AHA Journals, Author Interviews, Diabetes, Heart Disease / 06.05.2015

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

Medical Research: What is the background for this study? Dr. Schmiegelow: Use of cardiovascular risk stratification models is highly encouraged by U.S. and European guidelines in order to prevent cardiovascular disease (CVD). Individuals with insulin resistance are likely to progress to type 2 diabetes, but measures of insulin resistance are not included in current risk stratification models, although this might improve prediction of CVD in patients without diabetes. The aim of this study was to evaluate whether measures of insulin resistance would improve CVD risk predictions based solely on traditional CVD risk factors in postmenopausal women without existing CVD or diabetes. The main outcome was risk of developing CVD, defined as non-fatal and fatal coronary heart disease and ischemic stroke, within ten years, and the measures of insulin resistance considered were fasting serum glucose, fasting serum insulin, “homeostasis model assessment-insulin resistance“ (HOMA-IR) and the ratio of triglycerides and high-density lipoprotein-cholesterol (TG/HDL-C). From the Women’s Health Initiative Biomarkers studies we identified 15,288 postmenopausal women with no history of CVD, atrial fibrillation, or diabetes at baseline (included 1993–1998), who over a mean follow-up of 9.2 years (standard deviation 1.9 years) had 894 first CVD events (5.8%).
Author Interviews, C. difficile, Hospital Acquired, JAMA / 05.05.2015

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

Professor James Bainbridge, MA, PhD, FRCOphthProfessor of Retinal Studies, UCL Institute of Ophthalmology NIHR Research Professor, NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of OphthalmologyMedicalResearch.com Interview with: Professor James Bainbridge, MA, PhD, FRCOphth Professor of Retinal Studies, UCL Institute of Ophthalmology NIHR Research Professor, NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of OphthalmologyConsultant Ophthalmologist, Moorfields Eye Hospital NHS Foundation Trust Medical Research: What is the background for this study? What are the main findings? Prof. Bainbridge : Leber Congenital Amaurosis (LCA) is one of the most common causes of inherited, untreatable blindness in children. There are at least 14 different types of Leber Congenital Amaurosis of which LCA Type 2 (LCA2), caused by defects in the gene RPE65, affects around one in 100,000 people worldwide. Evidence from animal studies support that LCA2 may be amenable to treatment with RPE65 gene replacement therapy. The main findings of this phase I/II clinical trial confirm our preliminary findings (published in NEJM, 2008) that gene therapy can improve night vision. Improvements peak within the first 12 months after treatment but then decline during the three-year follow-up period which is consistent with the published results and interim findings from other studies of RPE65 gene therapy.
Author Interviews, Brain Injury, JAMA, Pediatrics / 04.05.2015

Thomas P. Dompier, PhD, ATC President and Injury Epidemiologist Datalys Center for Sports Injury Research and Prevention, Inc Indianapolis, IN 46202 Adjunct Faculty Appointments Ohio University Rocky Mountain University of Health Professions University of South CarolinaMedicalResearch.com Interview with: Thomas P. Dompier, PhD, ATC President and Injury Epidemiologist Datalys Center for Sports Injury Research and Prevention, Inc Indianapolis, IN 46202 Adjunct Faculty Appointments Ohio University Rocky Mountain University of Health Professions University of South Carolina Medical Research: What is the background for this study? D: Dompler: Per the Institute of Medicine’s recent recommendations to better describe the incidence of concussion in sport across the entire spectrum of youth sports (5-23 years), this study is the first to provide an apples-to-apples comparison using epidemiologic data provided by healthcare providers (athletic trainers) who attended all practices and games and used the same methodology to report concussions and student-athlete exposure information. Medical Research: What are the main findings? D: Dompler: a.  The main findings are that the risk (how many players out of 100 can expect to suffer at least one concussion during the season) is lowest in the youth, and increases with age. b. Game concussion rates (how many players out of 1000 exposed during a practice or game, includes multiple concussions to the same player) are highest in college but practice concussion rates are lowest in college during practice.  This suggests more can be done during high school and youth practices to reduce concussion frequency (e.g. limiting how much time can be devoted to full contact, reducing player-to-player contact by teaching proper tackling without using full contact drills such as the Oklahoma drill and others). c. While the rate is higher, there is still a substantial number of concussions that occur during practice (because there are more practices), therefore sports medicine staff should be available at both if possible (this is difficult at the youth level because of cost, however).
Alcohol, Author Interviews, Pediatrics, Pediatrics / 04.05.2015

MedicalResearch.com Interview with: Jennifer A. Emond, M.Sc., PhD Research Instructor Department of Epidemiology Geisel School of Medicine at Dartmouth College Cancer Control Research Program Lebanon, NH  03756 Medical Research: What is the background for this study? What are the main findings? Dr. Emond: Several studies have documented a link between consuming alcohol mixed with energy drinks and an increased risk of negative outcomes while drinking, including binge drinking. It is known that mixing energy drinks with alcohol increases the risk for binge drinking--the high caffeine intake consumed when mixing energy drinks with alcohol may cause individuals to feel what is been called "wide-awake drunk," and they may underestimate their level of intoxication. However, most studies to date have been conducted among undergraduate college students, and we wanted to know if those same associations were also observed among adolescents. In our study of 3,342 adolescents and young adults between the ages of 15-23, we also found a positive link between a history of consuming alcohol mixed with energy drinks and abusive alcohol use. Specifically, 22.3% of participants had ever consumed an energy drink mixed with alcohol (including 9.7% of 15-17 year olds), and such a history of mixed use was associated with a more than 4-fold increased likelihood of engaging in binge drinking. Importantly, that association was just as strong among 15-17 year olds as it was among the older participants. One critical component of our study was that we also looked at a validated outcome for alcohol use disorder (i.e., the participants completed the Alcohol Use Disorders Identification Test [AUDIT]), and participants with a history of consuming alcohol mixed with energy drinks were also 4.2 times more likely to meet that clinically defined criteria for alcohol use disorder as defined for adolescents. Again, those associations were observed for all participants, regardless of age. Our study has limitations. It was cross-sectional, so we cannot prove that mixed use of alcohol and energy drinks causes abusive alcohol use behaviors. However, our study does support that mixed use of alcohol with energy drinks can identify adolescents at risk for alcohol abuse.
Author Interviews, Cancer Research, Nature, UT Southwestern / 03.05.2015

