Author Interviews, Diabetes, JAMA, Pharmacology / 01.03.2016

MedicalResearch.com Interview with: [caption id="attachment_22181" align="alignleft" width="200"]Dr. John Buse MD Ph.D Professor, Medicine Director, Diabetes Care Center Chief, Division of Endocrinology Executive Associate Dean, Clinical Research University of North Carolina School of Medicine Dr. John Buse[/caption] Dr. John Buse MD Ph.D Professor, Medicine Director, Diabetes Care Center Chief, Division of Endocrinology Executive Associate Dean, Clinical Research University of North Carolina School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Buse: Degludec is an longer acting basal insulin analog recently approved in the US.  Liraglutide is a once-daily GLP-1 receptor agonist.  Both are among the most powerful glucose lowering drugs available in the setting of type 2 diabetes.  They have very different properties.  Degludec is best at lowering fasting glucose. Liraglutide has effects on postprandial glucose as well.  The major side effects of degludec are hypoglycemia and weight gain. Liraglutide on the other hand has not an inherent effect to cause hypoglycemia and does promote weight loss.  Liraglutide does cause nausea and in fewer patients vomiting in a dose dependent manner. In developing the fixed dose combination the idea was to amplify glucose lowering efficacy and minimize the adverse effects of both components.  Prior studies have basically shown that this has been accomplished.  In this study we looked at the very common clinical scenario of the patient with type 2 diabetes inadequately controlled on basal insulin glargine and asked the question of whether switching from glargine to IDegLira (the combination product) would do better than continued titration of glargine.
Author Interviews, Cancer Research, Diabetes, Diabetologia / 01.03.2016

MedicalResearch.com Interview with: [caption id="attachment_22195" align="alignleft" width="160"]Bendix Carstensen Bendix Carstensen[/caption] Bendix Carstensen Department of Clinical Epidemiology Steno Diabetes Center Gentofte Medical Research: What is the background for this study? What are the main findings? Response: It has long been known that all diabetes patients have elevated risk of cancer (10-15%). Patients on insulin slightly more (20-25%). Type 1 patients is only a small fraction (10%) of all diabetes patients, but they ALL take insulin. If insulin has a role in cancer occurrence it would be expected to be particularly pronounced in type 1 patients, and increasing by duration. But it is not, the risk of cancer is 15% elevated (if we disregard prostate, breast and other cancers only occurring in one of the sexes), and there is no increase in the excess risk by duration of insulin use. Breast cancer risk is 10% lower and prostate cancer risk some 40% lower. Overall there is very little increased cancer risk - 1% for men 7% for women.
Author Interviews, JACC, Thromboembolism, Yale / 01.03.2016

MedicalResearch.com Interview with: [caption id="attachment_21981" align="alignleft" width="110"]Behnood Bikdeli MD Department of Internal Medicine and Center for Outcomes Research and Evaluation (CORE) Yale University School of Medicine New Haven, CT 06510 Dr. Behnood Bikdeli[/caption] Behnood Bikdeli MD Department of Internal Medicine and Center for Outcomes Research and Evaluation (CORE) Yale University School of Medicine New Haven, CT 06510  Medical Research: What is the background for this study? What are the main findings? Response: The idea of closing the path of inferior vena cava (IVC) to prevent blood clots migrating to the pulmonary circulation and causing a pulmonary embolism (PE) has been around for over 150 years. We were aware than many practitioners might think of IVC filters for that reason, and specifically with the introduction of retrievable filters in recent years; that have made it more palatable for referring physicians. However, there is a paucity of high-quality data to suggest the efficacy of IVC filters. The two existing large trials did not show a mortality benefit from use of filters, and the guidelines have very narrow indications for use of IVC filters in patients who have already had a pulmonary embolism. Having said that, we wondered whether despite the absence of high-quality comparative effectiveness data, filters might be commonly used in patients with PE, particularly among older adults who are a vulnerable population (at higher risk of PE, at higher risk of PE complications; but also less likely to receive other advanced therapies for PE). Our study common use of IVC filters among older adults in the US; with over 75% relative increase in use of IVC filters from 1999 to 2010 (from ~5000 patients with PE in 1999 to ~9000 patients with PE in 2010). We also noted wide regional variations in the use of IVC filters (e.g. highest in the South Atlantic and lowest in the Mountain region). Such differences fundamentally persisted over time. In addition, we noted declining short-term and 1-year mortality rates in patients with pulmonary embolism over time, irrespective of whether or not they received an IVC filter.
