Author Interviews, Geriatrics, Heart Disease, Personalized Medicine, UCLA / 12.12.2017 Interview with: Joseph A. Ladapo, MD, PhD Principal Substudy Investigator, PRESET Registry Subgroup Analysis, Elderly Patients Associate Professor, Division of General Internal Medicine and Health Services Research David Geffen School of Medicine University of California, Los Angeles What is the background for this study?  Response: The mapping of the Human Genome 14 years ago ushered in a new era of precision medicine. Many people are familiar with advances in oncology using precision medicine, but recently, new developments in precision medicine in cardiology have allowed us to develop a tool to differentiate patients likely to have obstructive coronary artery (CAD) from those who have non-cardiac causes of their symptoms. Diagnosing CAD in the elderly is challenging. Aging individuals often present with atypical symptoms of CAD which can complicate the evaluation process. The typical diagnostic pathway for possible CAD often starts with less invasive testing and progresses to invasive testing, especially in older patients. Invasive procedures pose greater risk in the elderly population than they do in younger patients because of the higher risk of side effects, including bleeding, vascular complications and kidney injury. Elderly adults evaluated for CAD have a higher pretest probability of CAD and are also at higher risk of experiencing procedure-related complications during their evaluation.[i],[ii] It is also important to note that elderly patients are often underrepresented in clinical trials and other types of comparative effectiveness research.[iii],[iv] For example, the 2013 American College of Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease Risk Algorithm is only formally approved to be used in individuals up to the age of 75, despite the fact that individuals exceeding this threshold in age experience higher rates of adverse cardiovascular events.[v] All of this means that the elderly population may have the most to gain from timely and accurate determination of their currently likelihood of obstructive CAD. This precision medicine tool, the age, sex and gene expression score (ASGES), and its clinical utility in the elderly population is the focus of this study. It was based on patient data from the PRESET Registry, a prospective, multicenter, observational study enrolling stable, symptomatic outpatients from 21 U.S. primary care practices from August 2012 to August 2014. (more…)
Author Interviews, Geriatrics, Heart Disease, JACC, UCLA / 14.11.2017 Interview with: Kevin S. Shah, M.D. Cardiology Fellow, University of California, Los Angeles Ronald Reagan UCLA Medical Center What is the background for this study? What are the main findings? Response: Heart failure (HF) is a chronic condition and progressive disease which is associated with a high-risk of hospitalization and death. One of the principle ways in which heart function is estimated is the use of ultrasound to calculate the ejection fraction of the heart, an estimate of the heart’s pump function. The ejection fraction can help predict how long patients will live and affects decision-making with regards to what medications may help their condition. A total of 39,982 patients from 254 hospitals who were admitted for Heart failure between 2005 and 2009 were included. They were followed over time to see if they were admitted to the hospital again or if they died during this period. We compared three subgroups within this large group of patients based on their estimated ejection fraction. Across subgroups, the 5-year risk of hospitalization and death was high when compared with the U.S. population. Furthermore, the survival for patients with a diagnosis of heart failure who have been hospitalized once for this condition have a similarly poor 5-year risk of death and re-hospitalization, regardless of their estimated ejection fraction. (more…)
Author Interviews, Heart Disease, NEJM, UCLA / 05.11.2017 Interview with: Bruno Péault PhD Professor and Chair, Vascular Regeneration Center For Cardiovascular Science MRC Centre for Regenerative Medicine Scientific Director, BHF Laboratories The University of Edinburgh and Professor, David Geffen School of Medicine at UCLA Orthopaedic Hospital Research Center University of California at Los Angeles Los Angeles, CA 90095-7358 What is the background for this study? Response: Kidney, lung, liver, muscle, heart are among the many organs which can be severely affected by fibrosis, a natural scarring process whereby healthy tissues are replaced by a fibrous non-functional substitute. For instance, the billions of cardiac muscle cells that die after a heart infarct, consequently to blood supply interruption, are replaced by a fibrotic scar that cannot contract, reducing the capacity of the heart to pump blood, and leading often to heart failure. There is currently no efficient treatment of fibrotic scars, the basic cellular component of which is the myofibroblast, a cell of unremarkable appearance and unclear origin. The transforming growth factor β (TGFβ) molecule triggers fibrosis development after being activated, via the extra-cellular matrix, by αv integrins, which are adhesion molecules present at the surface of the target cells. To gain further insight into the cells that drive fibrosis in the heart and skeletal muscle, and explore ways to control this deleterious process, mice were used in which cells expressing the β receptor for PDGF (platelet derived growth factor) have been genetically tagged with a green fluorescent protein, a system previously used by Prof. Neil Henderson to trace fibrosis in the diseased liver (cells naturally expressing PDGFRβ are, in their vast majority, perivascular cells surrounding small blood vessels, as well as some interstitial fibroblasts). Skeletal muscle was injured by a small incision or with a targeted injection of cardiotoxin, a snake venom compound that locally kills myofibers, while the heart was damaged by prolonged infusion of angiotensin II. In both settings, progression of fibrosis was followed over time and contribution of green fluorescent cells – i.e. those expressing PDGFRβ – was assessed. (more…)
