Author Interviews, HIV, Pharmacology / 24.05.2017

MedicalResearch.com Interview with: Martin Markowitz MD Clinical Director and Staff Investigator Aaron Diamond AIDS Research Center Aaron Diamond Professor at The Rockefeller University MedicalResearch.com: What is the background for this study? What are the main findings? Response: Cabotegravir ((CAB) is an inhibitor of HIV-1 integrase and is amenable to formulation in both oral and long acting injectable forms. In preclinical studies injectable CAB protected against low dose intrarectal challenge using an HIV-like virus in the rhesus macaque model. These results support the clinical development of CAB as prevention. This study was a first attempt to establish a dosing regimen and evaluate safety and acceptability of intramuscular injections of CAB. The study was a placebo controlled blinded study of approximately 120 subjects with a 5:1 randomization active/placebo. Subjects received 800mg CAB given as 2 2mL injections or placebo every 12 weeks for 3 injections after a 4 week safety lead in of oral therapy. Safety acceptability and PK were assessed. The main findings were that injections were associated with injection site reactions in the vast majority of participants that were mild to moderate and of short duration. Only 4 subjects who entered the injection phase discontinued due to injection intolerance. There were no additional safety signals and the participants considered the injections acceptable when asked to complete questionnaires. PK analysis found that despite modeling that suggested that the 800mg q 12 week dose would be adequate, this was not the case. More rapid uptake and release from the depot resulted in lower than anticipated drug levels at trough. Alternate dosing regimens are under study. Another finding is that there were participants (14%) who had detectable drug in plasma detected at 52 weeks after last injection suggesting the presence of a tail in some individuals. (more…)
Author Interviews, BMJ, Heart Disease, Pain Research, Pharmacology / 10.05.2017

MedicalResearch.com Interview with: Michèle Bally, BPharm, MSc, PhD Epidemiologist, Department of Pharmacy, CHUM Researcher, Health Innovation and Evaluation Hub, CRCHUM MedicalResearch.com: What is the background for this study? Response: The objective of this study was to better understand the risk of heart attack associated with using oral prescription non-steroidal anti-inflammatory drugs or NSAIDs (ibuprofen, diclofenac, celecoxib, and naproxen) the way people usually do to treat pain and inflammation in real life circumstances. A lot of people take medication, but they do not understand that some can be more harmful than beneficial, especially with consistent use. Unfortunately, something like a heart attack can happen anywhere. You could be at work and show signs of an attack. If this does happen, hopefully you have someone who is first aid trained to at least help you deal with these symptoms, until you get to the hospital. This is why having someone who knows that they are doing is beneficial in any environment. If it wasn't for companies like Coast2Coast in Ottawa, the chances of someone who was suffering from a heart attack may not have made it to the hospital if it wasn't for the assistance of someone who was first aid trained. In clinical trials, NSAIDs were typically taken on a continuous basis in high standardized doses, as assigned by the trial protocol. However, the dosages and the treatment durations studied in trials may not represent the reality of many patients who use NSAIDs in low or varying doses, use these drugs on and off, or switch between NSAID medications. We were particularly interested in determining the onset of the risk, that is how soon does the risk of heart attack start increasing? Also, we wanted to investigate the effect of dose and duration of treatment. To do this, we studied the use of a low or high dose level of NSAIDs over certain set periods of time, including taking these medications only for 1 to 7 days. (more…)
Author Interviews, JAMA, Pharmacology, UCLA / 03.05.2017

MedicalResearch.com Interview with: Ian Larkin, PhD Assistant Professor of Strategy UCLA Anderson School of Management MedicalResearch.com: What is the background for this study? Response: The study examined whether restrictions put in by medical centers on salesperson visits to physicians, known as “detailing,” affected subsequent physician prescribing behavior. Detailing represents the most prominent form of pharmaceutical marketing. Detailing visits allow the sharing of scientific information, but they also often involve small gifts for physicians and their staff, such as meals. Pharmaceutical companies incur far greater expenditures on detailing visits than they do on direct-to-consumer marketing, or even on research and development of new drugs. Specifically, the study examined detailing restrictions put into place by 19 academic medical centers (AMCs) in five states in the U.S. It compared changes in prescribing by thousands of AMC physicians whose practices limited typical elements of detailing visits, such as provisions of meals and educational gifts, to a carefully matched control group of similar physicians practicing in the same geographic regions but not subject to such detailing restrictions. The study, which included more than 25,000 physicians and all 262 drugs in eight major drug classes — from statins to sleep aids to antidepressants, representing more than $60 billion in aggregate sales in the United States — was, to date, by far the most comprehensive to examine the impact of detailing restrictions. The comprehensive and quasi-experimental methodology, which compared prescribing behavior before and after implementation of policies, and which included a large matched control group of physicians not subject to policy changes, was an important innovation relative to prior research. The study used prescription data from CVS Caremark, one of the largest pharmacy benefit managers in the United States. (more…)
Author Interviews, JAMA, Pain Research, Pharmacology, UT Southwestern / 01.05.2017

