Author Interviews, Breast Cancer, JNCI, Surgical Research / 11.05.2015

Bernadette A.M. Heemskerk-Gerritsen, Ph.D. Department of Medical Oncology Erasmus MC Cancer Institute Roterdam, the NetherlandsMedicalResearch.com Interview with: Bernadette A.M. Heemskerk-Gerritsen, Ph.D. Department of Medical Oncology Erasmus MC Cancer Institute Roterdam, the Netherlands Medical Research: What is the background for this study? What are the main findings? Dr. Heemskerk-Gerritsen: Women with a BRCA1 or BRCA2 mutation have substantially higher risks of developing both primary and contralateral breast cancer (BC) and ovarian cancer than women from the general population. Options to reduce these increased cancer risks include risk-reducing mastectomy (RRM) and/or risk-reducing salpingo-oophorectomy (RRSO). The latter intervention obviously reduces the risk of developing ovarian cancer, but has been reported also to reduce the risk of developing a subsequent breast cancer with approximately 50%. However, studies on the efficacy of risk-reducing surgery in BRCA1/2 mutation carriers are confined to observational studies, thus challenging several methodological issues. Consequently, previous studies on breast cancer risk-reduction after RRSO may have been influenced by bias associated with selection of study subjects, bias associated with start of follow-up, or by confounding, and breast cancer risk-reduction may have been overestimated. In the current study, we revisited the association between risk-reducing salpingo-oophorectomy and breast cancer risk in BRCA1/2 mutation carriers, focusing on the impact of different analytical methods and potential types of bias. First, we replicated the analyses of four previously performed studies, to examine if our Dutch cohort was comparable with the cohorts used in the previous studies. We replicated the approximately 50% breast cancer risk reduction after RRSO in the Dutch cohort. Second, we estimated the effect of RRSO on breast cancer risk in the Dutch cohort using a revised analytical approach for observational studies in BRCA1/2 mutation carriers in order to minimize bias as much as possible. Using this method of analysis, we found no evidence of first BC risk-reduction after RRSO in BRCA1/2 mutation carriers. (more…)
Author Interviews, BMJ, Emergency Care, Hospital Readmissions / 11.05.2015

dr-brian-roweMedicalResearch.com Interview with: Dr. Brian Rowe, MD, MSc, CCFP(EM), FCCP Professor, Department of Emergency Medicine University of Alberta, Edmonton, Alberta, Canada MedicalResearch: What is the background for this study? Dr. Rowe: Frequent users are also called “familiar faces” or “heavy users” and they represent an important sub-group of patients in the emergency setting, with often complex needs that contribute to overcrowding and excess health care costs. The evidence suggests that frequent users account for up to one in 12 patients seeking emergency care, and for around one in four of all visits. MedicalResearch: What are the main findings? Dr. Rowe: Frequent users of emergency department care are more than twice as likely to die, be admitted to hospital, or require other outpatient treatment as infrequent users, concludes an analysis of the available evidence, published in Emergency Medicine Journal. These conclusions are based on a thorough search of seven electronic databases of relevant research relating to the frequency and outcomes of emergency department use by adults. Out of a total of more than 4000 potential studies, 31 relevant research reports published between 1990 and 2013 were included in the final analysis. Frequent users were variably defined as visiting emergency care departments from four or more times up to 20 times a year. Among the seven studies looking at deaths, the analysis showed that frequent attenders at emergency care departments were more than twice as likely to die as those who rarely sought emergency care. Most of the studies included hospital admission as an outcome, and these showed that frequent users were around 2.5 times as likely to be admitted as infrequent users. Ten studies looked at use of other hospital outpatient care, and these showed that frequent users were more than 2.5 times as likely to require at least one outpatient clinic after their visit to the emergency care department. (more…)
Author Interviews, Infections, PLoS / 11.05.2015

MedicalResearch.com Interview with: Dr. Gordon Langsley Laboratoire de Biologie Cellulaire Comparative des Apicomplexes, Institut Cochin, INSERM U1016, CNRS UMR 8104, Faculté de Medecine Université Paris Descartes, Paris Medical Research: What is the background for this study? What are the main findings? Response: We have been studying the role of cAMP-dependent PKA signaling in Plasmodium falciparum-infected red blood cells for some time; see just a few examples: PMID: 25522250; PMID: 22626931; PMID: 18248092; PMID: 11559352 and we came to the conclusion that intra cellular cAMP levels regulate infected red blood cell deformability and adhesion to for example, brain endothelial cells. (more…)
Author Interviews, Sleep Disorders / 10.05.2015

Hans P.A. Van Dongen, Ph.D. Director, Sleep and Performance Research Center Research Professor, College of Medical Sciences Washington State University Spokane, Spokane, WA MedicalResearch.com Interview with: Hans P.A. Van Dongen, Ph.D. Director, Sleep and Performance Research Center Research Professor, College of Medical Sciences Washington State University Spokane, Spokane, WA On behalf of the authors: Paul Whitney PhD, John Hinson PhD, Melinda Jackson PhD, Hans Van Dongen PhD MedicalResearch: What is the background for this study? What are the main findings? Research: Our main interest is in better understanding why people sometimes are able to manage perfectly well with sleep loss, while at other times sleep loss can have profoundly negative effects. We found that sleep deprivation reduces the effectiveness of signals used to tell when you are right or wrong, an effect we labeled feedback blunting. Subjects in the study performed a decision making task that was simple but required feedback, i.e., a signal indicating the response was correct or incorrect, to perform correctly. We found that people who were sleep deprived were no longer able to use the feedback information to make correct responses. And when people had to adapt to unexpected changes in when to respond, sleep deprived people were completely unable to adapt to these changing circumstances. The finding of feedback blunting in this study indicates that people who are sleep deprived not only have trouble sustaining attention to details in the environment (a well established effect of sleep loss), they also have trouble changing the focus of attention to deal with changing circumstances. An interesting paradox in the research literature has been that people have been shown in many circumstances to perform complex tasks at a very high level while sleep deprived. Yet, we know from real-world experience that sleep deprived people can make catastrophic, life-threatening decisions that they would never have made if they were well rested. The current study is the first to shed light on this issue. It showed that sleep deprived people who get feedback, telling them that their actions are not effective, are less capable of changing their behavior. The study is part of a line of research in which we are trying to identify how sleep loss changes specific components of cognition, and how these changes may lead to serious problems in everyday life activities. Being able to study and understand these effects of sleep deprivation under controlled conditions is an important step toward preventing human error under real world conditions. (more…)
Author Interviews, Biomarkers, UCSF / 10.05.2015

