Author Interviews, NEJM, Prostate Cancer / 13.07.2017

MedicalResearch.com Interview with: Dr. Timothy Wilt, MD MPH Core Investigator: Minneapolis VA Center for Chronic Disease Outcomes Research Staff Physician: Section of General Internal Medicine, Minneapolis VA Health Care System Professor: Medicine, University of Minnesota School of Medicine  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Prostate cancer is common and potentially serious. However, the comparative benefits and harms of surgery versus observation in men with localized prostate cancer are not known. After nearly 20 years, surgery did not significantly reduce all-cause or prostate cancer mortality compared to observation, particularly in men with low risk disease. Surgery was associated with more harms than observation, causing complications within 30 days in about 20% of men and large long term increases in urinary incontinence, sexual dysfunction and dissatisfaction, as well as treatment related bother and reductions in daily functioning.
Author Interviews, Brigham & Women's - Harvard, Environmental Risks, NEJM, Race/Ethnic Diversity / 29.06.2017

MedicalResearch.com Interview with: Qian Di, M.S, Doctoral Student Department of Environmental Health and Francesca Dominici, Ph.D. Principal Investigator of this study Professor of Biostatistics co-Director of the Harvard Data Science Initiative Harvard T.H. Chan School of Public Health Boston, MA MedicalResearch.com: What is the background for this study? What are the main findings? Response: The Clean Air Act requires Environmental Protection Agency to set National Ambient Air Quality Standard (NAAQS). Currently the annual NAAQS for PM2.5 is 12 microgram per cubic meter; and there is no annual or seasonal ozone standard. However, is current air quality standard stringent enough to protect human health? This is our main motivation. We conducted the largest attainable cohort study, including over 60 million Medicare participants, to investigate the association between long-term exposure to ozone/PM2.5 and all-cause mortality. We found significant harmful effect of PM2.5 even below current NAAQS. Each 10 microgram per cubic meter increase in PM2.5 is associated with 13.6% (95% CI: 13.1%~14.1%) increase in all-cause mortality. For ozone, 10 ppb increase in ozone exposure is associated with 1.1% (95% CI: 1.0%~1.2%) increase in mortality. Also, there is no appreciable level below which mortality risk tapered off. In other words, there is no “safe” level for PM2.5 and ozone. In other words, if we would reduce the annual average of PM2.5 by just 1 microgram per cubic meter nationwide, we should save 12,000 lives among elder Americans every year; 5 microgram --- 63,817 lives every year. Similarly, if we would reduce the annual summer average of ozone by just 1 ppb nationwide, we would save 1,900 lives every year; 5 ppb --- 9537 lives. Besides, we found black people, males and people of low SES are more vulnerable to air pollution.
Author Interviews, Flu - Influenza, NEJM, Vaccine Studies / 22.06.2017

MedicalResearch.com Interview with: [caption id="attachment_35441" align="alignleft" width="200"]Lisa M. Dunkle, M.D. Chief Medical Officer Protein Sciences Corporation 1000 Research Parkway Meriden, CT  Dr. Dunkle[/caption] Lisa M. Dunkle, M.D. Chief Medical Officer Protein Sciences Corporation 1000 Research Parkway Meriden, CT MedicalResearch.com: What is the background for this study? What are the main findings? Response: The first and only recombinant protein influenza vaccine (RIV, Flublok) was approved in 2013 as a trivalent formulation for use in adults 18 years of age and older. This approval was based on demonstration of clinical efficacy (full approval) in adults 18-49 years of age and accelerated approval was granted for adults 50 years of age and older. Two clinical trials were conducted in 2014-2015 with RIV4 (Flublok Quadrivalent), of which the trial reported in the current NEJM is one. These studies supported full approval of Flublok in adults 50 years of age and older and approval of Flublok Quadrivalent in all adults 18 years of age and older. The second trial of immunogenicity of Flublok Quadrivalent in adults 18-49 years of age will be the subject of another publication in the near future. The main findings of the current trial are well summarized in the Conclusion of the Abstract: “RIV4 provided better protection than standard-dose IIV4 against confirmed influenza-like illness in older adults.” Additionally, the recombinant vaccine (RIV4, Flublok Quadrivalent) demonstrated significantly less injection site pain and tenderness following vaccination. Based on the characteristics of the study participants, one can conclude that RIV4 is safe and effective in most individuals with underlying chronic diseases
Author Interviews, NEJM, Stroke / 22.06.2017