Dr. Alec (Chengcheng) Zhang Michael L. Rosenberg Scholar in Medical Research Associate Professor of Physiology and Developmental Biology Member of the Harold C. Simmons Comprehensive Cancer Center UT Southwestern Medical CenterMedicalResearch.com Interview with: Dr. Alec (Chengcheng) Zhang Michael L. Rosenberg Scholar in Medical Research Associate Professor of Physiology and Developmental Biology, Member of the Harold C. Simmons Comprehensive Cancer Center UT Southwestern Medical Center Medical Research: What is the background for this study? What are the main findings? Response: Acute myeloid leukemia (AML) is the most common acute leukemia affecting adults. Treatments for AML yield poor outcomes, especially for the typical senior patients. The medical need for new therapies for AML is underscored by the fact that no new therapies for AML have been approved in over 30 years. There are over 50 experimental agents in clinical trials for the treatment of AML today, although only a few agents have promising data to date. New molecular targets and therapeutic strategies are needed for AML treatment. In 2012, we published a paper showing that we cloned the human leukocyte immunoglobulin-like receptor B2 (LILRB2) as a receptor for several angiopoietin-like proteins (Angptls) (Zheng et al 2012 Nature 485:656-660). The LILRB family receptors contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and are classified as inhibitory receptors because ITIM motifs can recruit phosphatases SHP-1, SHP-2, or SHIP to negatively regulate immune cell activation. Surprisingly, in that work, we showed that PirB, the mouse ortholog of LILRB2, is expressed by AML stem cells (AML-SCs) and supports AML development. Although counterintuitive, this result is consistent with the generally immune-suppressive and thus tumor-promoting roles of the inhibitory receptors in the immune system. In the current paper, we continued the research and report that a number of receptors containing the ITIMs are crucial for the development of AML. We mainly focus on studying the function and downstream signaling of LAIR1 as a representative ITIM-containing receptor. We found that the deletion of LAIR1 does not affect normal hematopoiesis but abolishes leukemia development in several different mouse leukemia models. We also identified a mechanism by which LAIR1 supports AML development, showing that the LAIR1/SHP-1/CAMK1/CREB pathway sustains the survival and self-renewal of AML cells. Importantly, our findings are well supported by bioinformatics analysis of AML patient databases and experimental results of human leukemia cells. Since certain ITIM-containing receptors are essential for AML cells but not critical for normal hematopoiesis, and blocking their signaling can boost immunity, these ITIM-containing receptors including LAIR1 represent ideal targets for treating AML.
Aging, Author Interviews, Nature / 03.05.2015

Juan Carlos Izpisua Belmonte PhD Professor, Gene Expression Laboratory Roger Guillemin Chair Salk Institute For Biological ScienceMedicalResearch.com Interview with: Juan Carlos Izpisua Belmonte PhD Professor, Gene Expression Laboratory Roger Guillemin Chair Salk Institute For Biological Science MedicalResearch: What is the background for this study? What are the main findings? Response: Werner protein (WRN) plays roles in DNA replication, transcription, repair as well as telomere maintenance. Mutations in WRN are associated with Werner syndrome. In the current study we discovered that WRN was interacting with proteins implicated in heterochromatin maintenance. We observed that mutations in the WRN protein led to alterations in heterochromatin and those alterations are drivers of the aging process.
Author Interviews, Genetic Research, PLoS / 02.05.2015

G. Mandela Fernández-Grandon PhDNatural Resources Institute,University of Greenwich,Chatham, United KingdomMedicalResearch.com Interview with: G. Mandela Fernández-Grandon PhD Natural Resources Institute, University of Greenwich, Chatham, United Kingdom Medical Research: What is the background for this study? Response: People often wonder why, when they are out with their friends or family, one person seems to get ravaged by mosquitoes but others come away relatively bite free. Mosquito bites can be a nuisance to many of us but they are no trivial matter. Mosquitoes are one of the most serious threats to public health through the transmission of diseases such as malaria, dengue fever, yellow fever, chikungunya and others. We knew that mosquitoes rely on odour to find their hosts but until now the link between our body odour and genes had only been shown using human sniffers1. In a strictly controlled laboratory environment, we were able to present the odours of individuals in identical and non-identical twin pairs to mosquitoes allowing them following the odour stream of whichever they found to be more attractive. Medical Research: What are the main findings? Response: Mosquitoes are equally attracted to identical twins in a pair but with non-identical twins they display a preference for one individual. The ability of mosquitoes to distinguish non-identical twins but not identical twins suggests a genetic basis for our odour profile, a genetic difference which plays a role in whether we get bitten more or less than others.
Artificial Sweeteners, Author Interviews, Diabetes, Diabetologia, Nutrition, Sugar / 02.05.2015

