Author Interviews, Colon Cancer / 13.07.2017

MedicalResearch.com Interview with: Dr.Yi Xu PhD Center for Infectious and Inflammatory Diseases Institute of Biosciences and Technology Department of Microbiology and Microbial Genetics, University of Texas Health Science Center Texas A&M Health Science Center College Station, Texas MedicalResearch.com: What is the background for this study? Response: Colorectal cancer is fairly treatable when caught early with regular screenings, but it is still the second-leading cause of cancer-related deaths in American men and the third-leading cause in women. Researchers at Texas A&M have found that a subspecies of the bacterium Streptococcus gallolyticus appears to actively promote the development of colorectal cancer, which could lead to potential treatment strategies. Their findings are published in the journal PLOS Pathogens. Scientists have known for some time that people infected with S. gallolyticus are more likely to have colorectal cancer. “This association was well established in the clinical literature,” said Yi Xu, PhD, associate professor at the Texas A&M Institute of Biosciences and Technology and principal investigator of the study. However, it was unclear if that relationship was cause or effect—that the bacteria promote cancer development—or if S. gallolyticus simply grows easily in the environment that the tumor cells provide.  (more…)
Author Interviews, Environmental Risks, Weight Research / 13.07.2017

MedicalResearch.com Interview with: Heather M. Stapleton PhD Dan and Bunny Gabel Associate Professor of Environmental Ethics and Sustainable Environmental Management EEH Program Chair Nicholas School of the Environment Duke University Durham, North Carolina 27708 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Building materials and products common to most homes (e.g. furniture, TVs, carpets, etc) are often treated with synthetic chemicals, which migrate out of the products over time and accumulate in house dust, where residents can be exposed to these chemicals on a daily basis. This study assessed approximately forty chemicals commonly detected and measured in house dust samples for their ability to stimulate the development of fat cells, using a mouse precursor fat cell model. Approximately two thirds of these chemicals were able to promote lipid accumulation by these cells and/or stimulate the proliferation of the precursor fat cells. We then assessed eleven extracts of indoor house dust samples (containing mixtures of these chemicals) and exposed our cells to these extracts, finding that even low levels of these extracts were sufficient to promote the accumulation of lipids and/or the proliferation of the fat precursor cells. (more…)
Author Interviews, Brigham & Women's - Harvard, Lifestyle & Health, NEJM, Nutrition / 13.07.2017

MedicalResearch.com Interview with: Mercedes Sotos Prieto PhD Research Fellow Department of Nutrition Harvard T. H. Chan School of Public Health MedicalResearch.com: What is the background for this study? What are the main findings? Response: Previous research have found that adherence to the 2010 Alternate Heathy Eating Index, the Mediterranean Diet pattern, and DASH pattern is associated with health benefits, but none of those studies have examined dynamic changes in diet quality over time and subsequent risk of mortality. This is the first study to demonstrate that improvement in these three diet scores over time is associated with reduced risk of total and cardiovascular mortality. In contrast, worsening diet quality over 12-years was associated with 6%-12% increased mortality. In addition, not only improvement in diet quality but maintaining a high adherence to any of the three dietary patterns over 12 years was significantly associated with 9%-14% lower total mortality. (more…)
Author Interviews, NEJM, Prostate Cancer / 13.07.2017

MedicalResearch.com Interview with: Dr. Timothy Wilt, MD MPH Core Investigator: Minneapolis VA Center for Chronic Disease Outcomes Research Staff Physician: Section of General Internal Medicine, Minneapolis VA Health Care System Professor: Medicine, University of Minnesota School of Medicine  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Prostate cancer is common and potentially serious. However, the comparative benefits and harms of surgery versus observation in men with localized prostate cancer are not known. After nearly 20 years, surgery did not significantly reduce all-cause or prostate cancer mortality compared to observation, particularly in men with low risk disease. Surgery was associated with more harms than observation, causing complications within 30 days in about 20% of men and large long term increases in urinary incontinence, sexual dysfunction and dissatisfaction, as well as treatment related bother and reductions in daily functioning. (more…)
Author Interviews, Depression, Gender Differences, Pediatrics / 12.07.2017

