Author Interviews, HIV, NEJM, University of Pennsylvania / 24.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29950" align="alignleft" width="148"]Katharine J Bar, MD Assistant Professor of Medicine Attending Physician, Infectious Diseases, Hospital of the University of Pennsylvania Physician, International Travel Medicine, Perelman Center for Advanced Medicine Director, Penn CFAR Viral and Molecular Core Dr. Katharine J Bar[/caption] Katharine J Bar, MD Assistant Professor of Medicine Attending Physician, Infectious Diseases, Hospital of the University of Pennsylvania Physician, International Travel Medicine, Perelman Center for Advanced Medicine Director, Penn CFAR Viral and Molecular Core MedicalResearch.com: What is the background for this study? What are the main findings? Response: The passive administration of monoclonal antibodies has revolutionized many fields of medicine. Anti-HIV monoclonal antibodies are being explored as components of novel therapeutic and curative strategies, as they can both neutralize free virus and kill virus-infected cells. We sought to determine whether passive administration of an anti-HIV monoclonal antibody, VRC01, to chronically HIV-infected individuals on antiretroviral medications (ART) would be safe and well tolerated and could delay virus rebound after discontinuation of their ART.
Author Interviews, NEJM, Outcomes & Safety, Surgical Research / 22.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29912" align="alignleft" width="200"]Alan Karthikesalingam MD PhD, NIHR Academic Clinical Lecturer in Vascular Surgery St George's Vascular Institute London, UK Dr. Alan Karthikesalingam[/caption] Alan Karthikesalingam MD PhD, NIHR Academic Clinical Lecturer in Vascular Surgery St George's Vascular Institute London, UK MedicalResearch.com: What is the background for this study? What are the main findings? Response: The background for this study was that the typical diameter at abdominal aortic aneurysm (AAA)  repair, and the population incidence of AAA repair, have been known to vary considerably between different countries. This study aimed to observe whether a discrepancy in the population incidence rate of AAA repair between England and the USA was seen alongside a discrepancy in population rates of AAA-related mortality or AAA rupture in those countries.
ALS, Author Interviews, NEJM, Technology / 19.11.2016

MedicalResearch.com Interview with: Mariska Van Steensel PhD Nick F. Ramsey, Ph.D. Department of Neurology and Neurosurgery Brain Center Rudolf Magnus University Medical Center Utrecht Utrecht, the Netherlands MedicalResearch.com: What is the background for this study? What are the main findings? Response: Patients who are severely paralyzed due to for example ALS or brain stem stroke are often unable to speak (also called ‘ Locked-in State'), and therefore need assistive devices, such as an eye tracker, for their communication. When these devices fail (e.g. due to environmental lighting or eye movement problems), people may indicate yes or no with eye blinks in response to closed questions. This leaves patients in a highly dependent position, since questions asked may or may not represent their actual wish or comment. In the current study, we used a technology called brain-computer interfacing (BCI), to allow a patient with late-stage amyotrophic lateral sclerosis (ALS) to control a communication device using her brain signals. The patient was implanted with subdural electrodes that covered the brain area that is normally responsible for hand movement. The electrodes were connected with wires, subcutaneously, to an amplifier/transmitter device that was placed subcutaneously under the clavicle. The patient was able to generate a signal equivalent to a mouse-click with this brain-computer interface by attempting to move her hand, and used it to make selections of letters or words on her communication device, with high accuracy and a speed of 2 letters per minute. She used the brain-computer interface system to communicate whenever she was outside, as her eye-tracker device does not function well in that situation.
Author Interviews, Critical Care - Intensive Care - ICUs, Kidney Disease, NEJM, Pediatrics / 18.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29776" align="alignleft" width="133"]Stuart L. Goldstein, MD, FAAP, FNKF</strong> Clark D. West Endowed Chair Professor of Pediatrics | University of Cincinnati College of Medicine Director, Center for Acute Care Nephrology | Associate Director, Division of Nephrology Medical Director, Pheresis Service | Co-Medical Director, Heart Institute Research Core Division of Nephrology and Hypertension | The Heart Institute Cincinnati Children’s Hospital Medical Center Cincinnati, OH 45229 Dr. Stuart L. Goldstein[/caption] Stuart L. Goldstein, MD, FAAP, FNKF Clark D. West Endowed Chair Professor of Pediatrics University of Cincinnati College of Medicine Director, Center for Acute Care Nephrology | Associate Director, Division of Nephrology Medical Director, Pheresis Service | Co-Medical Director, Heart Institute Research Core Division of Nephrology and Hypertension | The Heart Institute Cincinnati Children’s Hospital Medical Center Cincinnati, OH 45229 MedicalResearch.com: What is the background for this study? What are the main findings? Response: This was a prospective international multi-center assessment of the epidemiology of acute kidney injury in children in young adults. Over 5,000 children were enrolled from 32 pediatric ICUs in 9 countries on 4 continents. The main findings are: 1) Severe AKI, defined by either Stage 2 or 3 KDIGO serum creatinine and urine output criteria carried an incremental risk of death after adjusting for 16 co-variates. 2) Patients with AKI by low urine output would have been misclassified as not having AKI by serum creatinine criteria and patients with AKI by urine output criteria have worse outcomes than patients with AKI by creatinine crtieria. 3) Severe AKI was also associated with increased and prolonged mechanical ventilation use, increased receipt of dialysis or ECMO
Author Interviews, Brigham & Women's - Harvard, Heart Disease, NEJM, Surgical Research / 17.11.2016