MedicalResearch.com Interview with: Una Makris MD, MSc Clinical Investigator at the VA North Texas Health System VA North Texas Health Care System Assistant Professor at UT Southwestern Medical Center Departments on Internal Medicine and Clinical Sciences Dr. Makris is a Rheumatologist, clinically, and spends the majority of time focused on clinical research investigating how to improve outcomes for adults with back pain. MedicalResearch.com: What is the background for this study? Response: Back pain is the most common type of musculoskeletal (MSK) pain. We know that expenditures for back pain exceed $100 billion each year (and this was in 2005). Back pain results in tremendous disability (including reduced mobility) and impaired quality of life (not exclusive to physical consequences, but also including important psychosocial repercussions). We also know that statins are prescribed very often, and frequently in younger populations who are active. Some reports suggest that statins may have a protective effect on  musculoskeletal conditions such as back pain. (more…)
Author Interviews, Opiods, Pharmacology, University Texas / 11.04.2017

MedicalResearch.com Interview with: Christina R. Merritt and Kathryn A. Cunningham Center for Addiction Research University of Texas Medical Branch Galveston, TX 77555 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Opioid use disorder (OUD) is one of the top public health problems in the United States. Overdoses on prescription opioids, heroin and fentanyl accounted for 33,091 deaths in the U.S. in 2015 (https://www.cdc.gov/mmwr/volumes/65/wr/mm655051e1.htm); each day, 91 Americans die from an opioid overdose (https://www.cdc.gov/drugoverdose/epidemic/). The first-ever Surgeon General’s Report on Alcohol, Drugs and Health (https://addiction.surgeongeneral.gov/ ) observed that more people used prescription opioids than tobacco in 2015. Furthermore, individuals with OUD, the most problematic pattern of opioid abuse, often relapse, particularly in environments associated with past drug use, and new means to help maintain abstinence are needed. Serotonin (5-hydroxytryptamine; 5-HT) function in the brain, particularly through its cognate 5-HT2C receptor, is an important regulator of the abuse liability of cocaine and other psychostimulants. Previous studies suggested that the weight loss medication and selective 5-HT2C receptor agonist lorcaserin (Belviq®) can curb cocaine- and nicotine-seeking in preclinical models, even when tested in tempting environments. We administered lorcaserin to rats who were trained to take the powerful painkiller oxycodone (OxyContin®), a prescription opioid currently approved for treatment of acute and chronic pain with characteristically high abuse potential. Lorcaserin suppressed oxycodone intake as well as the drug-seeking behaviors observed when rats were exposed to cues such as the lights and sounds previously associated with drug intake. Taken together, these findings highlights the therapeutic potential for lorcaserin to extend abstinence and enhance recovery from OUD. (more…)
Author Interviews, Pharmacology, Thyroid Disease, UCLA / 07.04.2017

MedicalResearch.com Interview with: Deborah Chon MD Endocrinology fellow UCLA David Geffen School of Medicine  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our study shows that drinking cow's milk concurrently with oral levothyroxine significantly reduces the absorption of the medication. Levothyroxine is used for the physiologic replacement of thyroid hormone in patients with hypothyroidism and for serum TSH suppression in patients with thyroid cancer. It is the mostly commonly prescribed medication in the United States as of 2014. Frequent dose adjustments of levothyroxine have been shown to be a costly burden to the national healthcare system. Previous studies have shown that certain foods and medication, such as calcium supplements, can interfere with levothyroxine absorption. However, this is the first study to demonstrate that ingesting cow?s milk, a common breakfast staple, affects oral levothyroxine absorption. To determine the possible effect of cow's milk ingestion, we measured levothyroxine absorption in humans with and without concurrent milk consumption. Pharmacokinetic studies were conducted in healthy adults without allergies to milk or levothyroxine, and who were not pregnant nor using oral contraceptives. All subjects had no history of known thyroid disease and normal thyroid hormone function at baseline. Following an overnight fast, serum total thyroxine T4 (TT4) concentrations were measured at baseline and at 1, 2, 4, and 6 hours after ingestion of 1,000 ?g of oral levothyroxine alone or when co-administered with 12 oz. of milk (2% fat). There was a four-week washout period between the two study visits. Ten subjects (mean age 33.7?10.2 years, 60% male) completed the study. The serum total T4 absorption over six hours, calculated as area under the curve (AUC), was significantly lower when taking cow?s milk concurrently with levothyroxine compared levothyroxine alone (mean?SD: 67.26?12.13 vs. 73.48?16.96; p = 0.02). Also, peak serum TT4 concentrations were significantly lower in those who ingested levothyroxine concurrently with milk, compared to taking levothyroxine alone (p=0.04). (more…)
Author Interviews, Heart Disease, Pharmacology / 20.03.2017