MedicalResearch.com Interview with: Jie-Yu Chuang PhD Department of Psychiatry University of Cambridge Cambridge, United Kingdom  MedicalResearch.com: What is the background for this study? Response: Men and women appear to suffer from depression differently, and this is particularly striking in adolescents. By 15 years of age, girls are twice as likely to suffer from depression as boys. There are various possible reasons for this, including body image issues, hormonal fluctuations and genetic factors, where girls are more at risk of inheriting depression. However, differences between the sexes don't just involve the risk of experiencing depression. Men are more liable to suffer from persistent depression, whereas in women depression tends to be more episodic. Compared with women, depressed men are also more likely to suffer serious consequences from their depression, such as substance abuse and suicide. Despite this, so far, most researchers have focused on depression in women, likely because it is more common. As a result, we'd like to make people more aware of the sex difference issue in depression. (more…)
Author Interviews, JAMA, Outcomes & Safety / 12.07.2017

MedicalResearch.com Interview with: Riyaz Bashir MD, FACC, RVT Professor of Medicine Director, Vascular and Endovascular Medicine Department of Medicine Division of Cardiovascular Diseases Temple University Hospital Philadelphia, PA 19140 MedicalResearch.com: What is the background for this study? Response: The use of inferior vena cava filters (IVCF) has been increasing in the United States (US) despite uncertainty about the effectiveness of IVCFs in reducing venous thromboembolism (VTE)-associated morbidity and mortality.  Prompted by the report of high prevalence of fracture and embolization of Bard IVCFs, the US Food and Drug Administration (FDA) issued a device safety warning on August 9th 2010. In this study, we evaluated national trends of IVCF placement in the US between 2005 and 2014 using the National Inpatient Sample database.  The authors found that there was a 29% reduction in filter use following the 2010 FDA advisory, even though the rates of VTE-related hospitalizations remained unchanged. (more…)
Author Interviews, Cost of Health Care, Heart Disease, JAMA / 11.07.2017

MedicalResearch.com Interview with: Sacha Bhatia, MD, MBA, FRCPC Scientist, Women's College Research Institute Director, Women’s College Hospital Institute for Health System Solutions and Virtual Care Cardiologist, Women's College Hospital and University Health Network Canada MedicalResearch.com: What is the background for this study? What are the main findings? Response: The USPSTF recommends against screening with resting electrocardiography (ECG) for the prediction of coronary heart disease (CHD) events in asymptomatic adults at low risk for CHD events. We conducted a retrospective cohort study of the frequency of resting ECGs in low risk patients within 30 days of an annual health exam. We found that 21.5% of low risk patients in Ontario, Canada had a ECG, with significant variation among primary care physicians (1.8% to 76.1%). Moreover, low risk patients who had a ECG were five times more likely to receive another cardiac test or cardiology consultation than those that did not receive an ECG. At one year the rate of mortality, cardiac hospitalizations and revascularization was <0.5% in each group. (more…)
Author Interviews, Infections, Lancet, STD, Vaccine Studies / 11.07.2017

MedicalResearch.com Interview with: Helen Petousis-Harris. BSc, PhD Senior Lecturer, Dept General Practice and Primary Health Care Academic Head, Immunisation Research and Vaccinology Immunisation Advisory Centre School of Population Health, Faculty of Medical and Health Sciences University of Auckland MedicalResearch.com: What is the background for this study? What are the main findings? Response: Early thinking came from two quarters. One, the observation that the NZ OMV vaccine appeared broadly protective – beyond the clone it was based on and two, the observation of graphs depicting annual number of cases from both Cuba and NZ. There is nothing to suggest other types of meningococcal vaccine have had any effect on gonorrhoea so we are interested in the OMV vaccines. This led to the hypothesis that as these two Neisseria species are related the meningococcal OMV in the form of a vaccine may offer some kind of cross protection. To explore this possibility we conducted a case-control study that compared the vaccination status of cases (gonorrhoea) and controls (Clamydia). We found that the cases with gonorrhoea were less likely to be vaccinated than the controls and after we controlled for confounders – ethnicity, SE deprivation, age we found a vaccine effectiveness of 31%. (more…)
Author Interviews, JAMA, Orthopedics / 11.07.2017

MedicalResearch.com Interview with: Mattias Lorentzon, PhD Professor, Senior Physician Head of Geriatric Medicine, Institute of Medicine, Sahlgrenska Academy Sahlgrenska University Hospital, Mölndal Mölndal, Sweden MedicalResearch.com: What is the background for this study? What are the main findings? Response: It was previously known that alendronate reduces the risk of vertebral fractures in patients using oral glucocorticoids, but there were no studies regarding hip fractures, which are the most severe osteoporotic fractures, often resulting in disability and mortality. We found that older patients prescribed alendronate after starting medium to high doses of oral prednisolone had a much lower risk of hip fracture than patients not taking alendronate. (more…)
AACR, Abuse and Neglect, Boehringer Ingelheim, Cancer Research / 11.07.2017