MedicalResearch.com Interview with: [caption id="attachment_35404" align="alignleft" width="133"]Craig Anderson | MD PhD FRACP Executive Director  Professor of Neurology and Epidemiology, Faculty of Medicine, UNSW Sydney Neurologist, Neurology Department, Royal Prince Alfred Hospital The George Institute for Global Health at Peking University Health Science Center Haidian District | Beijing, 100088 P.R. China Prof. Anderson[/caption] Craig Anderson | MD PhD FRACP Executive Director Professor of Neurology and Epidemiology, Faculty of Medicine, UNSW Sydney Neurologist, Neurology Department, Royal Prince Alfred Hospital The George Institute for Global Health at Peking University Health Science Center Haidian District | Beijing, 100088 P.R. China MedicalResearch.com: What is the background for this study? What are the main findings? Response: Preliminary small studies indicate that lying flat increases blood flow and oxygenation to the brain.  Thus, patients with acute ischemic stroke may benefit from lying flat in bed.  Conversely, sitting up in bed, with the head elevated to at least 30 degrees, may reduce swelling in the brain for patients who have large ischemic or hemorrhagic forms of stroke.  The optimal head position to produce the best outcome from acute stroke, and avoid potential risks, such as aspiration pneumonia, is unknown.  We undertook a large scale multicentre randomized controlled trial where 114 hospitals were randomised to sequentially apply lying flat or sitting up head positioning as a policy of care to a consecutive series of patients, that overall totalled over 11000 patients, presenting with acute stroke.  The study showed there was no difference in the chance of good physical recovery for patients between the two head positions but also that there were no excessive harms for either. In other words, head positioning alone didn’t produce any benefits or harms in patients with acute stroke
Author Interviews, Brigham & Women's - Harvard, NEJM, Ophthalmology / 08.06.2017

MedicalResearch.com Interview with: [caption id="attachment_35083" align="alignleft" width="142"]Elisabetta Patorno, MD, DrPH Assistant Professor of Medicine, Harvard Medical School Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital Dr. Patorno[/caption] Elisabetta Patorno, MD, DrPH Assistant Professor of Medicine, Harvard Medical School Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital MedicalResearch.com: What is the background for this study? Response: Lithium, a widely used medicine to treat bipolar disorder, has been associated with a 400 fold increased risk of Ebstein’s anomaly, a congenital malformation of the heart, and a 5 fold increased risk of cardiac defects overall in infants when taken early in pregnancy, based on the results from the International Register of Lithium Babies in the 1970’s. Beyond this data, most of the information on the safety of lithium during pregnancy accumulated in the last 40 years is based on case reports and small studies with conflicting results. Despite these concerns and the limited information, lithium remains a first-line treatment for the 1% of women of reproductive age with bipolar disorder in the U.S. population, due to its recognized efficacy during pregnancy and the postpartum period, and due to the presence of a larger body of evidence showing increased risk of congenital malformations for other mood stabilizers, such as valproate.
Author Interviews, Hepatitis - Liver Disease, NEJM / 31.05.2017