Alan H.B. Wu, PhD, DABCC Professor Laboratory Medicine Chief, Clinical Chemistry Laboratory University of California San Francisco, CAMedicalResearch.com Interview with: Alan H.B. Wu, PhD, DABCC Professor Laboratory Medicine Chief, Clinical Chemistry Laboratory University of California San Francisco, CA Medical Research: What is the background for this study? What are the main findings? Response: Clinical trials are conducted for validation of novel biomarkers.  There is considerable heterogeniety in the quality design and documentation of findings. This can have a major impact on the conclusions rendered. (more…)
Author Interviews, Heart Disease, Mediterranean Diet, Nutrition / 10.05.2015

Miguel Á. Martínez-González, MD, MPH, PhD Department of Preventive Medicine & Public Health School of Medicine, University of Navarra Navarra, SpainMedicalResearch.com Interview with: Miguel Á. Martínez-González, MD, MPH, PhD Department of Preventive Medicine & Public Health School of Medicine, University of Navarra Navarra, Spain Medical Research: What are the main findings? Response: The diet-heart hypothesis has been researched during decades. A common mistake was to assume that a high intake of all types of fat was detrimental for cardiovascular health and could cause heart attacks and strokes. Therefore a low-fat diet was proposed as the best way to prevent heart attacks and strokes. This was wrong. Alternatively, the Mediterranean diet, rich in fat from natural vegetable sources (olive oil, tree nuts), was also considered a healthy dietary pattern. However, most of the evidence to support these benefits of a fat-rich Mediterranean diet came from observational studies and no randomized clinical trial had ever assessed the Mediterranean diet in PRIMARY prevention (i.e. in initially healthy people) (more…)
Author Interviews, Genetic Research / 09.05.2015

Rebecca Todd Ph.D. Assistant Professor University of British Columbia Department of Psychology Centre for Interactive Research on Sustainability Vancouver, BCMedicalResearch.com Interview with: Rebecca Todd Ph.D. Assistant Professor University of British Columbia Department of Psychology Centre for Interactive Research on Sustainability Vancouver, BC Medical Research: What is the background for this study? What are the main findings? Dr. Todd: This study brings together two lines of research. First, a couple of years ago my colleagues and I reported that in general people literally see emotional aspects of the world as more vivid - as if they burn more brightly on the eye - than mundane things. We call this effect emotionally enhanced vividness, or EEV. Here we wanted to look at how this phenomenon of emotionally enhanced vividness might differ between individuals. Second, in another previous study we found that people who carry a very common variation in the ADRA2b gene, which influences levels of norepinephrine (a neuromodulator in the brain that is important to the stress response and for emotional influences on memory) were more likely to have their attention captured by emotionally relevant aspects of the world. We also found that how arousing they perceived an event to be at the time it happened predicted how well they remembered it better than for people who did not carry this variation. Here we continued to examine what is unique to this group of people by testing to see if they showed higher levels of the other phenomenon we had found, emotionally enhanced vividness, and what patterns of brain activation would play a role. (more…)
Author Interviews, Nutrition, Sugar, Weight Research / 08.05.2015

Dr. Dragos Petrescu Department of Public Health and Primary Care CambridgeMedicalResearch.com Interview with: Dr. Dragos Petrescu Department of Public Health and Primary Care Cambridge Medical Research: What is the background for this study? What are the main findings? Response: Consumption of sugar-sweetened beverages is a major contributor to obesity, particularly in children. Recent systematic reviews provide good evidence that reducing portion size reduces consumption. Similarly, evidence suggests that container shapes and product placement in supermarkets can influence consumption. The public acceptability of "nudging" -- altering properties such as the size, the shape, and location of sugar-sweetened beverages -- to improve public health is unknown. Here we compared the acceptability in UK and USA samples of government interventions to reduce consumption of sugar-sweetened beverages: three nudge interventions (limiting portion size, changing container shape, and changing shelf location) and two traditional interventions (increased taxation and an education campaign). We found that for the majority of UK and USA samples, the education campaign and the three nudge interventions were acceptable, with education attracting most support.  By contrast, only a minority of participants supported taxation. (more…)
Accidents & Violence, Author Interviews, Weight Research / 08.05.2015

MedicalResearch.com Interview with: Claudia Sikorski Dr. rer. med. Claudia Sikorski, Dipl.-Psych. Institut für Sozialmedizin, Arbeitsmedizin und Public Health (ISAP) Institute of Social Medicine, Occupational Health and Public Health Universität Leipzig, Medizinische Fakultät Leipzig Medical Research: What is the background for this study? What are the main findings? Response: Obesity is a highly stigmatized condition. People with obesity are often regarded a lazy, slow and sloppy. One consequence of these negative attitudes may be discrimination, e.g. the unfair treatment of individuals with obesity. This study, conducted by Jenny Spahlholz, myself and colleagues reviews observational and experimental studies that investigated the occurrence and nature of discrimination in obesity. (more…)
Author Interviews, Weight Research / 08.05.2015

