Author Interviews, Education, JAMA, Pharmacology, UCSF / 21.06.2016

MedicalResearch.com Interview with: Colette DeJong Medical student at UCSF and Research Fellow at the UCSF Center for Healthcare Value. MedicalResearch.com: What is the background for this study? Response: Data released under the U.S. Sunshine Act reveals that in the last five months of 2013, over half of American physicians received free meals, gifts, or payments from the pharmaceutical industry. Recent studies have shown that doctors who receive large payments from drug companies—such as speaking fees and royalties—are more likely to prescribe expensive brand-name drugs, even when generics are available. Our findings, however, suggest that physicians’ prescribing decisions may be associated with much smaller industry payments than previously thought. We found that doctors who receive a single industry-sponsored meal—with an average value under $20—are up to twice as likely to prescribe the brand-name drug being promoted. (more…)
Annals Internal Medicine, Author Interviews, Pharmacology / 17.06.2016

MedicalResearch.com Interview with: Steven Woloshin, MD Professor of The Dartmouth Institute Professor of Medicine Professor of Community and Family Medicine New Hamphsire MedicalResearch.com: What is the background for this study? Dr. Woloshin: Drug companies are required by law to post results of trials used to support drug applications to the FDA on the clinicaltrials.gov website - but it is not clear whether posted results are complete and accurate. Recent studies attempting to validate posted results by comparing them to corresponding peer reviewed medical journal publications suggest that discrepancies are relatively common. But it is which source is more likely to be correct. We tried to validate posted results against an arguably better gold standard, the drug approval packages from the FDA (ie, the medical and statistical reviews posted on the drugs@fda.gov website). FDA reviews have an advantage over peer reviewed publications: unlike medical journal editors and peer reviewers, FDA has access to the individual participant data from the trials. This means FDA can see all the trials and all the outcomes (avoiding sleective publication) and it means FDA can independently reanalyze according to what they believe to be the best statistical practices (data can be analyzed in many ways - and different decisions, for example, how to account for missing data, can yield very different results). (more…)
Author Interviews, Diabetes, Pharmacology / 15.06.2016

MedicalResearch.com Interview with: Professor Philip Home D.M., D.Phil Professor of Diabetes Medicine Newcastle University MedicalResearch.com: What is the background for this study? What are the main findings? Prof. Home: MK1293 is a biosimilar insulin designed with the same amino acid sequence, manufacturing process and formulation as originator insulin glargine (Lantus). This is the clinical proving study in type 1 diabetes, being a 24-week randomized study in 508 participants between MK1293 and Lantus. The primary efficacy endpoint of non-inferiority of HbA1c was met, as was a secondary of equivalence (difference in change from baseline 0.04 (95% CI -0.11, 0.19) %-units), with other measures including hypoglycaemia, insulin antibodies and adverse events also consistent with similarity. (more…)
Author Interviews, JAMA, Pharmacology, UCSD, Weight Research / 15.06.2016

MedicalResearch.com Interview with: Siddharth Singh, MD, MS Postdoctoral Fellow, NLM/NIH Clinical Informatics Fellowship Division of Biomedical Informatics Clinical Assistant Professor of Medicine, Division of Gastroenterology, Department of Internal Medicine, University of California San Diego, La Jolla MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Singh: Over the last 4 years, four new medications have been approved for long-term use for weight loss by the FDA. We sought to evaluate the comparative effectiveness and tolerability of these medications through a systematic review and network meta-analysis. Based on 28 trials in over 29,000 overweight or obese patients, we observed that magnitude of weight loss achieved with these agents is variable, ranging from 2.6kg with orlistat to 8.8kg with phentermine-topiramate. Over 44-75% of patients are estimated to lose at least 5% body weight, and 20-54% may lose more than 10% of body weight; phentermine-topiramate was the most efficacious, whereas lorcaserin was the best tolerated. (more…)
Author Interviews, Pharmacology, Sleep Disorders / 14.06.2016

MedicalResearch.com Interview with: Anna-Therese Lehnich Zentrum für Klinische Epidemiologie (ZKE) c/o Institut für Medizinische Informatik Biometrie undEpidemiologie (IMIBE) MedicalResearch.com: What is the background for this study? What are the main findings? Response: Sleep disturbances and their consequences are often underestimated but they are of high importance with respect to public health. We were interested in the question whether drugs labeled as sleep disturbing in the summary of product characteristics actually lead to more sleep disorders like difficulties falling asleep, difficulties maintaining sleep, and early morning arousal. To answer this question, we analyzed data of 4,221 persons from Germany. (more…)
Author Interviews, Diabetes, Kidney Disease, Pharmacology / 13.06.2016

