Author Interviews, Breast Cancer, Chemotherapy, Lancet / 04.03.2016

MedicalResearch.com Interview with: Massimo Cristofanilli, MD, FACP Professor of Medicine Associate Director of Translational Research and Precision Medicine Department of Medicine-Hematology and Oncology Robert H Lurie Comprehensive Cancer Center Feinberg School of Medicine Chicago, IL 60611  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Cristofanilli: The majority of breast cancer are estrogen-receptor positive and therefore candidate for treatment with endocrine therapy in the adjuvant and advanced settings. The most significant issue in the management of estrogen-receptor positive metastatic breast cancer is the development of drug resistance. Very few effective options are available for patients that demonstrate progression of disease while on standard endocrine therapy, particularly in premenopausal women and/or women that have even progressed on chemotherapy. The study demonstrated that the combination of fulvestrant with palbociclib, a novel inhibitor of CDK4/6 kinases, significantly improve response to treatment and delays disease progression with minimal toxicity.  (more…)
Author Interviews, Cost of Health Care, Medicare, NYU, Orthopedics / 04.03.2016

MedicalResearch.com Interview with: Richard Iorio, MD Dr. William and Susan Jaffe Professor of Orthopaedic Surgery Chief of the Division of Adult Reconstructive Surgery NYU Langone Medical Center  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Iorio: NYU Langone Medical Center’s Department of Orthopaedic Surgery realized early that alternate payment strategies based on value rather than volume were going to be increasing in prevalence and represent the future of compensation strategies  As leaders in orthopaedics, we knew that we must embrace this change and develop strategies and effective protocols to successfully navigate this alternative payment universe. In 2011, NYU Langone’s Hospital for Joint Diseases was chosen as a pilot site for CMS’s Bundled Payment Care Initiative, focusing on Medicare patients undergoing a total joint replacement. Beginning in 2013, we implemented protocols developed at our hospital focusing on preoperatiive patient selection criteria in an effort to ensure better outcomes for Medicare patients who underwent total joint replacements. Under a bundled payment program, hospitals assume financial responsibility for any complications over the entire episode of care 90 days after surgery, including postsurgical infections and hospital readmissions. We compared year over year outcomes from year 1 to year 3 of this program, and found:
  • Average hospital length of stay decreased from 3.58 days to 2.96 days;
  • Discharges to inpatient rehabilitation or care facilities decreased from 44 percent to 28 percent;
  • Average number of readmissions at 30 days decreased from 7 percent to 5 percent; from 11 percent to 6.1 percent at 60 days; and from 13 percent to 7.7 percent at 90 days;
  • The average cost to CMS of the episode of care decreased from $34,249 to $27,541 from year one to year three of the program.
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Author Interviews, Heart Disease, Lipids, Pharmacology, University of Pennsylvania / 03.03.2016

MedicalResearch.com Interview with: Dr. Richard L. Dunbar MD MS Assistant Professor of Medicine, Attending Physician, Preventive Cardiovascular Medicine Clinic, Member, Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of MedicineMember, Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania School of Medicine and Dr. Harsh Goel WellSpan Academic Hospitalists Department of Medicine, York Hospital, PA  MedicalResearch.com: What is the background for this analysis? Response: Niacin is the first cholesterol lowering treatment to prevent heart attacks and lower long term mortality. It thus provided the first proof that lowering cholesterol reduces cardiovascular risk. However, it is generally poorly tolerated due to almost universal flushing, limiting use. The better-tolerated statin drugs overshadowed niacin, rightly dominating hyperlipidemia therapy. Despite their advantages, statins are far from perfect, leaving important gaps. Firstly, at least 10% of patients simply don’t tolerate statins. Secondly, about 40% of patients have insufficient cholesterol lowering, leaving them far from their target LDL-cholesterol levels. Finally, even though statins lower cardiovascular risk, they by no means eliminate it and significant residual risk remains even in patients who respond to them. The relatively poor tolerance of niacin motivated development of an extended-release alternative which was dosed very differently from the established cardioprotective regimen used in the Coronary Drug Project (CDP) and the Stockholm Ischemic Heart Disease Study (SIHDS), the two landmark trials that proved niacin's benefits. These trailblazing trials used 3 grams of niacin divided throughout the fed portion of the day as 1 gram thrice daily with meals. In sharp contrast, the alternative regimen was severely handicapped by a profoundly lower dose of only 2 grams per day. Perhaps worse, the alternative regimen dosed all of the niacin at one sitting, at bedtime before the overnight fast, rather than three times a day before meals. We believe these were critical departures from the established cardioprotective niacin regimen, insofar as they severely undermined the alternative regimen’s efficacy. Accordingly, when added to statins, the alternative regimen failed to recapitulate the benefits seen with the established cardioprotective regimen in two recent large clinical trials, the AIM-HIGH trial and the HPS2-THRIVE trial. Besides the inherent flaws of the alternative regimen, there were also major issues with the trial designs which likely contributed to null results. From a practice standpoint, this is worrisome, because clinicians may draw erroneous conclusions from the trials of the alternative regimen, and thereby deny a significant population of hyperlipidemic patients the benefits of a well-proven cardioprotective therapy, i.e. the population which does not tolerate or does not respond adequately to statins (almost 50% of at risk patients). Hence, we embarked on a critical analysis and review of the alternative regimen with a special focus on the AIM-HIGH and HPS2-THRIVE trials to bring to light the pitfalls of comparing radically different regimens of what is nominally the same drug. (more…)
Author Interviews, Geriatrics, JAMA, Ophthalmology, Primary Care / 03.03.2016

