Author Interviews, Cancer Research, Columbia, Genetic Research / 19.02.2016

MedicalResearch.com Interview with: Jeanine D'Armiento, M.D., Ph.D. Associate Professor of Medicine in Anesthesiology Director of the Center for Molecular Pulmonary Disease in Anesthesiology and Physiology and Cellular Biophysics Director, Center for LAM and Rare Lung Disease New York, NY 10032 Medical Research: What is the background for this study? What are the main findings? Dr. D'Armiento: I am the Director of the Center for Lymphangiomyomatosis (LAM) and Rare Lung Disease at Columbia University; the Center focuses on this proliferative lung disease, which arises spontaneously or as the pulmonary manifestation of the Tuberous Sclerosis Complex (TSC). We have one of the largest cohorts of these patients in the country. Through an understanding of the pathogenesis of LAM our research aims to identify novel therapeutic targets of the disease to improve the care of these patients. Building on our previous research we demonstrated that the HMGA2 gene and its signaling pathway (the route of information which begins an action within cells), are required to produce tumors in the lung and kidneys in individuals with Tuberous Sclerosis Complex. (more…)
Author Interviews, Blood Pressure - Hypertension, OBGYNE, Stroke / 19.02.2016

MedicalResearch.com Interview with: Dr. Adnan Qureshi MD Professor of Neurology, Neurosurgery and Radiology University of Minnesota  Medical Research: What is the background for this study? Dr. Quershi: Women who have the last pregnancy at advanced age (usually defined as pregnancy at age of 40 years or greater) have higher risk of developing hypertension, hypertension related disorders, and diabetes mellitus during pregnancy. There is some evidence that disproportionately higher rates of cardiovascular risk factors continue years after the pregnancy. Perhaps there are unknown medical conditions triggered during pregnancy at advanced age. These changes continue to progress without being clinically evident until years later manifesting as a cardiovascular event. Medical Research: What are the main findings? Dr. Quershi: We analyzed the data for 72,221 women aged 50-79 years who were enrolled in the observational arm of the Women's Health Initiative Study. We determined the effect of pregnancy in advanced age (last pregnancy at age≥40 year) on risk of ischemic stroke, hemorrhagic stroke, myocardial infarction, and cardiovascular death over a mean period  of 12 years. A total of 3306 (4.6%) of the 72,221 participants reported pregnancy in advanced age. Compared with pregnancy in normal age, the rate of ischemic stroke (2.4% versus 3.8%, p<0.0001), hemorrhagic stroke (0.5% versus 1.0%, p<0.0001), myocardial infarction (2.5% versus 3.0%, p<0.0001), and cardiovascular death (2.3% versus 3.9%, p<0.0001) was significantly higher among women with pregnancy in advanced age. In multivariate analysis, women with pregnancy in advanced age were 60% more likely to experience a hemorrhagic stroke even after adjusting for differences in age, race/ethnicity, congestive heart failure, systolic blood pressure, atrial fibrillation, alcohol use and cigarette smoking were adjusted. (more…)
Author Interviews, Cancer Research, Compliance / 19.02.2016

MedicalResearch.com Interview with: Dr. Madhur Garg MD Professor, Clinical director, Department of Radiation Oncology Montefiore Einstein Center for Cancer Care Albert Einstein College of Medicine. Bronx, NY 10467 Medical Research: What is the background for this study? What are the main findings? Dr. Garg: In most curative settings, external beam radiotherapy (RT) for the treatment of solid tumors is delivered five days each week over multiple weeks in an outpatient setting. Unintended treatment prolongation, generally attributed to treatment toxicity or inter-current illness, has been associated with inferior tumor control in a number of disease sites. Montefiore Einstein Center for Cancer Care recently identified radiotherapy (RT) noncompliance as a prevalent issue among patients receiving RT with curative intent. Approximately 20% of patients were deemed to be noncompliant, and statistically significant predictors of noncompliance risk included diagnosis, treatment course length, and socioeconomic status (SES). In this report, we examined if radiotherapy noncompliance is associated with clinical outcomes in our patient population. In this analysis, we have found that treatment noncompliance is associated with inferior clinical outcomes for patients receiving radiotherapy with curative intent. The associations we detected were both statistically significant and clinically meaningful and consistent across disease sites. This is a novel finding that may have significant implications for how cancer care delivery can be improved, particularly in disadvantaged patient populations. Our finding that  radiotherapy noncompliance is strongly associated with inferior outcomes, even after adjusting for confounders such as comorbidity index and SES, suggests to us that noncompliance may serve as a behavioral biomarker for other risk factors that contribute to poor outcomes. These may include noncompliance with other important clinician visits and procedures, lack of social support, and mood disorders. (more…)
Author Interviews, Autism, JAMA, Pediatrics / 18.02.2016

MedicalResearch.com Interview with: Dr. David Grossman MD MPH Vice chair of the U.S. Preventive Services Task Force Professor at the University of Washington Schools of Public Health and Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Grossman: The Task Force cares deeply about the challenges that children affected by autism and their families face in getting the care and support they need. This was the first time that we assessed the evidence around screening young children for autism, and our recommendation was informed by a review of the most up-to-date science, which included randomized trials, observational studies, and research from a number of Federal health agencies. We concluded that the current evidence is insufficient to assess the balance of benefits and harms of screening for autism spectrum disorder in children for whom no concerns of autism have been raised by their parents or a clinician. This is an I statement, which is not a recommendation against screening, but a call for more research on screening and treatment in young children who don’t have obvious symptoms. It is important to note that this recommendation will not affect insurance coverage for autism screening, which is currently covered under the Affordable Care Act as a result of the American Academy of Pediatrics’ Bright Futures Guidelines. (more…)
Author Interviews, BMJ, Weight Research / 18.02.2016

