Author Interviews, JAMA, Weight Research / 12.05.2016
Optimal BMI With Lowest Mortality Has Shifted to Higher Weight
MedicalResearch.com Interview with:
Shoaib Afzal, MD, PhD
Department of Clinical Biochemistry
Copenhagen General Population Study
Herlev and Gentofte Hospital,
Faculty of Health and Medical Sciences
University of Copenhagen, Copenhagen, Denmark
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Afzal: Previous findings indicate that while average BMI has increased over time in most countries, the prevalence of cardiovascular risk factors may be decreasing among obese individuals. Thus, the BMI associated with the lowest all-cause mortality may have changed over time. This study included three cohorts from the same general population enrolled at different times: the Copenhagen City Heart Study in 1976-1978 (n = 13,704) and 1991-1994 (n = 9,482) and the Copenhagen General Population Study in 2003-2013 (n = 97,362).
The increased risk for all-cause mortality that was associated with obesity compared to normal weight decreased from 30% in 1976-1978 to 0% in 2003-2013, that is, over a 30-year period. In addition, the optimal BMI for lowest all-cause mortality increased by 3.3 from 23.7 in 1976-1978 through 24.6 in 1991-1994 to 27 in 2003-2013. Another interesting finding in this study is that the optimal BMI in relation to lowest mortality is placed in the overweight category in the most recent 2003-2013 cohort.
Dr. Erica Spatz[/caption]
Erica Spatz, MD, MHS
Assistant Professor, Section of Cardiovascular Medicine
Center for Outcomes Research and Evaluation
Yale University School of Medicine/Yale-New Haven Hospital
New Haven, CT 06520
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Spatz: Rates of heart attack have declined during the last 15 years. But whether communities of different economic status or in different geographic regions experienced similar declines is unknown, especially as efforts to prevent cardiovascular disease and manage heart attacks may not have been equally successful in communities with different resource capacity.
Our study shows that trends in the incidence of and mortality from heart attack were similar in low, average and high income communities. However, low-income communities had higher hospitalization rates than average and high income communities throughout the 15 year study period. Interestingly mortality rates were similar.
Dr. Natalia Trayanova[/caption]
Natalia Trayanova PhD, FHRS, FAHA
Murray B. Sachs Endowed Chair
Professor of Biomedical Engineering
Joint Appointment, Medicine
Johns Hopkins University
Institute for Computational Medicine
Johns Hopkins University
Baltimore, MD
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Trayanova: The methodology for modeling cardiac electrical function has matured sufficiently that we can now create computational models of the electrical functioning of the entire heart. My research is focused on translating this methodology into the clinic. The goal is to create, if you will, "a virtual heart for every patient", that will enable the physician to play our scenarios that manifest the heart dysfunction in the given patient, and to enable physicians to make personalized decisions about patient treatment. The present paper is the first application of this overall vision.
The motivation for this particular paper was that determining which patients are at risk for sudden cardiac death represents a major unmet clinical need. Patients at risk receive life-saving implantable defibrillators (ICDs), but because of the low sensitivity and specificity of current approach (based on low ejection fraction), risk assessment is inaccurate. Thus, many patients receive ICDs without needing them, while others die of sudden cardiac death because they are not targeted for 
Dr. Yeh[/caption]
Dr. James Song-Jeng Yeh, MD
Brigham and Women's Hospital
Boston MA
MedicalResearch.com: What is the purpose for this study?
Dr. Yeh: A number of factors influence physicians’ prescribing behavior, including physician’s knowledge and understanding of the drugs. Pharmaceutical detailing and financial incentives may affect such behavior. My interest in evidence-based medicine and how medical knowledge is translated into practice lead me to think about how physicians’ financial relationships with the pharmaceutical industry may affect prescribing patterns.