MedicalResearch.com Interview with: Rebecca Jones, MSPH Nutrition and Health Sciences Program Graduate Division of Biological and Biomedical Sciences Emory University Medical Research: What is the background for this study? What are the main findings? Response: Obesity in children is associated with a wide range of conditions later in life including heart disease, cancer, and diabetes. Even prior to adulthood, children can be affected by a host of non-communicable diseases which are affected by weight status of the child. With an increase in children who are overweight or obese globally, Dr. Chan, Director-General of the World Health Organization, announced a new initiative to combat childhood obesity at the 2014 World Health Assembly. Within childhood obesity the pre-school (under age 5) years are a critical period for prevention due the association of adiposity rebound and obesity in later years as well as the early establishment of taste preferences and attitudes around healthy eating habits. Recent evaluation of incident obesity in the United States has demonstrated a component of the course to obesity is already established by the age of five years. Our main finding is the necessity for better surveillance and comparability of weight status, particularly overweight and obesity, in children under five across countries in the European region. 60% of countries within the region have some form of published data on this particular population however they vary based on level of national representation, cut-off criteria, age and gender. All these different factors can significantly change the prevalence estimates making it very difficult to ascertain the full nature of the problem. Based on the data which was available the European Region has reason for concern about overweight and obesity in young children. (more…)
AHA Journals, Author Interviews, Outcomes & Safety, Stroke / 08.05.2015

James S McKinney, MD, FAHAAssistant Professor of Neurology Rutgers-Robert Wood Johnson Medical School Medical Director, RWJUH Comprehensive Stroke Center New Brunswick, NJ 08901MedicalResearch.com Interview with: James S McKinney, MD, FAHA Assistant Professor of Neurology Rutgers-Robert Wood Johnson Medical School Medical Director, RWJUH Comprehensive Stroke Center New Brunswick, NJ 08901 Medical Research: What is the background for this study? What are the main findings? Dr. McKinney: The current study evaluated outcomes of patients admitted to New Jersey hospitals with hemorrhagic stroke, including intracerebral hemorrhage (bleeding into the brain) and subarachnoid hemorrhage (bleeding along the surface of the brain) between 1996 and 2012 using the Myocardial Infarction Data Acquisition System (MIDAS) administrative database.  The New Jersey Department of Health and Senior Services designates certain hospitals as comprehensive stroke centers (CSCs).  We found that patients admitted to comprehensive stroke centers with hemorrhagic stroke were less likely to die than those admitted to other hospital types.  This was particularly true for those patients admitted with subarachnoid hemorrhage, which is usually caused by a ruptured aneurysm. (more…)
Author Interviews, Diabetes, General Medicine, Statins, UT Southwestern / 08.05.2015

Ishak Mansi, MD Staff Internist, VA North Texas Health System. Professor in Department of Medicine & Department of Clinical Sciences, Division of Outcomes and Health services Research, University of Texas Southwestern, Dallas, TXMedicalResearch.com Interview with: Ishak Mansi, MD Staff Internist, VA North Texas Health System. Professor in Department of Medicine & Department of Clinical Sciences, Division of Outcomes and Health services Research, University of Texas Southwestern, Dallas, TX MedicalResearch: What is the background for this study? What are the main findings? Dr. Mansi:  Statin use is associated with increased incidence of diabetes, and possibly increased body weight, and less exercise capacity. Data on the long-term effects of these associations in healthy adults are very limited. Additionally, the effects of these associations on diabetic complications have not been adequately studied. Dr. Mansi at VA North Texas Health System, Dallas and Professor of Medicine and Clinical Sciences at the University of Texas Southwestern, Dallas, TX and his colleagues found that among generally healthy individuals, statin-users in comparison to non-users had a higher odds of being diagnosed with new onset diabetes, diabetes with complications, and overweight/obesity. The researchers examined the records of tens of thousands of Tricare beneficiaries, during the period from 10/1/2003 to 3/1/2012. After excluding patients who had at baseline a preexisting cardiovascular diseases or severe chronic diseases that may be life-limiting (including diabetes mellitus), they identified a cohort of 25,970 patients as “healthy cohort”. They, further, matched 3,351 statins-users and 3,351 nonusers on several baseline characteristics to ensure comparability. There are 3 main important findings for our study:
  1. Statin use was associated with significantly higher risk of new onset diabetes even in a very healthy population. Whereas the risk of diabetes with statins is known, it was thought that this may be due to the overall multiple risks of statin-users (that caused them to receive statins as a therapy).
  2. Statin use was associated with very high risk of diabetes complications in this healthy population: this was never shown before.
  3. Statin use is associated with higher risk of obesity: this also is widely unknown. However, few studies have noted this (one study using patient survey noted this, another study using Mendelian randomization showed it, and post-hoc analysis of a clinical trial showed that statin user gained more weight). Our study, which used a different methodology (retrospective cohort study) add another piece of evidence. Obesity is at endemic level in the US and treatment options are limited.
High-intensity statins was associated with greater risks of all outcomes. This article is published in the Journal of General Internal Medicine (JGIM). JGIM is the official journal of the Society of General Internal Medicine. (more…)
Author Interviews, Opiods, Orthopedics, Pain Research, Pharmacology / 08.05.2015

