Author Interviews, Biomarkers, Melanoma / 25.06.2015

Mitchell S. Stark Senior Research Assistant/PhD Student Oncogenomics Group QIMR Berghofer Medical Research Institute Herston, Brisbane, AustraliaMedicalResearch.com Interview with: Mitchell S. Stark Senior Research Assistant/PhD Student Oncogenomics Group QIMR Berghofer Medical Research Institute Herston, Brisbane, Australia Medical Research: What is the background for this study? What are the main findings? Response: Melanomas are among the most commonly occurring cancers with the number of new cases rising each year. Melanoma is currently is listed as the 4th and 6th most common cancer in Australia and the USA with >11,000 and >76,000 news diagnoses each year.  The overall 5-year survival for melanoma is 91%, which is largely due to curative surgery for early stage disease. However, cure rates are <15% if distant metastasis occurs (stage IV). We now have evidence that current therapeutic options for late stage disease are more effective if the disease is treated with a lower disease burden.  2010). Hence, melanoma must be treated in earlier stages to maximize the chances of patient survival. Therefore, the ability to identify signs of melanoma progression sooner would be a valuable clinical tool. The use of melanoma progression markers have been used for many years however it is clear from the survival rates that melanoma must be detected before disease progresses thus highlighting that the current methods of progression detection are inadequate. We have identified a seven-microRNA panel (MELmiR-7) that has the ability to detect the presence of melanoma with high sensitivity and specificity which is superior to currently used markers for melanoma progression, recurrence, and survival. This panel may enable more precise measurement of disease progression and may herald an increase in overall survival. (more…)
Author Interviews, Autism, JAMA, OBGYNE / 25.06.2015

MedicalResearch.com Interview with: Ali S. Khashan, Ph.D. Irish Centre for Fetal and Neonatal Translational Research (INFANT) Cork, Ireland Medical Research: What is the background for this study? What are the main findings? Dr. Khashan: The Caesarean section rate is increasing worldwide reaching 30% in some western countries and 50% in China and Brazil. As a result, it is becoming increasingly important to understand the long-term effects this procedure may have on both mother and child. Previously, our group conducted a systematic review and meta-analysis of published literature and found birth by Caesarean to be associated with approximately 20% increased risk of autism spectrum disorder (ASD), compared to birth by vaginal delivery. This means if the risk of ASD in children born by vaginal delivery were 1%, and the association was causal, the risk of autism spectrum disorder in children born by Caesarean section is 1.2% i.e. two additional ASD cases per 1000 births. However, studies were limited, and we were unable to determine what was driving this association. In our new study, now published in JAMA Psychiatry, we investigated this issue further with the largest study on this subject to date, including all children born in Sweden between 1982 and 2010. Our study included data on over 2.9 million people and accounted for variety of factors known to be associated with both Caesarean section and autism spectrum disorder. After controlling for known confounders, such as maternal age and psychiatric history as well as various other perinatal and socio-demographic factors, we confirmed our previous findings that birth by Caesarean was associated with approximately 20% increased risk of autism spectrum disorder, compared to birth by vaginal delivery. However, with this analysis it remained unclear whether the increased risk was due to the Caesarean section itself, or some genetic or environmental factor that we were unable to measure. To determine if it was birth by Caesarean section or another unknown factor which led to an increased risk of ASD, we compared children with autism spectrum disorder to their non-diagnosed brothers and sisters. In other words, we analysed pairs of siblings in which one was diagnosed with ASD and one was not, to determine if birth by Caesarean was associated with increased risk of ASD within families. In this way, we attempted to indirectly account for genetic and family environment factors that are shared by siblings but we were unable to measure in the general population. In this analysis, which included data on over 13,000 sibling pairs, there was no longer any association between birth by Caesarean section and ASD. Overall, these results indicate that though birth by Caesarean section may be associated with an increased risk of ASD, it is likely due to family factors such as genetics or environment, rather than the Caesarean section itself. These findings are more informative than many previous studies as we had the largest sample size on this topic to date and estimated the association between Caesarean section and the risk of autism spectrum disorder while comparing siblings born by different methods of delivery. This allowed us to control for many factors that other studies did not. (more…)
Author Interviews, Cannabis, JAMA, Johns Hopkins / 25.06.2015

