Author Interviews, JAMA, NEJM, OBGYNE, University Texas / 09.08.2018

MedicalResearch.com Interview with: George R. Saade, MD Professor Jennie Sealy Smith Distinguished Chair Professor, Obstetrics & Gynecology, and Cell Biology Chief of Obstetrics and Maternal Fetal Medicine Director, Perinatal Research Division Department of Obstetrics and Gynecology Division of Maternal Fetal Medicine UTMB at Galveston MedicalResearch.com: What is the background for this study? Response: Several analyses show that the lowest risk to the baby is if delivered at 39 weeks. As pregnancy goes beyond 39 weeks, the risk to the baby increases. On the other hand, the general belief was that induction of labor at 39 increases the risk of cesarean and may not be good for the baby. The guideline were that induction without medical indication, or what we call elective induction of labor, should not be done. However, the studies on which this belief was based were not appropriately designed or analyzed. These studies compared women who were induced at 39 weeks to those who had spontaneous labor at 39 weeks. This comparison is not appropriate. While induction is a choice, having spontaneous labor at 39 weeks is not by choice.  So the correct comparison should be between women who were induced at 39 weeks to those who were not induced and continued their pregnancy beyond 39 weeks. In other words, they continued until they had spontaneous labor or developed an indication to be delivered (expectantly managed). That is how the study was done. First time pregnant women were randomized between these 2 options. The reason the study was done in first time mothers is that they have the highest risk of cesarean compared with women who had delivered vaginally before. (more…)
Author Interviews, Endocrinology, NEJM / 01.08.2018

MedicalResearch.com Interview with: Prof. Dr. Mirjam Christ-Crain Professor of endocrinology, diabetes and metabolism Heads the Department of Clinical Research University and University Hospital of Basel   MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by Diabetes Insipidus? Response: Drinking more than three litres per day with the equivalent increase in urination is regarded as too much. This drinking by the liter – known as “polyuria polydipsia syndrome" – usually develops over time through habit, or can be a side effect of a mental illness. In rare cases, however, it may be caused by diabetes insipidus. This is when the pituitary gland lacks the hormone vasopressin, which regulates the water and salt content in our body. Patients have a decreased ability to concentrate the urine, therefore lose a lot of fluid and have to increase their fluid intake accordingly to prevent dehydration (= Diabetes insipidus). The distinction between what is considered a "harmless" primary polydipsia and a diabetes insipidus is crucial, as their therapy is fundamentally different. Diabetes insipidus must be treated with the hormone vasopressin, while patients with primary polydipsia require behavioural therapy to reduce their habitual drinking. A wrong therapy can have life-threatening consequences as treatment with vasopressin without indication can lead to water intoxication. (more…)
Author Interviews, Biomarkers, Infections, NEJM, University of Pittsburgh / 19.07.2018

MedicalResearch.com Interview with: David T. Huang, MD, MPH Associate Professor, Critical Care Medicine, Emergency Medicine, Clinical and Translational Science Director, MACRO (Multidisciplinary Acute Care Research Organization) Director, CRISMA Administrative Core (Clinical Research, Investigation, and Systems Modeling of Acute illness) University of Pittsburgh MedicalResearch.com: What is the background for this study? Response: The overuse of antibiotics has become a serious threat to global public health, causing antibiotic resistance and increasing health care costs. Physicians have long known that antibiotics are usually unnecessary for acute bronchitis and for some other cases of lower respiratory tract infections, and that antibiotics treat only bacterial infections, not viral. But in daily practice, many physicians often prescribe them. Previous research had reported that using a biomarker blood test and following an antibiotic guideline tied to the test results could reduce antibiotic use in lower respiratory tract infections. In February 2017, the U.S. Food and Drug Administration approved the biomarker test that measures procalcitonin – a peptide that typically increases in bacterial infections, but not viral. We conducted the Procalcitonin Antibiotic Consensus Trial (ProACT) trial to evaluate whether a procalcitonin antibiotic prescribing guideline, implemented for the treatment of suspected lower respiratory tract infection with reproducible strategies, would result in less exposure to antibiotics than usual care, without a significantly higher rate of adverse events. The ProACT trial involved 14 predominately urban academic hospitals. We enrolled 1,656 adult patients who presented to the hospital emergency department and were initially diagnosed with a lower respiratory tract infection. All the patients were tested for their procalcitonin levels, but the results were shared only with the physicians of the patients randomly assigned to procalcitonin-guided antibiotic prescription. (more…)
Author Interviews, Infections, NEJM / 05.07.2018