MedicalResearch.com Interview with: Mandeep R. Mehra, MD, FACC, FESC, FHFSA, FRCP Medical Director, Brigham and Women’s Hospital Heart and Vascular Center Executive Director, Center for Advanced Heart Disease Professor of Medicine, Harvard Medical School Editor in Chief, The Journal of Heart and Lung Transplantation Brigham and Women's Hospital Boston, MA Mandeep R. Mehra, MD, FACC, FESC, FHFSA, FRCP Medical Director, Brigham and Women’s Hospital Heart and Vascular Center Executive Director, Center for Advanced Heart Disease Professor of Medicine, Harvard Medical School Editor in Chief, The Journal of Heart and Lung Transplantation Brigham and Women's Hospital Boston, MA MedicalResearch.com: What is the background for this study? Response: 10% of patients with heart failure and a reduced ejection fraction transition into Advanced Stages of disease where they become unresponsive to life prolonging traditional medications. Such patients typically require intravenous inotropic therapy to preserve cardiac function but most remain profoundly limited in their quality of life. In such cases a heart transplant is desirable but this is an option for only a few patients. Left Ventricular Assist Devices (LVADs) have become the mainstay for treating such patients either while they await a transplant or as a permanent option. However, there are challenges leading to infections, strokes, bleeding and most importantly pump malfunction due to thrombosis of the LVAD itself. The HeartMate 3 LVAD is a centrifugal pump that is designed to overcome the problem of pump thrombosis by virtue of 3 engineering attributes: (a) A frictionless rotor that is based on a fully magnetically levitated platform (b) wide blood flow passages that reduce red cell destruction and (c) an artificial intrinsic pulse that prevents stasis of blood within the pump.
Author Interviews, Heart Disease, Lipids, NEJM, Pharmacology / 14.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29622" align="alignleft" width="133"]Kevin Fitzgerald, Ph.D. Alnylam Pharmaceuticals Cambridge, MA 02142 Dr. Kevin Fitzgerald[/caption] Kevin Fitzgerald, Ph.D. Alnylam Pharmaceuticals Cambridge, MA 02142 MedicalResearch.com: What is the background for this study? Response: Inclisiran (ALN-PCSsc) is a subcutaneously administered RNAi therapeutic targeting PCSK9 in development for the treatment of hypercholesterolemia. The Phase 1 trial of inclisiran was conducted in the U.K. as a randomized, single-blind, placebo controlled, single ascending-and multi-dose, subcutaneous dose-escalation study in 69 volunteer subjects with elevated baseline LDL-C (≥ 100 mg/dL). The primary objective of the study was to evaluate the safety, side effect profile, and pharmacodynamics effects of inclisiran.
Author Interviews, NEJM, Prostate Cancer / 21.10.2016

MedicalResearch.com Interview with: [caption id="attachment_29065" align="alignleft" width="151"]Professor Jenny Donovan OBE FMedSci NIHR-SI AcSS FFPHM Director, NIHR CLAHRC West (National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care West) at University Hospitals Bristol NHS Trust Lewins Mead, Bristol Professor of Social Medicine School of Social and Community Medicine University of Bristol Prof. Jenny Donovan[/caption] Professor Jenny Donovan OBE FMedSci NIHR-SI AcSS FFPHM Director, NIHR CLAHRC West (National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care West) at University Hospitals Bristol NHS Trust Lewins Mead, Bristol Professor of Social Medicine School of Social and Community Medicine University of Bristol  MedicalResearch.com: What is the background for this study? What are the main findings? Response: PSA testing identifies many men with prostate cancer, but they do not all benefit from treatment. Surgery, radiation therapy and various programs of active monitoring/surveillance can be given as treatments for fit men with clinically localized prostate cancer. Previous studies have not compared the most commonly used treatments in terms of mortality, disease progression and patient-reported outcomes. In the ProtecT study, we used a comprehensive set of validated measures, completed by the men at baseline (before diagnosis), at six and 12 months and then annually for six years. The main finding is that each treatment has a particular pattern of side-effects and recovery which needs to be balanced against the findings from the paper reporting the clinical outcomes (Hamdy et al).
Author Interviews, Infections, NEJM / 10.10.2016

MedicalResearch.com Interview with: [caption id="attachment_28693" align="alignleft" width="155"]Simon I. Hay, BSc, DPhil, DSc Professor of Global Health University of Washington Director of Geospatial Science Institute for Health Metrics and Evaluation (IHME). Prof. Simon Hay[/caption] Simon I. Hay, BSc, DPhil, DSc Professor of Global Health University of Washington Director of Geospatial Science Institute for Health Metrics and Evaluation (IHME). MedicalResearch.com: Why did you undertake this study? Response: As malaria control has not been routinely informed by subnational variation of malaria burden, we undertook the study to highlight the potential for high-resolution maps of disease burden to better understand the epidemiology of malaria as well as the contribution of recent control efforts as well as to better inform future malaria control efforts.
Author Interviews, Columbia, NEJM, Orthopedics, Osteoporosis / 21.09.2016

