Author Interviews, Biomarkers, Breast Cancer / 30.07.2015

Karla M. Gonye, MBA President, sphingotec LLC Cambridge, MassachusettsMedicalResearch.com Interview with: Karla M. Gonye, MBA President, sphingotec LLC Cambridge, Massachusetts MedicalResearch: What is the background for this study? Response:
  • Met- and Leu-Enkephalin: are endogenous pentapeptides of the family of opioid peptides known as opiod-growth factors (OGF)
  • Enkephalins have been widely studied and play a major role in a variety of physiological processes
    • Perception of pain
    • Regulation of stress
    • Regulation of cardiovascular function
    • Regulation of bone formation
    • Regulation of immune responses
  • Alcohol and pain relievers reduce synthesis of Enkephalins
  • Met-Enkephalin (opioid growth factor) inhibits tumor progression and metastasis and enhances natural killer cell activity1,2
  • Mechanisms3-7:
    • Opioids can directly interact with tumor cells to cause a cytotoxic or antiproliferative effect
    • Opioids can modulate host antitumor immune mechanisms
  • Opiods can also induce apoptosis
  • We need enkephalins to help inhibit tumor progression
  • At sphingotec, it was hypothesized that disease progression begins earlier than symptoms are present and that reduced enkephalins in the blood would be an indicator of future breast cancer; measurement of this hormone peptide was possible with the company’s expertise, and that test could be developed to precisely measure enkephalin.
  • This method is published in a separate publication by Ernst et al (2006) in Peptides.
  • To test this hypothesis, Sphingotec measured enkephalin levels in the MDC and MPP study populations to determine if an association could be made between lower enkephalins and risk of breast cancer: We related proenkephalin (P-ENK) in fasting plasma from 1929 healthy women (mean age 58±5.9 years) of the population based Malmö Diet and Cancer Study (MDCS) to incidence of breast cancer (n=123) using multivariate Cox proportional hazards models during 14.8 years of follow-up. For replication, P-ENK was related to risk of breast cancer (n=130) in an older independent sample from the Malmö Preventive Project (MPP) consisting of 1569 women (mean age 70.0±4.4 years), using multivariate logistic regression.
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.
Author Interviews, C. difficile, Infections / 30.07.2015

Dr. Monika Pogorzelska-Maziarz PhD MPH Thomas Jefferson University, Jefferson School of Nursing Philadelphia, PA 19107MedicalResearch.com Interview with: Dr. Monika Pogorzelska-Maziarz PhD MPH Thomas Jefferson University, Jefferson School of Nursing Philadelphia, PA 19107 Medical Research: What is the background for this study? What are the main findings? Dr. Pogorzelska-Maziarz: Sharps disposal containers are ubiquitous in healthcare facilities and there is a growing trend toward hospitals using reusable sharps containers. Several research studies have raised concerns about the potential for sharps containers to become a source of pathogen transmission within the healthcare setting but this issue that has not been systematically studied. This is an important issue given that contamination of the hospital environment has been shown to be an important component of pathogen transmission. To examine whether the use of reusable versus single use sharps containers was associated with rates of Clostridium difficile, we conducted a cross-sectional study of acute care hospitals. Survey data on the different types of sharps containers used were collected from over 600 hospitals and this data was linked to the Medicare Provider Analysis and Review (MedPAR) dataset, which contains facility characteristics and C. diff infections data. We found that hospitals using single-use containers had significantly lower rates of C. diff versus hospitals using reusable containers after controlling for hospital characteristics such as geographic region, teaching status, ownership type, hospital size and urbanicity. This is an important finding giving the ubiquitous nature of sharps containers in the health care setting, the growing trend toward hospitals using reusable sharps containers and the high burden of C. diff in the hospital setting.
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.
Author Interviews, CDC, Cost of Health Care / 30.07.2015