Hassan R. Mir, MD, MBA Associate professor of Orthopaedics and Rehabilitation Vanderbilt Orthopaedic InstituteMedicalResearch.com Interview with: Hassan R. Mir, MD, MBA Associate professor of Orthopaedics and Rehabilitation Vanderbilt Orthopaedic Institute and and Brent J. Morris, M.D. Shoulder and Elbow Surgery Fellowship Texas Orthopaedic Hospital in affiliation with the University of Texas Houston Health Science Center, Houston, TexasDr. Brent J. Morris, M.D. Shoulder and Elbow Surgery Fellowship Texas Orthopaedic Hospital University of Texas Houston Health Science Center, Houston, Texas Medical Research: What is the background for this study? What are the main findings? Dr. Mir: The past few decades have seen an alarming rise in opioid use in the United States, and the negative consequences are dramatically increasing. The US represents less than 5% of the world's population, yet consumes 80% of the global opioid supply. Management of pain is an important part of patient care, however, the increased usage of opioids for the treatment of pain has led to several unanticipated aftereffects for individual patients and for society at large. Orthopaedic surgeons are the third highest prescribers of opioid prescriptions among physicians in the United States. Orthopaedic patients can experience a tremendous amount of pain with acute injuries and chronic conditions, and the treatment plan may involve opioid prescriptions for relief of discomfort. A significant number of orthopaedic patients and their families are at risk for repercussions from opioid use. We must work together to decrease the use of opioids for musculoskeletal pain. Clinicians should aim to control pain and improve patient satisfaction while avoiding overprescribing opioids. A comprehensive strategy of risk assessment is needed to identify patients who may be at risk for opioid abuse. Objective measures including patient history, recognition of aberrant behavior, urine drug testing, state prescription drug–monitoring programs, and opioid risk-assessment screening tools may be necessary in select cases. (more…)
Author Interviews, NEJM, Pediatrics / 08.05.2015

MedicalResearch.com Interview with: Mr. Matthew A. Rysavy, B.S and Edward Bell, MD Department of Pediatrics, University of Iowa Iowa City, IA Medical Research: What is the background for this study? What are the main findings? Response: We were interested in understanding reasons for differences in outcomes among extremely preterm infants among hospitals.  This has been shown in many studies.  We found that differences among hospitals in whether treatment was initiated for infants born at very early gestations (22, 23, 24 weeks' gestation) accounted for a lot of the variation in hospital-level outcomes at these gestational ages. (more…)
Author Interviews, Genetic Research, Infections, Inflammation, NYU / 07.05.2015

Dr. Ludovic Desvignes. PhD. Assistant Professor, Departments of Medicine and Pathology NYU Langone Medical CenterMedicalResearch.com Interview Dr. Ludovic Desvignes PhD. Assistant Professor, Departments of Medicine and Pathology NYU Langone Medical Center MedicalResearch: What is the background for this study? Dr. Desvignes: This study is the result of a collaboration at NYU Langone Medical Center, between the laboratories of Dr. Stefan Feske and Dr. Joel Ernst, my mentor. Dr. Feske and colleagues had developed a mouse model of rare, inherited mutations he had identified in infants. These mutations occur in the genes for STIM1 and ORAI1, which are crucial for calcium flux in cells of the immune system. The young patients affected by these mutations suffer from severe, recurrent and chronic infections that often cause death before their first birthday. In particular, some of these patients cannot control infection with BCG, which is a normally innocuous strain of mycobacteria administered to protect against tuberculosis (TB). TB is a chronic infection and one of the leading causes of infection-related death worldwide. Going into this study, Dr. Feske and colleagues knew that without functional calcium channels, immune cells do not function properly. However, they did not fully understand how these channels contribute to immune responses to infectious pathogens in a living organism and in particular, for pathogens that cause chronic infections such as TB. This is why Dr. Ernst and I collaborated with Dr. Feske and provided him with our clinical and research expertise in TB. MedicalResearch: What are the main findings? Dr. Desvignes: Dr. Feske’s mice are genetically engineered to lack STIM1 in a certain type of immune cells, known as T cells or T lymphocytes. We infected these mice with Mycobacterium tuberculosis, the bacterium causing TB. Mycobacterium tuberculosis causes chronic infection by manipulating the immune system even in healthy people. The first very surprising result of our study was that mice lacking calcium flux in T cells handled acute TB fairly well. Only during the chronic phase of infection did they become unable to control mycobacterial growth and developed a strong inflammation in their lungs, which was due to an infiltration by different types of immune cells, including T cells. We discovered that the accumulation of STIM1-deficient T cells in the lungs resulted from the cells’ inability to die, which is a normal mechanism to limit an immune response and prevent excessive inflammation. Another immune control mechanism that failed in the absence of STIM1 is mediated by a subset of T cells called induced regulatory T cells, or iTreg cells. These cells are essential to prevent normal immune responses from going “overboard” by suppressing the functions of other immune cells, including T cells. We found that calcium signals are required for the development of iTreg cells and that their numbers were strongly reduced in the lungs of infected STIM1-deficient mice. We therefore think that the lack of iTreg cells in the absence of STIM1 contributes to the severe lung inflammation in chronic TB. The third finding that really surprised us was that T cells accumulating in the lungs of STIM1-deficient mice produced large amounts of a protein called interferon gamma. While interferon gamma is required to control Mycobacterium tuberculosis, it is also a very potent promoter of inflammation and too much of it can lead to tissue damage. Dr. Feske and colleagues had previously observed that calcium fluxes promote the production of interferon gamma in T cells cultured in vitro and we expected the STIM1-deficient T cells to be defective in the production of that protein. During chronic TB, however, calcium signaling turned out to be not only dispensable for the production of interferon gamma by T cells but it was actually required to limit its production and thus, to control inflammation. (more…)
Author Interviews, CDC, Pediatrics, Vaccine Studies / 07.05.2015

