Author Interviews, NEJM, Stroke / 30.04.2018

MedicalResearch.com Interview with: [caption id="attachment_41321" align="alignleft" width="200"]A/Prof Bruce Campbell MBBS(Hons), BMedSc, PhD, FRACP Dr. Campbell[/caption] A/Prof Bruce Campbell MBBS(Hons), BMedSc, PhD, FRACP Consultant Neurologist, Head of Stroke Department of Neurology, Royal Melbourne Hospital Principal Research Fellow,Melbourne Brain Centre @ RMH Department of Medicine University of Melbourne Australia  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Patients with stroke due to a large blood vessel in the brain receive a clot-dissolving medication followed by clot retrieval surgery performed via an angiogram. The standard clot dissolving medication "alteplase" rarely opens the artery prior to clot retrieval surgery. Tenecteplase is genetically modified form of alteplase that may be more effective and is widely available (it is the standard clot dissolving medication used for heart attacks). It can be given over 10 seconds instead of the 1 hour required to infuse alteplase, meaning that patients can be transferred between hospitals to receive treatment more easily. Tenecteplase is also less expensive than alteplase. In EXTEND-IA TNK we found that tenecteplase doubles the number of patients who have blood flow restored to the brain earlier than is possible with clot retrieval surgery (22% vs 10%) and improves patient outcomes compared to the current standard medication called alteplase. 1 in 5 tenecteplase treated patients have blood flow rapidly restored and do not require clot retrieval surgery compared to 1 in 10 with alteplase.
Author Interviews, Blood Pressure - Hypertension, NEJM / 20.04.2018

MedicalResearch.com Interview with: “Blood Pressure” by Bernard Goldbach is licensed under CC BY 2.0José R. Banegas, M.D. Department of Preventive Medicine and Public Health Universidad Autónoma de Madrid Madrid, Spain MedicalResearch.com: What is the background for this study? What are the main findings? Response: Population-based studies and a few relatively small clinical investigations have defined the prognostic role of ambulatory blood pressure monitoring (ABPM) in hypertensive patients. However, previous studies were mostly limited by relatively small number of outcomes. Our study is the largest worldwide and provides unequivocal evidence that ABPM is superior to clinic pressure at predicting total and cardiovascular mortality across a wide range of clinical scenarios – the differences are striking. Also, whether white-coat hypertension is a benign phenotype is still debated. Our study demonstrates that white-coat hypertension was not benign. Lastly, masked hypertension patients (clinic BP normal but ABPM elevated) experienced the greatest risk of death.  
Author Interviews, Diabetes, NEJM, Pediatrics, Weight Research / 05.04.2018

MedicalResearch.com Interview with: [caption id="attachment_40992" align="alignleft" width="166"]Lise Geisler Bjerregaard PhD Dr. Geisler Bjerregaard[/caption] Lise Geisler Bjerregaard PhD Postdoc, PhD, M.Sc. Public Health Center for Klinisk Forskning og Sygdomsforebyggelse/ Center for Clinical Research and Disease Prevention Sektion for Klinisk Epidemiologi Frederiksberg Hospital, Frederiksberg MedicalResearch.com: What is the background for this study? What are the main findings? Response: Being overweight in childhood and early adulthood is associated with an increased risk of developing type 2 diabetes in adulthood. We wanted to know whether or not remission of overweight before early adulthood can reduce the risks of type 2 diabetes later in life. We studied the associations between different combinations of weight status in childhood, adolescence and early adulthood, and later development of type 2 diabetes. We found that men who had been overweight at 7 years of age but normalised weight by age 13 years and were normal weight as young men had similar risks of type 2 diabetes as men who were never overweight. Men who normalised weight between age 13 years and early adulthood had increased risks of type 2 diabetes, but lower risks than men who were overweight at all ages. 
Author Interviews, Dermatology, Global Health, NEJM, Zika / 15.03.2018

MedicalResearch.com Interview with: [caption id="attachment_40591" align="alignleft" width="233"]This image depicts a posterior view of a patient’s back, captured in a clinical setting, upon presenting with this blotchy rash. After a diagnostic work-up, it was determined that the rash had been caused by the Zika virus. Note: Not all patients with Zika get a rash CDC image This image depicts a posterior view of a patient’s back, captured in a clinical setting, upon presenting with this blotchy rash. After a diagnostic work-up, it was determined that the rash had been caused by the Zika virus.
Note: Not all patients with Zika get a rash
CDC image[/caption] Professor Bruno Hoen, M.D., Ph.D Dept of Infectious Diseases, Dermatology, and Internal Medicine University Medical Center of Guadeloupe  MedicalResearch.com: What is the background for this study? Response: Zika virus (ZIKV) infection during pregnancy has been identified only recently to cause severe birth defects, including microcephaly, other brain defects, and the congenital Zika syndrome. However, the magnitude of this risk was not clearly defined, with discrepancies between observational data from Brazil and the U.S. Zika Pregnancy Registry. We implemented a cohort study of pregnant women who have been exposed to ZIKV throughout the outbreak that hit the Caribbean in 2016.
Asthma, Author Interviews, NEJM, Pulmonary Disease / 09.03.2018

MedicalResearch.com Interview with: “Asthma Inhaler” by NIAID is licensed under CC BY 2.0Timothy Harrison, MBBS, BSc, FRCP, MD, MSc Professor and Honorary Consultant Faculty of Medicine & Health Sciences University of Nottingham MedicalResearch.com: What is the background for this study? What are the main findings? Response: Self management plans are recommend for patients with asthma but previous studies have shown that doubling the dose of inhaled steroids when asthma starts deteriorating is ineffective at preventing the development of an exacerbation. This study shows that quadrupling the dose is effective and in a real-life setting can reduce severe exacerbations by about 20%
Author Interviews, Critical Care - Intensive Care - ICUs, NEJM, Vanderbilt / 01.03.2018

