Author Interviews, Genetic Research, Ophthalmology / 17.07.2015

Professor Robert E MacLaren MB ChB DPhil FRCOphth FRCS Nuffield Laboratory of Ophthalmology Nuffield Department of Clinical Neurosciences, University of Oxford Oxford Biomedical Research Centre, University of Oxford, Oxford, UK Moorfields Eye Hospital & UCL NIHR Biomedical Research Centre for Ophthalmology London, UK.MedicalResearch.com Interview with: Professor Robert E MacLaren MB ChB DPhil FRCOphth FRCS Nuffield Laboratory of Ophthalmology Nuffield Department of Clinical Neurosciences Oxford Biomedical Research Centre, University of Oxford, Moorfields Eye Hospital & UCL NIHR Biomedical Research Centre for Ophthalmology London, UK.
Medical Research: What is the background for this study? What are the main findings? Prof. MacLaren: The study shows that gene therapy can be used to release a protein in the eye that arrests the development of retinitis pigmentosa, a blinding disease caused by degeneration of the retina. The study was performed in mice which had a similar genetic defect to that found in humans with the disease. The mice also had fluorescent green “glow in the dark” light sensing cells known as cones, which we could see and count by looking into the eye – like counting stars in the night sky. By counting the green fluorescent cones we were able to work out the exact dose of gene therapy needed to keep these cells alive indefinitely. The study was funded by Fight for Sight, a UK charity that supports finding cures for eye diseases.
Author Interviews, Fertility, Genetic Research, Science / 17.07.2015

Stephen A. Krawetz, Ph.D. Associate Director C.S. Mott Center for Human Growth and Development, Charlotte B. Failing Professor of Fetal Therapy and Diagnosis, Department of Obstetrics and Gynecology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, 48201MedicalResearch.com Interview with: Stephen A. Krawetz, Ph.D. Associate Director C.S. Mott Center for Human Growth and Development, Charlotte B. Failing Professor of Fetal Therapy and Diagnosis, Department of Obstetrics and Gynecology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, 48201 Medical Research: What is the background for this study? What are the main findings? Dr. Krawetz: The current study developed over approximately the past 20 years of work in my laboratory.  In the mid 1990s, along with David Miller, we independently discovered that sperm contain RNA.  This was followed by our joint publication in The Lancet that began to describe the RNAs in normal fertile males along with our paper in Nature that showed that RNA was delivered to the oocyte at fertilization.  Following these studies we assessed the ability of RNAs to be used as markers of morphologically abnormal sperm (teratozoospermia).  My laboratory then had the opportunity to explore the complexity of the population of sperm RNAs using Next Generation Sequencing.   We recently began the translation of this work from the bench to bedside which takes us to the current paper in Science Translational Medicine that was a multi-institutional collaborative effort.  Members of the team include Dr. Meritxell Jodar, Edward Sendler, Robert Goodrich, from my laboratory, along with Dr. Clifford L. Librach, Dr. Sergey I. Moskovtsev, and Sonja Swanson - CReATe Fertility Center, University of Toronto; Dr. Russ Hauser -Harvard University and Dr. Michael P. Diamond, Georgia Regents University. Here we tackled the issue of idiopathic infertility, that is, unknown infertility, since the couple appears normal in all respects.  We specifically framed our study as the contribution of the male and female as a couple towards the birth of a healthy child focusing on male idiopathic infertility within the setting of a Reproductive Clinic.  Representative publications from my laboratory that outline this part of my research program appear below. 1)            Jodar, M., Sendler, E., Moskovtsev, S. Librach, C., Goodrich, R., Swanson, S., Hauser, R., Diamond, M. and Krawetz, S.A. (2015) Absence of sperm RNA elements correlates with idiopathic male infertility. Science Translational Medicine, 7(295):295re6. 2)            Sendler, E., Johnson, G.D., Mao, S., Goodrich, R.J., Diamond, M.P., Hauser, R., and Krawetz, S.A. (2013) Stability, Delivery and Functions of Human Sperm RNAs at Fertilization.  Nucleic Acids Research 41:4104-4117. PMID: 23471003 3)            Platts, A.E., Dix, D. J., Chemes, H.E., Thompson, K.E., Goodrich, R., Rockett, J. C., Rawe, V.Y., Quintana, S., Diamond, M.P., Strader, L.F. and Krawetz, S.A. (2007)  Success and failure in human spermatogenesis as revealed by teratozoospermic RNAs.  Human Molecular Genetics. 16:763-773.  PMID: 17327269 4)            Ostermeier, G.C., Miller, D., Huntriss, J.D., Diamond, M.P. and Krawetz, S.A. (2004) Delivering spermatozoan RNA to the oocyte.  Nature 429:154.  PMID: 15141202 5)            Ostermeier, G.C., Dix, D.J., Miller, D., Khatri, P. and Krawetz, S.A. (2002) Spermatozoal RNA profiles of normal fertile men. The Lancet. 360:773-777.  PMID: 12241836
Author Interviews, Clots - Coagulation, Heart Disease, JACC / 17.07.2015

