AHA Journals, Author Interviews, Blood Pressure - Hypertension, Salt-Sodium / 31.07.2015

Salt-SodiumMedicalResearch.com Interview with: Tomonori Sugiura, MD, PhD Department of Cardio‐Renal Medicine and Hypertension Nagoya City University Graduate School of Medical Sciences Nagoya  Japan Medical Research: What is the background for this study? What are the main findings? Dr. Sugiura: Although there is a close relationship between dietary sodium and hypertension, the concept that individuals with relatively high dietary sodium are at increased risk of developing hypertension compared to those with relatively low dietary sodium, has not been intensively studied in a cohort. Therefore, the present observational study was designed to investigate whether individual levels of dietary sodium critically affect future increases in blood pressure in the general population. The main findings of this study were that a relatively high level of dietary sodium intake and also a gradual increase in dietary sodium, estimated by urinary sodium excretion, are associated with a future increase in blood pressure and the incidence of hypertension in the general population.
Author Interviews, Heart Disease, JACC, Johns Hopkins / 31.07.2015

Alan Cheng, MD, FACC, FAHA, FHRS Associate Professor of Medicine Associate Professor of Pediatrics Director, Arrhythmia Device Service Johns Hopkins University School of Medicine Baltimore, MD 21287MedicalResearch.com Interview with: Alan Cheng, MD, FACC, FAHA, FHRS Associate Professor of Medicine and Pediatrics Director, Arrhythmia Device Service Johns Hopkins University School of Medicine Baltimore, MD Medical Research: What is the background for this study? What are the main findings? Dr. Cheng: Sudden cardiac death (SCD) has been the most common way in which people in the United States die. While it's hard to accurately identify who is a higher risk for SCD, we have learned from a number of studies over the past 30-40 years that people with significant reductions in their heart function (measured as the ejection fraction (EF)) is one group of individuals at high risk for Sudden cardiac death. In fact, the current American College of Cardiology and American Heart Association guidelines state that people with an EF below 35% are at high enough risk for Sudden cardiac death that these patients should undergo implantation of an implantable cardioverter defibrillator (or ICD for short), a device capable of monitoring the heart 24/7 and shocking the heart out of any arrhythmias that could lead to Sudden cardiac death. The data they cite for this recommendation are so compelling that they currently recommend implanting ICDs in patients not only among those who already experienced an Sudden cardiac death event, but also those who have not. Implanting an ICD to prevent Sudden cardiac death before they have had Sudden cardiac death is known as primary prevention and this accounts for about 70-80% of all ICD implants in the United States. While the EF is the best metric out there to determine if a patient should get an ICD, it has its limitations. Because of these limitations, we have been interested for a long time in better understanding how the EF and other metrics affect a patient's risk for Sudden cardiac death. In this study, we followed 538 patients who were recipients of a primary prevention ICD who underwent repeat assessment of their EF during followup in order to determine if changes in their EF over time altered their risk for ICD shocks for ventricular arrhythmias or death. Over a median of almost 5 years of followup, we found that 40% of the cohort had improvements in their EF. And when the EF does improve, the risk goes down for ICD shocks for ventricular arrhythmias as well as for death.
Author Interviews, Brigham & Women's - Harvard, JAMA, Mental Health Research / 30.07.2015

Alexander C. Tsai, MD, PhD Center for Global Health, Massachusetts General Hospital, Boston Harvard Center for Population and Development Studies, Cambridge, MassachusettsMedicalResearch.com Interview with: Alexander C. Tsai, MD, PhD Center for Global Health Massachusetts General Hospital, Boston Harvard Center for Population and Development Studies Cambridge, Massachusetts Medical Research: What is the background for this study? What are the main findings? Dr. Tsai: Suicide is one of the leading causes of death among middle aged women, and the rates have been climbing over the past decade. At the same time, we know that Americans are becoming more and more isolated. As one example, over the past two decades, there has been a tripling in the number of people who say they don't have anyone to confide in about important matters. In our study, we tracked more than 70,000 American women over two decades and found that the most socially isolated women had a threefold increased risk of suicide.
Annals Internal Medicine, Author Interviews, Pain Research, Rheumatology / 30.07.2015

MedicalResearch.com Interview with: Raveendhara R Bannuru MD, PhD, FAGE Director, Center for Treatment Comparison and Integrative Analysis (CTCIA) Asst Professor of Medicine, Tufts University School of Medicine Special & Scientific Staff, Center for Arthritis and Rheumatic Diseases Tufts Medical Center Boston, MA Medical Research: What is the background for this study? Dr. Bannuru: Placebos are used to determine the efficacy of a wide variety of treatments for medical conditions such as osteoarthritis. A sound understanding of potential differences among placebos is essential for determining the relative efficacy of such treatments. Medical Research: What are the main findings? Dr. Bannuru: Our results indicate that different types of placebos do in fact differ in efficacy. Placebo injections and topical placebos were both found to be more effective than orally administered placebos for reducing knee osteoarthritis pain.
Accidents & Violence, Author Interviews, PLoS, Technology / 29.07.2015