MedicalResearch.com Interview with: [caption id="attachment_40231" align="alignleft" width="150"]Todd W. Rice, MD, MSc Associate Professor of Medicine Director, Vanderbilt University Hospital Medical Intensive Care Unit Division of Allergy, Pulmonary, and Critical Care Medicine Nashville, TN   Dr. Rice[/caption] Todd W. Rice, MD, MSc Associate Professor of Medicine Director, Vanderbilt University Hospital Medical Intensive Care Unit Division of Allergy, Pulmonary, and Critical Care Medicine Nashville, TN   MedicalResearch.com: What is the background for this study? Response: Our study (called the SMART study) evaluates the effects of different types of intravenous fluids used in practice in critically ill patients.  It is very similar to the companion study (called the SALT-ED study and published in the same issue) which compares the effects of different types of intravenous fluids on non-critically ill patients admitted to the hospital.  Saline is the most commonly used intravenous fluid in critically ill patients.  It contains higher levels of sodium and chloride than are present in the human blood.  Balanced fluids contain levels of sodium and chloride closer to those seen in human blood. Large observational studies and studies in animals have suggested that the higher sodium and chloride content in saline may cause or worsen damage to the kidney or cause death.  Only a few large studies have been done in humans and the results are a bit inconclusive.
Author Interviews, Critical Care - Intensive Care - ICUs, Kidney Disease, NEJM, Vanderbilt / 01.03.2018

MedicalResearch.com Interview with: [caption id="attachment_40216" align="alignleft" width="142"]Wesley H. Self, MD, MPH Associate Professor Department of Emergency Medicine Vanderbilt University Medical Center Nashville, TN  Dr. Self[/caption] Wesley H. Self, MD, MPH Associate Professor Department of Emergency Medicine Vanderbilt University Medical Center Nashville, TN   MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Doctors have been giving IV fluids to patients for more than 100 years. The most common IV fluid during this time has been saline; it has high levels of sodium and chloride in it (similar to table salt).  Balanced fluids are an alternative type of IV fluid that has lower levels of sodium and chloride that are more similar to human blood. Our studies were designed to see if treating patients with these balanced fluids resulted in better outcomes than saline.  We found that patients treated with balanced fluids had lower rates of death and kidney damage than patients treated with saline.
Author Interviews, Hematology, NEJM, Orthopedics, Thromboembolism / 22.02.2018

MedicalResearch.com Interview with: [caption id="attachment_40142" align="alignleft" width="200"]Dr. David R. Anderson, MD, FRCPC, FACP Faculty of Medicine Dean, Professor Dean, Faculty of Medicine Division of Hematology, Department of Medicine  & Nova Scotia Health Authority Dr. Anderson[/caption] Dr. David R. Anderson, MD, FRCPC, FACP Faculty of Medicine Dean, Professor Dean, Faculty of Medicine Division of Hematology, Department of Medicine & Nova Scotia Health Authority MedicalResearch.com: What is the background for this study? What are the main findings? Response: Blood clots in the lungs (pulmonary embolism) and veins of the legs (deep vein thrombosis) are well recognized complications following total hip and knee arthroplasty surgeries.  Prior to the routine use of antithrombotic prophylaxis, pulmonary embolism was the most common cause of death following these procedures.  Oral anticoagulants such as rivaroxaban are commonly prescribed for the indication of preventing blood clots following total hip or knee arthroplasty.  For maximal benefit these agents are continued following surgery for up to five weeks following total hip arthroplasty and for two weeks following total knee arthroplasty. There is evidence that aspirin has some benefit for the prevention of deep vein thrombosis and pulmonary embolism following total hip or knee arthroplasty.  However there is less evidence for its benefit than for oral anticoagulants.  We reasoned that aspirin would potentially be an attractive alternative for extended out of hospital prophylaxis following total hip or knee arthroplasty for patients who received a short course (5 days )of rivaroxaban following surgery.  Aspirin would be attractive for this indication because of its low cost, ease of use, and low rates of side effects. Our study demonstrated that in a randomized controlled trial involving a large group (over 3400) of patients undergoing total hip or knee arthroplasty that extended therapy with aspirin was comparable to rivaroxaban for the prevention of deep vein thrombosis and pulmonary embolism following surgery.  Low rates of complications (< 1%) were observed with both treatment arms.  We also found that rates of clinically important bleeding complications (the most common side effect with antithrombotic drugs) were uncommon and similar with the two agents.
Abbvie, Author Interviews, Hepatitis - Liver Disease, NEJM, Pharmaceutical Companies / 29.01.2018