Author Interviews, Genetic Research, MD Anderson, Nature, Prostate Cancer / 01.03.2016

MedicalResearch.com Interview with [caption id="attachment_22239" align="alignleft" width="169"]Dr. Dingxiao Zhang Ph.D Department of Epigenetics and Molecular Carcinogenesis University of Texas MD Anderson Cancer Center Smithville, TX 78957, USA Dr. Dingxiao Zhang[/caption] Dr. Dingxiao Zhang Ph.D Department of Epigenetics and Molecular Carcinogenesis University of Texas MD Anderson Cancer Center Smithville, TX 78957, USA MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Zhang: Prostate cancer (PCa) is a heterogeneous malignancy harboring phenotypically and functionally diverse subpopulations of cancer cells. To better understand PCa cell heterogeneity, it is crucial to dissect the biology of normal prostate epithelial lineages. The background for the current study is to annotate the gene expression profiles of normal prostate epithelial cells, through which we hope to gain insight on Prostate cancer subtypes and the cellular heterogeneity in PCa. The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. In this study, we have performed a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. One of our major findings is that the differential gene expression profiles in basal versus luminal prostate epithelial cells account for their distinct functional properties. Specifically, basal cells preferentially express gene categories associated with stem cells, MYC-transcriptional program, neurogenesis, and ribosomal RNA (rRNA) biogenesis regulated by Pol I. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene expression profile is enriched in advanced, anaplastic, castration-resistant, and metastatic prostate cancers. Therefore, we link the cell-type specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features.
Author Interviews, Lancet / 01.03.2016

[caption id="attachment_22242" align="alignleft" width="150"]Theresa Wimberley PhD student National Centre for Register-based Research School of Business and Social Sciences Aarhus University Theresa Wimberley[/caption] MedicalResearch.com Interview with: Theresa Wimberley PhD student National Centre for Register-based Research School of Business and Social Sciences Aarhus University MedicalResearch.com: What is the background for this study? What are the main findings? Response: Approximately 30% of patients with schizophrenia suffer from treatment-resistant schizophrenia, i.e. they do not respond to first-line antipsychotic treatment. Identification of high-risk patients as early as possible is crucial in order to optimize treatment and improve prognosis. In a large population-based cohort of patients diagnosed with schizophrenia we found the following candidate predictors of treatment resistance:
  • younger age at diagnosis,
  • living in less urban areas,
  • paranoid schizophrenia subtype,
  • a history of psychiatric hospital admission,
  • personality disorder,
  • suicide attempt, and
  • psychotropic drug use. Additionally, as opposed to other studies using treatment-based proxies for treatment-resistant schizophrenia, this study not only considered clozapine users as treatment resistant. We extended the proxy definition to include patients eligible for clozapine, as clozapine is considered to be under-prescribed. We found similar results regardless of definition used.
Accidents & Violence, Author Interviews, BMJ, Brain Injury, CDC, Pediatrics / 29.02.2016

MedicalResearch.com Interview with: [caption id="attachment_16316" align="alignleft" width="200"]Joanne Klevens, MD, PhD Division of Violence Prevention US Centers for Disease Control and Prevention Atlanta, Georgia Dr. Joanne Klevens[/caption] Dr. Joanne Klevens, MD, PhD, MPH Division of Violence Prevention US Centers for Disease Control and Prevention Atlanta, Georgia Medical Research: What is the background for this study? What are the main findings? Dr. Klevens: Pediatric abusive head trauma is a leading cause of fatal child maltreatment among young children and current prevention efforts have not been proven to be consistently effective. In this study, compared to seven states with no paid family leave policies, California’s policy showed significant decreases of hospital admissions for abusive head trauma in young children. This impact was observed despite low uptake of policy benefits by Californians, particularly among populations at highest risk of abusive head trauma.