MedicalResearch.com Interview with: Kathrine Bach Søndergaard MD, Research Fellow Gentofte University Hospital Department of Cardiology Hellerup  MedicalResearch.com: What is the background for this study? Response: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used and have in previous studies been associated with an increased risk of cardiovascular adverse events, such as myocardial infarction and heart failure. Cardiac arrest is the ultimate adverse event; however, no research exists of the association between cardiac arrest and use of NSAIDs, which we aimed to assess in this study. (more…)
Author Interviews, Boehringer Ingelheim, Dermatology, Pharmacology / 08.03.2017

MedicalResearch.com Interview with: Andrew Blauvelt, M.D., M.B.A. President and Investigator Oregon Medical Research Center  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Findings from the Phase 3 VOYAGE 1 study showed that patients with moderate to severe plaque psoriasis receiving guselkumab, an human anti-interleukin (IL)-23 monoclonal antibody, achieved significant improvement in skin clearance and in comparison with Humira® (adalimumab), a TNF blocker.  The Phase 3 study and head-to-head analysis of guselkumab vs. adalimumab showed the significant and durable efficacy of guselkumab as maintained through one year when compared with adalimumab, and the robust efficacy of this novel IL-23 targeted therapy in meeting all primary and major secondary endpoints. (more…)
ASCO, Author Interviews, Outcomes & Safety, Pharmacology, Prostate Cancer, University of Michigan / 03.03.2017

MedicalResearch.com Interview with: Megan Elizabeth Veresh Caram MD Clinical Lecturer Internal Medicine, Hematology & Oncology University of Michigan   MedicalResearch.com: What is the background for this study? Response: Abiraterone and enzalutamide are oral medications that were approved by the Food & Drug Administration in 2011 and 2012 to treat men with metastatic castration-resistant prostate cancer. Most men with advanced prostate cancer are over age 65 and thus eligible for Medicare Part D. We conducted a study to better understand the early dissemination of these drugs across the United States using national Medicare Part D and Dartmouth Atlas data. (more…)
Author Interviews, BMJ, Flu - Influenza, Karolinski Institute, OBGYNE, Pediatrics, Pharmacology / 01.03.2017

MedicalResearch.com Interview with: Dr. Sophie Graner Department of Women's and Childrens Health Karolinska Institute, Stockholm, Sweden MedicalResearch.com: What is the background for this study? What are the main findings? Response: Pregnant women are at increased risks of severe disease and death due to influensa infection, as well as hospitalization. Also influenza and fever increase the risk of adverse pregnancy outcomes for their infants such as intrauterine death and preterm birth. Due to this, the regulatory agencies in Europe and the US recommended post exposure prophylaxis and treatment for pregnant women with neuraminidase inhibitors during the last influenza pandemic 2009-10. Despite the recommendations, the knowledge on the effect of neuraminidase inhibitors on the infant has been limited. Previously published studies have not shown any increased risk, but they have had limited power to assess specific neonatal outcomes such as stillbirth, neonatal mortality, preterm birth, low Agar score, neonatal morbidity and congenital malformations. (more…)
Author Interviews, Epilepsy, Pharmacology / 28.02.2017