MedicalResearch.com Interview with: Dr. Jordi Bruix, MD Professor of Medicine University of Barcelona Director of the Barcelona Clinic Liver Cancer (BCLC) Group Liver Unit Hospital Clinic of Barcelona MedicalResearch.com: What is the background for this study? What are the main findings? Response: The RESORCE Phase III pivotal trial is an international, multicenter, placebo-controlled trial which investigated the efficacy of Stivarga (regorafenib) in adults with Child-Pugh A and Barcelona Clinic Liver Cancer Stage Category B or C hepatocellular carcinoma (HCC) who had documented disease progression following first-line treatment with Nexavar (sorafenib). Trial participants were administered a daily oral 160mg dose (three weeks on/ one week off) of regorafenib plus best supportive care (BSC), or placebo plus BSC. Results from the trial demonstrated that participants treated with regorafenib experienced a statistically significant and clinically meaningful improvement in the study’s primary endpoint—overall survival (OS). Participants treated with regorafenib demonstrated a median overall survival of 10.6 months vs. 7.8 months with placebo. At ASCO 2017, an exploratory analysis evaluated the impact of baseline alpha-fetoprotein (AFP) and c-Met as predictors of poor prognosis in patients enrolled in the RESORCE trial (Abstract #4078). (more…)
Author Interviews, BMC, Prostate Cancer, Race/Ethnic Diversity, Weight Research / 11.07.2017

MedicalResearch.com Interview with: Aurora Perez-Cornago, PhD Cancer Epidemiology Unit Nuffield Department of Population Health University of Oxford MedicalResearch.com: What is the background for this study? What are the main findings? Response: Greater height and adiposity have been suggested as possible prostate cancer risk factors, but these associations are not clear, probably because most previous studies have not looked separately at different tumour subtypes. For this reason, we wanted to look at these associations splitting tumours into subtypes according to tumour stage and histological grade, looking as well at death from prostate cancer. We found a marked difference in risks looking at low and high risk tumours. Taller men and men with greater adiposity had an elevated of high-grade prostate cancer and prostate cancer death. (more…)
Annals Internal Medicine, Author Interviews, Coffee / 11.07.2017

MedicalResearch.com Interview with: Marc J. Gunter, PhD  From International Agency for Research on Cancer Lyon, France MedicalResearch.com: What is the background for this study? Response: U.S. and Japanese studies have previously found that drinking more coffee was related with a lower risk of death. However, in European populations, where coffee consumption and preparation methods are more varied, the relationship was less certain as relatively small studies had previously been conducted. Our analysis was undertaken in ~500,000 men and women from 10 European countries, the largest study to date investigating the coffee and mortality relationship. (more…)
Addiction, Author Interviews, CDC, Opiods / 11.07.2017

MedicalResearch.com Interview with: Deborah Dowell, MD, MPH Chief Medical Officer, Division of Unintentional Injury Prevention National Center for Injury Prevention and Control Centers for Disease Control and Prevention  MedicalResearch.com: What is the background for this study? Response: CDC analyzed retail prescription data from QuintilesIMS which provides estimates of the number of opioid prescriptions dispensed in the United States from approximately 59,000 pharmacies, representing 88% of prescriptions in the United States. CDC assessed opioid prescribing in the United States from 2006 to 2015, including rates, amounts, dosages, and durations prescribed. CDC examined county-level prescribing patterns in 2010 and 2015. (more…)
Author Interviews, Biomarkers, Brain Injury / 10.07.2017

MedicalResearch.com Interview with: Dr Lisa J Hill PhD Institute of Inflammation and Ageing Research Fellow Neuroscience and Ophthalmology Institute of Inflammation and Ageing College of Medical and Dental Sciences University of Birmingham UK  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Traumatic brain injury (TBI) is the leading cause of death and disability among young adults and, according to the World Health Organization, by 2020 TBI will become the world’s leading cause of neurological disability across all age groups.  Early and correct diagnosis of traumatic brain injury is one of the most challenging aspects faced by clinicians. Being able to detect compounds in the blood that help to determine how severe the brain injury is would be of great benefit to patients and aid in their treatment.  Inflammatory markers are particularly suited for biomarker discovery as TBI leads to very early alterations in inflammatory proteins.  The discovery of reliable biomarkers for the management of TBI would improve clinical interventions. We collected blood samples from 30 injured patients within the first hour of injury prior to the patient arriving at hospital and analysed them. Analysis of protein biomarkers from blood taken within the first hour of injury has never been carried out until now. We used a panel of 92 inflammation-associated human proteins when analysing the blood samples. The analysis identified three inflammatory proteins, known as CST5, AXIN1 and TRAIL, as novel biomarkers of TBI. (more…)
Author Interviews, Exercise - Fitness, Technology / 10.07.2017

