Author Interviews, BMJ, Brigham & Women's - Harvard, Education, Outcomes & Safety / 06.02.2017

MedicalResearch.com Interview with: Yusuke Tsugawa, MD, MPH, PhD Research Associate at Department of Health Policy and Management Harvard T.H. Chan School of Public Health   MedicalResearch.com: What is the background for this study? What are the main findings? Response: Prior evidence has been mixed as to whether or not patient outcomes differ between U.S. and foreign medical graduates. However, previous studies used small sample sizes or data from a small number of states. Therefore, it was largely unknown how international medical graduates perform compared with US medical graduates. To answer this question, we analyzed a nationally representative sample of Medicare beneficiaries admitted to hospitals with a medical condition in 2011-2014. Our sample included approximately 1.2 million hospitalizations treated by 40,000 physicians. After adjusting for severity of illness of patients and hospitals (we compared physicians within the same hospital), we found that patient treated by international medical graduates had lower mortality than patients cared for by US medical graduates (adjusted 30-day mortality rate 11.2% vs 11.6%, p<0.001). We observed no difference in readmissions, whereas costs of care was slightly higher for international medical graduates. (more…)
Author Interviews, Heart Disease, JAMA, Tobacco Research, UCLA / 01.02.2017

MedicalResearch.com Interview with: Holly R. Middlekauff, MD Professor UCLA Division of Cardiology David Geffen School of Medicine UCLA MedicalResearch.com: What is the background for this study? What are the main findings? Response: E-cigarettes are the fastest rising tobacco product in the US today, but almost nothing is known about their cardiovascular effects. Rather than wait decades for epidemiological data in e-cigarette users to become available, we reasoned that investigations into the known mechanisms by which tobacco cigarettes increase heart disease would provide insights into the health risks of e-cigarettes. We focused on 2 critical mechanisms: 1) cardiac adrenaline activity, and 2) oxidative stress, measured in chronic e-cigarrete users compared to matched, healthy controls. The major findings were that, compared to healthy controls, e-cig users had increased cardiac adrenaline activity (measured by a technique called "heart rate variability"). Furthermore, compared to healthy controls, the e-cig users had increased susceptibility to oxidative stress. (more…)
Author Interviews, Health Care Systems, Johns Hopkins / 01.02.2017

MedicalResearch.com Interview with: Chester G. Chambers, Ph.D. Director, Enterprise Risk Management Program, Johns Hopkins Carey Business School Joint Appointment in Anesthesiology and Critical Care Medicine Maqbool Dada, Ph.D. Joint Appointment in Anesthesiology and Critical Care Medicine John Hopkins Medicine Kayode Ayodele Williams, M.B.A., M.B.B.S., M.D Medical Director : Blaustein Pain Treatment Center Associate Professor of Anesthesiology and Critical Care Medicine John Hopkins Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: The result is based on a retrospective analysis of three specialty clinics in the Johns Hopkins System: a private practice low-volume clinic with one physician and no residents; a medium volume clinic that used one attending physician for each clinic session and included residents; and a high-volume clinic with multiple attending physicians and several residents. Our main finding is that physicians adjust face time based on congestion in the clinic, and seem to do this without always knowing they are doing it. Patients who arrive early and whose service begins before their appointment times, tend to get more face-time then other patients. This is similar to other service systems in which first-line providers speed-up when they see long queues at their stations.This is important because most of the prior research in this setting assumed that this never takes place. We verified that it does happen in multiple settings and the changes in processing rates are statistically significant. This means we need to rethink many earlier conclusions about how clinics run. (more…)
Author Interviews, Heart Disease, NEJM, NIH, Pediatrics / 30.01.2017

