Anesthesiology, Author Interviews, BMJ, Surgical Research / 24.06.2015

Dr. Andrea Tricco Ph.D Dalla Lana School of Public Health University of TorontoMedicalResearch.com Interview with: Dr. Andrea Tricco Ph.D Dalla Lana School of Public Health University of Toronto Medical Research: What is the background for this study? What are the main findings? Dr. Tricco: We were commissioned by Health Canada to assess the safety and effectiveness of serotonin (5-HT3) receptor antagonists in patients undergoing surgery. In order to examine this research question, we conducted a systematic review and network meta-analysis including >450 studies. We found that more patients receiving granisetron plus dexamethasone experienced arrhythmia compared to all other interventions and placebo. No differences were observed regarding mortality and QT prolongation in meta‐analysis; no studies reported on PR prolongation or sudden cardiac death. Granisetron plus dexamethasone was often the most effective antiemetic, with the number needed to treat ranging from two to nine. We found that ondansetron plus droperidol intravenous (IV) was also a highly effective antiemetic for decreasing the risk of vomiting and post-operative nausea and vomiting (PONV). (more…)
Allergies, Author Interviews, OBGYNE / 24.06.2015

MedicalResearch.com Interview with: Professor of Pediatrics Hans Bisgaard, MD, DMSc Copenhagen Prospective Studies on Asthma in Childhood Herlev and Gentofte Hospital, University of Copenhagen, Denmark Medical Research: What is the background for this study? Prof. Bisgaard: Programming of the immune response in perinatal life seems to contribute to the increased prevalence of immune-mediated diseases We hypothesized that initiation of labor could affect the developing newborn immune system. Medical Research: What are the main findings? Prof. Bisgaard: Pre-labor cesarean section is associated with a distinct and gestational age-related distribution of circulating immune cells in newborns suggesting that changes in specific immune compartments occur during the approach of labor. (more…)
Author Interviews, OBGYNE, Technology, University of Pennsylvania / 24.06.2015

Dan Dongeun Huh, Ph.D. Wilf Family Term Chair & Assistant Professor Department of Bioengineering University of Pennsylvania Philadelphia, PA 19104MedicalResearch.com Interview with: Dan Dongeun Huh, Ph.D. Wilf Family Term Chair & Assistant Professor Department of Bioengineering University of Pennsylvania Philadelphia, PA 19104 Medical Research: What is the background for this study? What are the main findings? Response: The placenta is a temporary organ central to pregnancy and serves as a major interface that tightly regulates transport of various endogenous and exogenous materials between mother and fetus.  The placental barrier consisting of the closely apposed trophoblast epithelium and fetal capillary endothelium is responsible for maintaining this critical physiological function, and its dysfunction leads to adverse pregnancy outcomes.  Despite its importance, barrier function of the placenta has been extremely challenging to study due to a lack of surrogate models that faithfully recapitulate the key features of the placental barrier in humans.  Our study aims to directly address this long-standing technical challenge by providing a microengineered in vitro system that replicates architecture, microenvironment, and physiological function of the human placenta barrier.  This “placenta-on-a-chip” device consists of microfabricated upper and lower cell culture chambers separated by a thin semipermeable membrane, and the placental barrier is generated by culturing human trophoblasts and fetal endothelial cells on either side of the membrane with steady flows of culture media in both chambers.  This microfluidic cell culture condition allowed the cells to form confluent monolayers on the membrane surface and to create a bi-layer tissue that resembled the placental barrier in vivo.  Moreover, the microengineered barrier enabled transport of glucose from the maternal chamber to the fetal compartment at physiological rates. (more…)
Author Interviews, Blood Pressure - Hypertension, Duke, Heart Disease, JACC / 24.06.2015

Satoru Kishi, MD Division of Cardiology Johns Hopkins University Baltimore, MarylandMedicalResearch.com Interview with: Satoru Kishi, MD Division of Cardiology Johns Hopkins University Baltimore, Maryland MedicalResearch: What is the background for this study? What are the main findings? Dr. Kishi: Blood pressure (BP) at the higher end of the population distribution may represent a chronic exposure that produces chronic injury to the cardiovascular system. Cumulative BP exposure from young adulthood to middle age may adversely influence myocardial function and predispose individuals to heart failure (HF) and other cardiovascular disease (CVD) later in life. The 2005 guidelines for the diagnosis and treatment of HF from the American College of Cardiology and American Heart Association highlight the importance of early recognition of subclinical cardiac disease and the importance of non-invasive tests in the clinical evaluation of heart failure. Our main objective was to investigate how cumulative exposure to high blood pressure from young to middle adulthood influence LV function. In the Coronary Artery Risk Development in Young Adults (CARDIA) study, multiple repeated measures of BP and other cardiovascular risk factors was recorded over a 25 year time span, starting during early adulthood (ages 18-30). (more…)
Author Interviews, Gastrointestinal Disease, Microbiome / 24.06.2015

