Allergies, Author Interviews, Genetic Research, Hepatitis - Liver Disease / 08.09.2020
Polygenic Diagnostic Testing Helps Determine Risk of Drug Induced Liver Disease
MedicalResearch.com Interview with:
[caption id="attachment_55352" align="alignleft" width="200"] Dr. Takebe[/caption]
Takanori Takebe MD
Director for Commercial Innovation, Center for Stem Cell and Organoid Research and Medicine (CuSTOM)
Assistant Professor, University Cincinnati
Department of Pediatrics, Cincinnati Children’s
Professor, Institute of Research
Tokyo Medical and Dental University, Japan
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Drug induced liver injury (DILI) is rare yet highly unpredictable disorder that oftentimes causes drug failure withdrawn from the market during clinical trial even at a very rare incidence of DILI (1/10,000). Indeed, one particular drug TAK875 (Fasigliam) was the case despite promising efficacy. This not only disappoints patient but impact significant financial risk to pharmaceuticals.
In collaboration with DILI genomics consortium at US, EU and UK, we’ve found +20,000 genetic make up (variants) defines potential risk of developing Drug induced liver injury thru amplifying cellular stress signal cascades that were investigated by human cell, organoid and patient datasets.
Dr. Takebe[/caption]
Takanori Takebe MD
Director for Commercial Innovation, Center for Stem Cell and Organoid Research and Medicine (CuSTOM)
Assistant Professor, University Cincinnati
Department of Pediatrics, Cincinnati Children’s
Professor, Institute of Research
Tokyo Medical and Dental University, Japan
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Drug induced liver injury (DILI) is rare yet highly unpredictable disorder that oftentimes causes drug failure withdrawn from the market during clinical trial even at a very rare incidence of DILI (1/10,000). Indeed, one particular drug TAK875 (Fasigliam) was the case despite promising efficacy. This not only disappoints patient but impact significant financial risk to pharmaceuticals.
In collaboration with DILI genomics consortium at US, EU and UK, we’ve found +20,000 genetic make up (variants) defines potential risk of developing Drug induced liver injury thru amplifying cellular stress signal cascades that were investigated by human cell, organoid and patient datasets.
Dr. Auger[/caption]
Katherine A. S. Auger, MD, MSc
Division of Hospital Medicine
James M. Anderson Center for Health Systems Excellence,
Cincinnati Children’s Hospital Medical Center
Department of Pediatrics, University of Cincinnati College of Medicine
Pediatric Research in Inpatient Settings Network
Cincinnati, Ohio
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: All states closed schools in the spring of 2020 to try to mitigate the spread of COVID-19. Our study demonstrated a large, significant association between school closure and fewer COVID-19 cases and deaths even when accounting for other state policies.
Dr. Ellingson[/caption]
Jarrod Ellingson PhD
Assistant Professor
Department of Psychiatry
Anschutz Medical Campus
University of Colorado Denver
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: We know that cannabis use is associated with many negative outcomes, but there could be many of reasons for that. For example, socioeconomic factors and peer influences both affect adolescent cannabis use and poorer cognitive functioning. To account for some of those risk factors, we studied nearly 600 sibling pairs with moderate to heavy cannabis use. We found that, as a person uses more cannabis than their sibling, they tend to have worse memory recall than their sibling.
Kyla Fergason[/caption]
Kyla Fergason
Senior Undergraduate Student
Michael K. Scullin, Ph.D.
Principal Investigator
Baylor University
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: There’s a fairly sizable literature suggesting that religious affiliation and religious engagement are associated with positive health outcomes. Therefore, we were surprised to find that agnostic/atheist individuals reported better sleep health than Christian individuals in the Baylor Religion Survey (BRS-5). 73% of agnostic/atheist individuals reported sleeping 7-9 hours/night whereas only 63% of Christian individuals met these consensus sleep guidelines. The most affected Christian denominations were Baptists (54.6%) and Catholics (62.3%). These results stood even after adjusting for age and gender. We predicted the opposite pattern.
And, it wasn’t just about longer sleep durations. Agnostic/atheist individuals even reported greater ease falling asleep compared to Christian individuals. 
Dr. Glicksberg[/caption]
Benjamin Glicksberg, PhD
Assistant Professor of Genetics and Genomic Sciences
Member of the Mount Sinai COVID Informatics Center
Member of the Hasso Plattner Institute for Digital Healt
Icahn School of Medicine at Mount Sinai
MedicalResearch.com: What is the background for this study?
Response: Reports from health systems that detailed the clinical characteristics and outcomes of their COVID-19 patients were instrumental in helping other health systems rapidly adapt and know what to expect. There are few studies, however, that assess what happens to these patients after they were discharged from the hospital.
In our work, we address this gap by determining both how many individuals re-present to the hospital within 14 days, and what clinical characteristics of these patients differ from those who do not. Such information is critical in order to continue to refine optimal treatment plans and discharge decisions for patients of all backgrounds and clinical profiles. To provide more context to the question, we also determined if and how these factors changed between initial presentation and readmission to the hospital.
Dr. Spitzer[/caption]
Sarabeth Spitzer, MD
Co-Chair of Board, Scrubs Addressing the Firearm Epidemic (SAFE)
Department of Surgery, Brigham and Women’s Hospital
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Firearm injury is a significant cause of morbidity and mortality in the United States, resulting in almost 40,000 deaths annually in the United States, but very little is known about the epidemiology of nonfatal firearm injuries. Nonfatal firearm injuries can have significant long-term morbidity and are associated with significant cost. We found that there were over 81,000 nonfatal firearm injuries in California over the study period. Over the period, there was a decrease in nonfatal firearm injuries by 38.1%, driven primarily by a decrease in assault injuries. 