MedicalResearch.com Interview with: Victoria Pemberton, RNC, MS, CCRC Program Officer Division of Cardiovascular Sciences National Heart, Lung, and Blood Institute, NIH Bethesda, Maryland MedicalResearch.com: What is the background for this study? What are the main findings?
  • Previous studies have examined cardiac arrest when it occurs outside of the hospital in both children and adults, with current guidelines recommending hypothermia (body cooling) or normothermia (maintenance of normal body temperature) after such an arrest.   This trial addresses pediatric cardiac arrest in a hospital setting, for which no previous data existed. Because children who experience an in-hospital cardiac arrest differ significantly from children who arrest outside of the hospital, it is important to test these treatments in this population.
  • The trial found no significant differences in survival and neurobehavioral functioning a year after cardiac arrest between children assigned to the hypothermia arm and those assigned to normothermia.
(more…)
Author Interviews, Education, Neurological Disorders, Neurology, University of Pittsburgh / 30.01.2017

MedicalResearch.com Interview with: Neil A. Busis, M.D. University of Pittsburgh Physicians Department of Neurology Chief of Neurology, UPMC Shadyside Director of Community Neurology MedicalResearch.com: What is the background for this study? Response: Previous studies showed that neurologists have both one of the highest rates of burnout and the lowest rates of satisfaction with work-life balance, compared to other physicians. The mission of the American Academy of Neurology (AAN) is to promote the highest quality patient-centered neurologic care and enhance member career satisfaction. This is why AAN President Dr. Terrence Cascino initiated this research, to better define the issue. Our findings can guide current and future programs to prevent and mitigate neurologist burnout, promote neurologist career satisfaction and well-being, and direct efforts to advocate on behalf of neurologists and their patients. (more…)
Accidents & Violence, Addiction, Author Interviews, NIH, Opiods, Race/Ethnic Diversity / 27.01.2017

MedicalResearch.com Interview with: Dr Meredith S Shiels Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda, MD MedicalResearch.com: What is the background for this study? Response: In most high-income countries, premature death rates have been declining, due to the overwhelming successes of public health efforts to prevent and treat chronic disease. The US is a major outlier, where death rates overall have plateaued, or even increased, as reported recently by our sister agency, the Centers for Disease Control and Prevention. Of particular concern are recent reports of increasing death rates among Americans during mid-life. To expand upon prior findings, we focused on premature death, which we defined as death occurring between the ages of 25 and 64. We examined finely detailed death certificate data for the entire U.S. population and described changes in death rates during 1999-2014 by cause of death, sex, race, ethnicity, and geography. To provide context to our findings, we compared trends in death rates in the U.S. to England and Wales and Canada. (more…)
Author Interviews, Metabolic Syndrome, Psychological Science, University of Pennsylvania, Weight Research / 27.01.2017

MedicalResearch.com Interview with: Rebecca L. Pearl PhD Department of Psychiatry, Center for Weight and Eating Disorders Perelman School of Medicine University of Pennsylvania, Philadelphia, Pennsylvania MedicalResearch.com: What is the background for this study?  Response: Weight bias is a pervasive form of prejudice that leads to weight-based discrimination, bullying, and the overall stigmatization of obesity. Some individuals with obesity may internalize weight bias by applying negative weight stereotypes to themselves and “self-stigmatizing.” Exposure to weight bias and stigma increases risk for poor obesity-related health (in part by increasing physiological stress), but little is known about the relationship between weight bias internalization and risk for cardiovascular and metabolic diseases. (more…)
Author Interviews, BMJ, Endocrinology, Mayo Clinic, OBGYNE, Thyroid Disease / 27.01.2017