MedicalResearch.com Interview with: Doctor Hiddo Lambers Heerspink Department of Clinical Pharmacy and Pharmacology University Medical Center Groningen the Netherlands MedicalResearch.com: What is the background for this study? What are the main findings? Response: SGLT2 inhibitors, including canagliflozin, have beneficial effects on multiple cardiovascular and renal risk parameters. This suggests that SGLT2 inhibitors may confer cardiovascular and renal protection. A recent large clinical trial with the SGLT2 inhibitor empagliflozin demonstrated marked reductions in cardiovascular morbidity and mortality and suggested possible renoprotective effects. Whether SGLT2 inhibition slows the progression of kidney function decline independent of its glucose-lowering effect, however, is unknown. We therefore assessed whether canagliflozin slows the progression of kidney function decline by comparing the effects of canagliflozin versus glimepiride on eGFR and albuminuria. (more…)
ASCO, Author Interviews, Cancer Research, Geriatrics, Lymphoma, NYU, Pharmacology / 07.06.2016

MedicalResearch.com Interview with: Dr. Catherine S. M. Diefenbach MD Assistant Professor of Medicine NYU Cancer Center New York, NY 10016 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Diefenbach: It is well known that age is important prognostic factor in non-Hodgkin’s lymphoma (NHL). Multiple studies have illustrated that elderly lymphoma patients have inferior survival outcomes as compared to their younger counterpart. While the tumor biology is often different in these two groups, and may play a role in this discordancy, elderly patients are often frail or have multiple medical comorbidities. These include geriatric syndromes, such as: cognitive impairment, falls, polypharmacy, and potentially inappropriate medication (PIM) use. All of these may contribute to poor outcomes for elderly patients. In addition, elderly patients are often under-treated for their aggressive lymphoma out of concern for toxicity or side effects, even though the data clearly demonstrates that elderly patients can still benefit from curative intent chemotherapy. (more…)
Author Interviews, Pharmacology / 02.06.2016

MedicalResearch.com Interview with: Professor Neil Carragher Principal Investigator Drug Discovery Institute of Genetics and Molecular Medicine University of Edinburgh MedicalResearch.com: What is the background for this study? What are the main findings? Prof. Carragher: The aim of the study was to generate novel small molecule inhibitors that target breast cancers using a strategy which we named: "dual ligand based phenotypic screening". From initial derivation of a small chemical library based on a promiscuous kinase inhibitor PP1, iterative screening across a suite of breast cancer phenotypic assays guided chemical design towards the novel compound eCF506. eCF506 is a highly potent, orally bioavailable and specific inhibitor of Src Kinase. (more…)
Author Interviews, Emory, PAD, Pharmacology / 15.05.2016

MedicalResearch.com Interview with: Shipra Arya MD, SM Assistant Professor, Division of Vascular Surgery Emory University School of Medicine Assistant Professor of Epidemiology (Adjunct) Rollins School of Public Health Staff Physician, Atlanta VA Medical Center Director, AVAMC Vascular Lab and Endovascular Therapy  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Arya: Peripheral Arterial Disease is the next cardiovascular epidemic. It is poorly recognized and not adequately treated compared to heart disease – and research is lacking on the optimal use of statins for PAD patients. Very few randomized clinical trials have been done specifically in PAD patients to assess the impact of statins on cardiovascular outcomes and none on limb related outcomes. The 2013 ACC/AHA guidelines for cholesterol lowering medications recommends high intensity statins for PAD patients extrapolated from the level 2 and 3 evidence and empirically based on CAD and stroke data. In this study we looked at the amputation and mortality risk based on statin dosage in a large cohort of patients from the VA population and found that high intensity statins are associated with a significant reduction in limb loss (~30%) and mortality (~25%) in PAD patients followed by a smaller risk reduction [~23% for amputation risk reduction and 20% reduction in mortality risk] by low-moderate intensity statins as compared to no statin therapy. (more…)
Author Interviews, Geriatrics, Pharmacology / 13.05.2016

