Author Interviews, Johns Hopkins, PLoS, Stem Cells / 26.02.2016

MedicalResearch.com Interview with: Dr. Andrew Jaffe PhD Investigator, Lieber Institute for Brain Development Assistant Professor Wendy Klag Center for Autism and Developmental Disabilities Johns Hopkins Bloomberg School of Public Health Medical Research: What is the background for this study? What are the main findings? Dr. Jaffe: Significant investments are being made worldwide in precision medicine, with much of the investment concentrated in the curation of stem cell lines for the generation of new tissues and organs. The most popular cell types for generating patient-specific stem cells are skin-derived and therefore receive potentially the highest amount of environmental exposure. In our study, we were interested in characterizing the genomic variability in fibroblast cells from two locations in the body across the lifespan. The two locations were the scalp, which is exposed to the environment, and the dura mater, which is the membrane under the skull and is largely protected from environmental insult. While the fibroblast cells from these two locations look indistinguishable under a microscope, we found widespread epigenetic and expression differences between the cells related to where they came from in the body and also related, to a lesser extent, to the age of the donor. As the field of personalized medicine continues to grow, this evidence necessitates further exploration into the epigenetic patterns in stem cells used for new tissue and organ generation. Additional research is required to determine which cells to cultivate and when, as researchers question how much epigenetic memory is actually erased when creating stem cell models. (more…)
AHA Journals, Author Interviews, Heart Disease, PAD, Surgical Research, University of Pennsylvania / 26.02.2016

MedicalResearch.com Interview with: Dr. Grace Wang MD FACS Assistant Professor of Surgery Division of Vascular and Endovascular Surgery Hospital of the University of Pennsylvania Medical Research: What is the background for this study? Dr. Wang: PAD is a major source of morbidity and mortality resulting in functional impairment, limb loss, as well as death. Despite epidemiologic studies which have contributed to our understanding of PAD prevalence and its association with traditional atherosclerotic risk factors, there have been conflicting studies published on the incidence of PAD and differences in treatment outcomes in women versus men. Patients with chronic kidney disease (CKD) are at particularly high risk for PAD. We set out to to define how the incidence of peripheral arterial disease (PAD) in chronic kidney disease (CKD) differs according to sex and age. (more…)
AHA Journals, Author Interviews, Gender Differences, Heart Disease, Race/Ethnic Diversity, Women's Heart Health / 26.02.2016

MedicalResearch.com Interview with: Karin H Humphries, MBA, DSc | Scientific Director BC Centre for Improved Cardiovascular Health UBC-HSF Professor in Women's Cardiovascular Health Vancouver, BC Medical Research: What is the background for this study? Response: Prior studies have shown that among patients with obstructive coronary artery disease (CAD), women have higher short- and long-term mortality rates as compared to men. Furthermore, a few studies have highlighted the existence of ethnic differences in the incidence of acute myocardial infarction (AMI) and outcomes following an AMI event. However, the joint contribution of sex and ethnicity on outcomes of patients with obstructive  coronary artery disease remains unknown. Our primary objective was to extend these findings by examining the joint impact of sex and ethnicity on long-term adverse outcomes of all patients with angiographic evidence of obstructive CAD presenting with myocardial ischemia. Our study included a population-based cohort of patients ≥ 20 years of age who underwent coronary angiography for acute coronary syndromes (ACS) or stable angina in British Columbia, Canada with angiographic evidence of ≥ 50% stenosis in any epicardial artery. (more…)
AHA Journals, Author Interviews, Heart Disease, Mental Health Research, Women's Heart Health / 26.02.2016

MedicalResearch.com Interview with: Dr. Kim Lavoie, Ph.D. CIHR New Investigator, FRQS Chercheur-Boursier Co-Director, Montreal Behavioural Medicine Centre Professor, Dept. of Psychology University of Quebec at Montreal Director, Chronic Disease Research Division, Hôpital du Sacré-Coeur de Montreal Adjunct Professor, Faculty of Medicine, University of Montreal Associate Researcher, Montreal Heart Institute Chair, Health Psychology and Behavioral Medicine Section Canadian Psychological Association Medical Research: What is the background for this study? Dr. Lavoie: We were interested in looking at whether rates of ischemia in men and women were different as a function of whether or not you had pre-existing heart disease (we would expect those with existing heart disease to have more ischemia because it’s a major marker of disease) or a comorbid anxiety or mood disorder (we expected anx/mood disorders would be associated with higher rates of ischemia because they reflect clinical levels of chronic stress, which has been linked to higher rates of ischemia in previous studies). Medical Research: What are the main findings? Dr. Lavoie: Overall, we found that men have higher rates of ischemia than women, and that anxiety or mood disorders overall aren't associated with higher or lower risk of ischemia (in those with or without previously diagnosed heart disease). HOWEVER, what we did find that was interesting and perhaps new, was that if you looked within women, those without previously diagnosed heart disease AND anxiety disorders (which including things like panic disorder and generalized anxiety - panickers and worriers) had higher rates of ischemia compared to those without anxiety disorders. This suggests higher rates of ischemia among women without heart disease, which seems counter-intuitive because you would expect those WITH disease to have more ischemia. The fact that anxiety disorders were present in those without previously diagnosed heart disease - and they were the ones with more ischemia, suggests that these women likely HAD heart disease that just hadn't been diagnosed up yet, and that the reason might have been because of their anxiety disorder, which can mask many symptoms of heart disease because many of them overlap (e.g., fatigue, decreased energy, heart palpitations, sweating, chest discomfort, hyperventilation, and fear/worry). This could lead physicians to misinterpret symptoms of real heart disease as those of anxiety - but this only appears to be the case in women according to our study, suggesting a possible sex/gender bias here. (more…)
Author Interviews, JACC, Metabolic Syndrome, OBGYNE, Race/Ethnic Diversity, Women's Heart Health / 26.02.2016