Prof. Johan Bosmans Interventional cardiologist University Hospital Antwerp, Wilrijkstraat 10, 2650, Edegem, BelgiumMedical Research Interview with: Prof. Johan Bosmans Interventional cardiologist University Hospital Antwerp, Wilrijkstraat 10, 2650, Edegem, Belgium MedicalResearch: What is the background for this study? What are the main findings? Prof. Bosmans : Transcatheter aortic valve replacement (TAVR) has become standard of care for patients who cannot undergo surgery. With this, it is important to ensure that the risks associated with TAVR be fully understood, and if possible prevented. Even at this stage of the adoption of TAVR, large trials continue to provide information to the clinician about how to select the right patients to ensure the best possible outcomes. The ADVANCE Study is a prospective, multicenter study that evaluated the use of TAVR in 1015 patients at 44 experienced TAVR centers, which was designed to reflect routine clinical practice. We know that the risk of serious adverse events, such as stroke or transient ischemic attack (TIA), in post-TAVR patients can vary based on the timing before and after the procedure. A patient’s baseline demographics and medical history can affect their risk of procedure-related events as well as long-term outcomes. The manipulations required crossing the aortic valve and appropriately positioning any type of TAV has been thought to be related to procedural stroke events. Therefore, we performed a multivariable analysis looking for predictors of stroke – or stroke and TIA at 3 unique time periods (periprocedural, early and late) following TAVR. The most striking result from our analyses was that we were not able to identify any predictors of periprocedural (either during the procedure or on the day after) stroke, illustrating this very multifactorial etiology. We were able to show that being female, experiencing acute kidney injury or a major vascular complication positively predicted stroke during the early (2-30 days post procedure) time period. When we combined the outcome of stroke or TIA, we found that a history of prior atrial fibrillation (AF) was also a predictor. The only late predictor (day 31-730 post-procedure) of stroke was a history of coronary artery bypass grafting, which could reflect the patients’ risk of vascular disease.
Author Interviews, Education, Electronic Records, PLoS, UCSF / 17.07.2015

Dr. Courtney Lyles Ph.D. Assistant Professor UCSF School of MedicineMedicalResearch.com Interview with: Dr. Courtney Lyles Ph.D. Assistant Professor UCSF School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Lyles: In our commentary (http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001852), we describe the Meaningful Use program sponsored by the federal government to incentivize healthcare systems to implement electronic health records (EHRs).  This Meaningful Use program also includes financial incentives for healthcare systems who can get substantial proportions of their patient population to access their electronic health records – that is, by logging into an online patient portal website to view medical information like lab results or immunization lists or to perform a healthcare task like requesting a medication refill or messaging their provider.  Because there are billions of dollars at stake in this program for EHR implementation, there is a lot of attention on this issue right now.  Many thought leaders are discussing how we can transform healthcare by digitizing medical information and connecting with patients in their everyday life outside of office or hospital visits.  Portals are key to a lot of changes we might make in healthcare delivery in an attempt to increase convenience and satisfaction for patients.  Perhaps most importantly, these online portal websites are also one of the first health technologies that will be relatively uniformly distributed across healthcare settings, from private doctor’s offices to public clinics/hospitals serving vulnerable patient populations. However, our main message is that we in the medical and healthcare fields should be paying more attention to how patients are able to understand and use the information provided through portal websites.  There is a lot of evidence that patients who have lower education/income, are from racial/ethnic minority groups, or have limited health literacy are significantly less likely to use the existing portal websites.  There is also evidence that portal websites are not extremely usable or accessible, which is an additional barrier for those with communication barriers like lower literacy or limited English proficiency.  Therefore, we don’t want widespread EHR implementation to result in only the most well-resourced individuals gaining the potential benefits of portal access.
Author Interviews, PLoS, Toxin Research, University of Pennsylvania / 17.07.2015

Reynold A. Panettieri, Jr., M.D. Robert L. Mayock and David A. Cooper Professor of Medicine Pulmonary, Allergy & Critical Care Division Director, Airways Biology Initiative Deputy Director, Center of Excellence in Environmental Toxicology Adjunct Professor, Wistar Institute Philadelphia, PA 19104-3413MedicalResearch.com Interview with: Reynold A. Panettieri, Jr., M.D. Robert L. Mayock and David A. Cooper Professor of Medicine Pulmonary, Allergy & Critical Care Division Director, Airways Biology Initiative Deputy Director, Center of Excellence in Environmental Toxicology Adjunct Professor, Wistar Institute Philadelphia, PA  19104-3413 Medical Research: What is the background for this study? What are the main findings? Dr. Panettieri: Over the past ten years in the US, unconventional gas and oil drilling (hydraulic fracturing) to generate natural gas has markedly increased.  In areas with hydraulic fracturing, there is a large increase in truck traffic, noise and potential air and water pollution.  Accordingly, residents may experience health consequences from such exposures.  We questioned whether proximity to active wells increases hospitalization rates in residents.  To address this question, we reviewed all hospitalizations in two counties in Pennsylvania, namely, Bradford and Susquehanna Counties, that experienced a meteoric increase in active wells.  In comparison, Wayne County, where there is a moratorium on hydraulic fracturing, is demographically identical to Bradford and Susquehanna Counties and served as a control population.  Having examined the 25 most common reasons for admission to the hospital, we determined that cardiovascular hospitalizations as well as neurologic, dermatologic and cancer hospitalizations were associated with living closer to active wells.  These data represent some of the first studies to associate active well drilling with hospitalizations in the United States.
Author Interviews, BMJ, Clots - Coagulation / 17.07.2015

MedicalResearch.com Interview with: Byung-Joo Park, MD, MPH, PhD Professor Department of Preventive Medicine Seoul National University College of Medicine Medical Research: What is the background for this study? What are the main findings? Response: Antidepressants and NSAIDs are each thought to increase the risk of abnormal bleeding.  However, previous studies found neither antidepressants nor NSAIDs alone to be associated with an increased risk of intracranial haemorrhage.  Our research found that combined use of NSADIs in antidepressant users showed the increased relative risk of intracranial haemorrhage risk within the initial 30-days of combined use.
AHRQ, Author Interviews, Cost of Health Care / 17.07.2015

