meta name="publication-media-verification"content="1ebe9089d92647b3b88294de308625d5
Author Interviews, Diabetes, Heart Disease, NEJM / 13.04.2017

MedicalResearch.com Interview with: Aidin Rawshani, MD, PhD student Sahlgrenska Academy University of Gothenburg MedicalResearch.com: What is the background for this study? What are the main findings? Response: Management of diabetes has improved in the past decades, studies have shown that mortality and cardiovascular disease among patients with diabetes has decreased, but these studies have not compared the trends among persons with type 1 diabetes and type 2 diabetes to those of the general population, where there have also been reductions in cardiovascular morbidity and mortality. We observed marked reductions in incidence for cardiovascular disease and mortality among individuals with diabetes, however, similar trends were observed for the general population. We observed a 43% (HR 1.43, 95% CI 1.25–1.62) greater event rate reduction for cardiovascular disease among individuals with type 1 diabetes compared to matched controls. The reduction in the rate of fatal outcomes did not differ significantly between patients with type 1 diabetes and controls, whereas patients with type 2 diabetes had a 13% (HR 0.87, 95% CI 0.85–0.89) lesser event rate reduction compared with matched controls. There was a 27% (HR 1.27, 95% CI 1.22–1.32) greater event rate reduction for cardiovascular disease among individuals with type 2 diabetes, compared with matched controls. Nevertheless, there remains a substantial excess overall rate of all outcomes analysed among persons with type 1 diabetes and type 2 diabetes, as compared with the general population. (more…)
Author Interviews, HPV, NEJM, OBGYNE, Vaccine Studies / 30.03.2017

MedicalResearch.com Interview with: Anders Hviid Senior Investigator, M.Sc.,Dr.Med.Sci. Department of Epidemiology Research Division of National Health Surveillance & Research MedicalResearch.com: What is the background for this study? Response: HPV vaccination targeting girls and young women has been introduced in many countries throughout the world. HPV vaccines are not recommended for use in pregnancy, but given the target group, inadvertent exposure will occur in early unrecognized pregnancies. However, data on the safety of HPV vaccination in pregnancy is lacking. (more…)
Author Interviews, Heart Disease, Medical Imaging, NEJM / 19.03.2017

MedicalResearch.com Interview with: Dr. Matthias Götberg MD PhD Department of Cardiology, Clinical Sciences Lund University, Skåne University Hospital Lund, Sweden MedicalResearch.com: What is the background for this study? Response: Cardiologists encounter patients with narrowing of the coronary arteries on a daily basis. They typically use visual estimation of the severity of narrowing when performing coronary angiography, but it is difficult to accurately assess, based on a visual estimation alone, whether a stent is needed to widen the artery and allow the blood to more freely. FFR (Fractional Flow Reserve) is more precise tool and results in better outcomes than using angiography alone to assess narrowing of the coronary arteries. With FFR, the doctor threads a thin wire through the coronary artery and measures the loss of blood pressure across the narrowed area. To acquire an accurate measurement, the patient must be given adenosine, which is a drug that dilates the blood vessels during the procedure. This drug causes discomfort; patients describe having difficulty breathing or feeling as if someone is sitting on their chest. The drug also adds to the cost of the procedure and can have other rare but serious side effects. iFR (Instantaneous Wave-Free Ratio) is also based on coronary blood pressure measurements using a thin wire, but unlike FFR, it uses a mathematical algorithm to measure the pressure in the coronary artery only when the heart is relaxed and the coronary blood flow is high. As a result, a vasodilator drug is not needed. iFR has been validated in smaller trials and have been found to be equally good as FFR to detect ischemia, but larger randomized outcome trials are lacking. iFR-Swedeheart is a Scandinavian Registry-based Randomized Clinical Trial (RRCT) in which 2000 patients were randomized between iFR and FFR as strategies for performing assessment of narrowed coronary vessels. The primary composite endpoint at 12 months was all-cause death, non-fatal myocardial infarction, and unplanned revascularization. RRCT is a new trial design originating from Scandinavia using existing web-based national quality registries for online data entry, randomization and tracking of events. This allows for a very high inclusion rate and low costs to run clinical trials while ensuring robust data quality.  (more…)
Author Interviews, NEJM, OBGYNE, Thyroid Disease, UT Southwestern / 01.03.2017