Dr. Shoaff[/caption]
Jessica Shoaff, MPH, PhD
Postdoctoral Research Fellow and
[caption id="attachment_55259" align="alignleft" width="150"]
Dr. Korrick[/caption]
Susan A. Korrick, MD
Pulmonary and Critical Care
Assistant Professor in the Department of Environmental Health
Harvard Medical School · Harvard T. H. Chan School of Public Health
Brigham and Women's Hospital
Channing Laboratory Boston, MA 02115
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Our study posed the question: Do teenagers’ exposures to chemicals that are often found in consumer products increase behaviors that are common among individuals diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD)? Our results suggest that teenagers exposed to chemicals often found in consumer products (particularly phthalates) may have increased behaviors that are common among individuals diagnosed with ADHD. However, we did not study the diagnosis of ADHD (most of our study teens did not have ADHD). This means our results cannot answer the question of whether these chemical exposures increase the likelihood of being diagnosed with ADHD. Also, in our study design, chemical exposures and ADHD-related behaviors were measured at the same time, so it is not possible to know with certainty whether the chemical exposures altered behavior or behavior altered chemical exposures. 
Dr. Wick[/caption]
Cameron C. Wick, MD
Assistant Professor, Otology/Neurotology
Washington University School of Medicine
St. Louis, MO
MedicalResearch.com: What do you see as the primary message of your findings for the general public?
Response: Older adults not satisfied with their hearing aids achieved clinically meaningful improvement in both hearing and quality of life with a cochlear implant compared to an optimized bilateral hearing aid condition.
MedicalResearch.com: Do you see your findings as changing the way older adults with hearing loss are managed?
Response: Yes and partially because this study is unique in its design and the outcomes that were measured. Specifically the study is a prospective, multicenter clinical trial conducted at 13 locations across the United States. All patients were setup with a 30-day optimized hearing aid experience before cochlear implantation (context: sometimes hearing aids are not appropriately optimized so baseline testing may not reflect the "best" that hearing aids can do). This study assesses both hearing data as well as quality of life data before and 6-months after cochlear implantation. After implantation patients were tested in both the unilateral (cochlear implant alone) and bimodal (cochlear implant plus hearing aid in the opposite ear) conditions. My paper is a subanalysis of adults 65 years and older (range 65 - 91 years) enrolled in the clinical trial. The principal investigator of the clinical trial is Dr. Craig Buchman. Dr. Buchman and myself are at Washington University in St. Louis which was the lead center for the clinical trial.
The findings of the study are meaningful because they demonstrate clear superiority of cochlear implants over hearing aids in many key areas, such as understanding speech, hearing in background noise, and ability to communicate. Hearing loss, which becomes more prevalent as we age, can negatively impact communication leading to social isolation, depression, frustration, and possibly cognitive decline. This study highlights that if patients are not satisfied with their hearing aid performance then they should be referred to a center that can evaluate for cochlear implantation. Cochlear implant indications have evolved considerably since they were first FDA approved in 1984. This study emphasizes that patients do not have to be profoundly deaf to experience significant hearing and social benefits from cochlear implants. Also, it demonstrates that cochlear implant surgery is well tolerated even as adults age and acquire other health ailments. 
Salim S. Virani, MD, PhD, FACC, FAHA, FASPC
Professor, Section of Cardiovascular Research
Director, Cardiology Fellowship Training Program
Baylor College of Medicine
Staff Cardiologist, Michael E. DeBakey Veterans Affairs Medical Center
Co-Director, VA Advanced Fellowship in Health Services Research & Development at the Michael E. DeBakey VA Medical Center, Houston, TX
Investigator, Health Policy, Quality and Informatics Program
Michael E. DeBakey Veterans Affairs Medical Center HSR&D Center of Innovation
Houston, TX @virani_md
MedicalResearch.com: What is the background for this study? What are the main findings? What do you think accounts for the gender differences?
Response: We know that women with ischemic heart disease (IHD) have lower prescription rates for statin and high-intensity statin therapy. In this study, we assessed whether the same trends hold true for women with other forms of atherosclerotic cardiovascular disease (ASCVD) i.e. women with peripheral artery disease (PAD) or ischemic cerebrovascular disease (ICVD). Maximally tolerated statin therapy is a Class-I indication in patients with clinical ASCVD which includes PAD and ICVD.
We also assessed statin adherence among men and women with PAD and ICVD.
Lastly, we performed exploratory analyses to assess whether statin therapy, statin intensity, and statin adherence in women with PAD and ICVD were associated with cardiovascular outcomes and/or mortality. 
Ruth Fernandez-Ruiz, MD
Post-Doctoral Fellow
Department of Rheumatology
NYU Langone Heath
MedicalResearch.com: What is the background for this study?
Response: Patients with systemic lupus erythematosus (SLE) represent a unique population in considering risk for COVID-19 with biologic, genetic, demographic, clinical and treatment issues at play. By the nature of their chronic inflammatory autoimmune condition, the presence of comorbidities, and regular use of immunosuppressants, these individuals would traditionally be considered at high risk of contracting SARS-CoV-2 and possibly having worse outcomes from the viral infection.
However, it might be speculated that inherently elevated type I Interferon, characteristic of the majority of patients with SLE, confers a protective effect as a first line anti-viral defense. Additionally, hydroxychloroquine, which was suggested as a potential therapeutic agent for COVID-19 early on, is used in most patients with SLE. Accordingly, we initiated this study to provide critical data needed to address the frequency and severity of COVID-19 in patients with SLE.