Author Interviews, JAMA, Menopause, Ophthalmology, UCLA / 31.10.2017 Interview with: Anne L. Coleman, MD, PhD Center for Community Outreach and Policy, Stein Eye Institute David Geffen School of Medicine Director, UCLA Mobile Eye Clinic Department of Epidemiology, Fielding School of Public Health UCLA What is the background for this study? Response: Cataracts are a leading cause of vision loss worldwide, and cataract surgery is an intervention that is known to be extremely effective to address the vision loss related to cataract. However, it is unclear if there are benefits of cataract surgery beyond vision improvement in people with cataracts. Previous studies have suggested that in addition to improving vision, cataract surgery may decrease the risk of fractures and accidents, improve mental health, and improve overall quality of life. The purpose of the present study was to further investigate the potential benefits of cataract surgery and to determine if cataract surgery was associated with increased survival in people with cataracts. (more…)
Author Interviews, Heart Disease, JAMA, Lipids, UCLA / 28.08.2017 Interview with: Gregg C. Fonarow, MD, FACC, FAHA Eliot Corday Professor of Cardiovascular Medicine and Science Director, Ahmanson-UCLA Cardiomyopathy Center Co-Chief of Clinical Cardiology, UCLA Division of Cardiology Co-Director, UCLA Preventative Cardiology Program David Geffen School of Medicine at UCLA Los Angeles, CA What is the background for this study? What are the main findings? Response: The study identifies the clinical and economic consequences of treating a population of patients with established atherosclerotic cardiovascular disease (ASCVD ) at high-risk of cardiovascular (CV) events and defines the cost-effectiveness of the PCSK-9 inhibitor evolocumab under various clinical scenarios. The analysis is based on the clinical outcomes from the Repatha Outcomes Study (FOURIER) in patients with established atherosclerotic cardiovascular disease (ASCVD), such as those who have already had a heart attack or stroke who require additional therapy. This is the first cost-effectiveness assessment of evolocumab using a model based on a high-quality outcomes trial, combined with U.S. clinical practice data. The analysis identifies the types of high-risk patients for whom this therapy is both clinically beneficial and cost-effective. This study utilized cost-effectiveness and value thresholds employed by the World Health Organization and the American College of Cardiology/American Heart Association. Evolocumab was found to exceed generally accepted cost-effectiveness thresholds at current list price. However, this medication could be a cost-effective treatment for patients with established ASCVD in the U.S. when the net price is at or below $9,669 per year. (more…)
AHA Journals, Author Interviews, Genetic Research, Heart Disease, Lipids, UCLA / 28.08.2017 Interview with: Tamer Sallam, MD PhD Assistant Professor of Medicine Co-Director UCLA Center for Lipid Management Lauren B. Leichtman and Arthur E. Levine CDF Investigator Assistant Director, STAR Program Division of Cardiology, Department of Medicine David Geffen School of Medicine at UCLA Los Angeles, California 90095-1679 What is the background for this study? What are the main findings? Response: This study is extension of our previous work published in Nature showing that a gene we named LeXis (Liver expressed LXR induced sequence) plays an important role in controlling cholesterol levels. What is unique about  LeXis is that it belongs to a group of newly recognized mediators known as long noncoding RNAs. These fascinating factors were largely thought to be unimportant and in fact referred to as “junk DNA” prior the human genome project but multiple lines of evidence suggest that they can be critical players in health and in disease. In this study we tested whether we can use  LeXis “gene therapy”  to lower cholesterol and  heart disease risk. This type of approach is currently approved or in testing for about 80 human diseases. Our finding was that a single injection of LeXis compared with control significantly  reduced heart disease burden in mouse subjects. Although the effect size was moderate we specifically used a model that mimics a very challenging to treat human condition known as familial hypercholesterolemia..Familial hypercholesterolemia is one of the most common genetic disorders affecting up to 2 million Americans and characterized by 20 fold  fold increase risk of early heart attacks and often suboptimal response to currently available treatments. (more…)