MedicalResearch.com Interview with: Robert Lutjens, PhD Head of Discovery at Addex Therapeutics Geneva, Switzerland MedicalResearch.com: What is the background for this study? What are the main findings? Response: Metabotropic glutamate receptors represent an attractive therapeutic target for various neurologic conditions. In particular, the metabotropic glutamate receptor subtype 2 (mGlu2) can affect excitatory synaptic transmission by decreasing glutamate release. As excess gluatamate is observed in epilepsy, targeting mGlu2 could lead to new avenues of therapy. Positive allosteric modulators (PAMs) of mGlu2 could be valuable candidate drugs as they do not directly activate receptors. Therefore, they may avoid tachyphylaxis and side effects emerging from direct receptor agonism.  The publication summarizes the effects obtained when the mGlu2 receptor is activated using an agonist or PAM, such as ADX71149, in the 6Hz psychomotor seizure test, considered to be the most relevant model of pharmacoresistant limbic seizures. The data show that while seizures are reduced when mGlu2-acting compounds are administered alone, their combination with the antiseizure drug levetiracetam (LEV) result in a potent reduction of doses required to produce full efficacy, which is important because higher doses of LEV are associated with dose-limiting side effects, such as aggression, nervousness/anxiety, somnolence and fatigue. In this study, a fixed dose of ADX71149 was seen to increase the potency of LEV, leading to an approximate 35-fold increase in its potency. Conversely, using a fixed dose of LEV with varying doses of ADX71149 resulted in an approximate 14-fold increase in ADX71149 potency. (more…)
Author Interviews, Dermatology, Pharmacology / 24.02.2017

MedicalResearch.com Interview with: Prof. Dr. med. Kristian Reich Dermatologie, Allergologie Psoriasis- und Neurodermitis-Trainer Hamburg MedicalResearch.com: What is the background for this study? What are the main findings? Response: Ustekinumab is an antibody against the p40 molecule shared by IL-12 and IL-23. The antibody shows a favorable benfit-risk profile in the treatment of psoriasis. IL-23 is regarded a key driver in psoriasis pathology. It is speculated that antibodies against the IL-23-specific subunit p19 may produce even higher levels of clinical response than ustekinumab or the anti-TNF antagonist adalimumab. Guselkumab is the first IL-23p19 antibody to publish phase III data in psoriasis.    (more…)
Author Interviews, Depression, JAMA, Pharmacology, Yale / 23.02.2017

MedicalResearch.com Interview with: Adam Chekroud PhD Candidate Human Neuroscience Lab Department of Psychology Yale University MedicalResearch.com: What is the background for this study? Response: We know that depression includes a wide range of symptoms, from low mood and feeling worthless, to problems sleeping, slowed thinking, and suicidal ideation. We wanted to know whether antidepressants work well in treating all of these symptoms, or whether they are primarily effective on certain kinds of symptoms. (more…)
Author Interviews, HIV, Pharmacology / 20.02.2017

MedicalResearch.com Interview with: Kati Vandermeulen Senior Director, Global Regulatory Leader and Compound Development Team Lead IDV Janssen MedicalResearch.com: What is the background for this study? What are the main findings? Response:  SWORD is the first large trial program specifically conducted to look at the combination of dolutegravir and rilpivirine as a complete, two-drug antiretroviral regimen. Results of the two identical Phase III SWORD studies have been positive and demonstrate that the two-drug regimen of dolutegravir and rilpivirine is as effective, with comparable tolerability, to traditional three- or four-drug (integrase inhibitor-, non-nucleoside reverse transcriptase inhibitor-, or boosted protease inhibitor-based) antiretroviral regimens for the maintenance treatment of HIV. (more…)
Author Interviews, Biomarkers, Pharmacology, Prostate Cancer / 19.02.2017

MedicalResearch.com Interview with: Teemu J Murtola, MD, PhD, adjunct professor University of Tampere, Faculty of Medicine and Life Sciences Tampere University Hospital, Department of Urology Tampere, Finland MedicalResearch.com: What is the background for this study? Response: A previous study called Prostate Cancer Prevention Trial (PCPT) showed that finasteride, which belongs to a drug group called 5alpha-reductase inhibitors lowers serum PSA and increases sensitivity of PSA to detect high-grade prostate cancer in men who had little or no symptoms of the lower urinary tract. We postulated that this effect would increase the accuracy and benefits of PSA-based prostate cancer screening. Finnish Randomized Study of Screening for Prostate Cancer was a large trial of over 80,000 men randomized either to be screened for prostate cancer with a PSA test at 4-year intervals or to be followed for prostate cancer incidence and mortality via national registries. Three consecutive screening rounds were commenced between 1996-2008. In the current study we compared the effects of PSA-based screening on prostate cancer risk and mortality separately among men who were using 5alpha-reductase inhibitors finasteride or dutasteride and among men who were not. (more…)
Author Interviews, Heart Disease, JACC, Pharmacology / 15.02.2017