In our study, we linked the Massachusetts physicians open payment database with the Medicare drug prescription claims database to determine if financial relationships with the industry are associated with increased brand-name statin drug prescribing. The open payment database reports payments that physicians receive from pharmaceutical and medical device industries. The open payment database when linked to the drug prescription claims database allowed us to answer this question.
We looked at year 2011, when two of the most commonly prescribed brand-name statin drugs (Lipitor and Crestor) were not yet available in generic formulation.
The outcome measured was what percentage of all statin prescription claims (both generic and brand-name) were brand-names.
Dr. Taylor-Phillips[/caption]
Dr Sian Taylor-Phillips PhD
Assistant Professor of Screening and Test Evaluation
Division of Health Sciences
Warwick Medical School
University of Warwick
Coventry
MedicalResearch.com: What is the background for this study?
Dr Taylor-Phillips : Psychologists have been investigating a phenomenon of a drop in performance with time on a task called ‘the vigilance decrement’ since World War 2. In those days radar operators searched for enemy aircraft and submarines (appearing as little dots of light on a radar screen). People thought that the ability to spot the dots might go down after too much time spent on the task. Many psychology experiments have found a vigilance decrement, but most of this research has not been in a real world setting.
In this research we wanted to know whether there was a drop in performance with time on a task for breast screening readers looking at breast x-rays for signs of cancer. (Breast x-rays or mammograms show lots of overlapping tissue and cancers can be quite difficult to spot). This was a real-world randomised controlled study in UK clinical practice.
In the UK NHS Breast Screening Programme two readers examine each woman’s breast x-rays separately for signs of cancer. They look at batches of around 35 women’s x-rays. At the moment both readers look at the x-rays in the same order as each another, so if they both experience a drop in performance, it will happen at the same time. We tested a really simple idea of reversing the batch order for one of the readers, so that if they have a low ebb of performance it happens when they are looking at different women’s breast x-rays.
Dr. Lynda Harris[/caption]
Lynda Harris PhD
Lecturer in Pharmaceutics
University of Manchester
Manchester Pharmacy School
Maternal and Fetal Health Research Centre
Manchester
MedicalResearch.com: What is the background for this study?
Dr. Harris: Pregnancy complications such as pre-eclampsia and fetal growth restriction remain a problem despite advances in antenatal care, and impact heavily on future health: small size at birth is associated with an increased risk of cardiovascular disease and diabetes in later life. Drugs to improve pregnancy outcome are severely lacking, as pregnant women are considered a high risk cohort by drug companies, who fear expensive lawsuits associated with side effects and teratogenicity. The majority of pregnancy complications are caused by a poorly growing or poorly functioning placenta. A number of potential drugs have been identified that enhance placental function in vitro, and improve fetal growth in animal models; however, there is currently no means of restricting their actions to the placenta, and systemic administration of these drugs to pregnant women is not feasible due to the risk of adverse effects in other tissues. To address this issue, we have identified a series of placental “homing peptides” which we have used to create nanocarriers for targeted delivery of drugs to the placenta.
Prof. Craig Anderson[/caption]
Professor Craig Anderson
Professor of Stroke Medicine and Clinical Neuroscience
Sydney Medical School at the University of Sydney
Institute of Neurosciences of Royal Prince Alfred Hospital
MedicalResearch.com: What is the background for this study?
Prof. Anderson: Intravenous use of the clot-busting drug, alteplase (or rtPA), at a dose of 0.9 mg/kg body weight is the only proven medical treatment of acute ischemic stroke. However, a major drawback to the treatment is an increased risk of major bleeding in the brain, or intracerebral hemorrhage (ICH), that occurs in about 5% of cases, and can be fatal. This balance of effectiveness (recovery from disability) and risks (ICH, and bleeding elsewhere and uncommon drug allergic reactions) has led to much of the controversy over the net benefit of the drug. The optimal dose of the drug has never been established, but the Japanese drug safety regulatory authority, has approved a lower dose (0.6mg/kg) on the basis of a small, non-randomized, open study which showed comparable outcomes and lower risk of ICH than historical controls. This ‘east-west’ divide over the approved dose of alteplase has led to much variation in the dose of alteplase used in clinical practice in Asia – according to a doctor’s perceived risk of ICH in individual patients and the affordability of this relatively expensive treatment in low resource settings. Data from the Get-with-the Guidelines Quality Registry in the United States suggests Asian patients are at higher risk of ICH after standard-dose alteplase than non-Asians.