Dr Nita Forouhi, MRCP, PhD, FFPHM MRC Programme Leader and Consultant Public Health Physician MRC Epidemiology Unit University of Cambridge School of Clinical Medicine Cambridge Biomedical Campus Cambridge UKMedicalResearch.com Interview with: Dr Nita Forouhi, MRCP, PhD, FFPHM MRC Programme Leader and Consultant Public Health Physician MRC Epidemiology Unit University of Cambridge School of Clinical Medicine Cambridge Biomedical Campus Cambridge UK Medical Research: What is the background for this study? What are the main findings? Dr. Forouhi: Consumption of soft drinks is known to cause obesity and may contribute to the development of type 2 diabetes. We had previously published findings from the EPIC-InterAct study in 8 European countries that habitual consumption of sugar sweetened beverages increases the risk of developing type 2 diabetes, and we now wanted to probe deeper to understand more about this relationship between sweet beverages and diabetes. We conducted research in the large EPIC-Norfolk study which included more than 25,000 men and women aged 40–79 years living in Norfolk, UK. Study participants recorded everything that they ate and drank for 7 consecutive days covering weekdays and weekend days, with particular attention to type, amount and frequency of consumption, and whether sugar was added by the participants. During approximately 11 years of follow-up, 847 study participants were diagnosed with new-onset type 2 diabetes. By using this detailed information on diet, we were able to study several different types of sugary beverages, including sugar-sweetened soft drinks, sweetened tea or coffee and sweetened milk drinks as well as artificially sweetened beverages (ASB) - such as diet soft drinks - and fruit juice, and to examine what would happen if plain water, unsweetened tea or coffee or artificially sweetened beverages were substituted for sugary drinks. Our study provided three main findings: First, there was an approximately 22% increased relative risk of developing type 2 diabetes per extra serving per day habitually of each of soft drinks, sweetened milk beverages and ASB consumed, even after accounting for a range of important factors including other lifestyle and social factors and for total energy intake. However, after further accounting for body mass index and waist girth as markers of obesity, there remained a higher risk of diabetes associated with consumption of both soft drinks and sweetened milk drinks, but the link with ASB consumption no longer remained, possibly because artificially sweetened beverages was likely to be consumed by those who were already overweight or obese. Second, when we estimated the likely effects of replacing a habitual serving of soft drinks with a serving of water or unsweetened tea or coffee, we found that the risk of diabetes could have been cut by 14%; and by replacing a habitual serving of sweetened milk beverage with water or unsweetened tea or coffee, that reduction could have been 20%–25%.  However, consuming ASB instead of any sugar-sweetened drink was not likely to reduce the risk of diabetes, when accounting for baseline obesity and total energy intake. Third, we found that each 5% of higher intake of energy (as a proportion of total daily energy intake) from total sweet beverages (soft drinks, sweetened tea or coffee, sweetened milk beverages, fruit juice) was associated with a 18% higher risk of diabetes. We estimated that if study participants had reduced the energy they obtained from sweet beverages to below 10%, 5% or 2% of total daily energy, 3%, 7% or 15% respectively of new-onset type 2 diabetes cases could have been potentially avoided.
Author Interviews, Genetic Research, Lancet, Pediatrics / 29.04.2015

MedicalResearch.com Interview with: Stephen F. Kingsmore MB ChB BAO DSc FRCPath Dee Lyons/Missouri Endowed Chair in Genomic Medicine, Children’s Mercy - Kansas CityMedicalResearch.com Interview with: Stephen F. Kingsmore MB ChB BAO DSc FRCPath Dee Lyons/Missouri Endowed Chair in Genomic Medicine, Children’s Mercy - Kansas City Medical Research: What is the background for this study? Response: The background to this study is that genetic diseases are the leading cause of death in infants and, especially, in infants in neonatal intensive care units. Making a molecular (etiologic) diagnosis of the specific genetic disease is critical for optimal care and decision making for acutely ill infants who are likely to have such diseases. However there are over 5000 known genetic diseases and their presentations overlap considerably in infants. Until now it has not been possible to make timely diagnoses in these infants. Medical Research: What are the main findings? Response: Rapid whole genome sequencing is a new way of making a genetic disease diagnosis in acutely ill newborns in neonatal intensive care units. It appears to be effective for diagnosis.
Author Interviews, Blood Pressure - Hypertension, JAMA, Salt-Sodium / 29.04.2015

Lynn L. Moore, DSc, MPH Department of Medicine Boston University School of Medicine Boston, Massachusetts MedicalResearch.com Interview with: Lynn L. Moore, DSc, MPH Department of Medicine Boston University School of Medicine Boston, Massachusetts Medical Research: What is the background for this study? Dr. Moore: The USDA’s current Dietary Guidelines for sodium intake have become increasingly controversial. Current recommendations include restricting sodium intake after the age of 2 years to no more than 2300 mg per day. For African-American adults and children, intakes should be restricted to no more than 1500 mg per day. Actual intake levels are much higher, with most Americans consuming about 3500 mg per day. Our goal was to estimate the effects of dietary sodium and potassium intakes on the change in blood pressure throughout adolescence. We used data from the National Growth and Health Study, a prospective study of more than 2000 girls who were 9-10 years of age at the time of enrollment. Lifestyle factors were assessed repeatedly throughout the study, and blood pressure was measured annually. Dietary sodium and potassium were assessed using multiple sets of three-day diet records. We used longitudinal modeling to estimate the effects of dietary sodium and potassium on blood pressure change over 10 years. Medical Research: What are the main findings? Dr. Moore: In this study, there was no evidence for a beneficial effect of reduced sodium intake on blood pressure change during adolescence. By 19-20 years of age, girls who consumed more than 4000 mg of sodium per day had systolic and diastolic blood pressure levels that were similar to those seen among girls with lower levels of sodium intake. Specifically, there was no beneficial effect on blood pressure associated with sodium intakes of less than 2500 mg per day. These results were similar for blacks and whites. In contrast, the repeated measures analyses showed that girls who consumed more than 2400 mg of potassium per day had lower blood pressures throughout adolescence compared with girls consuming less than 1800 mg per day of potassium.
Author Interviews, Brigham & Women's - Harvard, CHEST, Sleep Disorders / 29.04.2015

dr-matthias-eikermann.jpgMedicalResearch.com Interview with: Matthias Eikermann, MD, PhD Associate Professor of Anaesthesia, Harvard Medical School Director of Research, Critical Care Division Massachusetts General Hospital Medical Research: What is the background for this study? What are the main findings? Dr. Eikermann: Obstructive sleep apnea occurs in about 5% of pregnant women, worsens as pregnancy progresses and is likely to persist into the early postpartum period. A main cause of anesthesia-related maternal death is postpartum airway obstruction. We observed among early postpartum women, that 45° upper body elevation increased upper airway diameter and mitigated sleep apnea, without adverse effects on quality of sleep after delivery.
Alzheimer's - Dementia, Author Interviews, Diabetes, JAMA / 28.04.2015

