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Drug induced liver injury (DILI) is rare yet highly unpredictable disorder that oftentimes causes drug failure withdrawn from the market during clinical trial even at a very rare incidence of DILI (1/10,000).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Drug induced liver injury (DILI) is rare yet highly unpredictable disorder that oftentimes causes drug failure withdrawn from the market during clinical trial even at a very rare incidence of DILI (1/10,000).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.
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. 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. 
Dr. Yonker[/caption]
Lael Yonker, MD
Pediatric Pulmonology
Director, MGH Cystic Fibrosis Center
Principal Investigator, Pediatric COVID biorepository
Mucosal Immunology and Biology Research Center
Massachusetts General Hospital
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Children were initially felt to be spared from the COVID-19 pandemic. Here, we show that children can become sick from SARS-CoV-2 infection, and even if the initial illness is mild, some go on to develop a severe inflammatory illness after the initial illness. We also show that children can carry very high levels of virus early in the course of infection, suggesting they may play a larger role in spreading the virus than previously thought.
Dr. Trudo[/caption]
Frank Trudo, MD MBA
Vice President, US Medical Affairs
Respiratory & Immunology
AstraZeneca
MedicalResearch.com: What is the background for this study?
Response: ETHOS was a randomized, double-blinded, multi-center, parallel-group, 52-week trial to assess the efficacy and safety of PT010 in symptomatic patients with moderate to very severe COPD and a history of exacerbation(s) in the previous year. A subset of patients participated in the 4-hour pulmonary function test (PFT) sub-study, with the following primary endpoints: change from baseline in morning pre-dose trough FEV1 at Week 24 at (both doses of budesonide/glycopyrrolate/formoterol fumarate MDI versus glycopyrrolate/formoterol fumarate MDI), and FEV1 area under the curve from 0-4 hours at Week 24 (both doses of budesonide/glycopyrrolate/formoterol fumarate MDI vs budesonide/formoterol fumarate MDI). 
Dr. Jimenez[/caption]
Monik Carmen Jimenez, Sc.D
Assistant Professor of Medicine
Brigham and Women's Hospital
MedicalResearch.com: What is the background for this study?
Response: We wanted to get a comprehensive picture of the epidemiology of COVID-19 in carceral facilities that included jails and was not restricted solely to prisons. We utilized publicly available data collected in Massachusetts, pursuant to a court order. These data included prison and jail systems and were used to calculate rates of confirmed cases of COVID-19 and testing rates among incarcerated individuals. We were also able to compare those to changes in the population size within each system.
Dr. Ratnasiri[/caption]
Anura Ratnasiri PhD
Senior Research Scientist
(Epidemiology and Biostatistics) Benefits Division
Department of Health Care Services
Sacramento, CA 95899-7417
MedicalResearch.com: What is the background for this study?
Response: Infant mortality rate (IMR) is a widely-reported indicator of population health and is used as a standardized measurement of deaths in the first year of life per thousand live births. While IMR has been steadily declining in the United States, it remains relatively high compared with other developed countries.
Even though significant improvements have been made in the quality and access to neonatal and infant care during the past decade, large educational, socioeconomic, racial, ethnic, geographic and behavioral disparities persist, and appear to be responsible for significant differences in IMR among different subgroups. Certain maternal and infant characteristics have important associations with IMR, and this study attempted to quantify major maternal and infant predictors, and trace associated mortality trends during the study period.
There were no recent studies on infant mortality using a large data set such as California State. Moreover, gestational age based on obstetric estimates from fetal ultrasound, prepregnancy obesity, and smoking during pregnancy were not available in prior population-based studies in California.
Dr. Walline[/caption]
Jeffrey J. Walline, OD PhD
Associate Dean for Research
The Ohio State University
Columbus, OH 43210-1240
MedicalResearch.com: What is the background for this study?
Response: Greater amounts of nearsightedness are related to higher risks of sight-threatening complications in adulthood, so anything we can do to slow the progression of nearsightedness in childhood can have meaningful benefits in the future.
As the prevalence of nearsightedness increases worldwide and affects approximately 1/3 of the people in the United States, a treatment that provides clear vision AND slows the progression of nearsightedness can have a profound effect.
Dr. Amy Kennedy, M.D., M.S
Clinician-Researcher Fellow, General Internal Medicine
University of Pittsburgh
MedicalResearch.com: What is the background for this study?
Response: UPMC uses a nucleic acid polymerase chain reaction (PCR) test for SARS-CoV-2 and specimen collection is done with a nasopharyngeal swab by trained clinicians. The health system developed its COVID-19 test in early March 2020 in anticipation of the tremendous need for diagnostic capabilities.
My colleagues and I worked with the Wolff Center at UPMC — the health system’s quality care and improvement center — to review the results of more than 30,000 COVID-19 tests performed on adult patients who received care through one of UPMC’s 40 academic, community and specialty hospitals, or 700 doctors’ offices and outpatient sites in Pennsylvania, New York and Maryland. The tests were performed between March 3 and May 3, 2020. Of those tests, 485 were repeated at least once.