MedicalResearch.com Interview with: Catherine J. Vladutiu, PhD, MPH Research Assistant Professor, Department of Obstetrics & Gynecology Adjunct Assistant Professor, Department of Epidemiology Chapel Hill, NC Medical Research: What is the background for this study? Dr. Vladutiu: During pregnancy, women experience physiological changes and are at risk of pregnancy-related complications, some of which are associated with a higher risk of cardiovascular health outcomes in later life.  Physiologic adaptations occurring across successive pregnancies may be associated with an even higher risk of adverse cardiovascular outcomes. Previous studies have found an association between higher parity (i.e., number of live births) and the metabolic syndrome (MetS). However, no studies have examined this association in a Hispanic/Latina population. Hispanic women have a higher prevalence of the MetS than non-Hispanic women.  Latinos are also the fastest growing minority population in the U.S. and Hispanic/Latina women report higher fertility and birth rates than their non-Hispanic counterparts. (more…)
AHA Journals, Author Interviews, Brigham & Women's - Harvard, Heart Disease, Women's Heart Health / 26.02.2016

MedicalResearch.com Interview with: Mercedes Sotos Prieto, PhD Research Associate, Department of Nutrition Harvard T.H. Chan School of Public Health Boston, MA, 02115 Medical Research: What is the background for this study? What are the main findings? Dr. Sotos-Prieto: Given that CVD remains the leading cause of death in the US, the prevention of risk factor development through healthy lifestyle factors, or primordial prevention, is of paramount importance to minimize the long-term risk of CVD. However, the prevalence of these healthy behaviors among US adults remains low. The Healthy Heart Score is a 20-year CVD risk prediction model based on modifiable lifestyle factors and we have shown previously that this score effectively predicted the 20-year risk of CVD in mid-adulthood. Whether this risk score is associated with clinically-relevant CVD risk factors is unknown. Therefore, in this study we analyzed the association between the Healthy Heart Score and incidence of clinical CVD risk factors, including diabetes, hypertension, and hypercholesterolemia among 69,505 U.S women in the Nurses’ Health Study II during 20 years of follow-up. The Healthy Heart Score is based on the 9 most critical lifestyle factors that best estimate CVD risk including: current smoking, higher BMI, low physical activity, lack of moderate alcohol consumption, low intakes of fruits, vegetables, cereal fiber, and nuts, and high intakes of sugar-sweetened beverages and red and processed meats. The Healthy Heart Score estimates the 20 –year CVD risk, thus a higher score reflected a higher predictive CVD risk. Over 20 years, we documented 3,275 incident cases of diabetes, 17,420 of hypertension, and 24,385 of hypercholesterolemia. Our main findings showed that women with higher predicted CVD risk based on the Healthy Heart Score (highest quintile vs. lowest) had significantly greater risk of developing each clinical risk factor individually. Specifically, women with a higher predictive CVD risk had an 18-fold higher risk of type 2 diabetes, 5-fold higher risk of hypertension, and 3-fold higher risk of hypercholesterolemia over 20-years. Further, a higher predictive CVD risk was associated with a 53-fold greater risk of developing a high CVD risk profile (defined as the diagnosis of all 3 clinical risk factors) and this association was most pronounced among women who were younger, did not smoke, and had optimal weight (more…)
AHA Journals, Author Interviews, Gender Differences, Heart Disease, University of Pennsylvania, Women's Heart Health / 26.02.2016