MedicalResearch.com Interview with: [caption id="attachment_28216" align="alignleft" width="118"]MedicalResearch.com Interview with: Felicia Cosman, M.D. Dr. Felicia Cosman[/caption] Felicia Cosman, M.D. Medical Director of the Clinical Research Center Helen Hayes Hospital Professor of Medicine Columbia University College of Physician and Surgeons New York Editor-in-Chief, Osteoporosis International MedicalResearch.com: What is the background for this study? What are the main findings? Response: Amgen and UCB presented detailed data from the Phase 3 FRAME study in an oral session at ASBMR 2016, and the data were also published in the New England Journal of Medicine. Additionally, the FRAME abstract has been awarded the 2016 ASBMR Most Outstanding Clinical Abstract Award. The FRAME data show significant reductions in both new vertebral and clinical fractures in postmenopausal women with osteoporosis. Patients receiving a monthly subcutaneous 210 mg dose of romosozumab experienced a statistically significant 73 percent reduction in the relative risk of a vertebral (spine) fracture through 12 months, the co-primary endpoint, compared to those receiving placebo (fracture incidence 0.5 percent vs. 1.8 percent, respectively [p<0.001]). By six months, new vertebral fractures occurred in 14 romosozumab and 26 placebo patients; between six to 12 months, fractures occurred in two versus 33 additional patients in each group, respectively. Patients receiving romosozumab experienced a statistically significant 36 percent reduction in the relative risk of a clinical fracture, a secondary endpoint, through 12 months compared to those receiving placebo (fracture incidence 1.6 percent vs. 2.5 percent, respectively [p=0.008]). In patients who received romosozumab in year one, fracture risk reduction continued through month 24 after both groups transitioned to denosumab treatment through the second year of the study: there was a statistically significant 75 percent reduction in the risk of vertebral fracture at month 24 (the other co-primary endpoint) in patients who received romosozumab followed by denosumab vs. placebo followed by denosumab (fracture incidence 0.6 percent vs. 2.5 percent, respectively [p<0.001]). Clinical fractures encompass all symptomatic fractures (both non-vertebral and painful vertebral fractures; all clinical fractures assessed in the FRAME study were symptomatic fragility fractures. A 33 percent reduction in relative risk of clinical fracture was observed through 24 months after patients transitioned from romosozumab to denosumab compared to patients transitioning from placebo to denosumab (nominal p=0.002, adjusted p=0.096).
Author Interviews, Global Health, Infections, NEJM / 21.09.2016

MedicalResearch.com Interview with: Dr. Heinke Kunst, M.D. Queen Mary University Hospital, London, United Kingdom MedicalResearch.com: What is the background for this study? What are the main findings? Response: Multidrug resistant tuberculosis (MDR-TB) has been on the increase worldwide over the past decade. Many patients who have been identified with MDR-TB live in the European region. Despite treatment with expensive second-line drug regimens, curing MDR TB remains a challenge and cure rates were thought to be very low. As part of the EU Commission funded TB-PANNET project 380 patients with MDR-TB were observed at 23 TB centers in countries of high, intermediate and low TB burden in Europe over a period of 5 years. Observation started from the time of diagnosis and lasted until one year after the end of the treatment. The TBNET proposed new definitions for “cure” and “failure” of MDR-TB treatment based on the sputum culture status at 6 month after the initiation of therapy and whether patients were free from disease recurrence one year after the end of therapy. The researchers found that the WHO criterion for “cure” could not be applied in the majority of patients, simply because most patients who were being treated successfully were not able to produce sputum after 8 months of therapy. The TB-PANNET study showed much higher cure rates using a new definition of cure and failure of treatment for MDR TB in the European region. (61% cure rates compared to only 31% when using WHO criteria.) The study also demonstrates that the results for “cure” from MDR-TB correlate very well with the level of drug resistance and the time to culture conversion that means the time when TB bacilli are no longer detectable in sputum. The new definitions are also independent of the total duration of treatment and can be applied to the standard 20 months MDR-TB regimen as well as to the 9-12 months shorter course MDR-TB treatment that was recently proposed by the WHO.
Author Interviews, NEJM, Prostate Cancer / 15.09.2016

