Author Interviews, Multiple Sclerosis, Pharmacology / 27.09.2016

MedicalResearch.com Interview with: Marcia Kayath, MD Vice President and Head US Clinical Development and Medical Affairs US General Medicines Novartis Pharmaceuticals Corporation MedicalResearch.com: What is the background for this study? What are the main findings? Response: Injectable disease-modifying therapies (DMTs) are typically used first-line in patients with multiple sclerosis (MS), but discontinuation of injectable DMTs is common, especially within the first 12 months of treatment1,2. PREFERMS is the largest, prospective, randomized, active-controlled, open-label study to evaluate patient retention in patients with relapsing-remitting multiple sclerosis (RRMS). In the 12-month, Phase IV study, a total of 875 patients were randomized (1:1) to Gilenya® (fingolimod) 0.5 mg or to a pre-selected injectable DMT (IFNβ-1a, IFNβ-1b or glatiramer acetate), and followed up quarterly for 12 months3. After a minimum of 3 months of treatment, a single on-study treatment switch was allowed, however, switches due to efficacy or safety were allowed (based on patient-doctor consultation) at any month following randomization3. The primary endpoint was to compare the patient retention on randomized treatment over 12 months3. This study was powered for the primary endpoint (retention rate)3. The study was not powered to detect the treatment difference in the secondary efficacy endpoints or treatment effects related to switching study medication3. (more…)
Author Interviews, JAMA, Pharmacology, Rheumatology / 23.09.2016

MedicalResearch.com Interview with: Jacques-Eric Gottenberg, MD, PhD Department of Rheumatology National Reference Center for Systemic Autoimmune Diseases Strasbourg University Hospital, Université de Strasbourg Strasbourg, FranceJacques-Eric Gottenberg, MD, PhD Department of Rheumatology National Reference Center for Systemic Autoimmune Diseases Strasbourg University Hospital, Université de Strasbourg Strasbourg, France MedicalResearch.com: What is the background for this study? What are the main findings? Response: There is no recommendation for the choice of the second biologic in patients with rheumatoid arthritis and insufficient response to a first anti-TNF, which is a common situation in our daily practice (approximately one third of patients treated with anti-TNF). We therefore conducted the first randomized trial to date to investigate the best strategy in such a setting. (more…)
Author Interviews, Columbia, Depression, Nature, Orthopedics, Pharmacology / 09.09.2016

MedicalResearch.com Interview with: Patricia Ducy, PhD Associate Professor Department of Pathology & Cell Biology Columbia University New York, NY 10032 MedicalResearch.com: What is the background for this study? Response: In the past few years, several large clinical studies have reported an association between the use of selective serotonin reuptake inhibitors (SSRIs) and an increased risk of bone fractures. Yet, a few studies conducted on small cohorts using these drugs for a short time showed a decrease in bone resorption parameters and thus minor bone gain. To understand this paradox and to define how the deleterious effect of SSRIs could be prevented we conducted a series of studies in mice treated with fluoxetine, the active molecule of the widely prescribed SSRI Prozac. (more…)
Author Interviews, Ophthalmology, Pharmacology, Technology / 08.09.2016

MedicalResearch.com Interview with: Heather Sheardown PhD PEng FCAE Scientific Director 20/20 NSERC Ophthalmic Materials Network Professor, Department of Chemical Engineering Canada Research Chair in Ophthalmic Biomaterials McMaster University MedicalResearch.com: What is the background for this study? What are the main findings? Response: Putting drops in the eye is well accepted from the standpoint of practitioners but is problematic for many patients. Therefore, particularly in cases where multiple drops are required in a day such as is the case with certain infections for example or a lifetime of drops is required such as is the case with diseases like glaucoma, patient compliance is a real issue. In addition, as much as 95% of any drop instilled in the eye is lost within the first 5 minutes, meaning that drug concentrations within the drop need to be higher to ensure that the required dose gets into the patient’s eye. Therefore there is a real need for a better alternative to traditional eyedrops is needed. We have developed a new method of formulating drugs for delivery as drops that adhere to the mucous layer of the tear film, allowing for smaller amounts of drug to be delivered over a prolonged period of time. This means that fewer drops with lower drug concentrations can be delivered. This is a micelle based system that allows for the formulation of more hydrophobic drugs. A mucoadhesive component associated with the micelle binds to the mucin layer of the tears, meaning that the residence time on the eye is similar to that of this layer - between 4 and 7 days. Drug is slowly released from the micelle, allowing for prolonged treatment. (more…)
Asthma, Author Interviews, NEJM, Pediatrics, Pharmacology / 01.09.2016