Ryan Vandrey, Ph.D. Associate Professor Behavioral Pharmacology Research Unit Johns Hopkins University School of Medicine Baltimore, MD 21224MedicalResearch.com Interview with: Ryan Vandrey, Ph.D. Associate Professor Behavioral Pharmacology Research Unit Johns Hopkins University School of Medicine Baltimore, MD 21224 Medical Research: What is the background for this study? What are the main findings? Dr. Vandrey: The background for the study was that I have had several conversations with individuals that led me to believe that there was insufficient regulation of products of all types being sold in medical cannabis dispensaries.  In order to evaluate that, we needed to do a study.  We decided to test edible products because that is a growing market, and, because it involves some level of manufacturing, there is greater chance for dose variability and inaccuracy.  The main finding was that the majority of products were purchased from retail stores selling cannabis products for medical use were significantly mislabeled with regards to the dose of THC and other cannabinoids. (more…)
Author Interviews, JAMA, Surgical Research, Technology / 25.06.2015

Vanita Ahuja, MD, MPH Department of General Surgery York Hospital, York, PennsylvaniaMedicalResearch.com Interview with: Vanita Ahuja, MD, MPH  Department of General Surgery York Hospital, York, Pennsylvania MedicalResearch: What is the background for this study? What are the main findings? Dr. Ahuja: Robotic-assisted surgery has been slowly accepted within the medical community. Felger et al. (1999), Falk et al. (2000), and Loumet et al. (2000) state that specific to cardiac surgery, the advantages of the robot in coronary artery bypass grafting (CABG) and valvular operations were demonstrated with increased visualization, ease of harvest, and quality of vascular anastomoses as early as 1999. However, Giulianotti, et al. (2003), Morgan et al. (2005), and Barbash et al. (2010) suggest that although safety and efficacy are supported, it is not conclusive yet that robot-assisted surgery is cost-effective, given the high cost of the robot itself, longer operating times, and the short life of the robotic instruments. The purpose of our paper was to compare outcomes of complications, length of stay (LOS), actual cost, and mortality between non-robotic and robotic-assisted cardiac surgery. In general surgery and subspecialties, the use of the robot has increased significantly over the past few years. It has been noted that robotic surgery improves on laparoscopic surgery by providing increased intra-cavity articulation, increased degrees of freedom, and downscaling of motion amplitude that may reduce the strain on the surgeon. The biggest growth in robotic surgery has been seen in the fields of gynecology and urology. Recently, Wright et al. reported an increase in robotic assisted hysterectomy from 0.5 percent of the procedures in 2007 compared to 9.5 percent in 2010 for benign disease. In their study, robotic assisted surgery had similar outcomes to laparoscopic surgery but higher total cost of $2,189 more per case. In urologic surgery, Leddy et al. reported in 2010 that radical prostatectomy remains the biggest utilization of robotic assisted surgery in urology with 1% in 2001 to 40% of all cases in 2006 performed in the United States. Utilizing a nationwide database from 2008-2011, subjects were propensity matched by 14 patient characteristics to reduce selection bias in a retrospective study. The patients were then divided into three groups by operation types: valves, vessels and other type. Univariate analysis revealed that robotic-assisted surgery, compared to non-robotic surgery, had higher cost ($39,030 vs. $36,340), but lower LOS (5 vs. 6 days) and mortality (1% vs. 1.9%, all p<0.001). For those who had one or more complications, robotic-assisted cardiac surgery had fewer complications (27.2%) to non-robotic cardiac surgery (30.3%, p < .001). (more…)
Author Interviews, Hand Washing, Infections / 25.06.2015