MedicalResearch.com Interview with: Dr. Dennis E. Hruby PhD Chief Science Officer of SIGA Technologies Corvallis, OR MedicalResearch.com: What is the background for this study?  Response: Naturally occurring smallpox was declared eradicated in 1980 following coordinated decades-long global vaccination campaigns. However, there is a significant concern that smallpox, which is both highly contagious and highly lethal, could be used as a potential bioweapon. DNA synthesis technology and the possibility of unaccounted for smallpox stocks pose significant risks. While there are two publicly acknowledged stocks of smallpox virus held by the United States and Russia, some believe that additional stores of the virus could be in the hands of governments or organizations that might use them to cause harm. The DNA sequence of the smallpox genome is in the public domain and could potentially be synthesized in a laboratory from scratch or created by genetically modifying a similar virus. Currently, there are no therapies approved for the treatment of smallpox infection. A smallpox bioterror attack could be especially damaging because the majority of today’s population is not immune to the virus, as routine vaccination ended in the 1970s. It is estimated that without vaccination or treatment, each person infected with smallpox would infect 5 - 7 others. Rapid spread from person-to-person can occur through speaking, breathing or touching. Smallpox also can be transmitted by direct contact with infected fluids and contaminated objects. Furthermore, vaccination must occur within 3-5 days of exposure to smallpox, when patients are still asymptomatic, to be effective. These limitations underscore the need for an effective smallpox antiviral therapy, in addition to any available vaccine. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Cancer Research, Duke, Immunotherapy, NEJM, Vaccine Studies / 26.06.2018

MedicalResearch.com Interview with: Annick Desjardins, M.D., F.R.C.P.C. Associate Professor of Neurology Associate Professor of Neurosurgery Director of Clinical Research The Preston Robert Tisch Brain Tumor Center at Duke Duke University School of Medicine Durham, NC 27710 MedicalResearch.com: What is the background for this study? What are the main findings? Response: The poliovirus receptor (CD155) is an onco-fetal cell adhesion molecule with widespread expression in all solid tumors and particularly in primary CNS tumors (adult and pediatric). Recombinant nonpathogenic polio–rhinovirus chimera (PVSRIPO) was generated by replacing a critical piece of the genetic information from the Sabin type 1 polio vaccine, making PVSRIPO incapable of harming or killing normal brain cells, but toxic/lethal in cancer cells. In preclinical models, it has been demonstrated that the infection of tumor cells, leads to the release of danger signals, which triggers a recruitment of dendritic/CD4/CD8 T cells and a destruction of tumor cells by anti-tumor T cells. The manuscript reports the results of the phase 1 trial of PVSRSIPO in recurrent WHO grade IV malignant glioma patients. Adult patients with recurrence of a single glioblastoma lesion, 1-5.5cm in dimension, in a non-eloquent area of the brain, were enrolled on study. PVSRIPO is injected slowly over 6.5 hours directly into the tumor via a small catheter inserted via a small bur hole. Once intratumoral injection is completed, the catheter is removed and patients are observed for localized tumor inflammation, followed by tumor contraction. A total of 61 patients were treated on study, 9 patients in a dose escalation phase and 52 in a dose expansion phase. Side effects observed were in relation to the localized inflammation of the tumor and depending on the cerebral functions in close proximity to the tumor: headaches, visual field changes, hemiparesis, etc. One patient experienced a brain hemorrhage at the time of catheter removal, which triggered right sided weakness and aphasia. The patient remained alive 57.5 months after PVSRIPO infusion at data cutoff of March 20th, 2018. Two on-study death were observed, a patient died from cerebral edema and seizures, which was later found to be due to tumor progression, and one patient died from the complications of an intracranial hemorrhage while receiving anticoagulation and bevacizumab. The median overall survival among all 61 patients who received PVSRIPO was 12.5 months (95% CI, 9.9 to 15.2), comparatively to 11.3 months (95% CI, 9.8 to 12.5) in a historical control group of patients treated at Duke and who would have met eligibility on trial, would have the trial been available to them. At 24 months, the survival plateaued in patients treated with PVSRIPO with an overall survival rate of 21% (95% CI, 11 to 33) at 24 months and 36 months in PVSRIPO treated patients, while overall survival in the historical control group continued to decline, with an overall survival rates of 14% (95% CI, 8 to 21) at 24 months and 4% (95% CI, 1 to 9) at 36 months in the historical control group.  (more…)
Author Interviews, Diabetes, NEJM / 26.06.2018

MedicalResearch.com Interview with: Roman Hovorka PhD FMedSci Director of Research University of Cambridge Metabolic Research Laboratories Wellcome Trust-MRC Institute of Metabolic Science Addenbrooke’s Hospital Cambridge MedicalResearch.com: What is the background for this study? What are the main findings? Response: Inpatient diabetes is generally not managed well when patients are admitted for a range of health issues on the general ward. (more…)
Author Interviews, Dermatology, Hepatitis - Liver Disease, NEJM / 07.06.2018