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

MedicalResearch.com Interview with: Aaron S. Kesselheim, M.D., J.D., M.P.H. Associate Professor of Medicine at Harvard Medical School Director, Program On Regulation, Therapeutics, And Law (PORTAL) Division of Pharmacoepidemiology and Pharmacoeconomics Brigham and Women's Hospital Boston MA 02120 MedicalResearch.com: What is the background for this study? What are the main findings? Response: It has been previously reported that the number of new cardiovascular drugs approved by the U.S. Food and Drug Administration (FDA) has declined in recent years. So we sought to empirically assess trends in the development of new cardiovascular therapeutics. (more…)
Author Interviews, Lipids, Pharmacology / 23.08.2016

MedicalResearch.com Interview with: Prof. Dr. Ioana Gouni-Berthold MD Center for Endocrinology, Diabetes and Preventive Medicine (ZEDP) University of Cologne Cologne, Germany MedicalResearch.com: What is the background for this study? Response: In Europe, up to half of the population aged between 35 and 64 has hypercholesterolemia (high levels of low-density lipoprotein cholesterol [LDL-C]), putting them at risk of heart disease. Despite increased treatment rates in recent years, many patients still do not receive adequate therapy, and heart disease remains the biggest cause of death in the USA and most European countries. Two drugs, alirocumab and evolocumab, have recently been approved for lowering LDL-C in patients with hypercholesterolaemia as an ‘add-on’ therapy to other lipid-lowering medication, or for use alone in patients unable to tolerate statins. These drugs have a unique mode of action– they inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that binds to LDL receptors and targets them for degradation. In the absence of PCSK9, the LDL receptor recycling is restored and the receptors are able to remove LDL from the blood. Both alirocumab and evolocumab have been tested in numerous patient populations in phase 3 trials; albeit evolocumab has an additional indication of homozygous familial hypercholesterolemia. We therefore felt that there was a need to collate the available data to assess the efficacy and safety of each agent. We chose reduction in LDL-C as our outcome of interest, because this was the primary endpoint of the pivotal clinical trials. (more…)
Addiction, Author Interviews, Compliance, Opiods, Pharmacology / 23.08.2016

MedicalResearch.com Interview with: F. Leland McClure III, MSci, PhD, F-ABFT Medical science liaison director Quest Diagnostics MedicalResearch.com: What is the background for this study? What are the main findings? Response: Many physicians associate Quest Diagnostics with their lab service needs because of our leadership in laboratory testing. But Quest is more than a lab, which is why we refer to ourselves as a diagnostic information services provider. This means that we help providers, health plans and even patients use the insights we derive from our lab testing data to deliver better care, quality and outcomes, both for the patient and the managed population. Our 2016 Quest Diagnostics Health Trends(TM) Prescription Drug Monitoring Report is an example of how we provide important health insights from Quest's laboratory data. Prescription drug misuse is a major epidemic in the United States. Laboratory testing can help identify if a patient is using or misusing prescribed medications. For instance, lab tests can show evidence of additional medications and other drugs in a patient’s urine specimen, suggesting potentially dangerous drug combinations. Earlier this year, the CDC issued guidelines that call for laboratory testing for patients prescribed certain medications, such as opioids, that carry a risk of abuse. Quest's prescription drug monitoring services help the physician identify if a patient is taking or not taking up to about four dozen drugs, such as oxycodone, Adderall XR® and Percocet®. For the Quest analysis, we analyzed more than 3 million de-identified lab test results. In this report, we found that 54 percent of patients’ results tested in 2015 showed evidence of drug misuse, slightly above the 53 percent misuse rate in 2014. That is certainly unacceptably high, but it’s a significant decline from the high of 63 percent we observed in 2011. We also found that an increasing proportion of patients who misuse medications combine their prescription medication with non-prescribed drugs. Among patients with inconsistent test results, forty-five percent of these patients showed evidence of one or more other drug(s) in addition to their prescribed drug regimen. That’s much higher than our findings of 35 percent in 2014 and 2013, 33 percent in 2012, and 32 percent in 2011. Finally, we were alarmed by the data showing the connection between heroin and benzodiazepines misuse. Our data showed one in three heroin users combine their drug use with benzodiazepines, the vast majority of which were unprescribed. This is an extremely dangerous practice given that benzodiazepines can have strong respiratory depressant effects when combined with other substances. Drug combinations, but particularly of heroin with benzodiazepines, can be potentially very dangerous, leading to coma and even death in some cases. (more…)
Author Interviews, Frailty, Hip Fractures, JAMA, Pharmacology / 22.08.2016