  H. Joanna Jiang, Ph.D. Agency for Healthcare Research and QualityMedicalResearch.com Interview with: H. Joanna Jiang, Ph.D. Agency for Healthcare Research and Quality MedicalResearch: What is the background for this study? What are the main findings? Dr. Jiang: A large proportion of health care resources in the United States are consumed by a relatively small number of individuals, who have been dubbed super-utilizers. Approximately 25% of U.S. health care expenses are incurred by 1% of the U.S. population, and 50% of expenses are incurred by 5% of the population. Our study found that across all types of payers of medical care (Medicare, Medicaid, and private insurance), super-utilizers on average had approximately 4 times as many hospital stays as other patients, and the 30-day hospital readmission rate for super-utilizers was 4 to 8 times higher than for other patients. Among Medicaid and privately insured patients, super-utilizers had longer hospital stays and higher average hospital costs than other patients. We also found that patients with multiple chronic conditions, such as diabetes, hypertension, and congestive heart failure, accounted for a greater share of hospital stays among super-utilizers than among other hospitalized patients. Mental health and substance use disorders were among the top 10 principal diagnoses for super-utilizers aged 1 to 64 years regardless of payer.
Author Interviews, Lancet, Lymphoma / 17.07.2015

MedicalRDr Yeow Tee Goh Department of Haematology Singapore General Hospital Republic of Singaporeesearch.com Interview with: Dr Yeow Tee Goh MBBS Department of Haematology Singapore General Hospital Republic of Singapore Medical Research: What is the background for this study? What are the main findings? Dr. Goh: Relapsed or refractory peripheral T-cell lymphoma after conventional chemotherapy is associated with a very poor prognosis and there is currently no recommendation on the standard approach to helping these patients. Novel targeted treatments for relapsed or refractory peripheral T-cell lymphoma such as romidepsin, pralatrexate, belinostat, and brentuximab vedotin has been approved by the US Food and Drug Administration (FDA) based on the results of their Phase II studies. With the exception of the remarkable efficacy of brentuximab vedotin in systemic anaplastic large cell lymphoma (86% of patients responding to treatment), the efficacy of romidepsin, pralatrexate, and belinostat in relapsed or refractory peripheral T-cell lymphoma is only modest with objective response rates between 25% and 29%. To our knowledge, no other clinical study has reported on the use of novel combination of targeted agents in in relapsed or refractory peripheral T-cell lymphoma. In our study, Of 23 patients assessable for responses, 10 (43%, 95% CI 23–63) patients had an objective response, of which 5 were complete responses. The combined proteasome and histone deacetylase inhibitor treatment shows promising activity for patients with peripheral T-cell lymphoma.
Author Interviews, Heart Disease, Lifestyle & Health / 17.07.2015

Carl "Chip" Lavie MD, FACC FACP, FCCP Medical Director, Cardiac Rehabilitation and Prevention Director, Exercise Laboratories John Ochsner Heart and Vascular Institute Professor of Medicine Ochsner Clinical School-UQ School of Medicine Editor-in-Chief, Progress in Cardiovascular DiseasesMedicalResearch.com Interview with: Carl "Chip"  Lavie MD, FACC FACP, FCCP Medical  Director, Cardiac  Rehabilitation and Prevention Director, Exercise Laboratories John Ochsner Heart and Vascular Institute Professor of Medicine Ochsner Clinical  School-UQ School of Medicine Editor-in-Chief, Progress in Cardiovascular Diseases Medical Research: What is the background for this study? What are the main findings? Dr. Lavie: This was a review of the literature on this topic.The main findings are that various lifestyle choices, including obesity,  hypertension, metabolic syndrome/diabetes, obstructive sleep apnea , moderate and  high alcohol intakes, and sedentary lifestyle but also very high exercise doses are all associated with increased risk of atrial fibrillation (AF).
Author Interviews, Genetic Research, Surgical Research, Yale / 17.07.2015

John A. Elefteriades, MD William W.L. Glenn Professor of Surgery Chief of Cardiothoracic Surgery Director, Aortic Institute at Yale-New Haven Yale University School of MedicineMedicalResearch.com Interview with: John A. Elefteriades, MD William W.L. Glenn Professor of Surgery Chief of Cardiothoracic Surgery Director, Aortic Institute at Yale-New Haven Yale University School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Elefteriades: The race to map the human genome was declared completed in 2003, at a cost of 3 billion dollars for the international collaborative university group and 300 million dollars for Craig Venter at Celera. Whole exome sequencing can now be performed at a cost of only several thousand dollars per individual. So, whole exome sequencing (also called Next Generation Sequencing) can now be applied to understand and treat diseases of many organ systems. In this study, we applied whole exome sequencing to study over 100 patients with thoracic aneurysm. In the late 1990s, both Dr. Diana Milewicz in Texas and our group at Yale had determined that many thoracic aortic aneurysms were genetically transmitted. Dr. Milewicz went on to identify many of the causative mutations. In this study, we were able to look, by whole exome sequencing performed on saliva, for all 21 mutations known to cause thoracic aortic aneurysm--all at one time in one comprehensive genetic test. We were able to protect patients with the most serious discovered mutations by early surgery, the need for which could not otherwise have been apparent. 
Author Interviews, Obstructive Sleep Apnea / 17.07.2015

Sunil Sharma, M.D Associate professor of pulmonary medicine Sidney Kimmel Medical College at Thomas Jefferson UniversityMedicalResearch.com Interview with: Sunil Sharma, M.D Associate professor of pulmonary medicine Sidney Kimmel Medical College at Thomas Jefferson University Medical Research: What is the background for this study? What are the main findings? Dr. Sharma: Obstructive sleep apnea (OSA) is a highly prevalent disorder with significant cardiovascular implications. In this condition the patient may repeatedly quit breathing during sleep, sometimes hundreds of times, leading to loss of oxygen and frequent arousals throughout the night. OSA has been associated with high blood pressure, congestive heart failure, coronary artery disease, arrhythmias and stroke, among other conditions. While overall awareness is improving, the condition is under-recognized in hospitalized patients. Due to multiple co-morbid conditions these patients may be at higher risk for complications. Recent studies have also shown that early recognition of OSA in hospitalized patients may reduce readmission rates. In our study, we used a simple and cost-effective clinical pathway to determine high-risk patients. Of the 149 patient's determined to be high risk by our protocol, 128 (87%) were confirmed with the diagnosis by a polysomnography (gold standard test). Furthermore, data derived from a simple and cost-effective oxygen measuring device (pulse-oximeter) was found to co-relate well with the polysomnography. 
Author Interviews, Technology / 17.07.2015