MedicalResearch.com Interview with: [caption id="attachment_39686" align="alignleft" width="247"]In the United States, hepatitis A, hepatitis B and hepatitis C are the most common types, but also included are hepatitis D and E. CDC/ E.H. Cook, Jr. In the United States, hepatitis A, hepatitis B and hepatitis C are the most common types, but also included are hepatitis D and E.
CDC/ E.H. Cook, Jr.[/caption] Stefan Zeuzem, M.D. Professor of Medicine Chief Internal Medicine Goethe University Hospital Frankfurt, Germany MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Chronic hepatitis C virus (HCV) infection is a major global public health problem with more than 71 million people infected worldwide, and can result in significant morbidity and mortality, including liver cirrhosis, hepatocellular carcinoma, and death.1 This publication describes the efficacy and safety results from two Phase 3 clinical trials, ENDURANCE-1 and ENDURANCE-3, in patients with chronic HCV genotypes (GT) 1 or 3 infection who were treated with an all-oral, once-daily combination regimen of direct-acting antiviral agents (DAA) glecaprevir (GLE) at 300 mg and pibrentasvir (PIB) at 120 mg. The findings from ENDURANCE-1 trial show that the GLE/PIB combination regimen (G/P) given for 8 weeks to HCV GT1 chronically infected non-cirrhotic treatment-naïve or treatment-experienced (with sofosbuvir and/or interferon with ribavirin) patients was safe and well-tolerated, achieved high efficacy with a sustained virologic response at post-treatment week 12 (SVR12) rate >99% and was non-inferior to 12-week treatment with G/P. The trial also included subjects who were co-infected with human immunodeficiency virus (HIV), and all of these subjects achieved SVR12 while maintaining HIV suppression throughout the study. ENDURANCE-3 trial results show that the G/P regimen given for 8 weeks to HCV GT3 chronically infected non-cirrhotic treatment-naïve patients was safe and well-tolerated, achieved high efficacy in this historically difficult to cure GT with an SVR12 rate >94%, and was non-inferior to 12-week treatment with G/P, which in turn was non-inferior to the treatment with 12-week DAA regimen of sofosbivir and daclatasvir. 
Author Interviews, Duke, NEJM, Rheumatology, Stem Cells, Transplantation / 04.01.2018

MedicalResearch.com Interview with: [caption id="attachment_39161" align="alignleft" width="300"]“Breastfeeding welcome here” by Newtown grafitti is licensed under CC BY 2.0 Picture of a female patient's left arm, showing skin lesions caused by Scleroderma
Wikipedia image[/caption] Keith M. Sullivan, M.D. James B. Wyngaarden Professor Of Medicine Division of Cellular Therapy Duke University Medical Center Durham, North Carolina 27710, USA  MedicalResearch.com: What is the background for this study? What are the main findings?
  • Scleroderma with internal organ involvement is a devastating  autoimmune disorder with considerable morbidity and high mortality which have not changed in 40 years of reporting. Effective new therapies are needed.
  • Despite 2 prior randomized trials showing benefit for reduced-intensity stem cell transplant vs. conventional cyclophosphamide immune suppression, clinical practice in the US did not change due in part due to concern about patient safety and durability of response (attached).
  • The current randomized trial compares 12 monthly infusions of cyclophosphamide with high-dose chemotherapy plus whole-body irradiation designed to wipe-out (myeloablate) the defective, self-reactive immune system and replace with the patients own stem cells which had been treated to remove self-reacting lymphocytes. This was the first study to test if myeloablative autologous could re-establish a normal functioning immune system in patients with scleroderma.
Author Interviews, Cancer Research, Hematology, NEJM / 15.12.2017

MedicalResearch.com Interview with: [caption id="attachment_38970" align="alignleft" width="200"]Dr. Meletios A. Dimopoulos MD Professor and Chairman Department of Clinical Therapeutics University Athens School of Medicine Athens, Greece Dr. Dimopoulos[/caption] DrMeletios A. Dimopoulos MD Professor and Chairman Department of Clinical Therapeutics University Athens School of Medicine Athens, Greece MedicalResearch.com: What is the background for this study? What are the main findings? Response: Updated data from the Phase 3 POLLUX trials showed DARZALEX, in combination with lenalidomide and dexamethasone, reduced the risk of disease progression or death by 56 percent, compared to lenalidomide and dexamethasone alone (Hazard Ratio [HR]=0.44; 95 percent CI [0.34-0.55], p<0.0001). After a median follow-up of 32.9 months, the median progression-free survival (PFS) in the DARZALEX arm has not been reached, compared with a median PFS of 17.5 months for patients who received lenalidomide and dexamethasone alone. DARZALEX in combination with lenalidomide and dexamethasone also significantly increased the overall response rate (ORR) compared to lenalidomide and dexamethasone alone (93 percent vs. 76 percent, p<0.0001), including rates of complete response (CR) or better (55 percent vs. 23 percent, p<0.0001). DARZALEX also showed significantly higher (>3-fold) MRD-negative rates compared to lenalidomide and dexamethasone alone. These data were featured as an oral presentation (Abstract #739) at the 59th American Society of Hematology (ASH) Annual Meeting in early December.
Author Interviews, NEJM, Surgical Research, Technology / 06.12.2017