MedicalResearch.com Interview with: Dr Marc Bourlière Professeur Associé CHP (Associate Professor PHC) Chef de service (Head of Department) Hôpital Saint Joseph Hépato-Gastroentérologie MedicalResearch.com: What is the background for this study? What are the main findings? Response: The majority of HCV patients can be cured with combinations of direct-acting antivirals (DAAs); however, there is still 5 to 10% of patients who relapse after treatment with DAAs for whom there are currently no approved therapeutic options available. In these two international phase 3 studies, we have demonstrated that a single tablet triple regimen combining sofosbuvir, velpastasvir and voxilaprevir (a pangenotypic protease inhibitor) for 12 weeks cured 96% of the patients who had relapsed following prior treatment with DAA regimens including NS5A inhibitors and 98% of the patients who had relapsed following prior treatment with DAA regimens without an NS5A inhibitor. These two studies demonstrate that a pangenotypic retreatment option for this patient population could be soon available.
Author Interviews, Blood Pressure - Hypertension, Cleveland Clinic, Critical Care - Intensive Care - ICUs, Infections, NEJM / 22.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34772" align="alignleft" width="159"]Ashish Khanna, MD, FCCP Assistant Professor of Anesthesiology, Cleveland Clinic Lerner College of Medicine Staff Intensivist Center for Critical Care and Department of Outcomes Research Cleveland Clinic, Cleveland Dr. Khanna[/caption] Ashish Khanna, MD, FCCP Assistant Professor of Anesthesiology, Cleveland Clinic Lerner College of Medicine Staff Intensivist Center for Critical Care and Department of Outcomes Research Cleveland Clinic, Cleveland MedicalResearch.com: How did you become interested in this topic? Response: Anesthesia forms the basis of my training but I also completed a fellowship in critical care and, at the present time, I do more work in critical care than anesthesia. About 75% of my time is spent in the Cleveland Clinic critical care units, including the Medical and surgical ICUs (Intensive Care Units).
Author Interviews, Critical Care - Intensive Care - ICUs, Emergency Care, Infections, NEJM, University of Pittsburgh / 21.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34724" align="alignleft" width="133"]Christopher W. Seymour, M.D., M.Sc. Assistant professor of Critical Care Medicine and Emergency Medicine, and member of Clinical Research Investigation and Systems Modeling of Acute Illness University of Pittsburgh Dr. Seymour[/caption] Christopher W. Seymour, M.D., M.Sc. Assistant professor of Critical Care Medicine and Emergency Medicine, and member of Clinical Research Investigation and Systems Modeling of Acute Illness University of Pittsburgh MedicalResearch.com: What is the background for this study? What are the main findings? Response: Following the tragic and widely publicized death of Rory Staunton, 12, from undiagnosed sepsis in 2012, New York became the first state to require that hospitals follow a protocol to quickly identify and treat the condition. The mandate led to widespread controversy in the medical community as to whether such steps would have saved Rory or anyone else’s life. Rory’s Regulations require hospitals to follow protocols for early identification and treatment of sepsis, and submit data on compliance and outcomes. The hospitals can tailor how they implement the protocols, but must include a blood culture to test for infection, measurement of blood lactate (a sign of tissue stress) and administration of antibiotics within three hours of diagnosis—collectively known as the “three-hour bundle.” We analyzed data from nearly 50,000 patients from 149 New York hospitals to scientifically determine if  Rory’s Regulations worked. We found that they did - 83 percent of the hospitals completed the bundle within the required three hours, overall averaging 1.3 hours for completion. For every hour that it took clinicians to complete the bundle, the odds of the patient dying increased by 4 percent.
Author Interviews, NEJM, OBGYNE, Yale / 21.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34696" align="alignleft" width="143"]Hugh S. Taylor, M.D. Anitta O’keeffe Young Professor and Chair Departemnt of Obstetrics, Gynecology and Reproductive Sciences Yale School of Medicine Chief of Obstetrics and Gynecology Yale-New Haven Hospital Dr. Taylor[/caption] Hugh S. Taylor, M.D. Anitta O’keeffe Young Professor and Chair Departemnt of Obstetrics, Gynecology and Reproductive Sciences Yale School of Medicine Chief of Obstetrics and Gynecology Yale-New Haven Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Response: Elagolix is an investigational, oral gonadotropin-releasing hormone (GnRH) receptor antagonist that blocks endogenous GnRH signaling by binding competitively to GnRH receptors. Administration results in rapid, reversible, dose-dependent inhibition of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion, leading to reduced ovarian production of the sex hormones, estradiol and progesterone, while on therapy. Data from two replicate Phase 3 studies evaluating the efficacy and safety of elagolix were published in the New England Journal of Medicine. Elagolix demonstrated dose-dependent superiority in reducing daily menstrual and non-menstrual pelvic pain associated with endometriosis compared to placebo. At month three and month six, patients treated with elagolix reported statistically significant reductions in scores for menstrual pain (dysmenorrhea, DYS) and non-menstrual pelvic pain (NMPP) associated with endometriosis as measured by the Daily Assessment of Endometriosis Pain scale. The safety profile of elagolix was consistent across both Phase 3 trials and also consistent with prior elagolix studies. Ultimately, the studies showed that both elagolix doses (150 mg QD and 200 mg BID) were effective in improving dysmenorrhea, non-menstrual pelvic pain and quality of life over 6 months in women with endometriosis-associated pain. The elagolix safety/tolerability profile was consistent with the mechanism of action.