Jared Fox, PhD CDC Office of the Associate Director for PolicyMedicalResearch.com Interview with: Jared Fox, PhD CDC Office of the Associate Director for Policy Medical Research: What is the background for this study? What are the main findings? Dr. Fox:  Increasing the number of people who get preventive care is important to keep people healthier, avoid complications from illnesses, reduce long-term health care costs, and prevent premature deaths. By one estimate, over 100,000 lives could be saved each year if more people got their recommended preventive care. By providing access to affordable insurance coverage and eliminating out-of-pocket costs for recommended preventive care in most health plans, the Affordable Care Act has reduced cost as a barrier to preventive care. This report could serve as a baseline for tracking the effects of some of the ACA’s preventive care provisions that might occur after 2012. The services in this study are recommended by the US Preventive Services Task Force and the Advisory Committee for Immunization Practices. The nine preventive services that were part of this study were:  screenings for blood pressure, breast cancer, cervical cancer, cholesterol, colon cancer, and diabetes; healthy diet counseling; and vaccination for hepatitis A and B. The data is from the 2011 and 2012 National Health Interview Survey. In 2011 and 2012, people with health insurance received needed preventive care at up to three times the rate of those without insurance. People with higher household incomes also got more recommended preventive care than those with lower incomes.
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, Biomarkers, Breast Cancer / 29.07.2015

Karla M. Gonye, MBA President, sphingotec LLC Cambridge, MassachusettsMedicalResearch.com Interview with: Karla M. Gonye, MBA President, Sphingotec LLC Cambridge, Massachusetts MedicalResearch: What is the background for this study? Response:
  • In experimental studies, Neurotensin and neurotensin expression was highly associated to breast cancer tissue
    • Dupouy et al (2009) investigated the expression of NTS and NTSR1 in normal human breast tissue and in invasive ductal carcinomas (IDCs) and found that NTS is expressed in ductal and invasive components of IDCs. The high expression of NTSR1 is associated with the SBR grade 3 (p<0.05), larger tumor size (p<0.01), and the number of metastatic lymph nodes (p<0.05).
    • It was concluded from this paper that NTS/NTSR1 is a contributor to breast cancer progression.
    • Souaze et al (2006)also studied IDCs and found 34% of all tumors were positive for neurotensin and 91% positive for the NT1 receptor, suggesting the contribution of neurotensin’s involvement in the signaling cascade within breast cancer progression.  In this study, it was found that disruption of neurotensin receptor signaling by silencing RNA or using a specific NT1 antagonist in nude mice xenografted with an aggressive cell line SR48692, caused the reversion of transforming functions that lead to tumor growth.
    • These findings support the contribution of neurotensin to breast cancer progression.
    • Wu, Z. et al (2013) reviewed the contribution of the neurotensinergic system to cancer progression, as well as the regulation and mechanisms of the system in order to highlight its potential as a therapeutic target, and its prospect for its use as a treatment in certain cancers.
    • This summarizes nicely the oncogenic effects of neurotensin after stimulation signaling proliferation, survival, migration, invasion and neoangeogeneis.
    • Several other papers published demonstrate the effects of neurotensin in cancers including breast cancer.
    • New studies such as Roselli et al (2015) further demonstrate the role of neurotensin in aggressive breast cancer.
    • At sphingotec, it was hypothesized that disease progression begins earlier than symptoms are present and that elevated expression of neurotensin in the blood would be an indicator of future breast cancer; measurement of this hormone peptide was possible with the company’s expertise, and that test could be developed to precisely measure neurotensin.
    • This method is published in Ernst et al (2006) in Peptides.
    • To test the hypothesis, the first clinical study was conducted in a cohort of normal healthy population that was indentified from the Malmo Diet and Cancer study, a prospective epidemiological study of 28,449 men and women. Of this group, a subset of 4632 randomly selected subjects were identified and neurotensin was measured in all subjects. Subjects were adjusted for known breast cancer risk factors such as age, age of menarche, heredity of cancer (all), hormone status, etc. (see Table 3, Melander et al JAMA 2012) so that the factors did not influence outcomes. On a 10-15 follow up period, of these subjects, 123 breast cancer events were found to be associated with higher levels of neurotensin, with the highest quartile associated with the highest levels of neurotensin and the lowest quartile associated with the lowest levels of neurotensin. The association of elevated neurotensin was found to be statistically significant for prediction of breast cancer.
Author Interviews, Fertility, NIH / 29.07.2015