MedicalResearch.com Interview with: Dr Christophe Corpechot Centre de Référence Maladie Rares: Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-immunes (MIVB-H) Filière Maladies Rares: Maladies Rares du Foie de l’Adulte et de l’Enfant Hôpital Saint-Antoine (APHP) et Sorbonne Universités Paris MedicalResearch.com: What is the background for this study? Response: Primary biliary cholangitis (PBC, previously known as "primary biliary cirrhosis") is a rare, chronic, slowly progressive liver disease of unknown cause, mainly affecting women of middle age. It is characterized by serum marks of autoimmunity (specific auto-antibodies), chronic inflammation and destruction of small intra-hepatic bile ducts, and consequent bile secretion impairment (chronic cholestasis) leading to the progressive development of cirrhosis and liver failure. Ursodeoxycholic acid (UDCA) is the only first-line approved treatment for PBC. It improves the biochemical measures of cholestasis and prolongs survival without liver transplantation. However, 30% to 40% of UDCA-treated patients continue to have clinically significant abnormalities of their biochemical liver tests and those patients remain at high risk of developing end-stage liver disease complications. Recently (2016), obeticholic acid (OCA) in association with UDCA has been conditionally approved in patients with an inadequate response to UDCA. This approval (FDA, EMA) was based one the results of a 1-year randomized, double-blind, placebo-controlled trial of OCA in patients with an incomplete response or intolerance to UDCA (POISE trial). In this trial, OCA was shown to improve the biochemical features of cholestasis (alkaline phosphatase (ALP) level < 1.67 times the upper limit of the normal range and a reduction of at least 15% from baseline) but was associated with a significant increase of pruritus, a characteristic, potentially debilitating symptom of PBC. BEZURSO is the first ever placebo-controlled phase 3 trial of a fibrate (a class of drugs known to be agonists of the peroxisome proliferator-activated receptors alpha) in PBC. In this 2-year randomized double-blind trial, 100 patients with an incomplete response to UDCA were assigned to bezafibrate 400 mg/day (n=50) or placebo (n=50), all in association with continued UDCA therapy. (more…)
Author Interviews, Cost of Health Care, Critical Care - Intensive Care - ICUs, End of Life Care, NEJM, University of Pittsburgh / 30.05.2018

MedicalResearch.com Interview with: Douglas B. White, M.D., M.A.S. Director of the Clinical Research Investigation and Systems Modeling of Acute Illness (CRISMA) Center’s Program on Ethics and Decision Making in  Department of Critical Care Medicine University of Pittsburgh  MedicalResearch.com: What is the background for this study?  Response: We set out to test the effectiveness of PARTNER (PAiring Re-engineered ICU Teams with Nurse-driven Emotional Support and Relationship-building). PARTNER is delivered by the interprofessional team in the ICU, consisting of nurses, physicians, spiritual care providers, social workers and others who play a part in patient care. The program is overseen by nurse-leaders in each ICU who receive 12 hours of advanced communication skills training to support families. The nurses meet with the families daily and arrange interdisciplinary clinician-family meetings within 48 hours of a patient coming to the ICU. A quality improvement specialist helps to incorporate the family support intervention into the clinicians’ workflow. PARTNER was rolled out at five UPMC ICUs with different patient populations and staffing. It was implemented in a staggered fashion so that every participating ICU would eventually get PARTNER. Before receiving PARTNER, the ICUs continued their usual methods of supporting families of hospitalized patients. None of the ICUs had a set approach to family communication or required family meetings at regular intervals before receiving PARTNER. A total of 1,420 adult patients were enrolled in the trial, and 1,106 of these patients’ family members agreed to be a part of the study and its six-month follow-up surveys. The patients were very sick, with about 60 percent dying within six months of hospitalization and less than 1 percent living independently at home at that point. (more…)
Author Interviews, Cancer Research, Gender Differences, Lung Cancer, NEJM, Smoking, Tobacco Research / 24.05.2018

MedicalResearch.com Interview with: “Woman smoking” by Pedro Ribeiro Simões is licensed under CC BY 2.0Ahmedin Jemal, DVM, PHD Scientific Vice President, Surveillance & Health Services Rsch American Cancer Society, Inc. Atlanta, GA 30303 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Historically, lung cancer rates have been higher in men than women at all ages because of the substantially higher cigarette smoking prevalence in men. However, cigarette smoking prevalences over the past few decades have become similar between young men and women. Consistent with this pattern, we previously reported the convergence of lung cancer rates between young men and young women. In this paper, we examined the lung cancer incidence rates in young women versus young men in the contemporary cohorts. We found that the historically higher lung cancer incidence rates in young men than in young women have reversed in whites and Hispanics born since the mid-1960s. However, this emerging incidence patterns were not fully explained by sex difference in smoking prevalence as cigarette smoking prevalences among whites and Hispanics were not higher in young women than young men. (more…)
Asthma, Author Interviews, NEJM / 22.05.2018

