Alzheimer's - Dementia, Author Interviews, JAMA, Pharmacology / 15.02.2016

MedicalResearch.com Interview with: Dr. Britta Haenisch PhD German Center for Neurodegenerative Diseases (DZNE)  Medical Research: What is the background for this study? Dr. Haenisch: Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal diseases, but have also been shown to be potentially involved in cognitive decline: There were hints from recent other studies that PPIs might affect cognition, e.g. Lam et al. (2013) report a significant association of PPI use with vitamin B12 deficiency in a population-based sample. Vitamin B12 deficiency has been shown to be associated with cognitive decline. In another study, PPIs were observed to enhance amyloid beta peptide (Aβ) levels in mouse brain by affecting the enzymes β- and γ-secretase which leads to increased Aβ levels in mice. Medical Research: What are the main findings? Dr. Haenisch: The current study provides a statistical association (applying a time-dependent analysis) between proton pump inhibitors prescription and occurrence of dementia with a focus on long-term regular PPI prescription in patients aged 75 years and older. In our analysis we focused on long-term regular PPI prescription for at least 18 months. It does not prove that proton pump inhibitors cause dementia. References -Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-2442. -Badiola N, Alcalde V, Pujol A, et al. The proton-pump inhibitor lansoprazole enhances amyloid beta production. PLoS One. 2013;8(3):e58837 (more…)
Author Interviews, Epilepsy, Lancet, Pharmacology / 15.02.2016

MedicalResearch.com Interview with: Dr. Michael Privitera MD Professor of the Department of Neurology and director of the Epilepsy Center University of Cincinnati Neuroscience Institute  Medical Research: What is the background for this study? What are the main findings? Dr. Privitera: Generic substitution of medications has saved the American health care system billions of dollars per year. However, based on a series of uncontrolled studies, patients and clinicians share concerns that generic substitution of antiepileptic drugs may lead to loss of efficacy or emergence of adverse effects. To answer this question we undertook a prospective, randomized study that tested bioequivalence of two generic products of the antiepileptic drug lamotrigine. Lamotrigine was identified in several publications as a possible source of problems after generic switches. FDA studies test a single generic versus the brand name product in a single dose study in normal volunteers. We designed a study that would be most likely to show a difference between generics if one existed. We compared the two generic lamotrigine products showing the most difference in prior testing in patients with epilepsy taking the drug daily using rigorous pharmacokinetic methods. Each patient took each of the two generics for 2 four week periods. Our study showed the two generics were essentially indistinguishable and easily met bioequivalence standards. No patient had loss of seizure control or unexpected adverse effects. (more…)
Author Interviews, Heart Disease, Pharmacology / 12.02.2016

MedicalResearch.com Interview with: Giuseppe Biondi-Zoccai MD Department of Medico-Surgical Sciences and Biotechnologies Sapienza University of Rome Corso della Repubblica Latina, Italy  Medical Research: What is the background for this study? Dr. Biondi-Zoccai: The main premise of our work is the historically established benefit of aspirin to reduce the risk of cardiovascular events in apparently healthy people, which is however substantially offset by the risk of bleeding. More recently, several pieces of evidence have highlighed the cancer benefits of aspirin, namely its capability of reducing the risk of cancer, in particular cancer in the colon and rectum, as well as deaths due to such cancer. Despite these potentially momentous benefits, there is uncertainty on which dose and preparation of aspirin is best suited to reduce cardiovascular and cancer events, while minimizing bleeding. Indeed, several dosages of aspirin have been tested and are commercially available (for instance from as little as 50 mg per day to more than 300 mg per day). In addition, aspirin is available in different pharmacologic preparations, for instance with specific gastro-protective coatings or controlled-release features, which may have impact on safety and efficacy.     Medical Research: What are the main findings? Dr. Biondi-Zoccai: Our results, building upon the recent research work of the US Government sanctioned Preventive Services Task Force (USPSTF), suggest that a dosage of aspirin of 100 mg per day, combined with enteric-coating, is most likely to be beneficial to reduce the risk of cancer and minimize stomach bleeding. The results, as often in biomedical research, are not however 100% certain, and thus this increased likelihood of benefit must be viewed in the context of our study design, as well as other procedural and patient factors. (more…)
Author Interviews, Cancer Research, Heart Disease, JAMA, Pharmacology / 06.02.2016