MedicalResearch.com Interview with: Suresh Vedantham, M.D. Principal Investigator, ATTRACT Trial Professor of Radiology & Surgery Mallinckrodt Institute of Radiology Washington University School of Medicine  MedicalResearch.com: What is the background for this study? What are the main findings? Response:   About 300,000 Americans each year are diagnosed with a blood clot (deep vein thrombosis, DVT) for the first time.  In total, about 600,000 Americans have a DVT each year, as noted in the 2008 Surgeon General’s Call to Action. Despite the use of standard treatment (blood thinning drugs and compression stockings), about 40% of DVT patients develop a long-term complication called post-thrombotic syndrome (PTS).  PTS impairs patients’ quality of life and typically causes chronic pain and swelling of the leg that occur on a daily basis. In many patients, this leads to major disability the prevents them from walking, working, or conducting normal daily activities. Some patients develop painful open sores on the leg called “venous ulcers”, that are difficult to heal. Pharmacomechanical catheter-directed thrombolysis (“PCDT”) is a minimally-invasive treatment that removes blood clots through a tiny (2-3 mm) incision using the clot-busting drug tissue plasminogen activator (TPA) along with catheter-based devices that can chew up the clots. The benefits and risks of PCDT have not before been evaluated for DVT treatment in a rigorous study.      The final results of the ATTRACT Trial, which was primarily sponsored by the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH), are being published in The New England Journal of Medicine.  ATTRACT, the most rigorous study to date of clot-busting treatment for DVT, was a multicenter randomized controlled trial comparing PCDT and standard therapy versus standard therapy alone in 692 patients with above-knee DVT. This landmark study, conducted in 56 U.S. hospitals, was led by Principal Investigator Dr. Suresh Vedantham, Professor of Radiology & Surgery at the Mallinckrodt Institute of Radiology at Washington University in St. Louis, along with outstanding DVT researchers at McMaster University (Hamilton, Ontario [Canada]), the Massachusetts General Hospital (Boston, MA), and the Mid America Heart Institute (Kansas City, MO).   The primary study result is that for most patients with DVT, the addition of PCDT to standard therapy does not prevent the development of PTS.  Because the use of PCDT involves a small but significant increase in major bleeding complications, it should not be routinely used as first-line DVT treatment.  However, PCDT did reduce the severity of PTS and appeared likely to provide better relief of DVT-related leg pain and swelling.  Further analyses will determine which DVT patients are most likely to experience these benefits.
Author Interviews, Breast Cancer, NEJM, OBGYNE / 06.12.2017

MedicalResearch.com Interview with: “Birth control pills” by lookcatalog is licensed under CC BY 2.0Lina Mørch PhD, MSc Senior Researcher Rigshospitalet MedicalResearch.com: What is the background for this study? What are the main findings? Response: There was a lack of evidence on contemporary hormonal contraception and risk of breast cancer. In particular the knowledge of risk with newer progestins was sparse.
Author Interviews, Brigham & Women's - Harvard, NEJM, Pediatrics, Weight Research / 30.11.2017

MedicalResearch.com Interview with: “Kovalam Beach - Obesity : a rising problem in India” by Miran Rijavec is licensed under CC BY 2.0Mr. Zachary Ward Center for Health Decision Science Harvard T.H. Chan School of Public Health Boston, MA 02115 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Although the current obesity epidemic in the US has been well documented in children and adults, less is known about the long-term risks of adult obesity for children given their current age and weight.  As part of the CHOICES project (Childhood Obesity Intervention Cost Effectiveness Study), we developed new methods to simulate height and weight trajectories across the life course based on individual-level data.  We also used a novel statistical approach to account for long-term population-level trends in weight gain, allowing us to make more realistic projections of obesity into the future. 
Author Interviews, Kidney Disease, Mayo Clinic, NEJM / 06.11.2017

MedicalResearch.com Interview with: Dr. TorresVicente E. Torres, M.D., Ph.D. Director of the Mayo Clinic Translational Polycystic Kidney Disease (PKD) Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Experimental work pioneered by Dr. Jared Grantham showed that cyclic AMP, an intracellular signaling molecule, promotes the development and growth of cysts. Vasopressin, a hormone produced by the pituitary gland, stimulates the production of cyclic AMP in the collecting ducts, from which most cysts derive in autosomal dominant polycystic kidney disease (ADPKD). While this effect of vasopressin is necessary for the kidneys to concentrate and reduce the volume of urine, it promotes the development and growth of cysts in patients with ADPKD. Dr. Vincent Gattone realized that inhibiting the action of vasopressin could be protective in polycystic kidney disease. Work in our and other laboratories confirmed that suppression of vasopressin production, release or action reduces cyst burden, protects kidney function, and prolongs survival in rodent models of the disease. This experimental work provided a strong rationale for clinical trials of tolvaptan, a vasopressin V2 receptor antagonist. Tolvaptan reduced the rate of kidney growth in the TEMPO 3:4 trial, in patients with early ADPKD. It also reduced the rate of decline in kidney function, measured by the estimated glomerular filtration rate (eGFR), from 10.1 to 6.8 mL/min/1.73 m2 over three years. The eGFR benefit was maintained during two additional years when all the patients were treated with tolvaptan in an open label extension of the TEMPO 3:4 trial (TEMPO 4:4). Safety laboratory tests performed every four months showed elevations of liver transaminases in blood in 4.4% of tolvaptan and 1% of placebo-treated patients. Three of 1,271 tolvaptan-treated patients during TEMPO 3:4 and TEMPO 4:4 had evidence of potentially serious drug-induced liver injury. These abnormalities occurred all within the first 18 months of exposure to tolvaptan. Based on the TEMPO 3:4 results, tolvaptan was approved for the treatment of rapidly progressive ADPKD in Japan, Canada, European Union, Switzerland and South Korea. In the United States, the Food and Drug Administration requested additional data to further evaluate the efficacy and safety of this drug. The REPRISE trial was performed to determine the efficacy and safety of tolvaptan in patients with later stage ADPKD.
Author Interviews, Heart Disease, NEJM, UCLA / 05.11.2017