Author Interviews, Exercise - Fitness, Geriatrics, NEJM, Weight Research / 17.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34649" align="alignleft" width="199"]Dennis T. Villareal, MD Professor of Medicine Division of Endocrinology, Diabetes & Metabolism Baylor College of Medicine Staff Physician, Michael E DeBakey VA Medical Center Dr. Villareal[/caption] Dennis T. Villareal, MD Professor of Medicine Division of Endocrinology, Diabetes & Metabolism Baylor College of Medicine Staff Physician, Michael E DeBakey VA Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: The prevalence of obesity in the elderly is rapidly increasing, given that the baby boomers are becoming senior citizens, but we do not know how best to manage obesity in the elderly population. Weight loss is the cornerstone of management for obesity but weight loss in the elderly is controversial because weight loss could cause not only fat loss but also muscle mass and bone mass losses, that could worsen rather than improve frailty. We tested the hypothesis that weight loss plus exercise training, especially resistance training, would improve physical function the most compared to other types of exercise (aerobic training or combined aerobic and resistance training added to diet-induced weight loss). Previous studies especially in younger adults have shown that combining aerobic with resistance exercise could lead to interference to the specific adaptations to each exercise, and thus less gain in strength with combined exercise compared to resistance training alone. On the other hand, contrary to our hypothesis, we found that there was no interference between aerobic and resistance exercise, and the most effective mode to improve physical function and thus reverse frailty was in fact weight loss plus the combination of aerobic and resistance exercise, which was also associated with some preservation of muscle and bone mass.
Author Interviews, Heart Disease, NEJM / 05.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34392" align="alignleft" width="200"]Kristian Kragholm, MD, PhD Departments of Cardiology and Epidemiology/Biostatistics, Aalborg University Hospital, Aalborg, DK Dr. Kragholm[/caption] Kristian Kragholm, MD, PhD Departments of Cardiology and Epidemiology/Biostatistics, Aalborg University Hospital, Aalborg, DK MedicalResearch.com: What is the background for this study? What are the main findings? Response: It is well known that early help from bystanders including cardiopulmonary resuscitation (CPR) before arrival of the emergency medical services can increase chances of 30-day survival by three to four times compared to situations where no bystander resuscitation was initiated. The main and novel finding of our study is that bystander interventions, in addition to increasing survival, also lowers the risk of damage to the brain and nursing home admission in 30-day survivors during the first year following out-of-hospital cardiac arrest.
Author Interviews, Gastrointestinal Disease, Immunotherapy, NEJM, UCSD / 04.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34246" align="alignleft" width="133"]William J. Sandborn, MD Professor of Medicine and Adjunct Professor of Surgery Chief, Division of Gastroenterology Vice Chair for Clinical Operations, Department of Medicine Director, UCSD IBD Center University of California San Diego and UC San Diego Health System Dr. Sandborn[/caption] William J. Sandborn, MD Professor of Medicine and Adjunct Professor of Surgery Chief, Division of Gastroenterology Vice Chair for Clinical Operations, Department of Medicine Director, UCSD IBD Center University of California San Diego and UC San Diego Health System MedicalResearch.com: What is the background for this study? What are the main findings? Response: There is still a substantial unmet need for new treatments for patients with ulcerative colitis. A previous Phase II study had suggested that tofacitinib might be effective for short term therapy of ulcerative colitis. The patients in that study for the most part had not failed anti-TNF therapy. Now we report the findings from 3 large Phase III trials, two short term trials and one long term trial, demonstrating that tofacitinib 10 mg twice daily is effective for short term therapy, and that both 5 mg and 10 mg twice daily is effective for long term therapy. We also demonstrated that tofacitinib is effective both in patients who have not failed anti-TNF therapy and patients who have failed anti-TNF therapy. The study demonstrated induction of clinical remission, clinical response and mucosal healing (flexible sigmoidoscopy improvement) over the short term, and maintenance of clinical remission, clinical response, and mucosal healing over the long term.
Author Interviews, Diabetes, NEJM, Ophthalmology, Personalized Medicine / 20.04.2017