MedicalResearch.com Interview with: Jonathan Douxfils Pharm.D. - Ph.D. Research assistant Faculty of Medicine - Department of Pharmacy NAmur Research Institute for LIfe Sciences (NARILIS) Namur Thrombosis and Hemostasis Center (NTHC) Medical Research: What is the background for this study? What are the main findings? Dr. Douxfils: We decided to perform this study based on the release of the FDA regarding the risk of arterial occlusive events associated with ponatinib. We then hypothesize that the risk was not only restricted to ponatinib but also to other TKIs. This study shows that dasatinib, nilotinib and ponatinib increase the risk of vascular occlusive events compared to imatinib. Medical Research: What should clinicians and patients take away from your report? Dr. Douxfils: We suggest that patients treated with these molecules should be more frequently monitored, i.e. by an intensive support of associated comorbidities. In addition, even if they appear to have a better efficacy in terms of molecular response, new generation TKIs does not improve the overall survival at one year. As we have not access to individual data, it was impossible to clearly identify categories of patients for whom the risk of cardiovascular occlusive events is predominant. Therefore, the intensive monitoring proposed should be applied to all patients treated with these molecules. Regarding the choice of the therapy, the physician should certainly consider the goals of the treatment. For elderly patients, improving survival is the main objective and in this context, imatinib remains an excellent choice. For patients with a life expectancy greater than 10 years in whom we aim to achieve a deep molecular response to potentially reach a point of treatment cessation, dasatinib and nilotinib could be preferred. However, the choice of dasatinib or nilotinib as first-line treatments should involve a screening for potential risk factors such as diabetes, prior vascular occlusive events or any risk that could increase these adverse events. For second- and third-line treatments, the choice of the treatment has to be based on mutational analysis, previous adverse events, and the medical condition of the patient. Thus, in case of intolerance or resistance, the switch to one of the other TKIs approved for first-line therapy is an option. If treatment failure still occurs, a more potent TKI, i.e. bosutinib, is preferred. Importantly, ponatinib is reserved to patients with the T315I mutation and must be avoided in patients with good prognosis. (more…)
Author Interviews, BMJ, Mental Health Research, Pediatrics, Pharmacology / 29.01.2016

MedicalResearch.com Interview with: Tarang Sharma, PhD candidate  Nordic Cochrane Centre, Rigshospitalet University of Copenhagen, Faculty of Health and Medical Sciences, Denmark Medical Research: What is the background for this study? What are the main findings? Response: These newer antidepressants are some of the most prescribed medications in the world and previous research in the area has suggested an increased suicide risk on these drugs in young people, but only when unpublished clinical study report data is used. Such risk is missing when the published articles are considered due to severe selective reporting and publication bias. In our study we found that the research design of most of the trials was very poor and there were major discrepancies in the reporting, leading to the under-estimation of harms. Despite these problems we still found that both suicidality and aggression were more than doubled in children and adolescents on antidepressants compared to those on placebo. (more…)
Author Interviews, BMJ, Cancer Research, Heart Disease, Pharmacology / 24.01.2016

More on Heart Disease on MedicalResearch.com MedicalResearch.com Interview with: Professor Ian C K Wong Fellow of Royal Pharmaceutical Society Fellow of Royal College of Paediatrics and Child Health (Honorary) Fellow of the Higher Education Academy Chair in Pharmacy Practice Head of Research Department of Practice and Policy UCL School of Pharmacy London  Medical Research: What is the background for this study? What are the main findings? Dr. Wong: Previous studies had showed an increased cardiovascular risk associated with clarithromycin (a widely used antibiotic) but the duration of effect remained unclear. Therefore, we conducted this study to investigate the duration of cardiovascular adverse effect provided that the risk exists after patients receiving clarithromycin in Hong Kong. We used three study designs to examine the  association (temporal relationship) between clarithromycin and cardiovascular adverse outcomes such as myocardial infarction, arrhythmia, stroke, cardiac mortality at different time points.