MedicalResearch.com Interview with: Tejpratap S.P. Tiwari, MD Meningitis and Bacterial Vaccine Preventable Diseases Branch Division of Bacterial Diseases National Center for Immunization and Respiratory Diseases Division of Global HIV/AIDS, Center for Global Health Centers for Disease Control and Prevention, Atlanta, Georgia Medical Research: What is the background for this study? What are the main findings? Dr. Tiwari: Infants younger than one year old in the United States are at highest risk for severe outcomes from pertussis and death. The first childhood pertussis vaccine dose is recommended at 2 months old, with additional doses in the first year of life at 4 and 6 months. Studies have established that pertussis vaccines can protect against pertussis disease, complications, and hospitalization in infants when 1 to 3 doses are administered by six months old. This study’s findings suggest that the first pertussis vaccine dose and appropriate antibiotic treatment protect infants against death, hospitalization, and pneumonia. Improved on-time infant vaccination (at 2, 4, and 6 months) could potentially prevent up to 1 out of every 4 infant pertussis deaths. (more…)
Author Interviews, CDC, OBGYNE / 07.05.2015

Dmitry Kissin, MD Health scientist CDC Division of Reproductive HealthMedicalResearch.com Interview with: Dmitry Kissin, MD Health scientist CDC Division of Reproductive Health Medical Research: What is the background for this study? Dr. Kissin: Due to the frequent transfer of more than one embryo during assisted reproductive technology (ART) treatments, such as in vitro fertilization (IVF), many ART-conceived children are born as multiples (twins, triplets and higher order). Multiple births, even twins, carry increased risk for both mothers and children. In the U.S., the practice guidelines published by the American Society for Reproductive Medicine (ASRM) and the Society for Assisted Reproductive Technology (SART) provide recommendations on how many embryos to transfer in order to balance safety with the effectiveness of assisted reproductive technology. In an effort to reduce multiple births and associated complications, it is important to evaluate embryo transfer practices that contribute to these outcomes. Medical Research: What are the main findings? Dr. Kissin: Using data from the CDC’s National ART Surveillance System (NASS), we found that the majority of ART-related multiple births in the U.S. resulted from assisted reproductive technology cycles practiced in accordance with ASRM/SART guidelines and involved the transfer of two embryos. Almost half of ART-related multiple births resulted from transferring two fresh blastocysts (embryos cultured for 5/6 days) to favorable- or average-prognosis patients less than 35 years and donor-egg recipients, or two frozen/thawed embryos to patients less than 35 years. (more…)
Author Interviews, Breast Cancer, Case Western, Genetic Research / 07.05.2015

Ahmad M. Khalil, PhD Assistant professor, Department of Genetics and Genome Sciences Case Western Reserve University School of MedicineMedicalResearch.com Interview with: Ahmad M. Khalil, PhD Assistant professor, Department of Genetics and Genome Sciences Case Western Reserve University School of Medicine MedicalResearch: What is the background for this study? What are the main findings? Dr. Khalil: This study aimed to identify other genes that work synergistically with the oncogene HER2 in HER2positive (HER+) breast cancer. The gene HER2 is amplified in those patients, which results in excess activities that promote uncontrolled cell growth. There are drugs that target HER2 and diminish its activity. However, these drugs can work initially, but patients relapse; or sometimes, the drugs don't work at all in some patients. Thus, by identifying other genes that work synergistically with the HER2 gene, we now have more genes to target by various drugs or compounds to destroy the tumor. The challenge was how to identify the key genes that work synergistically with HER2, especially in human subjects. To that end, we used clinical samples from a clinical trial of a drug that is known to inhibit HER2 activity to identify those genes. To further refine our list, we used cell culture models of the disease to also inhibit HER2. By combining those data sets, we identified 44 protein-coding genes. Next, we wanted to make sure that those genes stand a third independent filter. For that part, we interrogated those 44 genes in HER2+ tumors vs matched normal tissues from The Cancer Genome Atlas database — a collection of hundreds of tumors and normal tissues. Of the 44 genes, 35 genes passed this third filter. By examining the known functions of those genes, we can deduce that those genes work cooperatively with HER2 to promote carcinogenesis. There are currently known drugs that target some of those genes. We will use these drugs in combination with a drug that target HER2 to determine if the combination works better at destroying the tumor entirely. Lastly, we found that a special type of genes that we previously discovered, called lincRNAs, could also affect the oncogenic activity of HER2. These lincRNAs can also be targeted with HER2 to eliminate the tumor. (more…)
Author Interviews, Cost of Health Care, Emergency Care, Primary Care / 07.05.2015

Karoline Mortensen, Ph.D. Assistant Professor Department of Health Services Administration University of Maryland College Park, MDMedicalResearch.com Interview with: Karoline Mortensen, Ph.D. Assistant Professor Department of Health Services Administration University of Maryland College Park, MD Medical Research: What is the background for this study? Dr. Mortensen: For twenty years, use of hospital emergency departments has been on the rise in the United States, particularly among low-income patients who face barriers to accessing health care outside of hospitals including not having an identifiable primary health care provider. Almost half of emergency room visits are considered “avoidable.” The Emergency Department-Primary Care Connect Initiative of the Primary Care Coalition, which ran from 2009 through 2011, linked low-income uninsured and Medicaid patients to safety-net health clinics. Medical Research: What are the main findings? Dr. Mortensen: “Our study found that uninsured patients with chronic health issues – such as those suffering from hypertension, diabetes, asthma, COPD, congestive heart failure, depression or anxiety – relied less on the emergency department after they were linked to a local health clinic for ongoing care,” says Dr. Karoline Mortensen, assistant professor of health services administration at the University of Maryland School of Public Health and senior researcher. “Connecting patients to primary care and expanding the availability of these safety-net clinics could reduce emergency department visits and provide better continuity of care for vulnerable populations.” (more…)
AHA Journals, Author Interviews, Heart Disease / 07.05.2015

