Author Interviews, Duke, Gastrointestinal Disease, Nature, Sugar / 17.01.2022

MedicalResearch.com Interview with: Laura Rupprecht, PhD Postdoctoral Fellow Kelly L Buchanan The Laboratory of Gut Brain Neurobiology Duke Medicine – GI Diego V. Bohórquez PhD Associate Professor in Medicine Duke Institute for Brain Sciences Durham, NC MedicalResearch.com:  What is the background for this study?  What are the main findings? Response: In 2018, my laboratory discovered that a cell type in the gut epithelium synapses with the vagus nerve, the nerve which connects the gut and the brain. These gut cells are called neuropod cells. Neuropod cells transduce sugar within milliseconds using the neurotransmitter glutamate. Since then, we have been interested in defining how this rapid communication between neuropod cells and the brain regulates behavior. – Diego Bohórquez Over a decade ago, it was shown that the gut is the key site for discerning sugar and non-caloric sweetener. But the specific cell in the gut that underlies this effect was unknown. – Kelly Buchanan   (more…)
Author Interviews, Duke, JAMA, Nursing, Sexual Health, STD / 12.08.2021

MedicalResearch.com Interview with: Vincent Guilamo-Ramos, PhD MPH, LCSW, RN, ANP-BC, PMHNP-BC, AAHIVS, FAAN Vincent Guilamo-Ramos is dean and professor at the Duke University School of Nursing, vice chancellor for nursing affairs, Duke University, and director of the Center for Latino Adolescent and Family Health (CLAFH) at Duke. Dr. Guilamo-Ramos served as a member of the National Academies of Sciences, Engineering, and Medicine (National Academies) Committee on Prevention and Control of STIs in the U.S. that wrote the recent consensus study report. He also serves as a member of the Presidential Advisory Council on HIV/AIDS (PACHA) and the HHS Panel on Antiretroviral Guidelines for Adults and Adolescents. MedicalResearch.com: What is the background for this study? Response: The National Academies of Sciences, Engineering, and Medicine (National Academies) recently released a consensus study report on prevention and control of sexually transmitted infections (STIs) in the United States. The report entitled “Sexually Transmitted Infections: Adopting a Sexual Health Paradigm” includes a strong emphasis on adolescents and young adults as an important priority population for the response to record-level STI rates that have reached an all-time high for the sixth year in a row in 2019. The report also highlights the well-supported and crucial role of parents in addressing STIs and promoting sexual health among adolescents and young adults. In this new Viewpoint article, my co-authors and I, who contributed to the National Academies report as committee members or consultants, discuss the practical implications for health care professionals of engaging parents in adolescent sexual health services. (more…)
Author Interviews, Duke, Electronic Records, Health Care Systems, JAMA / 20.04.2021

MedicalResearch.com Interview with: Eugenia McPeek Hinz MD MS FAMIA Associate CMIO - DHTS Duke University Health System MedicalResearch.com: What is the background for this study? Response: Clinician burnout rates have hovered around 50% for much of the past decade.  Burnout is a significant concern in healthcare for its effects on care givers and associated downstream adverse implications on patient care for quality and safety. The ubiquitous presence of Electronic Health Records (EHR) along with the increased clerical components and after hours use has been a significant concern for contributing to provider burnout.  (more…)
Author Interviews, Diabetes, Duke, Telemedicine / 15.06.2020

MedicalResearch.com Interview with: Matthew J. Crowley, MD Core Investigator, Durham Center of Innovation to Accelerate Discovery and Practice Transformation (ADAPT) Affiliated Investigator, VA Office of Rural Health Staff Physician, Endocrinology Section, Durham VA Health Care System Elizabeth Kobe, BS Medical Student Durham VA Health Care System Duke University School of Medicine MedicalResearch.com: What is the background for this study? With whom were the telehealth sessions performed? (MDs, PAs, Dieticians etc). Response: Diabetes management in rural populations is especially challenging due to limited access to specialty care and self-management programs. Telehealth is a potential strategy for extending high-quality diabetes care to rural areas. The Veterans Health Administration (VHA) has a robust Home Telehealth (HT) system that is currently used for telemonitoring patient blood glucose values. In order to address the challenges of managing diabetes in rural areas in a clinically feasible manner, we strategically designed an intensive diabetes management intervention – Advanced Comprehensive Diabetes Care (ACDC) – for delivery using existing VHA HT infrastructure and clinical staffing. ACDC is a 6-month telehealth intervention that combines telemonitoring with module-based self-management support and medication management. ACDC is delivered entirely by existing clinical staff (a clinical HT nurse and a medication manager (typically a PharmD)) through bimonthly, 30-minute calls. Our initial randomized controlled trial found that ACDC improved HbA1c by a clinically and statistically significant  -1.0% relative to usual care at 6 months, while also improving blood pressure and diabetes self-care. Our goal with the present work was to improve diabetes care in clinical practice for rural Veterans whose type 2 diabetes remained uncontrolled despite receiving available services. To this end, we partnered with the VA Office of Rural Health to implement ACDC into VA sites across the country with large rural populations.  (more…)
Author Interviews, COVID -19 Coronavirus, Duke / 27.03.2020