MedicalResearch.com Interview with: Jeffrey Munson, MD, MSCE Assistant Professor The Dartmouth Institute for Health Policy & Clinical Practice Assistant Professor, Department of Medicine Geisel School of Medicine at Dartmouth MedicalResearch.com: What is the background for this study?  Response: Fragility fractures due to osteoporosis are a common and costly event among older Americans. Patients who experience one fragility fracture are at increased risk to have a second fracture. Our group is interested in exploring ways in which the risk of a second fracture could be reduced. In this paper, we studied prescription drug use both before and after fracture. We know many prescription drugs have been shown to increase the risk of fracture, but we don’t know whether doctors try to reduce the use of these drugs after a fracture has occurred. Our study was designed to answer this question. (more…)
Author Interviews, JAMA, Pediatrics, Pharmacology / 16.08.2016

MedicalResearch.com Interview with: Dr Evie Stergiakouli Lecturer in Genetic Epidemiology and Statistical Genetics MRC Integrative Epidemiology Unit University of Bristol Bristol UK MedicalResearch.com: What is the background for this study? What are the main findings? Response: Acetaminophen is considered safe to use during pregnancy. However, research suggests that acetaminophen use in pregnancy is associated with abnormal neurodevelopment. It is possible that this association might be confounded by unmeasured behavioural factors linked to acetaminophen use. We compared acetaminophen use during pregnancy to postnatal acetaminophen use and partner's acetaminophen use. Only acetaminophen use during pregnancy has the potential to cause behavioural problems in the offspring. Any associations with postnatal acetaminophen use and partner's acetaminophen use would be due to confounding. Behavioural problems in the offspring were only associated with acetaminophen use during pregnancy. (more…)
Author Interviews, Dermatology, Pharmacology / 15.08.2016

MedicalResearch.com Interview with: Kin F. Chan, PhD Executive Vice President of Research and Technology BioPharmX Corporation MedicalResearch.com: What is the background for this study? What are the main findings? Response: There were two studies in this series.  The purpose is to get a better understanding of the blood plasma and skin levels of minocycline in a relevant animal model (minipig) for both the oral form of minocycline (Solodyn) and topical BPX-01, and to elucidate the same for oral minocycline only in a clinical study. The results provided valuable guidance and assurance to our upcoming Clinical Phase 2b dose-ranging study design. (more…)
Author Interviews, Immunotherapy, Lymphoma, Pharmacology / 14.08.2016

MedicalResearch.com Interview with: Dirk Huebner, MD Senior Medical Director Oncology Therapeutic Area Unit Takeda Pharmaceutical Company MedicalResearch.com: What is the background for this study? What are the main findings? Response: Cutaneous lymphomas are a category of non-Hodgkin lymphoma that primarily involve the skin. Cutaneous T-cell lymphoma, also known as CTCL, is the most common type of cutaneous lymphoma and typically presents with red, scaly patches or thickened plaques of skin that often mimic eczema or chronic dermatitis. ADCETRIS® (brentuximab vedotin) is an antibody-drug conjugate directed to CD30, which is expressed on skin lesions in approximately 50 percent of patients with CTCL. The Phase 3 ALCANZA trial compared the use of single-agent ADCETRIS to a control arm of investigator’s choice of standard therapies, methotrexate or bexarotene, in 131 patients with CD30-expressing CTCL who received prior systemic or radiation therapy. The study met its primary endpoint, demonstrating a highly statistically significant improvement in the rate of objective response lasting at least four months (ORR4). The ORR4 was 56.3 percent in the ADCETRIS arm compared to 12.5 percent in the control arm. (more…)
Author Interviews, Pharmacology / 11.08.2016