MedicalResearch.com Interview with: Gavin Y Oudit, MD, PhD, FRCPC Associate Professor, Department of Medicine, University of Alberta Clinician-Scientist Mazankowski Alberta Heart Institute Canada Research Chair in Heart Failure Division of Cardiology Edmonton, Alberta Heart specialist Gavin Oudit and his research team discovered a molecule — angiotensin converting enzyme 2 (ACE2)—that works to restore balance to the pathways responsible for chronic and acute heart failure, including in hearts from patients with advanced heart failure who underwent heart transplants. In developing the new drug, Oudit and his team discovered to an extent not seen before how the renin-angiotensin system (RAS), which regulates the body’s sodium balance, fluid volume, and blood pressure, is at play in both acute and chronic heart failure. In collaboration with Dr. Oudit, recombinant human ACE2 was made by Apeiron Biologics, purchased by GlaxoSmithKline, and has recently completed phase II clinical trial. (more…)
Author Interviews, Lancet, Multiple Sclerosis, Neurological Disorders, Pharmacology / 12.02.2017

MedicalResearch.com Interview with: Tomas Kalincik, MD, PhD, PGCertBiostat Neurologist and Senior Research Fellow Melbourne Brain Centre | Department of Medicine | University of Melbourne Department of Neurology | Royal Melbourne Hospital Melbourne | Victoria | Australia MedicalResearch.com: What is the background for this study? What are the main findings? Response: Multiple sclerosis is a disease predominantly of young adults, with the peak of incidence in the 3rd and 4th decades. It is the most common cause of neurological disability in young adults. Only in Australia, 23,000 people are living with MS, with MS representing an annual cost of almost 1 billion $AU to the Australian society. It is a disease that presents with broad range of neurological symptoms and signs, which are typically temporary (these are called relapses) that with time can lead to permanent neurological disability. While there is currently no cure for MS, with appropriate therapy, its symptoms can be controlled and the disability progression slowed down. (more…)
Author Interviews, Infections, Pharmacology / 09.02.2017

MedicalResearch.com Interview with: Dr. Fernanda Buzzola IMPaM, UBA-CONICET MedicalResearch.com: What is the background for this study? Response: Staphylococcus aureus represents a serious problem to public health due to methicillin-resistance and the bacterial persistence over a long period of time in the host. Approximately the 20% of the human population is at risk to acquire an endogenous infection by S. aureus as a consequence of its asymptomatic nasal colonization. Aspirin, the main source of salicylic acid in the human host, is currently taken by millions of human beings worldwide without medical prescription and widely indicated for defined purposes, including prevention of coronary thrombosis. Salicylic acid is a plant hormone known too for its use as a key ingredient in anti-acne preparations and medications for skin conditions. We also consume mild doses of salicylic acid when we eat fruits and vegetables. Iron is an important trace element for the human body and plays an essential role in blood formation. The metabolism of many bacteria, including S. aureus, also depends on the availability of iron molecules. Salicylic acid forms complexes with iron ions in the blood and so deprives not only us but also the staphylococcal bacteria of this element. S. aureus modifies its metabolism if the iron content is insufficient. The microorganism reacts to the changed – from its perspective, negative – conditions through the intensified formation of a biofilm, a sort of layer of slime formed by the aggregation of individual bacteria. The enhanced biofilm production allows the bacteria to survive for an even longer period under unfavourable living conditions. (more…)
Author Interviews, BMJ, Pain Research, Pharmacology / 07.02.2017

MedicalResearch.com Interview with: Dr. Gustavo Machado BPhty (Hons) Cert.MDT The George Institute for Global Health Sydney Medical School, University of Sydney Sydney, New South Wales, Australia MedicalResearch.com: What is the background for this study? What are the main findings? Response: People with back pain are usually told by their health care practitioners to take analgesic medications to relieve their pain. But our previous research published in the BMJ showed that paracetamol does not have a measurable impact on patient’s symptoms. This resulted in recent changes in guidelines' recommendations. The 2017 National Institute for Health and Care Excellence (NICE) guidelines/UK no longer recommend paracetamol as a stand-alone intervention for back pain. So now non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as the analgesic of first choice. However, our results show that compared to placebo, commonly used NSAIDs, such as Ibuprofen (e.g. Nurofen) and Diclofenac (e.g. Voltaren), provide only small benefits for people with back pain while increasing the risk of gastrointestinal adverse effects by 2.5 times. (more…)
Author Interviews, Diabetes, Endocrinology, Heart Disease, Lipids, Pharmacology, Weight Research / 30.01.2017