MedicalResearch.com Interview with: Jacob Barkley, Ph.D., College of Education, Health and Human Services Kent State  MedicalResearch.com: What is the background for this study? Response: Our group has demonstrated that cellular telephone (cell phone) use is positively associated with sedentary behavior (i.e., sitting). To that end, high cell phone users sit for 80 to 100 minutes longer than their lower-use peers. We have also shown that cell phone use during exercise decreases exercise intensity and slows free-living walking speed. In other words, cell use may be comparable to traditional sedentary screen use in that it promotes sitting and may interfere with physical activity. However, some cell phone functions may actually promote positive health behaviors. Fitness apps, connecting with active peers and administering health recommendations via the cell phone all may have utility in promoting physical activity and reducing sedentary behavior. While not well studied, novel physically-interactive cell phone games may also promote physical activity. One such game, Pokémon Go! requires users to walk through real environments and locate avatars in the game using GPS. The purpose of the game is to find these avatars. In order to find more avatars, the player will need to walk to more areas. Therefore, playing Pokémon Go! may promote walking. (more…)
Author Interviews, JAMA, Nutrition, Pediatrics / 10.07.2017

MedicalResearch.com Interview with: Dr. Anne-Louise M. Heath and Professor Rachael Taylor Co-Principal Investigators for the BLISS study. MedicalResearch.com: What is the background for this study? What are the main findings? Response: Conventional approaches to complementary feeding generally advise parents to spoon-feed their infant pureed foods, gradually progressing to greater variety and texture so that by the time the infant is one year of age, they are eating more or less what the family does. Baby-led weaning (BLW) is an alternative approach where the infants feeds themselves right from the start of complementary feeding. Because children of this age cannot use utensils, this means hand-held foods are necessary. Advocates of BLW suggest that children have a lower risk of obesity because they remain in control of their own food intake, but research examining this issue directly is scarce. Health professionals have also expressed concern that BLW might put the infant at increased risk of iron deficiency (parents might avoid red meat for fear of the infant choking, and iron-fortified cereals are not easy for the infant to feed themselves), growth faltering (if only low energy foods are offered) and choking (from the infant feeding themselves ‘whole’ foods). Our study therefore examined a version of BLW that had been modified to address these issues (called BLISS - a Baby-Led Introduction to SolidS). Two hundred families took part in our 2-year intervention, with half following traditional feeding practices and half receiving guidance and support to follow our BLISS approach. We found that BLISS children were not less likely to be overweight than those following traditional feeding practices, nor was growth faltering an issue. BLISS child ate about the same amount of food as control children, and their ability to eat to appetite was not different either. However, it seems that children following a baby-led approach to complementary feeding are less fussy about food, and have a healthier attitude to food, which might make a difference to their health long term. (more…)
Author Interviews / 10.07.2017

MedicalResearch.com Interview with: Alice Baniel, PhD Postdoctoral Research Fellow Institute for Advanced Study in Toulouse Manufacture des Tabacs  MedicalResearch.com: What is the background for this study? What are the main findings? Response: In many primate societies, sexually receptive females actively solicit copulations from multiple males, which has long been regarded as the expression of their free mating preferences. Few studies have investigated whether this apparent sexual freedom may, in fact, be constrained by male behaviour. We tested whether males coerce females to mate with them using aggression in wild chacma baboons, where males are much larger and stronger than females. We asked whether male baboons harass females until they mate with them, punish females after they have copulated with rivals, or use long-term sexual intimidation (where male aggression is not immediately followed by mating but increases the chances that female victims accept matings in the long-term). We collected data on sex and aggression across four years in two large baboon groups living in Namibia. We found that: (1) fertile females suffer more aggression from males than pregnant and lactating females; (2) aggression from males is a major source of injury for fertile females; and (3) a male who was more aggressive toward a certain female has better chances to mate with her when she is close to ovulation. Males did not seem to use sexual harassment, since females did not receive higher rates of aggression from males shortly before mating, nor punishment since females did not received higher rates of aggression shortly after mating with rival males. Instead, males appear to attack and chase particular females repeatedly during the 3-4 weeks preceding their ovulation, to increase their chances of monopolizing sexual access to them in the days surrounding ovulation, which can be seen as a form of long-term sexual intimidation. (more…)
Author Interviews, Opiods, Pharmacology / 10.07.2017