MedicalResearch.com Interview with: Dr. Mark A Green PhD Department of Geography & Planning University of Liverpool Liverpool UK Medical Research: What is the background for this study? What are the main findings? Dr. Green: Previous research on trends in body mass index (BMI) have focused on changes in the middle value (average BMI). We extended this investigation by exploring trends both in the middle (using the median – the mid-point of BMI values), the 5th centile (the BMI value at which bottom 5% of the population with the lowest BMIs fall below) and the 95th centile (the BMI value at which the top 5% of the population with the highest BMIs fall above) to examine how trends have changed both in the middle, and at the top and bottom of the distribution. We found that median BMI increased in England in the 1990s, before beginning to slow its rate of change. This is contrary to the 95th centile which has continued to increase at a higher rate throughout the period, with little change in the 5th centile. (more…)
Author Interviews, Lipids, Nutrition, Omega-3 Fatty Acids, Red Meat / 18.02.2016

MedicalResearch.com Interview with: Professor Chris Seal and Professor Carlo Leifert Nafferton Ecological Farming Group (NEFG),School of Agriculture, Food and Rural Development, Newcastle University Nafferton Farm, Stocksfield, Northumberland UK Medical Research: What is the background for this study? Response: In 2009 an FSA-sponsored study by Dangour et al. was published and concluded that there are no composition differences between organic and conventional crops and animal (meat and dairy) products. This contradicted the results of literature reviews, field experiments and retail surveys that many of the scientists involved in the EU-FP7 project QualityLowInputFoods (www.qlif.org/) had carried out or were in the process of completing in 2009. We therefore decided to put together an international team of scientists and carry out a larger, updated systematic literature reviews and meta-analyses to determine whether or not the Dangour et al (2009) study was justified in drawing the conclusions they had.  This took 5 years to complete. We reported on crops in 2014 (http://research.ncl.ac.uk/nefg/QOF/crops/) and the studies published now report the results on meat (http://research.ncl.ac.uk/nefg/QOF/meat/) and milk/dairy products (http://research.ncl.ac.uk/nefg/QOF/dairy/). Medical Research: What are the main findings? Response: 
  • both organic milk and meat contain around 50% more beneficial omega-3 fatty acids than conventionally produced products
  • organic meat had slightly lower concentrations of two saturated fats (myristic and palmitic acid) that are linked to an increased risk of cardiovascular disease
  • organic milk contains 40% more conjugated linoleic acid (CLA)
  • organic milk contains slightly higher concentrations of iron, Vitamin E and some carotenoids
  • conventional milk contained around 70% more of the essential mineral iodine and slightly more selenium
We feel the most important results in terms of nutrition is that both organic milk and meat contain around 50% more beneficial omega-3 fatty acids than conventionally produced products. Omega-3s are linked to reductions in cardiovascular disease, improved neurological development and function, and better immune function. Organic milk had 57% higher concentrations of the nutritionally most desirable, very long chain (VLC) omega-3 fatty acids eicosapentaenic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). Fatty acid profiles in milk are known to change very little during processing in to high fat dairy products such as butter and cheese. Omega-3s are linked to reductions in cardiovascular disease, improved neurological development and better immune function. The European Food safety Authority (EFSA) estimates that average dietary intakes of VLC omega-3 fatty acids account for less than half of what we need for optium health. The finding of substantially higher concentrations of iodine in conventional milk is also important information, especially for UK consumers, where iodized table salt is not widely available and dairy products are an important source of this nutrient. However, it should be pointed out that the Organic Milk Marketing Co-operative (OmsCo) has recently increased iodine fortification of organic dairy feeds and reports that levels of iodine in organic milk are now similar to those found in conventional milk (www.omsco.co.uk/_clientfiles/pdfs/omsco-iodine-levels.pdf). (more…)
Author Interviews, Lipids, Nutrition / 18.02.2016

MedicalResearch.com Interview with: Sachin A. Shah, Pharm.D. Residency Director & Regional Coordinator - Travis AFB Associate Professor of Pharmacy Practice TJ Long School of Pharmacy and Health Sciences University of the Pacific Medical Research: What is the background for this study? What are the main findings? Dr. Shah: The link between serum cholesterol and cardiovascular mortality has been well established. Dietary sources of cholesterol can play a major role toward a beneficiary or unfavorable lipid profile. Fatty acids in foods typically fall within one of the four categories: saturated fats (SFAs), common in animal sources, trans fats (TFAs), common in processed foods, polyunsaturated fats (PUFAs), and monounsaturated fats (MUFAs), both common in plant-derived sources. Although low-fat diets are generally recommended, studies have indicated that altering the types of fats you consume may further modify the risk of dyslipidemia. We performed a meta-analysis of existing studies to determine the impact of avocados on the lipid profile. Ten unique studies incorporating 229 subjects were included. Avocado consumption significantly reduced TC, LDL-C, and TG by 18.80 mg/dL, 16.50 mg/dL, 27.20 mg/dL respectively. HDL-C decreased non-significantly. (more…)
Author Interviews, Stroke / 18.02.2016