MedicalResearch.com Interview with: Willemien J. Kruik-Kollöffel, PharmD Medisch Spectrum Twente in Enschede Netherlands, MedicalResearch.com: What is the background for this study? Response: Safety concerns of the concomitant use of clopidogrel and proton pump inhibitors (PPIs) were published in 2009 and 2010 by the medicines regulatory agencies, including a direct healthcare professional communication. Those publications caused a lot of turmoil. We examined the association between various safety statements and prescription behavior for gastroprotective drugs in naïve patients in the Netherlands during the years 2008–2011. (more…)
Author Interviews, Heart Disease, Kidney Disease, Pharmacology, UCLA / 09.08.2016

MedicalResearch.com Interview with: Jenny Shen, MD, MS Assistant Professor of Medicine David Geffen School of Medicine at UCLA Los Angeles Biomedical Institute at Harbor-UCLA Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: With cardiovascular disease being the No. 1 cause of death in end-stage kidney disease patients on peritoneal dialysis, we examined two classes of medications commonly prescribed to prevent cardiovascular events in these patients and found no significant difference in outcomes. The two classes of medications, angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB), have slightly different mechanisms and could theoretically have differing outcomes. Previous studies had suggested that ACEI may lead to a kinin-mediated increase in insulin sensitivity not seen with ARB. This could potentially lower the cardiovascular risk in patients on peritoneal dialysis because they are exposed to high glucose loads in their dialysate that may lead to insulin resistance and its associated cardiovascular risk. Using a national database, the U.S. Renal Data System, we surveyed records for all patients enrolled in Medicare Part D who initiated maintenance peritoneal dialysis from 2007 to 2011. Of those, we found 1,892 patients using either drug class. Surveying their medical records, we found no difference in cardiovascular events or deaths between the users for each class of medication. (more…)
Author Interviews, Pharmacology / 01.08.2016

MedicalResearch.com Interview with: PD Dr. Andreas Koeberle Lehrstuhl für Pharmazeutische/Medizinische Chemie Institut für Pharmazie Biologisch-Pharmazeutische Fakultät Friedrich-Schiller-Universität Jena Philosophenweg Jena MedicalResearch.com: What is the background for this study? What are the main findings? Response: Natural products from plants used in traditional medicine are valuable sources for identifying novel strategies as well as lead structures for drug development. The diterpenoids carnosol and carnosic acids from Salvia spp. (sage) represent such candidate compounds. They exert prominent anti-inflammatory activities though their molecular mechanisms are incompletely understood, which hampers their pharmacological use. Our study investigated the potential of carnosol and carnosic acid in inflammatory pain and addressed the cellular consequences and the molecular interactions with key targets. We demonstrate that the two diterpenoids have anti-inflammatory and anti-nociceptive effects in established mouse models of inflammation, and describe 5-lipoxygenase and microsomal prostaglandin E2 synthase-1, two key enzymes of inflammation, as primary targets. Moreover, we characterized the functional consequences of enzyme inhibition in a cellular context and investigated structural aspects of ligand/target interactions. (more…)
Author Interviews, Diabetes, Pharmacology / 25.07.2016

MedicalResearch.com Interview with: Stig Ejdrup Andersen MD, PhD Clinical Pharmacology Unit Zealand University Hospital Roskilde Denmark MedicalResearch.com: What is the background for this study? Response: For decades, we have used sulphonylurea derivates in the medical treatment of type 2 diabetes. Although several newer drugs have become available, adding an SU is still a recommended and acceptable strategy when metformin monotherapy fails. The SUs are among the cheapest glucose lowering drugs on the marked but the risk of hypoglycaemia make clinicians prefer a newer oral drug such as a DPP-IV inhibitor or a SGLT-2 inhibitor to ansulphonylurea because even mild hypoglycaemia may affect the patients’ quality of life negatively. Several meta-analyses have examined the effectiveness and safety of noninsulin antidiabetic drug, all of which have considered the SUs a homogenous drug class. Pharmacologically, however, the SU agents are quite different. In 2004, a randomized controlled trial by Shernthaner et al. indicated that in comparison with glimepiride, gliclazide MR is equally effective and is associated with fewer hypoglycaemic episodes. Still, head-to-head comparisons of the SU-agents as add-on to metformin are few. In the absence of robust designed comparative trials, we decided to compare the relative risk of hypoglycaemia among the newer SU-agents in a network meta-analysis. (more…)
Author Interviews, Mental Health Research, Pharmacology, Schizophrenia / 21.07.2016