MedicalResearch.com Interview with: Dimitry S. Davydow, MD, MPH Associate Professor Department of Psychiatry and Behavioral Sciences University of Washington School of Medicine Seattle, WA 98195 Dr, Davydow wishes to acknowledge Dr. Wayne Katon, the lead investigator of the study, who passed away on March 1, 2015. Medical Research: What is the background for this study? Dr. Davydow: The medical and public health communities have known for quite a while that diabetes and depression are both potential risk factors for developing dementia later in life. Dr. Wayne Katon previously published two articles detailing the results of two studies of relatively large groups of patients (one with nearly 4,000 patients and the other with 29,000 patients) with diabetes showing that those with diabetes and co-existing depression had a greater risk of developing dementia later in life than those patients with just diabetes. These initial studies were important since patients with diabetes are 3 to 4-times more likely to suffer from depression compared to the general population. However, it remained unclear when comparing to a population without either diabetes or depression, to what extent each independently raised the risk of developing dementia, and then to what extent having both conditions increased an individual’s subsequent risk of dementia. We sought to answer these questions with this study. In addition, with the growing obesity epidemic, which carries with it higher burdens of both diabetes and depression, there is reason to be concerned that the risk of dementia could be higher at even younger ages. To address this issue, we also wanted to see if there was a differential impact of the combination of diabetes and co-existing depression on dementia risk among those younger than 65 compared to individuals 65 or older. We were fortunate to be able to examine health data from all Danish citizens 50 or older over a 6 year period, a population numbering nearly 2.5 million people to be able to answer these questions. Medical Research: What are the main findings? Dr. Davydow: We found that compared to individuals without diabetes or depression, those with diabetes alone had about a 15% greater risk of developing dementia, those with depression alone had about an 83% greater risk of developing dementia, and those with both diabetes and co-existing depression had a 107% greater risk of developing dementia compared to those without either condition. We also found that of all of the cases of dementia diagnosed in Denmark among individuals 50 or older between 2007 through 2013, 6% were potentially due to combination of having both diabetes and depression. This was also true for those 65 or older, where 6% of all diagnosed dementia was potentially attributable to the combination of both diabetes and depression. However, among individuals under age 65, we found that 25% of all cases of dementia may have been directly attributable to the combination of diabetes and co-existing depression.
Author Interviews, End of Life Care, Heart Disease, JAMA, Kidney Disease / 27.04.2015

MedicalResearch.com Interview with: Susan P. Y. Wong, M.D. Acting Instructor & Senior Research Fellow Division of Nephrology University of Washington Medical Research: What is the background for this study? What are the main findings? Dr. Wong: There is a paucity of information on the use of cardiopulmonary resuscitation (CPR) and its outcomes among patients receiving maintenance dialysis. To address this knowledge gap, we performed a retrospective study to define contemporary trends in in-hospital CPR use and its outcomes among a nationally representative sample of 663,734 patients receiving maintenance dialysis between 2000 and 2011. We found that in-hospital CPR use among this cohort of patients was very high—nearly 20 times more common than that found in the general population. The rate of in-hospital CPR use has also been increasing among patients receiving maintenance dialysis despite evidence of poor long-term survival among these patients. Median survival after hospital discharge for members of this cohort was only 5 months, and this has not change substantially in the recent decade. We also found that a large proportion  of dialysis patients who died in hospital settings had received CPR during their terminal hospitalization. This proportion has also been steadily increasing over time, and in 2011, 1 in 5 dialysis patients who died in hospital had received CPR during their terminal hospitalization.
Annals Internal Medicine, Author Interviews, Hepatitis - Liver Disease / 26.04.2015

Stefan Zeuzem, MDProfessor of Medicine Chief Department of Medicine Goethe University Hospital FrankfurtMedicalResearch.com Interview with: Stefan Zeuzem, MD Professor of Medicine Chief Department of Medicine Goethe University Hospital Frankfurt Medical Research: What is the background for this study? What are the main findings? Dr. Zeuzem: Interferon- and ribavirin-free regimens are needed to treat HCV infection. The objective of the study was to evaluate the safety and efficacy of grazoprevir (NS3/4A-protease-inhibitor) and elbasvir (NS5A-inhibitor) in previously untreated patients with chronic hepatitis C (without and with liver cirrhosis). Among 421 participants, 194 (46%) were women, 157 (37%) were non-white, 382 (91%) had genotype-1 infection, and 92 (22%) had cirrhosis. Of 316 patients receiving immediate treatment, 299/316 achieved SVR12 (undetectable HCV 12 weeks after treatment), including 144/157  with genotype-1a, 129/131  with genotype-1b, 18/18  with genotype-4, 8/10 with genotype-6, 68/70 with cirrhosis, and 231/246 without cirrhosis. Virologic failure occurred in 13 patients including 1 breakthrough and 12 relapses, and was associated with baseline NS5A-polymorphisms and emergent NS3- and/or NS5A-variants. Serious adverse events occurred in 9 (2.8%) and 3 (2.9%) patients in the active and placebo arms, respectively; none were considered drug-related.
Author Interviews, CDC, Infections, Lancet, Vaccine Studies / 25.04.2015