We found that there was an increased short-term risk of myocardial infarction, arrhythmia and cardiac mortality associated with clarithromycin in all study designs. However, no long-term risk was observed. In every 1000 patients, there was 1.90 extra myocardial infarction events in current use of CLARITHROMYCIN when compared with the use of amoxicillin.

(more…)
Asthma, Author Interviews, Lancet, Pharmacology / 20.01.2016

More on Asthma on MedicalResearch.com MedicalResearch.com Interview with: Hans Bisgaard, MD, DMSc Professor of Pediatrics The Faculty of Health Sciences University of Copenhagen Head of the Copenhagen Prospective Studies on Asthma in Childhood University  of Copenhagen and Naestved Hospital Medical Research: What is the background for this study? Dr. Bisgaard: Childhood asthma is often preceded by recurrent asthma-like symptoms in relation to airway infections in the first years of life. Bacteria and viruses are equally associated with the risk of episodes of asthma-like symptoms in these children, suggesting antibiotics as a potential treatment for such episodes. Medical Research: What are the main findings? Dr. Bisgaard: Our study demonstrates a clinically significant shortening of symptom duration by 63% after intervention. The effect size increased with early initiation of treatment, showing a reduction in episode duration of 83% if treatment was initiated before day 6 of the episode. Azithromycin was effective in shortening the episodes even though no pathogenic bacteria was detected. This study is, to our knowledge, the first randomized trial of azithromycin treatment of acute episodes of asthma-like symptoms in young children with a history of recurrent episodes. (more…)
Author Interviews, Diabetes, JAMA, Mental Health Research, Pediatrics, Pharmacology / 20.01.2016

More on Mental Health on MedicalResearch.com MedicalResearch.com Interview with: Christoph U. Correll, MD Professor of Psychiatry and Molecular Medicine Hofstra Northwell School of Medicine Hempstead, New York, USA Investigator, Center for Psychiatric Neuroscience Feinstein Institute for Medical Research Manhasset, New York, Medical Director, Recognition and Prevention The Zucker Hillside Hospital, Department of Psychiatry  Medical Research: What is the background for this study? Dr. Correll: Antipsychotics have been used increasingly for psychotic, but also for many non-psychotic conditions, including for disorders and conditions for which they have not received regulatory approval. Moreover, antipsychotics have been associated with weight gain and abnormalities in blood fat and blood glucose levels. Although data in youth have been less available than in children and adolescents, youth appear to be more sensitive to the cardiometabolic adverse effects of antipsychotics than adults in whom significant weight gain might have already occurred due to long-term prior antipsychotic treatment. Nevertheless, type 2 diabetes, which is related to weight gain, overweight and obesity, seemed to be more common in adults than youth, likely due to the fact that it takes a long time for the body to develop diabetes. Recently, several individual epidemiologic or database studies with sufficient long-term follow-up durations suggested that the type 2 diabetes risk was higher in youth exposed to antipsychotics than healthy control youth and, possibly, even compared to psychiatrically ill patients treated with non-antipsychotic medications. However, a meta-analytic pooling of all available data has not been available to estimate the absolute and relative risk of type 2 diabetes in youth receiving antipsychotic treatment.  Medical Research: What are the main findings? Dr. Correll: The main findings of the study that meta-analyzed data from 13 studies with 185,105 youth exposed to antipsychotics (average age 14.1 and 59.5 percent male) are that the absolute rates of type 2 diabetes are fortunately still relatively low, i.e. a cumulative type 2 diabetes  risk of 5.7/1,000 patients and an exposure adjusted incidence rate of 3.1/1,000 patient-years. Nevertheless, the cumulative risk of type 2 diabetes and its exposure adjusted incidence rate per patient were 2.6 times and three times higher compared with 298,803 healthy controls. Furthermore, the cumulative risk of type 2 diabetes and its exposure adjusted incidence rate per patient were 2.1 times and 1.8 times higher compared with 1,342,121 psychiatric patients not exposed to antipsychotics. Main modifiable risk factors for type 2 diabetes development in antipsychotic-treated youth were treatment with the antipsychotic olanzapine and longer antipsychotic exposure time. (more…)
Author Interviews, Brigham & Women's - Harvard, Pancreatic, Pharmacology, PLoS / 15.01.2016