MedicalResearch.com Interview with: Dr. Rupesh Agrawal, MD Associate Professor Senior Consultant Ophthalmologist Duke-NUS Medical School, Singapore MedicalResearch.com: What is the background for this study? Wasn't Dr Li Wenliang, the Chinese physician who first alerted his community of coronavirus an opthalmologist, with possible exposure to tears from this surgical work with glaucoma patients? Response: Since the start of the pandemic, there have been multiple reports which suggested the transmission of SARS-CoV-2 via ocular fluids. As ophthalmologists, we come into close contact with tears on a daily basis during our clinical examination. Furthermore, many equipment in the clinic like the Goldman tonometer come into direct contact with such ocular fluids, providing a channel for viral transmission. The evidence, as of date, were mainly anecdotal reports included in newspaper articles and media interviews. We wanted to know if the virus can truly be found in tears, so we decided to embark on this study. (more…)
Author Interviews, Blood Pressure - Hypertension, Duke, Pediatrics / 22.01.2020

MedicalResearch.com Interview with: Yuichiro Yano MD Assistant Professor in Family Medicine and Community Health Duke University  MedicalResearch.com: What is the background for this study? Response: The blood pressure (BP) guideline in the US recommend using an “average” of multiple BP measurements over time for screening for and management of high BP in young adults. While it is well known that BP varies across visits, that “variability” (i.e., visit-to-visit blood pressure variability) is dismissed as a random fluctuation in the clinical setting. Little is known regarding the clinical relevance of visit-to-visit blood pressure variability over time in young adults. (more…)
Alzheimer's - Dementia, Author Interviews, Cognitive Issues, Duke, Neurology / 24.09.2019

MedicalResearch.com Interview with: Juan Helen Zhou, PhD, on behalf of the co-authors Associate Professor and Principal Investigator Neuroscience and Behavioural Disorders (NBD) Programme Duke-NUS Medical School, SingaporeJuan Helen Zhou, PhD, on behalf of the co-authors Associate Professor and Principal Investigator Neuroscience and Behavioural Disorders (NBD) Programme Duke-NUS Medical School, Singapore  MedicalResearch.com: What is the background for this study? Response: Alzheimer’s disease and cerebrovascular disease are among the leading disorders affecting the elderly, with up to 50 per cent of dementia patients showing co-occurrence of both disorders. It is therefore of great interest to understand the influence of co-occurring Alzheimer’s disease and cerebrovascular disease pathologies on brain changes, and examine if such changes are able to track early differential disease progression. Past cross-sectional studies have suggested that Alzheimer's disease and cerebrovascular disease pathologies contribute independently to brain functional and structural changes, and cognitive decline. Our study sought to demonstrate the independent contributions of both pathologies to brain functional networks in a longitudinal cohort of mild cognitive impairment patients, often regarded as early stage of the disease. (more…)
Author Interviews, Dengue, Duke, Vaccine Studies / 21.09.2019

MedicalResearch.com Interview with: Dr Shee-Mei Lok, PhD Professor in the Emerging Infectious Disease program Duke-NUS, a school of National University of Singapore MedicalResearch.com: What is the background for this study? Response: Dengue virus consists of four different serotypes (DENV1-4) and within each serotypes, there are multiple strains. In terms of the viral particle shape, our previous research work using some laboratory adapted strains showed these DENV2 strains are very interesting in that it can change shape from the smooth spherical surface particles when grown at mosquito physiological temperature (29oC) and then becomes bumpy surfaced particles when incubated at human physiological temperature (37oC). This ability to transform into different virus surface structures helps the virus to escape from the immune system of the human host. Hence understanding the mechanism of how this occur is important for therapeutics and vaccine development. Here we also identified a laboratory adapted virus strain that do not showed this structural changes. We showed some differences in their amino acid sequences and We showed some differences in their amino acid sequences and mutating these residues coupled with observing their surface structures showed which residues are important for this temperature induced structural change. Results showed that subtle mutations at different places on the envelope protein can destabilize the virus allowing them to change in structure when temperature is elevated. Due to the poor selection pressure of the artificial laboratory tissue culture system, gradual mutations of the virus is accumulated causing the virus to have bumpy surface morphology. (more…)
Author Interviews, Blood Pressure - Hypertension, Duke, Heart Disease, JAMA, Race/Ethnic Diversity / 14.08.2019

MedicalResearch.com Interview with: Yuichiro Yano MD Assistant Professor in Family Medicine and Community Health Duke University  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: African Americans are disproportionally affected by hypertension-related cardiovascular disease compared with other racial/ethnic groups in the United States and have higher blood pressure levels inside and outside the clinic than whites and Asians. However, little is known, among African Americans, regarding whether higher mean blood pressure measured outside of the clinic setting on 24-hour ambulatory blood pressure monitoring is associated with an increased risk for cardiovascular disease events, independent of blood pressure measured in the clinic setting. (more…)
Author Interviews, Dermatology, Duke / 15.07.2019