MedicalResearch.com Interview with: Professor Brian Casey, M.D. Gillette Professorship of Obstetrics and Gynecology UT Southwestern Medical Center  MedicalResearch.com: What is the background for this study? Response: For several decades now, subclinical thyroid disease, variously defined, has been associated with adverse pregnancy outcomes.  In 1999, two studies are responsible for increasing interest in subclinical thyroid disease during pregnancy because it was associated with impaired neuropsychological development in the fetus.  One study showed that children born to women with the highest TSH levels had lower IQ levels.  The other showed that children of women with isolated low free thyroid hormone levels performed worse on early psychomotor developmental tests. Together, these findings led several experts and professional organizations to recommend routine screening for and treatment of subclinical thyroid disease during pregnancy. Our study was designed to determine whether screening for either of these two diagnoses and treatment with thyroid hormone replacement during pregnancy actually improved IQ in children at 5 years of age. (more…)
Author Interviews, Heart Disease, MRI, NEJM / 25.02.2017

MedicalResearch.com Interview with: Robert Russo, MD, PhD, FACC The Scripps Research Institute The La Jolla Cardiovascular Research Institute  MedicalResearch.com: What is the background for this study? Response: For an estimated 2 million people in the United States and an additional 6 million people worldwide, the presence of a non-MRI-conditional pacemaker or implantable cardioverter defibrillator (ICD) is considered a contraindication to magnetic resonance imaging. This creates a dilemma for at least half of these patients, who are predicted to require an MRI scan during their lifetime after a cardiac device has been implanted. Safety concerns for patients with an implanted cardiac device undergoing MRI are related to the potential for magnetic field-induced cardiac lead heating resulting in myocardial thermal injury, and a detrimental change in pacing properties. As a result, patients with an implanted device have long been denied access to MRI, although it may have been the most appropriate diagnostic imaging modality for their clinical care. Despite the development of MRI-conditional cardiac devices, a strategy for mitigating risks for patients with non MRI-conditional devices and leads will remain an enduring problem for the foreseeable future due to an ever increasing demand for MRI and the large number of previously and currently implanted non-MRI-conditional devices. (more…)
Author Interviews, NEJM, OBGYNE, Pediatrics / 17.02.2017

MedicalResearch.com Interview with: Carla M. Bann, Ph.D. Division of Statistical and Data Sciences RTI International Research Triangle Park, NC MedicalResearch.com: What is the background for this study? What are the main findings? Response: Several medical advances have been made over the past two decades to improve the care and survival of infants born pre-term. However, approaches to care differ greatly among providers for infants born at the limits of viability (22 to 24 weeks gestation), far earlier than the 40 weeks generally expected for a pregnancy to reach full-term. Little is known about the outcomes of these infants, particularly whether those who survive experience significant neurodevelopmental impairments. RTI served as the data coordinating center for this research that examined the survival and neurodevelopmental impairment at 18-22 months corrected age of over 4,000 infants born at 22 to 24 weeks gestation during 2000 to 2011 at medical centers participating in a national research network funded by the NIH. In this group of babies, infant survival improved over time from survival rates of 30 percent in 2000-2003 to 36 percent in 2008-2011. The proportion of infants who survived without a neurodevelopmental impairment also increased from 16 percent in 2000-2003 to 20 percent in 2008-2011. (more…)
Author Interviews, CDC, NEJM, Zika / 16.02.2017