Kristian Kragholm, MD, PhD-student Cardiovascular Research Center, Department of Anesthesiology, Aalborg University HospitalMedicalResearch.com Interview with: Kristian Kragholm, MD, PhD-student Cardiovascular Research Center, Department of Anesthesiology, Aalborg University Hospital Medical Research: What is the background for this study? Dr. Kragholm: During 2001-2010 in Denmark, survival to 30 days and 1 year more than doubled. Whether this substantial improvement in survival was accompanied by good functional recovery in survivors was not clear. Discharge neurological status or post-discharge follow-up assessments were not systematically recorded in Denmark but through nationwide registries employment outcomes were available. Therefore, we examined return to work as a marker of favorable neurological outcome in 30-day survivors of out-of-hospital cardiac arrest in a nationwide study in Denmark between 2001-2011. Medical Research: What are the main findings? Dr. Kragholm: More than 75% of all 30-day out-of-hospital survivors in Denmark during 2001-2011 who were employed prior to arrest returned to work Not only did the majority of these survivors return to work, survivors also sustained work without any long-term sick absences for a median time of 3 years and maintained the same income after arrest as before arrest. Finally, relative to survivors who did not receive bystander cardiopulmonary resuscitation (CPR), chances for return to work were increased by approximately 40% if bystanders had provided CPR in multivariable adjusted modeling. (more…)
Author Interviews, Electronic Records, Emergency Care, Heart Disease, JACC / 07.05.2015

Justin A. Ezekowitz, MBBCh MScAssociate Professor, University of Alberta Co-Director, Canadian VIGOUR Centre Director, Heart Function Clinic Cardiologist, Mazankowski Alberta Heart InstiMedicalResearch.com Interview with: Justin A. Ezekowitz, MBBCh MSc Associate Professor, University of Alberta Co-Director, Canadian VIGOUR Centre Director, Heart Function Clinic Cardiologist, Mazankowski Alberta Heart Institute Medical Research: What is the background for this study? Dr. Ezekowitz: Heart Failure is a prevalent health issue that carries high morbidity and mortality. Most epidemiologic research derives information from hospital discharge abstracts, but emergency department visits are another source of information. Many have assumed this code is accurate in the emergency department but uncertainty remains. In our study, we assessed patients at their presentation to Emergency Department, which is usually the first medical contact for acutely ill patients with heart failure. The objective of our study was to compare administrative codes for acute heart failure (I50.x) in the emergency department against a gold standard of clinician adjudication. Medical Research: What are the main findings? Dr. Ezekowitz: Emergency department administrative data is highly correlated with a clinician adjudicated diagnosis. The positive predictive value of acute heart failure as the main diagnosis was 93.3% when compared to clinician adjudication, supported by standardized scoring systems and elevated BNP. (more…)
Author Interviews, OBGYNE / 06.05.2015

MedicalResearch.com Interview with: Dr Jonathan McGuane PhD. Robinson Research Institute and Discipline of Obstetrics and Gynaecology School of Paediatrics and Reproductive Health University of Adelaide, Adelaide, South Australia, Australia Medical Research: What is the background for this study? Dr. McGuane: Epidemiological studies suggest that endometriosis is present more often in women who report having intercourse during menstruation compared to those who don’t (Filer and Wu, J Reprod Med 1989:887-890). The idea for this study came from our research showing that seminal plasma induces marked changes in the immunology of the female reproductive tract, which are essential for optimal implantation of an embryo and subsequent fetal development. However, some of these immunological changes could increase the likelihood of endometrial tissue developing into an endometriotic lesion if it subsequently ends up in the peritoneum via retrograde menstruation (a la Sampson's hypothesis). This could help to explain the epidemiological findings cited above. Our study was designed to explore "proof-of-principle" of this concept by exposing human endometrial tissue directly to seminal plasma or control medium in vitro, and transplanting it under the skin of receptive mice. Medical Research: What are the main findings? Dr. McGuane: After two weeks, endometrial tissue exposed to seminal plasma was significantly larger than control tissue. This appeared to be the result of increased cell proliferation and tissue survival. Although we hypothesised that an immune-mediated mechanism would underlie the changes induced by seminal plasma, we did not find much evidence to support this idea; however, more work needs to be done on this aspect of the research. (more…)
Author Interviews, OBGYNE, UCLA / 06.05.2015

Anita L. Nelson, MD Professor, Department of Obstetrics and Gynecology at Harbor-UCLA Medical Center Los Angeles BioMedical Research Institute Harbor-UCLA Medical Center Torrance, California MedicalResearch.com Interview with: Anita L. Nelson, MD Professor, Department of Obstetrics and Gynecology at Harbor-UCLA Medical Center Los Angeles BioMedical Research Institute Harbor-UCLA Medical Center Torrance, California Medical Research: What is the background for this study? What are the main findings? Dr. Nelson: The clinical impact heavy menstrual bleeding has often been expressed in terms of quality of life issues, but many women have heavy and prolonged bleeding that can lead to serious medical problems. The frequency with which women were treated at Harbor-UCLA Medical Center with profoundly low hemoglobin levels prompted us to do a comprehensive review of such women during a recent five year period to remind readers that even in the 21st century, this is not an uncommon problem. Overall 149 woman were treated 168 times for severe anemia (hemoglobin < 5.0 g/dL); 40% had previously been transfused (but not effectively treated). Over a quarter had reactive thrombocytosis which placed them at high risk for thrombosis (DVT, PE, and stroke). Over a third were discharged without therapy to prevent recurrence. (more…)
AHA Journals, Author Interviews, Diabetes, Heart Disease / 06.05.2015