Kathy Magnusson D.V.M., Ph.D Professor Oregon State College of Veterinary Medicine Principal Investigator with the Linus Pauling InstituteMedicalResearch.com Interview with: Kathy Magnusson D.V.M., Ph.D Professor Oregon State College of Veterinary Medicine Principal Investigator with the Linus Pauling Institute Medical Research: What is the background for this study? Dr. Magnusson: There is increasing evidence that the gut microbiome can communicate with our brain. Others had also shown that high-energy diets could alter the composition of the gut microbiome (i.e., shift the percentages of different bacteria within the population) and could alter cognitive function. We decided to use that dietary model to determine whether there was a relationship between the bacterial changes and the behavioral changes. Medical Research: What are the main findings? Dr. Magnusson: We found decreases in Bacteroidales and increases in Clostridiales orders of bacteria, similar to that seen in obese humans and animals on high energy diets. We also found problems with early learning for long-term memory, with delayed short-term memory and with cognitive flexibility, the ability to adapt to new rules and changing conditions. The alterations in Bacteroidales and Clostridiales showed a relationship to this decline in cognitive flexibility. (more…)
Accidents & Violence, Annals Internal Medicine, Author Interviews, Brigham & Women's - Harvard, Pediatrics / 24.06.2015

MedicalResearch.com Interview with: Lois K. Lee, MD, MPH Division of Emergency Medicine Boston Children's Hospital Boston, MA 02115 Medical Research: What is the background for this study? What are the main findings? Response: Motor vehicle crashes remain a leading cause of death for children and adults in the U.S. Seat belts are the single most effective protective device to decreased death and mitigate injuries in the event of a motor vehicle crash. Our study found that states with primary seat belt laws, where a motorist can be ticketed only for not wearing a seat belt, demonstrated a 17% decreased fatality rate, compared to states with secondary seat belt laws, where a motorist must be cited for another violation first before also getting ticketed for not wearing a seat belt. We found this difference was robust even after controlling for other motor vehicle safety legislation and state demographic factors. We found that although seatbelts prevent deaths, they don't completely stop injury so if you have been in an accident that wasn't your fault then you might want to look for a place like the Parnall Law Firm to see if they can help you get compensation for your injuries. (more…)
Author Interviews, CDC, Toxin Research / 23.06.2015

MedicalResearch.com Interview with: Ayana R. Anderson, MPH Division of Toxicology and Human Health Sciences Agency for Toxic Substances and Disease Registry MedicalResearch: What is the background for this study? What are the main findings? Response: Large mass casualty gas explosions and oil spills are widely reported in the media and receive considerable regulatory attention. However, smaller less catastrophic events are less likely to receive publicity. The Agency for Toxic Substances and Disease Registry (ATSDR) analyzed 2010–2012 data from the National Toxic Substance Incidents Program (NTSIP) to describe the causes and public health impacts of petroleum product release incidents and to better focus and prioritize prevention efforts. There were a total of 1,369 petroleum product releases reported from 7 states resulting in 512 injured persons and 36 deaths.          Approximately one fourth of the incidents were associated with utilities.          Approximately one fifth were associated with private vehicles or residences.          Approximately 10 percent of petroleum product releases resulted from inadvertent damage to utility lines. (more…)
Author Interviews, Cannabis, JAMA / 23.06.2015

MedicalResearch.com Interview with: Penny F. Whiting, PhD School of Social and Community Medicine, University of Bristol The National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care West at University Hospitals, Bristol NHS Foundation Trust, Bristol UK Kleijnen Systematic Reviews Ltd, Escrick, York, United Kingdom MedicalResearch: What is the background for this study? What are the main findings? Dr. Whiting: Cannabis is one of the most popular recreational drugs - only tobacco, alcohol and caffeine are more popular. It can result in an alteration to mood and a feeling of “high”. An estimated 141 million people use cannabis worldwide – this is equivalent to 2.5% of the world’s population. Cannabis has a long history of use for the relief of a wide variety of medical symptoms. There is evidence of its use for medical purposes going back to early Egyptian times. The pen-ts’ao ching the world’s oldest herbal book includes reference to cannabis as medicine for rheumatic pain, constipation, disorders of the female reproductive system, and malaria amongst others, this herbal book also contains the first reference to cannabis as a psychoactive drug. However, its use is controversial as it has been included as a controlled drug in the United Nations Single Convention on Narcotic Drugs since 1961, and the use of cannabis is illegal in most countries. Medical cannabis (or medical marijuana) refers to the use of cannabis or cannabinoids (any compound, natural or synthetic, that can mimic the actions of plant-derived cannabinoids) as medical therapy to treat disease or alleviate symptoms, this is different from CBD oil that also has been found to help with certain medical conditions, click to see details about CBD oil. Some countries have legalised medicinal-grade cannabis to chronically ill patients but in others its use remains illegal even for medicinal purposes. Canada and the Netherlands have government-run programmes where specialised companies supply quality controlled herbal cannabis. There are different strains of cannabis can help with aliments, those who are interested in finding out more about a list of low odor strains by GreenBudGuru.com might be interested in visiting or doing some research to find out more. These programmes have been running since 2001 and 2003 respectively. In the US around half of the states have introduced laws to permit the medical use of cannabis; other countries have similar laws. Kleijnen Systematic Reviews Ltd (see below) were commissioned by the Swiss Federal Office of Public Health to conduct a systematic review for the effects and adverse events of medical cannabis to inform policy decision making. Systematic reviews are studies of studies that offer a systematic approach to reviewing and summarising evidence. They follow a defined structure to identify, evaluate and summarise all available evidence addressing a particular research question. We were asked to focus on the following ten indications which were of particular interest to our commissioners: nausea and vomiting due to chemotherapy, patients with HIV/AIDS, chronic pain, spasticity in patients with multiple sclerosis or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, glaucoma, and Tourette’s syndrome. We only included randomised trials, the most robust design for evaluating the effects of an intervention. We included almost 80 trials (nearly 6500 participants). We had most evidence for chronic pain (28 trials), nausea and vomiting due to chemotherapy (28 trials) and spasticity due to MS or paraplegia (14 trials) with less than five studies included for each of the other indications and none for depression. With the exception of the nausea and vomiting due to chemotherapy population, studies general compared cannabinoids to placebo with only single studies for each indication comparing cannabinoid with an active comparator. In the nausea and vomiting population the majority of studies compared cannabinoids to an active comparator, most commonly prochlorperazine. Most trials reported greater improvement in symptoms with cannabinoids compared to control groups, however, these did not always reach statistical significance. Cannabinoids were also associated with a greater risk of short term adverse events, including serious adverse events. Common adverse events included dizziness, dry mouth, nausea, fatigue, sleepiness, and euphoria. Overall we found that there was moderate quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity and low-quality evidence to suggest that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep quality, and Tourette syndrome. When determining the quality of the evidence we considered the risk of bias in trials, the consistency of the evidence across the trials, the directness of the evidence (was the trials research question directly applicable to our review question), and the precision of the evidence. (more…)
Author Interviews, Heart Disease, Nature, Nutrition / 23.06.2015