MedicalResearch.com Interview with: Gabriela Paz-Bailey MD PhD Senior Epidemiologist Centers for Disease Control and Prevention  MedicalResearch.com: What is the background for this study? Response: Zika virus is recognized as a cause of microcephaly and other severe birth defects when a woman is infected during pregnancy. Additionally, it has been associated with potentially fatal complications, such as Guillain-Barré syndrome. It is not well understood how often Zika virus particles can be detected in semen and other body fluids and for how long they remain detectable. Existing evidence is based on case reports and cross-sectional observations, primarily from returning travelers. A more comprehensive description of the dynamics of the early stages of Zika virus infection, observed within infected people over time, is needed to inform diagnostic testing as well as prevention recommendations and interventions. (more…)
Author Interviews, Heart Disease, NEJM, NIH, Pediatrics / 30.01.2017

MedicalResearch.com Interview with: Victoria Pemberton, RNC, MS, CCRC Program Officer Division of Cardiovascular Sciences National Heart, Lung, and Blood Institute, NIH Bethesda, Maryland MedicalResearch.com: What is the background for this study? What are the main findings?
  • Previous studies have examined cardiac arrest when it occurs outside of the hospital in both children and adults, with current guidelines recommending hypothermia (body cooling) or normothermia (maintenance of normal body temperature) after such an arrest.   This trial addresses pediatric cardiac arrest in a hospital setting, for which no previous data existed. Because children who experience an in-hospital cardiac arrest differ significantly from children who arrest outside of the hospital, it is important to test these treatments in this population.
  • The trial found no significant differences in survival and neurobehavioral functioning a year after cardiac arrest between children assigned to the hypothermia arm and those assigned to normothermia.
(more…)
Author Interviews, NEJM, Smoking, Tobacco Research / 27.01.2017

MedicalResearch.com Interview with: Andrew Hyland, PhD Chair of the Department of Health Behavior at Roswell Park Cancer Institute and Karin Kasza, MA Senior Research Specialist in the Department of Health Behavior Roswell Park Cancer Institute MedicalResearch.com: What is the background for this study? What are the main findings? Response: The PATH Study is unique because it is a large, nationally representative study of more than 45,000 youth and adults who are interviewed at multiple points over time and asked about their use of a wide array of tobacco products. The data reported in this study are from the baseline wave, and we find that while cigarettes are by far the most commonly used product for both youth and adults, we see a lot of use of non-cigarette products. E-cigarettes trailed only cigarettes in popularity for youth and water pipe smoking was high among 18-24 year olds. However, we see different patterns of use for different products with cigarettes being used much more frequently that other products like e-cigarettes. Another surprising finding was that about 4 in 10 youth and adult tobacco users were currently using two or more tobacco products. (more…)
Author Interviews, Cancer Research, Immunotherapy, NEJM, Transplantation / 19.01.2017

MedicalResearch.com Interview with: Kenar D. Jhaveri, MD Professor of Medicine Division of Kidney Diseases and Hypertension Hofstra Northwell School of Medicine, 100 Community Drive, Great Neck, NY 11021 MedicalResearch.com: What is the background for this study? What are the main findings? Response: The immune check point inhibitors are novel anti cancer agents being used rapidly in various cancers. Many cancers don’t allow our natural immune system to attack the cancer. These immunotherapy agents “activate” the immune system to attack the cancer. These agents have been reported to cause multiple end organ side effects as noted by this recent NYT article. We also recently reported the known renal effects of immunotherapy. In the kidney transplant patient who is on immunosuppressive agents, the physicians need to keep the immune system suppressed to preserve the kidney. When one of these agents are used for a cancer in a kidney transplant patient, prior reports have suggested severe rejection episodes and loss of the transplanted kidney. Our case in the NEJM is the first report of a preventive strategy used to allow for simultaneous treatment of cancer and preventive rejection of the kidney. We used a regimen of steroids and sirolimus( an anti-proliferative agent that is used to treat cancer and also is an immunosuppresant) along with the immunotherapy. The cancer started regressing and the kidney did not reject. (more…)
Author Interviews, Baylor College of Medicine Houston, Genetic Research, NEJM / 09.01.2017