MedicalResearch.com Interview with: Leigh Purvis, MPA Director of Health Services Research AARP Public Policy Institute MedicalResearch.com Editor’s Note: The May AARP Bulletin has a important article “Black Market Meds Are Flooding the Nation’s Pharmacies And Hospitals” by Joe Eaton, discussing the growing problem of counterfeit medications entering the US pharmaceutical supply chain. Ms. Leigh Purvis of the AARP Policy Institute discussed this important issue for the readers of MedicalResearch.com. Ms. Purvis’ areas of expertise include prescription drug pricing, biologic drugs, and Medicare prescription drug coverage.  MedicalResearch.com: Is pharmaceutical theft and fraud a new or growing problem? Ms. Purvis: I think it’s safe to say that pharmaceutical theft is a growing problem. Skyrocketing prices have made pharmaceuticals a lucrative target for criminals. Trucks transporting pharmaceuticals are a common target, although some thieves have stolen prescription drugs directly from manufacturers’ warehouses. Pharmaceutical fraud is also a growing concern. FDA does a great deal to ensure the safety of US pharmaceuticals. However, problems can still arise, particularly when people purchase drugs online. (more…)
Abuse and Neglect, Author Interviews, NYU, Pharmacology, Urology / 11.05.2016

MedicalResearch.com Interview with: Dr. Jed Kaminetsky MD Clinical Assistant Professor Department of Urology NYU Langone Medical Center  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Kaminetsky: Nocturia is a voiding disorder not well treated by available drugs for overactive bladder and benign prostatic hypertrophy. Desmopressin stimulates the kidneys to concentrate the urine which results in a greatly reduced volume of urine formation for a period of time. Serenity Pharmaceuticals has spent many years developing a low dose nasal spray version of desmopressin called Noctiva specifically for nocturia. The study reported now is a large, placebo controlled phase 3 trial to confirm the statistical efficacy and clinical benefit of this treatment for nocturia. (more…)
Author Interviews, OBGYNE, Pharmacology, Science / 11.05.2016

MedicalResearch.com Interview with: Lynda Harris PhD Lecturer in Pharmaceutics University of Manchester Manchester Pharmacy School Maternal and Fetal Health Research Centre Manchester MedicalResearch.com: What is the background for this study? Dr. Harris: Pregnancy complications such as pre-eclampsia and fetal growth restriction remain a problem despite advances in antenatal care, and impact heavily on future health: small size at birth is associated with an increased risk of cardiovascular disease and diabetes in later life. Drugs to improve pregnancy outcome are severely lacking, as pregnant women are considered a high risk cohort by drug companies, who fear expensive lawsuits associated with side effects and teratogenicity. The majority of pregnancy complications are caused by a poorly growing or poorly functioning placenta. A number of potential drugs have been identified that enhance placental function in vitro, and improve fetal growth in animal models; however, there is currently no means of restricting their actions to the placenta, and systemic administration of these drugs to pregnant women is not feasible due to the risk of adverse effects in other tissues. To address this issue, we have identified a series of placental “homing peptides” which we have used to create nanocarriers for targeted delivery of drugs to the placenta. (more…)
Author Interviews, Lipids, Pharmacology / 06.05.2016

MedicalResearch.com Interview with: Martha M. Rumore, PharmD, JD, MS, LLM, FAPhA Associate Professor, Social, Behavioral & Administrative Pharmacy Touro College of Pharmacy New York, NY 10027 & Of Counsel Sorell, Lenna, & Schmidt, LLP MedicalResearch.com: What is the background for this study? Dr. Rumore: The management of lipid therapy is only one component that affects overall cardiovascular outcomes.This study is one of the first to look at the benefits of dose titration versus intensity-based statin therapy.  To evaluate whether patients titrated on statin therapy using ATPIII algorithm with an LDL goal of <100mg/dL also met the 2013 ACC/AHA Guideline for Management of Blood Cholesterol goal of ≥40% LDL reduction from baseline compared to inpatients initiated on high-moderate intensity statin (HIS).  Other objectives included comparison of algorithms to lower LDL ≥40%, final dose, adverse drug events (ADEs), clinic visits to goal, and cardiovascular event occurrence. MedicalResearch.com: What are the main findings? Dr. Rumore: 981 patients were included- 43% were titrated and 57% achieved LDL<100; 38% achieved both LDL <100mg/dL and LDL ≥40% reduction; 58% received HIS and 53% achieved LDL <100; 43% achieved both LDL <100mg/dL and LDL ≥40% reduction. Initiating patients on  High Intensity statins was not more effective than dose titration in achieving <100mg/dL and ≥40% LDL reduction;X2=0.006,N=159,p=0.938. A 50% LDL reduction in patients that also achieved an LDL <100 was 54% and 48%, in titration and HIS groups, respectively; X2=0.611,N=159,p=0.434.  The titration group required an average of 4.3 clinic visits to achieve goal, compared to 3.1 visits for HIS; p=0.309; 95% CI(-1.36,1.06). (more…)
Author Interviews, Outcomes & Safety, Pharmacology / 06.05.2016