MedicalResearch.com Interview with: Prof. Wilhelm Krek Institute of Molecular Health Sciences Zürich, Switzerland MedicalResearch: What is the background for this study? What are the main findings? Prof. Krek: Fructose and glucose are major components of dietary sugars consumed in the western world. A current prevailing view holds that glucose is used directly by various tissues as an energy source while fructose is first and foremost metabolized to fat by the liver arguing that these dietary sugars are metabolized differently despite having identical caloric values. Accordingly, overconsumption of fructose causes fatty liver disease and through dissemination of fat to peripheral organs such that adipose tissue contributes to obesity. The key enzyme in fructose metabolism is ketohexokinase (KHK). KHK-A and KHK-C are two isoforms of KHK that are produced through mutually exclusive alternative splicing of the KHK pre-mRNA. KHK-C displays a much higher affinity for fructose than KHK-A. Unlike other tissues that normally express KHK-A, the liver produces predominantly KHK-C providing a possible explanation of the above-noted pathologies upon overconsumption of fructose. Whether fructose metabolism is subject to signal-induced changes in alternative splicing of KHK isoform expression as a mechanism to mediate context-dependent changes in cell metabolism is not known. In this work, we identify the splicing factor SF3B1 as a key mediator of ketohexokinase alternative splicing and thus activator of fructose metabolism and further show that the SF3B1-KHK system is a direct target of regulation by hypoxia and promoter of heart disease. From the analysis of a series of genetic mouse models of pathologic cardiac hypertrophy and human samples of heart disease, we conclude that activation of the newly identified HIF1α-SF3B1-KHK-C axis and the ensuing promotion of fructose metabolism is essential for pathologic stress-induced anabolic growth and the development of heart disease. (more…)
Author Interviews, Clots - Coagulation, NEJM / 23.06.2015

MedicalResearch.com Interview with: Dr. Charles Pollack Jr., MA, MD, FACEP Thomas Jefferson University Clinical Professor of Emergency Medicine Philadelphia, PA 19107 MedicalResearch: What is the background for this study? What are the main findings? Dr. Pollack: There are currently no approved specific reversal agents for non–vitamin K antagonist oral anticoagulants. Idarucizumab, an antibody fragment, was developed to specifically reverse the anticoagulant effects of the oral thrombin inhibitor, dabigatran. RE-VERSE AD is an ongoing, global Phase III patient study initiated in 2014 to investigate idarucizumab in emergency settings in patients taking dabigatran. We undertook this prospective cohort study to determine the safety of 5 g of intravenous idarucizumab and its capacity to reverse the anticoagulant effects of dabigatran in patients who either presented with serious bleeding (group A) or required an urgent invasive procedure (group B) which could not be delayed by eight hours. We intentionally designed the study with very broad inclusion criteria to reflect the types of patients who would require urgent anticoagulant reversal in real-world emergency settings. The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the determination at a central laboratory of the dilute thrombin time or ecarin clotting time. We also diligently collected clinical outcomes as secondary outcomes, being conscious that these may vary considerably due to the heterogeneity of the patients we included in the study. In our publication in the New England Journal of Medicine, we present the first results from the study, in an interim analysis of the data from the first 90 patients. The data showed that idarucizumab rapidly and completely reversed the anticoagulant effect of dabigatran in 88 to 98% of the patients who had had elevated clotting times at baseline. The reversal effect was evident within minutes. There were no safety concerns related to idarucizumab among the 90 patients involved in this study - including patients who were given idarucizumab on clinical grounds but were later found to have had normal results on clotting tests at baseline. This is consistent with the experience from the more than 200 volunteers who were administered idarucizumab in previous studies. (more…)
Author Interviews, Brigham & Women's - Harvard, Dermatology, Nature, Surgical Research / 23.06.2015