Michelle Schmiegelow MD, PhD Student Gentofte Hospital Copenhagen Area, Capital Region, DenmarkMedicalResearch.com Interview with: Michelle Schmiegelow MD, PhD Student Gentofte Hospital Copenhagen Area, Capital Region, Denmark

Medical Research: What is the background for this study? Dr. Schmiegelow: Use of cardiovascular risk stratification models is highly encouraged by U.S. and European guidelines in order to prevent cardiovascular disease (CVD). Individuals with insulin resistance are likely to progress to type 2 diabetes, but measures of insulin resistance are not included in current risk stratification models, although this might improve prediction of CVD in patients without diabetes. The aim of this study was to evaluate whether measures of insulin resistance would improve CVD risk predictions based solely on traditional CVD risk factors in postmenopausal women without existing CVD or diabetes. The main outcome was risk of developing CVD, defined as non-fatal and fatal coronary heart disease and ischemic stroke, within ten years, and the measures of insulin resistance considered were fasting serum glucose, fasting serum insulin, “homeostasis model assessment-insulin resistance“ (HOMA-IR) and the ratio of triglycerides and high-density lipoprotein-cholesterol (TG/HDL-C). From the Women’s Health Initiative Biomarkers studies we identified 15,288 postmenopausal women with no history of CVD, atrial fibrillation, or diabetes at baseline (included 1993–1998), who over a mean follow-up of 9.2 years (standard deviation 1.9 years) had 894 first CVD events (5.8%). (more…)
Author Interviews, Education, Vanderbilt / 06.05.2015

Candace McNaughton, MD MPH Assistant Professor Department of Emergency Medicine Vanderbilt University, Nashville, TNMedicalResearch.com Interview with: Candace McNaughton, MD MPH Assistant Professor Department of Emergency Medicine Vanderbilt University, Nashville, TN Medical Research: What is the background for this study? Dr. McNaughton: Heart failure affects more than 5 million Americans, is a frequent cause of hospitalization, and by 2030 is projected to cost as much $70 billion, so there is a lot of interest in helping patients with heart failure manage their condition. Health literacy, or the ability to use and understand healthcare information, is important for all patients, but the stakes are very high for patients with heart failure. Some people who are highly literate or highly educated in other areas may have difficulty reading and understanding healthcare information. Patients with lower health literacy skills may have difficulty communicating with healthcare providers, navigating the healthcare system, recognizing signs of health decline, and knowing when and who to contact when they do become ill. Medical Research: What are the main findings? Dr. McNaughton: To our knowledge, this is the first study in which health literacy was measured by nurses when patients were admitted to the hospital for heart failure. Nurses asked patients three questions about whether they have problems learning about their medical condition, their confidence filling out medical forms, and how often they have someone help them read hospital materials. With these three questions, information about the health literacy level of individual patients can be made easily available their healthcare providers. We found that among 1,379 patients hospitalized for acute heart failure, those with low health literacy had 32% greater risk of death compared to patients with a literacy score of 10 or higher, even after adjusting age, sex, race, insurance status, education, other medical conditions, and how long they were in the hospital.  (more…)
Author Interviews, Heart Disease / 06.05.2015

MedicalResearch.com Interview with: Hueiming Liu | BA (Hons), MBBS, MIPH Research Fellow, Renal & Metabolic Division The George Institute for Global Health NSW Australia Medical Research: What is the background for this study? Dr. Liu: Cardiovascular disease is a major cause of mortality and morbidity worldwide and is projected to be the leading cause of death in 2030. A major part of the problem is large treatment gaps globally. Cardiovascular polypills which are fixed dose combinations of frequently indicated cardiovascular medications for high risk primary prevention and secondary prevention have been trialled internationally to improve provider prescribing and patient medication use. Encouragingly, recent results from randomised controlled trials have shown effectiveness in improving adherence.   This study is part of a process evaluation of a pragmatic randomised, controlled trial evaluating a polypill-based strategy for high-risk primary and secondary cardiovascular disease prevention in Australian primary health care. The trial results showed that “ After a median of 18 months, the polypill-based strategy was associated with greater use of combination treatment (70% vs. 47%; relative risk 1.49, (95% confidence interval (CI) 1.30 to 1.72) p < 0.0001; number needed to treat = 4.4 (3.3 to 6.6)) without differences in systolic blood pressure (-1.5 mmHg (95% CI -4.0 to 1.0) p = 0.24) or total cholesterol (0.08 mmol/l (95% CI -0.06 to 0.22) p = 0.26).” Ultimately, the trial was underpowered for clinical outcomes, but in a separate meta-analysis that included 2 other trials using a near identical protocol in other countries, the polypill strategy was associated with significant reductions in blood pressure and LDL cholesterol. A within-trial cost analysis of polypill-based care versus usual care with separate medications showed a statistically significantly lower mean pharmaceutical expenditure and thus potential cost savings to tax payers and the Australian government should the polypill strategy be introduced. In this qualitative study, we explored health provider and patient attitudes towards the use of a cardiovascular polypill as a health service strategy to improve cardiovascular prevention in Australia through in-depth, semi-structured interviews with 47 health providers and 47 patients involved in the trial. (more…)
Author Interviews, Prostate Cancer, Radiology / 06.05.2015

Matthias Eiber, MD Department of Nuclear Medicine Munich, GermanMedicalResearch.com Interview with: Matthias Eiber, MD Department of Nuclear Medicine Munich, Germany Medical Research: What is the background for this study? What are the main findings? Dr. Eiber: The background of the study is the investigation of a novel 68Ga-PSMA ligand using PET/CT in the workup of patients with recurrent prostate cancer after radical prostatectomy. Hereby, we found substantial higher detection rate compared to other methods. In total 222 (89.5%) patients showed pathological findings in 68Ga-PSMA-ligand PET/CT. Stratified by PSA-level the detection rates were 96.8%,93.0%,72.7% and 57.9% of ≥2,1-<2, 0.5-<1 and 0.2-<0.5ng/mL, respectively. (more…)
Author Interviews, C. difficile, Hospital Acquired, JAMA / 05.05.2015