MedicalResearch.com Interview with: [caption id="attachment_37907" align="alignleft" width="100"]Bruno Péault PhD Professor and Chair, Vascular Regeneration Center For Cardiovascular Science MRC Centre for Regenerative Medicine Scientific Director, BHF Laboratories The University of Edinburgh and Professor, David Geffen School of Medicine at UCLA Orthopaedic Hospital Research Center University of California at Los Angeles Los Angeles, CA 90095-7358 Dr. Péault[/caption] Bruno Péault PhD Professor and Chair, Vascular Regeneration Center For Cardiovascular Science MRC Centre for Regenerative Medicine Scientific Director, BHF Laboratories The University of Edinburgh and Professor, David Geffen School of Medicine at UCLA Orthopaedic Hospital Research Center University of California at Los Angeles Los Angeles, CA 90095-7358 MedicalResearch.com: What is the background for this study? Response: Kidney, lung, liver, muscle, heart are among the many organs which can be severely affected by fibrosis, a natural scarring process whereby healthy tissues are replaced by a fibrous non-functional substitute. For instance, the billions of cardiac muscle cells that die after a heart infarct, consequently to blood supply interruption, are replaced by a fibrotic scar that cannot contract, reducing the capacity of the heart to pump blood, and leading often to heart failure. There is currently no efficient treatment of fibrotic scars, the basic cellular component of which is the myofibroblast, a cell of unremarkable appearance and unclear origin. The transforming growth factor β (TGFβ) molecule triggers fibrosis development after being activated, via the extra-cellular matrix, by αv integrins, which are adhesion molecules present at the surface of the target cells. To gain further insight into the cells that drive fibrosis in the heart and skeletal muscle, and explore ways to control this deleterious process, mice were used in which cells expressing the β receptor for PDGF (platelet derived growth factor) have been genetically tagged with a green fluorescent protein, a system previously used by Prof. Neil Henderson to trace fibrosis in the diseased liver (cells naturally expressing PDGFRβ are, in their vast majority, perivascular cells surrounding small blood vessels, as well as some interstitial fibroblasts). Skeletal muscle was injured by a small incision or with a targeted injection of cardiotoxin, a snake venom compound that locally kills myofibers, while the heart was damaged by prolonged infusion of angiotensin II. In both settings, progression of fibrosis was followed over time and contribution of green fluorescent cells – i.e. those expressing PDGFRβ – was assessed.
Author Interviews, Diabetes, Lipids, NEJM / 01.11.2017

MedicalResearch.com Interview with: M. Loredana Marcovecchio, M.D. Clinical Scientist and Professor David Dunger M.D. Director of Research Professor of Paediatrics University of Cambridge MedicalResearch.com: What is the background for this study? What are the main findings? Response: The efficacy and safety of ACE Inhibitors and statins in adolescents have been shown in the context of hypertension and familial hypercholesterolemia, respectively. However, there is a lack of data on the long-term use of these drugs in those with type 1 diabetes and, in particular, there is no clear indication for their use in patients with increased albumin excretion. The Adolescent type 1 Diabetes cardio-renal Intervention Trial (AdDIT) was a multi-centre, international study, set up by investigators in the UK, Australia and Canada to explore if drugs already used to lower blood pressure (ACE inhibitors) and cholesterol levels (Statins) in adults with diabetes could reduce the risk of kidney, eye and cardiovascular disease in adolescents with Type 1 diabetes. Neither ACE inhibitors nor statins significantly reduced the albumin-creatinine ratio during the 2-4 year trial period. However, some of the secondary outcomes suggest that the drugs may have important benefits. Treatment with the ACE inhibitor resulted in a 43% reduction in the rates of progression to microalbuminuria, which was not statistically significant, but it could have important clinical implications. Preventing even intermittent cases of microalbuminuria is known to reduce the future risk of kidney and cardiovascular complications. Statin therapy led to reduced levels of lipid levels, which could reduce long-term risk for cardiovascular complications. These findings could translate into long-term benefits, but follow-up of this unique cohort will be essential. The essential biological samples and data provided by the participants will continue to inform our future understanding and our options for effective therapies for this vulnerable group of young people with type 1 diabetes.
Author Interviews, Epilepsy, NEJM, Neurological Disorders, Pediatrics, Surgical Research / 25.10.2017

MedicalResearch.com Interview with: Dr. Manjari Tripathi Professor, Epileptology, Neurology Dr. P Sarat Chandra, Chief epilepsy Neurosurgeon AIIMS, New Delhi MedicalResearch.com: What is the background for this study?:
  1. Surgery for drug resistant epilepsy (DRE) is an accepted procedure for children and there have been multiple surgical series and surgical techniques published in literature. However, till date there are no randomized controlled trials (RCT) available to objectively demonstrate the safety and efficacy of surgical therapy in children with DRE. There are till date only 2 randomized trials for adult patients with drug resistant epilepsy (both for mesial temporal sclerosis only, Wiebe S et al, New Eng J Med, 2001 & Engel J et al, JAMA, 2012).
  2. Children constitute a significant proportion of patients undergoing surgical therapy for DRE (close to 50% in tertiary centers). They have unique problems associated due to uncontrolled epilepsy and some of these include epileptic encephalopathy and status epilepticus. In addition, surgery is also associated with problems like hypothermia, issues related to blood loss etc. Thus the senior author (Manjari Tripathi) and her team felt that a RCT would be very important to objectively assess the role of surgery and hence designed this study.
Author Interviews, Exercise - Fitness, NEJM, Orthopedics / 04.10.2017

MedicalResearch.com Interview with: [caption id="attachment_37336" align="alignleft" width="116"]Monika Bayer PhD. Institute of Sports Medicine Copenhagen Bispebjerg Hospital Denmark Dr. Bayer[/caption] Monika Bayer PhD. Institute of Sports Medicine Copenhagen Bispebjerg Hospital Denmark MedicalResearch.com: What is the background for this study? What are the main findings? Response: Acute muscle strain injuries display a major clinical problem with a high incidence rate for both professional and amateur athletes and are associated with substantial risk for recurrence. Common clinical practice advices to follow the RICE (Rest – Ice – Compression – Elevation) principle after strain injuries but it has not been investigated whether patients really benefit from a period of rest or whether an early of loading following the injury would improve recovery. In this study, amateur athletes were divided into two groups: one group started rehabilitation two days after the trauma, the other group waited for one week and began rehabilitation after nine days. All athletes had a clear structural defect of the muscle-connective tissue unit following explosive movements. We found that protraction of rehabilitation onset caused a three-week delay in pain-free recovery. In all athletes included, only one suffered from a re-injury.
Author Interviews, Diabetes, NEJM, Surgical Research, Weight Research / 20.09.2017