MedicalResearch.com Interview with: Glorimar Ortiz, MS Senior Researcher/Statistician NRI-National Association of State Mental Health Program Directors Research Institute Falls Church, VA 22042 MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Despite the lack of empirical evidence that antipsychotic polypharmacy produces greater outcomes to antipsychotic monotherapy, and that several clinical guidelines recommend against it, patients with a diagnosis of schizophrenia continue to being discharged on polypharmacy. Over the past few years, attempts have been made to lower the rate of antipsychotic polypharmacy throughout the country. Most of the existing literature on this topic are based on Medicaid claims data which exclude data for patients discharged from state psychiatric inpatient hospitals. Our study is very important because it is the first time that data on the use of antipsychotic medications are analyzed using a large sample of discharges from state psychiatric inpatient hospitals. These hospitals now have the opportunity to benchmark their antipsychotic medication use rate with national rates more accurately, and therefore, develop and implement performance improvement activities that are more precise. The study found that 12% of all discharges were prescribed two or more antipsychotic medications. Of those patients discharged on at least one antipsychotic medication, 18% were prescribed two or more antipsychotics. The study also found that patients with a schizophrenia diagnosis and an inpatient hospital stay of 3 months or longer are more likely of being discharged on polypharmacy, and that the main reason for this was to reduce patient’s symptoms. Antipsychotic polypharmacy affects nearly 10,000 patients with schizophrenia annually in state psychiatric inpatient hospitals. (more…)
Author Interviews, Microbiome, Pharmacology / 19.07.2016

MedicalResearch.com Interview with: Mark Pimentel, MD Associate Professor, Medicine Director, GI Motility Program Director, GI Motility Laboratory Cedars-Sinai IBS-C Clinical Advisory Board (Chair) at Synthetic Biologics Los Angeles, CA MedicalResearch.com: What is the background for this study? Dr. Pimentel: The SYN-010 program is based on research from my group at Cedars-Sinai Medical Center, and other researchers and collaborators worldwide, investigating the role of intestinal methane production in functional gastrointestinal disorders. Low levels of intestinal methane are a ubiquitous by-product of normal intestinal microbial digestion; however, elevated intestinal methane levels are correlated with decreased intestinal motility and increased symptom severity in patients with irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC). Methane in humans is produced almost exclusively by the intestinal microorganism Methanobrevibacter smithii (M. smithii). Highest levels of M. smithii are found in the colon; however, overgrowth of M. smithii into the small intestine has also been observed. Previous work from my laboratory demonstrated that methane production by M. smithii in stool samples from IBS-C patients is inhibited by the lactone form of lovastatin. Lovastatin lactone does not appear to eradicate microbial species in the intestine, which should reduce the risk of intestinal dysbiosis and/or the development of microbial resistance. SYN-010 is a proprietary, modified-release, oral formulation of lovastatin lactone, designed to protect lovastatin lactone from the stomach and release the active ingredient in two different locations of the intestinal tract where the M. smithii reside. SYN-010 exerts its therapeutic effect at the level of the intestinal microbiome and does not require absorption into the systemic circulation or conversion of the active ingredient (lovastatin lactone) to the cholesterol lowering β-hydroxyacid form. (more…)
Author Interviews, Diabetes, Heart Disease, JAMA, Pharmacology / 19.07.2016

MedicalResearch.com Interview with: Principal investigator A/Prof Suetonia Palmer PhD University of Otago, New Zealand Senior investigator Prof. Giovanni Strippoli MD, PhD, MPH, MM University of Sydney, Australia and Diaverum, Sweden MedicalResearch.com: What is the background for this study? Response: Network meta-analysis is a new technique that allows us to evaluate ALL medical therapies for a specific clinical problem. We wondered whether any of the usual drugs used to treat glucose levels in people with diabetes were safest or most effective. (more…)
Author Interviews, Pharmacology / 13.07.2016