Conrad Earnest, PhD, FACSM Texas A&M University College Station, TXMedicalResearch.com Interview with: Conrad Earnest, PhD, FACSM Texas A&M University College Station, TX Medical Research: What is the background for this study? Dr. Earnest: The study presented here is a thesis project performed by Robbyne Smith and Sammy Licence, under the direction of Professor Conrad Earnest. We were curious to about the effects of walking, texting and doing both while simultaneously being cognitively distracted by common tasks - in our case a maths test. Much of our curiosity was born from watching a YouTube video and reading an article on inattentional blindness where people did not notice a unicycling clown while using their mobile phones. https://www.youtube.com/watch?v=Ysbk_28F068 Several reports suggest that this type of pedestrian behavior leads to more pedestrian accidents, possibly increases the risk of tripping and increases riskier road crossing behavior due to a lack of attention. While much of the literature has examined this question using a “straight line” model to look at walking characteristics and deviations within ones walking path, we elected to build an obstacle course that imitated common barriers that we measured in the city of Bath, England, that pedestrians might encounter during their walking day. Medical Research: What are the main findings? Dr. Earnest: Our main findings were that people slowed their walking speed, took more steps in their approach to common obstacles, and increased the height of their step to go up steps and over curbs. Interestingly, we did not see an increase in what we called barrier contacts, which were used as a surrogate measure for tripping.
Author Interviews, Breast Cancer, Journal Clinical Oncology, Sexual Health / 29.07.2015

Martha F. Goetsch, MD, MPH Oregon Health & Science University Portland, OR 97239MedicalResearch.com Interview with: Martha F. Goetsch, MD, MPH Oregon Health & Science University Portland, OR 97239 MedicalResearch: What is the background for this study? Dr. Goetsch: Women who are survivors of breast cancer now number about 3 million in the US.  Therapy for breast cancer is anchored in creating a state of postmenopause in which estrogen is eliminated from the system. One of the most difficult symptoms of lack of estrogen is dyspareunia, the term for pain with intercourse. The old term “vulvovaginal atrophy” has been changed to “genitourinary syndrome of menopause” by agreement of two specialty societies. Because of my focus in the gynecologic specialty of vulvar pain, I have felt that this menopausal symptom is more than a condition of atrophy.  Additionally, my clinical experience has led me to believe that the exquisite tenderness is located in the vulvar vestibule rather than in the vagina. The vestibule is the inner vulva or entryway before the vagina. This study was devised to answer these hypotheses. I predicted that the population most likely to represent the worst examples of postmenopausal dyspareunia was the population of women who cannot use estrogen due to being survivors of breast cancer. I treated the problem as a pain problem rather than solely a problem of dryness.
Author Interviews, JCEM, Sleep Disorders / 29.07.2015

Jonathan Cedernaes M.D., Ph.D. Department of Neuroscience Uppsala University SwedenMedicalResearch.com Interview with: Jonathan 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: Previous studies have demonstrated that experimental sleep loss and simulated shift work (i.e. misalignment of circadian rhythms) reduces energy expenditure and insulin sensitivity, providing links to why sleep loss may increase the risk of e.g. type-2 diabetes and obesity. Such phenotypes have also been observed in animals in which clock genes are ablated. Clock genes regulate the circadian rhythms of all cells and variants in these have also been associated with increased risk of obesity, insulin resistance and type-2 diabetes in humans. Almost no study has however investigated whether overnight wakefulness - mimicking a situation which recurrently occurs in shift work - can affect the expression of such clock genes in metabolically important tissues, i.e. adipose tissue and skeletal muscle, in humans. Such gene expression changes may both acutely and more long-term be regulated by changes in methylation, i.e. an epigenetic change, which have been found in blood of e.g. shift workers and in e.g. adipose tissue of type-2 diabetic subjects. However, whether sleep loss can lead to epigenetic changes has been unknown, and therefore also whether this could affect genes important for metabolism, such as the core clock genes which are essential for orchestrating and synchronizing downstream metabolic processes according to our circadian rhythms. With this background in mind, I and associate professor Christian Benedict set out to conduct a study to investigate how one night of sleep loss altered gene transcription and methylation of core clock genes in adipose tissue and skeletal muscle, and whether this would be reflected at the systemic level by an impaired glucose tolerance test in healthy young individuals. For the study, we had 15 participants undergo two almost 2-day long sessions in our lab, with the first night of each session serving as a baseline or habituation night, with a normal sleep period. On the second night, in random order, participants slept a full night (8.5 hours) in one session, and were kept awake the entire night while being bed-restricted in the other of two sessions. After each of these conditions, we took biopsies in the fasting condition from the subcutaneous adipose tissue and the skeletal muscle. In collaboration with researchers from the Karolinska Institute, Gothenburg University and the German Institute of Human Nutrition, we were able to observe transcriptional repression of clock genes in the muscle, but not in the adipose tissue following sleep loss compared with normal sleep. Instead, we found methylation of regulatory elements of clock genes to be increased in the adipose tissue but not the skeletal muscle following sleep loss compared with normal sleep. Finally, we observed that participants had an impaired glucose tolerance test when they had been kept awake as compared with their response after sleep.
Author Interviews, Endocrinology, JAMA, Radiology, Surgical Research, UCSF / 28.07.2015