MedicalResearch.com Interview with: Dr. Albert Siu M.D., M.S.P.H. Chair of the U.S. Preventive Services Task Force Chairman and professor of the Brookdale Department of Geriatrics and Palliative Medicine Icahn School of Medicine at Mount Sinai Director of the Geriatric Research, Education, and Clinical Center James J. Peters Veterans Affairs Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Siu: Impaired vision is a serious and common problem facing older adults and can affect their independence, ability to function, and quality of life. When the Task Force reviewed the research around screening older adults for vision impairment in a primary care setting, we concluded that the current evidence is insufficient to assess the balance of benefits and harms. As a result, we issued an I statement, which is consistent with the 2009 final and 2015 draft recommendations. MedicalResearch.com: What should clinicians and patients take away from your report? Dr. Siu: Older adults who are having problems seeing should talk to their primary care doctor or an eye specialist. Primary care doctors can explore the various causes of vision problems and do an eye exam to check for refractive error. An eye specialist can do a full eye exam to look for and treat refractive errors and other eye conditions that affect vision, such as cataracts and age-related macular degeneration (AMD). With regards to clinicians, in the absence of clear evidence, they should use their clinical judgment when deciding whether to screen patients who have not reported any concerns about their vision. (more…)
ASCO, Author Interviews, Biomarkers, Breast Cancer, Chemotherapy, Genetic Research, Journal Clinical Oncology / 03.03.2016

MedicalResearch.com Interview with: Oleg Gluz, MD West German Study Group Breast Center Niederrhein Evangelical Hospital Bethesda Moenchengladbach, Germany MedicalResearch.com: What is the background for this study? Dr. Gluz: PlanB trial is a Phase III chemotherapy study performed in patients with clinically high risk HER2 negative breast cancer. After early amendement, Recurrence Score (Oncotype Dx) as a selection criterion for or against chemotherapy together with central pathology review were included into the study. Patients with very low RS of below 12 and up to 3 positive lymph nodes were recommended to omit chemotherapy based on the low genomic recurrence risk. Chemotherapy was omitted in about 15% of all patients. For the first time we present prospective data comparing a genomical tool (Oncotype Dx) and an independent central pathology review for grade, ER, PR, and Ki-67 from a large phase III study combined with an exploratory analysis on early relapse risk. MedicalResearch.com: What are the main findings? Dr. Gluz: The study has two major findings: We have found a significant discordance in risk assessment between prognostic tools (grade by local and central lab, Oncotype Dx, Ki-67). Patients treated by endocrine therapy alone based on very low Recurrence Score had an excellent disease free survival of 97% after 3 years of follow up. (more…)
Author Interviews, Biomarkers, Brain Injury / 03.03.2016