MedicalResearch.com Interview with: Gianluca Iacobellis MD PhD Professor of Clinical Medicine Division of Endocrinology, Diabetes and Metabolism Department of Medicine University of Miami, FL MedicalResearch.com: What is the background for this study? What are the main findings? Response: We know that epicardial fat, the visceral fat of the heart, is associated with coronary artery disease, diabetes and obesity. My studies have shown that epicardial fat can be easily measured with non invasive imaging procedures. Remarkably, epicardial fat has recently emerged as therapeutic target responding to medications targeting the fat. Liraglutide, a GLP-1 analog has shown to provide modest weight loss and beneficial cardiovascular effects beyond its glucose lowering action. So , we sought to evaluate the effects of liraglutide on epicardial fat. (more…)
Anemia, Author Interviews, Kidney Disease, Pharmacology, Stanford / 16.01.2017

MedicalResearch.com Interview with: Dr. Glenn M. Chertow, MD Professor Medicine, Nephrology Stanford University School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: Iron deficiency is common in persons with moderate to advanced (non-dialysis-dependent) chronic kidney disease (CKD), for a variety of reasons. Conventional iron supplements tend to be poorly tolerated and of limited effectiveness. In earlier studies of patients treated with ferric citrate for its effect as a phosphate binder, we saw increases in transferrin saturation and ferritin (markers of iron stores) and hemoglobin and hematocrit (the “blood count”). Therefore, we thought we should test the safety and efficacy of ferric citrate specifically for the treatment of iron deficiency anemia (IDA). With respect to the key findings, more than half (52%) of patients treated with ferric citrate experienced a sizeable (>=1 g/dL) increase in hemoglobin over the 16-week study period compared to fewer than one in five (19%) patients treated with placebo. Rates of adverse events (“side effects”) were similar to placebo; diarrhea in some patients and constipation in others were the most common. There were also favorable effects of ferric citrate on laboratory metrics of bone and mineral metabolism. (more…)
Author Interviews, Cancer Research, Diabetes, Pharmacology, Science / 05.01.2017

MedicalResearch.com Interview with: Dr. Don Gary Benjamin Biozentrum, University of Basel Basel, Switzerland. MedicalResearch.com: What is the background for this study? What are the main findings? Response: We initiated the study to find a co-drug that would increase the anti-cancer effect of the commonly prescribed anti-diabetic drug metformin. Metformin is a very well tolerated medication, however the dosage required to show anti-cancer activity is higher than that usually prescribed, hence the aim of the study. We found that metformin in combination with a second drug, syrosingopine (an anti-hypertensive), potently kills cancer cells in a variety of pre-clinical models. Quite nicely, both these drugs combine to kill the cells at a concentration where they have no impact on cell growth when applied singly. (more…)
Annals Thoracic Surgery, Author Interviews, Diabetes, Duke, Heart Disease, Hepatitis - Liver Disease, Pharmacology / 04.01.2017

MedicalResearch.com Interview with: Matthew J. Crowley, MD, MHS Assistant Professor of Medicine Member in the Duke Clinical Research Institute Duke University Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Although metformin is widely considered to be the first-line drug for type 2 diabetes, concerns about lactic acidosis have traditionally limited its use in some populations. However, FDA now indicates that metformin may be used safely for patients with mild-moderate chronic kidney disease and other historical contraindications like congestive heart failure. With the lactic acidosis question addressed for these groups, this review asked “what do we know about how metformin affects mortality and other outcomes for patients with historical contraindications and precautions?” The main take-home message is that metformin appears associated with lower mortality in patients with mild-moderate chronic kidney disease, congestive heart failure, and chronic liver disease. (more…)
Author Interviews, Cost of Health Care, Immunotherapy, Melanoma, Pharmacology / 22.12.2016