Adam Friedman, MD, FAADAssociate Professor of Dermatology Residency Program Director Director of Translational Research Department of Dermatology George Washington School of Medicine and Health ScienceMedicalResearch.com Interview with: Adam Friedman, MD, FAAD Associate Professor of Dermatology Residency Program Director Director of Translational Research Department of Dermatology George Washington School of Medicine and Health Sciences Medical Research: What is the background for this study? What are the main findings? Dr. Friedman: Acne vulgaris is one of the most  common skin disease that affects approximately 40-50 million people in the United States.    Acne’s multifactorial etiology, resulting from a mix of androgen-induced elevations in sebum production, abnormal follicular epithelial desquamation and proliferation, hypercolonization of Propionibacterium acnes and host inflammatory reactions, make treatment often times challenging. In looking at the topical therapeutic armament for Acne Vulgaris, which includes benzoyl peroxide, salicyclic acid, topical antibiotics such as clindamycin, and retinoids, all suffer from various related side effects including irritation, erythema, dryness, peeling and scaling, bacterial resistance, and resulting dyschromia from the associated irritation in patients of darker skin types. These adverse events often serve as major limiting factors influencing patient compliance and ultimately impacting efficacy. Therefore new treatments which target all of the complexities of acne are needed, especially given we have not had anything really new brought to market in years. Here, we looked to biology for the answer. Our bodies generate Nitric Oxide, a diatomic lipid loving gaseous molecule, to perform a broad range of biological activities, including but not limited to killing bacteria/fungi/viruses  and inhibiting inflammation - key elements in Acne. Its action however is very short lived and therefore using Nitric Oxide as a treatment is difficult as one would need a delivery system that would allow for continued and controlled release. Enter nanotechnology. We designed exceedingly small particles (of note, 1 nanometer = 1 billionth of a meter) which allow for the generation of nitric oxide gas from nitrite salt, and will only release the gas when exposed to moisture over time. The size of the particles also enables them to better interact with their environment, i.e. cells, pathogens, improving their activity as compared to large sized treatments In this study, we showed that the nitric oxide generating/releasing nano particles effectively killed the organism, P. acnes but was not toxic to both human skin cells and a live vertebrae model (embryonic zebra fish). More importantly, we found that the nano particles inhibits the activation of a newly recognized but exceedingly important inflammatory pathway that is directly tied to the formation of an acne lesion, called the NLRP3 inflammasome. Research has shown that our bodies already regulate this pathway with nitric oxide, and therefore once again, we are looking to biology for answers. As opposed to a drug that may only have one target, the nanoparticles inhibited multiple components/elements of the inflammasome pathway, giving some insight into its potential as a treatment for acne as well as other inflammatory diseases.
Author Interviews / 17.07.2015

MedicalResearch.com Interview with: Patrick O’Neill CASIS Communications Manager and Tara Ruttley Ph.D. NASA Staff Scientist NASA Office of the Chief Scientist Editor’s note: CASIS, the four year old Center for the Advancement of Science in Space, presented an informative update and display at the Biotech Conference 2015, in Philadelphia June 2015. CASIS, the manager of the International Space Station U.S. National Laboratory, facilitates space-based research for the good of mankind. To accomplish it’s goal of ‘driving scientific inquiry toward developing groundbreaking new technologies and products’, CASIS has at its disposal Seed Money, Expertise, Access to Launch, Administrative Support and Educational Outreach. Mr. O’Neill and Dr. Ruttley spoke with MedicalResearch.com about the work CASIS is doing and the opportunities CASIS is creating for entrepreneurs, educators and scientists. CASIS Laboratory in Space Station               MedicalResearch: Why don’t you tell us a little about the background for CASIS? Response: The mission of NASA is space exploration, while the complementary mission of CASIS is to use ISS (the International Space Station) to better life on earth. CASIS is the non-profit arm of NASA that recruits, selects and manages the scientific research projects conducted on the space station. [caption id="attachment_15795" align="alignleft" width="500"]Astronaut Scott Kelly will spend a year in space overseeing multiple research projects. Astronaut Scott Kelly will spend a year in space overseeing multiple research projects.[/caption]    
Author Interviews, Breast Cancer, Cancer Research, Nutrition / 16.07.2015

Dr. Vincent L. Cryns MD Chief of the Division of Endocrinology, Diabetes and Metabolism Department of Medicine University of Wisconsin Carbone Cancer Center University of Wisconsin School of Medicine and Public Health Madison, WisconsinMedicalResearch.com Interview with: Dr. Vincent L. Cryns MD Chief of the Division of Endocrinology, Diabetes and Metabolism Department of Medicine University of Wisconsin Carbone Cancer Center University of Wisconsin School of Medicine and Public Health Madison, Wisconsin Medical Research: What is the background for this study? What are the main findings? Dr. Cryns: It’s been known for quite some time that many tumors are highly vulnerable to deficiencies in certain amino acids such as methionine, causing tumor cells to stop growing or die. What’s been missing is a molecular explanation for these effects that would allow us incorporate this approach into a rationally designed clinical trial. In our work, we have demonstrated that “starving” triple-negative breast cancer cells of methionine uncovers a “fatal flaw” by increasing the expression of a cell death receptor (TRAIL-R2) that we can activate with a therapeutic antibody to efficiently kill the tumor cells. What’s especially exciting is that we can use a specific diet to metabolically prime cancer cells to respond to a targeted cancer therapy.
Author Interviews, CDC, Endocrinology, JCEM / 16.07.2015