More on Pancreatic Cancer on MedicalResearch.com MedicalResearch.com Interview with: Dai Fukumura, M.D., Ph.D. Joao Incio, M.D. and Rakesh K. Jain, Ph.D Edwin L. Steele Laboratory Department of Radiation Oncology Massachusetts General Hospital Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Fukumura: This study focused on pancreatic ductal adenocarcinoma, the most common form of pancreatic cancer, which accounts for almost 40,000 cancer death in the U.S. ever year. Half of those diagnosed with this form of pancreatic cancer are overweight or obese, and up to 80 percent have type 2 diabetes or are insulin resistant. Diabetic patients taking metformin – a commonly used generic medication for type 2 diabetes – are known to have a reduced risk of developing pancreatic cancer; and among patients who develop the tumor, those taking the drug may have a reduced risk of death. But prior to the current study the mechanism of metformin’s action against pancreatic cancer was unclear, and no potential biomarkers of response to metformin had been reported. We have uncovered a novel mechanism behind the ability of the diabetes drug metformin to inhibit the progression of pancreatic cancer. Metformin decreases the inflammation and fibrosis characteristic of the most common form of pancreatic cancer. We found that metformin alleviates desmoplasia – an accumulation of dense connective tissue and tumor-associated immune cells that is a hallmark of pancreatic cancer – by inhibiting the activation of the pancreatic stellate cells that produce the extracellular matrix and by reprogramming immune cells to reduce inflammation. Our findings in cellular and animal models and in patient tumor samples also indicate that this beneficial effect may be most prevalent in overweight and obese patients, who appear to have tumors with increased fibrosis. (more…)
Author Interviews, Lung Cancer, Pharmacology / 12.01.2016

MedicalResearch.com Interview with: Glen Weiss, MD, MBA Director of Clinical Research & Medical Oncologist and Dr. Zoltan Lohinai MD National Koranyi Institute of Pulmonology Budapest, Hungary Western Regional Medical Center Cancer Treatment Centers of America Goodyear, Arizona MedicalResearch: What is the background for this study? What are the main findings? Response: With nearly 1.4 million deaths each year, lung cancer is the world’s leading cause of cancer-related mortality. In the U.S., more than 162,000 die annually of this disease. One subtype of this cancer, small cell lung cancer (SCLC), is one of the most progressive tumor types. No new class of systemic treatment has been adopted as a new benchmark for standard therapy against SCLC for nearly three decades. Lung cancer researchers focus on SCLC not only because of its scientific challenge, but also because of their great desire to help patients suffering from this aggressive tumor. Drug repurposing bioinformatical analysis, a new research direction, has found that FDA-approved drugs in non-malignant diseases may have antitumor effects. Our study attempted to evaluate the recent laboratory findings in a clinical setting. Statins are a class of drugs primarily used to lower cholesterol in patients at risk for heart disease. They have been hypothesized by preclinical data to affect tumor cells through the extracellular signal-regulated kinase (ERK) pathway, which regulates many cellular functions. Our study of 876 metastatic-stage  small cell lung cancer patients, published Jan. 6, 2015, in the peer-reviewed scientific journal PLOS ONE, showed that statins appeared to provide an increase in overall survival for those cancer patients who were prescribed those medications. Patients prescribed other classes of drugs, including aspirin, antidepressants, and blood pressure-lowering agents, have reportedly shown anti-SCLC activity in previous preclinical studies. However, our study found no such survival benefits. All in all, our study is a good example of how to evaluate drug repurposing in oncology, and that statins might have clinical relevance in the treatment of SCLC. (more…)
Author Interviews, Blood Clots, Endocrinology, Hormone Therapy, Pharmacology / 07.01.2016

