalResearch.com: What is the background for this study? Response: Previous studies have yielded mixed results regarding the association between elevated cholesterol levels and increased risk of atherosclerotic cardiovascular disease in individuals above age 70 years; with some studies showing no association and others only minimal association. However, these previous studies were based on cohorts recruiting individuals decades ago where life-expectancy were shorter and where treatment of comorbidities were very different from today
Author Interviews, Cancer Research / 10.11.2020

MedicalResearch.com Interview with: Brianna M. Jones, MD Icahn School of Medicine at Mount Sinai New York, NY MedicalResearch.com: What is the background for this study? Response: Oral tongue cancer has traditionally been a diagnosis associated with older age and habitual tobacco or alcohol use. However, in the past few decades there has been a disproportionate increase in oral tongue cancer in young patients, particularly in those without a prior history of significant alcohol or tobacco use. In the literature, these young patients without traditional risk factors seem to represent a distinct clinical entity with worse oncologic outcomes. The purpose of this study was to compare young patients (age ≤45) to older patients (>45) with oral tongue squamous cell carcinoma (OTSCC) without habitual smoking or drinking history. 
Author Interviews, BMJ, Breast Cancer, Cancer Research, Radiation Therapy / 10.11.2020

MedicalResearch.com Interview with: Professor Jayant S Vaidya MBBS MS DNB FRCS PhD Professor of Surgery and Oncology University College London MedicalResearch.com: What is the background for this study? What type of single dose radiation is used?  [caption id="attachment_55895" align="alignleft" width="500"]Prof Jeffrey S Tobias, Prof Jayant S Vaidya, Prof Max Bulsara and Prof Michael Baum Prof Jeffrey S Tobias, Prof Jayant S Vaidya, Prof Max Bulsara.                             and Prof Michael Baum[/caption] Response: The findings of the large international randomised trial (TARGIT-A trial), published in the British Medical Journal (BMJ 2020;370:m2836), confirm the long-term effectiveness of Targeted Intraoperative Radiotherapy (TARGIT-IORT): a breast cancer treatment which is increasingly available throughout the world. For most women with early breast cancer, a single dose of targeted radiotherapy during surgery is just as effective as conventional radiotherapy, which requires several visits to hospital after surgery. Conventional external beam radiotherapy (EBRT) is delivered from outside the body via a radiotherapy machine (linear accelerator), and consists of a daily treatment session (known as fractions) to the whole breast, over a period between three to six weeks. Each of these treatments is given over a few minutes, but requires 15 to 30 hospital visits, which could be a significant distance from where the patient lives. TARGIT-IORT is delivered immediately after lumpectomy (tumour removal), via a small ball-shaped device placed inside the breast, directly where the cancer had been. The single-dose treatment lasts for around 20 to 30 minutes and replaces the need for extra hospital visits, benefiting both patient safety and well-being. The device used is called INTRABEAM. More details are described on the BMJ and UCL webpages: https://www.bmj.com/company/newsroom/single-dose-radiotherapy-as-good-as-conventional-radiotherapy-for-most-women-with-early-breast-cancer/ https://www.ucl.ac.uk/news/2020/aug/single-dose-radiotherapy-effective-treating-breast-cancer https://blogs.bmj.com/bmj/2020/08/20/targeted-intraoperative-radiotherapy-for-early-breast-cancer-new-evidence/
Author Interviews, COVID -19 Coronavirus, Race/Ethnic Diversity, Rheumatology, UCSF / 07.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55874" align="alignleft" width="151"]Milena Gianfrancesco, PhD, MPH Assistant Professor. Education Division of Rheumatology, Department of Medicine University of California, San Francisco Dr. Gianfrancesco[/caption] Milena Gianfrancesco, PhD, MPH Assistant Professor. Education Division of Rheumatology, Department of Medicine University of California, San Francisco MedicalResearch.com: What is the background for this study? Response: This study utilized data from the COVID-19 Global Rheumatology Alliance Provider Survey, which launched on March 25th. To date, it has collected information on over 6,000 patients with rheumatic disease diagnosed with COVID-19 from over 40 countries worldwide. As COVID-19 spread across the world in the spring, and especially within the United States, it became clear that the disease was impacting certain groups more than others. Growing attention and research began to illustrate the disproportionate burden of COVID-19 among racial/ethnic minorities in the United States. We know that racial and ethnic minorities experience a higher burden of rheumatic disease risk and severity; therefore, our group was interested in examining whether the disproportionate burden of COVID-19 also affected this susceptible population.
Author Interviews, Columbia, JAMA, OBGYNE, Weight Research / 05.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55855" align="alignleft" width="139"]Dr-Marissa-N-Spann Dr. Spann[/caption] Marisa N. Spann, PhD, MPH Columbia University Irving Medical Center New York, New York MedicalResearch.com: What is the background for this study? Response: Prior research has demonstrated that higher maternal pre-pregnancy body mass index is associated with adverse long-term outcomes for offspring including obesity, poorer cognitive and social abilities, and increased risk of psychiatric disorders.  MedicalResearch.com: What are the main findings? Response: In this study, we investigated the association of maternal pre-pregnancy body mass index with fetal growth and neonatal functional connectivity and found that maternal pre-pregnancy BMI has a significant positive correlation with fetal weight and with greater thalamic connectivity of the brain. 
Author Interviews, Brigham & Women's - Harvard, COVID -19 Coronavirus / 05.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55840" align="alignleft" width="225"]Duane Wesemann, MD, PhD Div. of Rheumatology, Immunology and Allergy Brigham and Women's Hospital Boston, MA 02115 Dr. Wesemann[/caption] Duane Wesemann, MD, PhD Div. of Rheumatology, Immunology and Allergy Brigham and Women's Hospital Boston, MA 02115 Wesemann Lab   MedicalResearch.com: What is the background for this study? Response: There is a lot of variability in how long antibodies to pathogens are produced in humans.  Some infections and vaccinations like measles induce high levels of antibodies that can be produced for a lifetime.  Other infections or vaccinations induce only short lived antibody responses. Also, some people make longer lasting antibodies compared to others.   We wanted to ask what the antibody durability dynamics looked like after COVID-19 and if we could tease out any insights—both with regard to COVID-19 as well as in general. 
Author Interviews, Surgical Research / 03.11.2020