MedicalResearch.com Interview with: Ted Adams PhD Adjunct Professor, Internal Medicine Adjunct Associate Professor, Nutrition & Integrative Physiology The University of Utah  MedicalResearch.com: Why did you decide to conduct this study? Response: The primary aim of the study was to determine the clinical outcomes in patients who underwent gastric bypass surgery. As NIDDK/NIH continued to fund the study, the aim was extended to determining the durability) long-term outcomes) of gastric bypass surgery when compared to non-surgical, severely obese patients.
Author Interviews, Boehringer Ingelheim, Columbia, Heart Disease, J&J-Janssen, Merck, NEJM / 14.09.2017

MedicalResearch.com Interview with: [caption id="attachment_36919" align="alignleft" width="150"]Professor Christopher P. Cannon MD Executive Director, Cardiometabolic Trials, Baim Institute Cardiologist Brigham and Women's Hospital Baim Institute for Clinical Research Columbia University College of Physicians and Surgeons Dr. Cannon[/caption] Professor Christopher P. Cannon MD Executive Director, Cardiometabolic Trials, Baim Institute Cardiologist Brigham and Women's Hospital Baim Institute for Clinical Research Columbia University College of Physicians and Surgeons MedicalResearch.com: What is the background for this study? What are the main findings? Response: The trial explored whether a dual therapy approach of anticoagulation and P2Y12 antagonist - without aspirin - in non-valvular atrial fibrillation (AF) patients following percutaneous coronary intervention (PCI) and stent placement would be as safe, and still efficacious, as the current standard treatment – triple therapy. For more detailed background on the study, readers may want to review the first paragraph of the article in the New England Journal of Medicine. Results showed significantly lower rates of major or clinically relevant non-major bleeding events for dual therapy with dabigatran, when compared to triple therapy with warfarin. In the study, the risk for the primary safety endpoint (time to major or clinically relevant non-major bleeding event) was 48 percent lower for dabigatran 110 mg dual therapy and 28 percent lower for dabigatran 150 mg dual therapy (relative difference), with similar rates of overall thromboembolic events.
Author Interviews, Infections, NEJM / 14.09.2017

MedicalResearch.com Interview with: [caption id="attachment_36972" align="alignleft" width="107"]Susan E. Dorman, M.D Associate Professor of Medicine, Division of Infectious Diseases Johns Hopkins University School of Medicine, Baltimore Dr. Dorman[/caption] Susan E. Dorman, M.D Associate Professor of Medicine, Division of Infectious Diseases Johns Hopkins University School of Medicine, Baltimore MedicalResearch.com: What is the background for this study? What are the main findings? Response: Tuberculosis, also called “TB” is one of the top 10 causes of death worldwide, according to the World Health Organization.  TB is caused by bacteria called Mycobacterium tuberculosis.  In 2015, over 10 million people became sick from TB and 1.8 million people died from TB.  This is a lot of people – diagnosing and treating TB to improve their health is important.  Because TB usually involves the lungs, it can be passed from person to person through the air, and thus, diagnosing and treating TB is critical to  reduce the spread of TB.   Drug-resistant TB -- TB caused by bacteria that are resistant to commonly used TB antibiotics -- is a serious problem.  In 2015 an estimated 480,000 people had multidrug-resistant TB. We have been working to develop better, faster ways to diagnose TB and drug-resistant TB.  A new test was developed as a partnership between Rutgers University and Cepheid (Sunnyvale, CA), and development was supported by the US National Institutes of Health (NIH).  The new test was designed to detect Mycobacterium tuberculosis bacteria in sputum, and to simultaneously detect whether the bacteria are resistant to several of the main antibiotics (isoniazid, fluoroquinolones, and aminoglycosides) used to treat TB.  The test takes about two hours from sample to result. The NEJM article describes the results of a study that was undertaken in China and South Korea to understand how well the new test works, compared against gold standard tests.
Author Interviews, Melanoma, NEJM / 14.09.2017

MedicalResearch.com Interview with: [caption id="attachment_36963" align="alignleft" width="116"]Dr Alexander Menzies BSc(Med) MBBS (Hons) FRACP PhD Medical Oncologist and Senior Research Fellow at Melanoma Institute Australia The University of Sydney and Royal North Shore and Mater Hospital  Dr. Menzies[/caption] Dr Alexander Menzies BSc(Med) MBBS (Hons) FRACP PhD Medical Oncologist and Senior Research Fellow at Melanoma Institute Australia The University of Sydney and Royal North Shore and Mater Hospital  MedicalResearch.com: What is the background for this study? Response: For early-stage melanoma, surgical resection is the standard treatment and is associated with an excellent long-term prognosis. However until now, Stage III melanoma patients (where the disease has spread to the lymph nodes) who have had their tumours surgically removed have simply had to play the waiting game to see if their melanoma would metastasise, with many ultimately dying of the disease. Checkpoint inhibitor immunotherapies and drugs that target the mitogen-activated protein kinase (MAPK) pathway have improved the outcome of patients with metastatic melanoma, but their role as adjuvant therapy is still being actively investigated. Prior Phase III trials (COMBI-D and COMBI-V) have shown improved overall survival in patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations. At Melanoma Institute Australia, we were keen to see if this improvement would be seen in the adjuvant setting also. This clinical trial was the first in the world to give targeted therapy to melanoma patients at an earlier stage of the disease to prevent spread and recurrence.
Author Interviews, Heart Disease, NEJM, Stroke, Surgical Research / 13.09.2017