Author Interviews, Health Care Systems, JAMA, Outcomes & Safety / 29.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22185" align="alignleft" width="180"]Dr. Alisa Khan, MD MPH Boston Children's Hospital Boston Dr. Alisa Khan[/caption] Dr. Alisa Khan, MD MPH Division of General Pediatrics Boston Children’s Hospital Department of Pediatrics, Harvard Medical School, Boston, Massachusetts Medical Research: What is the background for this study? What are the main findings? Dr. Khan: Medical errors, or mistakes in the process of caring for patients, occur frequently. While methods of detecting errors have improved, parents and families are not typically included in routine hospital safety monitoring systems. We found that nearly 1 in 11 parents reported their child had experienced a safety incident during hospitalization. Most of these reports were confirmed to be medical errors when reviewed by physicians, and many were not otherwise documented in the patient’s medical record.
Author Interviews, Emergency Care, Infections, JAMA, Pediatrics, Pulmonary Disease, Respiratory / 29.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22065" align="alignleft" width="150"]Suzanne Schuh, MD, FRCP(C), ABPEM The Hospital for Sick Children affiliated with the University of Toronto Dr. Suzanne Schuh[/caption] Suzanne Schuh, MD, FRCP(C), ABPEM The Hospital for Sick Children affiliated with the University of Toronto Medical Research: What is the background for this study? Dr. Schuh: Routine measurement of oxygen saturation in bronchiolitis is sometimes used as a proxy for illness severity, despite poor correlation between these parameters. This focus on oximetry may in part relate to lack of evidence on the natural history of desaturations in bronchiolitis which are often transient, and frequently not accompanied by increased respiratory distress. Desaturations occurring in infants with mild bronchiolitis in an ED often result in hospitalizations or prolonged hospital stay. They occur in healthy infants and may also occur in infants with mild bronchiolitis at home. The main objective of this study of infants with acute bronchiolitis was to determine if there is a difference in the proportion of unscheduled medical visits within 72 hours of ED discharge in infants who desaturate during home oximetry monitoring versus those without desaturations. Our study shows that the majority of infants with mild bronchiolitis experience desaturations after discharge home.
Accidents & Violence, Author Interviews, JAMA / 29.02.2016

MedicalResearch.com Interview with: Anna-Karin Numé MD, PhD student Copenhagen University Gentofte Hospital Department of Cardiology Cardiovascular Research Hellerup Denmark  Medical Research: What is the background for this study? Dr. Numé: While it is obvious that a loss of consciousness while driving a car is very dangerous, what is not known is whether individuals who have had an episode of fainting (syncope) have a significantly higher risk of having car crashes in the future. Because about one third of patients with syncope are likely to have a recurrence, physicians face a difficult judgment about whether patients with syncope are fit to drive. Medical Research: What are the main findings? Dr. Numé: In this nationwide study of patients with syncope, having a history of syncope were associated with a 2-fold-higher risk of later motor vehicle crashes requiring medical attention at an emergency department or hospital compared with the general population – a risk that remained elevated throughout a follow-up of 5 years. This risk was small in absolute terms, yet raises important questions about policies towards driving.