MedicalResearch.com Interview with: Ida Martinelli MD, PhD A Bianchi Bonomi Hemophilia and Thrombosis Center Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan, Italy  Medical Research: What is the background for this study? What are the main findings? Dr. Martinelli: Hormonal therapies are associated with an increased risk of venous thromboembolism. Patients with acute deep-vein thrombosis or pulmonary embolism require anticoagulation, but women of childbearing potential require also an adequate contraception, as oral anticoagulants cross the placenta potentially leading to embryopathy or fetal bleeding. This study was aimed to evaluate the safety of hormonal therapies together with anticoagulant therapies in terms of recurrent venous thrombosis and uterine bleeding. We demonstrated for the first time that women who take oral anticoagulants can safely use hormonal therapies, as their risk of recurrent venous thromboembolism or uterine bleeding is not increased. (more…)
Author Interviews, BMJ, Brigham & Women's - Harvard, OBGYNE, Pharmacology / 07.01.2016

MedicalResearch.com Interview with: Brittany M. Charlton, ScD Instructor Boston Children's Hospital and Harvard Medical School Researcher, Harvard Chan School Department of Epidemiology Boston, MA 02115   Medical Research: What is the background for this study? What are the main findings? Dr. Charlton: Even though oral contraceptives can be over 99% effective with perfect use, almost 10% of women become pregnant within their first year of use. Many more women will stop using oral contraceptives when planning a pregnancy and conceive within just a few months. In both of those examples, a woman may inadvertently expose her offspring during pregnancy to exogenous sex hormones. We conducted a nationwide cohort study in Denmark in order to investigate whether oral contraceptive use shortly before or during pregnancy was associated with an increased risk of major birth defects in the offspring. Our main finding was that there was no increased risk of having a birth defect associated with oral contraceptive exposure. These results were also consistent when we broke down the birth defects into different subgroups, like limb defects. (more…)
Author Interviews, Depression, OBGYNE, Pharmacology / 06.01.2016

MedicalResearch.com Interview with: Anick Bérard PhD FISPE Research chair FRQ-S on Medications and Pregnancy and Director, Réseau Québécois de recherche sur le médicament (RQRM) and Professor, Research Chair on Medications, Pregnancy and Lactation Faculty of Pharmacy University of Montreal and Director, Research Unit on Medications and Pregnancy Research Center CHU Ste-Justine  Medical Research: What is the background for this study? What are the main findings? Dr. Bérard: Paroxetine (one of the most used antidepressant during pregnancy) has been studied extensively over the past 10-12 years. In 2005, a black box warning was put on the Paxil label to caution against use during pregnancy due to the increased risk of cardiac defects. The ACOG 2010 guidelines also suggested switching to other antidepressants during pregnancy. Over the past decade, many studies, including meta-analyses, were performed on on paroxetine use during pregnancy and the risk of cardiac malformations - but results were sometimes statistically significant or not, although a consistent increased risk was observed. It was thought that these variations could be explained by different study designs, patient populations, and because maternal depression was not always taken into account correctly. Hence, we undertook another meta-analysis (the most recent and updated) to quantify the risk of cardiac defects overall as well as specific cardiac defects associated with paoxetine use during pregnancy and to assess the impact of study designs, maternal depression and patient population on the effect of the risk. We found that women using paroxetine during the first trimester of pregnancy (critical time-window for malformations) were 23% more at risk of having a child with malformations (15 studies combined) - baseline risk of malformation is 3-5% and thus a 23% increased risk is 3.69-6.15% absolute risk; women using paroxetine during the first trimester of pregnancy were 28% more at risk of having a child with cardiac malformations (18 studies combined) - baseline risk of cardiac malformation is 1% and thus a 28% increased risk is 1.28% absolute risk. We found that paroxetine was increasing the risk of many specific cardiac defects as well. Although the estimates varied depending on the comparator group, study design, and malformation detection period, a trend towards increased risk was observed. (more…)
Author Interviews, Pharmacology / 04.01.2016

