AstraZeneca, Author Interviews, NEJM, Pulmonary Disease / 29.06.2020

MedicalResearch.com Interview with: [caption id="attachment_54747" align="alignleft" width="200"]Frank Trudo, MD MBA Vice President, US Medical Affairs Respiratory & Immunology AstraZeneca Dr. Trudo[/caption] Frank Trudo, MD MBA Vice President, US Medical Affairs Respiratory & Immunology AstraZeneca MedicalResearch.com: What is the background for this study? Response: ETHOS is a randomized, double-blinded, multi-center, parallel-group, 52-week trial to assess the efficacy and safety of PT010 in symptomatic patients with moderate to very severe COPD and a history of exacerbation(s) in the previous year. Outcomes in the ETHOS trial included, as a primary endpoint, the rate of moderate or severe exacerbations. MedicalResearch.com: How does PT010 differ from other treatments for COPD?
  • Highly competitive: PT010’s Phase III clinical trial program demonstrates it has a highly competitive clinical profile in decreasing moderate or severe exacerbations. Severe exacerbations were defined as exacerbations leading to hospitalization or death.
  • All-cause mortality: In a secondary endpoint, PT010 showed a 46% reduction in the risk of all-cause mortality compared with glycopyrronium/formoterol fumarate. The data from ETHOS show that reducing risk of all-cause mortality is achievable for patients with this progressive disease and could transform treatment goals in COPD.
  • Two potential dose options: This is also the first time we have seen the benefit of closed triple-combination therapy at two ICS doses, which could transform care by allowing physicians to select the optimal dosing option for individual patients. 
Author Interviews, COVID -19 Coronavirus, Heart Disease / 24.06.2020

MedicalResearch.com Interview with: [caption id="attachment_54655" align="alignleft" width="200"]Spyridon G. Deftereos MD PhD Section of Cardiovascular Medicine Yale University Dr. Deftereos[/caption] Spyridon G. Deftereos MD PhD Prof. of Cardiology, Medical School National and Kapodistrian University of Athens Greece MedicalResearch.com: What is the background for this study? Response: Research on COVID-19 early revealed that inflammation plays a crucial role in the pathophysiology of the disease. Therefore, we designed GRECCO-19 study in order to evaluate the effect of colchicine, a relatively safe drug with known anti-inflammatory properties, in patients hospitalized for SARS-CoV-2 infection.
Author Interviews, Gout, Kidney Disease, NEJM / 24.06.2020

MedicalResearch.com Interview with: [caption id="attachment_50193" align="alignleft" width="84"]Sunil Badve MBBS, MD, DNB, FRACP, PhD, FASN Senior Research Fellow, Renal & Metabolic Division Staff specialist nephrologist | St George Hospital University of New South Wales The George Institute for Global Health Australia Dr. Badve[/caption] Sunil Badve MBBS, MD, DNB, FRACP, PhD, FASN Staff specialist nephrologist | St George Hospital Conjoint Associate Professor | University of New South Wales Senior Research Fellow, Acute Kidney Injury and Trials The George Institute for Global Health Australia  MedicalResearch.com: What is the background for this study? Response: Elevated serum urate levels are associated with progression of chronic kidney disease (CKD). CKD patients often have elevated serum urate levels due to decreased excretion. We conducted this placebo-controlled randomized trial to evaluate if urate-lowering treatment with allopurinol would attenuate decline in estimated glomerular filtration rate (eGFR) over 2 years in patients with CKD. We enrolled 369 CKD patients with high progression risk and no prior history of gout.
Author Interviews, Brigham & Women's - Harvard, Critical Care - Intensive Care - ICUs, NEJM, Pediatrics / 24.06.2020

MedicalResearch.com Interview with: [caption id="attachment_54694" align="alignleft" width="155"]Christopher P. Landrigan, MD, MPH  Chief, Division of General Pediatrics, Boston Children’s Hospital Director, Sleep and Patient Safety Program, Brigham and Women's Hospital William Berenberg Professor of Pediatrics, Harvard Medical School Boston Children's Hospital, Boston, MA 02115  Dr. Landrigan[/caption] Christopher P. Landrigan, MD, MPH Chief, Division of General Pediatrics, Boston Children’s Hospital Director, Sleep and Patient Safety Program, Brigham and Women's Hospital William Berenberg Professor of Pediatrics, Harvard Medical School Boston Children's Hospital Boston, MA 02115 MedicalResearch.com: What is the background for this study? Response: An enormous body of literature demonstrates that sleep deprivation adversely affects the safety and performance of resident physicians, as well as individuals across other occupations.  Resident physicians are at greatly increased risk of suffering motor vehicle crashes and needlestick injuries, and are at substantially increased risk of making medical errors, when working on traditional schedules that include 24-hour shifts. We previously conducted a randomized controlled trial in two intensive care units that found resident physicians made 36% fewer medical errors when a scheduling intervention was introduced that eliminated 24-hour shifts but held resident workload constant. The current study, ROSTERS, was a 6-center study that again introduced a scheduling intervention to eliminate 24-hour shifts in intensive care units.  Due to varying resources and unit organization across sites, each hospital developed its own staffing plan to accommodate the intervention​.
Author Interviews, CDC, NEJM, Pulmonary Disease / 23.04.2020