Laila Cure, Ph.D. Assistant Professor Dept. of Industrial and Manufacturing Engineering Wichita State UniversityMedicalResearch.com Interview with: Laila Cure, Ph.D. Assistant Professor Dept. of Industrial and Manufacturing Engineering Wichita State University Medical Research: What is the background for this study? What are the main findings? Response: It is widely known that healthcare work, particularly inpatient care work, is mostly knowledge-based. Healthcare workers are constantly assessing the clinical state of their patients and making decisions that affect their workflow. This type of work is difficult to study and organize as a whole using traditional work design techniques, which are mostly designed for routine, repetitive work. Nevertheless, there are components of inpatient work that can be improved using basic workstation design principles. Hand hygiene is one of them. Hand hygiene is still the single most important intervention to prevent infection in hospitals. Guidelines state that health care workers should clean their hands before touching a patient, before an aseptic procedure, after body fluid exposure, after touching a patient, after touching patient surroundings. Hand sanitizer dispensers are practical resources to support hand hygiene because they can be placed almost anywhere throughout hospital units. This study aimed at determining whether “good” placement of sanitizer dispensers correlates with compliance of staff in using the sanitizer. “Good placement” was defined in terms of usability characteristics extracted from hand hygiene literature recommendations. Of the usability characteristics included in the study, visibility and accessibility had some statistical influence on improving compliance. (more…)
Author Interviews, Cancer Research, JAMA / 25.06.2015

Dr. Ayalew Tefferi, M.D.Department of Medicine, Mayo Clinic Rochester, Minnesota MedicalResearch.com Interview with: Dr. Ayalew Tefferi, M.D. Department of Medicine, Mayo Clinic Rochester, Minnesota MedicalResearch: What is the background for this study? What are the main findings? Dr. Tefferi: William Vainchenker discovered and reported an activating JAK2 mutation (JAK2V617F) in myelofibrosis and related myeloproliferative neoplasms in 2005 (Nature. 2005;434:1144-1148). This seminal observation led to the recognition of activated JAK-STAT as the potential disease-driving pathway in myeloproliferative neoplasms and development of several JAK inhibitors, including fedratinib, ruxolitinib and momelotinib, for treatment of myelofibrosis. In phase 2 studies, these JAK inhibitors showed similar activity in alleviating constitutional symptoms and reducing spleen size. However, none of them were able to induce complete or partial remissions or reversal of bone marrow fibrosis or significant lowering of JAK2 mutant allele burden. A subsequent phase 3 study provided the information required for FDA approval of ruxolitinib and the current phase 3 study was meant to do the same for fedratinib. (more…)
AHA Journals, Author Interviews, Lipids, Race/Ethnic Diversity / 25.06.2015

Carlos J. Rodriguez, MD, MPH Division of Public Health Sciences Department of Medicine Wake Forest School of Medicine Winston‐Salem, NC 27152MedicalResearch.com Interview with: Carlos J. Rodriguez, MD, MPH Division of Public Health Sciences Department of Medicine Wake Forest School of Medicine Winston‐Salem, NC 27152 MedicalResearch: What prompted you to study cholesterol in the Latino population? Please explain in detail. Dr. Rodriguez: Early in my career I noted that there were race-ethnic differences in the cholesterol profile between hispanics, african americans and non-hispanic whites. Hispanics are the largest ethnic minority group in the us yet prior studies of cholesterol in hispanics were relatively small, lacked adequate representation of diverse hispanic background groups for comparisons, and were not necessarily representative of nor generalizable to the hispanic population. The hispanic/latino adults in the hispanic community health study / study of latinos helped filled this critical gap. MedicalResearch: What do you think are the most significant findings from your study? What could have the greatest clinical implications and applications? Dr. Rodriguez: Several findings are important: less than half of those with high cholesterol were aware of their condition; less than a third of those with high cholesterol were being treated; and  among those receiving treatment, only two-thirds had cholesterol concentrations that were adequately controlled. (more…)
Author Interviews, Education, Outcomes & Safety / 24.06.2015

MedicalResearch.com Interview with: Stephen M. Shortell, PhD, MPH, MBA Blue Cross of California Distinguished Professor of Health Policy and Management and Director, Center for Healthcare Organizational and Innovation Research (CHOIR) School of Public Health UC-Berkeley Medical Research: What is the background for this study? What are the main findings? Dr. Shortell: To meet quality and expenditure targets, Accountable Care Organization (ACOs) need to change how care is delivered to patients to reduce preventable hospitalizations, readmissions, emergency department visits, and unnecessary tests. To do this they need to increase their engagement with patients and patient families. With support from the Gordon and Betty Moore Foundation, we undertook the study to assess the extent to which ACOs are engaging their patients and patient families and to identify some of the barriers and facilitators of such engagement. We did a survey of 101 ACOs, in-depth phone interviews with eleven ACOs and two on site visits. Among our key findings are: 1) There are some "early adopters" of patient engagement activities with, for example, respondents reporting an average of 62 percent of primary care physicians working with patients/families to set treatment goals and 61 percent of high risk chronic illness patients participating in formal care transition programs; but 2) Only 18 percent of ACO high risk chronic illness patients participate in peer support groups or group visits, and only 24 percent of patients have access to both medical records and clinical notes in the record; 3) ACO leaders strongly believe patient activation and engagement is critical to ACO success and those who have such beliefs do have greater patient engagement at the actual point of care; 4) Engaging patients is very difficult challenging work as it often involves a total re-organization of workflow within physician practices including the re-allocation of tasks to other healthcare professionals, reorganization of time commitments, adjustment to use of electronic health records and training in communication methods. (more…)
Author Interviews, Heart Disease, JACC, University of Michigan / 24.06.2015