MedicalResearch.com Interview with: Michael D Hill, MD MSc FRCPC Calgary Stroke Program Professor, Dept Clinical Neurosciences Hotchkiss Brain Institute Cumming School of Medicine, University of Calgary Calgary, Canada  Medical Research: What is the background for this study? What are the main findings? Dr. Hill: The HERMES collaboration is a pooled analysis of 5 randomized controlled trials of endovascular stroke therapy.  The purpose is of this analysis is to assess the relationship between time from stroke onset and effect size. The main finding is that there is a declining effect size as time elapses from stroke onset.  Shorter onset to reperfusion times are associated with better outcomes.  However, the slope of the decline is shallow compared to past estimates.  We believe this is because imaging selection identifies a group a patients in whom there is slow growth of the core infarct. (more…)
Alzheimer's - Dementia, Author Interviews, Dental Research, Infections, Stroke / 18.02.2016

MedicalResearch.com Interview with: Dr. Robert Friedland MD Mason C. and Mary D. Rudd Endowed Chair In Neurology Professor, Dept. of Neurology University of Louisville Health Care Outpatient Center Louisville, KY 40292 Medical Research: What is the background for this study? What are the main findings? Dr. Robert Friedland: Oral infectious diseases are associated with stroke. Previous research by this group has shown that oral bacteria, cnm-positive Streptococcus mutans, was associated with cerebral microbleeds and intracerebral hemorrhage. We developed this study to investigate the roles of this bacteria in patients entering the hospital for all types of stroke. Among the patients who experienced intracerebral hemorrhage (ICH), 26 percent were found to have a specific bacterium in their saliva, cnm-positive S. mutans. Among patients with other types of stroke, only 6 percent tested positive for the bacterium. We also evaluated MRIs of study subjects for the presence of cerebral microbleeds (CMB), small brain hemorrhages which may cause dementia and also often underlie ICH. We found that the number of CMBs was significantly higher in subjects with cnm-positive S. mutans than in those without. (more…)
Author Interviews, Duke, Exercise - Fitness / 18.02.2016

MedicalResearch.com Interview with: Richard Moon, MD, CM, MSc, FRCP(C), FACP, FCCP Medical Director, Hyperbaric Center Professor of Anesthesiology Department / Division Anesthesiology / GVTU Division Medicine / Pulmonary Duke University School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Moon: This study was performed to investigate the reason why young, fit individuals develop a condition usually associated with severe heart disease: pulmonary edema. Immersion pulmonary edema (also known as swimming-induced pulmonary edema, SIPE) develops in certain susceptible individuals while swimming or scuba diving, usually in cold water. Some SIPE-susceptible people include highly conditioned triathletes and Navy SEAL trainees. The prevalence of SIPE in triathletes is around 1.5%, and in open sea swimming trials in naval special forces trainees has been reported to be 1.8-60%. SIPE often requires hospitalization and has caused death. Medical Research: What should clinicians and patients take away from your report? Dr. Moon: We directly measured arterial pressure, pulmonary artery pressure (PAP) and PA wedge pressure (PAWP) during submersed exercise in cold water. We found that both PAP and PAWP were higher in swimming-induced pulmonary edema-susceptible individuals compared with a group of volunteers of similar age who had never experienced SIPE. This confirmed that SIPE is a form of hemodynamic pulmonary edema, which is curious since all of the people we studied had normal hearts. We hypothesized that the cause could be differences between the groups in venous tone or LV diastolic compliance. When we retested the SIPE-susceptibles under the same conditions after a dose of sildenafil, pulmonary artery pressures were decreased, with no adverse effects on hemodynamics. We concluded that by dilating pulmonary vessels and systemic venous sildenafil could be an effective prophylaxis against SIPE.  (more…)
AHA Journals, Author Interviews, NEJM, Surgical Research / 18.02.2016

MedicalResearch.com Interview with: Dr. William A Gray, MD Chief of the Division of Cardiovascular Disease Main Line Health President of Main Line Health’s Lankenau Heart Institute  Medical Research: What is the background for this study? What are the main findings? Dr. Gray: The basis for this study was two-fold: the ACST-1 trial had shown, in asymptomatic patients with severe carotid disease, that immediate Carotid Endarterectomy reduced subsequent stroke as compared to deferred Carotid Endarterectomy---so the next logical question was, could Carotid Artery Stenting (CAS) compare as an equal alternative to Carotid Endarterectomy (CEA) in this same, standard risk, population with severe carotid stenosis. The CREST trial, as originally constructed and at the time ACT 1 was conceived did not include this population (although it later expanded to encompass asymptomatic patients as well), so it was an open question. The second reason had to do with Abbott Vascular, the study sponsor, achieving FDA regulatory approval for their stent system in this population---as well as in the symptomatic population being studied n CREST (which they were also the device sponsor). The main findings were that the primary endpoint of death/stroke and MI at 30 days plus ipsilateral stroke out to 1 and 5 years was not different between CAS and CEA in asymptomatic patients with severe carotid stenosis on good medical secondary prevention therapy. (more…)
Author Interviews, Cannabis, Genetic Research, Memory / 17.02.2016