MedicalResearch.com Interview with: Serene I. Chen MD Dr. Chen is an emergency medicine resident at Highland Hospital, in Oakland, California. She was a student at the Yale School of Medicine when this research was conducted. MedicalResearch.com: What is the background for this study? Dr. Chen: To address the rise in U.S. drug shortages, the Food and Drug Administration Safety and Innovation Act (FDASIA) was passed in 2012—and early evidence does suggest that the overall number of new shortages have decreased. However, we found that drugs that are frequently used emergency departments and other acute settings are still affected by more frequent and increasingly prolonged shortages. (more…)
Author Interviews, Depression, Mental Health Research, OBGYNE, Pediatrics, Pharmacology / 02.05.2016

MedicalResearch.com Interview with: Heli Malm, MD, PhD Specialist in Obstetrics and Gynecology Teratology Information Service Helsinki University and Helsinki University Hospital  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Malm: Animal studies have demonstrated that exposure to SSRIs during early brain development can result in depression-like behavior in adolescence. Today 6% of pregnant women in the US and 4% in Finland are on selective serotonin reuptake inhibitors (SSRIs) at some stage of pregnancy. SSRIs pass the placenta but no prior studies have followed children beyond childhood to monitor the development of depressive disorders, which typically emerge after puberty onset. Results on autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorders (ADHD) have been conflicting. The study material is based on national register data from Finland. We investigated offspring psychiatric diagnoses, including depression, anxiety, ASD, and ADHD, of nearly 16,000 mothers who had used SSRIs during pregnancy between 1996 and 2010. Children in this cohort ranged in age from 0 to 15 years old. Because maternal psychiatric illness can affect offspring neurodevelopment in the absence of SSRIs, primary comparisons were made between offspring of the SSRI group and offspring of mothers with a psychiatric disorder diagnosis but no antidepressant use. Children exposed to SSRIs during gestation were diagnosed with depression at an increasing rate after age 12, reaching a cumulative incidence of 8.2% by age 15, compared to 1.9% in the group of children exposed to maternal psychiatric illness but no antidepressants. Rates of anxiety, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD) diagnoses did not differ significantly between the two groups. (more…)
Author Interviews, Pediatrics, Pharmacology / 29.04.2016

MedicalResearch.com Interview with: Jonathan Slaughter, MD, MPH Assistant Professor of Pediatrics Center for Perinatal Research Nationwide Children's Hospital/The Ohio State University Columbus, OH 43205  MedicalResearch.com: What is the background for this study? Dr. Slaughter:   Increasing data has emerged over the last decade showing potential harm following acid suppression use in newborns, older children, and adults.  There are virtually no published data that show acid suppression via histamine-2-receptor antagonists (H2RAs) or proton-pump inhibitors (PPIs) is effective for gastroesophageal reflux disease (GERD) treatment or for other indications (stress ulcer prophylaxis, post-operative acid suppression) in healthy or sick newborns. Given the potentially limited effectiveness of these medications and increasing safety concerns following H2RA/PPI use in infants, we wanted to evaluate the frequency and duration of H2RA/PPI use among infants hospitalized within US children's hospital neonatal intensive care units (NICUs) to determine if these drugs appeared to be overused and if use appears to have changed over time.  We also evaluated neonatal diagnoses associated with acid suppression to identify targets for future studies that may evaluate the usefulness of acid suppression in neonates following a given diagnosis. (more…)
Author Interviews, Diabetes, Pharmacology / 21.04.2016