MedicalResearch.com Interview with: Dr. Alexander Golberg Ph.D. Center for Engineering in Medicine Department of Surgery, Massachusetts General Hospital Harvard Medical School, and Shriners Burns Hospital Boston, MA, 02114 Porter School of Environmental Studies Tel Aviv University, Israel MedicalResearch: What is the background for this study? What are the main findings? Dr. Golberg: Well, the population grows and becomes older. Degenerative skin diseases affect one third of individuals over the age of sixty. Current therapies use various physical and chemical methods to rejuvenate skin; but since the therapies affect many tissue components including cells and extracellular matrix, they may also induce significant side effects, such as scarring. We report on a new, non-invasive, non-thermal technique to rejuvenate skin with pulsed electric fields. The fields destroy cells while simultaneously completely preserving the extracellular matrix architecture and releasing multiple growth factors locally that induce new cells and tissue growth. We have identified the specific pulsed electric field parameters in rats that lead to prominent proliferation of the epidermis, formation of microvasculature, and secretion of new collagen at treated areas without scarring. Our results suggest that pulsed electric fields can improve skin function and thus can potentially serve as a novel non-invasive skin therapy for multiple degenerative skin diseases. (more…)
Author Interviews, Emory, Flu - Influenza, PLoS / 23.06.2015

MedicalResearch.com Interview with: Brooke Bozick Ph.D. Candidate Population Biology, Ecology, & Evolution Program Emory University MedicalResearch: What is the background for this study? Response: Previous research at the global scale has shown that air travel is important for the spread of disease. For example, much work has focused on the recent Ebola epidemic in Africa, identifying where this disease emerged and then using air travel networks to predict the path of spread from there. At a more local scale, other modes of transportation may be more important to structuring pathogen populations. We were interested in investigating seasonal influenza in the United States. Previous research has shown that once the winter influenza epidemic starts, it spreads very rapidly across the continental states, suggesting that the US may act as one large, well-mixed population. Previous work using genetic data to look for spatial structure at this scale didn’t identify any patterns. However, these studies used geographic proximity to define the distance between states; we wanted to see whether similar patterns existed at this spatial scale if we instead used movement data as a proxy for the distance between locations. Commuter movements have previously been shown to correlate with influenza timing and spread based on influenza-like-illness and mortality data. MedicalResearch: What are the main findings? Response: We found that spatial structure is detectable within the US. We used data on the genetic distance between sequences collected from different states and compared that to different measures of ‘distance’ between states—geographic proximity, the daily number of people flying between states and the daily number of commuters traveling between states using ground transportation—to see whether any correlations were present. Further, we did this for two different subtypes of seasonal influenza: A/H3N2 and A/H1N1. These subtypes have different epidemiological properties, so there was reason to believe that the observed patterns might differ depending on subtype. We found that some correlations were present for all the distance metrics studied, but that they were observed a greater proportion of the time when looking at commuter movements, and when looking at the A/H1N1 subtype. Since A/H1N1 is generally milder and spreads more slowly throughout the US compared to A/H3N2, we interpret this to mean that spatial structure is likely more easily detected in this subtype. If A/H3N2 spreads rapidly from coast to coast, any signature of spatial structure is likely obscured before we have a chance to observe it. (more…)
Author Interviews, End of Life Care / 23.06.2015

MedicalResearch.com Interview with: Gabrielle Rocque MD Division of Hematology & Oncology University of Alabama Birmingham, Alabama MedicalResearch: What is the background for this study? What are the main findings? Dr. Rocque: This study grew out of a retrospective study we conducted in 2010 in which we evaluated the characteristics of patients admitted to our solid tumor oncology service, what occurred during their hospitalization, and what their outcomes were after discharge.  We identified that the average life expectancy of the population was less than 4 months and therefore, inpatient admission was an opportunity for palliative care support.  Therefore, we conducted a sequential, prospective cohort study of patients before and after implementation of triggered palliative care consults for patients with advanced cancer. We found that patients’ prognostic awareness meaningfully and significantly improved after the implementation of consults, but there was little impact on utilization of health services. We did identify that providing consults to the entire population of patients was logistically challenging due to short stays, high-acuity symptoms, and individual provider resistance, but overall the oncology providers found the consults to be beneficial. (more…)
Author Interviews, Cancer Research, JAMA, NIH / 22.06.2015