Quan-Yang Duh MD Endocrine surgeon UCSF Medical CenterMedicalResearch.com Interview with: Quan-Yang Duh MD Chief, Section of Endocrine Surgery UCSF Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Quan-Yang Duh: At UCSF we have a monthly Adrenal Conference (involving surgeons, endocrinologists and radiologists) to discuss patients we are consulted for adrenal tumors. About 30% of these are for incidentally discovered adrenal tumors (versus those found because of specific indications such as clinical suspicion or genetic screening). Of these 15-20% has bilateral adrenal tumors. The evaluation of unilateral incidentaloma has been very well studied and many national guidelines have been published with specific management recommendations. So during our monthly adrenal conference, we have a routine "script" for evaluation and recommendations (rule out metastasis by looking for primary cancer elsewhere, rule out pheochromocytoma and Cushing, resect secreting tumors or large tumors, and if no operation recommended repeat scan in 6 months, etc.). This “script” has worked very well for patients with unilateral incidentaloma. However, we were less certain when we made recommendations about bilateral incidentalomas because there was very little literature or guidelines written about it. We had some gut feelings, but we were not sure that we were recommending the right things. We needed more data. That was the main reason for the study. What we found in our study was that although the possible subclinical diseases were the same – hypercortisolism and pheochromocytoma, the probabilities were different. The patients with bilateral incidentalomas were more likely to have subclinical Cushing’s and less likely to have pheochromocytomas than those with unilateral incidentalomas.
Author Interviews, Brigham & Women's - Harvard, Cost of Health Care, JAMA / 28.07.2015

Benjamin D. Sommers, MD, PhD Assistant Professor of Health Policy & Economics Harvard T. H. Chan School of Public Health / Brigham & Women's Hospital Boston, MA 02115MedicalResearch.com Interview with: Benjamin D. Sommers, MD, PhD Assistant Professor of Health Policy & Economics Harvard T. H. Chan School of Public Health / Brigham & Women's Hospital Boston, MA 02115 Medical Research: What is the background for this study? What are the main findings? Response: The Affordable Care Act (ACA) expanded insurance options for millions of adults, via an expansion of Medicaid and the new health insurance Marketplaces, which had their first open enrollment period beginning in October 2013.  We used a large national survey to assess the changes in health insurance, access to care, and self-reported health since these expansions began.  What we found is that the beginning of the ACA’s open enrollment period in 2013 was associated with significant improvements in the trends of insurance coverage, access to primary care and medications, affordability of care, and self-reported health.  Among low-income adults in Medicaid expansion states, the ACA was associated with improvements in coverage and access to care, compared to non-expansion states. Gains in coverage and access to medicines were largest among racial and ethnic minorities.
Author Interviews, Critical Care - Intensive Care - ICUs, JAMA, Pediatrics / 28.07.2015

MedicalResearch.com Interview with: Wade Harrison, MPH The Dartmouth Institute for Health Policy & Clinical Practice Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire Medical Research: What is the background for this study? What are the main findings? Dr. Harrison: This study used national birth certificate data to examine time trends in Neonatal Intensive Care Unit (NICU) admission rates for all U.S. newborns and the composition of the cohort of admitted newborns.  Most of the existing studies of neonatal intensive care are limited in examining specific groups of newborns (e.g. those <1500 g, those with a specific complication, within limited geographies, etc.) or only looking at how care is delivered after a baby is admitted, leaving aside the question of whether to admit them in the first place.  This is an important area to study because the newborn period is a critical time for babies and their families to establish good feeding practices and increase bonding among other important needs; also, neonatal intensive care is very expensive and like all medical interventions can carry certain risks.  We found that NICU admission rates increased for all newborns across the birth weight spectrum.  Additionally, although NICUs were initially developed to care for very small and premature newborns, just under half of current NICU admissions are for normal birth weight and full term infants, who are likely to be less ill.
Author Interviews, FDA, JAMA / 27.07.2015