Our research aimed to resolve this uncertainty over the optimal dose of alteplase, as an international, active-comparator, open-label, blinded outcome assessed, clinical trial of low-dose (0.6 mg/kg) versus standard-dose (0.9mg/kg) in 3310 patients recruited from over 100 hospitals in 13 countries between 2012 and 2015.
Dr. Corrine Leach[/caption]
Corinne Leach, MPH, MS, PHD
Strategic Director, Cancer and Aging Research
American Cancer Society, Inc.
Atlanta, GA 30303
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Leach: Using linked data from cancer registries and the Medicare Health Outcomes Survey, we prospectively examined the short-term impact of cancer on the functioning, development of and worsening of age-related health conditions among 921 older adults who developed cancer compared to 4,605 propensity score matched controls. We found that cancer groups demonstrated greater declines in activities of daily living and physical functioning compared to controls with the greatest change for lung cancer patients. Having a cancer diagnosis increased risk for depression but did not increase the odds of developing arthritis in the hand/hip, incontinence (except for prostate cancer), or vision/hearing problems. Having a cancer diagnosis also did not exacerbate the severity of arthritis or foot neuropathy.
Dr. Atul Sharma[/caption]
Atul Sharma MD, MSc(Statistics), FRCPC
Researcher, Children’s Hospital Research Institute of Manitoba; Assistant Professor, Department of Pediatrics and Child Health, University of Manitoba; Senior Consultant, Biostatistics Group, George and Fay Yee Center for Healthcare Innovation
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Sharma: Between 1978 and 2004, a previous comparison of directly measured heights and weights demonstrated an alarming increase in the prevalence of overweight or obesity in Canadian children aged 2-17y, from 23.3% (95% CI = 20.5-26.0) to 34.7% (33.0-36.4) based on the new 2007 WHO criteria.
In Canada, the definitions of overweight and obesity changed with the introduction of the new '2010 WHO Growth Charts for Canada’, Previous definitions were based on Body Mass Index (BMI) percentiles from the 2000 Centers for Disease Control and Prevention (CDC) growth chart’s. In addition to revising the percentile thresholds for diagnosing overweight or obesity, the WHO charts were based on a very different reference population. As a result, the proportion of Canadian children being classified as overweight or obese increased with the introduction of the new WHO charts.
Our current study applied current Canadian definitions of overweight and obesity to a contemporary sample of Canadian children age 3-19y to assess recent trends in the rates of overweight and obesity. By pooling data from the Canadian Community Health Survey (CCHS, cycle 2.2) and the Canadian Health Measures Survey (CHMS, cycles 2 and 3), we were able to study a representative sample of more than 14000 Canadian children from the period 2004-2013. The sample was evenly split between boys and girls and approximately 80% white.
Dr. Serena Nik Zainal[/caption]
Serena Nik-Zainal MD PhD
Wellcome Beit Fellow & Honorary Consultant in Clinical Genetics
CDF Group Leader
Wellcome Trust Sanger Institute
United Kingdom
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Nik-Zainal: We have used the massive improvement in speed of "sequencing" (reading the human genetic material) in order to obtain comprehensive whole genome maps of 560 human breast cancer patients. This is the largest whole genome sequencing study of a single cancer type in the world. We wanted to forensically search these cancers, find all the important genes that drive breast cancer, find all the important mutation patterns that tell us something about why breast cells turn into cancer cells and then to pull it altogether for each patient. We wanted to be able to "profile" each cancer patient, to see if we could further our understanding of personal cancer genomes.