Carmen J. Williams, M.D., Ph.D. Principal Investigator National Institute of Environmental HealthMedicalResearch.com Interview with: Carmen J. Williams, M.D., Ph.D. Principal Investigator National Institute of Environmental Health Medical Research: What is the background for this study? Dr. Williams: G-protein coupled receptors are used by almost all cells to receive signals from the outside of the cell and transduce these signals into actions within the cell. There are hundreds of these receptors, but many of them link to a protein named Gq to transmit their signals to other cellular proteins. Gq is found in most cells, including eggs, and activating Gq protein is one way to artificially activate the egg to begin developing into an embryo, even though it is not the way sperm normally do this. In fact, if the egg is activated before the sperm arrives it prevents the sperm from binding and fusing with the egg, so fertilization cannot take place. As a result, we thought that a mechanism might be in place within eggs to prevent them from being activated prematurely by signals that could activate Gq by triggering G-protein coupled receptors. RGS2 was a good candidate for this function because it binds to Gq in a way that prevents Gq from transmitting signals to other cellular proteins.
Author Interviews, Blood Pressure - Hypertension, NYU/NYMC, Race/Ethnic Diversity / 29.07.2015

MedicalResearch.com Interview with: Sripal Bangalore, MD, MHA, FACC, FAHA, FSCAI, Director of Research, Cardiac Catheterization Laboratory, Director, Cardiovascular Outcomes Group, The Leon H. Charney Division of Cardiology, Associate Professor of Medicine, New York University School of Medicine, New York, NY 10016.Sripal Bangalore, MD, MHA, FACC, FAHA, FSCAI Director of Research, Cardiac Catheterization Laboratory, Director, Cardiovascular Outcomes Group, The Leon H. Charney Division of Cardiology, Associate Professor of Medicine, New York University Langone School of Medicine, Principal Investigator ISCHEMIA-CKD trial

Medical Research: What is the background for this study? What are the main findings? Dr. Bangalore: Angiotensin converting enzyme inhibitors (ACEi) are a common class of antihypertensive agents used for the management of hypertension. In many national and international hypertension guidelines, they are recommended as a first line agent. However, their efficacy and safety in hypertensive Blacks is not known. In an analysis of hypertensive blacks we found that ACEi were consistently inferior to that of calcium channel blockers or thiazide diuretics with a higher risk of cardiovascular events. Medical Research: What should clinicians and patients take away from your report? Dr. Bangalore: Although ACEi are recommended as first line agents by national and international guidelines, they likely are not a great choice for hypertensive blacks. In fact few of the guidelines recognize this and recommend calcium channel blockers or diuretics for hypertensive blacks--consistent with the results seen in our study.
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, Nutrition, University Texas, Weight Research / 28.07.2015

Junfeng Jiao, PhD Assistant Professor, The University of Texas at Austin School of Architecture Director, Urban Information Lab Austin, TexasMedicalResearch.com Interview with: Junfeng Jiao, PhD Assistant Professor, The University of Texas at Austin School of Architecture Director, Urban Information Lab Austin, Texas Medical Research: What is the background for this study? Dr. Jiao: The increase in obesity rates has been explained by dietary changes including the consumption of high-energy, low-nutrient foods. Over the past thirty years, trends reveal increases of eating away from home. Public Health professionals have hypothesized that the heightened exposure to the ubiquitous fast food establishments may be an avenue through which health and diets are impacted. Medical Research: What are the main findings? Dr. Jiao: This study examined whether the reported health impacts of eating at a fast food or quick service establishment on a frequent basis were associated with having such a restaurant near home. Results indicated that eating at a fast food or quick service restaurant two times or more per week was related with perceived poor health status, overweight, and obese. Simply living close to such establishments was not related to negative health outcomes such as being overweight or obese, having cardiovascular disease (CVD) or diabetes.
Author Interviews, Dermatology, Melanoma / 28.07.2015