Dr. Pinar Karaca-Mandic Ph.D Associate Professor, Health Policy & Management School of Public Health Division of Health Policy & Management Minneapolis MN University of MinnesotaMedicalResearch.com Interview with: Dr. Pinar Karaca-Mandic Ph.D Associate Professor, Health Policy & Management School of Public Health Division of Health Policy & Management Minneapolis MN University of Minnesota Medical Research: What is the background for this study? What are the main findings? Dr. Karaca-Mandic: Drug safety has received a lot of attention recently, and FDA's post-marketing drug surveillance program (FAERS) offers and important opportunity to monitor drug safety and update drug warnings. There has been an increasing trend in reports to FAERS of serious adverse drug events and earlier studies suggested that these trends were primarily driven by increased manufacturer reports of serious and unexpected adverse events. While these studies highlighted the overall increase in adverse event rates, manufacturer timeliness in reporting and compliance with the 15 calendar day regulation for expedited reports was unknown, though some recent media coverage has offered anecdotal examples of delay. My co-authors and I were interested in studying not only the reporting of these events, by manufacturers to FDA, but also their timely reporting as required by the Federal regulation. Delays in reporting can have important public health consequences because the FDA uses this information to update drug warnings. We found that about 10% of serious and unexpected adverse events that are subject to the 15-day regulation were not reported by 15 days. We also found that events that involved a patient death were more likely to be delayed. For example, we found that after adjusting for other characteristics of the report and the patient, about 12% of events that involved patient death, and 9% of those that did not involve patient death were delayed beyond 15 days.
Author Interviews, JACC, Radiology, Stanford / 27.07.2015

MedicalResearch.com Interview with: Patricia Kim Phuong Nguyen MD and Joseph C. Wu, MD, PhD Stanford Cardiovascular Institute Stanford University School of Medicine, Stanford, California Medical Research: What is the background for this study? What are the main findings? Response: The application of CT imaging has greatly increased in the last two decades, raising concern over the effects of low dose radiation exposure from medical imaging. In this study, we recruited 67 patients who underwent CT imaging for various cardiovascular indications including: 1) Pre atrial fibrillation ablation 2) Pre Trans-catheter valve replacement 3) Aortic dissection, and 4) coronary artery disease. A wide range of doses were sampled. We detected damage to DNA and a small percentage of death of T lymphocytes isolated from patients  who were exposed to greater than 7.5 mSv of radiation. No damage was detected in patients exposed to very low doses (less than or equal 7.5 mSv). This study did not look at the relationship between radiation and cancer.
Author Interviews, Genetic Research, Heart Disease, PNAS, Rheumatology / 27.07.2015

MedicalResearch.com Interview with: Philippe Bouillet, PhD Walter and Eliza Hall Institute Parkville, Vic Australia Medical Research: What is the background for this study? What are the main findings? Dr. Bouillet: This study was initiated when we discovered mice that developed rheumatoid arthritis as a result of what was obviously a spontaneous dominant genetic mutation. Using several approaches, we identified the mutation as the insertion of a mobile genetic element called retrotransposon into the regulatory sequences of the gene encoding tumor necrosis factor (TNF). The mutation caused excessive amounts of TNF to be produced, a known cause of rheumatoid arthritis. The surprise came when some mice with the mutation died prematurely and suddenly with from heart disease. We showed that excess TNF also led to inflammation of the aortic and mitral valves, causing aortic regurgitation. Depending on the genetic background of the mice, the disease could also culminate in aortic aneurysm and death. We also investigated the regulatory region of the TNF gene and identified novel regulators and a new genetic element that normally make sure that levels of serum TNF are kept within reasonable limits, high enough to ensure its numerous physiological functions, low enough to prevent its harmful effects such as those described here.
AHA Journals, Author Interviews, Clots - Coagulation, Outcomes & Safety, Surgical Research / 27.07.2015

Riyaz Bashir MD, FACC, RVTProfessor of Medicine Director, Vascular and Endovascular Medicine Department of Medicine Division of Cardiovascular Diseases Temple University Hospital Philadelphia, PA 19140MedicalResearch.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 Medical Research: What is the background for this study? Dr. Bashir: Catheter-based thrombus removal also known as Catheter Directed Thrombolysis (CDT) is a minimally invasive therapeutic intervention that has evolved over the past two decades to reduce the incidence of post thrombotic syndrome (PTS), a very frequent and disabling complication of proximal deep vein thrombosis (DVT). Catheter-based thrombus removal has been shown to reduce this lifestyle limiting complication of DVT and as a result we have observed a significant increase in the utilization rates of CDT across United States. Recent nationwide observational data suggests that higher adverse events such as intracranial hemorrhage rates and need for blood transfusions are seen with CDT use. Nonetheless specific reasons for these findings have not been explored prior to this study. Thread veins, also known as spider veins, are small veins which can appear on your face, thighs or calves and are an issue that many patients want help with. However, they are a cosmetic issue rather than a medical problem. People who suffer from the spider veins often feel that they affect their appearance and confidence and question why do we get thread veins? Medical Research: What are the main findings? Dr. Bashir: This study showed a significant inverse relationship between the institutional Catheter-based thrombus removal volumes and safety outcomes like death and intracranial hemorrhage. The institutions with higher volume of CDT cases annually (greater than or equal to 6 cases) were associated with lower in-hospital mortality rates and lower intracranial hemorrhage rates as compared to institutions, which performed less than 6 cases annually. This study also showed that at high volume institutions there was no difference in terms of death or intracranial bleeding rates between CDT plus anticoagulation versus anticoagulation alone.
Author Interviews, JAMA, NYU/NYMC, PTSD / 24.07.2015