MedicalResearch.com Interview with: Pedro L. Herrera, PhD Professor Dept. Genetic Medicine & Development, room #F09.2770 Faculty of Medicine, University of Geneva Geneva, Switzerland MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Herrera: After meals, the digestion of food leads to an accumulation of sugar (glucose) in the blood (hyperglycemia). This triggers the release of the hormone insulin from the pancreas (beta-cells), which allows the tissues (liver, muscle and fat) to use and store it. Another pancreatic hormone, glucagon, is released by alpha-cells during fasting or exercising, and opposes the action of insulin: it tells the liver to release glucose, which increases blood sugar levels. The balance between insulin and glucagon keeps blood sugar levels steady. Persistent hyperglycemia due to insulin deficiency is diabetes. Glucagon production is exacerbated in diabetes, which aggravates hyperglycemia. (more…)
Author Interviews, Diabetes, Pharmacology / 12.04.2016

MedicalResearch.com Interview with: Christopher Sorli, MD SUSTAIN 1 investigator and Chair of the Department of Diabetes, Endocrinology and Metabolism Billings Clinic, Billings, Montana MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Sorli: GLP-1 receptor agonists (GLP-1 RAs) have been found to be useful in the treatment of Type 2 diabetes with potent effects on blood glucose lowering while minimizing the risk of hypoglycemia and weight gain often seen with other classes of hypoglycemic agents. Semaglutide is a novel GLP-1RA that is currently in clinical development. The molecule shares 94% amino acid homology with native GLP-1 and has a half-life of approximately one week allowing for once weekly dosing. SUSTAIN 1 was designed to demonstrate superiority of semaglutide 0.5 mg and 1.0 mg once weekly over placebo in lowering HbA1c after 30 weeks of treatment. Additional secondary endpoints included weight loss versus placebo, percent of patients achieving HbA1c goals, percent of patients achieving 5% and 10% weight loss, and safety and tolerability. (more…)
Author Interviews, Bone Density, Endocrinology, Hip Fractures, Pharmacology / 08.04.2016

MedicalResearch.com Interview with: Bente Langdahl Professor, Consultant, PhD, DMSc Department of Endocrinology and Internal Medicine THG Aarhus University Hospital Aarhus Denmark MedicalResearch.com: What is the background for this study? What are the main findings? Response: Romosozumab is a humanised antibody against sclerostin currently in development for the treatment of osteoporosis. Romosozumab has a dual effect on bone; it stimulates bone formation and inhibits bone resorption. If this new treatment obtains regulatory approval and becomes available for the treatment of osteoporosis, some of the patients who will be candidates for this new treatment will already have been treated with other available treatments, for example, bisphosphonates. This study compared the effects of romosozumab and teriparatide, a currently available bone forming treatment, on bone mass, bone structure and bone strength. The results showed that the percent change from baseline in BMD at the total hip through month 12 (the primary endpoint) was significantly greater with romosozumab compared with teriparatide: 2.6 percent versus –0.6 percent, respectively (p<0.0001). For the secondary endpoints; lumbar spine BMD by DXA, total hip and femoral neck BMD by DXA and QCT and bone strength estimated by finite element analysis patients treated with romosozumab had significantly larger increases from baseline compared with those taking teriparatide, with mean differences ranging from 3.1 percent to 4.6 percent (all p-values <0.0001). (more…)
Author Interviews, NEJM, Pharmacology / 18.03.2016

MedicalResearch.com Interview with: Prof. Bruce Guthrie Primary Care Medicine and Honorary Consultant NHS Fife University of Dundee Dundee, Scotland MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Guthrie: Most drug-related harm is caused by commonly prescribed drugs with moderate risk. This prescribing is not always inappropriate, because risk of harm may be outweighed by benefit in an individual, but we have previously shown that high-risk prescribing like this is common and highly variable between primary care practices, consistent with it being improvable. We therefore developed a complex intervention combining education, informatics to make it easy to identify and review patients, and a small financial incentive to review. We evaluated this intervention in a cluster-randomised trial in 33 Scottish primary care practices, targeting nine measures of high-risk non-steroidal anti-inflammatory drug (NSAID) and antiplatelet prescribing (for example, prescription of an NSAID to someone with chronic kidney disease; prescription of an antiplatelet to someone taking an anticoagulant without also prescribing a gastroprotective drug). The intervention reduced the targeted prescribing by just over one third, and this reduction was sustained in the year after the intervention (including the payment to review) ceased. We also observed reductions in related hospital admissions with gastrointestinal bleeding and heart failure, although not acute kidney injury which was reduced but not statistically significantly. (more…)
Author Interviews, Gastrointestinal Disease, Heart Disease, Pharmacology / 18.03.2016