MedicalResearch.com Interview with: Luis Garza, M.D., Ph.D. Associate Professor of Dermatology Johns Hopkins University School of Medicine. MedicalResearch.com: What is the background for this study? What are the main findings? Response: We wanted to find out what might stimulate regeneration in mice and humans. We find that in both species during wounding, released “loose” dsRNA induces production of retinoic acid that stimulates regeneration. (more…)
Author Interviews, Clots - Coagulation, Duke, Genetic Research, Heart Disease, JAMA / 30.05.2019

MedicalResearch.com Interview with: Thomas J. Povsic, MD, PhD Interventional Cardiologist Duke Clinical Research Institute Duke University School of Medicine Durham, North Carolina  MedicalResearch.com: What is the background for this study?  Response: The background for this study is that it is unknown how mandatory reporting of CYP2C19 metabolizer status affects how doctors treat patients or to what degree provision of this information would affect choice of a P2Y12 inhibitor within a clinical trial. As part of the GEMINI-ACS trial, all patients underwent CYP2C19 metabolizer testing.  This trial enrolled patients with a recent acute coronary syndrome and randomized them to aspirin or a low dose of rivaroxaban.  All patients were also to be treated with ticagrelor or clopidogrel, which was at the discretion of the investigator.  Investigators were given information regarding the CYP2C19 metabolizer status about a week after randomization.  Importantly prior to randomization, all investigators were asked how they expected to use this information, and then we followed what they actually did. (more…)
Anesthesiology, Author Interviews, Duke, OBGYNE, Opiods, Pain Research, Surgical Research / 29.05.2019

MedicalResearch.com Interview with: Ashraf Habib, MDChief of the Division of Women’s Anesthesia and Professor of AnesthesiologyDuke University Ashraf Habib, MD Chief of the Division of Women’s Anesthesia Professor of Anesthesiology Duke University  MedicalResearch.com: What is the background for this study? What are the main findings? Response: This was a multicenter study conducted in 13 clinical sites in the United States enrolling patients undergoing elective Cesarean-section and receiving spinal anesthesia. 186 patients were enrolled and randomized to receive EXPAREL, a long-acting, non-opioid option to manage postsurgical pain, administered via transversus abdominis plane (TAP) field block, mixed with plain bupivacaine or TAP block with plain bupivacaine alone. A TAP block numbs the nerves that supply the abdominal wall. We presented the data at the 51st Annual Meeting of the Society of Obstetric Anesthesia and Perinatology (SOAP) in Phoenix, AZ. We aimed to collect clinical evidence that a multimodal postsurgical pain regimen using a TAP block with EXPAREL (bupivacaine liposome injectable suspension) together with regularly scheduled acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) could reduce opioid consumption more so than a standard multimodal pain control approach that combines TAP block with standard bupivacaine, regularly scheduled acetaminophen, and NSAIDs. (more…)
Author Interviews, Duke, Endocrinology, Environmental Risks, Thyroid Disease, Weight Research / 27.03.2019

MedicalResearch.com Interview with: Christopher D. Kassotis, Ph.D. NRSA Postdoctoral Research Scholar Stapleton Lab Duke University Nicholas School of the Environment Durham, NC 27708  MedicalResearch.com: What is the background for this study? What are the main findings?
  • So this was something that Heather Stapleton had been curious about for years, as she's been one of several researchers characterizing the hundreds of chemicals that have been measured in indoor house dust. Before I came to Duke, one of her PhD students had measured the ability of many common indoor contaminants to activate the peroxisome proliferator activated receptor gamma (PPARg). The majority of these chemicals did, often quite well, which led to them testing indoor house dust extracts, also finding that the majority of dust extracts were also able to do so at very low levels. As PPARg is often considered the master regulator of fat cell development, the next obvious question was whether these common contaminants (and house dust) could promote fat cell development in cell models. My first work at Duke evaluated a suite of common indoor contaminants, finding that many of these chemicals could promote fat cell development, and that low levels of house dust extracts did as well.
  • We next explored this more systematically in a group of adults involved in a thyroid cancer cohort (this was just recently published in Science of the Total Environment: https://www.sciencedirect.com/science/article/pii/S0048969719307715?dgcid=author
  • In this study we evaluated the extent to which house dust extracts could promote fat cell development in a common cell model, and associated this with the metabolic health of adults living in these homes. We found that the greater extent of fat cell development was associated with significantly greater thyroid stimulating hormone concentrations (control residents only, with no evidence of thyroid dysfunction) and lower free triiodothyronine (T3) and thyroxine (T4). We further found a significant and positive association between extent of fat cell development and the body mass index (BMI) of all adults in the study. So this suggested that the indoor environment might play a role in the BMI and metabolic health of residents, and we next wondered if this would be more pronounced in children, who may be exposed to these contaminants during a critical window of development.
  • The next step, for our current work, was to substantiate these effects in a larger group of households, each with children.
  • Our major conclusions thus far have been that ~80% of house dust extracts promote significant fat cell development in a cell model - either via development from precursor cells into mature fat cells, measured via accumulation of lipids into the cells, or via the proliferation of those precursor fat cells. We also reported positive correlations of fat cell development with the concentrations of 70 different contaminants in the dust from these homes, suggesting that mixtures of contaminants are likely all acting weakly to produce these effects in combination. We’ve also begun to assess the other chemicals present in dust - chemistry can be either targeted (measuring concentrations of specific known chemicals in a sample), or non-targeted, where you try and determine the identity of the other chemicals in a sample. This has greater utility for identifying many more chemicals, though you will often not get chemical concentrations from this, nor absolute confirmed identification - just varying degrees of certainty based on evidence. Thus far we report approximately 35,000 chemicals in house dust samples across this study, and differential analyses have begun to pick out the few (less than 10 in each case) chemicals most differentially expressed between samples that exhibit high degrees of fat cell development in the lab vs inactive samples, for example, or which are differentially present in the homes of children categorized as obese or overweight. We are now working to confirm identity of these select contaminants that are more likely to be causative factors in the results we have observed.
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Author Interviews, Clots - Coagulation, Duke, Heart Disease, NEJM / 21.03.2019