MedicalResearch.com Interview with: Vinay Prasad, MD, MPH Medical Oncology Service, National Cancer Institute National Institutes of Health Bethesda, Maryland MedicalResearch: What is the background for this study? What are the main findings? Dr. Prasad: In medicine, there are two types of endpoints:  clinical endpoints and surrogate endpoints. Clinical endpoints, such as survival or quality of life, measure how a patient, feels, functions or lives.  In contrast, a surrogate endpoint is not a measure of patient benefit. Instead, it is merely hoped to correlate with one.  LDL levels are a surrogate for cardiovascular risk, for instance. Oncologists use and trust surrogate endpoints, such as response rate, progression free survival and disease free survival.  The majority of drug approvals and many guideline recommendations are based on improvements in surrogates.  Surrogates are assumed to correlate with overall survival, but we wanted to know if this was true, and under what circumstances. We reviewed all well done studies of surrogate-survival association.  We found that the majority--especially in the setting of metastatic disease--found a poor correlation between a surrogate and survival.  In fact, correlations were strong in only a handful of settings, such as adjuvant colorectal cancer.  Moreover, we found that correlations were always based on a subset of potentially informative literature, even when authors surveyed unpublished trials.  Missing data in these association studies raises the concern that correlations would be different if all data had been considered. Our overall conclusion was that most surrogate-survival correlations in oncology are based on weak evidence and are poor. (more…)
Author Interviews, Surgical Research, UCSF, Weight Research / 22.06.2015

MedicalResearch.com Interview with: Leslee L. Subak, MD University of California, San Francisco Professor, Departments of Obstetrics, Gynecology & Reproductive Sciences, Urology and Epidemiology & Biostatistics Chief of Gynecology, SF Veterans Affairs Medical Center UCSF Women's Health Clinical Research Center MedicalResearch: What is the background for this study? What are the main findings? Dr. Subak: Urinary incontinence is very common, affecting an estimated 30 million adults in the U.S., and may account for as much as $60 billion in annual medical costs. Incontinence can cause significant distress, limitations in daily functioning, and reduced quality of life. Obesity is an important risk factor, with each 5-unit increase in body mass index – a ratio of someone’s weight divided by the square of their height – above normal weight associated with far higher rates of incontinence.   The prevalence of incontinence has been reported to be as high as 70 percent among severely obese women, and 24 percent among severely obese men (BMI greater than 40, or more than about 100 pounds greater than ideal body weight). Since obesity is a risk factor for incontinence, several studies have examined whether weight loss is a treatment for incontinence among obese people with the condition.  Clinical trials have shown the low calorie diets, behavioral weight reduction, and bariatric surgery are associated with improvement in incontinence in obese women and men through one year, but evidence on the durability of this effect is lacking. We performed this study to examine changes in urinary incontinence and identify factors associated with improvement among women and men in the first 3 years following bariatric surgery. This study included 1987women and men in the Longitudinal Assessment of Bariatric Surgery-2 (LABS-2) study performed at 10 hospitals at 6 clinical centers in the U.S. who underwent bariatric surgery between 2005 and 2009.  The study participants ranged in age from 18 to 78 years old – the median age was 47. The analysis controlled for factors such as age, race, smoking status and recent pregnancy.  Nearly 79 percent of the participants in the study were women with 49% reporting at least weekly incontinence, compared with 2% of men reporting incontinence. Following surgery and large weight loss of 29% for women and 26% for men, substantial improvements in incontinence were observed, with a majority of women and men achieving remission at 3 years post-surgery. The more weight lost, the higher the chances of improvement. While the risk of relapse rose with each gain of about 10 pounds, overall there was substantial improvement for both women and men. People who were older, had severe walking limitations or were recently pregnant showed less improvement. (more…)
Author Interviews, Heart Disease, Race/Ethnic Diversity / 22.06.2015

MedicalResearch.com Interview with: Dr. Mary Vaughan Sarrazin Ph.D. Associate Professor University of Iowa Roy and Lucille Carver College of Medicine, and Iowa City VA Medical Center, Center for Comprehensive Access & Delivery Research and Evaluation (CADRE) Iowa City, IA Dr. Rajesh Kabra MD Division of Cardiology, Department of Internal Medicine University of Tennessee Health Science Center, Memphis, Tennessee MedicalResearch: What is the background for this study? What are the main findings? Response: Atrial fibrillation is associated with high risk of stroke and death. It is not known if these outcomes are different in whites, blacks and Hispanics. In our study of over 500,000 Medicare patients over the age of 65 years with newly diagnosed atrial fibrillation, we noted that compared to whites, blacks and Hispanics had a higher risk of mortality (46% and 11% higher respectively) and stroke (66% and 21% respectively). However after correcting for other co-morbidities and illnesses, the risk of mortality was the same in all the races; the higher risk of stroke was decreased in blacks and eliminated in Hispanics. This suggests that in blacks and Hispanics, atrial fibrillation is a marker for higher mortality and identifies patients at higher risk of death. (more…)
Author Interviews, Heart Disease, JACC / 21.06.2015

MedicalResearch.com Interview with: José C. Nicolau, MD, PhD, FACC Professor -University of São Paulo Medical School Director - Acute Coronary Disease Unit, Heart Institute MedicalResearch: What is the background for this study? Dr. Nicolau: Previous studies, mainly performed in patients undergoing percutaneous coronary intervention (PCI), have shown that concomitant use of proton-pump inhibitors (PPIs) diminishes the antiplatelet effect of the drug clopidogrel. This diminished response to clopidogrel has in turn been associated with an increased risk of stent thrombosis and ischemic events. Our paper presented results from a secondary analysis performed in patients enrolled in the TRILOGY ACS randomized clinical trial. Our study is the first to examine the influence of interactions between PPIs and clopidogrel or the newer, more potent antiplatelet drug prasugrel, as well as correlations with platelet reactivity and clinical outcomes in high-risk patients who were receiving medical management without revascularization following acute coronary syndrome (ACS). (more…)
Author Interviews, Technology / 21.06.2015