MedicalResearch.com Interview with: Mr. Jim Joyce Chairman and CEO of Aethlon MedicalResearch.com: What is the background for this study? What are the main findings? Mr. Joyce: Our research into the neurodegenerative disease Chronic Traumatic Encephalopathy (CTE), was inspired by the death of Tom McHale, who was a former teammate and the second person diagnosed with CTE by our colleagues at the Boston University CTE Center. CTE is characterized by exposure to repetitive head trauma and at present, can only be diagnosed post-mortem, thus creating a significant need for a non-invasive method to diagnose and monitor CTE in living individuals. The aim of our study was to examine exosomal tau levels in plasma as a potential CTE biomarker. Our research team originally discovered the presence of exosomal tau in circulation and then established methods to quantify exosomal tau, which we refer to as a TauSome™, which we believe to be the first potential blood test to detect CTE living individuals. For this study, researchers examined 78 former National Football League players and 17 former athletes of non-contact sports, with preliminary findings suggesting that exosomal tau in plasma may be a noninvasive, accurate biomarker for CTE. The study results, published in the journal of Alzheimer’s disease, can be accessed here: http://content.iospress.com/articles/journal-of-alzheimers-disease/jad151028?resultNumber=7&totalResults=48&start=0&q=exosome&resultsPageSize=10&rows=10. (more…)
Author Interviews, Breast Cancer, Cancer Research, JNCI, Lymphoma / 03.03.2016

MedicalResearch.com Interview with: David Hodgson, MD, MPH, FRCPC Associate Professor University of Toronto Toronto, ON Canada   MedicalResearch.com: What is the background for this study? Dr. Hodgson: We know that treatment for childhood Hodgkin lymphoma can cause some side effects that arise years after treatment is  finished. In particular, radiotherapy given to the chest of adolescent females increases the risk of developing breast cancer in young adult survivors. But there are very little data about whether the early initiation of breast cancer screening will prevent breast cancer deaths in these survivors, and what kinds of screening is optimal. This is important because less than half of these young survivors are undergoing breast cancer screening, and in some jurisdictions early screening is not covered by insurance. MedicalResearch.com: What are the main findings? Dr. Hodgson: Because there has not been, and likely never will be, a large randomized screening trial for these patients, we used all the available information about their breast cancer risk, other health issues and the effectiveness of screening, and created a mathematical model that allows us to estimate the number of breast cancer deaths prevented by starting screening at age 25 for women who had received chest RT as teenagers. We found that one would have to invite about 260 survivors to early mammographic screening to prevent one breast cancer death, which compares favorably to other accepted reasons for breast cancer screening. Using MRI for screening, approximately 80 women would have to be invited to prevent one breast cancer death, because MRI is so much more sensitive than mammography. One of the problems with MRI, however, is that a substantial number of women will have "false positive" tests - abnormal findings that are not really cancer. (more…)
Author Interviews, Dental Research, Esophageal, Infections / 02.03.2016

MedicalResearch.com Interview with: Dr. Huizhi Wang Assistant Professor Department of Oral Immunology and Infectious Diseases University of Louisville School of Dentistry Louisville, KY  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Wang: Esophageal cancer is the eighth most frequent tumor and sixth leading cause of cancer death worldwide, characterized by rapid development and poor prognosis, including high mortality. Whereas the majority of cases occur in Asia, particularly in central China, recent data suggest that the frequency of new cases is rising in Western Europe and the USA. Mounting evidence suggests a causal relationship between specific bacterial infections and the development of certain malignancies. However, the possible role of the keystone periodontal pathogen, Porphyromonas gingivalis, in esophageal squamous cell carcinoma (ESCC) was unknown before our study. We found P. gingivalis infects epithelium of cancerous tissues up to 61%, as compared with 12% of adjacent tissues and non-infected in normal esophageal mucosa. A similar distribution of lysine-specific gingipain, a catalytic endoprotease uniquely secreted by P. gingivalis, and P. gingivalis DNA was observed. Moreover, we found infection of P. gingivalis was positively associated with the multiple clinicopathologic characteristics, including differentiation status, metastasis, and overall survival rate.  (more…)
Aging, Author Interviews, Exercise - Fitness, Heart Disease / 02.03.2016