Charles R. Marmar, MD The Lucius Littauer Professor and Chair, Department of Psychiatry, NYU Langone Medical Center and Director of the Steven and Alexandra Cohen Veterans Center at NYU LangonMedicalResearch.com Interview with: Charles R. Marmar, MD The Lucius Littauer Professor and Chair, Department of Psychiatry, NYU Langone Medical Center and Director of the Steven and Alexandra Cohen Veterans Center at NYU Langone MedicalResearch: What is the background for this study? What are the main findings? Dr. Marmar: Approximately 2.7 million men and women served in Vietnam, and, for those who returned, many have suffered for decades from a variety of psychological problems resulting from their experiences and other injuries such as traumatic brain injury (TBI). The 25-year National Vietnam Veterans Longitudinal Study (NVVLS) was a way we could determine at various points in time how veterans were faring emotionally four decades after their service. While the vast majority are resilient, there are still over 270,000 Vietnam veterans who still have some form of post-traumatic stress disorder (PTSD) and one-third of these veterans have depression. We followed up with veterans who participated in the National Vietnam Veterans Readjustment Study (NVVRS) from 1984 to 1988 who were evaluated for PTSD. The NVVRS group represented a probability sample of those who served in Vietnam. Of the 1,839 participants still alive, 1,409 participated in at least one phase of the NVVLS, which involved a health questionnaire, health interview and clinical interview. The results showed that between 4.5 percent and 11.2 percent of male Vietnam veterans and 6.1 and 8.7 percent of the female veterans are currently experiencing some level of PTSD. About 16 percent of veterans in the study reported an increase of more than 20 points on a PTSD symptom scale compared to 7.6 percent who reported a decrease of greater than 20 points.
Author Interviews, Breast Cancer, Journal Clinical Oncology, NIH / 24.07.2015

Mitchell H. Gail, M.D., Ph.D. Senior Investigator Biostatistics Branch Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Rockville MD 20850-9780MedicalResearch.com Interview with: Mitchell H. Gail, M.D., Ph.D. Senior Investigator Biostatistics Branch Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Rockville MD 20850-9780 Medical Research: What is the background for this study? Dr. Gail: In the United States, breast cancer survival following diagnosis has been improving since the 1970s. We wanted to understand what might explain these shifts, to fully characterize the changes over time, and to explore whether tumor size and estrogen receptor status could help explain the  trends in age- and stage-specific breast cancer death rates after diagnosis. We evaluated survival from breast cancer from the date of diagnosis of all women diagnosed with invasive breast cancer in the US SEER Cancer Registries between 1973 and 2010. We excluded women with ductal or lobular carcinoma in situ.  We analyzed separate age groups (<50, 50-69, 70+ years) and SEER stage of disease (local, regional, distant). Medical Research: What are the main findings? Dr. Gail: Between 1973 and 2010, breast cancer death rates after diagnosis in the United States have fallen for each age group of women diagnosed with local or regional stage disease, not only in the first five years after diagnosis, but also thereafter.  For women under age 70, rates also fell for women with distant disease. Changes in tumor size or estrogen-receptor status do not explain much of the improvement among women under age 70 years, but do explain roughly half the improvement in 70+ year old women in the first five years after diagnosis.
Author Interviews, Heart Disease, JCEM, University of Pittsburgh, Women's Heart Health / 24.07.2015