MedicalResearch.com Interview with: M. N. V. Ravi Kumar PhD Professor of Pharmaceutical Sciences Texas A&M Rangel College of Pharmacy MedicalResearch.com: What is the background for this study? What are the main findings? Response: The use of ligands for receptor-mediated drug delivery offers potential for improving both the safety and efficacy of pharmaceuticals. Research to date, however, has yet to overcome some of the significant challenges of targeted drug delivery, one of which is competitive affinity with endogenous ligands. This competition for the receptor binding site can impair both natural cell processes and uptake of the drug complex across the cell wall. This article presents a unique, non-competitive active transport strategy for crossing the intestinal barrier. Gambogic acid (GA), as a ligand, was coupled with a polymer called poly(lactic-co--glycolic acid) (PLGA) that in turn can encapsulate drugs forming nanosystems to bind to transferrin receptors within the intestinal wall, which facilitated active gut barrier crossing. The study results show peak plasma concentrations of Cyclosporine A (CsA) in orally dosed rodents at 6 hours with the GA-ladened nanosystems vs 24 hours without GA. Additionally, brain concentrations of CsA are twice as high dosing with PLGA-GA NS compared with PLGA-NS (without GA). (more…)
Author Interviews, Cost of Health Care, Geriatrics, Pharmacology / 13.07.2016

MedicalResearch.com Interview with: Leigh Purvis, MPA Director of Health Services Research AARP Public Policy Institute Editors’ note: In conjunction with the AARP’s new investigative piece, 'Supplement Pills That Promise Too Much', Leigh Purvis, Director of the AARP Health Services Research program discussed the issue of the proliferation of supplements, often with labels that make extraordinary health benefit claims. MedicalResearch.com: How many Americans use nutritional supplements? How big is the business of supplements? Response: Supplements are very popular in the United States. This is particularly true for older adults. A recent study found that the proportion of older adults using supplements increased from 52 percent in 2005 to 64 percent in 2011, and the share using multiple supplements grew by nearly 50 percent. According to the National Institutes of Health, American spent an estimated $36.7 billion on dietary supplements in 2014. (more…)
Author Interviews, Heart Disease, Pharmacology / 04.07.2016

MedicalResearch.com Interview with: Robert Sheldon, MD, PhD Division of Cardiology, Department of Cardiac Sciences University of Calgary, Calgary, Canada MedicalResearch.com: What is the background for this study? What are the main findings? Response: Vasovagal syncope is very common and more debilitating than most people appreciate. Probably up to 50% of people faint from this in their lives, making it the most common cardiovascular symptom. Around 15-20 years ago we had learned that the recurrence rates for vasovagal syncope were quite high, and that quality of life was correspondingly low. From the results of our earlier Vasovagal Pacemaker Study II and Prevention of Syncope Trial I (POST I) we knew that neither pacemakers nor beta blockers helped most patients with vasovagal syncope. However there was ample evidence that a reduction in venous return and cardiac preload were important early steps in the vasovagal cascade. Florinef is a salt-retaining mineralocorticoid that is successful in treating orthostatic hypotension with tantalizing early evidence that it might prevent vasovagal syncope induced by tilt tests. We therefore set out to test whether it prevented vasovagal syncope in a randomized placebo-controlled clinical trial. One important early part of designing a clinical trial is estimating the event rate in the untreated and treated arms. Based on our earlier work we could predict the untreated event rate but there were no data on which we could estimate the treated outcome rate. We therefore surveyed numerous colleagues for what they considered a Minimal Clinically Important Difference, and the answer was a 40% relative risk reduction. That is, to make fludrocortisone appealing to clinicians it should cause a relative risk reduction of 40%. We used this estimate to design the study. There are two main conclusions.
  • First, we studied the right population, people who would clearly be considered for active biomedical treatment. They had fainted 15-20 times in their lives and 3-4 times in the preceding year.
  • Second, we found that fludrocortisone reduced syncope by 31%, and this narrowly missed conventional statistical significance. However when we adjusted for the first two weeks that were allotted for dose adjustment we found that fludrocortisone reduced syncope by up to 50% in people who were taking 0.2 mg daily. This is quite a low dose, deliberately picked to be safe in this young and predominantly female population.
(more…)
Addiction, Author Interviews, Cancer Research, Pharmacology / 04.07.2016