MedicalResearch.com Interview with: Jennifer E Posey MD, PhD Assistant Professor Department of Molecular and Human Genetics Baylor College of Medicine Tamar Harel MD, PhD Clinical Genetics Academic Research Fellow Department of Molecular and Human Genetics Baylor College of Medicine Current affiliation: Department of Genetic and Metabolic Diseases Hadassah-Hebrew University Medical Center Jerusalem, Israel MedicalResearch.com: What is the background for this study? What are the main findings? Response: As physician scientists and geneticists, our goal is to understand how genetic variation in each of us can impact health and disease. Physicians are often taught that the simplest explanation for a medical condition is the most correct explanation, and have historically searched for a single unifying diagnosis. However, in our own practice, we have met – and learned from – individuals who have more than one genetic condition affecting their health. In the past, it was difficult for physicians to diagnose such individuals. Genetic testing required a physician to recognize the potential for more than one genetic diagnosis in an individual. Single-gene and gene panel testing provided an additional barrier to accurate diagnoses, as they are more narrow in scope, and more than one molecular test was often needed to identify all conditions. Targeted testing also required a physician to accurately pre-suppose which combination of genetic conditions was most likely, and choose the correct targeted tests. The clinical availability of whole exome sequencing (WES) has removed these barriers: WES is a broad-based, unbiased analysis of an individual’s genetic variation that does not pre-suppose a specific genetic cause. If analysis is pursued systematically, WES can identify more than one genetic diagnosis in an individual, even when not suspected. In our study, we have been able to assess the frequency with which individuals can have more than one genetic diagnosis, and have begun to understand how genetic variation at more than one place in the genome can affect how a condition may present. We found that among 7,374 individuals referred for WES, 2,076 (28%) had a molecular diagnosis. Of these 2,076, 5% had two, three, or four molecular diagnoses. In our analyses of the clinical features that may be observed in an individual with two genetic conditions, we found that pairs of diagnoses with overlapping clinical features may be incompletely diagnosed as having one or the other condition, and pairs of diagnoses with very distinct clinical features may be erroneously diagnosed in the clinic as having an entirely new condition. (more…)
Author Interviews, Cost of Health Care, NEJM / 08.01.2017

MedicalResearch.com Interview with: John Z. Ayanian, MD, MPP Director of the Institute for Healthcare Policy and Innovation and Alice Hamilton Professor of Medicine University of Michigan MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our study assessed the broad economic impact of Medicaid expansion in Michigan – one of several Republican-led states that have chosen to expand Medicaid under the Affordable Care Act. About 600,000 low-income adults in Michigan are covered through the program, known as the Healthy Michigan Plan, which began in April 2014. Using an economic modeling tool that is also used to advise the state government for fiscal planning, we found that federal funding for the Healthy Michigan Plan is associated with over 30,000 additional jobs, about $2.3 billion in increased personal income in Michigan, and about $150 million in additional state tax revenue annually. One third of the new jobs are in health care, and 85 percent are in the private sector. The state is also saving $235 million annually that it would have spent on other safety net programs if Medicaid had not been expanded. Thus, the total economic impact of the Healthy Michigan Plan is generating more than enough funds for the state budget to cover the state’s cost of the program from 2017 through 2021. Beginning in 2017, states are required to cover 5 percent of the costs of care for Medicaid expansion enrollees, and the state share of these costs will rise to 10 percent in 2020. The remaining costs are covered by federal funding. (more…)
Asthma, Author Interviews, Fish, NEJM, Pediatrics / 06.01.2017