MedicalResearch.com Interview with: Dr. Robert L. Wilensky MD Director, Interventional Cardiology Research Director, Interventional Cardiology Training Program Professor of Medicine Hospital of the University of Pennsylvania Medical Research: What is the background for this study? Dr. Wilensky: We wanted to evaluate whether young women, under the age of 50 years, had an increased risk for recurrent ischemic events after percutaneous coronary intervention (PCI) compared to young men or older women. Medical Research: What are the main findings?  Dr. Wilensky: Despite having less severe coronary artery disease,  had an increased risk of repeated events, generally need for repeat PCI in either the exact location of the original procedure or within the artery that underwent the procedure. This despite the finding that young women were treated with the same medications as young men. (more…)
Author Interviews, HIV / 26.02.2016

MedicalResearch.com Interview with: Wim Parys MD Global Head R&D Global Public Health Janssen  Medical Research: What is the background for this study? What are the main findings? Dr. Parys: In collaboration with ViiV Healthcare, we are working to develop the first long acting all-injectable combination regimen of Janssen’s rilpivirine and ViiV’s cabotegravir. Yesterday, we have announced promising Phase 2b data of this combination regimen which when given together every 4 or 8 weeks was able to maintain viral suppression with similar efficacy to a daily oral regimen of three HIV medicines. The results show that the combination met its primary endpoint at week 32. The study will now continue in its randomized controlled design for another 64 weeks enabling us to assess longer term outcomes. In parallel to this we will work to initiate the next stages of clinical development. (more…)
Author Interviews, Diabetes, Technology / 26.02.2016

MedicalResearch.com Interview with: Professor Tilak Dias College of Art & Design and Built Environment, School of Art & Design and Dr. Pasindu Lugoda Industrial Design, Fashion Design, Experimental Physics Electronic and Communication Engineering Nottingham Trent University Medical Research: Why are diabetics more prone to foot ulcers?  How prevalent is the problem? Response: Diabetic neuropathy contributes to foot ulcers that increases the chances of amputations if not treated. Every 30 seconds a limb is lost to diabetics. Medical Research: What is the background for the Siren Smart Sock System? What information is transmitted via the socks? Does the information go to the patient or a health care provider? Response: The temperature difference in between different points of the two feet are transmitted from the sensors in the sock. The information can be sent to the doctor or the patient’s mobile phone depending on what is needed.   (more…)
Author Interviews, Genetic Research, UCLA / 26.02.2016

MedicalResearch.com Interview with: April D. Pyle PhD Associate Professor, Microbiology, Immunology & Molecular Genetics Molecular Biology Institute Center for Duchenne Muscular Dystrophy Edythe Broad Center of Regenerative Medicine and Stem Cell Research University of California, Los Angeles, CA Medical Research: What is the background for this study? What are the main findings? Dr. Pyle: We have developed a CRISPR/Cas9 gene editing platform that is applicable for approximately 60 percent of Duchenne muscular dystrophy patients. Duchenne is a devastating muscle wasting disorder affecting approximately1 in 5000 boys worldwide. It is caused by lack of the dystrophin protein. In our study, we demonstrate that we can restore the dystrophin reading frame by deleting up to 725kb of the DMD gene between exons 45 and 55, the largest deletion shown to date in this gene, which results in a functional dystrophin protein being expressed. We demonstrated feasibility of this platform in Duchenne patient-derived human induced pluripotent stem cells differentiated to skeletal and cardiac muscle cells. (more…)
Author Interviews, Johns Hopkins, Kidney Disease, Race/Ethnic Diversity, Transplantation / 26.02.2016

MedicalResearch.com Interview with: Tanjala S. Purnell, PhD MPH Assistant Professor, Transplant Surgery and Epidemiology Johns Hopkins University School of Medicine  Medical Research: What is the background for this study? Dr. Purnell:  Kidney transplantation (KT) is the best treatment for most patients with end stage renal disease (ESRD), offering longer life expectancy and improved quality of life than dialysis treatment. Despite these benefits, previous reports suggest that black KT recipients experience poorer outcomes, such as higher kidney rejection and patient death, than white KT recipients. Our team wanted to examine whether this disparity has improved in recent decades. We hypothesized that advances in immunosuppression and post- kidney transplantation  management might differentially benefit black KT recipients, who were disproportionately burdened by immunological barriers, and contribute to reduced racial disparities in kidney transplantation outcomes. Medical Research: What are the main findings? Dr. Purnell: 
  1. From 1990 to 2012, 5-year failure rates of the transplanted kidney after Deceased Donor Kidney Transplantation (DDKT) decreased from 51.4% to 30.6% for blacks and from 37.3% to 25.0% for whites; 5-year failure after Living Donor Kidney Transplantation (LDKT) decreased from 37.4% to 22.2% for blacks and from 20.8% to 13.9% for whites.
  2. Among DDKT recipients in the earliest group of patients, blacks were 39% more likely than whites to experience 5-year failure, but this disparity narrowed to 10% in the most recent group.
  3. Among LDKT recipients in the earliest group, blacks were 53% more likely than whites to experience 5-year failure, but this disparity narrowed to 37% in the most recent group.
  4. There were no statistically significant differences in 1-year or 3-year failure rates of transplanted kidneys after LDKT or DDKT in the most recent groups.
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Author Interviews, Cancer Research, Colon Cancer, Journal Clinical Oncology, Radiation Therapy / 26.02.2016