Author Interviews, JAMA, Sexual Health / 29.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22058" align="alignleft" width="200"]Loes Jaspers MD, PhD scientist Dept. of Epidemiology, Erasmus University Medical Center Rotterdam, the Netherlands Dr. Loes Jaspers[/caption] Loes Jaspers MD, PhD scientist Dept. of Epidemiology Erasmus University Medical Center Rotterdam, the Netherlands Medical Research: What is the background for this study? What are the main findings? Dr. Jaspers: In August 2015, the U.S. Food and Drug Administration approved flibanserin as a medical treatment for women with hypoactive sexual desire disorder (HSDD). The approval was accompanied by considerable attention in the media. Some people were positive about the approval, while others questioned whether benefits outweigh the risks. That is why we systematically reviewed eight clinical trials (five published and three unpublished) that included 5,914 women to examine the efficacy and safety of the medication for treatment of hypoactive sexual desire disorder. We found that women taking flibanserin experienced one-half additional satisfying sexual event per month, and that they experienced 2-4 times more side-effects, such as dizziness, sleepiness, nausea, and tiredness, compared to placebo. The overall improvement that women reported while taking the drug was low. It ranged from ‘minimal improvement’ to ‘no change’. The quality of the evidence was graded using established and transparent guidelines, the Grades of Recommendation, Assessment, Development and Evaluation approach (GRADE), which have been adopted by leading scientific organizations globally. Although the studies reviewed were randomized clinical trials, the quality of the evidence was very low, particularly because of limitations in design, the indirectness of evidence, and more favorable efficacy outcomes in published compared with unpublished studies.
Author Interviews, JAMA, Ophthalmology / 27.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22149" align="alignleft" width="180"]MedicalResearch.com Interview with: Jason Hsu, MD Retina Service, Wills Eye Hospital Assistant Professor of Ophthalmology Thomas Jefferson University Mid Atlantic Retina Medical Research: What is the background for this study? What are the main findings? Dr. Hsu: There are some patients with the wet type of age-related macular degeneration (AMD) who have persistent swelling in the retina despite regular, repeated eye injections with the anti-vascular endothelial growth factor (anti-VEGF) medications (e.g., Avastin, Lucentis, and Eylea). I had postulated that if we could decrease the turnover of fluid inside the eye, it might allow the injected medicine to stay in the eye for a longer period of time. I chose dorzolamide-timolol (brand name: Cosopt), a commonly available prescription eye drop used for glaucoma, since it is a very potent aqueous suppressant. By slowing down the production of eye fluid, I theorized it might decrease the outflow of fluid and medicine from the eye. Our study was a small, nonrandomized, exploratory pilot study. We enrolled 10 patients with wet AMD who had persistent retinal swelling despite chronic, fixed interval anti-VEGF injections. We kept patients on the exact same anti-VEGF medication and continued to see them at the exact same interval that they had been on before study enrollment. Once enrolled, the only difference is that we had them start using dorzolamide-timolol eye drops twice a day for the course of the study. The results were fairly striking with the retinal thickness decreasing from around 420 microns to 334 microns at the final visit. This decrease in swelling was significant at the first study visit after starting the drops and remained significant throughout the course of the study. Medical Research: What should clinicians and patients take away from your report? Dr. Hsu: I think it’s important to recognize that this is a short-term, uncontrolled pilot study. However, it does suggest that the addition of a commonly available glaucoma drop (dorzolamide-timolol) may boost the effect of anti-VEGF injections in patients with wet AMD who have persistent swelling. Medical Research: What recommendations do you have for future research as a result of this study? Dr. Hsu: We are about to start a larger randomized clinical trial to confirm the findings of this pilot study. In addition, we are performing a similar study in patients with swelling in the retina from diabetes and vein