MedicalResearch.com Interview with: Dafna Merom, PhD School of Science and Health University of Western Sydney Penrith New South Wales Australia Medical Research: What is the background for this study? What are the main findings? Dr. Merom: It is well established that moderate-intensity physical activity can reduced the risk of having cardiovascular disease (CVD), yet we know very little about the CVD benefits  that is associated with specific activity type. Considering that different types of physical activity challenge muscular-skeletal, neurological and cardio-respiratory systems differently, and that they involves different levels of psychosocial or cognitive demands, one may expect that different types of PA/sport may have differential relationships with health. Previous research found that frequent dancing protected against dementia, to a larger extent than walking. Since  cardiovascular disease and dementia share similar risk factors we hypothesised that dancing will also protect against CVD, even more than walking given the multi-dimensional nature of dance; Dance integrate physical, cognitive, emotional and social elements in its execution. We found that light-intensity dancing as well as light-intensity walking were not protective against  cardiovascular disease mortality. However, dancers who were at least slightly out of breath or sweaty had 46% lower risk of Cardiovascular death. Compared to fast walkers, dancing further reduced the risk of dying from cardiovascular disease by 21%.” (more…)
Author Interviews, Weight Research / 02.03.2016

MedicalResearch.com Interview with: Samuel Klein, M.D. William H. Danforth Professor of Medicine and Nutritional Science Director, Center for Human Nutrition Washington University School of Medicine St Louis, MO 63110 Medical Research: What is the background for this study? What are the main findings? Dr. Klein: Most obesity treatment guidelines, including those recently proposed by several major medical and scientific societies, recommend moderate weight loss of 5%-10% to achieve improvements in metabolic function and health outcomes. However, it is much easier to achieve a 5% weight loss than it is to achieve a 10% weight loss, so it is important to understand the benefits that occur with a 5% weight loss and what additional benefits, if any, can be expected with more weight loss in people with obesity. (more…)
Author Interviews, Diabetes, JAMA, Pharmacology / 01.03.2016

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Cancer Research, Diabetes, Diabetologia / 01.03.2016

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, JACC, Thromboembolism, Yale / 01.03.2016

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Diabetes, Ophthalmology / 01.03.2016

MedicalResearch.com Interview with: Adam Glassman, M.S. Director, DRCRnet Coordinating Center Jaeb Center for Health Research Tampa, FL 33647 Medical Research: What is the background for this study? What are the main findings? Response:  Diabetic macular edema (DME) involves a build-up of blood and fluid in the macula, the part of the eye needed for sharp, straight-ahead vision. Diabetic macular edema can occur in people with diabetic retinopathy and is the most common cause of diabetes-related vision loss.  Anti-VEGF agents are the first line treatment for most U.S. retinal specialists to treat vision loss from DME.  There are three commonly used agents to treat DME, EYLEA, Avastin, and Lucentis.  Eylea and Lucentis are FDA approved for Diabetic macular edema treatment.  However, Avastin is used off-label in repacked aliquots containing approximately 1/500th of the systemic dose used in cancer therapy.  The costs of these agents vary substantially, with Eylea priced at $1,850 per injection, Lucentis at $1,170, and repackaged Avastin at $60.  Results of this study, conducted by the Diabetic Retinopathy Clinical Research Network (DRCR.net) and funded by the NIH, found that all three agents are effective at improving vision and reducing DME over 2 years.  When vision loss is relatively mild at baseline (20/32-20/40), all three agents are similarly effective at improving visual acuity.  However, when vision loss at baseline is worse, Eylea outperforms Avastin at 2-years and also outperforms Lucentis at one year, but the difference between Eylea and Lucentis diminishes and is no longer statistically different at 2 years.  The percentage of participants that experienced a systemic adverse events such as heart attack, stroke, or death from an unknown cause was greater with Lucentis (12%) versus Eylea (5%) and Avastin (8%).  However, similar findings have not been seen in most previous studies. (more…)
Author Interviews, Genetic Research, MD Anderson, Nature, Prostate Cancer / 01.03.2016

MedicalResearch.com Interview with 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. (more…)
Author Interviews, Lancet / 01.03.2016

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.
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Author Interviews, Social Issues / 01.03.2016

MedicalResearch.com Interview with: Stephen Aichele PhD University of Geneva in Switzerland MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Aichele: The study was initiated over 30 years ago by professor Patrick Rabbitt (U. Oxford), who sought to investigate age-related changes in health, lifestyle, and cognitive abilities in more than 6000 residents of Greater Manchester and Newcastle-upon-Tyne, UK. Our most recent findings show that two psychological variables, lower self-rated health and age-related decrements in mental processing speed, appear to be especially important indicators of elevated mortality risk in middle-age and older adults. (more…)
Author Interviews, Emory, HIV / 01.03.2016