MedicalResearch.com Interview with: Herbert H F Loong MBBS(HK), PDipMDPath(HK), MRCP(UK), FHKCP, FHKAM(Medicine) Specialist in Medical Oncology Clinical Assistant Professor, Department of Clinical Oncology Deputy Medical Director, Phase 1 Clinical Trials Centre The Chinese University of Hong Kong Prince of Wales Hospital Hong Kong SAR MedicalResearch.com: What is the background for this study?  Response: Advanced melanoma have previously been known to be a disease with a dismal prognosis. Over the last few years, clinical trials data and real-world clinical experience of checkpoint inhibitors have significantly changed the treatment landscape for advanced melanoma patients. This was first demonstrated with the Anti-CTLA4 Ab Ipilimumab, and more recently with the Anti-PD1 Ab pembrolizumab. Whilst we have seen dramatic improvements in disease control with the use of these agents, the high costs of these drugs may be prohibitive to the average patient who has to pay out-of-pocket and potentially may place significant burdens on healthcare systems. There is a need to rationally assess the cost-effectiveness of these new agents, specifically addressing the potential benefits to the individual patient and to society, whilst balancing the costs that such a treatment may entail. The assessment of cost-effectiveness of a particular treatment is extremely important in Hong Kong, as this has direct implications on drug reimbursement and accessibility of the particular drug in question at public hospitals in Hong Kong. The aim of the study is to assess the cost-effectiveness of pembrolizumab in patients with advanced melanoma used in the first-line setting in Hong Kong, and comparing it to (1) ipilimumab and (2) cytotoxic chemotherapy. Cytotoxic chemotherapy chosen for comparison were drugs commonly used in the first line setting in Hong Kong, which included dacarbazine, temozolomide and carboplatin+paclitaxel combination. It is important to note that whilst ipilimumab is registered for this indication in Hong Kong, there is no reimbursement of this drug by the Hospital Authority in Hong Kong and patients have to pay out-of-pocket. The cost of ipilimumab and the associated side effects has been prohibitive to most advanced melanoma patients in the public setting. (more…)
AHA Journals, Author Interviews, Lipids, Pharmacology / 16.12.2016

MedicalResearch.com Interview with: Dr. Eli M. Roth MD, FACC President, Medical Director Sterling Research Group Cincinnati, OH MedicalResearch.com: What is the background for this study? What are the main findings? Response: At this year’s AHA 2016, we presented a pharmacodynamics analysis of ODYSSEY CHOICE I, which evaluated the effects of Praluent 300 mg administered every four weeks (Q4W) for 24 weeks in hypercholesterolemia patients at moderate to very high cardiovascular risk who were on maximally tolerated statin or no statin and/or other lipid-lowering therapies. The pharmacodynamic analysis of CHOICE I in patients on statins supports the use of Praluent 300 mg Q4W as an alternative starting dose for patients who prefer a Q4W dosing regimen and demonstrates the value of LDL-C based dosing interval adjustment. The findings from this analysis were consistent with prior ODYSSEY Phase 3 studies, showing that Praluent substantially reduced circulating free PCSK9 concentration, resulting in significant LDL-C reductions. Additionally, Praluent was generally well tolerated. (more…)
Author Interviews, Depression, JAMA, McGill, Pharmacology, Stroke / 09.12.2016

MedicalResearch.com Interview with: Christel Renoux, MD, PhD Assistant Professor, Dept. of Neurology & Neurosurgery McGill University Centre For Clinical Epidemiology Jewish General Hospital - Lady Davis Research Institute Montreal  Canada MedicalResearch.com: What is the background for this study? Response: Selective serotonin reuptake inhibitors (SSRIs) increase the risk for abnormal bleeding, in particular, gastrointestinal tract bleeding. Previous studies also suggested an increased risk for intracranial hemorrhage (ICH) in patients treated with SSRIs compared to non users. However, even if this risk exists, the comparison with a non-treated group may exaggerate the strength of a potential association and the comparison with a group of patients treated with other antidepressants may help better delineate the risk. The potential bleeding effect of antidepressants is linked to the strength of serotonin inhibition reuptake, and antidepressants that are strong inhibitors of serotonin reuptake have been associated with the risk for gastrointestinal or abnormal bleeding compared with weak inhibitors but the risk of ICH is unclear. (more…)
Author Interviews, Pharmacology / 02.12.2016