Author Interviews, Education, JAMA, UCLA / 22.08.2017 Interview with: Christian de Virgilio, MD LA BioMed lead researcher and corresponding author for the study He also is the former director of the general surgery residency program Harbor-UCLA Medical Center and the recipient of several teaching awards. What is the background for this study? What are the main findings? Response: Recent forecasts have predicted the United States will have a deficit of as many as 29,000 surgeons by 2030 because of the expected growth in the nation’s population and the aging of the Baby Boomers. This expected shortfall in surgeons has made the successful training of the next generation of surgeons even more important than it was before. Yet recent studies have shown that as many as one in five general surgery residents leave their training programs before completion to pursue other specialties. Our team of researchers studied 21 training programs for general surgeons and published our findings in the Journal of the American Medical Association Surgery (JAMA Surgery) on August 16, 2017. What we found was the attrition rate among residents training in general surgery was lower than previously determined – just 8.8% instead of 20% – in the 21 programs we surveyed. Our study also found that program directors’ attitudes and support for struggling residents and resident education were significantly different when the authors compared high- and low-attrition programs. General surgeons specialize in the most common surgical procedures, including abdominal, trauma, gastrointestinal, breast, cancer, endocrine and skin and soft tissue surgeries. General surgery residency training follows medical school and generally requires five to seven years. The programs are offered through universities, university affiliated hospitals and independent programs. In this study, the research team surveyed 12 university-based programs, three program affiliated with a university and six independent programs. In those programs, 85 of the 966 general surgery residents failed to complete their training during the five-year period the research team studied, July 1, 2010 to June 30, 2015. Of those who failed to complete their general surgery training, 15 left during the first year of training; 34 during the second year, and 36 during the third year or later. Notably, we found a nearly seven-fold difference between the training program with the lowest attrition rate, 2.2%, and the one with the highest rate, 14.3%, over the five-year period surveyed. In the programs with lower attrition rates, we found about one in five residents received some support or remediation to help ensure they would complete their In the programs with higher attrition rates, the research team reported that only about one in 15 residents received such remediation. (more…)
Author Interviews, Education, Heart Disease, JAMA, Lifestyle & Health, Primary Care, UCLA / 28.07.2017 Interview with: Carol M. Mangione, MD, MSPH, FACP Barbara A. Levey, MD, and Gerald S. Levey, MD Endowed chair in medicine David Geffen School of Medicine University of California, Los Angeles Professor of public health at the UCLA Fielding School of Public Health What is the background for this study? Response: Americans can experience several health benefits from consuming healthy foods and engaging in physical activity. The Task Force recommends that primary care professionals work together with their patients when making the decision to offer or refer adults who are not obese and do not have hypertension, high cholesterol, high blood sugar, or diabetes to behavior counseling to promote healthful diet and physical activity. Our focus was on the impact of a healthful diet and physical activity on cardiovascular risk because this condition is the leading cause of premature morbidity and mortality. The Task Force evaluates what the science tells us surrounding the potential benefits and harms of a particular preventive service. In this case, the Task Force found high quality evidence focusing on the impact a healthful diet and physical activity can have on a patient’s risk of cardiovascular disease. Relying on this evidence, the Task Force was able to conclude that there is a positive but small benefit of behavioral counseling to prevent cardiovascular disease. (more…)
Author Interviews, Infections, JAMA, UCLA / 31.05.2017 Interview with: Gregory John Moran, MD, FACEP Emergency Medicine Dept. & Infectious Diseases Service UCLA Medical Center What is the background for this study? What are the main findings? Response: The bacterial etiology of cellulitis is difficult to determine because there is usually no material for culture, but streptococci are believed to be the most common etiology. Since the emergence of MRSA as a common cause of skin infections in the community, many clinicians add a second antibiotic with MRSA activity to an oral cephalosporin, such as a combination of cephalexin plus trimethoprim-sulfamethoxazole. It is unknown if there is an additional benefit to adding MRSA activity for treatment of cellulitis. This randomized, blinded trial compared cephalexin plus placebo to cephalexin plus trimethoprim-sulfamethoxazole for outpatient treatment of cellulitis without an abscess or wound. Bottom line: We did not find a benefit from addition of trimethoprim-sulfamethoxazole. (more…)
Author Interviews, Autism, Genetic Research, Schizophrenia, UCLA / 26.05.2017 Interview with: Carrie Bearden, Ph.D. Professor, Departments of Psychiatry and Biobehavioral Sciences and Psychology Semel Institute for Neuroscience and Human Behavior University of California, Los Angeles What is the background for this study? What are the main findings? Response: A 22q11.2 deletion confers the highest known genetic risk for schizophrenia, but a duplication in the same region is strongly associated with autism and is less common in schizophrenia cases than in the general population. Thus, we became interested in trying to understand whether there were differences in brain development that might predispose to one condition vs. the other. (more…)