Mary J Hamel, M.D. Chief, Strategic and Applied Sciences Unit, And Deputy Branch Chief for Science, CDC Malaria Branch US Centers for Disease Control and Prevention 1600 Clifton Rd, NE, MS A06 Atlanta GA 30333MedicalResearch.com Interview with: Mary J Hamel, M.D. Chief, Strategic and Applied Sciences Unit, And Deputy Branch Chief for Science, CDC Malaria Branch US Centers for Disease Control and Prevention 1600 Clifton Rd, NE, MS A06 Atlanta GA 30333 Dr. Hamel was principal investigator at the Siaya site in western Kenya. Medical Research: What is the background for this study? What are the main findings? Dr. Hamel: Major progress has been made in malaria control during the past decade with the scale up of proven interventions including insecticide treated nets (ITNs), indoor residual spraying, effective diagnosis and treatment for malaria, and intermittent preventive treatment of malaria in pregnancy. Nonetheless, malaria remains a major cause of morbidity and mortality, and a leading cause of pediatric death worldwide. An estimated 198 million cases of malaria and 580,000 deaths occurred in 2013 – most of these in African children. Now we face additional challenges in malaria control – the emergence of insecticide and drug resistance threatens some of our most effective interventions. New tools are needed to reach the goal of malaria elimination and eventual eradication. Vaccines are some of our most cost-effective interventions, and an effective malaria vaccine would be an important addition to our current malaria control tools. This week, the RTS,S Clinical Trials Partnership published the final vaccine efficacy and safety results from the RTS,S/AS01 malaria vaccine phase 3 trial in the Lancet (Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial, http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60721-8/abstract). This large randomized controlled double-blind phase 3 clinical trial was conducted in 11 sites in 7 African countries across a range of malaria transmission levels. In all, 15,460 children and young infants were enrolled in two age-categories, those first vaccinated at 5-17 months of age (referred to as children), and those first vaccinated at 6-12 weeks of age (referred to as young infants) who received the RTS,S/AS01 vaccine along with their routine childhood immunizations. Participants were randomized into 3 groups – the first group received three doses of the RTS,S/AS01 vaccine followed 18 months later by a booster dose; the second group received three doses of the RTS,S/AS01 vaccine without a booster; and the third group received a comparator vaccine. All participants received an ITN. Children were followed for an average of 48 months and infants for an average of 38 months. We found that vaccine efficacy was modest. Vaccine efficacy against clinical malaria in children was 36% with a booster and 28% without, and vaccine efficacy against severe malaria was 32% with a booster and non-significant without.   Efficacy results in young infants were lower than those in children– vaccine efficacy against clinical malaria was 36% with a booster and 28% without, and vaccine efficacy against severe malaria was non-significant. However, impact, defined as the number of cases averted per 1000 participants vaccinated, was substantial in both age-categories, and highest where malaria burden was greatest. In children who received the booster, during 4 years follow-up, 1700 cases of clinical malaria were averted per 1000 children vaccinated. In young infants, during 3 years follow-up, nearly 1000 cases were averted per 1000 young infants vaccinated. The safety findings were comparable overall in the different study arms, but two safety findings are notable. Meningitis occurred more frequently among children (but not young infants) who received RTS,S/AS01 than among those who received the comparator vaccines. There was no relationship between when the vaccine was administered and when meningitis occurred, most cases occurred in only two study sites, and the finding may be due to chance. If RTS,S/AS01 is licensed, post-licensing studies will be done to establish the significance of this finding. Both children and young infants experienced more episodes of fever and associated febrile convulsions during the 7 days following vaccination; convulsions occurred in 2.2 - 2.5/1000 vaccine doses.
Author Interviews, Heart Disease, JACC, Stroke, University of Pennsylvania / 25.04.2015

Jay Giri, MD MPH Director, Peripheral Intervention Assistant Professor of Clinical Medicine University of PennsylvaniaMedicalResearch.com Interview with Jay Giri, MD MPH Director, Peripheral Intervention Assistant Professor of Clinical Medicine University of Pennsylvania MedicalResearch: What is the background for this study? What are the main findings? Dr. Giri: Carotid artery stents are placed by vascular surgeons or interventional cardiologists to decrease the risk of long-term stroke in patients with severe atherosclerotic disease of the carotid artery.  When these procedures are performed, there is a risk of releasing small amounts of debris into the brain’s circulation, causing a stroke around the time of the procedure (peri-procedural stroke).  In order to mitigate this issue, embolic protection devices (EPD) have been developed to decrease the chances of small debris reaching the brain. Two types of EPD exist.  The first is a small filter meant to catch the debris released by placement of the carotid stent (distal filter EPD). The second is a more complex device type that leads to transient halting of blood flow to the brain in the carotid artery being stented (proximal EPD). Debris-containing blood is removed from the body prior to allowing normal blood flow to proceed back to the brain after stent placement. Our prior research has shown that nearly all (>95%) of domestic carotid stenting procedures are performed with utilization of one of these devices.  We sought to compare important clinical outcomes of stroke and death between these 2 device types within a large national sample of patients undergoing carotid stenting. Some small prior studies have investigated whether the total amount of debris reaching the brain is less with proximal embolic protection devices.  These studies have shown mixed results.  However, no prior study has investigated important clinical outcomes of stroke and death in relation to these devices. We found that overall uptake of proximal embolic protection devices utilization in America has not been robust.  Less than 7% of all domestic CAS procedures are performed with this technology.   Our analysis showed that in-hospital and 30-day stroke/death rates with proximal EPD and distal filter EPD were similar (1.6% vs. 2.0%, p = 0.56 and 2.7% vs. 4.0%, p = 0.22, respectively).
AHA Journals, Author Interviews, Depression, Duke, Heart Disease, Race/Ethnic Diversity / 24.04.2015