MedicalResearch.com Interview with: Mehdi Ardavan Concordia University/Université Concordia Medical Research: What is the background for this study? Response: That thousands patients die each year in US hospitals due to ​medical errors that could be prevented if medical staff were provided with instant access to patient records. Wireless technology (such as portable tablets) is one way of providing this instant access. But using such devices can cause electromagnetic interference ​(EMI) ​ with electronic medical devices and can lead to dangerous consequences for patients. Hospitals may have a policy of minimum separation distance (MSD) which means that the staff members carrying wireless devices cannot approach sensitive medical devices closer than the specified MSD. The problem was that the recommend values of the minimum separation distance were not based on a quantitative and thorough analysis of the problem. We wanted to see what is the correct value of MSD, and how it's determined. Medical Research: What are the main findings? Response: We developed new and fast methods for estimating the electromagnetic field distribution. We also mathematically modeled the roaming nature of the staff members carrying the wireless transmitters. Then we modeled the minimum separation distance policy and added an option to account for a possibility of non-compliance with the policy. First, we assumed a full compliance with MSD policy and found that the risk of interference decreased constantly as the minimum separation distance was increased. Quantitative recommendations are made for the value of the MSD. But once we considered a small non-compliance probability, an interesting ​and unexpected ​ phenomenon was observed: the EMI risk does not decrease beyond a certain value and remains almost constant for all ​MSDs bigger than a value we call the optimal MSD. If we increase the minimum separation distance beyond its optimal value, the risk of EMI does not decrease but more restrictions and thus more inconvenience is put on the staff members. So larger values of MSD are not necessarily safer and are not recommended. ​We also find that the risk and the optimal minimum separation distance are both sensitive to the rate of compliance with the MSD policy.​ (more…)
Abuse and Neglect, Aging, Weight Research / 21.06.2015

MedicalResearch.com Interview with: Dr. Min Du Ph.D Department of Animal Sciences Washington Center for Muscle Biology Washington State University Pullman, WA Medical Research: What is the background for this study? What are the main findings? Response: The beige fat is only recently identified and is highly inducible. we observed that polyphenolic compounds including resveratrol enhances AMPK activity, and hypothesized that resveratrol might enhance the formation of beige fat through activation of AMPK. Therefore, we used resveratrol, a very well characterized polyphenolic compound as a representative of polyphenolic compounds in fruits, to check its effects on the formation of beige fat. We found that resveratrol induced the formation of beige adipocytes both in vitro and in vivo. We further found that the lipid oxidation rate was enhanced due to the formation of beige fat, which is correlated with the anti-obesity effect of resveratrol. (more…)
Anesthesiology, Author Interviews, Emergency Care, JAMA / 21.06.2015

MedicalResearch.com Interview with: Christoph Czarnetzki MD, MBA Division of Anesthesiology Geneva University Hospitals Geneva, Switzerland Medical Research: What is the background for this study? What are the main findings? Dr. Czarnetzki: In the US, about 40 million patients undergo a general anesthetic each year, and approximately 12,000 broncho-aspirate. Broncho-aspiration of gastric juice may lead to acute respiratory distress syndrome, carrying a 40% mortality rate. The risk is increased 10-fold in patients undergoing emergency surgery. Trauma patients may have ingested food before their accident, or have swallowed blood from oral or nasal injuries. Also, gastric emptying is delayed due to head injury, stress, pain, and opioid medication. Non-trauma patients may have delayed gastric emptying due to paralytic ileus and critical illness, leading to significant residual stomach content even after long fasting periods. Erythromycin, a macrolide antibiotic, and motilin receptor agonist induces antral contractions, and increases the lower esophageal sphincter tone, which is an important barrier against gastro-esophageal reflux. Although gastric emptying properties of erythromycin are well known, its efficacy in patients undergoing emergency surgery has never been investigated before to our knowledge. In our study we included 132 patients undergoing general anesthesia for emergency procedures and we could show that erythromycin increased the proportion of clear stomach and decreased acidity of residual gastric liquid. Dependent of the definition of empty stomach (less than 40 ml and absence of solid food or completely empty stomach) the absolute risk reduction ranged from 17% to 24%, equivalent to a number needed to treat of four to six patients to produce one completely cleared stomach. Erythromycin was particularly efficacious in non-trauma patients. Adverse effects were minor. (more…)
Author Interviews, Diabetes, Endocrinology, JAMA / 21.06.2015

MedicalResearch.com Interview with: Francis de Zegher, MD, PhD Department of Development and Regeneration, University of Leuven Leuven, Belgium & Lourdes Ibáñez, MD, PhD Hospital Sant Joan de Déu, University of Barcelona Barcelona, Spain Medical Research: What is the background for this study? Response: Hyperinsulinemic androgen excess is the most frequent hormonal disorder of adolescent girls. It seems to be mainly driven by an excessive and/or inappropriate storage of fat due to a chronically positive energy balance. The traditional approach (not approved by FDA or EMA) is to silence the ovaries by giving an oral contraceptive. An alternative approach is to change the storage of fat by giving an insulin-sensitizing combination of generics in low dose. (more…)
AHA Journals, Author Interviews, Heart Disease, Social Issues / 21.06.2015