MedicalResearch.com Interview with: Christina Y. Lee BA Department of Dermatology Pedram Gerami, MD Robert H. Lurie Cancer Center Feinberg School of Medicine Northwestern University Chicago, Illinois Medical Research: What is the background for this study? What are the main findings? Response: Melanoma is responsible for the majority of skin cancer-related mortality. While AJCC staging of melanoma provides highly valuable information that helps predict the behavior of cutaneous melanoma, there are likely a number of other variables not included that may help predict which melanomas may result in metastasis. Some of these data points are not be easily assessed or available in large databases. In this study, we sought to assess a broad range of specific clinical factors directly obtained from clinic notes that may help predict melanoma behavior. The study consisted of a large cohort of patients with clinical follow up from our melanoma center at Northwestern University. Some examples of evaluated characteristics include a documented history of tanning bed use, blistering sunburns, or outdoor activity. In our study, patients who were older or immunosuppressed at the time of diagnosis were associated with aggressive tumor behavior in multivariate statistical analysis, when controlled for traditional AJCC factors such as  tumor depth, ulceration, and mitotic figures.
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, Geriatrics, Heart Disease, Surgical Research / 27.07.2015

Yigal Abramowitz, MD Cedars-Sinai Heart InstituteMedicalResearch.com Interview with: Yigal Abramowitz, MD Cedars-Sinai Heart Institute Medical Research: What is the background for this study? Dr. Abramowitz: The number of elderly patients with severe symptomatic aortic stenosis (AS) that require aortic valve replacement has been significantly increasing in recent years. However, a decade ago, third of the patients were not referred to surgery, in particular because of advanced age, and /or multiple comorbidities. TAVR has emerged as a treatment option for elderly inoperable or high-risk surgical patients with severe aortic stenosis. There is scarce evidence on the feasibility and safety of TAVR in very old patients. Medical Research: What are the main findings? Dr. Abramowitz: We compared 136 patients that were at least 90 years old at the time of TAVR (mean age: 92.4years) to 598 younger patients (mean age: 79.7years). Device success was excellent in both groups (96% for both). All-cause mortality at 30-days and 1-year was 2.9% and 12.5% vs. 2.8% and 12.3%  in patients aged ≥ 90 and ˂ 90, respectively. All major complication rates were similar between groups.
Author Interviews, Dermatology, Toxin Research / 27.07.2015

Andrew T. Patterson, MD The Ohio State University College of Medicine The Ohio State University Wexner Medical Center Columbus, OhioMedicalResearch.com Interview with: Andrew T. Patterson, MD The Ohio State University College of Medicine The Ohio State University Wexner Medical Center Columbus, Ohio Medical Research: What is the background for this study? What are the main findings? Dr. Patterson: The utilization of Agent Orange (AO) and other herbicides by the United States during the Vietnam War was controversial at the time and remains a prominent topic of scrutiny even today due to the potential long-term health effects facing exposed military and civilian personnel. The Institute of Medicine (IOM) in accordance with the National Academy of Sciences publishes a semi-annual review of the scientific and medical data regarding the resultant medical effects of Agent Orange and other organochlorine chemical exposures, however, skin diseases are no longer comprehensively assessed. This represents an important practice gap, as in our experience, we had encountered a significant number of patients inquiring whether their cutaneous ailment could be the result of Agent Orange exposure. Our goal was to perform a systematic review of the literature and produce a practical summary of the current evidence regarding cutaneous manifestations of organochlorine exposures that could be utilized by military and non-military dermatologists alike when responding to questions related to prior Agent Orange contact. After examining the literature, there appears to be an increased risk for chloracne, porphyria cutanea tarda, cutaneous lymphoma, and soft-tissue sarcomas including dermatofibrosarcoma protuberans and leiomyosarcomas in organochlorine-exposed patients. Some evidence exists for a possible increased incidence of melanomas, non-melanoma skin cancers, milia, eczema, dyschromias, dysesthesias, and rashes not otherwise specified, but the data is not conclusive. Even less support exists for an association with psoriasis, seborrheic dermatitis, neurodermatitis, and hypertrichosis
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.
Author Interviews, Lymphoma, Nutrition / 27.07.2015