MedicalResearch.com Interview with: [caption id="attachment_53973" align="alignleft" width="200"]Angela K. Werner, PhD, MPH Environmental Public Health Tracking Program National Center for Environmental Health CDC Dr. Werner[/caption] Angela K. Werner, PhD, MPH Environmental Public Health Tracking Program National Center for Environmental Health CDC MedicalResearch.com: What is the background for this study? Response: In August 2019, emergency department (ED) visits related to e-cigarette, or vaping, product-associated lung injury (EVALI) increased sharply, followed by a peak in September. This was followed by a gradual but persistent decline in the number of cases. As of February 18, 2020 (CDC’s latest and final published update), there were a total of 2,807 hospitalized EVALI cases or deaths reported to CDC from all 50 states, the District of Columbia, and two U.S. territories (Puerto Rico and U.S. Virgin Islands). Sixty-eight deaths were confirmed in 29 states and the District of Columbia. Although clinical presentations and outcomes of EVALI patients have been reported, data on patients who died are more limited. This article fills a gap by reporting on a national study assessing detailed demographic, substance use, and clinical characteristics of EVALI patients who have died, and comparing them to the characteristics of EVALI patients who survived.
Author Interviews, COVID -19 Coronavirus, NEJM / 28.03.2020

MedicalResearch.com Interview with: [caption id="attachment_53025" align="alignleft" width="205"]Bin Cao, MD, PhD Professor, China-Japan Friendship Hospital Department of Pulmonary and Critical Care Medicine Beijing 100029, China Dr. Bin Cao[/caption] Bin Cao, Yeming Wang, Guohui Fan, Lianghan Shang, Jiuyang Xu, DingyuZhang, Chen Wang on behalf of LOTUS-China Study Group China-Japan Friendship Hospital; Wuhan Jintinyan Hospital; Institute of Respiratory Medicine, Chinese Academy of Medical Science  MedicalResearch.com: What is the background for this study? Response: In the past two months, the outbreak of Coronavirus Disease 2019 (COVID-19) has been spreading rapidly across the world. Science and technology is the most powerful weapon for human to fight against diseases, especially in such a pandemic setting. Seeking for effective antiviral medication is the most critical and urgent among the many scientific tasks in the pandemic. At the most critical moment in the fight against COVID-19, Chinese clinical scientists have stepped forward under extremely difficult research conditions to carry out clinical trials in antiviral treatment including lopinavir–ritonavir and remdesivir, in a swift, decisive and effective manner. These trials have attracted worldwide attention. Recently, the Lopinavir–ritonavir Trial for suppression of SARS-CoV-2 in China (LOTUS-China) has been completed, which, with great clinical significance, can provide strong evidence for the treatment of COVID-19 both in China and around the world.
Author Interviews, Cancer Research, CT Scanning, Lung Cancer / 04.02.2020

MedicalResearch.com Interview with: [caption id="attachment_53081" align="alignleft" width="200"]Carlijn M. van der Aalst, Ph.D. MPH Department of Public Health Erasmus MC Dr. van der Aalst[/caption] Carlijn M. van der Aalst, Ph.D. MPH Department of Public Health Erasmus MC MedicalResearch.com: What is the background for this study? Response: Lung cancer is the leading cause of cancer-related mortality among both men and women. About 70% of patients with lung cancer are diagnosed with advanced disease, which results in only 15% surviving five years. About 70% of patients with lung cancer are diagnosed with advanced disease, a stage in which cure is problematic. This results in only 15% surviving five years. Although quit smoking is most effective in preventing lung cancer, about half of all lung cancers are currently diagnosed in former smokers, who remain at high risk for decades after quitting smoking. The National Lung Screening Trial (NLST; U.S.) reported a 20% lung cancer-related mortality reduction and a 6.7% reduction in all-cause mortality for CT screening compared with chest radiography screening for lung cancer in 53,454 enrolled subjects at high risk for lung cancer.1 As a consequence, the United States Preventive Services Task Force (USPSTF) requested an independent review and a modelling study. Based on these NLST data, an efficient strategy with a reasonable harm-benefit ratio could be established, resulting in the recommendation to annually screen persons aged 55-80 with ≥30 pack-years of smoking history, who currently smoke or quit smoking <15 years ago. However, data of only one trial provides limited evidence and more trial data are needed. NELSON is the second largest lung cancer screening trial that is adequately designed to provide the evidence that is needed to conclude whether CT screening can reduce lung cancer mortality.
Author Interviews, Endocrinology, NEJM, Thyroid Disease / 23.01.2020