In all, we had 556 female and four male patients, and they were sought from all over the world – USA, Europe and Asia.
Dr. Alexander Turchin[/caption]
Alexander Turchin, MD, MS
Associate Physician, Brigham and Women's Hospital
Associate Professor of Medicine, Harvard Medical School
Brigham and Women's Hospital
Department of Medicine
Endocrinology
Boston, MA 02115
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Turchin: It is known that fewer women than men at high risk for cardiovascular disease are treated with statins.
However, the reasons for this sex disparity are not fully understood.
Our study identified 4 factors that accounted for over 90% of the difference in statin therapy between women and men with coronary artery disease:
Dr. Anna Pease[/caption]
Dr Anna Pease
Senior Research Associate
University of Bristol
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Pease: We tried to gather evidence of whether there was an association between swaddling for sleep and SIDS. This was a review, not a new original study, but it is the first time these data have been brought together to try to quantify any risk between swaddling and SIDS. We only found 4 studies and they were quite different making it difficult to pool the results. We did find, however, that the risk of SIDS when placing infants on their side or front for sleep increased when infants were swaddled.
Wenpeng You[/caption]
Wenpeng You, PhD student
Biological Anthropology and Comparative Anatomy Research Unit
University of Adelaide | School of Medicine
Adelaide, Australia
[caption id="attachment_24262" align="alignleft" width="180"]
Dr. Maciej Henneberg[/caption]
Maciej Henneberg, PhD, DSc, FAIBiol
Wood Jones Professor of Anthropological and Comparative Anatomy
University of Adelaide School of Medicine;
Institute for Evolutionary Medicine, University of Zurich
Editor in Chief, Journal of Comparative Human Biology HOMO
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Type 1 diabetes disease has very strong genetic background. Prevalence of type 1 diabetes has been increasing globally. Previous studies focusing on regional genetics and environmental factors cannot fully explain this phenomenon. Due to insufficient medical knowledge up until early 20th century, people with type 1 diabetes disease would most commonly die during their teens or early 20s. Therefore, they did not have the opportunity to pass on their genes providing background for the development of type 1 diabetes to their next generations. Since discovery and introduction of insulin to modern medicine in early 1920s, more and more type 1 diabetes patients have been able to survive their reproduction cycle (up until and past 50 years of age). This has made more and more genes related to type 1 diabetes to accumulate in human populations.
We applied the Biological State Index which measures a probability to pass genes on to the next generation at population level. We found that the rapid increase in type 1 diabetes over the last few decades was correlated with increases of the Biological State Index and its proxy, human life expectancy, especially in more developed world in which natural selection has been relaxed most. This correlation was found after statistically excluding differences in countries income, levels of urbanization, sugar consumption and obesity prevalence.
Dr. Charu Kaushic[/caption]
Charu Kaushic. PhD.
Professor
OHTN Applied HIV Research Chair
Department of Pathology and Mol. Medicine
McMaster Immunology Research Center,
McMaster University
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Kaushic: Female sex hormones, estradiol and progesterone have been shown to regulate immune responses in many experimental and clinical studies. We and others have shown previously that these hormones also regulate susceptibility to and outcome of sexually transmitted infections (STIs), including Chlamydia, HSV-2, SIV and HIV-1. Most studies show that progesterone generally increases susceptibility while estradiol generally confers protection against STIs. This has recently gained much more widespread attention because of the controversy surrounding use of injectable hormonal contraceptives in geographical areas where there is high prevalence of HIV-1. The most frequently used injectable contraceptive uses a progestin-based formulation which has been correlated with 2-fold increase in HIV acquisition and transmission in epidemiological studies. Oral contraceptives that contain a combination of estradiol and progesterone do not show similar correlation with increased infection. This is currently a very important women’s health issue, which is being carefully monitored by many public health agencies, including WHO. Many researchers are focusing efforts in understanding how sex hormones can increase or decrease susceptibility of women to STIs.