Mara Meyer Epstein, ScD Assistant Professor Meyers Primary Care Institute University of Massachusetts Medical SchoolMedicalResearch.com Interview with: Mara Meyer Epstein, ScD Assistant Professor Meyers Primary Care Institute University of Massachusetts Medical School MedicalResearch: What is the background for this study? What are the main findings? Dr. Epstein: Hodgkin lymphoma is a relatively rare cancer, with about 9,000 new cases diagnosed in the US each year. Hodgkin lymphoma is most commonly diagnosed in earlier (aged 15-34 years) or later adulthood (aged ≥50 years). The causes of the disease are not well understood, and most identified risk factors are not modifiable (for example, age, sex, family history, and infection with Epstein-Barr virus [EBV]). Previous studies have suggested that chronic inflammation may play a role in the development of Hodgkin lymphoma. Therefore, it is possible that a factor that can influence inflammation, such as diet, may be associated with risk of Hodgkin lymphoma. Discovering modifiable risk factors for Hodgkin lymphoma could offer a means for preventing this disease. The few existing studies of diet and Hodgkin lymphoma risk have focused on individual nutrients or foods; this is the first study to examine dietary pattern and risk of Hodgkin lymphoma. By examining dietary patterns instead of individual foods, we sought to assess Hodgkin lymphoma risk from the food combinations that may more closely reflect typical dietary habits. The current study includes 435 cases of Hodgkin lymphoma and 563 controls with no history of cancer from Massachusetts and Connecticut who were enrolled in the study between 1997 and 2000. Cases and controls provided information about their average intake of 61 food and beverage items over the year prior to the study. By evaluating foods commonly consumed by the study participants, we identified four major dietary patterns; high vegetable intake, high meat intake, high intake of fruit and low-fat dairy, and high intake of desserts and sweets. We looked for associations between each dietary pattern and risk of Hodgkin lymphoma overall, and also separately by age group (<50 years or ≥50 years old), tumor EBV status (positive or negative), and by tumor cell pattern (nodular sclerosis or mixed cellularity). The dietary pattern characterized by high intake of desserts and sweets was associated with a statistically significant increased risk of Hodgkin lymphoma among younger adults, and in particular, a 2-fold increased risk among younger adults with EBV-negative tumors. The dietary pattern featuring high meat intake was associated with a 3-fold increased risk of Hodgkin lymphoma among older adults, and again, we saw a stronger association among older adults with EBV-negative tumors, although the number of such cases in this group was small. We did not observe a clear association between the high vegetable dietary pattern, or the dietary pattern high in fruit and low-fat dairy intake, with Hodgkin lymphoma risk, and we also did not find any clear associations with EBV-positive tumors, which were relatively infrequent in the study population. The findings described above were obtained from statistical calculations that also took into account known Hodgkin lymphoma risk factors, other lifestyle factors, total caloric intake, and body mass index.
Aging, Author Interviews, Cost of Health Care, Electronic Records, Geriatrics / 27.07.2015

MedicalResearch.com Interview with: Nisha C. Hazra MSc Department of Primary Care and Public Health Sciences, King's College London, London, UK Medical Research: What is the background for this study? What are the main findings? Response: Our study was motivated by limited evidence about the health status of very old people, the fastest growing group of the UK population with significant implications for future NHS health-care costs. Our findings indicated an increasing number of people reaching the age of 100 years, with the increase being higher among women comparing to men (a ratio of 4 to 1). Another interesting finding was that men reaching 100 years tended to be healthier than their female counterparts. In particular, women were more likely to present multiple chronic diseases compared to men and tended to be more frail, experiencing more falls, fractures, incontinence and hearing/visual impairments.
Author Interviews, Cost of Health Care, Social Issues / 27.07.2015