Dr. Robert J. Mentz MD Assistant Professor of Medicine Director, Duke University Cooperative Cardiovascular Society Advanced Heart Failure and Cardiac Transplantation Duke University Medical Center Duke Clinical Research InstituteMedicalResearch.com Interview with: Dr. Robert J. Mentz MD Assistant Professor of Medicine Director, Duke University Cooperative Cardiovascular Society Advanced Heart Failure and Cardiac Transplantation Duke University Medical Center Duke Clinical Research Institute Medical Research: What is the background for this study? What are the main findings? Dr. Mentz: Previous studies have shown that depression is associated with worse outcomes in heart failure patients; however, most of these prior studies were conducted in primarily white patient populations. The impact of depressive symptoms on outcomes specifically in blacks with heart failure has not been well studied. We used data from the HF-ACTION trial of exercise training in heart failure patients, which collected data on depressive symptoms via the Beck Depression Inventory (BDI-II), to assess the association between depressive symptoms and outcomes in black patients as compared with white patients. We found that in blacks with heart failure, baseline symptoms of depression and worsening of symptoms over time were both associated with increased all-cause mortality/hospitalization.
Author Interviews, CDC, Cost of Health Care, Heart Disease, JACC, Stroke / 22.04.2015

Guijing Wang, PhD Senior health economist Division for Heart Disease and Stroke Prevention Centers for Disease Control and PreventionMedicalResearch.com Interview with: Guijing Wang, PhD Senior health economist Division for Heart Disease and Stroke Prevention Centers for Disease Control and Prevention Medical Research: What is the background for this study? What are the main findings? Dr. Wang: Our study is one of the first to analyze the impact of hospital costs related to atrial fibrillation (or AFib) in a younger stroke population. To determine these findings, we examined more than 40,000 hospital admissions information involving adults between the ages of 18 and 64 with a primary diagnosis of ischemic stroke between 2010 and 2012. Although AFib is more common among those ages 65 and older, with strokes among younger adults on the rise in the U.S., we wanted to take a comprehensive look at AFib’s impact on hospital costs for these patients. AFib is associated with a 4- to 5-fold increased risk of ischemic stroke, which is the most common type of stroke. Overall, our research found that AFib substantially increased hospital costs for patients with ischemic stroke – and that was consistent across different age groups and genders of those aged 18-64. Of the 33,500 first-time stroke admissions, more than seven percent had AFib, and these admissions cost nearly $5,000 more than those without the condition. In addition, we found that both the costs of hospitalization, as well as the costs associated with AFib, were higher among younger adults (18-54) than those aged 55 to 64.
Author Interviews, Autism, Education, Emory, JAMA, Pediatrics / 22.04.2015

MedicalResearch.com Interview with: Lawrence Scahill, MSN, PhD and Karen Bearss, PhD Department of Pediatrics, Marcus Autism Center Children’s Healthcare of Atlanta and Emory University Atlanta, Georgia Medical Research: What is the background for this study? What are the main findings? Response: Autism spectrum disorder (ASD) affects an estimated 0.6 to 1% of children worldwide. In young children with ASD (e.g. 3 to 7 years of age) up to 50% also have disruptive behaviors such as tantrums, aggression, self-injury and noncompliance. When present, these disruptive behaviors interfere with the child’s readiness to make use of educational and other supportive services. The presence of disruptive behaviors also hinders the acquisition of routine daily living skills. Parent Training has been shown to be effective for young children with disruptive behaviors who do not have Autism spectrum disorder – but it has not be well-studied in children with ASD. The current multisite study shows that parent training is effective in reducing serious behavioral problems in young children with ASD. This is the largest randomized trial of a behavioral intervention in children with ASD.  180 children were randomly assigned to parent training or parent education. Both treatments were delivered individually to parents over 24 weeks. Serious behavioral problems were reduced by almost 50% in the parent-training group compared to about 30% for parent education. A clinician who was blind to treatment assignment rated positive response in 69% of children in the parent training group compared to 40% for parent education. In addition, 79% of children who showed a positive response to parent training at the end of the 24-week trial maintained benefit at 6 months post treatment. Parent training provided parents with specific strategies on how to manage tantrums, aggression, self-injury and noncompliance in children with autism spectrum disorder. Parent education provided up-to-date and useful information about ASD, but no instruction on how to address behavioral problems. Parents were engaged in the study treatments as evidenced by the low drop-out rate of 10% .
Author Interviews, Heart Disease, JACC, NYU/NYMC, Obstructive Sleep Apnea, Sleep Disorders / 22.04.2015

Dr. Larry Chinitz MD Professor of Medicine and Director, Cardiac Electrophysiology NYU Langone Medical CenterMedicalResearch.com Interview with: Dr. Larry Chinitz MD Professor of Medicine and Director, Cardiac Electrophysiology NYU Langone Medical Center MedicalResearch: What is the background for this study? What are the main findings? Dr. Chinitz: The treatment algorithms proposed currently for maintenance of sinus rhythm in patients with atrial fibrillation focus on use of anti-arrhythmic drugs and catheter ablation. Data available to evaluate the effect of modification of known adverse clinical factors on atrial fibrillation recurrence is scant. Obstructive sleep apnea in a known factor associated with both new onset atrial fibrillation as well as its recurrence after catheter ablation. Through a meta-analysis of available data we found that use of continuous positive airway pressure in patients with sleep apnea was associated with a 42% relative risk reduction in recurrence of atrial fibrillation. This effect was similar across patient groups irrespective of whether they were medically managed or with catheter ablation.
Author Interviews, Hearing Loss, JCEM, Mineral Metabolism / 21.04.2015