Jaana Halonen Ph.D Finnish Institute of Occupational Health Kuopio, FinlandMedicalResearch.com Interview with: Jaana Halonen Ph.D Finnish Institute of Occupational Health Kuopio, Finland MedicalResearch: What is the background for this study? What are the main findings? Dr. Halonen: Research on predictors of cardiovascular disease has increasingly focused on exposures to risk factors other than the conventional behavioral and biological ones, such as smoking, hypertension, dyslipidaemia, or diabetes. One of the potential predictors beyond the conventional risks is exposure to childhood psychosocial adversities. Previous studies have found that people who had experienced financial difficulties, serious conflicts and long-term disease in the family in childhood have a higher level of cardiovascular risk factors and increased cardiovascular morbidity in adulthood, but the underlying mechanisms linking childhood exposure to adult disease remain unclear. It is possible that childhood adversity sets an individual on a risk pathway leading to adverse future exposures. An important source of adversity experienced in adulthood is residence in a socioeconomically disadvantaged neighborhood. However, no previous study had examined the combined effect of childhood psychosocial adversity and adult neighborhood disadvantage on cardiovascular disease risk. We found that exposure to childhood psychosocial adversity and adult neighborhood disadvantage in combination was associated with a doubling of the risk of incident cardiovascular disease in adulthood when compared to the absence of such exposures. This association was not explained by conventional cardiovascular risk factors. Neither childhood psychosocial adversity nor adult neighborhood disadvantage alone were significantly associated with incident CVD, although they were associated with CVD risk factors. (more…)
Author Interviews, Biomarkers, Breast Cancer / 21.06.2015

MedicalResearch.com Interview with: Kristian Pietras, Ph.D. Göran & Birgitta Grosskopf Professor of Molecular Medicine Strategic Director of Cancer Research Lund University Dept of Laboratory Medicine Lund Div of Translational Cancer Research Lund, Sweden Medical Research: What is the background for this study? What are the main findings? Dr. Pietras: Breast cancer is the largest malignant disease among women with 1.7 million new cases worldwide each year (25% of all new cancer cases for women). The prognosis for breast cancer patients is relatively good when the disease is detected at early stages (close to 90% of patients are still alive 5 years after diagnosis). Nevertheless, metastatic disease is the cause of 90% of all cancer-related deaths. Thus, learning more about the metastatic process and finding new cures for widespread disease is justifiably at the center of clinical attention. The current study is part of our ongoing efforts to map support functions performed by the various cell types comprising the tumor stroma with the premise that decisive treatment benefit can only be achieved by targeting multiple, but distinct, cell types and pathways that collectively sustain the growth of tumors. The development of a rich vascular supply  is recognized as a key hallmark of a growing tumor necessary for the development into a clinically relevant disease. Our focus is the role of the tumor vasculature in preventing or promoting metastatic dissemination from the primary tumor. For a metastasis to form, a cancer cell must, 1) detach from its neighboring cells in the mother tumor, 2) traverse the vascular wall to escape into the blood stream, 3) exit the vasculature to enter the metastatic site, and 4) colonize the metastatic site. Recent evidence points to that the transmigration into and out of the vasculature is a regulated process of previously unrecognized importance for the metastatic process. Importantly, the fact that the process of escape into/from the vasculature is regulated also implies that it is possible to use drugs to block this process. In the present study, we have combined functional studies in advanced models of cancer and computational biology approaches to investigate the specific contribution to the metastatic process of a molecular signaling pathway emanating from the ALK1 protein expressed by endothelial cells in the vasculature. Using information from 2 different patient cohorts including a total of  nearly 2000 breast tumors, we found that patients specifically having high levels of ALK1 in the vasculature of their tumor were much more likely to develop metastatic/recurrent disease. Accordingly, therapeutic administration of a drug (dalantercept) blocking the action of ALK1 prevented metastatic dissemination in multiple mouse models of breast cancer to a large degree. In addition, combination therapy of dalantercept and a commonly used chemotherapeutic drug (docetaxel) was exceedingly effective in preventing spread of the primary tumor to the lungs. Our results suggest that the molecular features of the tumor vasculature are important to consider as potential determinants of breast cancer dissemination and that metastatic spread can be delayed by targeting the tumor vasculature. (more…)
Author Interviews, Breast Cancer, JAMA, Race/Ethnic Diversity, Surgical Research, University Texas / 21.06.2015