MedicalResearch.com Interview with: Dr Wai Liu Senior Research Fellow St George's University of London London MedicalResearch.com: What is the background for this study? What are the main findings? Response: Naltrexone is a drug commonly used to wean addicts off alcohol and heroin, but clinical evidence has shown that when the drug is used at lower doses, patients would exhibit alter immunity. The symptoms that patients with a number of autoimmune diseases and those associated with chronic pain would ease significantly. Additionally, a number of reports showed patients with some forms of cancer would experience therapeutic benefit. Interestingly, the doses of the drug was crucial, and the non-conventional effects of naltrexone was only achieved at doses that were lower that what was conventionally used. We set about to understand why a drug could have such different effects when used at differing doses. Our results show that the genetic profile of the drug is subtly different at the two different doses, which helped us identify novel ways in which the drug could be used to induce an anticancer effect. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Pharmacology / 29.06.2016

MedicalResearch.com Interview with: Dr Kieran Breen PhD Director of Research, Brain Tumour Research University of Portsmouth, UK MedicalResearch.com: What is the background for this study? What are the main findings? Response: There is evidence that aspirin (acetyl salicylic acid) can be toxic to brain tumour cells. However, its existing preparations cannot readily enter the brain because the drug is a suspension rather than being completely soluble. Furthermore, there can be significant side effects associated with the existing form of the drug including gastric bleeding. The object of this research was to develop a new formulation of aspirin which is truly soluble. When combined with two other compounds, the drug enters the brain and can therefore target the tumour cells. This study also showed that aspirin can kill tumour cells without causing any damage to the normal nerve cells. (more…)
Author Interviews, Heart Disease, JAMA, Pharmacology, UCSF / 27.06.2016

MedicalResearch.com Interview with: Dr. Gregory M. Marcus MD Gregory M Marcus, MD, MAS, FACC, FAHA, FHRS Director of Clinical Research Division of Cardiology Endowed Professor of Atrial Fibrillation Research  University of California, San Francisco MedicalResearch.com: What is the background for this study? What are the main findings? Response: Conduction system disease, or blockages in the electrically system (as opposed to blockages in the blood vessels, of which most are well-aware), is a common condition responsible for both heart failure in many patients as well as the need for pacemaker implantation. Although treatments for the disease are available, there are no known means to prevent it. This is important as the primary treatment, a pacemaker, can itself cause problems (including procedural complications, a long-term risk of infection with repeated battery changes, and even a greater risk of heart failure). In addition, predictors of what types of individuals are at risk for developing conduction disease has largely remained unknown. Based on the fact that the majority of conduction disease is due to fibrosis, or scarring, of the conduction system, we sought to test the hypothesis that a common drug for high blood pressure with anti-fibrotic properties, Lisinopril, might reduce the risk of new conduction system disease. We took advantage of the fact that more than 20,000 patients with hypertension were randomized to three common high blood pressure drugs that work via different mechanisms in the ALLHAT trial: Lisinopril, amlodipine, and chlorthalidone. We found that participants randomly assigned to Lisinopril were statistically significantly less likely to develop conduction disease. In addition, our analyses revealed several risk factors for the development of conduction disease: older age, male sex, diabetes, smoking, a thicker heart, and white race (compared to black race). (more…)
Author Interviews, Infections, Pharmacology, Urinary Tract Infections / 25.06.2016

MedicalResearch.com Interview with: Amanda Paschke, MD Director, Infectious Disease Clinical Research Merck Research Laboratories MedicalResearch.com: What is the background for this study? What are the main findings? Response: Relebactam is an investigational beta-lactamase inhibitor being developed as a fixed-dose combination with imipenem/cilastatin, which is a broad-spectrum antibiotic in the carbapenem class. In preclinical studies, this combination demonstrated antibacterial activity against a broad range of multidrug-resistant Gram-negative pathogens, including those producing extended-spectrum beta-lactamases such as Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae and AmpC-producing Pseudomonas aeruginosa. Many of the most concerning infections caused by “superbugs” are caused by Gram-negative bacteria. These bacteria have evolved to be resistant to commonly used antibacterials, and even to antibacterials used as “last resort” treatment, which is why finding ways to treat them has become urgent. The addition of relebactam to imipenem is designed to restore activity of imipenem against certain imipenem-resistant strains of Gram-negative bacteria known to cause serious infections among people who often have other underlying medical conditions, which complicates treatment. This was a Phase 2, multicenter, randomized, double-blind, non-inferiority study. The study looked at the use of relebactam plus imipenem versus imipenem alone for the treatment of adult patients with complicated urinary tract infections. The primary endpoint for the trial was microbiological response at the completion of IV study therapy. The study met its primary endpoint, demonstrating that the combination of relebactam with imipenem was as at least as effective as imipenem alone for the treatment of complicated urinary tract infections. The trial also demonstrated that the combination of relebactam plus imipenem is well-tolerated, with a safety profile similar to that of imipenem alone in this patient. (more…)
Author Interviews, Brigham & Women's - Harvard, Cost of Health Care, Heart Disease, JAMA, Pharmacology / 22.06.2016