occlusions. Medical Research: Is there anything else you would like to add? Dr. Hsu: Anecdotally, I have been using dorzolamide-timolol in patients outside the study. In addition, some of the original study patients wished to remain on the eye drop even after the study was completed. In some of these patients, the eye drop has not only kept the swelling down in the retina, but it has allowed me to space out the time between their injections further. They seem to require less frequent injections to keep the swelling under control while using the eye drop. We hope to demonstrate this additional clinical benefit in future studies. Citation: Sridhar J, Hsu J, Shahlaee A, et al. Topical Dorzolamide-Timolol With Intravitreous Anti–Vascular Endothelial Growth Factor for Neovascular Age-Related Macular Degeneration. JAMA Ophthalmol. Published online February 25, 2016. doi:10.1001/jamaophthalmol.2016.0045. Dr. Jason Hsu[/caption] Jason Hsu, MD Retina Service, Wills Eye Hospital Assistant Professor of Ophthalmology Thomas Jefferson University Mid Atlantic Retina Medical Research: What is the background for this study? What are the main findings? Dr. Hsu: There are some patients with the wet type of age-related macular degeneration (AMD) who have persistent swelling in the retina despite regular, repeated eye injections with the anti-vascular endothelial growth factor (anti-VEGF) medications (e.g., Avastin, Lucentis, and Eylea). I had postulated that if we could decrease the turnover of fluid inside the eye, it might allow the injected medicine to stay in the eye for a longer period of time. I chose dorzolamide-timolol (brand name: Cosopt), a commonly available prescription eye drop used for glaucoma, since it is a very potent aqueous suppressant. By slowing down the production of eye fluid, I theorized it might decrease the outflow of fluid and medicine from the eye. Our study was a small, nonrandomized, exploratory pilot study. We enrolled 10 patients with wet AMD who had persistent retinal swelling despite chronic, fixed interval anti-VEGF injections. We kept patients on the exact same anti-VEGF medication and continued to see them at the exact same interval that they had been on before study enrollment. Once enrolled, the only difference is that we had them start using dorzolamide-timolol eye drops twice a day for the course of the study. The results were fairly striking with the retinal thickness decreasing from around 420 microns to 334 microns at the final visit. This decrease in swelling was significant at the first study visit after starting the drops and remained significant throughout the course of the study.
Author Interviews, JAMA, Ophthalmology, Surgical Research, Toxin Research / 27.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22143" align="alignleft" width="160"]Yu-Chih Hou, MD Department of Ophthalmology National Taiwan University Hospital Taipei, Taiwan Dr. Yu-Chih Hou[/caption] Yu-Chih Hou, MD Department of Ophthalmology National Taiwan University Hospital Taipei, Taiwan MedicalResearch: What is the background for this study? Dr. Yu-Chih Hou: We have encountered 3 patients with right eye pain and corneal edema after left orofacial surgery under general anesthesia since December 6. 2010. The first patient underwent a left tongue tumor excision by an ENT doctor. Postoperative day one, corneal epithelial defect and edema with mild anterior chamber reaction were noted in the right eye. Because his presentation was different from corneal abrasion which was the most common eye injury after general anesthesia, we suspected this ocular complication could be due to toxic reaction to antiseptic. Although corneal edema decreased, corneal endothelial cell density decreased and cataract developed later in the first patient. Two months later, the second patient had a similar toxic keratopathy but with severe corneal edema in his right eye after wide tumor excision of left lower gingival cancer by dentist surgeons. We found the antiseptic they used contained alcohol. We recommended not to use alcohol-containing antiseptics in oral surgery. Unfortunately, more severe toxic keratopathy occurred in the third patient after a left nasal tumor excision by other ENT doctor one year later. Because these severe ocular complications may occur again, it raised us to do detail study and we found all antiseptics they used contained alcohol. We hope to prevent occurrence of this toxic keratopathy in nonocular surgery by reporting our findings to other clinicians.