Author Interviews, Infections, UCLA / 22.05.2017 Interview with: Dr. James A. McKinnell, MD LA BioMed Assistant Professor of Medicine David Geffen School of Medicine at UCLA What is the background for this study? Response: Pneumonia is the leading cause of death from infectious disease in the United States. We conducted this study because current community-acquired pneumonia guidelines from the American Thoracic Society and the Infectious Disease Society America, published in 2007, provide some direction about prescribing antibiotics for community-acquired pneumonia. But large-scale, real-world data are needed to better understand and optimize antibiotic choices and to better define clinical risk factors that may be associated with treatment failure. Antibiotic failure for community-acquired pneumonia is associated with substantial morbidity and mortality and results in significant medical expenditures. We examined databases containing records for 251,947 adult patients who were treated between 2011 and 2015 with a single class of antibiotics (beta-lactam, macrolide, tetracycline, or fluoroquinolone) following a visit to their physician for treatment for community-acquired pneumonia. We defined treatment failure as either the need to refill antibiotic prescriptions, antibiotic switch, ER visit or hospitalization within 30 days of receipt of the initial antibiotic prescription. (more…)
Author Interviews, Gender Differences, UCLA, Weight Research / 22.05.2017 Interview with: Arpana Gupta, Ph.D. Assistant Professor G. Oppenheimer Center for Neurobiology of Stress and Resilience Ingestive Behavior and Obesity Program Vatche and Tamar Manoukin Division of Digestive Diseases David Geffen School of Medicine, UCLA What is the background for this study? Response: Past studies have demonstrated how an imbalance in the processing of rewarding and salient stimuli results in maladaptive or excessive eating behaviors. However, stress and drug use are known to affect how sex and sex hormones modulate responses of the dopamine system involved in reward, and are thought to underlie sex differences in the pathophysiology of drug addiction and treatment response. These results suggest similar sex effects on the mesolimbic reward system may also be at play in obesity. (more…)
Author Interviews, JAMA, Pharmacology, UCLA / 03.05.2017 Interview with: Ian Larkin, PhD Assistant Professor of Strategy UCLA Anderson School of Management What is the background for this study? Response: The study examined whether restrictions put in by medical centers on salesperson visits to physicians, known as “detailing,” affected subsequent physician prescribing behavior. Detailing represents the most prominent form of pharmaceutical marketing. Detailing visits allow the sharing of scientific information, but they also often involve small gifts for physicians and their staff, such as meals. Pharmaceutical companies incur far greater expenditures on detailing visits than they do on direct-to-consumer marketing, or even on research and development of new drugs. Specifically, the study examined detailing restrictions put into place by 19 academic medical centers (AMCs) in five states in the U.S. It compared changes in prescribing by thousands of AMC physicians whose practices limited typical elements of detailing visits, such as provisions of meals and educational gifts, to a carefully matched control group of similar physicians practicing in the same geographic regions but not subject to such detailing restrictions. The study, which included more than 25,000 physicians and all 262 drugs in eight major drug classes — from statins to sleep aids to antidepressants, representing more than $60 billion in aggregate sales in the United States — was, to date, by far the most comprehensive to examine the impact of detailing restrictions. The comprehensive and quasi-experimental methodology, which compared prescribing behavior before and after implementation of policies, and which included a large matched control group of physicians not subject to policy changes, was an important innovation relative to prior research. The study used prescription data from CVS Caremark, one of the largest pharmacy benefit managers in the United States. (more…)
Author Interviews, Cost of Health Care, JAMA, Primary Care, UCLA / 10.04.2017 Interview with: John N. Mafi, MD, MPH Assistant Professor of Medicine Division of General Internal Medicine and Health Services Research UCLA David Geffen School of Medicine Los Angeles, CA 90024 Affiliated Natural Scientist in Health Policy RAND Corporation 1776 Main St, Santa Monica, CA 90401 What is the background for this study? What are the main findings? Response: Between 10-30% of healthcare costs are due to low value care, or patient care that provides little to no benefit to patients, and can sometimes cause harm (e.g., radiation exposure from diagnostic imaging tests). In this study, we found that hospital-based primary care practice provide more low value care than community-based primary care practices across the United States. Understanding where and why low value care occurs is going to be essential if we want to get serious about eliminating it. (more…)