MedicalResearch.com Interview with: Dr. Pravesh S. Gadjradj, MD Department of Neurosurgery, Leiden University Medical Center, University Neurosurgical Center Holland Leiden, Netherlands neurosurgery brain surgery ct scan MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Many healthcare professionals throughout the world face issues surrounding medical malpractice at some point in their careers. Unfortunately, a number of these cases turn into medical malpractice lawsuits. As a specialty that treats acute pathology and refractory pain, neurosurgery is at risk for high liability. By the means of a survey among members of the Congress of Neurological Surgeons (CNS), we aimed to illustrate how malpractice lawsuits affect neurosurgeons professionally, emotionally and financially.   MedicalResearch.com: What are the main findings?  Response: Some 490 members of the CNS shared their experiences with us. Among these members, 81% faced a medical malpractice lawsuit. The main concerns expressed about being sued included losing confidence and practicing defensive medicine, personal assets being at risk, and being named in the National Practitioner Data Bank. Of the respondents, 40% stated they were frequently or always concerned about being sued, and 77 % stated their fear had led to a change in how they practice medicine. For 58 %, this change led to the practice of defensive medicine, while for others it led to more extensive documentation (14%) and/or to referring or dropping complex cases (12%). Given the medical malpractice environment, 59% of respondents considered referring complex patient cases, whereas 37% considered leaving the practice of medicine.
Author Interviews, Brigham & Women's - Harvard, COVID -19 Coronavirus, Occupational Health / 03.11.2020

MedicalResearch.com Interview with: Fan-Yun Lan, MD, MS PhD candidate in Population Health Sciences | Environmental Health Graduate School of Arts and Sciences & T.H. Chan School of Public Health Harvard University MedicalResearch.com: What is the background for this study? Response: Existing evidence has indicated that essential workers are heavily affected by the COVID-19 pandemic, as they are not able to benefit from mitigation policies. Their occupational exposures increase their own risk to SARS-CoV-2 infection, and increase the risk of secondary transmissions to their colleagues, families and communities. Research, however, has largely focused on healthcare workers with relatively limited literature investigating non-healthcare essential workers.
Asthma, Author Interviews / 03.11.2020

MedicalResearch.com Interview with: https://www.gsk.com/en-gb/home/Beth Hahn, PhD, Director U.S. Value Evidence and Outcomes, GlaxoSmithKline, Research Triangle Park, NC MedicalResearch.com: What is the background for this study? Response: Biologic therapies are increasing as a treatment for patients with severe asthma, with multiple therapies approved by the FDA.  There is also an increasing understanding of the factors influencing preference for and adherence to biologic therapies for patients with severe asthma; however, little is known about why patients discontinue biologic therapy. In patients who have access to biologic treatment, understanding the circumstances and asthma characteristics associated with discontinuation of biologic therapy may allow for the identification of barriers to treatment success . The objective of this study of cross-sectional physician and patient survey data was to assess the patient characteristics and the given reasons for treatment discontinuation in a US patient cohort with severe asthma treated with biologic therapy. A total of 117 physicians and 285 patients completed surveys with 70% of patients continuing biologic therapy (N=200). This study included a number of different FDA approved biologics. From the perspectives of the physicians included in the current study (85 providing a rationale for discontinuation), the majority reported a lack of symptom control, particularly shortness of breath (46%), exacerbations (26%) and other chronic symptoms (29%), as a key reason for discontinuing biologic therapy in severe asthma. Symptom control was also key for patients, with these three symptom categories among their top six reasons for biologic discontinuation. The cost of biologic treatment was also an important factor, cited as the 5th most common reason for discontinuation among physicians and the 3rd among patients.