MedicalResearch.com Interview with: [caption id="attachment_52898" align="alignleft" width="142"]Raymond S Douglas MD PhD Professor of Surgery, Division of Ophthalmology Director of the Orbital and Thyroid Eye Disease Program Cedars Sinai Medical Center Dr. Douglas[/caption] Raymond S Douglas MD PhD Professor of Surgery, Division of Ophthalmology Director of the Orbital and Thyroid Eye Disease Program Cedars Sinai Medical Center MedicalResearch.com: What is the background for this study? Response: Thyroid eye disease (TED) is a debilitating disease that affects all aspects of a patients life. It is often associated with Graves' disease and thyroid abnormalities. TED causes profound bulging of the eyes impairing vision, causing eye pain and facial disfigurement.
Abbvie, Author Interviews, NEJM, OBGYNE / 23.01.2020

MedicalResearch.com Interview with: [caption id="attachment_52895" align="alignleft" width="150"]William D Schlaff MD Chair, Department of Obstetrics & Gynecology Jefferson University Dr. Schlaff[/caption] William D Schlaff  MD Chair, Department of Obstetrics & Gynecology Jefferson University MedicalResearch.com: What is the background for this study? Response: Symptomatic uterine fibroids are the most common indication for hysterectomy in the US.  Heavy bleeding is the most common and troublesome symptom.  The primary treatment for this problem is surgery—either hysterectomy or (less commonly) myomectomy.  Medical treatment which reduces the bleeding related to fibroids without surgery is a valuable treatment for many women.  Existing medications include, most commonly GnRH agonists.  These are injectable medications that are given every 1 or 3 months (depending on the formulation) and have been shown to reduce bleeding related to fibroids.  They work by initially stimulating the ovaries to increase estrogen levels for 10-14 days before suppressing estrogen and thereby reducing bleeding.  Even though the medication is given every 1 or 3 months, the effect of the medication can last quite a bit longer; in cases of adverse response, the medication cannot be immediately stopped.  The medication reported in this trial, Elagolix, is a GnRH antagonist given by mouth twice daily and resulting in suppression of estrogen secretion within a matter of hours.  The effect of this medication wears off much more rapidly than the depot formulations described and can be stopped in the uncommon cases of adverse side effects. 
Author Interviews, Johns Hopkins, NEJM, Weight Research / 02.01.2020

MedicalResearch.com Interview with: [caption id="attachment_52623" align="alignleft" width="230"]Mark P. Mattson, Ph.D. Adjunct Professor of Neuroscience Johns Hopkins University School of Medicine Dr. Mattson[/caption] Mark P. Mattson, Ph.D. Adjunct Professor of Neuroscience Johns Hopkins University School of Medicine  MedicalResearch.com: What is the background for this study? Response: The usual eating pattern of most people in modern societies is breakfast, lunch, dinner plus a snack(s) every day.   Animals used for most biomedical research – rats and mice – are usually fed ‘ad libitum’ (food is always available for them to eat).    During the past 25 years, myself and the many scientists who trained in my laboratory discovered that when rats or mice are fed intermittently such that they have no food every other day or eat only during a 4-6 hour time period each day, their overall health improves in many ways.  Animals on such intermittent fasting (IF) regimens exhibit signs of slowed aging and they live much longer than those fed ad libitum. The editors of the New England Journal of Medicine invited me and Rafa de Cabo (a former postdoc in my laboratory at the National Institute on Aging) to write this review article for two main reasons.   First, there have been a sufficient number of studies demonstrating the health benefits of IF in humans and knowledge of the underlying mechanisms to justify a review article.  Second, many physicians are being asked about IF by their patients and the physicians are not privy as to if they should recommend IF and how to prescribe specific IF eating patterns and follow-up to increase the likelihood that the patient will be successful in changing their eating pattern. 
Alcohol, Author Interviews, Heart Disease, NEJM / 02.01.2020

MedicalResearch.com Interview with: [caption id="attachment_52609" align="alignleft" width="200"]Professor Peter M Kistler MBBS, PhD, FRACP Head of Clinical Electrophysiology Research Baker Heart and Diabetes Institute Head of Electrophysiology at The Alfred hospital Professor of Medicine University of Melbourne. Dr. Kistler[/caption] Professor Peter M Kistler MBBS, PhD, FRACP Head of Clinical Electrophysiology Research Baker Heart and Diabetes Institute Head of Electrophysiology at The Alfred hospital Professor of Medicine University of Melbourne. MedicalResearch.com: What is the background for this study? Response: There is a well known association between alcohol intake and atrial fibrillation form population based studies which demonstrate that for every 1 standard drink the incidence of AFib increases by 8%. This is the first randomised study to determine of alcohol reduction/abstinence leads to a reduction in AFib episodes and time to recurrence.
Author Interviews, Epilepsy, NEJM, NIH / 11.12.2019