Medical Research.com Interview with: Dr. Christian Heidbreder, PhD Chief Scientific Officer Indivior Inc. Richmond, VA 23235, USA MedicalResearch.com: What is the background for this study? What are the main findings? Response: This pivotal Phase 3 clinical trial (RB-US-13-0001) evaluated the efficacy and safety of RBP-6000, an investigational once-monthly injectable buprenorphine in the ATRIGEL® delivery system for the treatment of adults with moderate-to-severe opioid use disorder (OUD) as part of a complete treatment plan to include counseling and psychosocial support1. The 24-week Phase 3 study met its primary and key secondary endpoints, demonstrating statistically significant differences in percentage abstinence and treatment success across both dosage regimens of RBP-6000 versus placebo1. The findings also showed that outcomes with RBP-6000 are consistent across other secondary clinical endpoints, including control of craving and withdrawal symptoms, as compared to placebo. These outcomes were associated with buprenorphine plasma concentrations ≥ 2 ng/mL and predicted whole brain mu-opioid receptor occupancy of ≥ 70%, and were also maintained for the one-month dosing intervals and for the entire treatment duration1. The results were confirmed by exposure-response analyses demonstrating a relationship between buprenorphine plasma concentrations, abstinence, withdrawal symptoms and opioid craving1. RBP-6000 was generally well tolerated and had a safety profile consistent with that of transmucosal buprenorphine. Injection site reactions were not treatment-limiting. The most common (reported in ≥ 5% of subjects) treatment-emergent adverse events (TEAEs) reported in the active total group were constipation, headache, nausea, injection site pruritus, vomiting, increased hepatic enzyme, fatigue and injection site pain1. (more…)
Author Interviews, Cost of Health Care, Diabetes / 10.07.2017

MedicalResearch.com Interview with: Maria L. Alva, DPhil Economist RTI International -  Research Triangle Institute MedicalResearch.com: What is the background for this study? What are the main findings? Response: We have strong evidence from trials of structured lifestyle intervention programs (e.g. the Diabetes Prevention Program (DPP)) showing that half of new diabetes cases could be avoided if persons with prediabetes changed their lifestyle habits to lose a modest amount of body weight. Moreover, the DPP has been successfully translated into cost-effective community-based prevention interventions, but nationally, these evidence-based interventions (EBIs) are not being used sufficiently. To scale up the implementation of diabetes prevention EBIs, we need to address the challenges of getting organizations to adopt EBIs, and community members to enroll. Because cost is a primary barrier we wanted to understand what was the perceived value and demand for diabetes prevention programs in NC. And in particular, the role that community health workers and technology could play in program delivery, from the perspectives of both potential recipients (adults at high risk or diagnosed with prediabetes) and decision-makers in healthcare/public health delivery. (more…)
Author Interviews, BMJ, Gastrointestinal Disease / 09.07.2017

MedicalResearch.com Interview with: Ziyad Al-Aly MD FASN Assistant Professor of Medicine Co-director for Clinical Epidemiology Center Department of Medicine, Washington University School of Medicine Saint Louis, Missouri Associate Chief of Staff for Research and Education Veterans Affairs Saint Louis Health Care System MedicalResearch.com: What is the background for this study? What are the main findings? Response: Proton Pump Inhibitors (PPI) are commonly used, and they are associated with adverse events including kidney disease, dementia, fractures, cardiovascular disease, and pneumonia. We asked the question of whether this translates to increased risk of death. We conducted this large cohort study to specifically examine the association between PPI use and risk of death. The results consistently showed an association between use of PPI and increased mortality risk. Moreover, there was a graded relationship between duration of PPI use and risk of death in that longer duration of use was associated with incrementally higher risk of death. (more…)
Author Interviews, Cancer Research, CDC / 07.07.2017