MedicalResearch.com Interview with: Dr Guy van Hazel Clinical Professor of Medicine, School of Medicine and Pharmacology, University of Western Australia  Medical Research: What is the background for this study? What are the main findings? Dr. van Hazel: The SIRFLOX study is based on original work by Dr Bruce Gray and myself almost two decades ago, when we studied the combination of Selective Internal Radiation Therapy (SIRT) with Y-90 resin microspheres – which was absolutely new at the time – with hepatic artery chemotherapy. This study showed an increase in liver control with the addition of SIRT [Gray B et al. Ann Oncol 2001; 12: 1711–1720.]. We then proceeded to initiate a trial comparing systemic SIRT plus 5-FU/LV according to the Mayo Clinic regimen compared to the Mayo Clinic regimen alone, but unfortunately this had to be abandoned because new chemotherapy became available which made it unethical to offer the control arm. However, in those patients who were treated up to that point with SIRT plus 5-FU/LV [van Hazel G et al. J Surg Oncol 2004; 88: 78–85.] we did see a very high response rates compared to the control arm, with an impressive survival of 29 months. We subsequently did a phase l/ll study of modified FOLFOX6 with or without SIRT and again found very high response rates [Sharma R et al. J Clin Oncol 2007; 25: 1099–1106.].  This led us to launch the SIRFLOX study in 2007. (more…)
Alzheimer's - Dementia, Author Interviews, Cognitive Issues, Education, Mayo Clinic, Neurology / 25.02.2016

MedicalResearch.com Interview with: Prashanthi Vemuri, PhD Mayo Clinic Rochester, Minnesota  Medical Research: What is the background for this study? What are the main findings? Dr. Vemuri: Lifetime Intellectual enrichment has been found to delay the symptoms of dementia but the impact on brain changes due to Alzheimer’s disease has been poorly understood. In this study we studied the impact of lifetime intellectual enrichment (education, occupation, and midlife cognitive activities) on the brain changes related to Alzheimer’s disease. We obtained serial imaging on 393 individuals from a population based sample. We found that in majority of the individuals, there were minimal effects of intellectual enrichment on brain changes due to Alzheimer’s disease. However in those with higher genetic risk of Alzheimer’s, lifetime intellectual enrichment had a protective effect on the brain. (more…)
Author Interviews, Orthopedics, Transplantation / 25.02.2016

MedicalResearch.com Interview with: Dr. Brett Crist MD FACS Associate Professor of Orthopaedic Surgery Co-Chief, Orthopaedic Trauma Division Associate Director, Joint Preservation Surgery Director, Trauma Orthopaedic Fellowship School of Medicine University of Missouri Health  Medical Research: What is the background for this study? What are the main findings? Dr. Crist: Some young patients have bone and/or cartilage problems on the femoral head due to disease or injury.  Resurfacing the femoral head with donated bone and cartilage tissue is often a better option for these young patients with active lifestyles, who would otherwise require an artificial joint that would limit their activities and eventually wear out. However, there is no standard method for implantation. Our study provides initial clinical evidence that larger, size-matched grafts have the potential to improve outcomes when resurfacing cartilage defects of the femoral head in the hip joint. (more…)
Author Interviews, Cancer Research, Esophageal, Lung Cancer, Radiology, Surgical Research, University of Michigan / 25.02.2016

MedicalResearch.com Interview with: Mark A. Healy, MD Department of Surgery Center for Healthcare Outcomes & Policy, University of Michigan Ann Arbor, MI   Medical Research: What is the background for this study? What are the main findings? Dr. Healy: In our study, we found high overall use of PET as a primary study for recurrence detection in lung and esophageal cancers, with substantial hospital-based variation in the use of PET. Despite this, there was not a significant difference in survival for patients across high and low PET use hospitals. (more…)
Author Interviews, Dengue, Zika / 25.02.2016