MedicalResearch.com Interview with: Hubert W. Vesper, PhD Director, Clinical Standardization Programs in the National Center for Environmental Health, Centers for Disease Control and Prevention Co-author, “Measuring Estrogen Exposure and Metabolism: Workshop Recommendations on Clinical Issues” Co-chair of the PATH Steering Committee Medical Research: What is the background for this study? What are the main findings? Dr. Vesper: Accurate data on estrogen levels are needed to ensure appropriate and effective patient care. Research studies found high inaccuracies among different estrogen tests, especially at low estrogen levels commonly observed in postmenopausal women, men and children. Accurate estrogen measurements can be achieved through standardization. Stakeholders should support standardization efforts of the Centers for Disease Control and Prevention (CDC) or alternative strategies to arrive at estrogen measurement methods that are accuracy-based and reliable.
Author Interviews, Cancer Research / 16.07.2015

Dr-Haining-Yang MedicalResearch.com Interview with: Haining Yang MD Ph.D Associate Professor Thoracic Oncology Program University of Hawaii Cancer Center University of Hawaii, Honolulu, HI Medical Research: What is the background for this study? Dr. Yang: Mesothelioma is often caused by asbestos and other carcinogenic mineral fibers.  When these fibers lodge in the pleura, mesothelial cells and macrophages try to phagocytize and eliminate them. However, asbestos is very bio-persistent and cannot be eliminated, which caused cells undergoing programmed necrosis that leads to the release of HMGB1 into the extracellular space.  HMGB1 is a damage-associated molecular pattern molecule (DAMP) that causes inflammation. Asbestos exposure induces HMGB1 release and chronic inflammatory process that overtime may lead to malignancy.  Mesothelioma cells develop out of an environment that is rich in HMGB1 and are often dependent on HMGB1 for their own growth.  In fact, most mesothelioma cells actively secrete HMGB1 extra-cellularly to promote their own tumor growth.  Accordingly HMGB1 levels are high in the serum of mesothelioma patients (reviewed in Yang and Carbone, Clinical Cancer Res 2013).  We tested several anti-inflammatory agents to see if we were able to reduce HMGB1-induced mesothelioma cell growth, and none of them worked except for aspirin, that led us to conduct a series of experiments in vitro and in vivo to test the hypothesis that aspirin inhibits HMGB1 activities, and that by doing so, inhibits mesothelioma growth. Medical Research: What are the main findings? Dr. Yang:  We found that aspirin inhibits the growth of human mesothelioma cells in a xenograft model, moreover in vitro experiments demonstrated that this effects was specifically mediated via inhibition of HMGB1 and not via COX2 inhibition.  We propose that the so far enigmatic anticancer activity of aspirin is mediated, at least partially, via inhibition of HMGB1, and that aspirin may help delay the onset of mesothelioma and may help inhibit the growth of mesothelioma.
CDC, Nutrition / 15.07.2015

MedicalResearch.com Interview with: Latetia V. Moore Ph.D. MSPH Epidemiologist, Centers for Disease Control Medical Research: What is the background for this study? Dr. Moore: For this study, CDC researchers analyzed the average daily fruit and vegetable intake from the 2013 Behavioral Risk Factor Surveillance System (BRFSS) for the 50 states and the District of Columbia (DC) and the percent of each state’s population meeting fruit and vegetable intake recommendations.  BRFSS is the sole source of dietary information (systematic surveillance) for most states. Medical Research: What are the main findings? Dr. Moore: Researchers found that in every state less than 1 in 5 adults in the U.S. are consuming enough fruits and about 1 in 10 are consuming enough vegetables. Estimates ranged from 8% meeting fruit recommendations in Tennessee up to 18% in California, and for vegetables from 6% in Mississippi to 13% in California.
Author Interviews, Compliance, Cost of Health Care, Emergency Care, Primary Care, UCSD / 15.07.2015

Nadereh Pourat, PhD Professor, Department of Health Policy and Management, UCLA Fielding School of Public Health Adjunct Professor, UCLA School of Dentistry Director of Research, UCLA Center for Health Policy ResearchMedicalResearch.com Interview with: Nadereh Pourat, PhD Professor, Department of Health Policy and Management, UCLA Fielding School of Public Health Adjunct Professor, UCLA School of Dentistry Director of Research, UCLA Center for Health Policy Research Medical Research: What is the background for this study? What are the main findings? Dr. Pourat: We have succeeded to insure most of the uninsured population in the U.S., but now have to figure out how to reduce costs while improving health. We had the opportunity to examine the role of continuity with a primary care provider, which is one of the pathways that looked promising in improving health and reducing costs. We were evaluating a major demonstration program in California called the Health Care Coverage Initiative (HCCI) and one of the participating counties implemented a policy to increase adherence by only paying for visits if patients went to their assigned providers. We examined what happened to patients who always or sometimes adhered to their provider versus those who never adhered. We found that adherence or continuity reduced emergency department use and hospitalizations. This would lead to savings because of the high costs of these services. Medical Research: What should clinicians and patients take away from your report? Dr. Pourat: The study shows that both patients and clinicians would benefit from continuity with the primary care provider. Clinicians can actually make a difference in helping patients: they can teach patients about self-care and help them manage their conditions better. Patients would benefit from following through with treatment plans and experience less medical error and duplication of services which are potentially harmful. Continuity fosters rapport and trust between patients and providers and can be beneficial to both.
Author Interviews, Emergency Care, FDA, Opiods, Pharmacology / 15.07.2015