MedicalResearch.com Interview with: Dr. Igho Ofotokun MD MSc Division of Infectious Diseases, Department of Medicine Emory University School of Medicine, Atlanta, Georgia Grady Healthcare System, Atlanta, Georgia MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Ofotokun:  This work is focused on preventing further bone loss in HIV-infected patients and thus reducing the risk of future bone fractures. HIV infection is associated with a state of enhanced bone loss. HIV treatment with highly active antiretroviral therapy (HAART) further worsens rather than improve bone loss. Almost all HAART regimens that have been examined have been associated with bone loss. The consequence of this skeletal assualt is markedly elevated fracture prevalence among individuals living with HIV across a wide age range. It turns that the predominance of HAART associated bone loss occur within the first year of initiating therapy. In this study, we administered a single dose of 5 mg IV zoledronic acid, a long-acting bisphosphonate at the same time of HAART initiation to prevent HAART associated bone loss. At this dose, zoledronic acid prevented enhance bone resorption in all participants and completely blunted bone mineral density loss over the 48 weeks study follow up period. (more…)
Author Interviews, Biomarkers, Cancer Research, Melanoma, Ophthalmology / 01.03.2016

MedicalResearch.com Interview with: J. William Harbour, MD Professor & Vice Chairman Dr. Mark J. Daily Endowed Chair Director, Ocular Oncology Service Bascom Palmer Eye Institute Interim Associated Director for Basic Research Leader, Eye Cancer Site Disease Group Sylvester Comprehensive Cancer Center Member Interdisciplinary Stem Cell Institute University of Miami Miller School of Medicine Biomedical Research Building, Room 824 Miami FL 33136 Medical Research: What is the background for this study? What are the main findings? Dr. Harbour: Gene expression profiling has become the predominant means of molecular prognostic testing in uveal melanoma, with primary tumors being divided into Class 1 (low metastatic risk, about two thirds of cases) and Class 2 (high metastatic risk, about one third of cases).  In this study, we identified a new biomarker for uveal melanoma that subdivides Class 1 tumors based on the mRNA expression of the oncogene PRAME. Class 1 tumors not expressing PRAME have an extremely low metastatic risk, whereas those expressing PRAME have an intermediate metastatic risk. (more…)
Accidents & Violence, Author Interviews, BMJ, Brain Injury, CDC, Pediatrics / 29.02.2016

MedicalResearch.com Interview with: 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. (more…)
AACR, Author Interviews, Ovarian Cancer, Technology / 29.02.2016

MedicalResearch.com Interview with: Janet A. Sawicki, Ph.D. Deputy Director and Professor Lankenau Institute for Medical Research 100 Lancaster Ave. Wynnewood, PA 19096 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Sawicki: This study addresses the need for a more effective therapy for ovarian cancer. HuR is an RNA-binding protein that is present in high amounts in ovarian tumor cells compared to amounts in normal cells. HuR regulates the expression of thousands of genes that promote the survival of tumor cells. Thus, it is an ideal therapeutic target to suppress ovarian tumor growth. In this study, we used a small interfering RNA (siRNA) to investigate the impact of suppressing HuR expression on ovarian tumor growth in an ovarian cancer mouse model. We made use of the ability to conjugate a novel DNA dendrimer nanocarrier, 3DNA®, to both siHuR and a tumor-targeting moiety to suppress HuR expression specifically in tumor cells following systemic administration while avoiding toxicity in healthy cells. Systemic administration of siHuR-conjugated FA-3DNA to ovarian tumor-bearing mice suppressed tumor growth and ascites development, and significantly prolonged lifespan. Gene expression analysis identified multiple HuR-regulated genes in tumor cells as evidenced by changes in their expression upon HuR inhibition. These HuR-regulated genes function in multiple essential cellular molecular pathways, a finding that sets this therapeutic approach apart from other therapies that target a single gene. (more…)
Author Interviews, Erectile Dysfunction, Prostate, Prostate Cancer, Surgical Research, Urology / 29.02.2016