MedicalResearch.com Interview with: Prof Paul Dyson Institute of Life Science Swansea University Medical School Singleton Park Swansea UK Medical Research: What is the background for this study? What are the main findings? Prof. Dyson: The spread of insect-vectored viruses such as Dengue and, more recently, Zika, underline the urgent necessity to develop new technologies to control insect disease vectors that, due to human activity, are spreading globally. The concept of using RNAi in insects is not new and is widely used as a research tool in the model organism Drosophila melanogaster. However, adapting RNAi for use in non-model insects has been slow, almost entirely due to the problem of delivering interfering RNA to the insect. Manual injection is a less than optimal means of delivery for larger insects, while including interfering RNA in a food source can be effective in smaller insects in the laboratory. But neither delivery system is suited for field applications of RNAi as a biocide. Faced with this challenge, we (myself and Dr Miranda Whitten) conceived the concept of symbiont-mediated RNAi and have advanced it with support from the UK BBSRC and the Gates Foundation, establishing it as a viable mechanism of delivery of RNAi in (a) a tropical disease vector, Rhodnius prolixus, a vector of Chagas disease, exemplified by targeting insect fertility, and (b) a globally invasive vector of plant disease, Western Flower Thrips, targeting larval growth. Interfering RNA is actively produced by symbiotic insect bacteria that multiply within the host. Critical to the technology is to ensure the stability of RNA synthesis by these bacteria. The interfering RNA is then released by the bacteria, absorbed and systemically circulated within the host, thereby causing knock-down of gene expression in specific tissues. We have exploited this technology to severely impair fertility of Rhodnius prolixus, and to cause mortality of developing larvae of Western Flower Thrips. As a biocide, the technology offers exquisite specificity due to the co-evolution and co-dependencies of the symbiont and its insect host, combined with the sequence-specificity of the RNAi. Moreover, development of resistance is highly improbable. (more…)
Author Interviews, Cancer Research / 25.02.2016

MedicalResearch.com Interview with: Ross Cagan, PhD Professor, Developmental and Regenerative Biology, Oncological Sciences, Ophthalmology Senior Associate Dean for the Graduate School of Biomedical Sciences Icahn School of Medicine at Mount Sinai Medical Research: What is the background for this study? What are the main findings? Dr. Cagan: Large scale screening for new cancer drugs typically rely on either cell culture or biochemical assays. These types of systems do not take into account the complexity of cancer and drug interactions at a whole animal level. We developed a whole animal screening method using Drosophila (fruit flies) as a model organism. Our model activates the Ras and PI3K oncogenic pathways specifically in lung-like Drosophila tissue. The end result is overproliferation, cell migration and animal lethality. These phenotypes were used to screen a large library of drugs, from which a number of hits were discovered. This study focused on the synergistic abilities of the Mek-inhibitor, trametinib, and a statin to rescue the cancerous phenotypes at a molecular, cellular and whole animal level. (more…)
Author Interviews, OBGYNE, Urology / 25.02.2016

MedicalResearch.com Interview with: Kari Aarne Olavi Tikkinen, M.D PHD Adjunct Professor Department of Urology Helsinki University Central Hospital and University of Helsinki Helsinki, Finland Medical Research: What is the background for this study? Dr. Tikkinen: ?Stress and urgency incontinence are the two most frequent and the most bothersome urinary symptoms among women. It has been estimated that about twelve percent of women report significant bother from stress incontinence and eight percent from urgency incontinence. Both stress urinary incontinence and urgency urinary incontinence are associated with substantial physical and psychological morbidity, and large societal costs. An extensive body of evidence suggests that delivering vaginally versus caesarean section increases rates of post-partum stress urinary incontinence. The magnitude of long term effects of different delivery modes on stress and urgency urinary incontinence remain, however, uncertain. ? (more…)
Author Interviews, Cost of Health Care, Health Care Systems, Hospital Readmissions, Technology / 25.02.2016

MedicalResearch.com Interview with: Andrey Ostrovsky, MD CEO | Co-Founder Care at Hand  Medical Research: What is the background for this study? Dr. Ostrovsky: Hospital readmissions are a large source of wasteful healthcare spending, and current care transition models are too expensive to be sustainable. One way to circumvent cost-prohibitive care transition programs is complement nurse-staffed care transition programs with those staffed by less expensive nonmedical workers. A major barrier to utilizing nonmedical workers is determining the appropriate time to escalate care to a clinician with a wider scope of practice. The objective of this study is to show how mobile technology can use the observations of nonmedical workers to stratify patients on the basis of their hospital readmission risk. (more…)
Author Interviews, Breast Cancer, Genetic Research, JAMA / 25.02.2016

MedicalResearch.com Interview with: Dr. Shoshana Rosenberg ScD, MPH Department of Medical Oncology Dana-Farber Cancer Institute Boston, Massachusetts Medical Research: Why would BRCA testing rates have increased among younger women with cancer?   Dr. Rosenberg: There has been increasing awareness surrounding genetic testing for breast cancer in more recent years, likely contributing to the trend that we saw over time  in our cohort. This has included more media attention, most notably Angelina Jolie’s sharing her story in 2013. Medical Research: Is this increase in testing a good thing? Dr. Rosenberg: Young women who are diagnosed with breast cancer should be getting tested so the fact that an increasing proportion of women have been undergoing BRCA testing in recent years indicates patients (and the physicians who treat them) are following recommendations. (more…)
Author Interviews, Heart Disease, NEJM, Pharmacology / 25.02.2016