Dr. Kai-Jen Tien MD Division of Endocrinology and Metabolism, Department of Internal Medicine Chi Mei Medical Center, Tainan, TaiwanMedicalResearch.com Interview with: Dr. Kai-Jen Tien MD Division of Endocrinology and Metabolism, Department of Internal Medicine Chi Mei Medical Center, Tainan, Taiwan Medical Research: What is the background for this study? What are the main findings? Response: Previous studies investigating the relationship between osteoporosis and sudden sensorineural hearing loss were rare. Most of the studies were of small sample size, or cross-sectional designs and their results were inconclusive. Our population-based study found an approximately 1.76-fold increase in the incidence of sensorineural hearing loss for patients with osteoporosis compared with the comparison group.Patients with more severe osteoporosis may have a higher risk of SSNHL than patients with osteoporosis of milder severity.
Author Interviews, Breast Cancer, Cancer Research, Cognitive Issues, JNCI / 19.04.2015

Dr. Kerstin Hermelink Senior psychologist Dept. of Gynecology and Obstetrics Ludwig Maximilian University of MunichMedicalResearch.com Interview with: Dr. Kerstin Hermelink Senior psychologist Dept. of Gynecology and Obstetrics Ludwig Maximilian University of Munich MedicalResearch: What is the background for this study? What are the main findings? Dr. Hermelink: Many breast cancer patients report problems of cognitive functioning that interfere considerably with their professional and private lives. In the last two decades, a number of studies have confirmed that subgroups of breast cancer patients show at least subtle cognitive impairment. Initially, the condition has entirely been attributed to chemotherapy effects and has therefore colloquially been named “chemobrain”. Meanwhile, however, cognitive impairment has also been found in patients who were managed without chemotherapy and, surprisingly, even in patients who had not yet received any systemic treatment at all. Several hypotheses on the causation of cognitive impairment that occurs already pretreatment have been put forward; for instance, biological effects of the cancer itself might affect cognitive functioning, or there might be shared genetic vulnerability for cancer and cognitive impairment. None of these hypotheses have been empirically confirmed; thus, pretreatment cognitive impairment is as yet unexplained. Our study was designed to investigate the effects of cancer-related post-traumatic stress on cognitive function in breast cancer patients before the start of treatment. Stress has a substantial influence on cognitive functioning, and post-traumatic stress disorder (PTSD) is associated with impairment of cognitive function. While the incidence of full diagnosis of stress disorder is low among breast cancer patients, many of these patients show symptoms of PTSD, with a peak shortly after diagnosis. We did not find an elevated risk of overall cognitive impairment in pretreatment breast cancer patients compared with matched non-cancer controls; however, the cancer patients scored worse than the controls on a small fraction of the cognitive indices that were used. Performance on these indices was indeed robustly associated with PTSD symptoms. Our results therefore indicate that pretreatment cognitive impairment in breast cancer patients may be largely caused by the stress of being diagnosed with cancer.
Author Interviews, BMJ, Cost of Health Care, Stanford / 18.04.2015

MedicalResearch.com Interview with: Donna Zulman MD MS Center for Innovation to Implementation, VA Palo Alto Health Care System, Menlo Park Division of General Medical Disciplines, Stanford University, Stanford California, USAMedicalResearch.com Interview with: Donna Zulman MD MS Center for Innovation to Implementation, VA Palo Alto Health Care System, Menlo Park Division of General Medical Disciplines, Stanford University, Stanford California, USA Medical Research: What is the background for this study? Dr. Zulman: Within the United States, a small number of individuals account for disproporationate health care spending. Many of these high-cost patients have complex chronic conditions such as heart failure and diabetes. Others have complicated mental health conditions. But the vast majority have multiple chronic conditions, which can create challenges when patients are navigating their health care. For this study, we examined patterns of chronic conditions among high-cost patients in the Veterans Affairs (VA) Health Care System, and studied the relationship between different chronic conditions patterns and health care utilization and costs. Medical Research: What are the main findings? Dr. Zulman: We found that within the VA, the 5% highest cost patients accounted for 47% of total VA health care costs. Approximately two-thirds of these patients had chronic conditions affecting 3 or more body systems (for example, cardiovascular disease, asthma, and depression). However, patients with severe, dominating diseases such as cancer and schizophrenia were less likely to have a lot of comorbid conditions. In addition, we found that even among these high-cost patients, having more conditions was associated with greater use of outpatient and inpatient services. However, as patients' multimorbidity across body systems increased, a greater share of their costs was generated in the outpatient setting and a smaller share of their costs was generated in the inpatient setting. This suggests that interventions focusing on high-cost patients should not only target costly hospitalizations, but should also coordinate and maximize efficiency of outpatient services across multiple conditions.
Author Interviews, Endocrinology, Nature, NYU/NYMC, Social Issues / 16.04.2015

Bianca Jones Marlin, PhD Froemke Laboratory New York University Langone School of MedicineMedicalResearch.com Interview with: Bianca Jones Marlin, PhD Froemke Laboratory New York University Langone School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Marlin: Oxytocin is a hormone that plays an important role in the expression of social and parental behaviors, but little is know about how it works in the brain to produce these behaviors. Virgin mice will usually ignore, and sometimes cannibalize newborn mouse pups. Our study has shown that oxytocin works in the auditory cortex of virgin mice to change both their neural responses, and eventually their behaviors, to mirror the maternal response.
Author Interviews, Cost of Health Care, NEJM, Ophthalmology, UCSF / 16.04.2015