MedicalResearch.com Interview with: Renato D. Lopes MD, MHS, PhD Professor of Medicine Division of Cardiology Duke University Medical Center Duke Clinical Research Institute MedicalResearch.com: What is the background for this study? What are the main findings? Response: In patients with acute coronary syndromes (ACS), approximately 20% to 30% of those with nonvalvular atrial fibrillation (NVAF) have concomitant coronary artery disease (CAD), and 5 to 10% of patients who undergo PCI have NVAF. These patients often receive both antiplatelet therapy and oral anticoagulants; and how best to combine these agents to minimize bleeding risk without compromising protection against thrombosis is an important unanswered question. Analysis of results for bleeding indicated no significant interaction between the two randomization factors permitting independent analysis of results for the two key comparisons. The first showed that apixaban was both non-inferior and significantly superior to VKA for the primary outcome with a 31% reduction in the relative risk for bleeding. Aspirin significantly increased the relative risk for bleeding versus placebo by 89%. Results for the composite of death and hospitalization showed that apixaban resulted in a relative risk reduction of 17%, primarily driven by a reduction in all cause hospitalization. There was no significant difference between results for aspirin versus placebo for this outcome. Analysis of the composite of death and ischemic events indicated no significant differences in results for apixaban versus VKA or aspirin versus placebo. (more…)
Author Interviews, Duke, Heart Disease, JAMA / 21.03.2019

MedicalResearch.com Interview with: Renato D. Lopes MD, MHS, PhD Professor of Medicine Division of Cardiology Duke University Medical Center Duke Clinical Research Institute Alexander C. Fanaroff, MD, MHS Division of Cardiology and Duke Clinical Research Institute Duke University, Durham, North Carolina MedicalResearch.com: What is the background for this study? What are the main findings? Response: About ten years ago, a group of researchers examined the evidence supporting guideline recommendations in cardiology for the first time. Quite surprisingly, they found that only 11% of recommendations in American College of Cardiology/American Heart Association (ACC/AHA) guidelines were supported by evidence from randomized controlled trials, the highest level of evidence. The researchers called for greater collaboration among investigators and funders in identifying key research questions, development of streamlined clinical trial methods, and expansion of funding for clinical research. Over the past 10 years, some of these steps have been taken, but it is unclear how the evidence supporting guideline recommendations has changed. We therefore analyzed the 51 current cardiovascular guideline documents -- 26 from the ACC/AHA and 25 from the European Society of Cardiology (ESC) -- including 6,329 recommendations. Overall, 8.5% of recommendations in ACC/AHA guidelines and 14.3% of recommendations in ESC guidelines were supported by evidence from randomized controlled trials. When looking specifically at guidelines that have been updated, we found no significant changes in the proportion of recommendations supported by evidence from randomized controlled trials. (more…)
Author Interviews, Duke, JAMA, Mental Health Research, Pediatrics, Toxin Research / 23.01.2019