MedicalResearch.com Interview with: Professor Paul Myles MBBS, MPH, MD, FCARCSI, FANZCA, FRCA Director, Dept of Anaesthesia and Perioperative Medicine Alfred Hospital and Monash University, Melbourne, Australia Medical Research: What is the background for this study? What are the main findings? Dr. Myles: When we set up this study 10 years ago there was marked variation in practice for  people taking aspirin waiting for coronary artery bypass surgery.  About half were being told that they must stop their aspirin 5-7 days before surgery, and the other half were told that they should stay on their aspirin. This variation existed across different countries, different cities, and even within a single hospital. Doctors had varied opinions because reliable medical research was sparse; the evidence was contradictory. We thus designed a definitive clinical trial in which half the patients were randomly assigned to receive aspirin and the other half received a placebo. Our study has shown that aspirin is safe (i.e. it does not increase the bleeding risk). We also found that there does not appear to be a benefit during and after surgery, but in view of the clear benefits that exist in daily life, including the preoperative waiting period, we recommend that people should stay on their aspirin if they are having coronary artery surgery. (more…)
Asthma, Author Interviews, Education, Pediatrics / 25.02.2016

MedicalResearch.com Interview with: Joy Hsu, MD, MS Air Pollution and Respiratory Health Branch Division of Environmental Hazards and Health Effects National Center for Environmental Health CDC Atlanta GA 30341 Medical Research: What is the background for this study? Dr. Hsu: Asthma is a leading cause of missed school days related to chronic illness. This study is based on survey data from 2006 to 2010 on children aged 17 years and younger with asthma from 35 states and the District of Columbia.  (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Infections, JAMA / 24.02.2016

MedicalResearch.com Interview with: Dr. Manu Shankar-Hari MB BS MD FRCA EDIC FFICM MSc[Epi] Consultant, Intensive Care Medicine; Guy’s and St Thomas’ NHS Foundation Trust Clinical Research Associate, Intensive Care National Audit and Research Centre Honorary Senior Lecturer in Intensive Care Medicine Division of Asthma Allergy and Lung Biology King’s College London, UK  Medical Research: What is the background for this study? What are the main findings? Dr. Shankar-Hari: Septic shock is a complex illness.  The previous Consensus Definitions (1991 and 2001) place emphasis on the circulatory abnormalities as the core concept and neither definitions provide data driven clinical criteria. In addition, last ten years of basic science research has established the concept that septic shock is associated with plethora of cellular and metabolic abnormalities (often referred to as cellular stress), alongside circulatory dysfunction. In this background, the paper published in JAMA provides an updated illness concept (definitions) and data driven clinical criteria for diagnosing septic shock at the bedside.

The updated illness concept: 'Septic shock is defined as a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone.’

The clinical criteria: 'Adult patients with septic shock can be identified using the clinical criteria of hypotension requiring vasopressor therapy to maintain mean arterial blood pressure 65 mm Hg or greater and having a serum lactate level greater than 2 mmol/L after adequate fluid resuscitation.' (more…)
Author Interviews, BMJ, Cancer Research, OBGYNE / 24.02.2016

MedicalResearch.com Interview with: Jiangrong Wang PhD Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm, Sweden Medical Research: What is the background for this study? What are the main findings? Dr. Wang: Cervical screening has been proved to effectively suppress the occurrence of cervical cancer, since it detects not only cervical cancer at early stages, but also precursor lesions that can be treated before progressing to invasive cancers. However, cervical screening has mainly reduced the occurrence of squamous cell cervical cancer, the most common type of invasive cervical cancer, but not adenocarcinoma of the cervix which originates from glandular cells. Although there is a well-known connection between adenocarcinoma in situ and invasive adenocarcinoma, questions remain on the magnitude of the cancer risk after detection of the glandular intraepithelial lesion-atypical glandular cells (AGC). We also wanted to study whether the current clinical management after detection of glandular abnormalities reduced the cancer risk as much as the standard management for squamous intraepithelial lesions does. Our findings show that 2.6% of women with  intraepithelial lesion-atypical glandular cells as the first abnormality developed invasive cervical cancer after 15 years of follow up and 74% of the cancers were adenocarcinoma. A moderately high proportion of women with AGC had prevalent cancer (diagnosed within 6 months from AGC), while there was considerably high incidence of cervical cancer within 0.5-6.5 years after a detection of AGC. The incidence of cervical cancer following AGC was significantly higher than for high-grade squamous intraepithelial lesions, and this increased risk remained even after having histology assessment in the initial half year.

The high risk of cervical cancer associated with AGC implies that the current clinical management following AGC does not prevent cervical cancer as sufficiently as the management for squamous intraepithelial lesions does.