Laura Rosella, PhD MHSc Assistant Professor, Dalla Lana School of Public Health, University of Toronto Scientist, Public Health Ontario Adjunct Scientist, Institute for Clinical Evaluative Sciences Toronto, OntarioMedicalResearch.com Interview with: Laura Rosella, PhD MHSc Assistant Professor, Dalla Lana School of Public Health, University of Toronto Scientist, Public Health Ontario Adjunct Scientist, Institute for Clinical Evaluative Sciences Toronto, Ontario Medical Research: What is the background for this study? What are the main findings? Response: High-cost users of health care generally refer to the top five per cent of health care users. They are a small portion of the population who consume a disproportionately high share of health care resources. We undertook a study to explore the social and economic determinants that were associated with future, high cost users. That is, the characteristics of these individuals before they proceed on a trajectory of high health care utilization. By understanding these associations we can better understand the role that socio-economic factors play in future health care utilizations and costs.
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, Nutrition, Weight Research / 25.07.2015

Benjamin D. Horne, PhD, MPH, FAHA, FACC Director, Cardiovascular and Genetic Epidemiology, Intermountain Heart Institute Adjunct Assistant Professor, Genetic Epidemiology Division, Department of Medicine, University of UtahMedicalResearch.com Interview with: Benjamin D. Horne, PhD, MPH, FAHA, FACC Director, Cardiovascular and Genetic Epidemiology, Intermountain Heart Institute Adjunct Assistant Professor, Genetic Epidemiology Division, Department of Medicine, University of Utah Medical Research: What is the background for this study? What are the main findings? Dr. Horne:  A rapidly expanding set of results from animal studies exists regarding the effects of intermittent fasting among animals. Many pilot studies of intermittent fasting have been performed now, too, but the body of literature regarding the human response to fasting is incomplete. This study sought to determine how preliminary and incomplete the evidence is in humans regarding the health benefits and the harmful side-effects of intermittent fasting. The purpose was to determine how reliable the evidence is that people should be engaging in fasting to improve their health. In particular, one major concern is that diet gurus and even some scientists are marketing intermittent fasting to the public through diet books and other methods that produce additional income for them, but it is unclear whether their claims can be supported. The main findings of the study are that only three controlled clinical trials of intermittent fasting in humans have been published that were designed rigorously and included a control group in addition to the fasting intervention arm of the study. One of the three had a pre-specified primary outcome (weight loss) and another used the Bonferroni correction to account for inflated false positive results due to multiple hypothesis tests (the third study unfortunately did neither, which is the common approach in human studies of intermittent fasting). These three controlled trials only used surrogate or intermediate endpoints, though, such as weight, cholesterol, or other risk factors for disease. The three trials also have substantial limitations, including small sample sizes (~30 people total), a fasting regimen that was studied for less than three months, and no evaluation of clinical safety outcomes. Only one of the three trials was registered on ClinicalTrials.gov, a site instituted as part of the FDA Modernization Act and a pre-requisite for trials that are published in scientifically sound medical journals and are to be reviewed by the FDA. Two observational studies of the association of intermittent fasting with clinical events (i.e., coronary artery disease diagnosis and diabetes diagnosis) also have been published. These two studies included 200 patients and 445 patients. They were performed in patients drawn from a general population in which a large proportion of people engage in fasting intermittently over a period of decades. These observational studies provide the only evidence that fasting is associated with a lower risk of disease outcomes. Such studies are limited, though, by adjustment for only known or measured confounders, making it possible that some important factors may be unobserved in the studies that would account for the fasting benefit that was observed. No randomized controlled clinical trial of fasting for clinical events or disease outcomes has been performed, though, thus these five studies are the whole body of reliable evidence that intermittent fasting is beneficial to humans.