MedicalResearch.com Interview with: Prof. Celia Morgan PhD Professor of Psychopharmacology University of Exeter  Medical Research: What is the background for this study? What are the main findings? Dr. Morgan: We know cannabis increases the risk of psychosis but it is unclear how we can predict who is vulnerable to these negative effects. This study suggested that cannabis may have stronger effects in people carrying a particular genetic variant. This might be related to their risk of developing psychosis. We also found that women are more susceptible to the short term memory impairing effects of cannabis. (more…)
Author Interviews, Pain Research / 17.02.2016

MedicalResearch.com Interview with: Souvik Sen, MD, MS, MPH, FAHA Professor and Chair,  Neurology Department, South Carolina Smart State Endowed Stroke Chair University of South Carolina School of Medicine  Medical Research: What was the catalyst for conducting this study examining the association between migraine with aura and ischemic stroke subtypes? Dr. Souvik Sen: South Carolina, North Carolina, and Georgia are located in the “buckle” of the stroke belt, with one of the highest stroke related death rates in the country. An unfortunate trend is that younger patients are having strokes leading to death and disability. As a part of the workup for young stroke we are interested in migraine with aura and the type of stroke associated with this condition. Medical Research: What did you conclude as a result of the findings and how did they compare with your expectations at the beginning of the study? (more…)
Author Interviews, Breast Cancer, JAMA, Outcomes & Safety, Surgical Research / 17.02.2016

MedicalResearch.com Interview with: Dr. Art Sedrakyan MD PhD ScD Professor of Healthcare Policy and Research in Cardiothoracic Surgery Department of Public Health Weill Cornell Medical College  Medical Research: What is the background for this study? What are the main findings? Dr. Sedrakyan: In the most recent years available to us for research(2011-2013) one in four women underwent repeat surgery within 90 days after breast conserving approach to cancer removal. Patients operated by higher volume physicians had lower chance of undergoing repeat surgery.Uniform guidelines and increased surgical training are needed to standardize the breast conserving surgery to reduce the high rate of repeat surgery. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Pharmacology / 17.02.2016

MedicalResearch.com Interview with: Professor Chris Thiemermann Centre for Trauma Sciences Queen Mary University of London Medical Research: What is the background for this study? What are the main findings? Prof. Thiemermann: Trauma is a leading cause of death with five million victims a year. About 40 per cent of trauma deaths are due to hemorrhagic shock, which is when severe blood loss makes it difficult for the heart to pump sufficient blood around the body, leading to multiple organ failure. Multiple organ failure affects one in three severely injured patients, and one in four of those will die.  Those that survive still experience prolonged periods in intensive care, infections and other complications. But despite its catastrophic impact, there are still no specific treatments for organ failure. We’ve now discovered that the drug Artesunate, which has already been used by thousands of people with malaria, is also effective for treating severe haemorrhage and blood loss in rats. Artesunate is based on an ancient Chinese herbal remedy, produced in large quantities in China, and is recommended by the World Health Organization as the treatment of choice for severe malaria. It has also been shown to have anti-cancer, anti-viral and anti-inflammatory effects. My study, which was funded by the Wellcome Trust and the Department of Health, shows that when injured rats were administered Artesunate, the drug had a marked protective impact on organ failure. The drug appears to work by enhancing the protection of organs by reducing the body’s excessive inflammatory response to injury and blood loss, and by activating well-known cell-survival pathways. The lower dose of Artesunate shown in the study to be effective in hemorrhagic shock is identical to the dose used in patients with malaria, many of which also have multiple organ dysfunction. (more…)
Addiction, Author Interviews, HIV / 16.02.2016

MedicalResearch.com Interview with: Pedro Mateu-Gelabert, Ph. D. Principal Investigator National Development Research Institutes, Inc. New York, NY 10010  Medical Research: What is the background for this study? What are the main findings? Dr. Mateu-Gelabert: Heroin production in Colombia increased dramatically in recent decades, and some studies point to an increase in local heroin consumption since the mid-1990s. Despite this rapid increase, little is known about the effects of these activities on heroin injection within Colombia. One of the biggest concerns surrounding heroin injection is the potential spread of HIV through drug user networks. Medical Research: What should clinicians and patients take away from your report? Dr. Mateu-Gelabert: The key take home message in the paper is that a widespread early implementation of harm reduction services (e.g. opioid substitution therapy, HIV testing, syringe exchange programs)  can prevent HIV among young PWID (People Who Inject Drugs) before it rapidly spreads within drug injection networks. Reducing HIV among young drug injectors could prevent the spread of HIV from PWID to the general population. (more…)
Author Interviews, Cleveland Clinic, Lancet, Multiple Sclerosis / 16.02.2016

MedicalResearch.com Interview with: Dr Jeffrey A Cohen MD Mellen Center, Neurological Institute Cleveland Clinic, Cleveland OH 44195, USA Medical Research: What is the background for this study? What are the main findings? Dr. Cohen: Fingolimod, a non-selective sphingosine 1-phosphate receptor (S1PR) modulator, was the first oral medication approved to treat relapsing multiple sclerosis.  Though generally well tolerated, fingolimod’s first dose cardiac effects and other potential adverse effects complicate its use.  Ozanimod is a selective S1PR modulator with several other potentially advantageous pharmacologic properties. The results of phase 2 RADIANCE trial were recently published.  In this trial, participants were randomized to placebo (n=88), ozanimod 0.5 mg (n=87), or ozanimod 1 mg (n=83) PO once daily for 24 weeks.  The mean cumulative number of gadolinium-enhancing lesions on monthly MRI scans at weeks 12-24, the primary endpoint, was reduced from 11.1 +/- 29.9 with placebo to 1.5 +/- 3.7 with ozanimod 0.5 mg and 1.5 +/- 3.4 with ozanimod 1 mg (both p<0.0001).  Other MRI endpoints supported the primary endpoint.  Ozanimod was well tolerated with good safety.  Importantly, the dose up-titration protocol effectively mitigated first dose cardiac effects. (more…)
Author Interviews, CDC, JAMA / 16.02.2016