MedicalResearch.com Interview with: Hans Bisgaard, M.D., D.M.Sc. COPSAC, Herlev and Gentofte Hospital University of Copenhagen Copenhagen, Denmark MedicalResearch.com: What is the background for this study? Response: Asthma and lower respiratory infections are leading causes of morbidity and mortality in pediatric populations. Thus, having low cost, effective, safe options for prevention could have important implications for both clinical practice and public health. The increased use of vegetable oils in cooking and of grain in the feeding of livestock has resulted in an increase in the intake of n−6 polyunsaturated fatty acids and a decrease in the intake of n−3 polyunsaturated fatty acids, especially the long-chain poly-unsaturated fatty acids (LCPUFAs) — eicosapentaenoic acid (20:5n–3, EPA) and docosahexaenoic acid (22:6n–3, DHA) — found in cold-water fish. N3-LCPUFAs are known to have immune-modulatory effects, and observational studies have suggested an association between a diet that is deficient in n−3 LCPUFA during pregnancy and an increased risk of asthma and wheezing disorders in offspring. Only a few randomized, controlled trials of n−3 LCPUFA supplementation during pregnancy have been performed and these have generally been underpowered and produced ambiguous results. Therefore, we conducted a double-blind, randomized, controlled trial of n−3 LCPUFA supplementation during the third trimester of pregnancy in a total of 736 Danish women to assess the effect on the risk of persistent wheeze and asthma in offspring. The clinical follow-up rate among children was 96% (N=664) by the end of the 3 years double-blind period and 93% (N=647) after an additional follow-up to age 5 years. (more…)
Author Interviews, Immunotherapy, Multiple Sclerosis, NEJM, University Texas / 22.12.2016

MedicalResearch.com Interview with: Jerry S. Wolinsky, MD Emeritus Professor in Neurology McGovern Medical School The University of Texas Health Science Center at Houston Houston’s Health University Department of Neurology Houston, Texas 77030 MedicalResearch.com: What is the background for this study? Response: Multiple sclerosis (MS) clinically is a very heterogeneous disease. It presents in considerably different ways and has a very poorly predictable clinical course. In an attempt to better communicate between experts in the field, there have been multiple attempts to categorize “typical” courses of the disease. How we think about the disease is in part driven by these somewhat artificial categories that lump our patients into those with relapsing forms of the disease (relapsing remitting with or without accumulating clinical disability, and secondary progressive with accumulating disability eventually occurring even in the absence of apparent clinical episodes of the disease), and primary progressive MS, where patients are slowly or sometimes rather rapidly accumulating disability in the absence of prior clinical relapses. However, the distinctions between multiple sclerosis patients are not always as clear as the definitions would suggest, and it is certain that patients with primary progressive multiple sclerosis sometimes have clinical relapses after years of never having had relapses, and show MRI evidence of having accumulated many lesions in the brain over the course of their disease. Until now, none of the drugs that have shown benefit for relapsing disease have been able to convincingly show clinical benefit for patients with primary progressive disease, and for that matter have shown variable results when attempted in patients categorized as having secondary progressive courses. While some of our currently approved drugs have shown hints of benefit when tried in major clinical trials in primary progressive MS, the results were not been robust enough to seek regulatory approval. The Oratorio study design was based on lessons learned from prior trials in primary progressive and relapsing forms of MS, as well as the recognition that B cells might play an important role in the immunopathogenesis of disease based on a considerable amount of preclinical work and observations in patients with multiple sclerosis. (more…)
Author Interviews, NEJM, Orthopedics, Surgical Research, Thromboembolism / 06.12.2016

MedicalResearch.com Interview with: Suzanne C. Cannegieter, M.D., Ph.D. Einthoven Laboratory Leiden University Medical Center The Netherlands MedicalResearch.com: What is the background for this study? What are the main findings? Response: Patients who undergo arthroscopic knee surgery and patients who are treated with casting of the lower leg are at increased risk for venous thromboembolism (VTE). It is uncertain whether thromboprophylaxis is effective in these situations to prevent VTE. For both indications, several trials have been performed to evaluate the effectiveness of anticoagulant prophylaxis. However, an overall risk–benefit balance could not be established because of methodologic shortcomings; hence, there has been reluctance to establish international guidelines regarding the use of anticoagulant therapy for either of these indications. (more…)
Author Interviews, HIV, NEJM / 03.12.2016