We have published in this area for more than a decade, including a series of papers showing that in a mouse model, the outcome of genital herpes (HSV-2) infection can depend on which hormone we treat the mice with. A few years ago, we showed for the first time that mice that received an HSV-2 vaccine under the influence of estradiol were much better protected and showed less disease pathology (Bhavanam et al, Vaccine 2008). These results were reproduced a year later by another group, using an actual HSV-2 vaccine formulation. Since then, we have been working to understand at a cellular level, the underlying mechanism of estradiol-mediated enhanced protection. In this PLOS Pathogens paper, we report for the first time a cellular mechanism by which estradiol was seen to enhance immune protection against HSV-2 infection in mice.
The main findings are that estradiol primes dendritic cells in the vaginal tract to induce enhanced anti-viral T cell responses. Dendritic cells are key immune cells that decide what type of immune responses will be mounted against an infection. Under the influence of estradiol, the dendritic cells in the vaginal tract of mice induced Th17 cells which in turn helped enhance anti-viral T cell responses (Th1), resulting in better protection against genital HSV-2. This regulation of anti-viral immunity was seen only in the reproductive tract.
Dr. Riyaz Bashir[/caption]
Riyaz Bashir MD, FACC, RVT
Professor of Medicine
Director, Vascular and Endovascular Medicine
Department of Medicine
Division of Cardiovascular Diseases
Temple University Hospital
Philadelphia, PA 19140
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Bashir: The use of compression stockings in the prevention of post thrombotic syndrome following an episode of deep vein thrombosis is common in clinical practice. However, the evidence to suggest its efficacy has been put into question by the recent publication of the SOX trial. Since this was the largest randomized controlled trial to date addressing this issue, it has led to clinicians questioning whether compression stockings should be used at all in these patients.
The main finding of this meta-analysis was that in patients with deep venous thrombosis, use of elastic compression stockings does not significantly reduce the development of post thrombotic syndrome. However the current body of evidence is limited and we believe at present it is too early to give up on the use of this therapy, which may benefit many subgroups of patients.
Dagfinn Anne[/caption]
Dagfinn Aune
Department of Epidemiology and Biostatistics
School of Public Health
Imperial College London
St. Mary's Campus
Norfolk Place, Paddington, London
MedicalResearch.com: What is the background for this study?
Response: The prevalence of overweight and obesity has increased rapidly over the past decades in all areas of the world. This has raised serious public health concerns because of the relationship between excess weight and increased risk of many chronic diseases including cardiovascular disease, several types of cancer, type 2 diabetes, gallstones, gout, osteoarthritis, and several other conditions as well as all-cause mortality.
Body mass index (BMI) is an established way of measuring adiposity and is calculated by dividing the weight in kilograms with the height in metres squared. Although overweight (BMI 25-29.9) and obesity (BMI ≥30) has been associated with increased risk of mortality in several previous studies, the largest previous study showed that when compared to normal weight, overweight was associated with reduced mortality, and only grade 2 obesity (BMI ≥35) was associated with increased risk of mortality.
However, there were several limitations in that study, for example, smoking and prevalent or prediagnostic illness were not taken into account, both of which can cause lower body weight and increased mortality and may therefore bias the optimal BMI range upwards. In addition, many large studies which did not use the standard WHO categories of normal weight, overweight and obesity, but had used smaller increments to categorize BMI to provide more detailed assessment of the dose-response relationship between BMI and mortality, had been excluded.