MedicalResearch.com Interview with: Philip J. Peters, M.D. HIV Testing and Biomedical Interventions Activity Lead Epidemiology Branch CDC’s Division of HIV/AIDS Prevention Medical Research: What is the background for this study? What are the main findings? Dr. Peters:  Acute HIV infection contributes disproportionately to HIV transmission and identifying individuals with acute HIV infection is critical to prevent further HIV transmission, as diagnosis can lead to several effective HIV prevention interventions. Acute HIV infection can be diagnosed with assays that detect either HIV RNA (the reference standard) or the p24 antigen (an HIV core protein), which are both detectable early after HIV infection and before an antibody response develops. HIV immunoassays that detect both the p24 antigen and anti-HIV antibody (fourth generation antigen/antibody [Ag/Ab] combination immunoassays) are currently being implemented as the initial screening test in the 2014 CDC and American Public Health Laboratories (APHL) recommended HIV diagnostic algorithm. In a prospective study we evaluated the performance of an HIV Ag/Ab combination assay to detect acute HIV infection compared with pooled HIV RNA testing in a high-prevalence population. All participants were first screened with a rapid HIV test to detect established HIV infection (antibody detectable).  All participants with a negative rapid HIV test result were then screened for acute HIV infection with an HIV Ag/Ab combination assay (index test) and pooled HIV-1 RNA testing.  HIV RNA testing was the reference standard, with positive reference standard result defined as detectable HIV-1 RNA on an individual RNA test. Among 86,836 participants with complete test results (median age, 29 years; 75.0% male; 51.8% men who have sex with men), acute HIV infection was diagnosed in 168 (0.19%). Acute HIV infection was detected in 134 (0.15%) participants with HIV Ag/Ab combination testing (acute HIV infection sensitivity, 79.8%) and in 164 (0.19%) with pooled HIV RNA testing (sensitivity, 97.6%; sensitivity comparison, p<0.001). Overall HIV Ag/Ab combination testing detected 82% of acute HIV infections detectable by pooled HIV RNA testing. Compared with rapid HIV testing alone (which detected established HIV infection), HIV Ag/Ab combination testing increased the relative HIV diagnostic yield (both established and acute HIV infections) by 10.4% and pooled HIV RNA testing increased the relative HIV diagnostic yield by 12.4%. (more…)
Author Interviews, Diabetes, OBGYNE, Weight Research / 16.02.2016

MedicalResearch.com Interview with: Katherine Bowers, PhD, MPH Division of Biostatistics and Epidemiology Cincinnati Children's Hospital MedicalResearch.com: What is the background for this study? What are the main findings?  Dr. Bowers: Autism spectrum disorder (ASD) affects approximately 1 in 68 children and the prevalence continues to rise. Past studies have suggested that conditions experienced by women during pregnancy (for example, obesity and gestational diabetes mellitus (GDM)) may be associated with having a child with ASD. We collected medical record data from patients who resided in the Cincinnati Children’s Hospital Medical Center’s primary catchment area and linked those data to data from birth certificates to identify metabolic risk factors. Two comparison groups were analyzed; one with developmental disabilities; and the other, controls without a reported ASD or other developmental disability. Descriptive statistics and regression analyses evaluated differences. We found that maternal obesity and  gestational diabetes mellitus were associated with an increased risk of Autism spectrum disorder in the offspring; however, no difference in risk of Autism spectrum disorder according to BMI and GDM was seen when comparing to the group with other developmental disabilities. The strongest observed association was the joint effect of obesity and GDM (compared to neither obesity nor GDM) :OR=2.53 (95% CI: 1.72, 3.73). (more…)
Author Interviews, Heart Disease, Hospital Readmissions / 16.02.2016

MedicalResearch.com Interview with: Rashmee U. Shah, MD MS Cardiovascular Medicine University of Utah School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Shah: The purpose of this study was to evaluate long term outcomes of acute myocardial infarction (AMI) survivors who have cardiogenic shock. We used the ACTION Registry-GWTG (from the NCDR), which is the largest database of AMI, or heart attack, patients in the United States. Some heart attack patients develop cardiogenic shock which is a condition in which the heart muscle becomes so weak that it cannot effectively pump blood to the rest of the body. These patients are critically ill, but with advances in our treatment for heart attacks, many will survive to hospital discharge. We wanted to know, after all the intense treatment and sometimes long hospitalization, how do these patients fare when they leave the hospital? From a total of 112,668 heart attack patients who survived hospitalization, we identified 5,555 who had cardiogenic shock. Over half of all patients were either hospitalized or died within one year of discharge, and this poor outcome was more common among patients who had cardiogenic shock. In fact, the risk of death or hospitalization seems to be clustered in the early post-discharge time period, within 60 days, for patients with cardiogenic shock. After 60 days, shock and non-shock patients experience similar risk. In other words, we found that heart attack patients who had cardiogenic shock are particularly vulnerable during the first 60 days after hospital discharge. (more…)
Author Interviews, Hospital Readmissions, JAMA, Pediatrics / 16.02.2016