MedicalResearch.com Interview with: Christopher M. Jones, Pharm D., M.P.H Senior advisor, Office of Public Health Strategy and Analysis Office of the Commissioner, Food and Drug Administration Medical Research: What is the background for this study? Dr. Jones: Opioid analgesics and benzodiazepines are the two most common drug classes involved in prescription drug overdose deaths. In 2010, 75% of prescription drug overdose deaths involved opioid analgesics and 29% involved benzodiazepines. Opioid analgesics and benzodiazepines are also the most common drugs associated with emergency department visits due to nonmedical use of prescription drugs. Combined opioid and benzodiazepine use has been suggested as a risk factor for overdose death. Opioids and benzodiazepines have complex drug interactions and in combination can result in synergistic respiratory depression, but the exact mechanisms by which benzodiazepines worsen opioid-related respiratory depression are not fully understood. Widespread co-use of benzodiazepines and opioids has been documented in both chronic pain and addiction treatment settings. Studies suggest that among patients who receive long-term opioids for chronic non-cancer pain, 40% or more also use benzodiazepines. Among patients who abuse opioids, benzodiazepine abuse also is prevalent, and co-users report using benzodiazepines to enhance opioid intoxication. This study builds on the prior literature by analyzing trends on how the combined use of opioids and benzodiazepines in the U.S. contributes to the serious adverse outcomes of nonmedical use–related ED visits and drug overdose deaths. A better understanding of the consequences of co-use of these medications will help identify at-risk populations, inform prevention efforts, and improve the risk–benefit balance of these medications. Medical Research: What are the main findings? Dr. Jones: From 2004 to 2011, the rate of nonmedical use–related Emergency Department visits involving both opioid analgesics and benzodiazepines increased from 11.0 to 34.2 per 100,000 population. During the same period, drug overdose deaths involving both drugs increased from 0.6 to 1.7 per 100,000. Statistically significant increases in Emergency Department visits occurred among males and females, non-Hispanic whites, non-Hispanic blacks, and Hispanics, and all age groups except 12–17-year-olds. For overdose deaths, statistically significant increases were seen in males and female, all three race/ethnicity groups, and all age groups except 12–17-year-olds. Benzodiazepine involvement in opioid analgesic overdose deaths increased each year, increasing from 18% of opioid analgesic overdose deaths in 2004 to 31% in 2011.
Author Interviews, Brigham & Women's - Harvard, Heart Disease, JAMA, Statins / 14.07.2015

Dr. Ankur Pandya Ph.D. Assistant Professor of Health Decision Science Department of Health Policy and Management Harvard T.H. Chan School of Public Health Boston, MA MedicalResearch.com Interview with: Dr. Ankur Pandya Ph.D. Assistant Professor of Health Decision Science Department of Health Policy and Management Harvard T.H. Chan School of Public Health Boston, MA Medical Research: What is the background for this study? What are the main findings? Dr. Pandya: The American College of Cardiology and the American Heart Association (ACC-AHA) cholesterol treatment guidelines were controversial when first released in November 2013, with some concerns that healthy adults would be over-treated with statins. We found that the current 10-year ASCVD risk threshold (≥7.5%) used in the ACC-AHA cholesterol treatment guidelines has an acceptable cost-effectiveness profile (incremental cost-effectiveness ratio of $37,000/QALY), but more lenient ASCVD thresholds would be optimal using cost-effectiveness thresholds of $100,000/QALY (≥4.0%) or $150,000/QALY (≥3.0%).
Author Interviews, Memory, Occupational Health, Sleep Disorders / 14.07.2015

MedicalResearch.com Interview with: Jonathan Cedernaes M.D., Ph.D. Department of Neuroscience Uppsala University SwedenJonathan Cedernaes M.D., Ph.D. Department of Neuroscience Uppsala University Sweden Medical Research: What is the background for this study? What are the main findings? Dr. Cedernaes: Sleep is known to facilitate the formation of long-term memory in humans, by transferring newly learned memories from short-term to long-term memory stores. Studies however indicate that even shorter periods of sleep - including naps - can ensure access to different types of memories under normal restful conditions. Furthermore, while some studies have shown that acute sleep loss can exacerbate e.g. physiological responses to acute stress, it it has not been studied whether shortened sleep in combination with acute cognitive stress can have a negative impact on the retrieval of newly learned memories. With this background in mind, we conducted a study where we aimed to investigate how nocturnal sleep duration impacts this memory transfer, and to what extent long-term memories formed by sleep remain accessible after acute cognitive stress. We recruited 15 participants who in each of two sessions first underwent a learning session in the evening, during which they learned 15 card pair locations on a computer screen. Then, in one of the two experimental session, subjects slept for half a night (4-hr), instead being able to sleep for a full night (8-hr) in the other session. On the morning after each sleep condition, we had the subjects try to recall as many card pair locations as possible. We found that following half a night of sleep (4-hr), participants were equally able to recall memories for the learned card pair locations, as after a full night of sleep (8-hr). However, we also showed that the ability to retrieve memories following 30 minutes of acute stress, in the morning after these two sleep conditions, was different depending on whether the participants had slept for 8 or 4 hours. Following short sleep, the 30-min long stress exposure reduced the participants' ability to recall the card pair locations that the participants had learned the previous night by around 10%. In contrast, no such stress-induced memory impairment was observed when the same men were allowed to sleep for a full night.
Author Interviews, PTSD / 14.07.2015

MedicalResearch.com interview with Dr. Ella James, Post-Doctoral Investigator Scientist Medical Research Council Cognition and Brain Sciences Unit Cambridge, UK. MedicalResearch: What is the background for this study? Dr. James: Post-traumatic stress disorder (PTSD) is experienced by some people after a traumatic event. While many people who’ve been involved in traumatic events don’t experience PTSD, those who do typically have repeated visual intrusive memories of certain moments in vivid detail that pop back into mind, seemingly out of the blue. For example, with PTSD after a car crash might repeatedly ‘see’ the moment the other car crashed into them. The recommended treatment for PTSD is cognitive behaviour therapy, a talking therapy that has been demonstrated to work well. But it is only delivered once intrusive memories have become established and PTSD is diagnosable – i.e. at least one month after the traumatic event occurred. At present, there is nothing readily available for use soon after trauma that has been shown to prevent symptoms building up and PTSD becoming established. In previous laboratory work our research team showed that playing Tetris shortly after viewing events with traumatic content (e.g. film footage of road safety campaigns – what we call an experimental trauma) could reduce intrusive memories of those events in healthy volunteers over the following week [2, 3] when played in a 4-hour time window after viewing. We reasoned that this was because having to follow and track the shapes, colour and movement of the coloured blocks in Tetris soon after seeing the experimental trauma (the film) disrupted aspects of the visual memory of that event from being ‘laid down’ in the sensory part of the brain, whilst leaving memory for the narrative and meaning of the events unaffected. However, it is hard to reach people so soon after a traumatic event in the real world and memories for events become ‘fixed’ in mind within hours after an event making them difficult to change. Therefore it was important to show whether we can change older, established memories of trauma.
Author Interviews, Cost of Health Care, OBGYNE, Pharmacology / 14.07.2015