MedicalResearch.com Interview with: Lisa C. Richardson, MD, MPH, Oncologist Director,Division of Cancer Prevention and Control CDC MedicalResearch.com: What is the background for this study? Response: This MMWR report is the first complete description of cancer incidence and mortality comparing rural and urban America.  From previous reports we know that rural residents are more likely to be older, have more comorbid conditions and participate in high risk behaviors that can lead to cancer. CDC researchers were interested in how these factors were related to new cancers and cancer deaths in rural counties compared to metropolitan counties. Researchers found that rates of new cases for lung cancer, colorectal cancer, and cervical cancer were higher in rural America. In contrast, rural areas were found to have lower rates of new cancers of the female breast, and prostate. Rural counties had higher death rates from lung, colorectal, prostate, and cervical cancers. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Dermatology, JAMA / 07.07.2017

MedicalResearch.com Interview with: Dr. Chrysalyne D. Schmults, MD, MSCE Associate Professor of Dermatology, Harvard Medical School Director, Mohs and Dermatologic Surgery Center and Mr. Pritesh S. Karia, MPH Department of Epidemiology Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland Department of Dermatology Brigham and Women's Faulkner Hospital Harvard Medical School, Boston, Massachusetts Jamaica Plain, MA 02130-3446  MedicalResearch.com: What is the background for this study? Response: Perineural nerve invasion (PNI) is a well-recognized risk factor for poor prognosis in patients with cutaneous squamous cell carcinoma (CSCC). Most cases of CSCC with PNI are identified on histologic examination at the time of surgery and the patient has no clinical symptoms or radiologic evidence of PNI. These cases are classified as incidental PNI (IPNI). However, some patients with PNI present with clinical symptoms and/or radiologic evidence of PNI. These cases are classified as clinical PNI (CPNI). A few studies have shown differences in disease-related outcomes between CSCC patients with IPNI and CPNI but consensus regarding adjuvant treatment and detailed guidelines on follow-up schedules have not yet materialized. (more…)
Author Interviews, Diabetes, Ophthalmology / 07.07.2017

MedicalResearch.com Interview with: Dr. David Kita, PhD Founder and Head of R&D Verseon CorporationDr. David Kita, PhD Founder and Head of R&D Verseon Corporation

MedicalResearch.com: What is the background for this study?

Dr. Kita: The preclinical data presented at the 2017 BIO International Conference provided details about Verseon’s plasma kallikrein inhibitors for the treatment of diabetic macular edema (DME). DME affects millions of people worldwide and is a major cause of vision loss in patients with diabetes mellitus. Upregulation of the kallikrein-kinin system in response to diabetes can result in retinal vascular permeability, which can damage the retina and eventually lead to the central vision loss associated with DME. The current treatment options for DME include intravitreal injections of anti-VEGF agents or corticosteroids into the eye and surgical laser treatments. Long-term use of intravitreal injections is associated with side effects such as inflammation, infections, and cataracts. For anti-VEGF drugs in particular, there is also a growing concern about geographic atrophy. In addition, about 50% of patients reported at most moderate vision improvements following anti-VEGF therapy in clinical trials. This highlights the need for a new treatment that can serve as a monotherapy or as an adjuvant to current therapies. At Verseon, we are working on inhibitors of the serine protease plasma kallikrein (KLKB1) that can be administered either topically or orally. Verseon’s unique computer-driven drug discovery platform allows us to design potent, selective drug candidates that are unlikely to be found using traditional approaches. We have generated a number of chemically distinct series of KLKB1 inhibitors and optimized multiple lead candidates, which show good activity, permeability, and solubility. (more…)
Author Interviews, Genetic Research, Ophthalmology, University Texas / 07.07.2017