MedicalResearch.com Interview with: Dr. Spyridoula Maraka Assistant professor of medicine Division of Endocrinology and Metabolism Center for Osteoporosis and Metabolic Bone Diseases University of Arkansas for Medical Sciences and Central Arkansas Veterans Health Care System Little Rock Arkansas MedicalResearch.com: What is the background for this study? What are the main findings? Response: Subclinical hypothyroidism, a mild thyroid dysfunction, has been associated in pregnancy with multiple adverse outcomes. Our aim was to estimate the effectiveness and safety of thyroid hormone treatment among pregnant women with subclinical hypothyroidism. Using a large national US dataset, we identified 5,405 pregnant women diagnosed with subclinical hypothyroidism. Of these, 843 women, with an average pretreatment TSH concentration of 4.8 milli-international units per liter, were treated with thyroid hormone. The remaining 4,562, with an average pretreatment TSH concentration of 3.3 milli-international units per liter, were not treated. Compared with the untreated group, treated women were 38 percent less likely to experience pregnancy loss. However, they were more likely to experience a preterm delivery, gestational diabetes or preeclampsia. Moreover, the benefit of thyroid hormone treatment on pregnancy loss was seen only among women with higher TSH levels (4.1 to 10 mIU/L) before treatment. We also found that for women with lower levels of TSH (2.5–4.0 mIU/L), the risk of gestational hypertension was significantly higher for treated women than for untreated women. (more…)
Author Interviews, Diabetes, Heart Disease, JACC, Stanford / 27.01.2017

MedicalResearch.com Interview with: Fumiaki Ikeno M.D. Program Director (U.S.) Japan Biodesign Stanford Biodesign Medical Director/Research Associate Experimental Interventional Laboratory Division of Cardiology Stanford University MedicalResearch.com: What is the background for this study? What are the main findings? Response: We sought to determine whether the extent of coronary disease in terms of the number of lesions and their complexity in Type 2 Diabetes patients could predict major cardiovascular events, and hypothesized that revascularization would have greater effectiveness relative to medical therapy among patients with more number of lesions and higher complexity in coronary artery disease. Coronary bypass surgery, catheter-based treatment, and medical therapy all had similar cardiovascular outcomes among patients with less complexity of coronary artery disease who had type 2 diabetes mellitus, stable ischemic heart disease, and no prior coronary revascularization. Among patients with mid or high complexity coronary artery disease, coronary revascularization with bypass surgery significantly reduced the rate of major cardiovascular events during 5 years of follow-up. (more…)
Author Interviews, Autism, Brigham & Women's - Harvard, Gastrointestinal Disease, Microbiome / 26.01.2017

MedicalResearch.com Interview with: Maria Rosaria Fiorentino, PhD Assistant Professor at Harvard Medical School Molecular Biologist at Mucosal Immunology and Biology Research Center Massachusetts General Hospital East Charlestown, MA 02129-4404 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Autism Spectrum Disorders (ASD) refers to complex neurodevelopmental disorders arising from the interaction of genes and environmental factors. There are no defined mechanisms explaining how environmental triggers can lead to these conditions. One hypothesis based on the gut-brain axis connection suggests that inappropriate antigens trafficking through an impaired intestinal barrier, followed by passage of these antigens through a permissive blood-brain barrier (BBB), can be part of the chain of events leading to the disease. Many Autism Spectrum Disorders children experience co-morbid medical conditions, including gastrointestinal (GI) dysfunctions whose underlying nature is poorly understood. Several clinical observations describe increased intestinal permeability in ASD with often conflicting findings. Permeability to neuroactive food antigens derived from the partial digestion of wheat (gliadorphins) and cow’s milk (casomorphins) has been reported in ASD. However, while evidence of a permeable gut barrier in ASD is increasingly reported, no information is available concerning a similar breach for the BBB. The BBB is a critical line of defense in the Central Nervous System, limiting the access of circulating solutes, macromolecules, and cells that could negatively impact neuronal activity. Dysfunctions of the BBB have been associated with numerous inflammatory neurologic disorders, such as stroke, epilepsy, multiple sclerosis, Parkinson’s and Alzheimer’s disease. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Infections, JAMA, University of Pittsburgh / 26.01.2017