MedicalResearch.com Interview with: Aaron Reuben, MEM Department of Psychology and Neuroscience Duke University, Durham, North Carolina MedicalResearch.com: What is the background for this study? What are the main findings? (1)  Study members with greater lead exposure in childhood tended to endorse more psychiatric symptoms when assessed for psychiatric disorders in adulthood (between 18 and 38 years of age).
  1. These individuals tended to report more internalizing (e.g., depression, anxiety) and thought disorder (e.g., OCD, schizophrenia, mania) symptoms.
  2. Compared to other findings from this sample, the associations reported in this article are similar to those reported for lead and IQ, and are stronger than those reported for lead and criminal offending.
    1. Informants who knew Study members well reported higher levels of difficult adult personality traits among Study members with greater lead exposure in childhood.
    2. Specifically, Study members with greater blood lead levels at age 11 were rated as more neurotic, less agreeable, and less conscientious by 38 years of age.
    3. These personality traits have been previously linked to a number of poor life outcomes, including greater psychopathology, worse physical health, less job satisfaction, and troubled interpersonal relationships
  3. Psychiatric problems related to lead exposure could be detected as early as 11 years of age. In the 1980’s, parents and teachers of children with higher blood-lead levels had described them as displaying more antisocial behavior, hyperactivity, and negative emotions (e.g., sadness, anxiety).
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Author Interviews, Blood Pressure - Hypertension, Duke, Heart Disease, JAMA / 05.12.2018

MedicalResearch.com Interview with: Taku Inohara MD, PhD Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina Department of Cardiology Keio University School of Medicine, Tokyo, Japan MedicalResearch.com: What is the background for this study? What are the main findings? Response: Transcatheter aortic valve replacement (TAVR) has been increasingly used for treating patients with severe aortic stenosis. Owing to the advancement of TAVR technology, the mortality and heart failure (HF) readmission after TAVR is decreasing over time, but 4.3% experienced readmission due to HF and 23.7% died within 1 year after TAVR. Inhibition of the renin-angiotensin system (RAS) with angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin-receptor blockers (ARBs) is known to improve clinical outcomes in patients with heart failure, but there remains unknown whether a RAS inhibitor is associated with a reduction in mortality and heart failure readmission after TAVR. Using the STS/ACC TVT Registry, a nationwide TAVR Registry in the US, we analyzed 15896 propensity-matched patients who underwent TAVR and found that receiving a prescription for a RAS inhibitor at discharge, compared with no prescription, was associated with a reduced risk for mortality ( 12.5% vs 14.9%) and HF readmission (12.0% vs 13.8%). (more…)
Author Interviews, Cost of Health Care, Duke, Geriatrics, Hearing Loss, Hospital Readmissions, JAMA / 08.11.2018

MedicalResearch.com Interview with: Nicholas S. Reed, AuD Assistant Professor | Department of Otolaryngology-Head/Neck Surgery Core Faculty | Cochlear Center for Hearing and Public Health Johns Hopkins University School of Medicine Johns Hopkins University Bloomberg School of Public Health MedicalResearch.com: What is the background for this study? Response: This study was a true team effort. It was funded by AARP and AARP Services, INC and the research was a collaboration of representatives from Johns Hopkins University, OptumLabs, University of California – San Francisco, and AARP Services, INC. Given all of the resent research on downstream effects of hearing loss on important health outcomes such as cognitive decline, falls, and dementia, the aim was to explore how persons with hearing loss interacted with the healthcare system in terms of cost and utilization. MedicalResearch.com: What are the main findings? Response: Over a 10 year period, untreated hearing loss (hearing aid users were excluded from this study as they are difficult to capture in the claims database) was associated with higher healthcare spending and utilization. Specifically, over 10 years, persons with untreated hearing loss spent 46.5% more, on average, on healthcare (to the tune of approximately $22000 more) than those without evidence of hearing loss. Furthermore, persons with untreated hearing loss had 44% and 17% higher risk for 30-day readmission and emergency department visit, respectively. Similar relationships were seen across other measures where persons with untreated hearing loss were more likely to be hospitalized and spent longer in the hospital compared to those without evidence of hearing loss. (more…)
Author Interviews, Blood Pressure - Hypertension, Duke, Heart Disease, JAMA / 06.11.2018

MedicalResearch.com Interview with: Yuichiro Yano MD PhD Assistant Professor in Community and Family Medicine Duke University MedicalResearch.com: What is the background for this study? Response: New blood pressure guidelines, issued in 2017 in the US, lowered the blood pressure thresholds for hypertension from systolic blood pressure/diastolic ≥140/90 mm Hg to systolic/diastolic ≥130/80 mm Hg. This change increased the prevalence of hypertension two- to three-fold among young adults. The guidelines also newly defined elevated blood pressure as, 120-129 mmHg systolic blood pressure over 80 mmHg diastolic or less. However, no study investigated that high blood pressure, as defined by the new criteria, is something that younger people should be concerned about as a potential precursor to serious problems. Our study is among the first to report that people younger than age 40 who have elevated blood pressure or hypertension are at increased risk of heart failure, strokes and blood vessel blockages as they age. (more…)
Author Interviews, Duke, Genetic Research, Neurology, Pediatrics / 30.07.2018