MedicalResearch.com Interview with: Giuseppe Gargiulo MD Research fellow in Cardiology Inselspital, University of Bern, Bern, Switzerland  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Gargiulo: Every year millions of people with coronary artery disease are treated worldwide with percutaneous coronary intervention (PCI). Consequently, they receive a dual  (DAPT) in order to prevent thrombotic life-threatening complications, such as stent thrombosis. DAPT often consists of aspirin and clopidogrel, but some studies have questioned the efficacy of clopidogrel in case of concomitant therapy with proton-pump inhibitors (PPI) due to pharmacodynamic interactions. Indeed, clopidogrel is a pro-drug needing to be activated, and this could be potentially affected by PPI. This is a relevant topic given that many patients treated with DAPT commonly receive also a PPI to prevent gastrointestinal complications (ulceration and bleeding) or due to pre-existing gastric disease. Some studies demonstrated that the use of a PPI, mainly omeprazole, was associated with an increased risk of cardiovascular adverse events, indeed the Food and Drug Administration (FDA) and the European Medicine Agency (EMA) discouraged the concomitant use of omeprazole and clopidogrel. On the contrary, some other studies did not confirm this finding. We performed a detailed analysis of the impact of PPI therapy on the 2-year clinical outcomes of 1970 patients undergoing PCI with stent implantation enrolled in the PRODIGY trial (a randomized trial comparing 2 DAPT regimens: 6-month versus 24-month DAPT). In our study population, 738 patients (38%) were treated with a PPI (lansoprazole 90%) concomitantly to DAPT. We found that the ischemic and bleeding events at 2 years of follow-up were similar in patients treated with or without a PPI, irrespective of DAPT duration (6-month or 24-month). These findings support the concept that the concomitant use of PPI, when clinically indicated, in patients receiving clopidogrel is not associated with adverse clinical outcomes. (more…)
Author Interviews, Heart Disease, Lipids, Pharmacology, University of Pennsylvania / 03.03.2016

MedicalResearch.com Interview with: Dr. Richard L. Dunbar MD MS Assistant Professor of Medicine, Attending Physician, Preventive Cardiovascular Medicine Clinic, Member, Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of MedicineMember, Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania School of Medicine and Dr. Harsh Goel WellSpan Academic Hospitalists Department of Medicine, York Hospital, PA  MedicalResearch.com: What is the background for this analysis? Response: Niacin is the first cholesterol lowering treatment to prevent heart attacks and lower long term mortality. It thus provided the first proof that lowering cholesterol reduces cardiovascular risk. However, it is generally poorly tolerated due to almost universal flushing, limiting use. The better-tolerated statin drugs overshadowed niacin, rightly dominating hyperlipidemia therapy. Despite their advantages, statins are far from perfect, leaving important gaps. Firstly, at least 10% of patients simply don’t tolerate statins. Secondly, about 40% of patients have insufficient cholesterol lowering, leaving them far from their target LDL-cholesterol levels. Finally, even though statins lower cardiovascular risk, they by no means eliminate it and significant residual risk remains even in patients who respond to them. The relatively poor tolerance of niacin motivated development of an extended-release alternative which was dosed very differently from the established cardioprotective regimen used in the Coronary Drug Project (CDP) and the Stockholm Ischemic Heart Disease Study (SIHDS), the two landmark trials that proved niacin's benefits. These trailblazing trials used 3 grams of niacin divided throughout the fed portion of the day as 1 gram thrice daily with meals. In sharp contrast, the alternative regimen was severely handicapped by a profoundly lower dose of only 2 grams per day. Perhaps worse, the alternative regimen dosed all of the niacin at one sitting, at bedtime before the overnight fast, rather than three times a day before meals. We believe these were critical departures from the established cardioprotective niacin regimen, insofar as they severely undermined the alternative regimen’s efficacy. Accordingly, when added to statins, the alternative regimen failed to recapitulate the benefits seen with the established cardioprotective regimen in two recent large clinical trials, the AIM-HIGH trial and the HPS2-THRIVE trial. Besides the inherent flaws of the alternative regimen, there were also major issues with the trial designs which likely contributed to null results. From a practice standpoint, this is worrisome, because clinicians may draw erroneous conclusions from the trials of the alternative regimen, and thereby deny a significant population of hyperlipidemic patients the benefits of a well-proven cardioprotective therapy, i.e. the population which does not tolerate or does not respond adequately to statins (almost 50% of at risk patients). Hence, we embarked on a critical analysis and review of the alternative regimen with a special focus on the AIM-HIGH and HPS2-THRIVE trials to bring to light the pitfalls of comparing radically different regimens of what is nominally the same drug. (more…)
Author Interviews, Diabetes, JAMA, Pharmacology / 01.03.2016