MedicalResearch.com Interview with: Marion R. Sills, MD, MPH Associate Professor, Departments of Pediatrics and Emergency Medicine University of Colorado School of Medicine Medical Research: What is the background for this study? Dr. Sills: My co-authors and I know that studies show that patients who are poorer or are minorities are readmitted at higher rates than other patients, and that readmissions penalties, which are far more commonly applied in relation to readmissions of adult patients, have been shown to punish hospitals for the type of patients that they serve, rather than purely for the quality of care they provide.  Currently, these penalties impact hospitals treating Medicare patients in all 50 states but only impact readmissions of children in 4 states, although other states are considering implementing these penalties.  This was our rationale for exploring the impact of patients’ social determinants of health (factors like race, ethnicity, health insurance and income) on how likely it was that a hospital would be penalized for readmissions under a typical state-level pay-for-performance measure based on hospital readmissions. Readmissions penalties are designed to penalize hospitals that provide lower quality care. However, without adjusting for social determinants of health factors, these pay-for-performance measures may unfairly penalize hospitals based on the type of patient they treat as well as the quality of care they provide. Medical Research: What are the main findings? Dr. Sills: We found that risk adjustment for social determinants of health factors changed hospitals’ penalty status on a readmissions-based pay-for-performance measure. Without adjusting the pay-for-performance measures for social determinants of health, hospitals may receive penalties partially related to patient factors beyond the quality of hospital care. (more…)
Author Interviews, Exercise - Fitness, Orthopedics / 15.02.2016

MedicalResearch.com Interview with: Pamela S. Hinton, Ph.D. Associate Professor Director of Graduate Studies, Nutritional Sciences Department of Nutrition and Exercise Physiology University of Missouri, Columbia MO 65211 Medical Research: What is the background for this study? What are the main findings? Dr. Hinton: Because bone mass declines with age, maximization of peak bone mass is recommended as the most effective way to prevent osteoporosis. Acquisition of at least 90% of peak bone mass occurs by the age of 18 years, with additional gains of 5% to 10% during young adulthood. Because mechanical loading induces a greater adaptive response in young, compared with old, bone, adolescence and young adulthood constitute a unique window of opportunity to increase bone mass via physical activity. Although physical activity during adolescence and young adulthood is a key determinant of peak bone mass and, therefore, of future bone health, exercise after skeletal maturation can also reduce the risk of osteoporosis and related fractures. Therefore, the objective of the present study was threefold: (a) to examine the relationships between current BMD of the whole body, hip, and lumbar spine and physical activity–associated bone loading during adolescence (13-18 years), young adulthood (19-29 years), and current physical activity–associated bone loading; (b) to investigate the effects of current participation in a high-impact physical activity and/or resistance training on BMD of the whole body, total hip, and lumbar spine in apparently healthy, physically active men; and, (c) to evaluate the effects of continuous participation in high-impact activity throughout the life span on BMD of the whole body, total hip, and lumbar spine. (more…)
Alzheimer's - Dementia, Author Interviews, JAMA, Pharmacology / 15.02.2016

MedicalResearch.com Interview with: Dr. Britta Haenisch PhD German Center for Neurodegenerative Diseases (DZNE)  Medical Research: What is the background for this study? Dr. Haenisch: Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal diseases, but have also been shown to be potentially involved in cognitive decline: There were hints from recent other studies that PPIs might affect cognition, e.g. Lam et al. (2013) report a significant association of PPI use with vitamin B12 deficiency in a population-based sample. Vitamin B12 deficiency has been shown to be associated with cognitive decline. In another study, PPIs were observed to enhance amyloid beta peptide (Aβ) levels in mouse brain by affecting the enzymes β- and γ-secretase which leads to increased Aβ levels in mice. Medical Research: What are the main findings? Dr. Haenisch: The current study provides a statistical association (applying a time-dependent analysis) between proton pump inhibitors prescription and occurrence of dementia with a focus on long-term regular PPI prescription in patients aged 75 years and older. In our analysis we focused on long-term regular PPI prescription for at least 18 months. It does not prove that proton pump inhibitors cause dementia. References -Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-2442. -Badiola N, Alcalde V, Pujol A, et al. The proton-pump inhibitor lansoprazole enhances amyloid beta production. PLoS One. 2013;8(3):e58837 (more…)
AHA Journals, Asthma, Author Interviews, Brigham & Women's - Harvard, Heart Disease / 15.02.2016