MedicalResearch.com Interview with: Prof. Daniel F. Klessig Boyce Thompson Institute for Plant Research, Department of Plant Pathology and Plant-Microbe Biology Cornell University, Ithaca, New York  MedicalResearch: What is the background for this study? Prof. Klessig: Acetyl salicylic acid, commonly called aspirin, has been the most widely used drug worldwide for more than a century. Currently, 80 million pounds of aspirin are produced worldwide every year and almost 30 billion tablets are consumed annually in the US alone. Long before German pharmacologist Johann Buchner identified the salicylic acid derivative salicin in 1828 as the ingredient in willow bark that is responsible for its therapeutic effects, different cultures throughout the world were, and many still are, using a variety of plants rich in salicylic acid derivatives, such as willow, wintergreen, and meadowsweet, to treat pain, fever, swelling, and other maladies. Aspirin also is used to reduce the risk of heart attack, stroke, and certain cancers. One might expect that aspirin’s mechanisms of action would be well understood, given its extraordinarily widespread use and the fact that it was first synthesized by the Bayer chemist Felix Hoffmann over 100 years ago. The prevailing view in the biomedical community has been that aspirin works primarily, if not exclusively, by irreversibly inhibiting the enzymatic activities of cyclooxygenases 1 and 2 (COX1 and COX2), thereby disrupting the synthesis of inflammation-inducing prostaglandins. However, this assumption ignores two important facts.
  • First, aspirin is rapidly converted to salicylic acid (SA) in the body. Indeed, almost all aspirin is metabolized to SA within an hour after ingestion.
  • Second, SA and many of its natural plant derivatives are rather poor inhibitors of COX1 and COX2 as compared to aspirin, yet SA and aspirin have nearly the same beneficial pharmacological effects. Thus, there must be additional targets through which aspirin/SA exerts its many effects. Over the past two decades, a number of proteins whose activities are altered by aspirin/SA have been identified; however, their relevance as aspirin/SA targets has been called into question due to the very high, non-physiological levels of aspirin/SA required to alter their activities.
In light of our unexpected discovery that SA mediates its physiological effects in plants via many targets, and given that SA is a key hormone produced by all plants, we hypothesized that there might be multiple targets through which SA acts in animals, regardless of whether it is obtained in low to moderate levels via the diet or in moderate to high doses through herbal-based medicines or aspirin usage. (more…)
Author Interviews, Autism, Pediatrics, Pharmacology / 02.01.2016

MedicalResearch.com Interview with: Diane C. Chugani, PhD Director, Nemours Neuroscience Research Nemours—AI DuPont Hospital for Children Wilmington, DE 19803  Medical Research: What is the background for this study? What are the main findings? Dr. Chugani: This clinical trial was performed at 5 sites throughout the country and was lead by our team at Wayne State University and Children’s Hospital of Michigan in Detroit.  The study was sponsored by the National Institutes of Health through an Autism Centers of Excellence Network grant.  Based upon our previous PET scanning studies showing low  serotonin synthesis  in the brains of young children with autism, we tested whether the serotonin-like drug buspirone would be beneficial in treating young children with Autism Spectrum Disorder.  We found that low doses of buspirone were effective in reducing repetitive behaviors with no significant side effects in this group of children. (more…)
Author Interviews, Dermatology, Pharmacology / 22.12.2015

MedicalResearch.com Interview with: Dr. Diana Lac, PhD Senior Scientist at BioPharmX Corporation. Dr. Lac received her PhD in Pharmacology and Toxicology from the University of California, Davis and currently focuses on the development of topical treatments for acne. MedicalResearch: What is the background for this study? What are the main findings? Dr. Lac: Acne affects almost 90% of people in western societies during their teenage years and may persist into adulthood. Currently, the oral tetracycline class of drugs dominates the acne treatment market. However, these treatments have been associated with a variety of adverse effects, such as headaches, dizziness, fatigue, nausea, photosensitivity, and severe itchiness. While a variety of acne treatments do exist, topical antibiotics particularly have had limited success due to formulation challenges. A topical minocycline formulation will provide a superior alternative for local treatment of acne, thereby limiting the amount of systemic exposure to the antibiotic and addressing the overall global antibiotic resistance problem. We believe that by directly delivering the drug to the skin we can decrease the amount of antibiotic exposure and also limit the off-target effects. We have developed a novel, stable minocycline gel formulation allowing for efficient delivery of minocycline directly to the pilosebaceous unit in the skin where Propionibacterium acnes typically reside. In this poster presentation we have demonstrated this effectively in live rats. A dose ranging study was conducted where drug delivery and safety of our novel formulation was assessed. A number of dose formulations were tested (up to 4% minocycline formulations) and were found to be non-irritating and safe for topical use. (more…)
Author Interviews, Cost of Health Care, Emory, Infections, Pharmacology / 17.12.2015