MedicalResearch.com Interview with: Sachin Yende, M.D., M.S., Associate professor University of Pittsburgh School of Medicine’s departments of Critical Care Medicine and Clinical and Translational and Vice president of Critical Care at the VA Pittsburgh. Florian B. Mayr, M.D., M.P.H. Faculty member in University of Pittsburgh Department of Critical Care Medicine and the Center for Health Equity Research and Promotion MedicalResearch.com: What is the background for this study? What are the main findings? Response: The Centers for Medicare and Medicaid Services and the Veteran Health Administration currently track readmission rates for pneumonia, acute heart attacks, heart failure and chronic obstructive lung disease for quality purposes and pay for performance. In our study, we were able to demonstrate that unplanned readmissions after sepsis (defined as life threatening organ failure due to the body's response to an overwhelming infection) are more common than readmission for these other conditions stated above and associated with significant excess costs. (more…)
Author Interviews, Brain Injury, Cost of Health Care, CT Scanning, Electronic Records, Emergency Care, Kaiser Permanente / 25.01.2017

MedicalResearch.com Interview with: Adam L. Sharp MD MS Research Scientist/Emergency Physician Kaiser Permanente Southern California Kaiser Permanente Research Department of Research & Evaluation Pasadena, CA 91101 MedicalResearch.com: What is the background for this study? Response: Millions of head computed tomography (CT) scans are ordered annually in U.S. emergency Departments (EDs), but the extent of avoidable imaging is poorly defined. Ensuring appropriate use is important to ensure patient outcomes and limited resources are optimized. A large number of stake holders have highlighted the need to reduce “unnecessary” CT scanning as part of their recommendations for the Choosing Wisely campaign. However, despite calls for improved stewardship, the extent of avoidable CT use among adults with minor trauma in community EDs is not known. The Canadian CT Head Rule (CCHR) is perhaps the most studied of many validated decision instruments designed to assist providers in evaluating patients with minor head trauma. This study aims to describe the scope of overuse of CT imaging by ED providers in cases where application of the CCHR could have avoided imaging. Secondarily, we sought to describe the extent to which avoidable CTs, if averted, would have resulted in “missed” intracranial hemorrhages requiring a neurosurgical intervention. (more…)
Author Interviews, Baylor College of Medicine Houston, OBGYNE, Outcomes & Safety / 25.01.2017

MedicalResearch.com Interview with; Dr. Amirhossein Moaddab Postdoctoral Research Fellow at Baylor College of Medicine Houston, Texas MedicalResearch.com: What is the background for this study? Response: Based on data from the Centers for Disease Control and Prevention, the United States maternal mortality ratio is three to four times higher than that of most other developed nations. Previous studies from the demonstrated a possible association between weekend hospital admissions and higher rates of mortality and poor health outcomes. We investigated differences in maternal and fetal death ratios on weekends compared to weekdays and during different months of the year. In addition we investigated the presence of any medical and obstetrics complications in women who gave birth to a live child and in their offspring by day of delivery. (more…)
ASCO, Author Interviews, Brigham & Women's - Harvard, Colon Cancer, Exercise - Fitness / 21.01.2017

MedicalResearch.com Interview with: Brendan John Guercio, M.D. Clinical Fellow in Medicine (EXT) Brigham and Women's Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Response: Sedentary lifestyle is a known risk factor for the development of colon cancer and has been associated with increased disease recurrence and mortality in patients with early stage colorectal cancer. This is the first study to our knowledge to show an association between increased physical activity (i.e. non-sedentary lifestyle) and improved survival and progression-free survival in patients with metastatic colorectal cancer. (more…)
Author Interviews, Dermatology, University of Pittsburgh / 20.01.2017

MedicalResearch.com Interview with: Westley Mori, fourth-year medical student (MSIV) University of Pittsburgh Medical School MedicalResearch.com: What is the background for this study? What are the main findings? Response: Tattooed skin represents an important diagnostic challenge for the dermatologist performing a skin cancer screening. Several case reports have described melanoma being hidden in tattoos. To our knowledge, our study is the first of its kind investigating the approach of the tattoo artist to skin with melanocytic nevi (moles) or other skin lesions. We found that the approach to tattooing skin spots is highly variable, with some artists tattooing around moles and others simply tattooing over them. The final cosmetic outcome—not the potential for skin cancer—is often the paramount concern for artists. Those artists with a personal or family history of skin cancer were more likely to refuse inking over a skin spot and recommend the client see a dermatologist. (more…)
Author Interviews, NIH, Nutrition, Weight Research / 20.01.2017