Nora V. Becker MD/PhD candidate Department of Health Care Management and Economics Wharton School, University of Pennsylvania, in Philadelphia. MedicalResearch.com Interview with: Nora V. Becker MD/PhD candidate Department of Health Care Management and Economics Wharton School, University of Pennsylvania, in Philadelphia. Medical Research: What is the background for this study? What are the main findings? Response: The Affordable Care Act mandates that private health insurance plans cover prescription contraceptives with no consumer cost sharing. The positive financial impact of this new provision on consumers who purchase contraceptives could be substantial, but it has not yet been estimated. Using a large administrative claims data set from a national insurer, we estimated out-of-pocket spending before and after the mandate. We found that mean and median per prescription out-of-pocket expenses have decreased for almost all reversible contraceptive methods on the market. The average percentages of out-of-pocket spending for oral contraceptive pill prescriptions and intrauterine device (IUD) insertions by women using those methods both dropped by 20 percentage points after implementation of the ACA mandate. We estimated average out-of-pocket savings per contraceptive user to be $248 for the IUD and $255 annually for the oral contraceptive pill.
Author Interviews, JAMA, OBGYNE / 13.07.2015

Diana W. Bianchi, M.D. Executive Director, Mother Infant Research Institute Vice Chair for Research and Academic Affairs, Department of Pediatrics Tufts Medical CenterMedicalResearch.com Interview with: Diana W. Bianchi, M.D. Executive Director, Mother Infant Research Institute Vice Chair for Research and Academic Affairs Department of Pediatrics Tufts Medical Center Medical Research: What is the background for this study? What are the main findings? Response: Noninvasive Prenatal Testing (NIPT) is the fastest growing genetic test. It has been available since late 2011. Over 2 million tests have been performed worldwide. Cancer in pregnancy is rare, and only occurs in 1 in 1,000 pregnant women. About 0.2 per cent of noninvasive prenatal tests that use sequencing of maternal plasma DNA have a so-called “false positive” result. In most cases this is not an error, but there is a biological explanation for the discrepancy between the abnormal noninvasive prenatal test result and a normal fetal chromosome result obtained from a diagnostic procedure, such as amniocentesis or chorionic villus sampling (CVS). We are very interested in the underlying biological explanations for the false positive cases, and it turns out that a clinically silent tumor in the mother is one of them. The mother’s tumor is shedding DNA into her blood that is detected by the prenatal test. In a large clinical dataset of over 125,000 pregnant women who had a DNA sequencing screen for fetal chromosome abnormalities there were 10 women who were subsequently found to have cancer. We retrospectively analyzed the DNA sequencing results in 8 of these women and found that they had abnormalities in multiple areas of the genome, suggesting that it was DNA from the tumor that was shed into the maternal blood and being detected by the prenatal screen. The noninvasive prenatal sequencing test result that was most suggestive of a cancer risk was the presence of more than one aneuploidy. This finding was present in 7 of the 10 women who had cancer. In three of the eight women we studied it was the abnormal prenatal test result that triggered a subsequent work-up that led to the diagnosis of cancer.
Author Interviews, Cost of Health Care, Heart Disease / 13.07.2015

MedicalResearch.com Interview with: Azfar B. Sheikh, M.D. Internal Medicine Resident Physician Staten Island University Hospital New York Medical Research: What is the background for this study? Dr. Sheikh: The background of this review article circles around the impact of atrial fibrillation on epidemiology, trends in hospitalizations, costs associated with hospitalization and outpatient care, in the United States. This article also describes the benefits of newer treatment modalities compared to the standard of care with regards to symptomatic improvement and prevention of thromboembolism. These findings are supported by several cost-utility analyses. Medical Research: What are the main findings? Dr. Sheikh:  The main findings of the study are:
  • The cost of hospitalization is three times higher for patients with atrial fibrillation than those without atrial fibrillation.
  • 5 million new cases are being reported annually.
  • The incidence of atrial fibrillation is projected to increase from 1.2 million cases in 2010 to 2.6 million cases by 2030. Due to this increase in incidence, the prevalence of atrial fibrillation is projected to increase from 5.2 million cases to 12.1 million cases by 2030.
  • The most common co-moribidites associated with atrial fibrillation were hypertension, diabetes mellitus, and chronic obstructive lung disease.
  • According to the NIS database, the atrial fibrillation. hospitalization rate has increased from 1552 to 1812 per one million US residents per year from 2000 to 2010 (relative increase 14.4%).
  • According to the NIS database, the mortality associated with atrial fibrillation hospitalizations has decreased significantly from 1.2% in 2000 to 0.9% in 2010 (relative decrease 29.2%).
  • The median length of stay in the hospital is 3 days and increases proportionally with a rise in CHADS2 score.
  • The largest source of direct healthcare costs associated with atrial fibrillation is hospitalization. According to the NIS database, the mean cost of inpatient atrial fibrillation hospitalization increased significantly from $6401 in 2001 to $8439 in 2010 (relative increase 24.0%). The mean cost of atrial fibrillation hospitalization also increases proportionally with a rise in CHADS2 score.
  • In the outpatient setting, the highest costs were associated with physician office visits in comparison to emergency room and urgent care visits.
  • With regards to prevention of thromboembolism, the new oral anticoagulant agents (dabigatran, rivaroxaban, and apixaban) have been found to be more cost-effective compared to warfarin.
  • Left atrial catheter ablation is more effective than rate control and rhythm control. It is more cost-effective in younger patients who are moderate risk for stroke.
AHA Journals, Author Interviews, Stroke / 13.07.2015