MedicalResearch.com Interview with: John M. Lachin, Sc.D. Research Professor of Biostatistics and of Epidemiology, and of Statistics The George Washington University Biostatistics Center and David Matthew Nathan, M.D. Professor of Medicine, Diabetes Unit Massachusetts General Hospital  MedicalResearch.com: What is the background for this study? Response: Traditional guidelines for screening for retinopathy, based on indirect evidence, call for annual examinations. The automatic annual screening for retinopathy, without considering potential risk factors for progression,  appears excessive based on the slow rate of progression through sub-clinical states of retinopathy.
Author Interviews, Diabetes, Heart Disease, NEJM / 13.04.2017

MedicalResearch.com Interview with: [caption id="attachment_33866" align="alignleft" width="141"]Aidin Rawshani, MD, PhD student Sahlgrenska Academy University of Gothenburg Dr. Rawshani[/caption] 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.
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.
Author Interviews, Heart Disease, Medical Imaging, NEJM / 19.03.2017

MedicalResearch.com Interview with: [caption id="attachment_33059" align="alignleft" width="200"]Dr. Matthias Götberg MD PhD Department of Cardiology, Clinical Sciences Lund University, Skåne University Hospital Lund, Sweden Dr. Matthias Götberg[/caption] 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. 
Author Interviews, NEJM, OBGYNE, Thyroid Disease, UT Southwestern / 01.03.2017

MedicalResearch.com Interview with: [caption id="attachment_32419" align="alignleft" width="70"]Professor, Brian Casey, M.D. Gillette Professorship of Obstetrics and Gynecology UT Southwestern Medical Center Dr. Casey[/caption] 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.
Author Interviews, Heart Disease, MRI, NEJM / 25.02.2017

MedicalResearch.com Interview with: [caption id="attachment_32206" align="alignleft" width="200"]Robert Russo, MD, PhD, FACC The Scripps Research Institute The La Jolla Cardiovascular Research Institute Dr. Robert Russo[/caption] 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.
Author Interviews, NEJM, OBGYNE, Pediatrics / 17.02.2017

MedicalResearch.com Interview with: [caption id="attachment_32143" align="alignleft" width="200"]Carla M. Bann, Ph.D. Division of Statistical and Data Sciences RTI International Research Triangle Park, NC Dr. Carla Bann[/caption] 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.
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.
Author Interviews, Heart Disease, NEJM, NIH, Pediatrics / 30.01.2017

MedicalResearch.com Interview with: [caption id="attachment_31628" align="alignleft" width="200"]Victoria Pemberton, RNC, MS, CCRC Program Officer Division of Cardiovascular Sciences National Heart, Lung, and Blood Institute, NIH Bethesda, Maryland Victoria Pemberton[/caption] 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.
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.
Author Interviews, Cancer Research, Immunotherapy, NEJM, Transplantation / 19.01.2017

MedicalResearch.com Interview with: [caption id="attachment_31344" align="alignleft" width="160"]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 Dr. Kenar Jhaveri,[/caption] 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.
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.
Author Interviews, Cost of Health Care, NEJM / 08.01.2017

MedicalResearch.com Interview with: [caption id="attachment_31066" align="alignleft" width="142"]John Z. Ayanian, MD, MPP</strong> Director of the Institute for Healthcare Policy and Innovation and Alice Hamilton Professor of Medicine University of Michigan Dr. John Z. Ayanian[/caption] 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.
Asthma, Author Interviews, Fish, NEJM, Pediatrics / 06.01.2017

MedicalResearch.com Interview with: [caption id="attachment_30990" align="alignleft" width="133"]Hans Bisgaard, M.D., D.M.Sc. COPSAC, Herlev and Gentofte Hospital University of Copenhagen Copenhagen, Denmark Dr. Hans Bisgaard[/caption] 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.
Author Interviews, Immunotherapy, Multiple Sclerosis, NEJM, University Texas / 22.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30711" align="alignleft" width="160"]Jerry S. Wolinsky, MD Emeritus Professor in Neurology McGovern Medical School part of UTHealth | The University of Texas Health Science Center at Houston Houston’s Health University Department of Neurology Houston, Texas 77030 Dr. Jerry Wolinsky,[/caption] 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.
Author Interviews, NEJM, Orthopedics, Surgical Research, Thromboembolism / 06.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30279" align="alignleft" width="187"]Suzanne C. Cannegieter, M.D., Ph.D. Einthoven Laboratory  Leiden University Medical Center  The Netherlands Dr. Suzanne Cannegieter,[/caption] 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.
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.
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.