Author Interviews, Pharmacology, Thyroid Disease, UCLA / 07.04.2017 Interview with: Deborah Chon MD Endocrinology fellow UCLA David Geffen School of Medicine What is the background for this study? What are the main findings? Response: Our study shows that drinking cow's milk concurrently with oral levothyroxine significantly reduces the absorption of the medication. Levothyroxine is used for the physiologic replacement of thyroid hormone in patients with hypothyroidism and for serum TSH suppression in patients with thyroid cancer. It is the mostly commonly prescribed medication in the United States as of 2014. Frequent dose adjustments of levothyroxine have been shown to be a costly burden to the national healthcare system. Previous studies have shown that certain foods and medication, such as calcium supplements, can interfere with levothyroxine absorption. However, this is the first study to demonstrate that ingesting cow?s milk, a common breakfast staple, affects oral levothyroxine absorption. To determine the possible effect of cow's milk ingestion, we measured levothyroxine absorption in humans with and without concurrent milk consumption. Pharmacokinetic studies were conducted in healthy adults without allergies to milk or levothyroxine, and who were not pregnant nor using oral contraceptives. All subjects had no history of known thyroid disease and normal thyroid hormone function at baseline. Following an overnight fast, serum total thyroxine T4 (TT4) concentrations were measured at baseline and at 1, 2, 4, and 6 hours after ingestion of 1,000 ?g of oral levothyroxine alone or when co-administered with 12 oz. of milk (2% fat). There was a four-week washout period between the two study visits. Ten subjects (mean age 33.7?10.2 years, 60% male) completed the study. The serum total T4 absorption over six hours, calculated as area under the curve (AUC), was significantly lower when taking cow?s milk concurrently with levothyroxine compared levothyroxine alone (mean?SD: 67.26?12.13 vs. 73.48?16.96; p = 0.02). Also, peak serum TT4 concentrations were significantly lower in those who ingested levothyroxine concurrently with milk, compared to taking levothyroxine alone (p=0.04). (more…)
Author Interviews, Dermatology, UCLA / 19.03.2017 Interview with: Madalene Heng MD, FRACP, FACD, FAAD Professor of Medicine/Dermatology UCLA School of Medicine What is the background for this study? What are the main findings? Response: Curcumin, the active ingredient in the spice, turmeric, is an excellent anti-inflammatory agent with unique healing properties. However, this is only observed with our preparation of topical curcumin but not with oral curcumin. This is because curcumin is not absorbed and does not cross cell membranes - low bioavailability. The biochemical basis for the efficacy of topical curcumin is based on the fact that it is a phosphorylase kinase inhibitor. Phosphorylase kinase is an enzyme released by injured tissue 5 mins following injury, and is responsible for activating the transcription activator (NF-kB), resulting in turning on over 200 genes responsible for inflammation, and scarring among others, resulting in redness, swelling, pain, and eventually scarring. By blocking phosphorylase kinase activity early in the injury pathway, topical curcumin (curcumin gel) results in rapid healing with minimal or no scarring following many types of healing, including burns and scalds. The unique healing properties are also due to the fact that curcumin induces cell death (apoptosis) to damaged cells, resulting in the "space" for replacement by new healthy cells, resulting in normal appearing skin following burns and scalds. The salutary result depends on when the curcumin gel is applied - the earlier the better. We observed that when curcumin gel was applied within 4 days to second degree burns- hourly applications, tapering after the patient is improved - we observed rapid healing within 5 days, with the skin returning to normal within 6 weeks to 2 months without redness or visible scarring. Minor burns and scalds heal even more rapidly. Pain was improved within hours. What should readers take away from your report? Response: If the readers happen to have curcumin gel (Psoria-Gold) in their first aid kit, they should apply curcumin gel multiple times as soon as possible. Within the first hour, they should apply it every 5-10 mins, tapering off when the pain and swelling is improved. If they do this, it is possible that blistering may be aborted. The scarring is also minimal. The curcumin gel should be applied twice daily until the skin returns to normal (no redness, swelling, pigmentation etc) and no visible scarring is seen. (more…)
Annals Internal Medicine, Author Interviews, Outcomes & Safety, UCLA / 11.03.2017 Interview with: John N. Mafi, MD, MPH Division of General Internal Medicine and Health Services Research Department of Medicine, Ronald Reagan UCLA Medical Center Los Angeles, CA What is the background for this study? What are the main findings? Response: Our country has a primary care physician shortage. Some have advocated that we expand the scope of practice for nurse practitioners and physician assistants to help alleviate this problem and improve access to primary care. But a 2013 study in the New England Journal of Medicine found that a large number of physicians believed that nurse practitioners provided lower value care when compared with physicians. We decided to put that belief to the test. We studied 29,000 U.S. patients who saw either a nurse practitioner, physician assistant, or physician in the primary care setting for common conditions, and we compared the rate of low-value or unnecessary services—for example, unnecessary antibiotics for the common cold, or MRI for low back pain, or a CT scan for headache. Things that don’t help patients and may harm. We found no difference in the rates of low value services between nurse practitioners, physician assistants, and physicians. In other words, they did equivalent amounts of inappropriate or bad care. (more…)