MedicalResearch.com Interview with: Dr. Ángel Chamorro Director, Comprehensive Stroke Center Hospital Clinic Barcelona, Spain Medical Research: What is the background for this study? What are the main findings? Dr. Chamorro: There is a great need of new therapies in patients with acute stroke and our study is based on the clinical observation that patients with acute stroke recover better if at the time of the stroke the levels of uric acid are increased in their blood. That first observation led to a long way of research and administrative challenges but we finally came out with a solution of uric acid (a potent antioxidant) manufactured according to the strict rules which apply to drugs aimed for human use. Thus, we performed a pilot study that showed that uric acid could be safely administered to these patients. We then performed a larger clinical trial in 421 patients which provided very encouraging results overall. Now we are reporting in the Stroke journal appearing on July 9, that women obtained a much greater benefit than men because they had lower levels of uric acid than men because estrogens (female hormones) are efficient excretors of uric acid. In consequence, women were in greater need of uric acid replenishment following the stroke than men.
Author Interviews, Cancer Research, Cognitive Issues, Radiation Therapy / 13.07.2015

MB. Pinkham, Clinical Oncology Christie NHS Foundation Trust Manchester UKMedicalResearch.com Interview with: MB. Pinkham, Clinical Oncology Christie NHS Foundation Trust Manchester UK Medical Research: What is the background for this study? Response: Brain metastases are a serious complication of advanced malignancy and for most patients the objective is to maximise quality of survival. As treatment decisions become increasingly tailored to the individual, patient-focussed measures of efficacy such as neurocognitive function (NCF) are an important consideration. This is illustrated by the NCCTG N0574 randomised study reported last month at the American Society of Clinical Oncology (ASCO) 2015 Annual Meeting. 208 patients with 1-3 brain metastases each <3cm were randomised to stereotactic radiosurgery (SRS) or SRS with whole brain radiotherapy (WBRT). The addition of WBRT improved intracranial disease control but did not translate into a survival benefit and was associated with a decline in neurocognitive function at 3 months. The objective of our study was to describe the types of changes in neurocognitive function that can occur, summarise how they are assessed and review approaches used to mitigate their effects. We wanted to provide busy physicians with a clear and comprehensive overview of the topic that could be used to inform clinical decisions. Medical Research: What are the main findings? Response: Using sensitive tests, most patients with brain metastases have deficits in neurocognitive function at diagnosis. Evaluating and understanding changes after treatment is complex because neurocognitive function is a dynamic process that is influenced by a long list of inter-related factors. For patients treated using whole brain radiotherapy alone, worsening neurocognitive function is observed in about two-thirds within 2-6 months. Deficits in verbal memory and fine motor control are most common. It is unclear what proportion relates to treatment toxicity as opposed to disease progression or pre-terminal decline because both are unfortunately also common events during this interval. By contrast, in other patients, NCF improves after WBRT due to treatment response. For patients with 1-4 brain metastases treated using SRS, the addition of WBRT improves intracranial disease control at the expense of deficits in verbal memory at 4 months but the impact of recurrence and salvage therapy on neurocognitive function later than this is uncertain. Scant data suggests that some deficits in neurocognitive function after WBRT may improve with time in long term survivors. For patients with ≥5 brain metastases, SRS and/or systemic therapies may be considered in select patients instead of upfront whole brain radiotherapy but high quality evidence is lacking. Advanced radiotherapy technologies, such as hippocampal-sparing WBRT and post-operative cavity SRS, can limit the dose delivered to unaffected areas of the brain in the hope of reducing toxicity. Randomised studies assessing their efficacy and cost-effectiveness in various clinical situations are underway prior to routine use. Small but statistically significant improvements in certain neurocognitive domains can also be achieved using medications such as memantine and donepezil. Preclinical data suggests that some commonly available drugs (such as ramipril, lithium and indomethacin) may have neuroprotective properties following WBRT; further evaluation is warranted.
Author Interviews, CHEST, Clots - Coagulation / 13.07.2015

MedicalResearch.com Interview with: David Jimenez PhD, FCCP Respiratory Department and Medicine Department Ramon y Cajal Hospital IRYCIS, and Alcala de Henares University Madrid Spain Medical Research: What is the background for this study? What are the main findings? Dr. Jimenez: Normotensive patients that have an estimated high-risk for pulmonary embolism (PE)-related complications (i.e., intermediate-risk PE) might benefit from surveillance in an intensive care setting or from the administration of specific advanced therapy. The Bova score was developed for identifying these patients. This study confirms the validity and reproducibility of the Bova score.
Author Interviews, Genetic Research / 13.07.2015

MedicalResearch.com Interview with: Chun Chieh Fan Ph.D student USCD Cognitive Science and Professor Anders M. Dale Ph.D Department of Cognitive Science, Multimodal Imaging Laboratory, Department of Radiology University of California, San Diego School of Medicine La Jolla, CA 92037 Medical Research: What is the background for this study? What are the main findings? Response: The shape of human skull is closely associated with the ancestral background. Forensics uses it for determining ethnicity. Anthropologists use it to infer neuroanatomical change in human evolution. Yet it is unclear the inner content of skull, human brain, contains how much information about individual’s ancestry. Our study found that different continental ancestries are associated with unique cortical folding patterns. Even for contemporary populations in modern day USA, a melting pot of ethnicities, cortical folding patterns are highly predictive of the percentage of each continental ancestry, as determined based on the person’s genotype. These shape differences between ancestral heritages are not necessarily related to brain function. It is highly possible that the shape differences are resulting from a random process accumulated along human history, without significant functional consequences.