AHA Journals, Author Interviews, CDC, Sugar / 26.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22125" align="alignleft" width="180"]Sohyun Park, PhD Epidemiologist Epidemiology and Surveillance Team Obesity Prevention and Control Branch Division of Nutrition, Physical Activity, and Obesity National Center for Chronic Disease Prevention and Health Promotion Centers for Disease Control and Prevention Atlanta, Georgia Dr. Sohyun Park[/caption] Sohyun Park, PhD Epidemiologist Epidemiology and Surveillance Team Obesity Prevention and Control Branch Division of Nutrition, Physical Activity, and Obesity National Center for Chronic Disease Prevention and Health Promotion Centers for Disease Control and Prevention Atlanta, Georgia  Medical Research: What is the background for this study? What are the main findings? Dr. Park: The 2013 BRFSS provides the most recent state data for this behavior using a short screener which showed that about 1 in 3 adults consumed sugar-sweetened beverages (SSBs) at least once per day, and SSB intake differed by state and by certain subgroups. The main findings of the study showed the following among the 23 states and DC surveyed the prevalence of adults who consumed sugar-sweetened beverages at least once daily was:
  • Aged 18-24 years (43.3%)
  • Men (34.1%)
  • Non-Hispanic Blacks (39.9%)
  • Unemployed (34.4%)
  • Had less than a high school education (42.4%)
  • Adult sugar-sweetened beverages intake was highest in Mississippi (47.5%), followed by Louisiana (45.5%) and West Virginia (45.2%).
  • The prevalence of  sugar-sweetened beverages intake one or more times per day among younger adults (18–24 years) was 2.3 times the prevalence among the older adults (aged 55 years and older)—43.3% versus 19.1%, respectively.
Author Interviews, Blood Pressure - Hypertension, BMJ, Diabetes / 26.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22121" align="alignleft" width="200"]Dr-Mattias-Brunström Dr-Mattias-Brunström[/caption] Mattias Brunström, MD PhD student Department of Public Health and Clinical Medicine Umeå University Hospital Umeå, SE  Sweden Medical Research: What is the background for this study? What are the main findings? Dr. Brunström: Current guidelines differ in their recommendations on blood pressure treatment targets for people with diabetes. We did a systematic review and meta-analysis of 49 studies, including almost 74 000 patients, to investigate the effect of treatment at different blood pressure levels. We found that treatment reduced the risk of death, stroke, myocardial infarction and heart failure if systolic blood pressure before treatment was above 140 mm Hg. However, if systolic blood pressure was below 140 mm Hg, treatment increased the risk of cardiovascular death.
Author Interviews, Johns Hopkins, PLoS, Stem Cells / 26.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22010" align="alignleft" width="133"]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 Dr. Andrew Jaffe[/caption] 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.
AHA Journals, Author Interviews, Heart Disease, PAD, Surgical Research, University of Pennsylvania / 26.02.2016

[caption id="attachment_20701" align="alignleft" width="180"]Dr. Grace Wang MD FACS Assistant Professor of Surgery Division of Vascular and Endovascular Surgery Hospital of the University of Pennsylvania Dr. Grace Wang[/caption] 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.
AHA Journals, Author Interviews, Gender Differences, Heart Disease, Race/Ethnic Diversity, Women's Heart Health / 26.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21794" align="alignleft" width="180"]Karin H Humphries, MBA, DSc | Scientific Director BC Centre for Improved Cardiovascular Health UBC-HSF Professor in Women's Cardiovascular Health Vancouver, BC Karin Humphries[/caption] 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.
AHA Journals, Author Interviews, Heart Disease, Mental Health Research, Women's Heart Health / 26.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21884" align="alignleft" width="133"]Dr. Kim Lavoie Dr.Kim Lavoie[/caption] 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.
Author Interviews, JACC, Metabolic Syndrome, OBGYNE, Race/Ethnic Diversity, Women's Heart Health / 26.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21829" align="alignleft" width="150"]Catherine J. Vladutiu, PhD, MPH Research Assistant Professor, Department of Obstetrics & Gynecology Adjunct Assistant Professor, Department of Epidemiology Chapel Hill, NC Dr. Catherine Vladutiu[/caption] 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.
AHA Journals, Author Interviews, Brigham & Women's - Harvard, Heart Disease, Women's Heart Health / 26.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21826" align="alignleft" width="166"]Mercedes Sotos Prieto, PhD Research Associate, Department of Nutrition Harvard T.H. Chan School of Public Health 665 Huntington Ave Boston, MA, 02115 Dr. Mercedes Sotos Prieto[/caption] 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
AHA Journals, Author Interviews, Gender Differences, Heart Disease, University of Pennsylvania, Women's Heart Health / 26.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21844" align="alignleft" width="148"]Dr. Robert L. Wilensky MD Director, Interventional Cardiology Research Director, Interventional Cardiology Training Program Professor of Medicine Hospital of the University of Pennsylvania Dr. Robert Wilensky[/caption] 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.