Author Interviews, Education, Gender Differences, JAMA, UCLA / 06.03.2017 Interview with: Julie R. Boiko, MD, MS Resident Physician, PGY1 Department of Pediatrics University of California, San Francisco What is the background for this study? What are the main findings? Response: Grand rounds is an over 100-year-old tradition in US medical school clinical departments of recurring, expert-delivered lectures to update physicians and physicians-in-training on recent advances in relevant medicine. We wanted to determine whether gender representation of speakers at grand rounds aligns with the gender distribution of people typically represented in grand rounds audiences -- faculty, residents, and medical students -- by clinical specialty according to national academic medical trainee and workforce statistics. We chose to focus on grand rounds speakers as visible representations of women in academic medicine. This is important because, despite women and men entering medicine at comparable rates, women are much more likely to depart academic medical careers. As current and recent medical students, we considered that consistent exposure to successful female role models in grand rounds speaking venues may positively reinforce women trainees’ desires to continue in academic medical careers. We found that the people at the podiums do not resemble the people in the audience. Only 26% of grand rounds speakers are women. Even accounting that some clinical specialties contain few women faculty and residents, grand rounds speakers in most specialties we studied were statistically less likely to be women as compared to faculty and residents. Across the specialties, grand rounds speakers are 44% less likely than medical students, 39% less likely than residents, and 21% less likely than faculty to be women. (more…)
Author Interviews, Heart Disease, JAMA, Testosterone, UCLA / 23.02.2017 Interview with: Ronald S. Swerdloff, MD Chief of the Division of Endocrinology, Department of Medicine and Director of a World Health Organization Collaborative Center in Reproduction a Mellon Foundation Center for Contraceptive Development and a NIH Contraceptive Clinical Trial Center Director of the Harbor-UCLA Reproductive Program LA BioMed Lead Researcher David Geffen School of Medicine UCLA Health What is the background for this study? Response: While we have long known that testosterone levels decrease as men age, very little was known about the effects of testosterone treatment in older men with low testosterone until last year. Our team of researchers from LA BioMed and 12 other medical centers in the U.S., in partnership with the National Institute on Aging, conducted a coordinated group of seven trials known as The Testosterone Trials (TTrials). We studied the effects of testosterone treatment for one year as compared to placebo for men 65 and older with low testosterone. The TTrials are now the largest trials to examine the efficacy of testosterone treatment in men 65 and older whose testosterone levels are low due seemingly to age alone. The first published research from the TTrials last year reported on some of the benefits to testosterone treatment. We have now published four additional studies in the Journal of the American Medical Association (JAMA) and JAMA Internal Medicine that found additional benefits and one potential drawback. (more…)
Author Interviews, Heart Disease, JAMA, Tobacco Research, UCLA / 01.02.2017 Interview with: Holly R. Middlekauff, MD Professor UCLA Division of Cardiology David Geffen School of Medicine UCLA 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…)
Alcohol, Author Interviews, Heart Disease, JACC, UCLA / 02.01.2017 Interview with: Gregory M Marcus, MD, MAS, FACC, FAHA, FHRS Director of Clinical Research Division of Cardiology Endowed Professor of Atrial Fibrillation Research University of California, San Francisco What is the background for this study? What are the main findings? Response: Moderate alcohol consumption has previously been associated with a decreased risk of heart attack. However, as we have previously shown that individuals who believe alcohol to be good for the heart tend to drink more, there is a concern that these previous data might appear to justify excessive alcohol consumption. In addition, previous research on the topic of alcohol consumption and heart disease has relied almost entirely on participant self-report, which is known to be particularly unreliable among heavy drinkers. Finally, previous research has sought to study relationships between alcohol and various types of heart disease, but there has not been an emphasis on individual-level characteristics that might influence these relationships. (more…)