MedicalResearch.com Interview with: [caption id="attachment_36953" align="alignleft" width="150"]Prof. Jean-Louis MAS Université Paris Descartes INSERM UMR S 894 Service de Neurologie et Unité Neurovasculaire Hôpital Sainte-Anne Paris  Prof. Jean Louis MAS[/caption] Prof. Jean-Louis MAS Université Paris Descartes INSERM UMR S 894 Service de Neurologie et Unité Neurovasculaire Hôpital Sainte-Anne Paris  MedicalResearch.com: What is the background for this study? Response: Stroke is a major cause of death, disability and dementia affecting 17 million people each year worldwide. About 80% of strokes are ischemic strokes due to occlusion of a cerebral artery by a thrombus, itself the consequence of various arterial or heart diseases. In 30 to 40% of cases, no definite cause of ischemic stroke can be identified. Cryptogenic stroke is the term used to refer to these strokes of unknown etiology. The patent foramen ovale (PFO) is a defect between the upper two heart chambers (called atria) though which a thrombus of venous origin may reach the systemic circulation and cause a stroke. This mechanism is called paradoxical embolism. Several case-control studies have shown an association between PFO and cryptogenic ischemic stroke, particularly in patients less than 60 years old, in those who have an atrial septal aneurysm (defined as an abnormal protrusion of the interatrial septum in the right or the left atrium or both) in addition to a PFO, and in those who have a PFO with a large right-to-left shunt. These findings suggested that a PFO might be responsible for stroke and that PFO closure with a device may decrease the risk of stroke recurrence. However, the causative relationship between PFO and stroke and the best strategy to prevent stroke recurrence have long been a hot topic of debate. Three previous randomized clinical trials failed to demonstrate any superiority of PFO closure over antithrombotic therapy.
Author Interviews, NEJM, Pulmonary Disease / 10.09.2017

MedicalResearch.com Interview with: Dr Prof Nanshan Zhong, MD (Edin), FRCS (Edin), FRCP and Pixin Ran PhD National Center for Respiratory Diseases, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Response:    According to the latest research, in 2015, 3.2 million people died from COPD globally, with an increase of 11.6% in mortality compared with that in 1990 (GBD 2015 Chronic Respiratory Disease Collaborators. Lancet Respir Med. 2017,5:691-706). COPD has now become the third leading cause of death worldwide and is estimated to become the disease with the seventh greatest burden worldwide in 2030. In China, the prevalence was 8.2% among people aged 40 years or greater, according to our epidemiological survey in 2007. Importantly, current international guidelines have been mainly focusing on the management of moderate-to-severe COPD. However, among this patient cohort, the severely impaired lung function can only be reversed to a very limited extent despite the most potent treatment combinations. Patients with more advanced COPD are frequently associated with a significantly higher mortality and incidence of re-hospitalization and disability, which cause tremendous economic burden for both the families and the society. However, more than 70% of COPD patients are currently categorized as having stage I to early stage II COPD, most of whom have no or very few respiratory symptoms (Zhong NS, et al. Am J Respir Crit Care Med. 2007, 176:753-760; Mapel DW, et al. Int J COPD 2011; 6: 573−581). The vast majority of these patients would have the “COPD assessment Test” (CAT) score of 10 or lower (range: 0 to 40, with higher scores indicating more severe COPD). Admittedly, no medication has been recommended for this patient cohort according to the latest international guidelines. In real-world practice, these patients are almost neglected by physicians and have received virtually no medication. Nonetheless, the annual lung function decline rates among these patients are the most rapid among all COPD patients. (Bhatt SP, et al. Am J Respir Crit Care Med 2015; 191: A2433). An important clinical question has been raised regarding whether an intervention strategy targeting at early stages of COPD can possibly make the airflow limitation more reversible or prevent from further deterioration.
Author Interviews, Blood Pressure - Hypertension, NEJM / 23.08.2017

MedicalResearch.com Interview with: Dan Berlowitz, MD, MPH Investigator, CHOIR Chief of Staff, Edith Nourse Rogers Memorial VA Hospital Professor, Boston University Schools of Public Health and Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: The main results from the SPRINT study, published in 2015, demonstrated that intensive hypertension therapy targeting a systolic blood pressure (SBP) of 120 mm Hg results in reduced cardiovascular morbidity and mortality when compared to standard therapy targeting a SBP of 140. Yet many have expressed concerns that lowering SBP to 120 may be associated with a variety of symptoms, including dizziness, fatigue, and depression, especially in older and frailer patients. This study using SPRINT data examined patient-reported outcomes including health-related quality of life, depressive symptoms, and satisfaction. The main findings are that there were no differences in patient-reported outcomes among patients receiving intensive therapy compared to standard therapy, even among older SPRINT participants with multiple comorbidities.
Author Interviews, Heart Disease, NEJM, Surgical Research / 16.08.2017