Author Interviews, Cancer Research, Colon Cancer, Journal Clinical Oncology, Radiation Therapy / 26.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22068" align="alignleft" width="133"]Dr Guy van Hazel Clinical Professor of Medicine, School of Medicine and Pharmacology, University of Western Australia Dr. Guy van Hazel[/caption] 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.
Author Interviews, Breast Cancer, Genetic Research, JAMA / 25.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22015" align="alignleft" width="175"]Dr. Shoshana Rosenberg ScD, MPH Department of Medical Oncology Dana-Farber Cancer Institute Boston, Massachusetts Dr. Shoshana Rosenberg[/caption] 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.
Author Interviews, Heart Disease, NEJM, Pharmacology / 25.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22006" align="alignleft" width="120"]Professor Paul Myles MBBS, MPH, MD, FCARCSI, FANZCA, FRCA Director, Dept of Anaesthesia and Perioperative Medicine Alfred Hospital and Monash University, Melbourne, Australia Prof. Paul Myles[/caption] 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.
Author Interviews, Critical Care - Intensive Care - ICUs, Infections, JAMA / 24.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22018" align="alignleft" width="200"]Dr-Manu-Shankar-Hari.jpg Dr. Manu Shankar-Hari[/caption] 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.'
Author Interviews, BMJ, Cancer Research, OBGYNE / 24.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21992" align="alignleft" width="150"]Jiangrong Wang PhD Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm, Sweden Dr. Jianrong Wang[/caption] 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.

 

Author Interviews, Hospital Acquired, Infections, Nature / 24.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21986" align="alignleft" width="200"]Ashootosh Tripathi, PhD Postdoctoral Research Fellow Life Sciences Institute I Sherman lab University of Michigan Ann Arbor, MI, USA Dr. Ashootosh Tripathi[/caption] 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.
Author Interviews, Heart Disease, JAMA, Kidney Disease, Pharmacology / 24.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21970" align="alignleft" width="158"]Frederic T. Billings Dr. Frederic T.Billings[/caption] 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.
Abuse and Neglect, BMJ, Imperial College, Microbiome, OBGYNE / 23.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21901" align="alignleft" width="214"]Dr. Aubrey Cunnington Faculty of Medicine, Department of Medicine Clinical Senior Lecturer Imperial College, London Dr. Aubrey Cunnington[/caption] 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",   
Author Interviews, Clots - Coagulation, Genetic Research, Heart Disease, JACC / 23.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21677" align="alignleft" width="150"]Professor Keith AA Fox Duke of Edinburgh Professor of Cardiology University of Edinburgh Prof. Keith Fox[/caption] Professor Keith AA Fox Duke of Edinburgh Professor of Cardiology University of Edinburgh Medical Research: What is the background for this study? Prof. Fox: From previous reports, certain alleles of CYP2C19 are associated with reduced enzymatic function and reduced conversion of clopidogrel to the active metabolite. Patients carrying these reduced function alleles (reduced metabolizers) exhibit higher platelet reactivity when treated with clopidogrel, compared with patients without reduced-function alleles (extensive metabolizers). However, the relationship of CYP2C19 genotype and outcomes in medically managed patients with acute coronary syndromes (ACS) is not known. Medical Research: What are the main findings? Prof. Fox: There was no association between CYP2C19 metabolizer status (EM vs. RM) and the primary composite endpoint of cardiovascular death, myocardial infarction (MI), or stroke (hazard ratio [HR]: 0.86). EM and RM patients had similar rates of the primary endpoint whether treated with prasugrel (HR: 0.82) or clopidogrel (HR: 0.91; p for interaction non significant).