MedicalResearch.com Interview with: Mario Castro, M.D., M.P.H. Alan A. and Edith L. Wolff Professor of Pulmonary and Critical Care Medicine, Professor of Medicine, Pediatrics, and Radiology Washington University School of Medicine  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: This is a confirmatory phase 3 pivotal study that assessed the efficacy and safety of dupilumab in a population of uncontrolled moderate to severe asthmatics. This was the largest phase 3 placebo controlled trial conducted in this population evaluating a biologic. It enrolled patients without any minimum requirement for any type of biomarker such as blood eosinophils. It clearly confirmed the efficacy of dupilumab in reducing severe asthma exacerbations, improving lung function, asthma control and quality of life in the overall population. It also showed that patients with evidence of type 2 inflammation (increased blood eosinophils or exhaled NO) had a greater magnitude of effect. (more…)
Author Interviews, NEJM, Stroke, University Texas / 16.05.2018

MedicalResearch.com Interview with: Dr. S. Claiborne "Clay" Johnston MD, PhD Dean Vice President for Medical Affairs Frank and Charmaine Denius Distinguished Dean’s Chair Dell Medical School The University of Texas at Austin MedicalResearch.com: What is the background for this study? What are the main findings? Response: Prior studies have shown that the risk of a stroke or other ischemic events is high in the days to weeks after a TIA or minor stroke. We sought to test whether blocking platelet aggregation more effectively with clopidogrel plus aspirin could reduce this risk compared to aspirin alone.  We found that the combination did reduce risk of major ischemic events.  It also showed a small increase in risk of major hemorrhage, but for most people the benefits would outweigh the potential risk. (more…)
Alzheimer's - Dementia, Author Interviews, Merck, NEJM / 02.05.2018

MedicalResearch.com Interview with: Dr. Michael F. Egan MD Merck & Co. North Wales, PA 19454   MedicalResearch.com: What is the background for this study? What are the main findings? Response: A leading theory of Alzheimer's Disease is that it is caused by the buildup of amyloid plaques in the brain. Amyloid is composed of a sticky peptide called Abeta.  Abeta production can be blocked by Inhibiting an enzyme called BACE.  In animal models, BACE inhibtion prevent amyloid accumulation.  We aimed to see if a potent BACE inhibitor would slow clinical decline in Alzheimer's Disease. EPOCH was a Phase 2/3 randomized, placebo-controlled, parallel-group, double-blind study evaluating efficacy and safety of two oral doses of verubecestat an investigational BACE inhibitor, administered once-daily versus placebo in patients with mild-to-moderate AD currently using standard of care treatment. The primary efficacy outcomes of the study are the change from baseline in cognition (assessed using the Alzheimer's Disease Assessment Scale Cognitive Subscale, or ADAS-Cog),  as well as the change from baseline in function (assessed using the Alzheimer's Disease Cooperative Study – Activities of Daily Living, or ADCS-ADL)  after 78 weeks of treatment. Following the recommendation of the external Data Monitoring Committee (eDMC), which assessed overall benefit/risk during  the trial,  the study was stopped early, as there was “virtually no chance of finding a positive clinical effect.” Verubecestat did not reduce cognitive or functional decline in patients with mild-to moderate Alzheimer’s disease and was associated with treatment-related adverse events.  (more…)
Author Interviews, NEJM, Stroke / 30.04.2018

MedicalResearch.com Interview with: 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. (more…)
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.   (more…)
Author Interviews, Diabetes, NEJM, Pediatrics, Weight Research / 05.04.2018

MedicalResearch.com Interview with: 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.  (more…)
Author Interviews, Dermatology, Global Health, NEJM, Zika / 15.03.2018

MedicalResearch.com Interview with: 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. (more…)
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% (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, NEJM, Vanderbilt / 01.03.2018

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Kidney Disease, NEJM, Vanderbilt / 01.03.2018

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Hematology, NEJM, Orthopedics, Thromboembolism / 22.02.2018

MedicalResearch.com Interview with: 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. (more…)
Abbvie, Author Interviews, Hepatitis - Liver Disease, NEJM, Pharmaceutical Companies / 29.01.2018

MedicalResearch.com Interview with: 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.  (more…)
Author Interviews, Duke, NEJM, Rheumatology, Stem Cells, Transplantation / 04.01.2018

MedicalResearch.com Interview with: 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.
(more…)
Author Interviews, Cancer Research, Hematology, NEJM / 15.12.2017

MedicalResearch.com Interview with: Dr. Meletios 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. (more…)
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. (more…)
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. (more…)
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.  (more…)
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. (more…)
Author Interviews, Heart Disease, NEJM, UCLA / 05.11.2017

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