MedicalResearch.com Interview with: [caption id="attachment_27922" align="alignleft" width="150"]Professor Jenny Donovan  PhD   OBE FMedSci NIHR-SI AcSS FFPHM Director, NIHR CLAHRC West (National Institute for Health Research Collaboration for  Leadership in Applied Health Research and Care West) at University Hospitals Bristol NHS Trust Bristol, UK Prof. Jenny Donovan[/caption] Professor Jenny Donovan  PhD OBE FMedSci NIHR-SI AcSS FFPHM Director, NIHR CLAHRC West (National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care West) at University Hospitals Bristol NHS Trust Bristol, UK MedicalResearch.com: What is the background for this study? What are the main findings? Response: PSA testing identifies many men with prostate cancer, but they do not all benefit from treatment. Surgery, radiation therapy and various programs of active monitoring/surveillance can be given as treatments for fit men with clinically localized prostate cancer. Previous studies have not compared the most commonly used treatments in terms of mortality, disease progression and patient-reported outcomes. In the ProtecT study, we used a comprehensive set of validated measures, completed by the men at baseline (before diagnosis), at six and 12 months and then annually for six years. The main finding is that each treatment has a particular pattern of side-effects and recovery which needs to be balanced against the findings from the paper reporting the clinical outcomes (Hamdy et al).
Author Interviews, Leukemia, NEJM, Transplantation / 08.09.2016

MedicalResearch.com Interview with: [caption id="attachment_27654" align="alignleft" width="133"]Dr. Filippo Milano, MD, PhD Assistant Member, Clinical Research Division Associate Director Cord Blood Transplantation Cord Blood Program Assistant Professor, University of Washington Fred Hutchinson Cancer Research Center Dr. Filippo Milano[/caption] Dr. Filippo Milano, MD, PhD Assistant Member, Clinical Research Division Associate Director Cord Blood Transplantation Cord Blood Program Assistant Professor, University of Washington Fred Hutchinson Cancer Research Center MedicalResearch.com: What is the background for this study? Response: When first introduced, cord blood (CB) graft was used only as a last resort when no suitable conventional donor could be identified, largely due to the limiting cell doses available in a cord blood graft. A CB graft, however, is attractive due to the increased level of HLA disparity that can be tolerated, without increased risk of graft versus host disease, allowing nearly all patients to find such a donor. The main intent of the study was to evaluate whether or not, at our Institution, cord blood SHOULD STILL BE considered only AS an alternative DONOR or IF instead outcomes were comparable to those obtained with more “conventional” types of transplants from matched and mismatched unrelated donors.
Author Interviews, NEJM, Pulmonary Disease / 07.09.2016

MedicalResearch.com Interview with: Jørgen Vestbo DMSc FRCP FERS Professor of  Respiratory Medicine Division of Infection, Immunity and Respiratory Medicine University of Manchester Education and Research Centre University Hospital of South Manchester Manchester MedicalResearch.com: What is the background for this study? What are the main findings? Response: Efficacy studies are limited in their usefulness to clinicians as there are often restricted inclusion criteria, with many exclusion criteria and patients are followed closely with high adherence to study treatment. They therefore show what the drugs can do but not necessarily what they do do in the real world. Randomised studies in everyday practice, not limiting the entry (effectiveness trials) are therefore needed. In our study we showed that it is feasible to do randomised studies in the “real world”. Our study showed that a simple treatment with a once-daily combination of an inhaled corticosteroid and a long-acting beta-agonist (Breo/Relvar) was superior to the usual care chose by the patients’ general practitioners to manage their COPD.
Asthma, Author Interviews, NEJM, Pediatrics, Pharmacology / 01.09.2016

MedicalResearch.com Interview with: David A Stempel, MD Medical Affairs Lead US Medical Affairs GlaxoSmithKline MedicalResearch.com: What is the background for this study? What are the main findings? Response: Long-acting beta-agonists (LABAs) have been shown to increase the risk of asthma-related death among adults and the risk of asthma-related hospitalization among children. It is unknown whether the concomitant use of inhaled glucocorticoids with LABAs mitigates those risks. This trial prospectively evaluated the safety of the LABA salmeterol, added to fluticasone propionate, in a fixed-dose combination in children.
Author Interviews, Heart Disease, NEJM, Surgical Research / 31.08.2016

MedicalResearch.com Interview with: Dr. Kaare Harald Bønaa Principal investigator University of Tromsø, Norway MedicalResearch.com: What is the background for this study? Response: The NORSTENT study was designed shortly after the “Barcelona fire storm” in 2006 that raised severe safety concerns against drug-eluting stents (DES). At that time there was evidence for increased risk of stent thrombosis with DES. How this could influence long term results compared to PCI with bare metal stents (MMS) was not known. Accordingly, we designed the NORSTENT study with the primary composite endpoint of all-cause mortality and non-fatal spontaneous myocardial infarction at a medial of 5 years of follow-up.
Author Interviews, Heart Disease, NEJM, Obstructive Sleep Apnea, Sleep Disorders / 30.08.2016

MedicalResearch.com Interview with: Prof. Craig Anderson, PhD Professor of Stroke Medicine and Clinical Neuroscience Medicine, The George Institute for Global Health University of Sydney MedicalResearch.com: What is the background for this study? What are the main findings? Response: We wished to prove whether treatment of obstructive sleep apnea with continuous positive airway pressure (CPAP ) can modify the risk of cardiovascular disease. The is a lot of association data from epidemiological and clinical studies but no large scale international clinical trials assessing the effects of CPAP on the prevention of serious cardiovascular events like heart attack and stroke. Our study in nearly 3000 adults with prior heart attack or stroke and moderate to severe obstructive sleep apnea showed that CPAP treatment did not prevent recurrent cardiovascular events or major cardiovascular risk factors. However CPAP did improve wearers' sense of wellbeing, mood and work productivity.
Author Interviews, Breast Cancer, Chemotherapy, Genetic Research, JAMA, NEJM / 26.08.2016