MedicalResearch.com Interview with: [caption id="attachment_36451" align="alignleft" width="133"]A. Laurie Shroyer, Ph.D., M.S.H.A. WOC Health Science Officer Northport VAMC Research and Development Office (151) Northport, NY 11768 Professor and Vice Chair for Research, Department of Surgery Stony Brook University, School of Medicine Stony Brook, NY Dr. Shroyer[/caption] A. Laurie Shroyer, Ph.D., M.S.H.A. WOC Health Science Officer Northport VAMC Research and Development Office (151) Northport, NY 11768 Professor and Vice Chair for Research, Department of Surgery Stony Brook University, School of Medicine Stony Brook, NY  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Since the 1990’s, two different approaches have been commonly used by cardiac surgeons to perform an adult coronary artery bypass graft (CABG) procedure, these approaches have been referred to as  “on-pump” (with cardiopulmonary bypass) or “off-pump” (without cardiopulmonary bypass) procedures. The Department of Veterans Affairs (VA) Randomized On/Off Bypass Follow-up Study” (ROOBY-FS) compared the relative performance of off-pump versus on-pump approaches upon 5-year patients’ clinical outcomes including mortality and major adverse cardiovascular events.
Author Interviews, Flu - Influenza, Kaiser Permanente, Merck, NEJM, Vaccine Studies / 10.08.2017

MedicalResearch.com Interview with: [caption id="attachment_36395" align="alignleft" width="139"]Michael Jackson  PhD, MPH Kaiser Permanente Washington Health Research Institute (KPWHRI) principal investigator for the United States Influenza Vaccine Effectiveness Network Dr. Jackson[/caption] Michael Jackson  PhD, MPH Kaiser Permanente Washington Health Research Institute (KPWHRI) principal investigator for the United States Influenza Vaccine Effectiveness Network  MedicalResearch.com: What is the background for this study?
  • Response: Each year, Kaiser Permanente Washington is one of five sites across the country that participate in the United States Influenza Vaccine Effectiveness Network. The Network reports its early interim results in the MMWRand presents additional interim results to the Advisory Committee on Immunization Practices (ACIP)This New England Journal of Medicine publication is an update of those interim results.
  • The findings in this New England Journal of Medicine are special because prior randomized controlled trials indicated that the nasal spray vaccine (FluMist)—also called live attenuated influenza vaccine (LAIV)—would work well to protect children and teens from the flu, whereas in actual practice we found that the flu shot worked much better, particularly against the predominant strain, A(H1N1)pdm09.
  • The nasal spray vaccine was first seen to be less effective for young children than the flu shot in 2013-2014 for the A(H1N1)pdm09 virus strain. In response, the A(H1N1)pdm09 virus strain used in the nasal spray vaccine was changed for the 2015-2016 influenza season. The 2016/17 season was the first since 2015-2016 to be dominated by the A(H1N1)pdm09 virus, making this our first opportunity to evaluate the updated nasal spray vaccine.
  • The Influenza Vaccine Effectiveness Network evaluated the impact of this change as part of our estimates of influenza vaccine effectiveness in 2015-2016. Preliminary findings from this study were presented to the ACIP in June 2016, which led to the nasal spray vaccine not being recommended in 2016-2017 in the US, although the nasal spray vaccine remains licensed in the US. In 2016-2017, the LAIV A(H1N1)pdm09 vaccine strain was unchanged from 2015-2016.
Author Interviews, Kidney Disease, NEJM, Transplantation / 04.08.2017

MedicalResearch.com Interview with: [caption id="attachment_36307" align="alignleft" width="143"]Stanley C. Jordan, M.D Director, Division of Nephrology Medical Director, Kidney Transplant Program Medical Director, Human Leukocyte Antigen and Transplant Immunology Laboratory Cedars-Sinai, Los Angeles, CA Dr. Jordan[/caption] Stanley C. Jordan, M.D DirectorDivision of Nephrology Medical DirectorKidney Transplant Program Medical Director, Human Leukocyte Antigen and Transplant Immunology Laboratory Cedars-Sinai, Los Angeles, CA  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The background for this study is as follows: Patients who are highly HLA sensitized have antibodies to transplant targets create an immunologic barrier to transplant. Currently, there are no approved therapies for elimination of these antibodies. Desensitization is available but is not always successful and most desensitized patients are still transplanted with a positive crossmatch. Thus, many patients are not able to receive life-saving kidney transplants unless newer therapies to remove antibodies are found. The findings of our study published in the New England Journal of Medicine revealed that the use of the enzyme from streptococcal pyogenes called IdeS® (IgG endopeptidase) is very effective in eliminating donor specific antibodies and allowing transplantation to occur. Antibodies were eliminated from one week up to two months after one treatment with Ides® allowing a safe environment for the transplant to occur. Rejections episodes did occur in some of the patients but were generally mild and easily treatable. Only one patient of 25 lost his allograft during the study. Thus, the study shows promising results for a new approach for elimination of pathogenic antibodies that did not exist before.
Author Interviews, Brigham & Women's - Harvard, Lifestyle & Health, NEJM, Nutrition / 13.07.2017

MedicalResearch.com Interview with: [caption id="attachment_35810" align="alignleft" width="166"]Mercedes Sotos Prieto PhD Research Fellow Department of Nutrition Harvard T. H. Chan School of Public Health  Dr. Sotos-Prieto[/caption] Mercedes Sotos Prieto PhD Research Fellow Department of Nutrition Harvard T. H. Chan School of Public Health MedicalResearch.com: What is the background for this study? What are the main findings? Response: Previous research have found that adherence to the 2010 Alternate Heathy Eating Index, the Mediterranean Diet pattern, and DASH pattern is associated with health benefits, but none of those studies have examined dynamic changes in diet quality over time and subsequent risk of mortality. This is the first study to demonstrate that improvement in these three diet scores over time is associated with reduced risk of total and cardiovascular mortality. In contrast, worsening diet quality over 12-years was associated with 6%-12% increased mortality. In addition, not only improvement in diet quality but maintaining a high adherence to any of the three dietary patterns over 12 years was significantly associated with 9%-14% lower total mortality.