MedicalResearch.com Interview with: Dr. John Buse MD Ph.D Professor, Medicine Director, Diabetes Care Center Chief, Division of Endocrinology Executive Associate Dean, Clinical Research University of North Carolina School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Buse: Degludec is an longer acting basal insulin analog recently approved in the US.  Liraglutide is a once-daily GLP-1 receptor agonist.  Both are among the most powerful glucose lowering drugs available in the setting of type 2 diabetes.  They have very different properties.  Degludec is best at lowering fasting glucose. Liraglutide has effects on postprandial glucose as well.  The major side effects of degludec are hypoglycemia and weight gain. Liraglutide on the other hand has not an inherent effect to cause hypoglycemia and does promote weight loss.  Liraglutide does cause nausea and in fewer patients vomiting in a dose dependent manner. In developing the fixed dose combination the idea was to amplify glucose lowering efficacy and minimize the adverse effects of both components.  Prior studies have basically shown that this has been accomplished.  In this study we looked at the very common clinical scenario of the patient with type 2 diabetes inadequately controlled on basal insulin glargine and asked the question of whether switching from glargine to IDegLira (the combination product) would do better than continued titration of glargine. (more…)
Author Interviews, Heart Disease, NEJM, Pharmacology / 25.02.2016

MedicalResearch.com Interview with: Professor Paul Myles MBBS, MPH, MD, FCARCSI, FANZCA, FRCA Director, Dept of Anaesthesia and Perioperative Medicine Alfred Hospital and Monash University, Melbourne, Australia Medical Research: What is the background for this study? What are the main findings? Dr. Myles: When we set up this study 10 years ago there was marked variation in practice for  people taking aspirin waiting for coronary artery bypass surgery.  About half were being told that they must stop their aspirin 5-7 days before surgery, and the other half were told that they should stay on their aspirin. This variation existed across different countries, different cities, and even within a single hospital. Doctors had varied opinions because reliable medical research was sparse; the evidence was contradictory. We thus designed a definitive clinical trial in which half the patients were randomly assigned to receive aspirin and the other half received a placebo. Our study has shown that aspirin is safe (i.e. it does not increase the bleeding risk). We also found that there does not appear to be a benefit during and after surgery, but in view of the clear benefits that exist in daily life, including the preoperative waiting period, we recommend that people should stay on their aspirin if they are having coronary artery surgery. (more…)
Author Interviews, Heart Disease, JAMA, Kidney Disease, Pharmacology / 24.02.2016

MedicalResearch.com Interview with: Frederic T. Billings IV, MD, MSc Assistant Professor of Anesthesiology and Medicine Additional Specialty: Cardiothoracic Anesthesiology Vanderbilt University Medical Research: What is the background for this study? What are the main findings? Dr. Billings: Acute kidney injury (AKI) affects up to 30% of patients following cardiac surgery and is associated with long-term kidney function decline as well as a 5-fold increase in death during hospitalization following surgery. Statins affect several mechanisms of AKI following cardiac surgery including improvement of endothelial function and attenuation of oxidative stress, so we performed a clinical trial to test the hypothesis that high-dose atorvastatin (brand name Lipitor) use prior to and following surgery reduces AKI following cardiac surgery. In 615 patients who completed the study high-dose atorvastatin treatment, compared to placebo administration, did not reduce the risk of AKI overall, among patients naïve to statins, or patients already using a statin. In fact, among patients naïve to statins with baseline chronic kidney disease we found some evidence that atorvastatin may increase risk for kidney injury, although the number of patients was small in this subgroup. (more…)
Annals Internal Medicine, Author Interviews, Emergency Care, Gout, Pharmacology / 23.02.2016