MedicalResearch.com Interview with: [caption id="attachment_27366" align="alignleft" width="150"]Prof. Laura van ’t Veer, PhD Leader, Breast Oncology Program, and Director, Applied Genomics, UCSF Helen Diller Family Comprehensive Cancer Center Angela and Shu Kai Chan Endowed Chair in Cancer Research UCSF Helen Diller Family Comprehensive Cancer Center Dr. Laura Van't Leer[/caption] Prof. Laura van ’t Veer, PhD Leader, Breast Oncology Program, and Director, Applied Genomics, UCSF Helen Diller Family Comprehensive Cancer Center Angela and Shu Kai Chan Endowed Chair in Cancer Research UCSF Helen Diller Family Comprehensive Cancer Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: MINDACT was designed to involve only patients with node negative and 1 to 3 positive lymph node breast cancer. Node negative breast cancer is a cancer that has not spread to the surrounding lymph nodes and therefore has a lower risk of recurrence. Scientists have also demonstrated that breast cancer which has spread to 1 to 3 lymph nodes may behave like node negative breast cancer. Patients with either node negative cancer or with a cancer that involves 1-3 lymph nodes are often prescribed chemotherapy, although physicians believe that approximately 15% of them do not require such treatment. MINDACT provides the highest level of evidence to show that using MammaPrint® can substantially reduce the use of chemotherapy in patients with node-negative and 1-to-3 node positive breast cancer – in other words, it can identify patients with these types of breast cancer who can safely be spared a treatment that may cause significant side effects, and will offer no to very little benefit.
Author Interviews, Diabetes, NEJM, OBGYNE, Technology / 19.08.2016

MedicalResearch.com Interview with: Professor Helen Murphy and Dr Zoe Stewart Institute of Metabolic Science University of Cambridge MedicalResearch.com: What is the background for this study? Response: Controlling blood glucose levels is a daily challenge for people with Type 1 diabetes and is particularly crucial during pregnancy. Previous research shows that women with type 1 diabetes spend only 12 hours per day within the recommended glucose target levels, leading to increased rates of complications including preterm delivery and large for gestational age infants. National surveys show that one in two babies suffer complications related to type 1 diabetes in the mother. The hormonal changes that occur in pregnancy make it difficult for women to predict the best insulin doses for every meal and overnight. Too much insulin causes low glucose levels harmful for the mother and too little causes problems for the developing baby. The artificial pancreas automates the insulin delivery giving better glucose control than we can achieve with currently available treatments. Previous studies show that the closed-loop system also known as artificial pancreas can be used safely in children and adults and our study aimed to investigate whether or not it was helpful for women with type1 diabetes during pregnancy.
Asthma, Author Interviews, Brigham & Women's - Harvard, NEJM, Pediatrics / 18.08.2016

MedicalResearch.com Interview with: [caption id="attachment_27010" align="alignleft" width="120"]Wanda Phipatanakul, MD, MS Associate Professor of Pediatrics Harvard Medical School Director, Asthma Clinical Research Center Boston Children's Hospital Asthma, Allergy and Immunology Boston, MA 02115 Dr. Wanda Phipatanakul[/caption] Wanda Phipatanakul, MD, MS Associate Professor of Pediatrics Harvard Medical School Director, Asthma Clinical Research Center Boston Children's Hospital Asthma, Allergy and Immunology Boston, MA 02115 MedicalResearch.com: What is the background for this study? What are the main findings? Response:  Acetaminophen (e.g., Tylenol, Panadol) and ibuprofen (e.g., Advil, Motrin) are the only available treatments for pain and fever in toddlers and the most commonly utilized medications worldwide. Recently there has been controversy and even alarm with suggestive observational data that acetaminophen makes asthma worse. This has led some experts to recommend the avoidance of acetaminophen in children with asthma. We sought to find the answer to this burning question through the first prospective, double-blind, randomized clinical trial comparing acetaminophen versus ibuprofen head to head for use when clinically indicated for fever or pain. Is there a difference in asthma morbidity (exacerbations) in young children between the age of 12-59 months, who have asthma?
Author Interviews, Hepatitis - Liver Disease, NEJM / 17.08.2016