Author Interviews, Cost of Health Care, JACC, UCLA / 28.12.2016 Interview with: Joseph A. Ladapo, MD, PhD David Geffen School of Medicine at UCLA Department of Medicine, Division of General Internal Medicine and Health Services Research Los Angeles, California What is the background for this study? What are the main findings? Response: Four million stable patients in the US undergo testing for suspected ischemic heart disease (IHD) annually. There is substantial variation in how these patients are managed by physicians, and both clinical and economic factors have been used to explain this variation. However, it is unknown whether patients’ beliefs and preferences influence management decisions, and we aimed to answer this question. Based on interviews of 351 stable patients at Geisinger Health System newly referred for cardiac stress testing/coronary computed tomographic angiography (CTA) for suspected IHD, we found that patients with an accurate understanding of their initial test result were less likely to undergo follow-up tests/procedures if the initial test was negative and more likely to undergo follow-up tests/procedures if the initial test was positive. (more…)
Author Interviews, OBGYNE, UCLA, Zika / 20.12.2016 Interview with: Karin Nielsen, MD, MPH Professor of Clinical Pediatrics Division of Pediatric Infectious Diseases David Geffen School of Medicine at UCLA Director, Center for Brazilian Studies What is the background for this study? What are the main findings? Response: Our research was a prospective study in which pregnant women in Rio de Janeiro who developed a rash in the last 5 days between the end of 2015 to mid 2016 were screened for possible infection with Zika virus by a special molecular test (PCR) which looked for the virus in blood or urine. Women who were found to have Zika virus in either blood, urine or both were followed throughout time to look for pregnancy and infant outcomes. We also followed women who had a negative PCR test for Zika as a comparison group. By July 2016, we had outcomes known for 125 Zika affected pregnancies, of these 58 had abnormal outcomes, with 9 fetal losses and 49 babies who had abnormal findings on physical exam or brain imaging, all consistent with neurologic abnormalities. This meant 46% of the pregnant women in our study had an abnormal pregnancy outcome, and 42% of live birth infants were found to have an abnormality in the first few months of life. (more…)
Author Interviews, Flu - Influenza, Pediatrics, Science, UCLA / 28.11.2016 Interview with: Katelyn M. Gostic and Monique Ambrose Department of Ecology and Evolutionary Biology University of California Los Angeles What is the background for this study? What are the main findings? Monique Ambrose: Influenza pandemics pose a serious, recurrent threat to human public health. One of the most probable sources of future pandemic influenza viruses is the pool of influenza A virus (IAV) subtypes that currently circulate in non-human animals. It has traditionally been thought that the human population is immunologically naïve and unprotected against these unfamiliar subtypes. However, our work suggests that an individual ‘imprints’ to the influenza A virus (IAV) encountered in early childhood in such a way that they retain protection against severe disease if they later encounter a novel IAV subtype that belongs to the same genetic group as their first exposure. Our research looked at human cases of H5N1 and H7N9, two avian IAV subtypes of global concern, to investigate what factors most strongly predicted risk of severe disease. The most striking explanatory factor was childhood IAV imprinting: our results suggest that individuals who had childhood imprinting on an IAV in the same genetic group as the avian IAV they encountered later in life experienced 75% protection against severe disease and 80% protection against death. (more…)
Author Interviews, JAMA, Neurological Disorders, Radiology, UCLA / 28.11.2016 Interview with: Joseph O’Neill, PhD Division of Child and Adolescent Psychiatry University of California–Los Angeles Semel Institute for Neuroscience Los Angeles What is the background for this study? What are the main findings? Response: Stuttering seriously diminishes quality of life. While many children who stutter eventually grow out of it, stuttering does persist into adulthood in many others, despite treatment. Like earlier investigators, we are using neuroimaging to explore possible brain bases of stuttering, aiming, eventually, to improve prognosis. What's novel is that our study deploy neuroimaging modalities-- arterial spin labelling and, in this paper, magnetic resonance spectroscopy (MRS)-- not previously employed in stuttering. MRS offers prospects of detecting possible neurochemical disturbances in stuttering. The MRS results showed differences in neurometabolite-- brain chemicals-- levels between people who stutter (adults and children) and those who don't in many brain regions where other neuroimaging has also observed effects of stuttering. In particular, MRS effects were apparent in brain circuits where our recent fMRI work detected signs of stuttering, circuits subserving self-regulation of speech production, attention and emotion. This reinforces the idea that stuttering has to do with how the brain manages its own activity along multiple dimensions: motivation, allocation of resources, and behavioral output. (more…)