MedicalResearch.com Interview with:  Paul C Marcogliese, Ph.D. Postdoctoral Associate, Laboratory of Dr. Hugo Bellen Department of Molecular and Human Genetics Baylor College of Medicine Houston, Texas 77030 Loren D. Pena, MD PhD Division of Human Genetics Cincinnati Children's Hospital Medical Center Department of Pediatrics University of Cincinnati Cincinnati, OH 45229 MedicalResearch.com: What is the background for this study? What are the main findings? Response: The Undiagnosed Diseases Network (UDN) is a multi-site collaboration across the US that seeks to help diagnose patients with rare disorders that are ill-defined. Dr. Loren D.M. Pena and Dr. Vandana Shashi at the Duke-Columbia clinical site of the UDN had seen a patient with a severe neurological disorder. While the patient had no symptoms at birth, the patient began falling at about 3 years of age, eventually losing motor coordination and developing seizures. In the interim, the regression has progressed to a severely debilitating state. Re-analysis of the participant’s exome data by our site bioinformatician at Columbia (Nicholas Stong) in Dr. David Goldstein’s laboratory revealed a truncating variant in the single exon gene IRF2BPL that could be the candidate disease-causing gene. The UDN clinicians at Duke then contacted the UDN Model Organism Screening Center (MOSC) led by Dr. Hugo Bellen at Baylor College of Medicine and the Howard Hughes Medical Institute for functional analysis. In parallel, four more patients were found with truncating mutations causing a similar disorder though the UDN and GeneMatcher.org. Additionally, two patients with missense variants in IRF2BPL were identified that displayed seizures and some developmental delay or autism spectrum disorder but no motor regression. Work in MOSC by Dr. Paul Marcogliese using fruit flies revealed that the IRF2BPL truncating variants are severe loss of function mutations and one of the missense variants was a partial loss of function. Additionally, it was found that the fruit fly IRF2BPL gene, called pits, is expressed in the neurons of the adult fly brain. Lowering the levels of pits by about 50% in fly neurons leads to progressive behavioural abnormalities and neurodegeneration. By combining the human genetics, bioinformatics and model organism data, IRF2BPL was found to be a novel disease-causing gene in humans. (more…)
Author Interviews, Duke, JAMA, Schizophrenia / 26.07.2018

MedicalResearch.com Interview with: Richard Keefe PhD Professor in Psychiatry and Behavioral Sciences Duke Institute for Brains Sciences MedicalResearch.com: What is the background for this study? What are the main findings? Response: A lot of studies have shown that cognitive deficits are present in young people at risk for psychosis. There have been calls for investigations of the idea that cognition declines over time in the young people who are at highest risk, but longitudinal studies are hard to conduct so not much work has been done to address this question. The main finding from our study is that the cognitive architecture – the way the various aspects of cognitive functioning appear to be organized in each individual’s brain based upon their pattern of performance – changes over time in those young people who are in the midst of developing psychosis. Interestingly, cognitive architecture also becomes more disorganized in those whose high-risk symptoms do not remit over a two year period, and is related to the functional difficulties they may be having. The young people whose high risk symptoms were present at the beginning of the study but remitted later actually improved cognitively over the two year period of the study. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Cancer Research, Duke, Immunotherapy, NEJM, Vaccine Studies / 26.06.2018

MedicalResearch.com Interview with: Annick Desjardins, M.D., F.R.C.P.C. Associate Professor of Neurology Associate Professor of Neurosurgery Director of Clinical Research The Preston Robert Tisch Brain Tumor Center at Duke Duke University School of Medicine Durham, NC 27710 MedicalResearch.com: What is the background for this study? What are the main findings? Response: The poliovirus receptor (CD155) is an onco-fetal cell adhesion molecule with widespread expression in all solid tumors and particularly in primary CNS tumors (adult and pediatric). Recombinant nonpathogenic polio–rhinovirus chimera (PVSRIPO) was generated by replacing a critical piece of the genetic information from the Sabin type 1 polio vaccine, making PVSRIPO incapable of harming or killing normal brain cells, but toxic/lethal in cancer cells. In preclinical models, it has been demonstrated that the infection of tumor cells, leads to the release of danger signals, which triggers a recruitment of dendritic/CD4/CD8 T cells and a destruction of tumor cells by anti-tumor T cells. The manuscript reports the results of the phase 1 trial of PVSRSIPO in recurrent WHO grade IV malignant glioma patients. Adult patients with recurrence of a single glioblastoma lesion, 1-5.5cm in dimension, in a non-eloquent area of the brain, were enrolled on study. PVSRIPO is injected slowly over 6.5 hours directly into the tumor via a small catheter inserted via a small bur hole. Once intratumoral injection is completed, the catheter is removed and patients are observed for localized tumor inflammation, followed by tumor contraction. A total of 61 patients were treated on study, 9 patients in a dose escalation phase and 52 in a dose expansion phase. Side effects observed were in relation to the localized inflammation of the tumor and depending on the cerebral functions in close proximity to the tumor: headaches, visual field changes, hemiparesis, etc. One patient experienced a brain hemorrhage at the time of catheter removal, which triggered right sided weakness and aphasia. The patient remained alive 57.5 months after PVSRIPO infusion at data cutoff of March 20th, 2018. Two on-study death were observed, a patient died from cerebral edema and seizures, which was later found to be due to tumor progression, and one patient died from the complications of an intracranial hemorrhage while receiving anticoagulation and bevacizumab. The median overall survival among all 61 patients who received PVSRIPO was 12.5 months (95% CI, 9.9 to 15.2), comparatively to 11.3 months (95% CI, 9.8 to 12.5) in a historical control group of patients treated at Duke and who would have met eligibility on trial, would have the trial been available to them. At 24 months, the survival plateaued in patients treated with PVSRIPO with an overall survival rate of 21% (95% CI, 11 to 33) at 24 months and 36 months in PVSRIPO treated patients, while overall survival in the historical control group continued to decline, with an overall survival rates of 14% (95% CI, 8 to 21) at 24 months and 4% (95% CI, 1 to 9) at 36 months in the historical control group.  (more…)
Author Interviews, Duke, Heart Disease, JAMA, Lipids, Race/Ethnic Diversity, Statins / 14.06.2018