Dr. Kevin Curl[/caption]
Dr. Kevin Curl, MD
Sidney Kimmel Medical College
Jefferson University
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Curl: If left untreated, half of coronary bypass vein grafts will become occluded within 10 years of surgery. We reviewed the health records of over 350 patients who had a previous coronary artery bypass graft (CABG) a minimum of three years prior. Our goal was to identify the long-term trends with medication adherence in this high risk population, namely aspirin and statin medications. The American College of Cardiology and the American Heart Association recommend both statins and aspirin medications unless they are unsafe for the individual patient. The mean age of the study population was 69 years, most patients had previously undergone "triple bypass" with 3 grafts, and the mean time from surgery was 11 years. We found that only 52 percent of patients were taking both aspirin and a statin medication. In addition, patients not taking a statin had higher (22 percent) low-density lipid or “bad” cholesterol.
Michael Daniel[/caption]
Michael Daniel
The Johns Hopkins University School of Medicine
M.D. Candidate 2016
Michael G. Daniel is a graduating medical student at the Johns Hopkins School of Medicine. He will be attending the Osler Internal Medicine Residency Training Program next year at the Johns Hopkins Hospital. His research focus is on Patient Safety, Quality, and Outcomes improvement.
Summary:
Medical error ranks as the third leading cause of death in the United States, but is not recognized in national vital statistics because of a flawed reporting process. Using recent studies on preventable medical error and extrapolating the results to the 2013 U.S. hospital admissions we calculated a mortality rate or 251,454 deaths per year.
MedicalResearch.com: What made you want to research this topic?
Response: I decided to study medicine because I wanted to improve patient health. However, I realized that improving patient health is not only about curing a disease but is sometimes about fixing the way we deliver healthcare.
MedicalResearch.com: Is this news surprising to you?
Response: Yes, because all previous estimates of medical error were much lower and when I started the research I couldn’t use the CDC statistics to get current data.
Dr. Uscher-Pines[/caption]
Lori Uscher-Pines, PhD
RAND Corporation
Arlington, Virginia
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Although many communities in the U.S. are underserved by dermatologists, access is particularly limited among Medicaid patients. Teledermatology may be one solution to improve access. Our goal with this study was to assess the effect of a novel teledermatology initiative on access to dermatologists among enrollees in a Medicaid Managed Care Plan in California’s Central Valley.
Among all patients who visited a dermatologist after the introduction of teledermatology from 2012-2014 (n=8614), 49% received care via teledermatology. Among patients newly enrolled in Medicaid following Medicaid expansion in 2014, 76% of those who visited a dermatologist received care via teledermatology. Patients of primary care practices that engaged in teledermatology had a 64% increase in the fraction of patients visiting a dermatologist (vs. 21% in other practices) (p<.01). Compared with in-person dermatology, teledermatology served more patients under age 17, male patients, nonwhite patients, and patients without comorbid conditions. Conditions managed across settings varied; teledermatology physicians were more likely to care for viral skin lesions and acne whereas in-person dermatologists were more likely to care for psoriasis and skin neoplasms.
Dr. Redlich[/caption]
Dipl.-Psych. R. Redlich
Neuroimaging Group
Klinik und Poliklinik für Psychiatrie und Psychotherapie
Westfaelische Wilhelms-Universitaet Muenster
MedicalResearch.com: What is the background for this study?
Response: Electroconvulsive therapy (ECT) is one of the most effective treatments for severe depression. The ability to advise psychiatrists and patients accurately regarding the chances of successful ECT is of considerable value, particularly since ECT is a demanding procedure and, despite having relatively few side effects, has a profound impact on patients. Therefore, the present study sought to predict ECT response in a psychiatric sample by using a combination of structural Magnetic Resonance Imaging data and machine-learning techniques.
Dr. Ben Freedman[/caption]
Dr. Ben Freedman OAM
Deputy Director Research Strategy, Heart Research Institute/Charles Perkins Centre
Professor of Cardiology, Sydney Medical School
Head Vascular Biology Anzac Research Institute
Honorary VMO, Concord Repatriation General Hospital
University of Sydney
MedicalResearch.com: What is the background for this study?