MedicalResearch.com Interview with: [caption id="attachment_52433" align="alignleft" width="160"]Robin Conwit, M.D Program Director, Division of Clinical Research NIH: National Institute of Neurological Disorders and Stroke Dr. Conwit[/caption] Robin Conwit, M.D Program Director, Division of Clinical Research NIH: National Institute of Neurological Disorders and Stroke MedicalResearch.com: What is the background for this study? Response: Approximately one-third of patients with intractable status epilepticus do not respond to benzodiazepines, often the first line medications given in the emergency department, leaving doctors to decide among three commonly prescribed anti-convulsants. In this study all of the anti-convulsants were equally effective. The trial gives doctors a way to clear the air of arguments that one of these drugs works any better than the others, or that any one of them is a lot safer.  It gives doctors a reason to choose a dosing strategy in status epilepticus for levetiracetam, which has otherwise been controversial and non-standard.  
Author Interviews, Lipids, NEJM, Neurological Disorders, Stroke / 18.11.2019

MedicalResearch.com Interview with: [caption id="attachment_52201" align="alignleft" width="200"]Dr-Pierre Amarenco Dr. Pierre Amarenco[/caption] Pierre Amarenco, MD Professor and Chairman Paris University, Paris, France INSERM Department of Neurology and Stroke Centre Bichat Hospital Paris, France MedicalResearch.com: What is the background for this study? Response: The rationale of the Treat Stroke to target trial was that after we published the SPARCL trial in 2006 (atorvastatin 80 mg/day vs placebo in patients with stroke) which showed a 16% relative risk reduction of recurrent stroke, we performed several pre specified and post hoc analyses, showing that in SPARCL patients randomized with "atherosclerotic disease" the risk reduction for the primary endpoint was much higher (33%), and in in patients achieving a LDL cholesterol of less than 70 mg/dL as compared to those achieving a LDL cholesterol 100 mg/dL or higher, the risk reduction was 28%. Therefore to confirm this findings, we designed the TST trial, which was an investigator initiated trial funded by the french ministry of health,  and enrolled patients with an ischemic stroke due to atherosclerotic stenosis and randomized them to either a target LDL cholesterol of less than 70 mg/dL or a target LDL cholesterol of 90 to 110 mg/dL. To achieve these goals, the investigators could use any statin available on the market, and titrate the dosage of the statin to get to the assigned target. They could also use ezetimibe on top of statin therapy if a high dosage of statin was not sufficient to get to the target level assigned by randomization.
Author Interviews, Education, NEJM, Surgical Research / 31.10.2019

MedicalResearch.com Interview with: [caption id="attachment_51961" align="alignleft" width="99"]Ryan J. Ellis, MD MS General Surgery Resident Surgical Outcomes and Quality Improvement Center (SOQIC) Northwestern Medicine  Dr. Ellis[/caption] Ryan J. Ellis, MD MS General Surgery Resident Surgical Outcomes and Quality Improvement Center (SOQIC) Northwestern Medicine  MedicalResearch.com: What is the background for this study? Response: Burnout has emerged as a significant problem affecting the entire healthcare workforce and it has been likely to myriad downstream problems such as increases in medical errors, alcoholism, and depression. Despite the attention on clinician burnout, there are significant gaps in our understanding of how the workplace environment may lead to burnout. Moreover, there are particular concerns about the workplace environment in training, specifically with regards to abuse, discrimination, and harassment. We had the opportunity to survey all U.S. general surgery residents to comprehensively define the frequency of workplace mistreatment and its relationship with burnout and suicidal thoughts among surgical residents.
Author Interviews, Heart Disease, NEJM / 02.10.2019

MedicalResearch.com Interview with: [caption id="attachment_51678" align="alignleft" width="225"]Dr Jean-Baptiste Lascarrou Dr. Baptiste Lascarrou[/caption] Dr Jean-Baptiste Lascarrou  Médecine Intensive Réanimation CHU de Nantes Nantes   MedicalResearch.com: What is the background for this study? What are the main findings? Response: Ancillary study of TTM1 trial & meta-analyses of nonrandomized studies have provided conflicting data on moderate therapeutic hypothermia, or targeted temperature management, at 33°C in patients successfully resuscitated after nonshockable cardiac arrest. Nevertheless, the latest recommendations issued by the International Liaison Committee on Resuscitation and by the European Resuscitation Council recommend moderate therapeutic hypothermia.
Author Interviews, Heart Disease, NEJM, Vanderbilt / 18.09.2019