MedicalResearch.com Interview with: Ms. Neliëtte Van Niekerk M.Com and Dr. Annalene Nel M.B., Ch.B., Ph.D. From International Partnership for Microbicides Silver Spring, MD MedicalResearch.com: What is the background for this study? What are the main findings? Response: Existing prevention methods have not done enough to stop the alarming rates of infection among women and girls, especially in sub-Saharan Africa, where young women are at least twice as likely to have HIV as young men. Rates of new infections among women aged 15-24 were more than four times greater than that of men the same age, and this age group accounted for 25 percent of new infections in South Africa. To provide women with more prevention options, the nonprofit International Partnership for Microbicides (IPM) developed a vaginal ring that contains an antiretroviral drug called dapivirine. Women insert the ring themselves and replace it every month. The Ring Study was a Phase III clinical trial that assessed the safety and long-term efficacy of the monthly dapivirine ring among nearly 2,000 women in South Africa and Uganda. We found that the ring reduced the risk of HIV-1 infection in about one-third of the women in the trial, and it was safe, with no difference in adverse effects between the active and placebo ring groups. (more…)
Author Interviews, Genetic Research, Lipids, NEJM / 01.12.2016

MedicalResearch.com Interview with: Brian A. Ference, M.D Division of Cardiovascular Medicine Wayne State University School of Medicine Detroit, MI MedicalResearch.com: What are the main findings? Response: Lifelong exposure to modestly lower plasma LDL-C levels caused by rare loss-of-function mutations in the PCSK9 gene is associated with a substantially lower lifetime risk of developing cardiovascular disease. This discovery motivated the development of monoclonal antibodies directed against PCSK9 which have now been shown to reduce plasma LDL-C levels by 50-60%. The cardiovascular medicine community is early anticipating the results of two large cardiovascular outcome trials that will determine if lowering LDL-C levels by inhibiting PCSK9 will reduce the risk of cardiovascular events. Because monoclonal antibodies and other therapies directed against PCSK9 are designed to recapitulate the phenotype of PCSK9 loss-of-function mutations, we reasoned that it may be possible to anticipate the efficacy and safety results of the ongoing cardiovascular outcome studies by more precisely characterizing the effect of genetic variants in the PCSK9 gene on the risk of both cardiovascular events and new onset diabetes. To do this, we a constructed genetic score consisting of multiple independently inherited variants in the PCK9 gene to create an instrument that mimics the effect of PCSK9 inhibitors. We then compared the effect of genetic variants that mimic the effect of PCSK9 inhibitors with the effect of genetic variants in the HMGCR gene that mimic the effect of statins to make inferences about the likely effect of PCSK9 inhibitors on the risk of cardiovascular events and new onset diabetes as compared to treatment with a statin. (more…)
Author Interviews, HIV, NEJM, University of Pennsylvania / 24.11.2016

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, NEJM, Outcomes & Safety, Surgical Research / 22.11.2016

MedicalResearch.com Interview with: 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. (more…)
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. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Kidney Disease, NEJM, Pediatrics / 18.11.2016

MedicalResearch.com Interview with: 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 (more…)
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. (more…)
Author Interviews, Heart Disease, Lipids, NEJM, Pharmacology / 14.11.2016

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, NEJM, Prostate Cancer / 21.10.2016

MedicalResearch.com Interview with: 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). (more…)
Author Interviews, Infections, NEJM / 10.10.2016

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Columbia, NEJM, Orthopedics, Osteoporosis / 21.09.2016

MedicalResearch.com Interview with: 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). (more…)
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. (more…)
Author Interviews, NEJM, Prostate Cancer / 15.09.2016

MedicalResearch.com Interview with: 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). (more…)
Author Interviews, Leukemia, NEJM, Transplantation / 08.09.2016

MedicalResearch.com Interview with: 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. (more…)
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. (more…)