MedicalResearch.com Interview with: Jessica Parsh MD Hitinder Gurm MBBS Department of Internal Medicineb University of Michigan Health System Medical Research: What is the background for this study? What are the main findings? Response: Chronic kidney disease (CKD) is associated with adverse events after percutaneous coronary interventions (PCI). Estimated glomerular filtration rate (eGFR) is used for CKD stage classification and there are several widely used eGFR equations, including the Cockcroft-Gault, CKD-EPI, and MDRD. Others have shown that the CKD-EPI equation is more accurate, more precise and less bias. The current Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend the use of CKD-EPI. Even so, there remains wide variability among equation choice between different institutions as well as between different health care providers (physicians, pharmacists, etc). In addition, in a recent survey, up to 12% of providers were "unsure" of which equation they used. Furthermore, the FDA has no clear guidelines regarding equation selection for pharmacokinetic studies of novel medications and the equation used for development of a particular drug is not always clearly labeled on package inserts. Using data from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium for almost 130,000 patients who underwent PCI, we investigated whether use of different eGFR equations would lead to discrepant eGFR output, how this would lead to CKD stage reclassification and whether CKD stage reclassification by a certain equation led to improved risk prognostication for adverse events. We also studied how calculation of eGFR by various equations would affect drug dosing recommendations for common renally-dosed antiplatelet and antithrombotic medications. We found that there was wide discrepancy among the eGFR output of the various equations and this led to significant CKD stage reclassification (with agreement on stage classification as low as 56% for CKD-EPI and Cockcroft-Gault). Further, our data from receiver operating characteristic analysis and net reclassification index analysis support CKD-EPI as superior for risk prognostication for renal adverse outcomes of acute kidney injury and new requirement for dialysis. In regards to drug dosing, agreement between all three equations on dosing adjustment was as low as 34% (bivalirudin with eGFR cutoff < 30 ml/min/1.732). (more…)
Author Interviews, Erectile Dysfunction, JAMA, Melanoma, NYU, Pharmacology / 24.06.2015

Dr. Stacy Loeb, MD, MScDepartment of Urology, Population Health, and Laura and Isaac Perlmutter Cancer CenterNew York University, New York MedicalResearch.com Interview with: Dr. Stacy Loeb, MD, MSc Department of Urology, Population Health, and Laura and Isaac Perlmutter Cancer Center New York University, New York Medical Research: What is the background for this study? Dr. Loeb: A paper published last year suggested a relationship between use of (Viagra) and melanoma.  That study had only 142 cases of melanoma, and of these men 14 had used sildenafil.  This study got a lot of publicity leading numerous patients to express concern over whether erectile dysfunction drugs could cause melanoma. Our goal was to look more closely at this issue in a larger population from Sweden (including 4065 melanoma cases of whom 435 used any type of erectile dysfunction drug- Viagra, as well as Levitra and Cialis).  Sweden has a national health system so we were able to access prescription records for men across the entire country, which we linked to the national registries for melanoma and basal cell skin cancer.   (more…)
Author Interviews, Duke, Heart Disease, JAMA / 24.06.2015