MedicalResearch.com Interview with: Professor Timothy H Rainer  MD MBBCh Director, Accident & Emergency Medicine Academic Unit The Chinese University of Hong Kong  Medical Research: What is the background for this study? What are the main findings? Prof. Rainer: Gout is a type of arthritis characterised by periodic attacks of acute joint swelling and severe pain, and  often treated with colchicine or nonsteroidal anti-inflammatory drugs (NSAIDs).  Two recent randomized, controlled trials showed that oral prednisolone, a corticosteroid, was as effective as NSAIDs in the treatment of acute gout, but these studies involved small numbers of patients.  The researchers investigatedwhether oral prednisolone was as effective and safe as indomethacin (a NSAID) in a larger sample of patients who had acute gout symptoms and who were seen in the emergency department (ED) setting. Patients in both the prednisolone and indomethacin groups had clinically meaningful decreases in their pain levels during the 2 hours they were observed in the ED as well as during the 14-day follow-up period. Both groups had a similar decrease in pain levels. No major adverse events were reported in either group although there were more minor adverse events in the indomethacin group. (more…)
Anemia, Author Interviews, Kidney Disease, Pharmacology / 22.02.2016

MedicalResearch.com Interview with: Dr. Navdeep Tangri Attending physician and Assistant Professor in the Division of Nephrology Department of Medicine and the Department of Community Health Sciences University of Manitoba and Dr. David Collister  Seven Oaks General Hospital Renal Program Winnipeg, Manitoba Canada.  Medical Research: What is the background for this study? What are the main findings? Response: Anemia is common in chronic kidney disease (CKD) including dialysis and its treatment with erythopoetin stimulating agents (ESAs) reduces the need for blood transfusions and has varying effects on morbidity and mortality. The optimal hemoglobin (HGB) targets for treating anemia in CKD are controversial with safety concerns around the normalization of hemoglobin levels due to an increase in cardiovascular (CV) events. The effects of ESAs on health related quality of life (HRQOL) are unclear with individualization o fhemoglobin targets being controversial as clinicians and patients attempt to balance perceived HRQOL benefits with cardiovascular risk. We performed an updated meta-analysis of randomized controlled trials (RCTs) that evaluated the treatment of anemia in CKD with ESAs that targeted higher versus lower hemoglobin targets using validated HRQOL metrics including SF-36 and KDQ. We included 17 studies and found that higher hemoglobin targets compared to lower HGB targets did result in a statistically significant difference in HRQOL and thus did not improve HRQOL beyond a clinically meaningful threshold. Any change in HRQOL was further attenuated in dialysis subgroups. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Pharmacology / 17.02.2016

MedicalResearch.com Interview with: Professor Chris Thiemermann Centre for Trauma Sciences Queen Mary University of London Medical Research: What is the background for this study? What are the main findings? Prof. Thiemermann: Trauma is a leading cause of death with five million victims a year. About 40 per cent of trauma deaths are due to hemorrhagic shock, which is when severe blood loss makes it difficult for the heart to pump sufficient blood around the body, leading to multiple organ failure. Multiple organ failure affects one in three severely injured patients, and one in four of those will die.  Those that survive still experience prolonged periods in intensive care, infections and other complications. But despite its catastrophic impact, there are still no specific treatments for organ failure. We’ve now discovered that the drug Artesunate, which has already been used by thousands of people with malaria, is also effective for treating severe haemorrhage and blood loss in rats. Artesunate is based on an ancient Chinese herbal remedy, produced in large quantities in China, and is recommended by the World Health Organization as the treatment of choice for severe malaria. It has also been shown to have anti-cancer, anti-viral and anti-inflammatory effects. My study, which was funded by the Wellcome Trust and the Department of Health, shows that when injured rats were administered Artesunate, the drug had a marked protective impact on organ failure. The drug appears to work by enhancing the protection of organs by reducing the body’s excessive inflammatory response to injury and blood loss, and by activating well-known cell-survival pathways. The lower dose of Artesunate shown in the study to be effective in hemorrhagic shock is identical to the dose used in patients with malaria, many of which also have multiple organ dysfunction. (more…)