MedicalResearch.com Interview with: [caption id="attachment_51303" align="alignleft" width="133"]Daniel Muñoz, M.D, M.P.A Assistant Professor of Medicine, Division of Cardiology Medical Director for Quality, Vanderbilt Heart & Vascular Institute Medical Director, Cardiovascular ICU Vanderbilt University Medical Center Nashville, Tennessee Dr. Munoz[/caption] Daniel Muñoz, M.D, M.P.A Assistant Professor of Medicine, Division of Cardiology Medical Director for Quality, Vanderbilt Heart & Vascular Institute Medical Director, Cardiovascular ICU Vanderbilt University Medical Center Nashville, Tennessee MedicalResearch.com: What is the background for this study? Response: Despite advances in the prevention and treatment of cardiovascular disease, it remains the number one global killer of both men and women. Patients face a variety of barriers to getting the care need, including cost and complexity of medication regimens. Innovative strategies are needed to improve the delivery of preventive care, especially when it comes to socio-economically vulnerable individuals. The polypill, a fixed-dose combination of 3 blood pressure lowering medications and a cholesterol lowering medication, may be a strategy for improving cardiovascular disease prevention. We enrolled 303 patients at a community health center in Mobile, Alabama. Half of the patients were assigned to take a daily polypill, while the other half received their usual medical care. Participants underwent a standard medical exam, blood pressure measurement, and blood cholesterol testing during their initial visit, a 2-month visit, and a 12-month visit. MedicalResearch.com: What are the main findings?
  • Participants in the polypill group experienced a greater reduction in both systolic blood pressure and LDL cholesterol level, as compared with participants in the usual care group. These differences translate to an approximate 25% reduction in the risk of experiencing a cardiovascular event.
  • At 12 months, adherence to the polypill regimen, as assessed based on pill counts, was 86%.
  • The vast majority of our study participants were African-American (96%), with three quarters reporting an annual income below $15,000.
Author Interviews, Environmental Risks, Global Health / 22.08.2019

MedicalResearch.com Interview with: Cong Liu, PhD Department of Environmental Health School of Public Health Fudan University Shanghai 200032, China MedicalResearch.com: What is the background for this study? Response: Numerous time-series studies have examined the short-term associations between particulate air pollution (PM10 and PM2.5) exposures and daily mortality. However, most evidence has been obtained from studies in single cities, regions, or countries. There are challenges in comparing these results and in synthesizing effect estimates because of different modeling approaches and potential publication bias. Furthermore, there has never been a global representative concentration-response function for risk assessment and policy making. We and our co-authors established the Multi-City Multi-Country (MCC) Collaborative Research Network to perform a global assessment of the effects of weather or climate on mortality. This network allowed us to examine and compare the associations of PM concentrations with daily mortality at the global, regional, and country level with the use of a standardized analytic framework.
Author Interviews, Cost of Health Care, Medicare / 14.08.2019

MedicalResearch.com Interview with: ABT-AssociatesMatthew Trombley, Ph.D. Associate/Scientist Abt Associates  MedicalResearch.com: What is the background for this study?   Response: CMS developed the Accountable Care Organization (ACO) Investment Model (AIM) as part of the Medicare Shared Savings Program (MSSP) to encourage the growth of ACOs in rural and underserved areas.  The goal of our study was to see if AIM ACOs could successfully decrease Medicare spending in these areas.
Author Interviews, Global Health, HIV, NEJM / 17.07.2019

MedicalResearch.com Interview with: [caption id="attachment_50304" align="alignleft" width="107"]Prof-Richard-Hayes.jpg Prof. Hayes[/caption] Dr. Richard J. Hayes, DSc, FMedSci Professor of Epidemiology and International Health London School of Hygiene and Tropical Medicine MedicalResearch.com: What is the background for this study? Response: HIV incidence rates remain at very high levels in many parts of southern Africa. Universal testing and treatment (i.e., ensuring that everyone in a community tests for HIV and that everyone diagnosed with HIV is started on treatment as soon as possible) has been proposed as a strategy to achieve steep reductions in HIV incidence in generalized epidemics. Prior trials have shown inconsistent results as to whether this strategy could be effective. HPTN 071 (PopART) was carried out in 21 urban communities in Zambia and South Africa, with individual communities randomly assigned into one of three arms: A, B or C. The 14 communities in Arms A and B received annual rounds of home-based HIV testing by community health workers who supported linkage to care, antiretroviral therapy (ART) adherence and other HIV services. The seven communities in Arm C received the local standard of care. We looked to see if the HIV incidence in the communities receiving universal testing and treatment would be lower (over time) compared to the incidence in the standard of care communities.
Author Interviews, Biomarkers, NEJM, Pulmonary Disease / 11.07.2019