MedicalResearch.com Interview with: Stephen P. Daiger, PhD Professor, Human Genetics Center Thomas Stull Matney, Ph.D. Professor in Environmental and Genetic Sciences Mary Farish Johnston Distinguished Chair in Ophthalmology The University of Texas Health Science Center at Houston   MedicalResearch.com: What is the background for this study? What are the main findings? Response: Thanks for your questions about our research.  My research group and I have a long-term interest in finding genes and mutations causing inherited retinal diseases.  Our main focus is on retinitis pigmentosa (RP) and, more specifically, the autosomal dominant form of RP. Inherited retinal diseases are progressive, degenerative diseases of the retina.  Onset can be very early in life, even at birth, or much later in life.  As the degeneration develops an affected person may first experienced limited loss of vision, progressing to severe loss of vision, ending, in many cases, in legal or complete blindness.  About 300,000 Americans are affected by inherited retinal disease and 50% of these have RP.  RP, like most hereditary conditions, can be inherited in an autosomal dominant, autosomal recessive or X-linked fashion. One of the surprising, and in some sense, disturbing findings in studying  retinitis pigmentosa is that mutations in many different genes can cause this disease.  We now know that mutations in more than 80 genes can cause RP and thousands of different mutations have been found in these genes.  With next-generations sequencing it is possible to find the cause of RP in from 50% to 80% of cases, depending on the underlying mode of inheritance.For example, in our research we can find the disease-causing mutation in about 75% of families with autosomal dominant RP.  Needless to say, a primary aim of our research is to find the cause in the remaining 25%. In looking for the cause of retinitis pigmentosa in the remaining 25%, that is, those in whom mutations were not detected by earlier methods, we found a potential dominant-acting mutation in the arrestin-1 gene (gene symbol “SAG”) using whole-genome sequencing.  Molecular modeling suggests this mutation is damaging.  This was unexpected because previously-reported mutations in this gene were associated with Oguchi disease, a recessive retinal disease with symptoms distinct from RP.  On further testing our cohort of patients with autosomal dominant RP, we found this mutation in nearly 4% of families.  Even more surprisingly, when we looked closely at the affected families, and worked with our collaborators to test other patients, we discovered that all of the families with the dominant-acting SAG mutation -- 12 total -- were of Hispanic origin.  By interviewing informative family members we learned that these families have their roots in the Southwestern United States.  Historically, the mutation may have arisen hundreds of years ago, consistent with genetic variation tracking with the mutation. (more…)
Author Interviews, Social Issues, Technology / 07.07.2017

MedicalResearch.com Interview with: Leon Sütfeld The Institute of Cognitive Science University of Osnabrück  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Self-driving cars, and especially future fully autonomous cars, pose a number of ethical challenges. One of these challenges is making the "right" decision when it comes to a so-called dilemma situation, in which a collision is unavoidable (or highly probable), but a decision can be made as to which of multiple different collisions to choose. Our study assesses the behavior of human participants in such dilemma situations and evaluates algorithmic models that are trained on this data to make predictions. Our main findings are that in a controlled virtual reality environment, the decisions of humans are fairly consistent and can be well described by simple value-of-life models. (more…)
Author Interviews, Cancer Research, Dermatology, JAMA, University of Pennsylvania / 06.07.2017

MedicalResearch.com Interview with: Mackenzie R. Wehner, MD, MPhil Department of Dermatology University of Pennsylvania Philadelphia, PA MedicalResearch.com: What is the background for this study? Response: For some diseases, we have national registries, in which information about every person with that disease is entered for research purposes. For other diseases, unfortunately, we do not have such registries. There are growing opportunities to use information like internet searches to better understand behaviors and diseases, however. Our study was a proof-of-concept: we aimed to find out whether internet searches for diseases correlated with known incidence (how many people are diagnosed with the disease) and mortality (how many people die of the disease) rates. E.g. does the number of people who searched 'lung cancer' online correlate with the number of people who we know were diagnosed with or who died of lung cancer during that same time period? This is important to know if researchers in the future want to use internet search data for diseases where we lack registry information. (more…)
Author Interviews, Prostate Cancer, Race/Ethnic Diversity / 06.07.2017

MedicalResearch.com Interview with: Dr. Norman Lee PhD Professor of Pharmacology and Physiology School of Medicine and Health Sciences George Washington University MedicalResearch.com: What is the background for this study? What are the main findings? Response: There are health disparities when it comes to prostate cancer. The African American population, in general, has a higher prostate cancer incidence and mortality rate compared to other racial groups such as European Americans. A major reason for this disparity is due to socioeconomic factors such as access to health care. There are also biological influences for the disparities, such as specific gene mutations and genetic polymorphisms that are found at a higher incidence in the African American population. My lab has been studying other potential contributing biological factors in prostate cancer disparities; namely, RNA splicing. RNA splicing is a cellular program that increases the diversity of expressed proteins by regulating which exons are included in an mRNA transcript, leading to mRNA variants encoding slightly different proteins (or isoforms) in different cells, organs, and individuals. One can think of RNA splicing as a form of genetic diversity. What we have found is that the repertoire of mRNA variants can differ in prostate cancer between African and European Americans. We also find that the mRNA variants in African American prostate cancer encode signal transduction proteins that are more oncogenic and resistant to targeted therapies, compared to the variants found in European American prostate cancer. (more…)
Author Interviews, Depression, JAMA / 06.07.2017