 

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Author Interviews, Hospital Acquired, Infections, Nature / 24.02.2016

MedicalResearch.com Interview with: Ashootosh Tripathi, PhD Postdoctoral Research Fellow Life Sciences Institute I Sherman lab University of Michigan Ann Arbor, MI, USA MedicalResearch: What is the background for this study? What are the main findings? Dr. Tripathi: Acinetobacter baumannii is a nosocomial opportunistic and resistant pathogen that can spread epidemically among patients causing ventilator-associated pneumonia and bacteremia. The mortality rates associated with it can be as high as 60%, representing a paradigm of pathogenesis, transmission and resistance. In addition, numerous reports have shown the startling emergence of multidrug-resistant A. baumannii in hospitals as well as the identification of pan-drug-resistant strains at some locations. Among the  various reasons for the antibiotic resistance of this pathogenic microbe, perhaps the most significant is mediated by its tendency to form biofilms (a highly structured extracellular polymeric matrix), which provide the microbe with the alarming ability to colonize medical devices. Interestingly, despite the well-understood role of bacterial biofilm behind aggravating antimicrobial resistance, there are currently no drugs specifically targeting biofilms in clinical trials to date. The study sought to solve this problem through the development of a biofilm inhibitor as a precision medicine, directed towards vulnerable patients, to avoid potential life-threatening infections. A crystal-violet based high throughput in vitro screen was developed to identify inhibitors of A. baumannii biofilms against our natural products extract (NPE) library. The vast NPE library of ~42,000 extracts has been under constant development in Prof David H. Sherman laboratory at University of Michigan, Ann Arbor, for over the past decade, from a relatively underexplored marine microbiome collected from different part of world viz., Costa Rica, Panama, Papua New Guinea, etc., and is available for any research group with a robust high-throughput screening (HTS) assay (http://www.lsi.umich.edu/centers/center-for-chemical-genomics). The HTS assay that was queried against a library of 9,831 NPEs aimed to identify extracts inhibiting biofilm formation as a primary screening. Further secondary  screening and   activity  threshold optimization revealed the extract from Streptomyces gandocaensis (collected from Costa Rica) to be of particular interest due to its ability to inhibit biofilm formation and had a limited effect on A. baumannii growth. Activity based chromatographic separation and analysis of extracts derived from S. gandocaensis resulted in the discovery of three peptidic metabolites (cahuitamycins A–C),   with cahuitamycin  C  being   the   most effective biofilm inhibitor (IC50 =14.5 µM)   with  negligible A.  baumannii growth inhibition (an important trait for ideal biofilm inhibitor). Following up on the exciting discovery, we also completely characterized the biosynthetic machinery involved in making the active molecules by S. gandocaensis, using sophisticated bioinformatics and molecular biology techniques. The knock out analysis revealed that the biosynthesis of cahuitamycin C proceeds via a convergent biosynthetic pathway, with one of the steps apparently being catalyzed by an unlinked gene encoding a 6-methylsalicylate synthase. Efforts to assess starter unit diversification through selective mutasynthesis led to production of unnatural analogues cahuitamycins D and E with increased potency (IC50=8.4 and 10.5 µM) against A. baumannii biofilm. (more…)
Author Interviews, OBGYNE, Pediatrics, Pulmonary Disease, Tobacco Research / 24.02.2016

MedicalResearch.com Interview with: Dr. med. Julia Dratva, MD MPH          Medical Specialist Prevention and Public Health FMH  Scientific project leader MAS Versicherungsmedizin/Studienkoordinationleitung Dept. Epidemiology and Public Health Swiss Tropical and Public Health Institute Socinstrasse 57, P.O. Box, 4002 Basel, Switzerland Medical Research: What is the background for this study? What are the main findings? Dr. Dratva: Early childhood is a critical time window for subsequent health. Early life environment is known to be important for lung development and respiratory health. Little is known on the potential impact on lung ageing and the potential mechanisms responsible for the long-term impact. We investigated early childhood factors and their association with lung function decline, a common marker of lung aging, in two long-standing adult cohorts, SAPALDIA and ECRHS. As recently published in scientific journal PlosONE, maternal smoking, early respiratory infections or season of birth are associated with a faster decline in lung function decline, while less rapid decline was found in persons who had attended daycare. The early exposures may not only have an independent adverse effect on lung aging but also increase the respiratory vulnerability to other adult risk factors. Stronger effects were observed in in smokers exposed to the aforementioned adverse factors. (more…)
Author Interviews, Heart Disease, JAMA, Kidney Disease, Pharmacology / 24.02.2016