MedicalResearch.com Interview with: Janet M. de Jesus, M.S., R.D. Program Officer, Implementation Science Center for Translation Research and Implementation Science (CTRIS) National Heart, Lung, and Blood Institute MedicalResearch.com: What is the background for the DASH diet? What are the main components? Response: The DASH eating plan was created for a clinical trial funded by the National Heart, Lung, and Blood Institute (NHLBI). DASH stands for Dietary Approaches to Stop Hypertension. The goal of the original DASH trial was to test the eating plan compared to a typical American diet (at the time in the 1990s) on the effect of blood pressure. The DASH eating plan is rich in fruits, vegetables, and whole grains. It includes low-fat dairy products, poultry, fish, legumes, vegetable oils, and nuts; and limits intake of sweets and sugar-sweetened beverages and high-fat meats. The eating plan is a good source of potassium, magnesium, and calcium. The DASH eating plan was shown to reduce blood pressure and improve lipid profiles. A second DASH trial, “DASH-sodium,” showed that adding sodium reduction to the DASH eating plan reduced blood pressure even more. (more…)
Author Interviews, Cost of Health Care, JAMA, Johns Hopkins, Medicare / 17.01.2017

MedicalResearch.com Interview with: Ge Bai, PhD, CPA Assistant Professor The Johns Hopkins Carey Business School Washington, DC 20036  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The average anesthesiologist, emergency physician, pathologist and radiologist charge more than four times what Medicare pays for similar services, often leaving privately-insured out-of-network patients stuck with surprise medical bills that are much higher than they anticipated. The average physician charged roughly 2.5 times what Medicare pays for the same service. There are also regional differences in excess charges. Doctors in Wisconsin, for example, have almost twice the markups of doctors in Michigan (3.8 vs. two). (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Emory, Neurological Disorders / 17.01.2017

MedicalResearch.com Interview with: Andres Rodriguez Ruiz, MD Clinical Neurophysiology and Neurology Emory School of Medicine MedicalResearch.com: What is the background for this study? Response: The Critical Care EEG monitoring research consortium (CCEMRC) was established with the goal of promoting collaboration and research among healthcare institutions highly involved in continuous EEG monitoring of critically ill patients. This group together with the American Clinical Neurophysiology Society (ACNS) established the standardized critical care EEG terminology that allowed uniform reporting of EEG findings in critically ill patients. As part of this effort, a database was developed for collection and clinical reporting of such EEG findings and was adopted for daily clinical use by Yale University, Emory University and Brigham and Women's Hospital. Prior retrospective reports have acknowledged an association between periodic discharges and seizures. However, many of these reports were small series and did not include specific characteristics of these patterns. Our goal was to ascertain whether features of periodic and rhythmic patterns such as location (generalized vs. lateralized), frequency and prevalence influenced seizure risk in a large cohort of critically ill adults. (more…)
Anemia, Author Interviews, Kidney Disease, Pharmacology, Stanford / 16.01.2017