MedicalResearch.com Interview with: Guo-Ping Shi, ScD and Dr. Cong-Lin Liu Cardiovascular Medicine Brigham and Women’s Hospital Boston, MA Medical Research: What is the background for this study? What are the main findings? Response: Abdominal aortic aneurysm (commonly called AAA) is an aortic disease that affects 1~5% men above 50, depending on the countries and regions. There is currently no effective medication or prevention besides surgical repair. Fast growth or unstable AAA often leads to aortic rupture and sudden death. Although ultrasound can be used to monitor the size and growth of AAA, our current annual health examination system in the US does not include this service. We report that mast cells are essential to AAA (J Clin Invest. 2007;117:3359-68). These cells are predominant immune cells in allergic asthmatic lungs from humans and experimental animals. Plasma immunoglobulin E (IgE) level elevation is also a signature of allergic asthma. We report that IgE contributes to experimental AAA by activating mast cells, as well as other immune cells such as macrophages and T cells (EMBO Mol Med. 2014;6:952-69). Direct evidence from our recent study demonstrates that production of allergic asthma in mice doubles the AAA sizes in experimental mice (Arterioscler Thromb Vasc Biol. 2016;36:69-77). All these prior studies suggest a role of allergic asthma to the pathogenesis of AAA. In this human population-based nationwide case-control study (Arterioscler Thromb Vasc Biol. 2016 Feb 11. [Epub ahead of print]), we reported two major findings: First, among 15,942 Danish AAA patients selected from 1996 to 2012, compared to those who did not have asthma, patients who had hospital-diagnosed asthma within the past 12 months had 60% more risk to experience aortic rupture, and those who had hospital-diagnosed asthma within the past 6 months had greater than 100% more risk to experience aortic rupture. Further, patients who received anti-asthmatic treatment, as evidence of asthma, also had 20~50% more risk of experiencing aortic rupture than those who did not have record of anti-asthmatic treatment, depending on how recent the patients received the treatments. Second, among a general men population aged from 65 to 74, patients who used bronchodilating drugs to treat asthma or reversible obstructive pulmonary disease had 45% more risk to have AAA compared with those who never used bronchodilators. This risk was not affected by smoking or other major AAA risk factors. (more…)
Author Interviews, Epilepsy, Lancet, Pharmacology / 15.02.2016

MedicalResearch.com Interview with: Dr. Michael Privitera MD Professor of the Department of Neurology and director of the Epilepsy Center University of Cincinnati Neuroscience Institute  Medical Research: What is the background for this study? What are the main findings? Dr. Privitera: Generic substitution of medications has saved the American health care system billions of dollars per year. However, based on a series of uncontrolled studies, patients and clinicians share concerns that generic substitution of antiepileptic drugs may lead to loss of efficacy or emergence of adverse effects. To answer this question we undertook a prospective, randomized study that tested bioequivalence of two generic products of the antiepileptic drug lamotrigine. Lamotrigine was identified in several publications as a possible source of problems after generic switches. FDA studies test a single generic versus the brand name product in a single dose study in normal volunteers. We designed a study that would be most likely to show a difference between generics if one existed. We compared the two generic lamotrigine products showing the most difference in prior testing in patients with epilepsy taking the drug daily using rigorous pharmacokinetic methods. Each patient took each of the two generics for 2 four week periods. Our study showed the two generics were essentially indistinguishable and easily met bioequivalence standards. No patient had loss of seizure control or unexpected adverse effects. (more…)
Author Interviews, Brigham & Women's - Harvard, Macular Degeneration / 15.02.2016

MedicalResearch.com Interview with: Demetrios Vavvas, M.D., Ph.D. Co-Director Ocular Regenerative Medical Institute Clinician scientist at Mass. Eye and Ear and Co-Director of the Ocular Regenerative Medicine Institute at Harvard Medical School Medical Research: What is the background for this study? Dr. Vavvas: There is a lack of effective therapies for dry age-related macular degeneration (AMD), one of the leading causes of blindness affecting millions. Although AMD shares similarities with atherosclerosis, prior studies on statins and AMD have failed to show improvement. A limitation of these studies has been the heterogeneity of  age-related macular degeneration disease and the lack of standardization in statin dosage. We were interested in studying the effects of high-dose statins, similar to those showing regression of atherosclerotic plaques, in age-related macular degeneration. Medical Research: What are the main findings? Dr. Vavvas: Here, we present for the first time evidence that treatment with high-dose atorvastatin (80mg) is associated with regression of lipid deposits and improvement in visual acuity, without atrophy or neovascularization, in high-risk age-related macular degeneration patients. Medical Research: What should clinicians and patients take away from your report? Dr. Vavvas:
  • High dose lipophilic statin administration was associated with regression of large soft drusen and vision gain in 10/23 age-related macular degeneration patients.
  • Duration of treatment before a positive response was observed was usually 1-1.5 years.
  • Patients on high-dose statin appeared to be protected from progression to “wet” neovascular-AMD.
Cholesterol reduction was similarly drastic in responders and non-responders, which suggests that genetic variation may be important in determine who will benefit and who may not. Age-related macular degeneration is a heterogeneous disease and that targeting the lipid pathway in the appropriate manner and to the appropriate populations we may have the potential not only to slow down or arrest the disease but all to reverse it. (more…)
Author Interviews, Genetic Research, Race/Ethnic Diversity, Science / 15.02.2016