MedicalResearch.com Interview with: Frederic T. Billings IV, MD, MSc Assistant Professor of Anesthesiology and Medicine Additional Specialty: Cardiothoracic Anesthesiology Vanderbilt University Medical Research: What is the background for this study? What are the main findings? Dr. Billings: Acute kidney injury (AKI) affects up to 30% of patients following cardiac surgery and is associated with long-term kidney function decline as well as a 5-fold increase in death during hospitalization following surgery. Statins affect several mechanisms of AKI following cardiac surgery including improvement of endothelial function and attenuation of oxidative stress, so we performed a clinical trial to test the hypothesis that high-dose atorvastatin (brand name Lipitor) use prior to and following surgery reduces AKI following cardiac surgery. In 615 patients who completed the study high-dose atorvastatin treatment, compared to placebo administration, did not reduce the risk of AKI overall, among patients naïve to statins, or patients already using a statin. In fact, among patients naïve to statins with baseline chronic kidney disease we found some evidence that atorvastatin may increase risk for kidney injury, although the number of patients was small in this subgroup. (more…)
Author Interviews, Brigham & Women's - Harvard / 24.02.2016

MedicalResearch.com Interview with: Michelle Dossett, MD, PhD, MPH Benson-Henry Institute for Mind Body Medicine Massachusetts General Hospital  Medical Research: What is the background for this study? What are the main findings? Dr. Dossett: In 2015 the FDA and FTC held public hearings on the regulation and advertising, respectively, of homeopathic drug products.  Among their questions, they were curious about the use and public perceptions of these products.  However, there is little data available to answer these questions.  Every 5 years, the National Center for Health Statistics at the CDC and the National Center for Complementary and Integrative Health (NCCIH) at the NIH team up to survey Americans about their use of complementary and integrative medicine (CIM) modalities.  We analyzed data from the 2012 survey to address some of the questions raised by the FDA and FTC. We found that 2.1% of U.S. adults had used homeopathic products within the past year, however, only 19% had seen a practitioner for homeopathic therapy.  The most common health complaints that homeopathic products were used to address included head and chest colds and other respiratory and otorhinolaryngology (ear, nose, and throat) complaints. The second most common category of conditions these products were used for was musculoskeletal pain such as muscle and joint pain.  Intriguingly, people who used homeopathic products were more likely to find them helpful for a health condition than supplement users found their use of supplements.  Moreover, homeopathy users who saw a practitioner were more likely to find that it helped their health problem “a great deal” than those who did not. (more…)
Author Interviews, Pain Research, Race/Ethnic Diversity / 24.02.2016

MedicalResearch.com Interview with: Adam T. Hirsh PhD Assistant Professor, Psychology Indiana University Indianapolis, IN  Medical Research: What is the background for this study? What are the main findings? Dr. Hirsh: Pain is highly prevalent and is a major cause of disability. How patients cope with pain affects how much pain they feel and how much that pain interferes with their lives. Compared to White individuals, Black individuals experience greater pain across a number of clinical conditions, as well as in response to experimentally-delivered stimuli. These race differences may be due to differences in pain-related coping. We conducted a meta-analysis of clinical and experimental studies (including 2,719 Black and 3,770 White adults) to quantify race differences in the overall use of pain coping strategies as well as specific coping strategies. The results indicated that, compared to White individuals, Black individuals used pain coping strategies more frequently overall. In particular, Black individuals more frequently used strategies that involved praying and catastrophizing, whereas White individuals more frequently used strategies that involved task persistence. These results suggest that Black individuals use coping strategies more frequently, specifically strategies associated with poorer pain outcomes. (more…)
Abuse and Neglect, BMJ, Imperial College, Microbiome, OBGYNE / 23.02.2016

MedicalResearch.com Interview with: Dr. Aubrey Cunnington Faculty of Medicine, Department of Medicine Clinical Senior Lecturer Imperial College, London Medical Research: What is the background for this study? What are the main findings? Dr. Cunnington: We noticed that increasing numbers of women who were having Caesarean section deliveries at our hospitals were requesting for their vaginal fluid to be swabbed onto their babies after birth – a process often termed “vaginal seeding”. The idea behind this, is that it transfers all the natural bacteria (microbiota) from the mother’s vagina to the baby. We know that early on in life, babies born by Caesarean section have different bacteria living on their bodies and in their guts to those of babies born by vaginal delivery. Some people think these differences in the microbiota may be responsible for differences in long-term health, although a causal link is unproven. The hope is that vaginal seeding might reduce the risk of the baby developing some diseases like obesity and asthma in the future. Unfortunately we are a long way from having the evidence to show that this is possible, and we do not know whether vaginal seeding is really safe. Babies born by elective Caesarean section are at lower risk of transfer of some potentially harmful bacteria and viruses from the birth canal, but these harmful bacteria and viruses could be transferred to the baby on a swab and potentially cause a devastating infection. MedicalResearch.com Editor's note:  'Vaginal Seeding' is also known as "microbirthing",    (more…)