MedicalResearch.com Interview with: Robb B. Rutledge, PhD Max Planck University College London Centre for Computational Psychiatry and Ageing Research University College London London, England MedicalResearch.com: What is the background for this study? What are the main findings? Response: Depression is associated with deficits in how the brain responds to rewards, something the neurotransmitter dopamine is strongly implicated in. Dopamine represents what is called a reward prediction error, the difference between experienced and predicted reward. This error signal is used for learning. For example, if the outcome of a decision is better than expected, you can update your expectations using this error signal and you should expect more next time. Previous research has shown that depression reduces these signals in the brain when people are learning about the world around them. We designed a task where participants did not have to learn anything during the experiment and we found that in this situation reward prediction error signals were not affected by depression. The signals we measured in the ventral striatum, a brain area with a lot of input from the dopamine neurons, looked the same in depressed and non-depressed individuals. We also found that the emotional impacts of reward prediction errors were similar in depressed and non-depressed individuals when we eliminated the need for learning during the task in both the lab and using a smartphone experiment with 1833 participants. (more…)
Author Interviews, JAMA, Pediatrics / 06.07.2017

MedicalResearch.com Interview with: Seetha Shankaran, M.D. Professor, Neonatology Wayne State University School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: The study was performed because infants with moderate or severe hypoxic-ischemic encephalopathy (abnormal neurological exam within 6 hours of birth due to lack of blood and oxygen supply to the brain at birth) have rates of death or survival with disability that were still high in spite of current intensive care including hypothermia. Whole-body hypothermia, cooling the infant for 72 hours at a depth of 33.5°C that was performed by the Neonatal Research Network funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development was the first trial of this therapy in the USA. We found that hypothermia therapy did decrease the rate of death or survival with disability from 62 to 44%. Since 44% is still high we wanted to see if longer cooling or deeper cooling or both would reduce this rate. This was a randomized controlled clinical trial to examine whether longer cooling or deeper cooling or both reduced the rate of death or survival with disability among full term neonates with hypoxic-ischemic encephalopathy. The study lasted from October of 2010 to January 2016. 364 infants were enrolled. Neonates were randomly assigned to 4 groups of cooling therapy and the major findings were that neither longer cooling nor deeper cooling nor both were more superior to cooling for 72 hours at 33.5°C. Our results were surprising because at the time we planned this study there were reports from animal model studies that longer/deeper cooling were more protective to the brain. (more…)
Author Interviews, Electronic Records, JAMA, UCSF / 05.07.2017

MedicalResearch.com Interview with: Neda Ratanawongsa, MD, MPH Associate Chief Health Informatics Officer for Ambulatory Services, San Francisco Health Network Associate Professor, Division of General Internal Medicine UCSF Center for Vulnerable Populations Physician, Richard H. Fine People's Clinic (RHPC) Zuckerberg San Francisco General Hospital San Francisco, CA 94110 MedicalResearch.com: What is the background for this study? What are the main findings? Response: U.S. federal incentives allowed many safety net healthcare systems to afford fully functional electronic health record systems (EHRs). Although EHRs can help clinicians provide care to vulnerable populations, clinicians may struggle with managing the EHR workload, particularly in resource-limited settings. In addition, clinicians’ use of EHRs during clinic visits may affect how they communicate with patients. There are two forms of EHR use during clinic visits.  Clinicians can multitask, for example, by ordering laboratory tests while chatting with a patient about baseball.  However, like distracted driving, using EHRs while talking with increases risks – in this case, the risk of errors in patient-provider communication or in the EHR task. Alternatively, clinicians can use EHRs in complete silence, which may be appropriate for high-risk tasks like prescribing insulin. However, silence during visits has been associated with lower patient satisfaction and less patient-centered communication. So we studied how primary and specialty care clinicians used EHRs during visits with English- and Spanish-speaking patients in a safety net system with an EHR certified for Centers for Medicare & Medicaid Services meaningful use incentive programs. We found that multitasking EHR use was more common than silent EHR use (median of 30.5% vs. 4.6% of visit time). Focused patient-clinician talk comprised one-third of visit time. We also examined the transitions into and out of silent EHR use. Sometimes clinicians explicitly stated a need to focus on the EHR, but at times, clinicians drifted into silence without warning. Patients played a role in breaking silent EHR use, either by introducing small talk or by bringing up their health concerns. (more…)