Samar R. El Khoudary, Ph.D., M.P.H. Assistant professor Graduate School of Public Health Department of Epidemiology University of Pittsburgh MedicalResearch.com Interview with: Samar R. El Khoudary, Ph.D., M.P.H. Assistant professor Graduate School of Public Health Department of Epidemiology University of Pittsburgh Medical Research: What is the background for this study? Dr. El Khoudary: Cardiovascular disease is the leading cause of death in women, and it increases after age 50 - the average age when a woman is going through menopause. Weight gain in women during and after menopause has long been attributed to aging, rather than menopause itself. However, recent research identified changes in body fat composition and distribution due to menopause-related hormonal fluctuations. No previous study had evaluated whether those changes in fat distribution during menopause affect cardiovascular fat. Increased and excess fat around the heart and vasculature can be more detrimental than abdominal fat, causing local inflammation and leading to heart disease. Doubling certain types of cardiovascular fat can lead to a more than 50 percent increase in coronary events. My team and I investigated whether there may be a link between menopause and cardiovascular fat using data from 456 women from Pittsburgh and Chicago enrolled in the Study of Women's Health Across the Nation (SWAN). The women averaged about 51 years of age and were not on hormone replacement therapy. Medical Research: What are the main findings? Dr. El Khoudary: Our study is the first to find that  late- and post-menopausal women have significantly greater volumes of fat around their hearts than their pre-menopausal counterparts. As concentrations of the sex hormone estradiol - the most potent estrogen - declined during menopause, greater volumes of cardiovascular fat were found. The finding held even after my colleagues and I took into account the effects of age, race, obesity, physical activity, smoking, alcohol consumption, medication use and chronic diseases.
Author Interviews, Diabetes, PLoS / 23.07.2015

Dr. Stephanie K. Venn-Watson Doctor of Veterinary Medicine, MS Director, Translational Medicine and Research Program National Marine Mammal FoundationMedicalResearch.com Interview with: Dr. Stephanie K. Venn-Watson Doctor of Veterinary Medicine, MS Director, Translational Medicine and Research Program National Marine Mammal Foundation
    Medical Research: What is the background for this study? What are the main findings? Dr. Venn-Watson: Bottlenose dolphins, just like people, can develop a condition called metabolic syndrome. In humans, metabolic syndrome is also called prediabetes, which affects 1 in every 3 adults in the U.S. Some human studies have suggested that eating a diet high in fish may lower the risk of developing metabolic syndrome. Other similar studies, however, have had inconsistent findings. To better understand how fish diets may be associated with dolphin metabolic health, we compared 55 fatty acids among 49 dolphins and their dietary fish. We were surprised to find that the strongest predictor of lower, healthier insulin levels in dolphins was a saturated fat called, heptadecanoic acid (or C17:0). When we provided a diet higher in C17:0 to six dolphins over six months, their insulin, glucose, and triglycerides normalized. We also saw an immediate decrease in ferritin, a protein which - at high levels - may be a risk factor for metabolic syndrome. In addition to some fish, C17:0 is present in dairy fat, including whole fat milk and butter. C17:0 was not present in nonfat dairy products. We hypothesize that movement towards nonfat dairy foods may be lowering human C17:0 blood levels, which may be contributing to the global rise in metabolic syndrome and type 2 diabetes.
Author Interviews, Lancet, Melanoma, Radiation Therapy / 23.07.2015

MedicalResearch.com Interview with: Michael A Henderson MBBS BMedSc MD FRACS Professor of Surgery, University of Melbourne Deputy Director Division of Cancer Surgery Head Skin and Melanoma Service Division of Cancer Surgery Peter MacCallum Cancer Centre East Melbourne Victoria  Australia Medical Research: What is the background for this study? What are the main findings? Dr. Henderson:  A number of retrospective reviews of adjuvant radiotherapy after lymphadenectomy for patients at high risk of further lymph node field relapse had all suggested that the risk of lymph node field relapse was reduced but there was controversy about whether there was any impact on survival. In addition many clinicians were concerned about the side effects of radiotherapy and in the absence of a proven survival benefit were reluctant to recommend it. Previously a phase 2 trial of adjuvant radiotherapy conducted by one of our co-authors Prof Bryan Burmiester confirmed that the morbidity of lymph node field radiotherapy was limited and the risks of recurrence was reduced. On that basis the current ANZMTG TROG randomised multicentre trial was initiated. In summary this final report updates information on overall survival, lymph node field relapse etc and provides information for the first time on long term toxicity of treatment, quality of life and lymphedema. Adjuvant lymph node field radiotherapy for patients at high risk of further lymph node field relapse reduces the risk of further lymph node field relapse by 50% but it has no effect on survival. Although radiotherapy toxicity was common (3 in 4 patients), mostly involving skin and subcutaneous tissue it was mild-to-moderate in severity and had little impact upon the patient's quality of life as measured by the FACT-G quality of life tool. Specific regional symptoms were more common in the radiated group. Limb volume measurements confirmed a significant but modest increase for patients receiving inguinal radiation (15%) but not for axillary radiation. In the design of this trial, a decision was made to allow patients in the observation arm who developed an isolated lymph node field relapse to be salvaged by surgery and or radiotherapy. There were only two patients in the radiotherapy arm who developed an isolated lymph node field relapse and both died of metastatic disease. In the observation arm 26 patients developed an isolated lymph node field relapse and the majority (23) achieved lymph node field control with a combination of surgery and or radiotherapy. The five-year survival FROM development of a lymph node field relapse in this group was 34% which is comparable to the overall survival of the entire cohort (42% five-year overall survival). This information whilst a subset analysis suggests that if it would be reasonable in some patients to consider a policy of observation only, reserving further surgery and or radiotherapy for a second relapse.
Author Interviews, Brain Injury, JAMA, Outcomes & Safety, UCLA / 23.07.2015