MedicalResearch.com Interview with: Dr. Glenn M. Chertow, MD Professor Medicine, Nephrology Stanford University School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: Iron deficiency is common in persons with moderate to advanced (non-dialysis-dependent) chronic kidney disease (CKD), for a variety of reasons. Conventional iron supplements tend to be poorly tolerated and of limited effectiveness. In earlier studies of patients treated with ferric citrate for its effect as a phosphate binder, we saw increases in transferrin saturation and ferritin (markers of iron stores) and hemoglobin and hematocrit (the “blood count”). Therefore, we thought we should test the safety and efficacy of ferric citrate specifically for the treatment of iron deficiency anemia (IDA). With respect to the key findings, more than half (52%) of patients treated with ferric citrate experienced a sizeable (>=1 g/dL) increase in hemoglobin over the 16-week study period compared to fewer than one in five (19%) patients treated with placebo. Rates of adverse events (“side effects”) were similar to placebo; diarrhea in some patients and constipation in others were the most common. There were also favorable effects of ferric citrate on laboratory metrics of bone and mineral metabolism. (more…)
Author Interviews, BMJ, Brigham & Women's - Harvard, Pain Research, Stroke / 13.01.2017

MedicalResearch.com Interview with: Dr. Matthias Eikermann, MD, PhD Associate Professor of Anaesthesia Harvard Medical School Clinical Director, Critical Care Division  MedicalResearch.com: What is the background for this study? Response: Up to one fifth of the general population have migraine, a primary, chronic-intermittent headache disorder affecting the neuronal and vascular systems and characterized by severe headache accompanied by nausea and/or sensory hypersensitivities such as photophobia and phonophobia. In approximately 20-30% of patients, the headache phase is preceded or accompanied by transient focal neurological disturbances presenting as visual symptoms but also sensory, aphasic, or motor symptoms known as migraine aura. Stroke is responsible for approximately 6.2 million deaths a year and is a leading global cause of long term disability. Considering that more than 50 million patients in hospital and 53 million ambulatory patients undergo surgical procedures in the United States every year. We found that patients with migraine, particularly migraine with aura, undergoing a surgical procedure are at increased risk of perioperative ischemic stroke and readmission to hospital within 30 days after discharge. (more…)
Author Interviews, Brigham & Women's - Harvard, Heart Disease, Lancet, Medical Imaging, MRI, Social Issues / 12.01.2017

MedicalResearch.com Interview with: Dr Ahmed Tawakol MD Co-Director, Cardiac MR PET CT Program Massachusetts General Hospital and Harvard Medical School  MedicalResearch.com: What is the background for this study? What are the main findings? Response: While the link between stress and heart disease has long been established, the mechanism mediating that risk hasn’t been clearly understood. Animal studies showed that stress activates bone marrow to produce white blood cells, leading to arterial inflammation.  This study suggests an analogous path exists in humans. Moreover, this study identifies, for the first time in animal models or humans, the region of the brain (the amygdala) that links stress to the risk of heart attack and stroke. The paper reports on two complementary studies. The first analyzed imaging and medical records data from almost 300 individuals who had PET/CT brain imaging, primarily for cancer screening, using a radiopharmaceutical called FDG that both measures the activity of areas within the brain and reflects inflammation within arteries.  All participants in that study had no active cancer or cardiovascular disease at the time of imaging and each had information in their medical records on at least three additional clinical visits after imaging. The second study enrolled 13 individuals with a history of post-traumatic stress disorder, who were evaluated for their current levels of perceived stress and received FDG-PET scanning to measure both amygdala activity and arterial inflammation. (more…)
Accidents & Violence, Author Interviews, Pediatrics, University of Pennsylvania / 12.01.2017

MedicalResearch.com Interview with: Daniel Romer, PhD Annenberg Public Policy Center University of Pennsylvania Philadelphia, Pennsylvania MedicalResearch.com: What is the background for this study? What are the main findings? Response: We have been studying trends in health compromising behaviors in popular films that were released since 1950, and in 2013 we reported that films rated PG-13 had just passed the rate of portrayed gun violence shown in popular R-rated films in 2012. In this report, we updated the trends in gun violence through 2015 and found that the trend has continued. In addition, we noted the strong contribution to this trend of films with comic book heroes whose heavy use of guns omits the harmful and otherwise realistic consequences of blood and suffering. (more…)
Author Interviews, Brigham & Women's - Harvard, Heart Disease, JACC, Surgical Research / 10.01.2017