MedicalResearch.com Interview with: [caption id="attachment_50147" align="alignleft" width="200"]Dr. Chris Butler,, BA MBChB DCH CCH MD FRCGP (Hon)FFPH FMedSci Professor of Primary Care Nuffield Department of Primary Care Health Sciences, Professorial Fellow at Trinity College Clinical Director Primary Care Clinical Trials Unit University of Oxford Dr. Butler[/caption] Dr. Chris Butler,, BA MBChB DCH CCH MD FRCGP (Hon)FFPH FMedSci Professor of Primary Care Nuffield Department of Primary Care Health Sciences, Professorial Fellow at Trinity College Clinical Director Primary Care Clinical Trials Unit University of Oxford  MedicalResearch.com: What is the background for this study? Response: More than a million people in the UK have COPD, which is a lung condition associated with smoking and other environmental pollutants. People living with the condition often experience exacerbations, or flare-ups, and when this happens, three out of four are prescribed antibiotics. However, two-thirds of these flare-ups are not caused by bacterial infections and antibiotics often do not benefit patients. A simple finger-prick blood test could help prevent unnecessary prescribing of antibiotics for people with the lung condition chronic obstructive pulmonary disease (COPD).  The finger-prick test measures the amount of C- reactive protein (CRP) - a marker of inflammation that rises rapidly in the blood in response to serious infections. People with a COPD flare-up who have a low CRP level in the blood appear to receive little benefit from antibiotic treatment. The General Practitioner (GP) use of a C-Reactive Protein (CRP) Point of Care Test (POCT) to help target antibiotic prescribing to patients with Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) who are most likely to benefit (The PACE Study) determined whether the using a POCT CRP to guide antibiotic treatment decisions for acute exacerbations of COPD reduced antibiotic use without harming patients.
Author Interviews, Brain Injury, Columbia, Critical Care - Intensive Care - ICUs, NEJM, Neurology / 27.06.2019

MedicalResearch.com Interview with: [caption id="attachment_49981" align="alignleft" width="134"]Jan Claassen, MD, PhD, FNCS Associate Professor of Neurology Division of Division of Critical Care and Hospitalist Neurology Columbia University Medical Center Dr. Claassen[/caption] Jan Claassen, MD, PhD, FNCS Associate Professor of Neurology Division of Division of Critical Care and Hospitalist Neurology Columbia University Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Unconsciousness is common and predicting recovery is challenging – often inaccurate. Many patients do not show movements on commands and typically this is interpreted as unconsciousness. Some of these patients may be able to have brain response to these commands raising the possibility of some preservation of consciousness. This has previously been shown months or years after the injury mostly using MRI. We were able to detect this activation at the bedside in the ICU shortly after brain injury. For this we applied machine learning to the EEG to distinguish the brain’s responses to commands. Patients that showed this activation were more likely to follow commands prior to discharge and had better outcomes one year later. 
Anesthesiology, Author Interviews, Geriatrics, NEJM / 23.06.2019

MedicalResearch.com Interview with: [caption id="attachment_49917" align="alignleft" width="128"]Yahya Shehabi  PhD, FANZCA, FCICM, EMBA, GAICD Director of Research, Critical Care and Peri-operative Medicine, Monash Health Professor, School of Clinical Sciences, Faculty of Medicine Nursing and Health Sciences, Monash University Professor Intensive Care Medicine, Clinical School of Medicine, University New South Wales Critical Care and Peri-Operative Medicine Lead – Monash Health Translational Precinct  Dr. Shehabi[/caption] Yahya Shehabi  PhD, FANZCA, FCICM, EMBA, GAICD Director of Research, Critical Care and Peri-operative Medicine, Monash Health Professor, School of Clinical Sciences, Faculty of Medicine Nursing and Health Sciences, Monash University Professor Intensive Care Medicine, Clinical School of Medicine, University New South Wales Critical Care and Peri-Operative Medicine Lead – Monash Health Translational Precinct MedicalResearch.com: What is the background for this study? Response: SPICE III was the final phase of a series of SPICE studies. SPICE I showed 2 important findings, first, deep sedation in the first 48 hours is strongly associated with higher mortality, longer ventilation time and higher risk of delirium. Second; that Dexmedetomidine is mainly used as an adjunct secondary agent 3-4 days after commencing mechanical ventilation and not as a primary sedative agent. In addition, albeit with several limitations, previous RCTs comparing Dexmedetomidine with conventional sedatives showed reduced iatrogenic coma, shortened ventilation time and reduced delirium with Dexmedetomidine treatment. So based on the above we hypothesized that using Dexmedetomidine soon after commencing ventilation as a primary sedative agent, through reducing early iatrogenic coma, ventilation time and delirium, would impact 90 day-mortality.
Author Interviews, Biomarkers, Genetic Research, Infections, NEJM, UCSF / 13.06.2019