Catherine L. Chen M.D., M.P.H. UCSF Dept of AnesthesiaMedicalResearch.com Interview with: Catherine L. Chen M.D., M.P.H. UCSF Dept of Anesthesia Medical Research: What is the background for this study? What are the main findings? Dr. Chen: Cataract surgery is a very common and safe surgery that most older adults have in their 70's or 80's. It usually happens as a same-day surgery and most patients only need eye drops to numb the eye with little or no intravenous sedation for a procedure that on average is only 18 minutes long. Given their age, these patients typically have other concurrent medical problems, so even though multiple research studies and professional societies have concluded that routine preoperative testing is not necessary before cataract surgery, we found that this testing still frequently occurs in these patients. More than half of the patients in our study had at least one preoperative test performed in the month before their surgery. We hypothesized prior to undertaking this study that the older and sicker patients were the ones who were most likely to get preoperative testing. Instead, what we found was that the most important factor that determined whether or not a patient got tested was the ophthalmologist who operated on the patient. This is an important finding because it shows that most patients are not getting extra testing, but the few that do are getting testing because that's the way their ophthalmologist typically prepares his patients for surgery. Most of the time, this testing is not needed and will not affect how well the patient does during and after surgery.
Author Interviews, Cancer, Cancer Research / 15.04.2015

Josée Savard, Ph.D. School of Psychology, Laval University Cancer Research Center Quebec City, Quebec, CanadaMedicalResearch.com Interview with: Josée Savard, Ph.D. School of Psychology, Laval University Cancer Research Center Quebec City, Quebec, Canada MedicalResearch: What is the background for this study? What are the main findings? Dr. Savard: This paper reports on a secondary analysis of an 18-month longitudinal study initially conducted in 962 patients about to receive surgery for various types of cancer. The main results of this larger study indicated that insomnia is a significant problem in cancer patients. More precisely, it was found to affect up to 59% of patients at the peri-operative period. In addition, 32% of patients who were good sleepers developed insomnia symptoms at some point during the study (Savard et al., 2009; Savard et al., 2011). The goal of this particular analysis was to determine the role of cancer treatments and their side effects in triggering/aggravating insomnia symptoms during the 18-month follow-up. Study participants completed questionnaires assessing insomnia severity and somatic symptoms at baseline, as well as 2, 6, 10, 14 and 18 months later. This analysis was conducted separately in women treated for breast cancer (n=465) and men treated for prostate cancer (n=263). In breast cancer patients, chemotherapy and radiation therapy, but not hormone therapy, were found to be associated with increased insomnia severity. This deleterious effect appeared to be due to a number of side effects (e.g., nausea, night sweats, urinary symptoms). In prostate cancer patients, androgen-deprivation therapy was associated with aggravation of insomnia, an effect that was mainly due to the occurrence of night sweats.
Author Interviews, Duke, Heart Disease, JACC, Women's Heart Health / 15.04.2015

Matthew E. Dupre, PhD Associate Professor of Medicine Department of Community and Family Medicine Department of Sociology Duke Clinical Research InstituteMedicalResearch.com Interview with: Matthew E. Dupre, PhD Associate Professor of Medicine Department of Community and Family Medicine Department of Sociology Duke Clinical Research Institute MedicalResearch: What is the background for this study? What are the main findings? Dr. Dupre: The negative health consequences of divorce have been known for some time. However, we showed that lifetime exposure to divorce can have a lasting impact on ones’ cardiovascular health, particularly in women. This is a good example of why people going through a divorce need a good divorce lawyer chicago in order to keep their stress levels down and help their cardiovascular health. Results from our study showed that risks for acute myocardial infarction (AMI) were significantly higher in women who had one divorce, two or more divorces, and among the remarried compared with continuously married women after adjusting for multiple risk factors. Risks for AMI were elevated only in men with a history of two or more divorces relative to continuously married men. We were especially surprised to find that women who remarried had risks for AMI that were nearly equivalent to that of divorced women. Men who remarried had no significant risk for acute myocardial infarction. The results of this study provide strong evidence that cumulative exposure to divorce increases the risk of acute myocardial infarction in older adults. Also somewhat unexpected was that the associations remained largely unchanged after accounting for a variety socioeconomic, psychosocial, behavioral, and physiological factors. However, we lacked information on several factors that we suspect may have contributed to the risks related to divorce – such as elevated stress, anxiety, and the loss of social support; as well as possible changes is medication adherence or other prophylactic behaviors. MedicalResearch: What should clinicians and patients take away from your report?
Author Interviews, End of Life Care, JAMA, Outcomes & Safety / 15.04.2015

Mihaela S Stefan, MD FACP Research Scientist, Center for Quality of Care Research Director of Outpatient Perioperative Clinic and Medical Consultation Program Academic Hospitalist Baystate Medical Center Assistant Professor of Medicine, Tufts University School of Medicine Springfield MA 01199MedicalResearch.com Interview with: Mihaela S Stefan, MD FACP Research Scientist, Center for Quality of Care Research Director of Outpatient Perioperative Clinic and Medical Consultation Program Academic Hospitalist Baystate Medical Center Assistant Professor of Medicine, Tufts University School of Medicine Springfield MA 01199 MedicalResearch: What is the background for this study? Dr. Stefan : Mortality rates for patients with pneumonia are publicly reported and are used to evaluate hospital performance. The rates are calculated using Medicare administrative claims data which provide limited insight into severity of illness and comorbidities that may be associated with death. The mortality measure does not take into consideration advance directives or changes in goals of care preferences during hospitalization. MedicalResearch: What are the main findings? Dr. Stefan : In this retrospective chart review of 202 adults who died with a principal diagnosis of pneumonia between January 2008 and December 2012 in 3 hospitals in MA, we assessed the proportion of patients for whom pneumonia was determined to play a major or a minor role in the patient death. Pneumonia was considered a minor cause if the patient had advanced life threatening illnesses and this was found in 82% of the deaths. More than half of the patients were DNR at admission to the hospital. The majority of patients who died were frail elderly with life-threatening conditions who decided to forgo aggressive care at some point during their admission. Only a small fraction of deaths in the pneumonia mortality measure were the direct result of pneumonia.