Dale N. Gerding, MD Research Physician, Edward Hines, Jr., VA Hospital Professor, Department of Medicine of Loyola University Chicago Stritch School of MedicineMedicalResearch.com Interview with: Dale N. Gerding, MD Research Physician, Edward Hines, Jr., VA Hospital Professor, Department of Medicine of Loyola University Chicago Stritch School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Gerding: Naturally occurring strains of C. difficile lack the genes for production of the toxins that cause C. difficile infection (CDI) and are known as non-toxigenic C. difficile (NTCD). These strains when ingested by patients whose normal microbiota is disrupted by antibiotic treatment will harmlessly colonize the colon and remain in the gut for weeks to months. Specific strains of NTCD found in patients were shown to colonize the gut and prevent C. difficile infection when challenged with toxigenic C. difficile strains in animal models. One such NTCD strain, NTCD-M3, was shown to be safe and well tolerated in human volunteer trials and was used in the present study to determine if it would prevent recurrence of C. difficile infection in patients who had just completed treatment with vancomycin or metronidazole of either their first CDI episode or first recurrence of C. difficile infection. 168 patients were randomized to receive by mouth in a liquid form, either 10,000 spores/day of NTCD-M3 for 7 days, 10 million spores/day for 7 days, 10 million spores/day for 14 days, or an identical placebo for 14 days.  Primary outcome was safety, and secondary outcomes were the percent who colonized the gut with NTCD-M3 in the time period from end of treatment to week 6, and the rate of recurrent CDI in the patients at week 6. The results showed that NTCD-M3 was safe and well tolerated, and colonized the gut of 69% of patients who received it. The C. difficile infection recurrence rate was 30% in the placebo patients and 11% in patients who received any of the NTCD-M3 doses (P<.006). The best dose tested was 10 million spores/day for 7 days which resulted in a recurrence rate of only 5% (p<.01 vs placebo). Colonization of the gut was not permanent, but lasted a maximum of 22 weeks. The summary conclusion is that NTCD-M3 is safe, colonized the gut, and when it colonized the gut, reduced recurrence of C. difficile infection to 2% (p<.001 vs patients who were not colonized). (more…)
Author Interviews, Infections / 05.05.2015

MedicalResearch.com Interview with: Gerardo U. Lopez, M.A.T, M.Ed., Ph.D. Research Associate Soil, Water and Environmental Science The University of Arizona Tucson, AZ 85721 Medical Research: What is the background for this study? What are the main findings? Dr. Lopez: The background for this study was based on the missing data gaps on fomite-to-finger transfer in the literature that could be used as input parameters for Quantitative Microbial Risk Assessments (QMRA). This research was supported by the Center for Advancing Microbial Risk Assessment, funded by the U.S. Environmental Agency’s Science To Achieve Results (STAR) program and the U.S. Department of Homeland Security. Two different studies were conducted: 1st “Transfer Efficiency of Bacteria and Viruses from Porous and Nonporous Fomites to Fingers under Different Relative Humidity Conditions”   Appl. Environ. Microbial. 2013, 79(18):5728 and 2nd “Evaluation of a Disinfectant Wipe Intervention on Fomite-to-Finger Microbial Transfer”. This research was supported by The Clorox Company. Based on the findings of these two studies along with other input parameters drawn from previous studies, we were able to develop a risk assessment that focused on forecasting the exposure to Campylobacter jejuni contaminated surfaces during preparation of chicken fillets and how using a disinfectant wipe intervention to clean a contaminated work area decreases the risk of infection following the preparation of raw chicken fillet in a domestic kitchen. The title of our new publication is “Impact of Disinfectant Wipes on  the Risk of Campylobacter jejuni Infection During Raw Chicken Preparation in Domestic Kitchens” Accepted for publication in Journal of Applied Microbiology. Editor's note: For EPA Registered Disinfectant Wipes The main findings were that the annual risk of C. jejuni infections showed a 99% reduction per person per event from 2 out of 10 to 2 out of 1000. (more…)
Author Interviews, Genetic Research, NEJM, Ophthalmology / 05.05.2015

Professor James Bainbridge, MA, PhD, FRCOphthProfessor of Retinal Studies, UCL Institute of Ophthalmology NIHR Research Professor, NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of OphthalmologyMedicalResearch.com Interview with: Professor James Bainbridge, MA, PhD, FRCOphth Professor of Retinal Studies, UCL Institute of Ophthalmology NIHR Research Professor, NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of OphthalmologyConsultant Ophthalmologist, Moorfields Eye Hospital NHS Foundation Trust Medical Research: What is the background for this study? What are the main findings? Prof. Bainbridge : Leber Congenital Amaurosis (LCA) is one of the most common causes of inherited, untreatable blindness in children. There are at least 14 different types of Leber Congenital Amaurosis of which LCA Type 2 (LCA2), caused by defects in the gene RPE65, affects around one in 100,000 people worldwide. Evidence from animal studies support that LCA2 may be amenable to treatment with RPE65 gene replacement therapy. The main findings of this phase I/II clinical trial confirm our preliminary findings (published in NEJM, 2008) that gene therapy can improve night vision. Improvements peak within the first 12 months after treatment but then decline during the three-year follow-up period which is consistent with the published results and interim findings from other studies of RPE65 gene therapy. (more…)