MedicalResearch.com Interview with: Prof. Dr. F. Nevens, MD, PhD Professor of Medicine Hepatology and liver transplantation University Hospitals KU Leuven, Belgium Prof. Dr. F. Nevens, MD, PhD Professor of Medicine Hepatology and liver transplantation University Hospitals KU Leuven, Belgium MedicalResearch.com: What is the background for this study? Response: Primary biliary cholangitis (PBC) is a rare, autoimmune cholestatic liver disease that puts patients at risk for life-threatening complications. PBC is primarily a disease of women, affecting approximately one in 1,000 women over the age of 40. If left untreated, survival of PBC patients is significantly worse than the general population. The POISE trial evaluated the safety and efficacy of once-daily treatment with Ocaliva® (obeticholic acid) in PBC patients with an inadequate therapeutic response to, or who are unable to tolerate, ursodeoxycholic acid (UDCA), the current standard of care. Ocaliva is the first PBC therapy that targets the farnesoid X receptor (FXR), a key regulator of bile acid, inflammatory, fibrotic and metabolic pathways. The trial’s primary endpoint was an alkaline phosphatase (ALP) level of less than 1.67 times the upper limit of the normal range, with a reduction of at least 15% from baseline, and a total bilirubin level at or below the upper limit of the normal range after 12 months of obeticholic acid therapy. These liver biomarkers have been shown to predict progression to liver failure and resulting liver transplant or premature death in patients with PBC.
Author Interviews, NEJM, Neurological Disorders, Surgical Research / 12.08.2016

MedicalResearch.com Interview with: [caption id="attachment_26807" align="alignleft" width="133"]Photograph: Douglas Levere Dr. Gil Wolfe[/caption] Gil I. Wolfe, MD, FAAN Irvin and Rosemary Smith Professor and Chair Dept. of Neurology/Jacobs Neurological Institute Univ. at Buffalo Jacobs School of Medicine and Biomedical Sciences/SUNY Buffalo General Medical Center Buffalo, NY 14203-1126 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Thymectomy has been used in myasthenia gravis (MG), in particular those patients who do not have a tumor of the thymus gland, known as a thymoma, for over 75 years without randomized data to support its use. A practice parameter in 2000 on behalf of the American Academy of Neurology stated that the benefits of thymectomy in this population of non-thymomatou smyasthenia gravis patients remained uncertain, classified thymectomy as a treatment option in this group, and called for rigorous, randomized studies. What we found is that compared to an identical prednisone protocol alone, that extended transsternal thymectomy confers significant benefits to non-thymomatous MG patients over a period of three years after the procedure. The benefits include better disease status, reduced prednisone requirements, fewer hospitalizations to manage  myasthenia gravis worsenings, and a lower symptom profile related to side effects from medications used to control the disease state.
Author Interviews, Exercise - Fitness, Hematology, NEJM, Stanford / 08.08.2016

MedicalResearch.com Interview with: D. Alan Nelson, MPAS, PhD Postdoctoral research fellow Stanford Medicine MedicalResearch.com: What is the background for this study? Response: The study was inspired by the uncertainty surrounding sickle cell trait (SCT) and its association with serious exertional collapse events and mortality in active populations. I conducted initial, exploratory analyses on these topics in 2014-15 while examining a range of military readiness predictors and outcomes. The early work indicated that the risk of mortality, rhabdomyolysis and other exertional events arising from SCT might be substantially lower than that suggested by prior work in the research literature. Dr. Lianne Kurina and I decided to conduct further, focused study at the Stanford University School of Medicine to confirm or refute these findings. In considering best approaches, we noted that there was an absence of prior research in which the  sickle cell trait status of an entire, large, physically-active study population was known. This limitation could introduce bias to inflate the apparent impact of a theorized predictive factor. Aside from the challenges in studying the impact of SCT on exertional outcomes, with respect to prevention, a further concern is that  sickle cell trait is a non-modifiable trait. If it were a serious risk factor for rhabdomyolysis and/or mortality, despite careful exertional injury precautions such as those employed by the Army, this might present great challenges for prevention efforts. To maximize the potential for new research to provide actionable prevention information, our interests included examining a range of modifiable risk factors for rhabdomyolysis. Dr. Kurina and I have employed large, longitudinal military datasets for about five years to examine critical military health outcomes, making this study a natural progression of our joint work. The research proceeded with the support of the Uniformed Services University of the Health Sciences, and in cooperation with a distinguished group of experts who co-authored the paper and advised the project. The study was conducted using de-identified records of all SCT-tested African American US Army soldiers on active duty during 2011 - 2014 (N = 47,944).
Asthma, Author Interviews, NEJM, Pediatrics / 04.08.2016