Dr. Freedman: Guidelines recommend that patients with atrial fibrillation (AF) at high enough risk for stroke should be treated with anticoagulant. Anticoagulant drugs are remarkably effective in reducing stroke risk by about two thirds, and death by between a quarter and a third. Unfortunately, strokes can still occur when patients are prescribed anticoagulant for Atrial Fibrillation, and it is often presumed this residual risk of stroke represents treatment failure, though there are few data about this important issue.
MedicalResearch.com: What are the main findings?
Dr. Freedman: We were able to compare the risk of stroke in a cohort of patients with AF commenced on anticoagulant, with a very large closely-matched cohort seen in general practice at the same time but without AF. This is a unique comparison. We found that the residual risk of stroke in such anticoagulant-treated patients was virtually identical to that in the matched control cohort. The implication is that the residual risk of stroke may not be treatment failure, but the risk of non-cardioembolic stroke in people of a similar age and stroke risk profile but without Atrial Fibrillation. The residual risk of death in those on anticoagulant was higher than the matched controls, and intermediate between the control rate and the mortality rate for untreated AF.
Dr. Fleming Dutra[/caption]
MedicalResearch.com: What is the background for this study?
Dr. Fleming-Dutra: One of the most urgent public health threats of our time is the emergence of antibiotic-resistant bacteria. The use of antibiotics is the single most important factor leading to antibiotic resistance around the world. Simply using antibiotics creates resistance. To combat antibiotic resistance we have to use antibiotics appropriately — only when needed and, if needed, use them correctly. In 2015, the White House released the National Action Plan for Combating Antibiotic-Resistant Bacteria (CARB), which set a goal for reducing inappropriate outpatient antibiotic use by 50% by 2020. However, the amount of antibiotic use in the outpatient setting that is inappropriate was unknown.
MedicalResearch.com: What are the main findings?
Dr. Fleming-Dutra: In this study, we estimate that at least 30% of antibiotics prescribed in doctors’ offices, emergency departments and hospital-based clinics are unnecessary—meaning that no antibiotic was needed at all, which equates to 47 million unnecessary antibiotic prescriptions written annually in these outpatient settings. Most of those unnecessary antibiotic prescriptions were written for acute respiratory conditions, a key driver of antibiotic overuse. Thus, in order to reach the White House goal of reducing inappropriate outpatient antibiotic use by 50%, a 15% reduction in overall antibiotic use in outpatient settings is needed by 2020.
Dr Lluís Ribas[/caption]
Lluís Ribas de Pouplana, Ph.D
IRB Barcelona
Barcelona 08028
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Ever since the discovery of the genetic code it became obvious that the system had not grown to its full theoretical potential of making proteins with 63 different amino acids.
Francis Crick called the code 'a frozen accident',
but it was unclear what had actually froze it.
In this article we offer an explanation to that, and we validate it experimentally.
What we find is that the central pieces of the genetic code, the transfer RNAs,
are unable to incorporate enough specific elements for the system to be able to
use 63 of them without confusion. Since you need a new tRNA for each new
amino acid, once the tRNA identification limit is reached you also reach the
maximum number of usable amino acids. This limit happened to be reached
at 20, and that's where it has stayed for 3 billion years.
Dr. Jennifer Graves[/caption]
Jennifer Graves, MD, PhD, MAS
Adult and Pediatric Multiple Sclerosis Centers
UCSF
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Graves: Cessation of medications with effects on immune trafficking may be more likely to cause rebound inflammatory activity in autoimmune diseases such as multiple sclerosis. We observed 5 strikingly severe relapses consistent with rebound events following cessation of fingolimod treatment and identified several similar cases in the literature. At our center the rebound events occurred with an approximate 10% frequency.
MedicalResearch.com: What should clinicians and patients take away from your report?
Dr. Graves: Fingolimod cessation may be complicated by rebound phenomena in some patients, similar to what has been observed with natalizumab. Both of these medications have effects on immune cell trafficking, likely explaining the association with rebound events. Careful consideration must be taken in stopping these medications.