MedicalResearch.com Interview with: Dr. Charles Pollack MD Professor of Emergency Medicine Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia. MedicalResearch.com: What is the background for this study? What are the main findings? Response: RE-VERSE AD™ is a multinational, open-label cohort Phase III trial studying the safety and efficacy of idarucizumab (PRAXBIND) to reverse the anticoagulant effects of dabigatran (PRADAXA) in patients with life-threatening or uncontrolled bleeding, or those who require emergency procedures. It is the largest patient study investigating a reversal agent for a novel oral anticoagulant (NOAC) in real world emergency settings. At the American Heart Association’s Scientific Sessions 2016, we presented updated results from 494 patients participating in the ongoing study, showing that administration of 5g of idarucizumab immediately reversed the anticoagulant effect of dabigatran. (more…)
Author Interviews, Electronic Records, Geriatrics, Pharmacology / 29.11.2016

MedicalResearch.com Interview with: Jashvant Poeran MD PhD Assistant Professor Dept. of Population Health Science & Policy Icahn School of Medicine at Mount Sinai New York, NY MedicalResearch.com: What is the background for this study? Response: Falls are an important patient safety issue among elderly patients and may lead to extended hospitalization and patient harm. Particularly important in elderly patients are high risk drugs such as sleep medications which are known to increase fall risk and should be dosed lower in elderly patients. In this study we looked at patients aged 65 years or older who fell during hospitalization. We found that in 62%, patients had been given at least one high risk medication that was linked to fall risk, within 24 hours before their fall. Interestingly, we found that also a substantial proportion of these medications were given at doses higher than generally recommended for elderly patients. (more…)
Author Interviews, HIV, Pharmacology / 28.11.2016

MedicalResearch.com Interview with: Arkaitz Imaz Vacas HIV and STD Unit, Department of Infectious Diseases Hospital Universitari de Bellvitge MedicalResearch.com: What is the background for this study? Response: Sexual transmission is the most common route of human immunodeficiency virus (HIV) acquisition in most regions of the world. The male genital tract is a separate reservoir for HIV and may contribute to HIV shedding in seminal fluid even in individuals receiving antiretroviral (ARV) therapy (ART). Treatment of HIV-infected patients with currently available combined ART suppresses HIV in blood and also in genital fluids and reduces the risk of HIV acquisition by their sexual partners. However, sexual HIV transmission is possible even in patients on ART, especially if treatment was initiated recently. Thus, the ability of ARV drugs to penetrate into the male genital tract is a key factor for achieving HIV suppression in seminal fluid and preventing sexual transmission of the virus. Dolutegravir (DTG) is a new integrase inhibitor (INI) with high antiviral potency and a high genetic barrier to resistance. In large phase III-a randomized clinical trials, DTG in combination with 2 nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) has shown noninferiority compared with raltegravir and superiority to efavirenz or ritonavir-boosted darunavir as first-line therapy in treatment-naive HIV-1 infected patients. A study in healthy volunteers showed that DTG penetration in seminal fluid was <7% of DTG exposure in blood plasma (BP), and the median seminal concentration at the end of the dosing interval (C24h) was lower than the in vitro protein-adjusted (PA) 90% inhibitory concentration (IC90) for wild-type HIV-1. However, information about protein unbound DTG fraction in seminal fluid is lacking and there is no information regarding DTG concentrations in the semen of HIV-1–infected patients or the antiviral activity of a DTG-based ARV combination in this compartment. The aim of this study was to compare viral decay kinetics and DTG concentrations (total drug and unbound fraction) in the seminal plasma (SP) and BP in a group of treatment-naive HIV-1 infected patients starting DTG plus abacavir (ABC) and lamivudine (3TC) once daily. (more…)
Author Interviews, Blood Pressure - Hypertension, Bone Density, JAMA, Kaiser Permanente, Osteoporosis, Pharmacology / 22.11.2016

MedicalResearch.com Interview with: Joshua I. Barzilay, MD Kaiser Permanente of Georgia Duluth, GA 30096 MedicalResearch.com: What is the background for this study? Response: Hypertension (HTN) and osteoporosis (OP) are age-related disorders. Both increase rapidly in prevalence after age 65 years. Prior retrospective, post hoc studies have suggested that thiazide diuretics may decrease the risk of osteoporosis. These studies, by their nature, are open to bias. Moreover, these studies have not examined the effects of other anti HTN medications on osteoporosis. Here we used a prospective blood pressure study of ~5 years duration to examine the effects of a thiazide diuretic, a calcium channel blocker and an ACE inhibitor on hip and pelvic fractures. We chose these fractures since they are almost always associated with hospitalization and thus their occurrence can be verified. After the conclusion of the study we added another several years of follow up by querying medicare data sets for hip and pelvic fractures in those participants with medicare coverage after the study conclusion. (more…)