MedicalResearch.com Interview with: Deepak L. Bhatt, MD, MPH, FACC, FAHA, FSCAI, FESC Executive Director of Interventional Cardiovascular Programs, Brigham and Women’s Hospital Heart & Vascular Center Professor of Medicine, Harvard Medical School Boston, MA 02115 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Cangrelor is a potent, fast on, fast off, intravenous ADP receptor antagonist that is now available for use during PCI. Glycoprotein IIb/IIIa inhibitors are intravenous antiplatelet agents that work by a different mechanism. Doctors have asked whether there is any advantage to combining them or whether one class is preferable to the other during PCI. We analyzed close to 25,000 patients from the CHAMPION trials. Cangrelor’s efficacy in reducing peri-procedural ischemic complications in patients undergoing PCI was present irrespective of glycoprotein IIb/IIIa inhibitor administration. However, glycoprotein IIb/IIIa inhibitor use resulted in substantially higher bleeding rates, regardless of whether the patient was randomized to cangrelor or to clopidogrel. Thus, in general, cangrelor and glycoprotein IIb/IIIa inhibitors should not routinely be combined. If an operator wishes to use a potent intravenous antiplatelet during PCI, cangrelor is similarly efficacious as glycoprotein IIb/IIIa inhibitors, but with less bleeding risk. (more…)
Author Interviews, Baylor College of Medicine Houston, Genetic Research, NEJM / 09.01.2017

MedicalResearch.com Interview with: Jennifer E Posey MD, PhD Assistant Professor Department of Molecular and Human Genetics Baylor College of Medicine Tamar Harel MD, PhD Clinical Genetics Academic Research Fellow Department of Molecular and Human Genetics Baylor College of Medicine Current affiliation: Department of Genetic and Metabolic Diseases Hadassah-Hebrew University Medical Center Jerusalem, Israel MedicalResearch.com: What is the background for this study? What are the main findings? Response: As physician scientists and geneticists, our goal is to understand how genetic variation in each of us can impact health and disease. Physicians are often taught that the simplest explanation for a medical condition is the most correct explanation, and have historically searched for a single unifying diagnosis. However, in our own practice, we have met – and learned from – individuals who have more than one genetic condition affecting their health. In the past, it was difficult for physicians to diagnose such individuals. Genetic testing required a physician to recognize the potential for more than one genetic diagnosis in an individual. Single-gene and gene panel testing provided an additional barrier to accurate diagnoses, as they are more narrow in scope, and more than one molecular test was often needed to identify all conditions. Targeted testing also required a physician to accurately pre-suppose which combination of genetic conditions was most likely, and choose the correct targeted tests. The clinical availability of whole exome sequencing (WES) has removed these barriers: WES is a broad-based, unbiased analysis of an individual’s genetic variation that does not pre-suppose a specific genetic cause. If analysis is pursued systematically, WES can identify more than one genetic diagnosis in an individual, even when not suspected. In our study, we have been able to assess the frequency with which individuals can have more than one genetic diagnosis, and have begun to understand how genetic variation at more than one place in the genome can affect how a condition may present. We found that among 7,374 individuals referred for WES, 2,076 (28%) had a molecular diagnosis. Of these 2,076, 5% had two, three, or four molecular diagnoses. In our analyses of the clinical features that may be observed in an individual with two genetic conditions, we found that pairs of diagnoses with overlapping clinical features may be incompletely diagnosed as having one or the other condition, and pairs of diagnoses with very distinct clinical features may be erroneously diagnosed in the clinic as having an entirely new condition. (more…)
Abuse and Neglect, Genetic Research, Schizophrenia, UCSD / 06.01.2017