MedicalResearch.com Interview with: Michael G. Nanna, MD Fellow, Division of Cardiology Duke University Medical Center Durham, NC MedicalResearch.com: What is the background for this study? Response: We know that African Americans are at higher risk for cardiovascular disease than white patients. We also know that African American individuals have been less likely to receive statin therapy compared to white individuals in the past. However, the reasons underlying these racial differences in statin treatment are poorly understood. We set out to determine if African American individuals in contemporary practice are treated less aggressively than whites and, if so, we wanted to investigate potential reasons why this might be the case. (more…)
Author Interviews, Duke, Education, Heart Disease, JAMA / 01.06.2018

MedicalResearch.com Interview with: Pamela S. Douglas, MD, MACC, FASE, FAHA Ursula Geller Professor of Research in Cardiovascular Disease Duke University School of Medicine Durham, NC 27715     MedicalResearch.com: What is the background for this study? What are the main findings? Response: For any profession to succeed, it needs to attract top talent. We surveyed internal medicine residents to find out what they valued most in their professional development, how they perceived cardiology as field and how these two areas are associated with  their choosing a career in cardiology or another specialty. We found that trainees were seeking careers that had stable hours, were family friendly and female friendly, while they perceived cardiology to  have adverse work conditions, interfere with family life and to not be diverse. We were able to predict career choice with 89-97% accuracy from these responses; the predictors are mix of things that attract to cardiology and those that are deterrents. For men, the attractors outnumber the deterrents, for women its just the opposite. (more…)
Author Interviews, Duke, Mental Health Research / 21.05.2018

MedicalResearch.com Interview with: Maxwell Elliott Clinical psychology PhD student Working with Ahmad Hariri and the Moffitt & Caspi lab Duke University MedicalResearch.com: What is the background for this study? What are the main findings? Response: The traditional clinical science model identifies individuals who meet specific criteria for mental illness diagnoses (e.g. Depression, Anxiety) and compares them to “healthy” controls to find brain correlates of mental illness.  However, this approach often overlooks the high rates of comorbidity and shared symptamatology across mental illnesses. Emerging research has identified a general factor of psychopathology that accounts for shared risk among internalizing, externalizing, and thought disorders across diverse samples. This general factor of psychopathology has been called the p-factor. In our study we investigate the brain correlates of the p-factor using a data-driven analysis of resting state functional connectivity. We find that higher p-factor scores and associated risk for common mental illness maps onto hyper-connectivity between visual association cortex and both frontoparietal and default mode networks. (more…)
Author Interviews, Diabetes, Duke, Heart Disease / 14.03.2018

MedicalResearch.com Interview with: Stephen J. Greene, MD Division of Cardiology Duke University Medical Center Durham, NC MedicalResearch.com: What is the background for this study? What are the main findings? Response: In 2008, the United States FDA issued an industry guidance specifying that diabetes drugs should routinely be tested in large cardiovascular outcome trials to confirm cardiovascular safety. The guidance specifically mentioned cardiovascular safety in terms of MACE, or major adverse cardiac events, including cardiovascular death, myocardial infarction, and stroke.  Largely because of this, these trials have traditionally had a focus on cardiovascular disease in terms of atherosclerotic events. Heart failure was not mentioned in the FDA document and these trials have had a lesser focus on it. As the years have gone by, we have learned more and more about the connection between diabetes and heart failure. There is tremendous overlap between the two patient populations. Also, as more and more of the large cardiovascular outcome trials have been completed, we have seen multiple examples of various glucose lowering therapies either increasing or decreasing risk of heart failure events. Given all these data on heart failure/ diabetes interactions, the goal of our research was to carefully examine all of the completed large cardiovascular outcome trials of diabetes therapies to systematically describe the type of heart failure-related data they capture. As an initial step in improving heart failure characterization in these trials, we wanted to first describe what trials have already been doing and where the gaps in understanding heart failure in these trials exist. Overall, we found major gaps in the amount and quality of the heart failure data capture in these trials. We looked at 21 large trials, including over 150,000 patients. Rates of patients with baseline heart failure were inconsistently provided, and among those trials that did provide it, heart failure patients tended to be underrepresented compared to the general population. Patients with baseline heart failure were also poorly characterized, with minimal data on functional status, ejection fraction, or heart failure medications. Only 6 trials reported rates of new-onset heart failure and the definitions used were non-specific. Most trials tended to report rates of heart failure hospitalization, but did not include data on fatal or other types of heart failure events. Only 2 trials included heart failure events within the primary study endpoint. More details are included in our full manuscript, which was published in the Journal of the American College of Cardiology to coincide with our presentation at the ACC conference. (more…)
Author Interviews, Duke, Heart Disease, JACC / 07.03.2018