Isabelle Bedrosian, M.D., F.A.C.S. Associate Professor, Department of Surgical Oncology, Division of Surgery, Medical Director, Nellie B. Connelly Breast Center The University of Texas MD Anderson Cancer Center, Houston, TXMedicalResearch.com Interview with: Isabelle Bedrosian, M.D., F.A.C.S. Associate Professor, Department of Surgical Oncology, Division of Surgery, Medical Director, Nellie B. Connelly Breast Center The University of Texas MD Anderson Cancer Center, Houston, TX Medical Research: What is the background for this study? What are the main findings? Dr. Bedrosian: There have been a number of reports on the rates of Breast Conserving Therapy (BCT) and mastectomy among women with early stage breast cancer. These reports have been discordant, with some suggesting that index mastectomy rates have increased and others suggestion Breast Conserving Therapy rates have actually increased. We hypothesized that these differences in reporting may be due to data source (ie tertiary referral centers vs population based studies) and turned to the NCDB, which captures 70% of cancer cases in the US and as such provides us with the most comprehensive overview on patient treatment patterns. (more…)
Author Interviews, BMJ, Imperial College / 21.06.2015

Mr. Angus Turnbull Imperial College School of Medicine, London UKMedicalResearch.com Interview with: Mr. Angus Turnbull Imperial College School of Medicine, London UK Medical Research: What is the background for this study? What are the main findings? Mr. Turnbull: Autopsy has been used to advance medical knowledge and understanding of pathological processes for millennia but increasing evidence indicates its decline in the UK and elsewhere. This study not only confirms that but suggests autopsy for learning purposes has almost disappeared. In the United Kingdom autopsy is divided into medico-legal autopsy (that required by law under the jurisdiction of HM Coroner) and consented autopsy (performed with the consent of the bereaved or their family). Over the past half-century, small single site studies have noted a marked decline in consented autopsy rates, however there has been no study for over 20 years to determine the extent of the decline nationwide. This study examined all acute NHS Trusts within England, NHS Boards in Scotland and Wales and Social Care Trusts in Northern Ireland. We found that the average autopsy rate (the percentage of adult inpatient deaths which under go consented autopsy) in the United Kingdom in 2013 was only 0.7%. The study showed that in nearly a quarter (23%) of all NHS Trusts in the United Kingdom, consented autopsy is now extinct. These findings may have implications for training, for research and for learning from mortality – a key aspect of patient safety. (more…)
Author Interviews, Lifestyle & Health, NYU / 19.06.2015

MedicalResearch.com Interview with: Stella Yi, PhD, MPH New York University Langone School of Medicine, Department of Population Health New York, NY 10016 MedicalResearch: What is the background for this study? What are the main findings? Dr. Yi: Sedentary behaviors, such as sitting time, are an emerging risk factor in the field of physical activity epidemiology. Recent studies have demonstrated the negative health consequences associated with extended sitting time, including metabolic disturbances and decreased life expectancy independent of the effects of regular exercise. We also assessed mean values of self-reported sitting time to characterize these behaviors in a diverse, urban sample of adults. The average New York City resident sits more than seven hours a day—greatly exceeding the three hours or more per day that is associated with decreased life expectancy. Among the findings:
  • At the lower economic end, individuals spent 6.3 hours per day sitting, while those with higher incomes spent 8.2 hours per day sitting
  • College graduates spent 8.2 hours per day sitting, compared with 5.5 hours per day for those with less than a high school education
  • Whites spent on average 7.8 hours per day sitting, African Americans spent 7.4 hours sitting, Hispanics spent 5.4 hours sitting, and Asian Americans spent 7.9 hours per day sitting
  • Sitting time was highest in Manhattan, compared to other boroughs.
In the current analysis, we also assessed the validity of a two-question survey method of sitting time during waking hours using accelerometers to measure sedentary time in a subsample of our study participants. The correlation between sitting time reported in the survey and accelerometer-measured sedentary time was modest (r=0.32, p<0.01) with wide limits of agreement. We interpreted this to mean that while self-reported sitting might be useful at the population-level to provide rankings and subgroups, it may be limited in assessing an individual’s actual behavior. (more…)
Author Interviews, Lancet / 19.06.2015

MedicalResearch.com Interview with: Dr. Stephan Glund Ph.D. Boehringer Ingelheim Pharma GmbH & Co. KG Transl. Medicine & Clin. Pharmacology Medical Research: What is the background for this study? What are the main findings? Dr. Glund: There are currently no specific reversal agents available for any of the non-Vitamin K antagonist oral anticoagulants (NOACs). We are working on the development of idarucizumab, a specific reversal agent to dabigatran, the first approved NOAC. The study now published in The Lancet investigated, for the first time in healthy volunteers, the reversal of the anticoagulant effect of dabigatran by idarucizumab. Our study in healthy male volunteers showed that idarucizumab led to immediate, complete and sustained reversal of the anticoagulant effect of dabigatran. Participants first received dabigatran and then idarucizumab. The specific reversal agent was given two hours after the last dose of dabigatran, when dabigatran concentrations were at peak levels. After a five-minute infusion of idarucizumab, anticoagulation was immediately reversed back to baseline levels. The reversal effect was sustained for more than 24 hours for all doses of 2g and above. Idarucizumab was well tolerated by the study participants. In addition, our study also showed that administration of idarucizumab reversed dabigatran-induced inhibition of wound-site fibrin formation, which plays a key role in the blood clotting mechanism. This suggests that idarucizumab might also reverse impaired haemostasis due to dabigatran anticoagulation at a wound site. (more…)