MedicalResearch.com Interview with: Brian P. Head, MS, PhD Associate Professor, UCSD Research Scientist, VASDHS Department of Anesthesiology VA San Diego Healthcare System San Diego, CA 92161-9125 MedicalResearch.com: What is the background for this study? What are the main findings? Response: DISC1 is a schizophrenia associated gene originally identified in a Scottish family. DISC1 protein is highly expressed in the developing brain and in the dentate gyrus of the adult hippocampus, and is involved in neuritogenesis and neuronal signaling. DISC1 is located in multiple intracellular locations including axons and synapses, and loss of DISC1 function causes deficits in neural development, neuronal proliferation, axonal growth, and cytoskeleton modulation, which are consistent with abnormal neural development in schizophrenia. SynCav1 means synapsin-driven caveolin construct. Synapsin promoter is neuronal specific which allows us to increase caveolin expression-specifically in neurons. We have previously shown that SynCav1 increases neuronal signaling and dendritic growth and arborization in vitro (Head BP JBC 2011), and when delivered in vivo augments functional neuroplasticity and improves learning and memory in adult and aged mice (Mandyam CD Biol Psych 2015). Since loss of DISC1 function equates to schizophrenic-like symptoms, then decreased DISC1 expression in Cav-1 KO mice agrees with this premise. Thus, loss of Cav-1 increases their likelihood of developing schizophrenia-like symptoms. Because re-espression of Cav-1 restored DISC1 expression as well as expression of key synaptic proteins, this proof-of-concept findings not only builds upon our previously results demonstrating that Cav-1 is critical for neuronal signaling and functional synaptic plasticity but also strongly links Cav-1 with maintaining normal DISC1 expression levels and potentially attenuating schizophrenia-like symptoms. (more…)
Author Interviews, Cost of Health Care, JAMA, Medicare, Orthopedics, University of Pennsylvania / 06.01.2017

MedicalResearch.com Interview with: Amol Navathe, MD PhD University of Pennsylvania Staff Physician, CHERP, Philadelphia VA Medical Center Assistant Professor of Medicine and Health Policy, Perelman School of Medicine Senior Fellow, Leonard Davis Institute of Health Economics, The Wharton School Co-Editor-in-Chief, HealthCare: the Journal of Delivery Science and Innovation MedicalResearch.com: What is the background for this study? Response: Bundled payments pay a fixed price for an episode of services that starts at hospital admission (in this case for joint replacement surgery) and extends 30-90 days post discharge (30 days in this study). This includes physician fees, other provider services (e.g. physical therapy), and additional acute hospital care (hospital admissions) in that 30 day window. (more…)
Allergies, Author Interviews, NIH, Pediatrics / 05.01.2017

MedicalResearch.com Interview with: Anna Nowak-Wegrzyn, MD Associate Professor of Pediatrics Icahn School of Medicine at Mount Sinai Jaffe Food Allergy Institute New York, NY 10029 MedicalResearch.com: What is the background for this study? Response: Peanut allergy can be fatal, is usually life-long and has no cure. Considering a dramatic increase in prevalence of peanut allergy over the past decades, affecting estimated 2-3% of infants and young children in the US, there is a dire need for prevention. Prior studies determined that risk of peanut allergy is highest in the infants with severe eczema, those with mutations in filaggrin gene resulting in an impaired skin barrier function and those not eating peanut but exposed to peanut in the household dust. In addition, the prevalence of peanut allergy was 10-fold higher among Jewish children in the United Kingdom compared with Israeli children of similar ancestry. In Israel, peanut-containing foods are usually introduced in the diet when infants are approximately 7 months of age and consumed in substantial amounts, whereas in the United Kingdom children do not typically consume any peanut-containing foods during their first year of life. Based on these observations, a landmark clinical trial (Learning Early about Peanut Allergy, LEAP) has been designed to evaluate whether early introduction of peanut into the diet of infant considered at high risk for peanut allergy can reduce the risk of peanut allergy compared to avoidance of peanut. LEAP and other studies suggested that peanut allergy can be prevented by introduction of peanut-containing foods in infancy. The overall reduction in peanut allergy among the infants in the LEAP trial randomized to an early introduction group compared to those who avoided peanut until age 5 years was 81%. (more…)