MedicalResearch.com Interview with: [caption id="attachment_49751" align="alignleft" width="150"]Dr. Charles Chiu, M.D./Ph.D. Professor, Laboratory Medicine and Medicine / Infectious Diseases Director, UCSF-Abbott Viral Diagnostics and Discovery Center Associate Director, UCSF Clinical Microbiology Laboratory UCSF School of Medicine Dr. Chiu[/caption] Dr. Charles Chiu, M.D./Ph.D. Professor, Laboratory Medicine and Medicine / Infectious Diseases Director, UCSF-Abbott Viral Diagnostics and Discovery Center Associate Director, UCSF Clinical Microbiology Laboratory UCSF School of Medicine MedicalResearch.com: What is the background for this study? Would you describe what is meant by metagenomic sequencing? Response: Metagenomic next-generation sequencing (mNGS) is the use of technology to generate millions of sequence reads to diagnose infection sin patients by characterizing the full range of potential pathogens (bacteria, viruses, fungi, and parasites) in a single sample. Although shown to be a promising diagnostic tool for  infectious diseases in case reports and limited case series (Chiu and Miller Nature Reviews Genetics 20, 341-355 (2019)), to date the “real-life” utility of this approach for patient care has hitherto not been demonstrated.  This study is the first prospective, multi-center study of clinical mNGS testing for the diagnosis of neurological infections in acutely ill hospitalized patients presenting with meningitis and/or encephalitis.
Author Interviews, Diabetes, Vitamin D / 09.06.2019

MedicalResearch.com Interview with: [caption id="attachment_49667" align="alignleft" width="142"]Anastassios G. Pittas, M.D MS Professor Co-Director, Diabetes and Lipid Center; Tufts University School of Medicine Dr. Pittas[/caption] Anastassios G. Pittas, M.D MS Professor Co-Director, Diabetes and Lipid Center; Tufts Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Observational studies have consistently reported an association between low blood vitamin D level and development of type 2 diabetes. However, whether vitamin D supplementation lowers risk of developing diabetes is not known. We designed and conducted the Vitamin D and diabetes (D2d) study to answer this question.  We randomized 2,423 people with prediabetes to 4,000 IU/day of vitamin D3 or placebo and followed them for new-onset diabetes with blood tests every 6 months for an average of 2.5 years. About 80% of participants had sufficient vitamin D level at baseline (25-hydroxyvitamin D level >= 20 ng/mL). The trial was designed to show a reduction of 25% or more in diabetes risk with vitamin D. The study was unable to show a reduction of 25% or more. At the end of the study, there was a 12% reduction in risk of developing diabetes with vitamin D, which missed statistical significance (hazard ration 0.88; 95% confidence interval 0.75 to 1.04). In a small subgroup of participants with vitamin D deficiency at baseline (25-hydroxyvitamin D level < 12 ng/mL) there was 62% reduction in risk of diabetes with vitamin D (hazard ration 0.38; 95% confidence interval 0.18 to 0.80).
Author Interviews, Boehringer Ingelheim, NEJM, Pharmaceutical Companies, Pulmonary Disease / 30.05.2019

MedicalResearch.com Interview with: [caption id="attachment_49455" align="alignleft" width="200"]Donald Zoz, M.D.,Senior associate directorClinical Development & Medical AffairsBoehringer Ingelheim Pharmaceuticals, Inc. Dr. Zoz[/caption] Donald Zoz, M.D., Senior associate director Clinical Development & Medical Affairs Boehringer Ingelheim Pharmaceuticals, Inc. MedicalResearch.com: What is the background for this study? How does nintedanib differ from other treatments for SSc-ILD? What are the main findings?  Response: SENSCIS is a Phase III double-blind, randomized placebo-controlled trial that included 576 patients in 32 countries. It is the largest trial to have been conducted in patients with systemic sclerosis associated interstitial lung disease (SSc-ILD). The primary endpoint was the annual rate of decline in forced vital capacity (FVC) over 52 weeks. At the end of the 52-week trial, patients receiving nintedanib had an adjusted annual rate of decline in FVC (mL/year) of -52.4 with nintedanib versus -93.3 with placebo (absolute difference 41.0mL/year [95% CI 2.9, 79.0]; p=0.04). This corresponds to a relative difference of 44% reduction in lung function decline. There are currently no approved treatments for SSc-ILD., BI conducted the SENSCIS study to evaluate in SSc-ILD patients the impact of nintedanib. Nintedanib, a selective tyrosine kinase inhibitor, is an antifibrotic agent. Results of the study, which were published in The New England Journal of Medicine and presented at the American Thoracic Society (ATS) International Conference, showed that nintedanib slowed the loss of pulmonary function by 44% in patients with SSc-ILD relative to placebo, as measured by FVC over 52 weeks. 
Author Interviews, Immunotherapy, NEJM, Pulmonary Disease / 22.05.2019