Sean D. Pokorney, MD, MBA Division of Cardiology, Duke University Medical Center Duke Clinical Research Institute, Durham, North Carolina MedicalResearch.com Interview with: Sean D. Pokorney, MD, MBA Division of Cardiology, Duke University Medical Center Duke Clinical Research Institute, Durham, North Carolina Medical Research: What is the background for this study? Dr. Pokorney: About 350,000 people die of sudden cardiac death in the US each year. Patients who have weakened heart function, particularly those with heart muscle damage as a result of a heart attack, are more likely to experience sudden cardiac death.  Defibrillators have been around since the 1980s, and have prolonged countless lives.  A previous study showed that 87% of patients who had a cardiac arrest were eligible for an implantable-cardioverter defibrillator (ICD) beforehand but did not get an ICD implanted prior to their arrest.  The timing of ICD implantation is critical, as studies have not found a benefit to ICD implantation early after myocardial infarction (MI).  Guidelines recommend primary prevention ICD implantation in patients with an EF ≤ 35% despite being treated with optimal medical therapy for at least 40 days after an MI.  Given the need to wait for at least 40 days after an MI, ICD consideration is susceptible to errors of omission during the transition of post-MI care between inpatient and outpatient care teams.  Also, the benefit of ICDs remains controversial among older patients, as these patients were underrepresented in clinical trials. Medical Research: What are the main findings? Dr. Pokorney: We looked at Medicare patients discharged from US hospitals after a heart attack between 2007 and 2010.  We focused on those patients who had weak heart function, and this left us with a little over 10,300 patients from 441 hospitals for our study.  This was an older patient population with a median age of 78 years.  We looked to see how many of these patients got an ICD within the first year after MI, and how many patients survived to 2 years after their heart attack.  Only 8% of patients received an ICD within 1 year of their heart attack.  ICD implantation was associated with a third lower risk of death within 2 years after a heart attack, and this was consistent with the benefit that were seen in the randomized clinical trials.  Importantly, 44% of the patients in our study were over 80 years old, and we found that the relationship between ICD use and mortality was the same for patients over and under age 80 years.  Increased patient contact with the health care system through early cardiology follow-up or re-hospitalization for heart failure or MI was associated with higher likelihood of ICD implantation.  Rates of ICD implantation remained around 1 in 10 patients within 1 year of MI even among patients with the largest heart attacks and the weakest hearts (lowest ejection fractions), who were least likely to have improvement in their heart function over time.  Similarly, even after excluding patients at highest risk for non-arrhythmic death (prior cancer, prior stroke, and end stage renal disease), ICD implantation rates remained around 1 in 10 patients. (more…)
Author Interviews, Social Issues, Weight Research / 24.06.2015

MedicalResearch.com Interview with: Ruopeng An, PhD Assistant Professor, Department of Kinesiology and Community Health College of Applied Health Sciences University of Illinois at Urbana-Champaign Champaign, IL 61820 Medical Research: What is the background for this study? What are the main findings? Response: Health disparity is a particular type of health difference that is closely linked with social, economic and environmental disadvantage. One fundamental goal in the Healthy People 2020 is to “achieve health equity, eliminate disparities, and improve the health of all groups”. Obesity is a leading risk factor for many adverse health outcomes such as type 2 diabetes, hypertension, dyslipidemia, coronary heart disease, and certain types of cancer. Sweeping across the nation during the past 3 decades, the prevalence of obesity increased from 15% in 1980 to 35% in 2012 among U.S. adults. The obesity epidemic is marked by salient demographic and socioeconomic disparities pertaining to gender, race/ethnicity, education, income and geographic location. In this study, we examined the annual trends in educational disparity in obesity among U.S. adults 18 years and older from 1984 to 2013 using data from a nationally-representative health survey. We found that the obesity prevalence among people with primary school or lower education increased from 17.46% or 3.41 times the prevalence among college graduates (5.12%) in 1984 to 36.16% or 1.73 times the prevalence among college graduates (20.94%) in 2013. In any given year, the obesity prevalence increased monotonically with lower education level. The obesity prevalence across education subgroups without a college degree gradually converged since early 2000s, whereas that between those subgroups and college graduates diverged since late 1980s. Absolute educational disparity in obesity widened by 60.84% to 61.14% during 1984-2013 based on the Absolute Concentration Index and the Slope Index of Inequality, respectively; meanwhile, relative educational disparity narrowed by 52.06% to 52.15% based on the Relative Index of Inequality and the Relative Concentration Index, respectively. The trends in educational disparity in obesity differed substantially by gender, race/ethnicity, age group, and obesity severity. (more…)
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…)