Author Interviews, Cancer Research, Dermatology, JAMA, UCLA / 22.11.2016 Interview with: Albert Yoon-Kyu Han, PhD Class of 2017 Medical Scientist Training Program David Geffen School of Medicine at UCLA What is the background for this study? What are the main findings? Response: Squamous cell carcinoma (SCC) of the lip makes up a large portion of oral cancers (25%). Most of the demographic and prognostic indicators for lip SCC are only available through retrospective case series. Thus, we used the national cancer database (Surveillance, Epidemiology, and End Results, or SEER) to examine the incidence, treatment, and survival of patients with lip SCC. The main findings of this study were that lip Squamous cell carcinoma predominantly affects white men in their mid-60s. We also found that the determinants of survival for lip SCC include age at diagnosis, primary site, T stage, and N stage. More specifically, on the primary site, SCC of the upper and lower lip had similar survival, whereas SCC of the oral commissure was associated with decreased survival. (more…)
Author Interviews, Ophthalmology, UCLA / 10.10.2016 Interview with: Pravin U. Dugel, MD Retina Consultants of Arizona Phoenix, Arizona; USC Roski Eye Institute Keck School of Medicine University of Southern California Los Angeles, California What is the background for this study? Response: OASIS is an acronym for “OcriplASmIn for Treatment for Symptomatic Vitreomacular Adhesion including Macular Hole”.  It was a Phase IIIB, randomized, prospective, sham-controlled, double-masked, multicenter clinical study. The goal of the study was to further evaluate the long-term (24 months) efficacy and safety of a single injection of 0.125mg of ocriplasmin in patients with symptomatic vitreomacular adhesion (VMA) and vitreomacular traction (VMT), including macular hole (MH). OASIS evaluated 220 patients with symptomatic VMA/VMT.  One hundred forty-six patients received ocriplasmin while 74 served as a sham control group. In the latter group, no intravitreal injection was administered.  (more…)
Author Interviews, Dermatology, Technology, UCLA / 05.10.2016 Interview with: Dr. Andrea M Armani PhD Fluor Early Career Chair and Associate Professor Mork Family Department of Chemical Engineering and Materials Science University of Southern California, Los Angeles, California What is the background for this study? Response: The “Internet of Things” (IoT) has seen an explosion in online sensor technologies, including UV sensors and monitors; for example, those from Apple and Samsung. However, they require connectivity and power, and they are integrated into delicate electronic systems that are not compatible with outdoor, athletic activities such as swimming, which is precisely when you should monitor UV exposure. Therefore, somewhat ironically, the technologies developed to meet the demands of the IoT are not ideal for cumulative UV exposure detection. Our goal was to develop a single use patch – like a smart “band-aid” – for the beach to alert users when they had been in the sun for an hour and needed to re-apply sunscreen or get out of the sun altogether. This application required a rugged system that was waterproof, bendable, and compatible with sunscreen. Additionally, the sensor readout needed to be easy to interpret. These requirements influenced our design and material selection. (more…)
Aging, Author Interviews, Genetic Research, UCLA / 17.08.2016 Interview with: Michael Gurven, Professor Department of Anthropology University of California Santa Barbara, CA 93106 What is the background for this study? Response: Understanding the sources of ethnic and sex disparities in health and longevity is critical in order to insure the health and well-being of everyone. We often hear about disparities due to differences in health care access, education, income, and sometimes genetic differences. But what we've done here is to employ a new biomarker developed by Steve Horvath, called the "epigenetic clock", which measures the cumulative changes to the epigenome, i.e. alterations to DNA that affects gene activity and expression but do not alter the DNA itself. This new measure is arguably one of the best biomarkers of aging out there today - so it's indeed a biological measure, but tells a different story than conventional genetic differences. Instead epigenetic age is influenced by the lived experience, physical and social environment, and genetic make-up of individuals. (more…)
Author Interviews, Heart Disease, Kidney Disease, Pharmacology, UCLA / 09.08.2016 Interview with: Jenny Shen, MD, MS Assistant Professor of Medicine David Geffen School of Medicine at UCLA Los Angeles Biomedical Institute at Harbor-UCLA Medical Center What is the background for this study? What are the main findings? Response: With cardiovascular disease being the No. 1 cause of death in end-stage kidney disease patients on peritoneal dialysis, we examined two classes of medications commonly prescribed to prevent cardiovascular events in these patients and found no significant difference in outcomes. The two classes of medications, angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB), have slightly different mechanisms and could theoretically have differing outcomes. Previous studies had suggested that ACEI may lead to a kinin-mediated increase in insulin sensitivity not seen with ARB. This could potentially lower the cardiovascular risk in patients on peritoneal dialysis because they are exposed to high glucose loads in their dialysate that may lead to insulin resistance and its associated cardiovascular risk. Using a national database, the U.S. Renal Data System, we surveyed records for all patients enrolled in Medicare Part D who initiated maintenance peritoneal dialysis from 2007 to 2011. Of those, we found 1,892 patients using either drug class. Surveying their medical records, we found no difference in cardiovascular events or deaths between the users for each class of medication. (more…)