Medicalresearch.com Interview with: Dr. Pedro Recabal, MD and Memorial Sloan Kettering Cancer Center Department of Surgery, Urology Service New York, NY Urology service, Fundacion Arturo Lopez Perez, Santiago, Chile Dr. Vincent P. Laudone, Memorial Sloan Kettering Cancer Center Department of Surgery Urology Service New York, NY Medicalresearch.com What is the background for this study? Response:  One of the most concerning adverse events that may arise following surgery for prostate cancer (radical prostatectomy) is postoperative erectile dysfunction. The loss of erectile function after surgery is most frequently caused by intraoperative injury to the neurovascular bundles, tiny packages of blood vessels and nerves that conduct the impulses responsible for erection. It is known that if both bundles are removed, patients seldom recover erectile function. Accordingly, neurovascular bundle preservation during Radical prostatectomy has proven benefits in terms of erectile function recovery. However, as these bundles are intimately associated with the posterolateral aspects of the prostate, they must be carefully separated from the surface of the prostate without cutting them, applying excessive traction, or using cautery, all of which could produce irreversible damage and the consequent loss of function. During this dissection, the surgeon risks cutting into the prostatic capsule , which could result in leaving tumor behind. In some cases, the tumor extends beyond the prostate into the neurovascular bundles, and an attempt to preserve these structures could also result in incomplete tumor removal, defeating the purpose of radical prostatectomy. Therefore, many urologists treating patients with “aggressive” tumors (such as the patients in our cohort) would try to avoid leaving cancer behind by removing not only the prostate but also the tissue around it, including the neurovascular bundles. In other words, if you had to chose between removing all the cancer but loosing erectile function, or preserving erectile function but risking an incomplete cancer removal, most patients and surgeons naturally lean towards the first option. Also, in many centers, patients with aggressive prostate cancers are managed with combined treatments (multimodal therapy), by adding hormonal therapy and/or radiotherapy, which could also result in erectile dysfunction. As such, many surgeons believe that there is no rationale for attempting to preserve the neurovascular bundles in these “high-risk” patients because most will end up with erectile dysfunction . However, with the advent of MRI (and integrating other clinical information such as location of the positive biopsies, and intraoperative cues), surgeons can now have a better idea of where the cancer is located, which may aid in surgical planning. For instance, if a tumor is located in the anterior prostate, removing the neurovascular bundles (located on the posterolateral aspects) would provide no oncologic benefit, regardless of the aggressiveness of the tumor. Similarly, if the tumor compromises only the left side, removing the right neurovascular bundle is unlikely to help the patient, but can instead result in harm. Moreover, neurovascular bundle preservation is not an all-or-none procedure; on each side, these bundles can be completely preserved (meaning dissecting exactly along the border between the prostate and the bundle); partially preserved (meaning preserving some of the nerves that are further away from the prostate, and removing the ones that are closer to the prostate); or completely removed along with the prostate (This has been graded in a scale from 1 to 4, where 1 represents complete preservation, and 4 represents complete removal of the neurovascular bundle, with 2 and 3 being partial preservation. This grade is recorded by the surgeon for each side, at the end of the procedure.) As such, sometimes it’s possible to preserve part of the bundle, even if there is a tumor on the same side We designed a retrospective study to look at how high volume surgeons at MSKCC performed radical prostatectomy in high risk patients (how frequently and to what extent where the neurovascular bundles preserved), and what were the outcomes in terms of positive surgical margins (a surrogate for “leaving tumor behind”); use of additional oncologic treatments such as hormone therapy or radiotherapy, and finally, erectile function recovery in patients with functional erections before the operation. The patients in our cohort had at least one NCCN-defined high risk criteria (Gleason score ≥ 8; PSA ≥ 20 ng/ml; Clinical stage ≥ T3). (more…)
Author Interviews, Health Care Systems, JAMA, Outcomes & Safety / 29.02.2016

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Emergency Care, Infections, JAMA, Pediatrics, Pulmonary Disease, Respiratory / 29.02.2016

MedicalResearch.com Interview with: 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. (more…)
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. (more…)
Author Interviews, JAMA, Sexual Health / 29.02.2016

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Neurological Disorders, Stroke / 29.02.2016