MedicalResearch.com Interview with: Michael Yudell, PhD, MPH Chair & Associate Professor Drexel University School of Public Health Community Health and Prevention Philadelphia, PA 19104 Medical Research: What is the background for this study? Dr. Yudell: We came together as a group of scholars from the natural sciences, social sciences, and humanities to address what we believe is a long-standing challenge: how to improve the study of human genetic diversity without recapitulating the controversial and problematic concept of race. We believe that the cross-disciplinary focus of our work—an examination of the historical, biological, and sociological aspects of the race concept—can shed new light on the long-standing debate about the use of the race concept in genetics research. We believe modern genetics remains stuck in a paradox: that on the one hand race is a tool to elucidate human genetic diversity, and on the other hand race is believedthree main concerns to be a poorly defined marker of that diversity and an imprecise proxy for the relationship between ancestry and genetics. This paradox is rooted in the nature of the field: it dates back to the evolutionary geneticist Theodosius Dozhansky, who in the 1930s redefined race in his work on what was known as biology’s evolutionary synthesis (the synthesis of population genetics with Darwinian thought). For much of his career, Dobzhansky believed race to be a useful tool to elucidate human genetic diversity. But by the end of his career he became worried that the study of human diversity had “floundered in confusion and misunderstanding” and was concerned over the nonscientific misuse of the term. He, like we and many others in genetics, anthropology, and the social sciences, have called on the field to devise better methods to improve the study of human genetic diversity. Can the race concept in genetics elucidate the relationship between humans and their evolutionary history, between humans and their health? In the wake of the human genome project the answer seemed to be a pretty resounding “no.” In 2004, for example, Francis Collins, then head of the National Human Genome Research Institute and now Director of the National Institutes of Health called race a “flawed” and “weak” concept and argued that science needed to move beyond race. Yet, as our paper highlights, the use of race persist in genetics, despite voices like Collins, like Craig Venter—leaders in the field of genomics-who have called on the field to move beyond it. They, of course, were not the first to do, but we hope they are among the last. We believe it is time to revisit this century-long debate and bring biologists, social scientists, and scholars from the humanities together in a to find better ways to study the ever-important subject of human diversity. (more…)
Author Interviews, Infections, PLoS / 14.02.2016

MedicalResearch.com Interview with: Tamar Kleinberger, Ph.D. Dept. of Molecular Microbiology Faculty of Medicine Technion – Israel Institute of Technology Haifa ISRAEL Medical Research: What is the background for this study? What are the main findings? Dr. Kleinberger: The cellular DNA damage response (DDR) is a conglomerate of pathways designed to detect DNA damage and signal its presence to cell cycle checkpoints and to the repair machinery, allowing the cell to pause and mend the damage, or if the damage is too severe, to trigger cell death or senescence. Replication intermediates and linear double-stranded genomes of DNA viruses are recognized by the cell as DNA damage and activate the DDR. If allowed to operate, the DDR will stimulate ligation of viral genomes and will inhibit virus replication. To prevent this outcome, many DNA viruses evolved ways to limit the DDR. For example, adenoviruses, a family of viruses that cause respiratory illnesses or gastrointestinal disease or eye infections, have been reported to inhibit the DDR by degrading DNA damage sensor proteins or by removing them from virus replication centers. Our present work reveals that adenovirus evolved an additional mechanism to inhibit the DDR, using its E4orf4 protein. The viral E4orf4 protein, together with its cellular partner, the PP2A phosphatase, inhibits damage signaling by reducing phosphorylation of proteins belonging to different DDR branches. As a result E4orf4 causes accumulation of DNA damage in the cells. Inhibition of the DDR regulators ATM and ATR as well as expression of E4orf4 enhance infection efficiency. We found that, at least in the cells we studied, ATM inhibition was important to the early stage of the virus life cycle, whereas ATR inhibition impacted mostly late protein expression and progeny virus production. Furthermore, we previously reported that E4orf4 induces cancer-specific cell death when expressed alone, and in the present report we found that E4orf4 sensitized cells to killing by sub-lethal concentrations of DNA damaging drugs, likely because it inhibited DNA damage repair. These findings provide one explanation for the cancer-specificity of E4orf4-induced cell death because many cancers have DDR deficiencies leading to increased reliance on the remaining intact DDR pathways and to enhanced susceptibility to DDR inhibitors such as E4orf4. Thus DDR inhibition by E4orf4 contributes both to the efficiency of adenovirus replication and to the ability of E4orf4 to kill cancer cells. (more…)
Author Interviews, Heart Disease, JACC, Surgical Research / 14.02.2016

MedicalResearch.com Interview with: Josep Rodés-Cabau, MD Director, Catheterization and Interventional Laboratories Quebec Heart and Lung Institute Professor, Faculty of Medicine, Laval University Quebec City, Quebec, Canada Medical Research: What is the background for this study? What are the main findings? Response: Several concerns have recently emerged regarding valve thrombosis post-TAVR. It has been also proposed that rapid changes in transvalvular gradients may be the hallmark of valve thrombosis despite of the absence of clinical symptoms. However, no data exist on the incidence of and factors associated with valve hemodynamic deterioration (VHD) following TAVR. We included 1,521 patients who underwent TAVR in 10 centers worldwide. VHD was defined as an absolute change in mean transvalvular gradient during follow-up ≥10 mm Hg compared with discharge assessment. Incidence of  valve hemodynamic deterioration was 4.5% during a mean echocardiographic FU of 20 months (2.8% within the first year). We found that the lack of anticoagulation therapy, a valve-in-valve procedure (TAVR in a surgical valve), a greater BMI, and the use of a 23mm transcatheter valve were the factors associated with higher rates of VHD post-TAVR. Also, the absence of anticoagulant therapy remained as an independent predictor of VHD in a sub-analysis excluding patients with small valves, valve-in-valve procedure, and aortic regurgitation at discharge ≥moderate. We think these results suggest a thrombotic mechanism as one of the factors underlying VHD. (more…)