MedicalResearch.com Interview with: [caption id="attachment_26649" align="alignleft" width="100"]Donata Vercelli, MD Professor of Cellular and Molecular Medicine, University of Arizona Director, Arizona Center for the Biology of Complex Diseases Associate Director, Asthma and Airway Disease Research Center The BIO5 Institute, Rm. 339 Tucson, AZ 85721 Dr. Donata Vercelli[/caption] Donata Vercelli, MD Professor of Cellular and Molecular Medicine, University of Arizona Director, Arizona Center for the Biology of Complex Diseases Associate Director, Asthma and Airway Disease Research Center The BIO5 Institute Tucson, AZ 85721 MedicalResearch.com: What is the background for this study? Response: By probing the differences between two farming communities—the Amish of Indiana and the Hutterites of South Dakota—our interdisciplinary team (which included, among others, Erika von Mutius from Ludwig-Maximilians University in Munich, Carole Ober and Anne Sperling from the University of Chicago, and myself) found that substances in the house dust from Amish, but not Hutterite, homes shape the innate immune system in ways that may prevent the development of allergic asthma. Growing up in a microbe-rich farm environment has been known to protect against asthma. Our current study extends these findings by showing that in both humans and mice protection requires engagement of the innate immune system. The Amish and Hutterite farming communities in the United States, founded by immigrants from Central Europe in the 18th and 19th centuries, provide textbook opportunities for comparative studies. The Amish and the Hutterites have similar genetic ancestry and share lifestyles (e.g., family size, diet, lack of exposure to indoor pets) known to affect asthma risk. However, their farming practices differ. The Amish have retained traditional methods, live on single-family dairy farms and rely on horses for fieldwork and transportation. In contrast, the Hutterites live on large communal farms and use modern, industrialized farm machinery. This distances young Hutterite children from the constant daily exposure to farm animals.
Author Interviews, Endocrinology, Genetic Research, NEJM, Weight Research / 21.07.2016

MedicalResearch.com Interview with: Dr. Peter Kühnen MD Institute for Experimental Pediatric Endocrinology Charité–Universitätsmedizin Berlin Berlin, Germany MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Kühnen: The patients, which were included in this study, are suffering from a genetic defect in a gene called POMC. This gene is cleaved into different hormones as e.g. MSH (melanocyte stimulating hormone). MSH is very important for the regulation of satiety by activation of the MC-4 receptor. For this reason these patients are persistent hyperphagic due to the lack of MSH and they gain weight very fast in the first months of their life. Setmelanotide activates the MC-4 receptor, which is important for the activation of satiety. By restoring the lost function Setmelanotide leads to a reduction of hyperphagia and to a reduction of body weight in this POMC deficient patients.
Author Interviews, Infections, NEJM, Vaccine Studies / 20.07.2016

MedicalResearch.com Interview with: [caption id="attachment_26324" align="alignleft" width="133"]Nicole E. Basta, PhD MPhil Assistant Professor Division of Epidemiology and Community Health School of Public Health University of Minnesota Dr. Nicole Basta[/caption] Nicole E. Basta, PhD MPhil Assistant Professor Division of Epidemiology and Community Health School of Public Health University of Minnesota MedicalResearch.com: What is the background for this study? Response: Meningococcal disease is a serious and often life-threatening condition. In the past several years, multiple outbreaks caused by meningococcal serogroup B (MenB) have occurred on college campuses in the US. Recently, a new meningococcal B vaccine known as 4CMenB or Bexsero was developed. The FDA granted special approval to use the vaccine to control an outbreak at a University in New Jersey prior to its licensure. We took advantage of this unique opportunity to investigate the impact of Bexsero during the outbreak. In doing so, we conducted the first clinical study of Bexsero among teens and young adults in the US.
Author Interviews, Education, NEJM / 09.07.2016