MedicalResearch.com Interview with: Renato D. Lopes MD, MHS, PhD Professor of Medicine, Division of Cardiology Duke University Medical Center Duke Clinical Research Institute Terrace Level, Durham, NC 27705 MedicalResearch.com: What is the background for this study? 1-      Digoxin is used in ≈ 30% of patients with atrial fibrillation (AF) worldwide, despite the lack of randomized clinical trials to assess its efficacy and safety in this setting. 2-      Current AF guidelines recommend digoxin for rate control in patients with AF with and without heart failure (HF). 3-      There are no specific recommendations about serum digoxin concentration monitoring in the atrial fibrillation guidelines. (more…)
Author Interviews, Cost of Health Care, Duke, Electronic Records, JAMA / 21.02.2018

MedicalResearch.com Interview with: Barak Richman JD, PhD Bartlett Professor of Law and Business Administration Duke University  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: The US not only has the highest health care costs in the world, we have the highest administrative costs in the world. If we can reduce non-value added costs like the ones we document, we can make substantial changes in the affordability of health care without having to resort to more draconian policy solutions. Our paper finds that administrative costs remain high, even after the adoption of electronic health records.  Billing costs, for example, constituted 25.2% of professional revenue for ED departments and 14.5% of revenue for primary care visits.  The other numbers are captured below. (more…)
Author Interviews, Duke, NEJM, Rheumatology, Stem Cells, Transplantation / 04.01.2018

MedicalResearch.com Interview with: Keith M. Sullivan, M.D. James B. Wyngaarden Professor Of Medicine Division of Cellular Therapy Duke University Medical Center Durham, North Carolina 27710, USA  MedicalResearch.com: What is the background for this study? What are the main findings?
  • Scleroderma with internal organ involvement is a devastating  autoimmune disorder with considerable morbidity and high mortality which have not changed in 40 years of reporting. Effective new therapies are needed.
  • Despite 2 prior randomized trials showing benefit for reduced-intensity stem cell transplant vs. conventional cyclophosphamide immune suppression, clinical practice in the US did not change due in part due to concern about patient safety and durability of response (attached).
  • The current randomized trial compares 12 monthly infusions of cyclophosphamide with high-dose chemotherapy plus whole-body irradiation designed to wipe-out (myeloablate) the defective, self-reactive immune system and replace with the patients own stem cells which had been treated to remove self-reacting lymphocytes. This was the first study to test if myeloablative autologous could re-establish a normal functioning immune system in patients with scleroderma.
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Author Interviews, Cancer Research, Cost of Health Care, Duke, JAMA / 11.08.2017

MedicalResearch.com Interview with: Dr. Fumiko Chino, MD Duke Radiation Oncology Duke School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: The financial burden of cancer treatment is a growing concern. Out-of-pocket expenses are higher for patients with cancer than for those who have other chronic illnesses. Fifty percent of elderly cancer patients spend at least 10% of their income on treatment-related out-of-pocket expenses. Additionally, high financial burden is associated with both increased risk of poor psychological well-being and worse health-related quality of life. A cancer diagnosis has been shown to be an independent risk factor for declaring personal bankruptcy, and cancer patients who declare personal bankruptcy are at greater risk for mortality. These potentially harmful outcomes resulting from financial burden have been recognized as the financial toxicity of cancer therapy, analogous to the more commonly considered physical toxicity. We conducted an IRB approved study of financial distress and cost expectations among patients with cancer presenting for anti-cancer therapy. In this cross-sectional, survey based study of 300 patients, over one third of patients reported higher than expected financial burden. Cancer patients with highest financial distress are underinsured, paying nearly 1/3 of income in cancer-related costs. In adjusted analysis, experiencing higher than expected financial burden was associated with high/overwhelming financial distress (OR 4.78; 95% CI 2.02-11.32; p<0.01) and with decreased willingness to pay for cancer care (OR 0.48, 95% CI 0.25-0.95, p=0.03). Sambla, a Scandinavian lender, has been working with many patients to prevent any financial distress resulting from unexpected medical bills. As a result of customer feedback, it has modified the terms of all loans it issues to allow for jumbo loan sizes and reduced interest rates, combined with longer repayment times to help its borrowers. (more…)