Aaron J. Dawes, MD Fellow, VA/RWJF Clinical Scholars Program Division of Health Services Research, University of California Los Angeles Los Angeles, CA 90024MedicalResearch.com Interview with: Aaron J. Dawes, MD Fellow, VA/RWJF Clinical Scholars Program Division of Health Services Research, University of California Los Angeles Los Angeles, CA 90024 Medical Research: What is the background for this study? What are the main findings? Dr. Dawes: In the fall of 2013, we formed the Los Angeles County Trauma Consortium, building upon a prior administrative relationship between LA County’s 14 trauma centers. We added health research researchers from UCLA and USC, and shifted the focus of the group from logistical issues to quality improvement. As a first project, our hospitals wanted to know if there was any variation in how traumatic brain injury patients are cared for across the county. Traumatic brain injury accounts for over 1/3 of all injury-related deaths in the U.S. and is the number one reason for ambulance transport to a trauma center in LA County. When we looked at the data, we found widespread variation in both how these patients were cared for at different hospitals and what happened to them as a result of that care. After adjusting for important differences in patient mix, we found that mortality rates varied by hospital from roughly 25% to 55%. As we tried to explain this variation, we looked into how often hospitals complied with two evidence-based guidelines from the Brain Trauma Foundation, hoping that we could eventually develop an intervention to boost compliance with these recommended care practices. While compliance rates varied even more widely than mortality—from 10 to 65% for intracranial pressure monitoring and 7 to 76% for craniotomy—they did not appear to be associated with risk-adjusted mortality rates. Put simply, we found no connection between how often hospitals complied with the guidelines and how likely their patients were to survive.
Author Interviews, Infections, NEJM / 22.07.2015

MedicalResearch.com Interview with: Alison E. Heald, M.D Harborview Medical Center Seattle, WA 98104 MedicalResearch: What is the background for this study? What are the main findings? Dr. Heald: Marburg virus causes a very serious, potentially fatal infection in humans for which there is currently no licensed or approved treatments or vaccines.  We demonstrated that AVI-7288, an investigational drug specifically directed against Marburg virus, is effective in preventing death in monkeys exposed to Marburg virus in an experimental model, and that AVI-7288 raises no safety concerns in parameters measured in the healthy human volunteers dosed at or above the estimated efficacious dose. Importantly, taken together, these results have allowed us to predict a dose that could be expected to protect humans exposed to Marburg virus.
Author Interviews, Heart Disease, JACC / 22.07.2015

Dr. Jagat Narula MD, PhD Associate Dean For Global Affairs Professor Medicine, Cardiology and Radiology Mt. Sinai Hospital, NYMedicalResearch.com Interview with: Dr. Jagat Narula MD, PhD Associate Dean For Global Affairs Professor Medicine, Cardiology and Radiology Mt. Sinai Hospital, NY Medical Research: What is the background for this study? What are the main findings? Dr. Narula: The cardiovascular diseases remain number one cause of mortality in men and women and in high as well as middle and low income countries. It is important that we identify those who are likely to die of preventable causes. Identification of the vulnerable plaques that are likely to result in acute events has been an interesting focus of investigators, and numerous intravascular imaging and noninvasive imaging strategies have been employed. CT angiography has offered fairly attractive accuracy. We were the first to establish the features of high-risk plaques (Motoyama, Narula JACC 2007) and their short-term prognostic implications (Motoyama, Narula JACC 2009). In this new paper in a large population we present intermediate- to long-term follow-up that critically analyzes the role of plaque characterization and puts it in perspective. Should we keep chasing plaques or should we treat the patient? Does the answer lie in high risk plaque busting or prevention be the mainstay? From the previous studies from us and others we have known that computed tomography angiography (CTA)-based plaque characteristics identify high-risk plaque (HRP) that predict short-term risk of acute coronary syndrome (ACS). We in this study wanted to evaluate whether plaque characteristics by CTA would predict intermediate- to long-term likelihood of acute events. The presence of high-risk plaque characteristics were evaluated in more than 3000 patients undergoing CTA and plaque progression (PP) in additional 450 patients who had two CTA one year apart. We recorded fatal and nonfatal acute events and outcomes during follow-up: mean about 4 years and maximum up to 10 years. Acute Coronary Syndrome occurred in about 40 of ~300 (16%) with high risk plaque and 40 (less than 1.5%) of the remaining patients with non high risk plaques. In patients with serial CTA, plaque progression also was an independent predictor of ACS, with HRP (27%) and without HRP (10%) compared with patients without plaque progression (0.3%).
Author Interviews, Duke, Education, Heart Disease, JAMA / 22.07.2015