MedicalResearch.com Interview with: [caption id="attachment_25942" align="alignleft" width="200"]Marsha Regenstein, Ph.D, Professor From the Department of Health Policy and Management Milken Institute School of Public Health George Washington University Washington, DC Prof. Marsha Regenstein[/caption] Marsha Regenstein, Ph.D, Professor From the Department of Health Policy and Management Milken Institute School of Public Health George Washington University Washington, DC MedicalResearch.com: What is the background for this study? Response: Despite the billions of dollars in public spending on graduate medical education (GME) in the United States, little is known about the true cost of training a resident, with the few studies that exist showing wide variation in their methods and results. At the same time, the U.S. appears to be producing too few primary care physicians to meet the health care needs of the population, and especially those who live in underserved areas with high health care needs and shortages of health professionals. The Teaching Health Center (THC) Graduate Medical Education funding program was established under the Affordable Care Act to increase the number of medical and dental residents training in six primary care specialties in underserved areas. The Teaching Health Center funding supports community-based residency training in settings such as Federally-qualified health centers, rural clinics, mental health clinics and other non-profit community-based organizations. Hospitals commonly serve as training partners, but THC funding goes directly to the community-based partner, bringing funding and training closer to the communities where underserved patients live. The Health Resources and Services Administration (HRSA), which manages and funds the program, set an interim payment of $150,000 per resident; currently, 59 THCs are training 690 residents in 27 states and the District of Columbia. The interim payment rate was based on the best available information at the time and was meant to cover the full cost of training a resident.
Author Interviews, Cancer Research, Leukemia, NEJM, Stanford / 29.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25621" align="alignleft" width="200"]Jason R. Gotlib, MD The Clinical Investigator Pathway Hematology Division at Stanford University Medical Cent Dr. Jason R. Gotlib[/caption] Jason R. Gotlib, MD The Clinical Investigator Pathway Hematology Division Stanford University Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: The background is that advanced forms of systemic mastocytosis, which are blood cancers characterized by accumulation of abnormal mast cells in the bone marrow and additional organs, represent a group of orphan diseases with a large unmet need. Approximately 90% of patients harbor the acquired KIT D816V mutation, a mutated receptor tyrosine kinase on the surface of mast cells which a primary driver of disease pathogenesis. Only 1 drug is approved for patients with one form of advanced systemic mastocytosis, termed ‘aggressive systemic mastocytosis, or ‘ASM’. This therapy is imatinib (Gleevec), but it is only approved for patients without the KIT D816V mutation, or with KIT mutation status unknown because the KIT D816V mutation is resistant to imatinib. Therefore, this drug may only be useful for approximately 10% of patients. Other drugs that have been used off-label for systemic mastocytosis (but are not approved for this indication) include interferon-alpha or cladribine, which show some activity, but their evaluation to date has been primarily limited to small case series which are usually retrospective in nature, and include mixed populations of systemic mastocytosis patients who have both early stage disease without organ damage (e.g. indolent systemic mastocytosis) and and advanced stage patients, as included in this trial, who have one or more findings of organ damage. Also, those trials employed differing response criteria and no central adjudication of eligibility and response assessments was undertaken. Midostaurin is a multikinase inhibitor with activity against both wild-type KIT, but most importantly, KIT D816V (in contrast to imatinib). Prior work demonstrated that cell lines transformed with the KIT D816V mutation can be inhibited at relatively low concentrations of midostaurin. These concentrations could also be achieved in vivo (e.g. at concentrations achievable in the blood of patients). Cell lines transformed by KIT D816V could not be inhibited by imatinib.
Author Interviews, Infections, NEJM, Vaccine Studies / 29.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25691" align="alignleft" width="136"]Philip Bejon, Ph.D. Professor of Tropical Medicine, Director of the Wellcome-KEMRI-Oxford Collaborative Research Programme, Group Head / PI, Consultant Physician and Unit Director Kilifi, Kenya Dr. Philip Bejon[/caption] Philip Bejon, Ph.D. Professor of Tropical Medicine, Director of the Wellcome-KEMRI-Oxford Collaborative Research Programme, Group Head / PI, Consultant Physician and Unit Director Kilifi, Kenya MedicalResearch.com: What is the background for this study? Response: According to the latest World Health Organisation (WHO) estimates more than 400,000 people died from malaria in 2015, with over 90% of these deaths occurring in sub-Saharan Africa. The vast majority who die are children under 5, and almost all cases are caused by the P. falciparum strain of malaria transmitted by female Anopheles mosquitoes. RTS,S, which protects only against P. falciparum, was developed by GlaxoSmithKline with support from the PATH Malaria Vaccine Initiative (MVI) and with grant funds from the Bill & Melinda Gates Foundation to MVI. In July 2015, it received a positive opinion from the European Medicines Agency. Earlier this year, the WHO recommended further evaluation of the four-dose regimen of RTS,S in a pilot implementation programme in sub-Saharan Africa, to address several knowledge gaps before the vaccine might be rolled out more widely.
Author Interviews, NEJM, OBGYNE, University Texas, Zika / 26.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25543" align="alignleft" width="129"]Abigail R.A. Aiken, MD, MPH, PhD Assistant Professor LBJ School of Public Affairs University of Texas at Austin Austin, TX, 78713 Dr. Abigail Aiken[/caption] Abigail R.A. Aiken, MD, MPH, PhD Assistant Professor LBJ School of Public Affairs University of Texas at Austin Austin, TX, 78713 MedicalResearch.com: What is the background for this study? Response: As Zika began to emerge as an epidemic in Latin America and its links with microcephaly began to be realized, we were aware that women in the region who were already pregnant or who would become pregnant would have a very limited set of reproductive options. Research and media attention about the possible biological effects of Zika in pregnancy began to appear rapidly. But much less attention was been paid to the impacts of Zika on women. We followed the responses of governments and health organizations and when they began to issue advisories warning women to avoid pregnancy, we knew it would be important to investigate the impacts of those advisories. A country-wide policy that is impossible to follow if you are pregnant or cannot avoid pregnancy is an unusual and important public issue. Accurate data on abortion are very difficult to obtain in Latin America because in most countries, abortion is highly restricted. We wanted to provide a window on the issue of how women were responding to the risks of Zika and its associated advisories, so we worked with Women on Web (WoW), an online non-profit telemedicine initiative that provides safe medical abortion to women in countries where safe, legal abortion is not universally available.
Author Interviews, NEJM, Occupational Health, Opiods / 24.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25503" align="alignleft" width="125"]Professor Ellen Meara, PhD Professor The Dartmouth Institute for Health Policy and Clinical Practice Prof. Ellen Meara[/caption] Professor Ellen Meara, PhD Professor The Dartmouth Institute for Health Policy and Clinical Practice MedicalResearch.com: What is the background for this study? Response: Responding to a fourfold rise in death rates, between 2006 and 2012, states collectively enacted 81 laws restricting prescribing and dispensing of prescription opioids. Jill Horwitz, PhD, JD, said “states hoped passing a range of laws might help. So they are enacting small fixes — forbidding patients from “doctor-shopping,” and requiring doctors to use tamper-resistant prescription forms. They are also implementing major efforts such as prescription drug monitoring programs (PDMPs) — online databases that allow law enforcement and clinicians to monitor prescriptions.”