MedicalResearch.com Interview with: Thomas Andrew Gaziano, MD, MSc Department of Cardiology Assistant Professor Harvard Medical School MedicalResearch.com: What is the background for this study? Response: Heart failure (HF) is the leading cause of admissions to hospitals in the United States and the associated costs run between $24-47 billion annually. Targeting neurohormonal pathways that aggravate the disease has the potential to reduce admissions. Enalapril, an angiotensin converting enzyme-inhibitor (ACEI), is more commonly prescribed to treat HF than Sacubitril/Valsartan, an angiotensin-receptor/neprilysin inhibitor (ARNI). The latter was shown to reduce cardiovascular death and hospitalizations due to heart failure in a multi-country, randomized clinical (PARADIGM-HF), compared to Enalapril. In order to assess the cost-effectiveness of Sacubitril/Valsartan, compared to Enalapril, in the United States, we created a model population with population characteristics equivalent to the population in the PARADIGM-HF trial. Using a 2-state Markov model we simulated HF death and hospitalizations for patients with a left ventricular ejection fraction (LVEF) of 40% or less. (more…)
Author Interviews, Heart Disease, JAMA, Pharmacology, UCLA / 22.06.2016

MedicalResearch.com Interview with: Gregg C. Fonarow, MD, FACC, FAHA Eliot Corday Professor of Cardiovascular Medicine and Science Director, Ahmanson-UCLA Cardiomyopathy Center Co-Chief of Clinical Cardiology, UCLA Division of Cardiology Co-Director, UCLA Preventative Cardiology Program David Geffen School of Medicine at UCLA Los Angeles, CA, 90095-1679 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Fonarow: Angiotensin receptor neprilysin inhibitors (ARNI) have been demonstrated to reduce mortality in patients with heart failure with reduced ejection fraction. However, to date, the population level impact of optimal implementation of this therapy in the United States has not been evaluated. This new analysis estimates that as many 28,484 deaths in heart failure with reduced ejection fraction patients annually could be prevented or postponed with optimal use of angiotensin receptor neprilysin inhibitors (with sensitivity analyses demonstrating a range of 18,230 to 41,017). (more…)
Annals Internal Medicine, Author Interviews, Diabetes, Hepatitis - Liver Disease, Pharmacology / 22.06.2016

MedicalResearch.com Interview with: Kenneth Cusi, M.D., F.A.C.P., F.A.C.E. Professor of Medicine VAMC staff Chief, Division of Endocrinology, Diabetes and Metabolism The University of Florida Gainesville, FL 32610-0226 MedicalResearch.com: What is the background for this study? Dr. Cusi: Many patients with prediabetes or Type 2 Diabetes Mellitus (T2DM) are not diagnosed with Nonalcoholic steatohepatitis (NASH), a disease that is the second cause of liver transplantation in the United States. It is also associated with worse cardiovascular disease and harder to control T2DM. We had done in this population a proof-of-concept study published in Nov 2006 in the NEJM. But we lacked a larger, long-term study for definitive proof. This is the largest SINGLE center study, and the longest ever (3 years). NASH is an overlooked problem for perhaps as many as one-third of patients with Type 2 Diabetes Mellitus. There is now a safe and effective treatment option for patients with T2DM and NASH – pioglitazone will become for NASH what metformin is to the treatment of T2DM: a safe, effective, the “backbone therapy" to which other treatments will be added. (more…)