Carolina Malta Hansen, M.D Duke Clinical Research InstituteMedicalResearch.com Interview with: Carolina Malta Hansen, M.D Duke Clinical Research Institute Medical Research: What is the background for this study? What are the main findings? Dr. Hansen: Approximately 300,000 persons in the United States suffer an out-of-hospital cardiac arrest every year and under 10% survive. Cardiopulmonary resuscitation (CPR) and defibrillation within the first few minutes of cardiac arrest can increase the chance of survival from under 10% to over 50%. In 2010, the HeartRescue program in North Carolina initiated statewide multifaceted interventions to improve care and outcomes for cardiac arrest patients in North Carolina. The project included public training programs in defibrillators and compression-only CPR at schools, hospitals and major events such as the N.C. State Fair, plus additional instruction for EMS and other emergency workers on optimal care for patients in cardiac arrest. We found that following these four years of initiatives to improve care and outcomes for cardiac arrest patients, the proportion of patients who received bystander CPR and first responder defibrillation increased by more than 25% to approximately 50%, the combination of bystander CPR and first responder defibrillation increased from 14% to 23%. Survival with favorable neurologic outcome increased from 7% to 10% and this increase was only observed among patients who received bystander CPR. Finally, we found that compared to patients who received CPR and defibrillation by emergency medical services (EMS), patients who received bystander and/or first responder CPR, defibrillation, or both, were more likely to survive. The combination of bystander CPR and bystander defibrillation was associated with the best survival rates but remained low during the study period with no increase over time.
Author Interviews, Heart Disease, JACC, Outcomes & Safety, Surgical Research / 22.07.2015

Dr Scot Garg FRCP PhD (Hons) FESC Cardiology Department, Royal Blackburn Hospital United KingdomMedicalResearch.com Interview with: Dr Scot Garg FRCP PhD (Hons) FESC Cardiology Department, Royal Blackburn Hospital United Kingdom Medical Research: What is the background for this study? Dr. Garg: In contrast to other countries, in particular the United States, the UK has seen a vast expansion in the number of PCI centres operating without on-site surgical support. Part of the reason for this is that outcome data from these centres are from modest populations at short-term follow-up; consequently the ACC/AHA have failed to give delivery of PCI in centres without surgical back-up a strong endorsement. The study was ultimately driven therefore to show whether any differences existed in mortality between patients having PCI in centres with- and without surgical support at long-term follow-up in large unselected population cohort. Medical Research: What are the main findings? Dr. Garg: The study included the largest population of patients treated in centres without off-site surgical support (n=119,036) and main findings were that following multi-variate adjustment there were no differences in mortality for patients treated at centres with- or without surgical support at 30-days, 1-year or 5-year follow-up irrespective of whether patients were treated for stable angina, NSTEMI or STEMI. Furthermore, similar results were seen in a sensitivity analysis of a propensity matched cohort of 74,001 patients.
Author Interviews, Breast Cancer, Journal Clinical Oncology, Race/Ethnic Diversity / 21.07.2015

Helmneh Sineshaw, MD, MPH Senior Epidemiologist, Health Services Researcher American Cancer Society, Inc Atlanta, GA 30303MedicalResearch.com Interview with: Helmneh Sineshaw, MD, MPH Senior Epidemiologist, Health Services Researcher American Cancer Society, Inc Atlanta, GA 30303 MedicalResearch: What is the background for this study? Dr. Sineshaw: Male breast cancer is a rare disease, and its incidence rate is increasing. Younger black men have a higher breast cancer incidence than their white counterparts. Although black/white disparities in treatment receipt and survival among women with breast cancer have been widely documented in the literature, there have been few similar studies in men with breast cancer. Previous studies were based on smaller sample size, older databases, or using data from elderly patients.
Author Interviews, BMJ, Nutrition, Weight Research / 20.07.2015

Fumiaki Imamura Ph.D. MRC Epidemiology Unit University of CambridgeMedicalResearch.com Interview with: Dr. Fumiaki Imamura Ph.D. MRC Epidemiology Unit University of Cambridge Medical Research: What is the background for this study? What are the main findings? Dr. Imamura: Soft drink consumption is associated with risk of diabetes, but whether or not the association persists after controlling for obesity status is not known. Diet drinks and fruit juice may be good alternatives to soft drinks. However, while obese individuals may consume diet drinks or fruit juice instead of sugar-sweetened soft drinks, evidence was weak to determine whether or not consuming these beverages is associated with risk of diabetes.
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.