MedicalResearch.com Interview with: [caption id="attachment_49320" align="alignleft" width="148"]Gerard J. Criner, MD, FACP, FACCPChair and Professor, Thoracic Medicine and SurgeryLewis Katz School of MedicineTemple University Dr. Criner[/caption] Gerard J. Criner, MD, FACP, FACCP Chair and Professor, Thoracic Medicine and Surgery Lewis Katz School of Medicine Temple University  MedicalResearch.com: What is the background for this study? Response: An earlier, Phase II trial of benralizumab found a non-statistically significant reduction in COPD exacerbation rate for patients with eosinophilic inflammation in the airways. In this Phase III trial, the researchers sought to discover whether benralizumab's ability to deplete the airways of blood eosinophils in patients with eosinophilic inflammation would lead to a reduction in COPD exacerbations. The Phase III, randomized, double-blind, placebo-controlled, parallel-group clinical trials GALATHEA and TERRANOVA evaluated the efficacy and safety of benralizumab for the prevention of exacerbations in patients with moderate to very severe COPD, eosinophilic inflammation, and increased risk of exacerbations. Benralizumab is a type of drug called an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody. It is approved by the FDA for the treatment of severe eosinophilic asthma.
Author Interviews, Clots - Coagulation, NEJM, Neurology / 09.05.2019

MedicalResearch.com Interview with: [caption id="attachment_49060" align="alignleft" width="165"]Geoffrey A Donnan AOMBBS, MD, FRCP, FRACP, FAAHMSProfessor of NeurologyUniversity of Melbourne, Melbourne Brain Centre,Royal Melbourne and Austin Hospitals Prof. Donnan[/caption] Geoffrey A Donnan AO MBBS, MD, FRCP, FRACP, FAAHMS Professor of Neurology University of Melbourne, Melbourne Brain Centre Royal Melbourne and Austin Hospital MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Currently the thrombolysis time window for acute ischemic stroke is restricted to less than 4.5 hours from stroke onset and patients with wake-up stroke are not eligible. EXTEND is a multi-centre randomised placebo-controlled trial involving patient with acute ischemic stroke who presented between 4.5 to 9 hours of stroke onset or with wake-up-stroke and had penumbral tissue demonstrated on automated perfusion imaging. Patients were randomised to receive either alteplase or placebo. In total there were 225 patients recruited and the patients who received alteplase had higher rate of excellent functional outcome at 3 months (35.4% vs 29.5% adjusted odd ration 1.44 with 95% confidence interval 1.01 – 2.06 p=0.04). Patients who received alteplase achieved higher rate of early neurological improvement at day 3, reperfusion and recanalization at 24 hours. There was numerically more haemorrhage in the alteplase group but this not negate the functional benefit and there was no difference in the rate of mortality between the two groups. 
Author Interviews, Global Health, Infections, NEJM / 08.05.2019

MedicalResearch.com Interview with: [caption id="attachment_49046" align="alignleft" width="133"]Birgit Nikolay PhDMATHEMATICAL MODELLING OF INFECTIOUS DISEASESInstitut Pasteur Dr. Nikolay[/caption] Birgit Nikolay PhD MATHEMATICAL MODELLING OF INFECTIOUS DISEASES Institut Pasteur  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Nipah virus was identified by the World Health Organization as an emerging infectious disease that may cause major epidemics if the pathogen evolves to become more transmissible, leading the organization to prioritize it for research to prevent future health emergencies. In the absence of efficient treatments or vaccines, the only way to control Nipah virus outbreaks is through targeted interventions that limit opportunities of spread. Designing such interventions is challenging in a context where transmission mechanisms remain poorly understood. The study provides important insights to better understand these mechanisms.
Alzheimer's - Dementia, Author Interviews, Merck, NEJM / 10.04.2019

MedicalResearch.com Interview with: Michael F. Egan, MDVice President,  NeuroscienceGlobal Clinical DevelopmentMerck Research LaboratoriesNorth Wales, PAMichael F. Egan, MD Vice President,  Neuroscience Global Clinical Development Merck Research Laboratories North Wales, PA  MedicalResearch.com: What is the background for this study?   Response: Alzheimer’s disease (AD) appears to be due to the gradual accumulation of amyloid over many years (the “amyloid hypothesis”). At some point, it is thought that amyloid triggers abnormalities in tau, which then forms deposits within neurons and leads to progressive neurodegeneration. Amyloid is made up of  a small, sticky peptide, Abeta, which is produced when the enzyme BACE cleaves a large protein called APP.  In our trial, we tested whether a potent BACE inhibitor, verubecestat, could slow disease progression in subjects with early AD (or prodromal AD) by blocking formation of Abeta.  A previous trial in subjects with dementia due to AD failed to find evidence of efficacy. One possible reason for this failure is that subjects had too much amyloid in their brain already.