MedicalResearch.com Interview with: Georgios Tsivgoulis , M.D., Ph.D., MSc, FESO Assistant Professor of Neurology University of Athens, Athens, Greece Visiting Associate Professor of Neurology Director of Stroke Research Department of Neurology University of Tennessee Health Science Center Medical Research: What is the background for this study? What are the main findings? Dr. Tsivgoulis: Literature data suggest that taking statins before an acute ischemic stroke may improve early outcomes including early neurological deterioration, mortality and disability in patients with acute ischemic stroke. However,the potential beneficial effect of statin pretreatment has never been investigated in acute ischemic stroke due to large artery atherosclerosis. The research question in this specific subgroup of ischemic stroke patients is of great importance, as large-artery atherosclerotic stroke carries the highest risk of early recurrent stroke in comparison to other acute ischemic stroke subtypes. Using prospectively collected data from over 516 consecutive patients with acute large-artery atherosclerotic stroke from seven tertiary-care stroke centers during a three-year period we found that statin pretreatment in patients with acute large-artery atherosclerotic stroke is associated with better early outcomes in terms of neurological improvement, disability, survival and stroke recurrence. (more…)
Author Interviews, Genetic Research, Sleep Disorders / 28.02.2016

MedicalResearch.com Interview with: Alice Gregory PhD Department of Psychology Goldsmiths, University of London London, UK Medical Research: What is the background for this study? What are the main findings? Dr. Gregory: Sleep paralysis involves a total inability to move just as someone is falling asleep or waking up. This experience typically ends within seconds to minutes and is not usually a sign of any wider problem – yet it can be extremely frightening. This is in part because this experience is often accompanied by hallucinations. To understand what is happening during episode of sleep paralysis it is useful to understand that there are different stages of sleep. One distinction is between Rapid Eye Movement (REM) and Non-Rapid Eye Movement (NREM) sleep. During REM sleep the body is paralysed. Dreaming often occurs during REM sleep, so it has been proposed that this paralysis keeps us safe, by preventing us from ‘acting out our dreams’. During an episode of sleep paralysis, someone may have woken up but has retained certain features of REM sleep (specifically the paralysis and sometimes dream-related hallucinations). While sleep paralysis is rather common and the public seem incredibly interested in learning more about this, it is surprising that there is such little research on this topic. Certain risk factors for sleep paralysis have been proposed previously, such as experiencing stress. However, those suffering from this experience are keen for more information, which is currently unavailable. For this reason, we wanted to see whether we could identify other factors which were associated with sleep paralysis. Furthermore, in reviewing the literature, we were stunned that while it seems obvious that genetic differences between people are likely to be important in explaining why certain people experience sleep paralysis and others do not – there was almost no work on this topic. We decided to investigate this further as well. (more…)
ASCO, Author Interviews, Breast Cancer, Cancer Research, University of Michigan / 28.02.2016

MedicalResearch.com Interview with: Sarah T. Hawley PhD MPH Professor of Medicine University of Michigan Medical Research: What is the background for this study? What are the main findings? Dr. Hawley: Research has shown that breast cancer patients do not have a good understanding of their risk of distant recurrence, and and that the fear of cancer spreading is one of the biggest concerns that patients have. The research that has been done shows that most patients over-esimate this risk, and think they have a bigger chance of the cancer coming back than they actually have. There has been relatively little done to investigate the association between patient over-estimation of risk and patient reported outcomes, specifically their quality of life. We therefore conducted our study to understand the extent of overestimation of risk in a population-based sample of breast cancer patients with very favorable prognosis (DCIS, low risk invasive breast cancer) using a numeric (number based) and descriptive (general understanding) measure, and to understand the association between over-estimation and quality of life. The main findings are that almost 40% of our sample of patients over-estimated their risk; 33% using a numeric measure and 15% using a descriptive measure. There was no clear “type” of patient who overestimated her risk of distant recurrence, though women with lower education more over overestimated numerically than those with higher education. Both numeric and descriptive over-estimation was associated with reduced quality of life outcomes, especially with frequency of worry about recurrence, however over estimating descriptively mattered the most. Women who overestimated their risk both numerically and descriptively had a nearly 10 fold odds of frequent worry compared to women who understood their risk. (more…)
Author Interviews, JAMA, Ophthalmology / 27.02.2016

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. (more…)