MedicalResearch.com Interview Questions Carlos del Rio, MD Chair, HIV Medicine Association Department of Medicine Hubert Professor and Chair of the Department of Global Health at the Rollins School of Public Health Professor of Medicine in the Division of Infectious Diseases Emory University School of Medicine MedicalResearch.com Editor's note:  Dr. Carlos del Rio discusses the statement from the Infectious Diseases Society of America (IDSA), HIV Medicine Association (HIVMA) and the Pediatric Infectious Diseases Society (PIDS) regarding the news that Express Scripts is taking steps to improve access to obtaining pyrimethamine for patients with toxoplasmosis. Medical Research: What is the background for this Express Scripts announcement? Dr. del Rio: The HIV Medicine Association (HIVMA) and the Infectious Diseases Society of America initially heard from our members (ID and HIV clinicians) in August about the 5000% price increase in Daraprim® (from $13.50 to $750 per tablet) following Turing Pharmaceuticals’ acquisition of the rights to distribute Daraprim® from Impax Laboratories, Inc.[1] ID and HIV clinicians told us they had been having difficulties obtaining pyrimethamine since earlier in the summer when Impax implemented a controlled distribution system making the drug available only through Walgreen’s Specialty Pharmacy. Despite HIVMA, IDSA and others urging Turing to reverse the price hike, no action was taken and providers continued to report the scarcity of the drug due to the cost and issues with the distribution system. [2] Due to these ongoing challenges, HIVMA and IDSA thought it was important to provide information to our members and other providers regarding the new lower cost option so they could evaluate this option in consultation with their patients. Initially Turing agreed to reconsider the price increase and to lower it; however, on Nov. 24th Turing announced that they would not lower the list price of Daraprim but instead planned to offer discounts of up to 50% to some hospitals. [3] The announcement reinforced the urgent need for affordable treatment options and failed to address that a majority of the eight to twelve month treatment course occurs on an outpatient basis. (more…)
Annals Internal Medicine, Author Interviews, Diabetes, Pharmacology / 13.12.2015

MedicalResearch.com Interview with: Francesco Zaccardi, MD Diabetes Research Centre Leicester General Hospital, Leicester, United Kingdom Medical Research: What is the background for this study? Dr. Zaccardi: Nowadays there are different classes of drugs for the treatment of hyperglycaemia in patients with type 2 diabetes and, within the same class, multiple drugs are available.Glucagon-like peptide-1 receptors (GLP-1RAs) are a relatively new class of treatments that improve glucose control and reduce body weight, without an increased risk for hypoglycaemia. To date, however, no direct comparisons between once-weekly GLP-1RAs have been reported. In this view, the aim was to assess the comparative efficacy and safety profile of GLP-1RAs using a network meta-analysis, a methodology that allows the estimation of the comparative effectiveness of multiple treatments in the absence of direct evidence. Medical Research: What are the main findings? Dr. Zaccardi: There are several differences in the efficacy and safety profiles of once-weekly glucagon-like peptide-1 receptor agonists (GLP-1RAs). Some of these drugs evidenced a better glucose control or body weight reduction, while other had an increased risk of side effects, such as nausea. Compared to other once-weekly GLP-1RAs, dulaglutide 1.5mg, once weekly exenatide, and taspoglutide 20mg showed a greater reduction of HbA1c, fasting plasma glucose, and body weight. Marginal or no differences were found for blood pressure and blood lipid levels. While taspoglutide 20mg had the highest risk of nausea, the risk of hypoglycaemia among once-weekly GLP-1RAs was comparable. (more…)
Author Interviews, Flu - Influenza, Pharmacology, Pulmonary Disease / 09.12.2015

MedicalResearch.com Interview with: Dr. Irene Braithwaite Deputy Director Medical Research Institute of New Zealand Wellington NZ Medical Research: What is the background for this study? What are the main findings? Dr. Braithwaite: We know from animal models that the reduction of fever is associated with an increased risk of dying from influenza. We also know that some influenza viruses cannot replicate well in the human febrile range (38 to 40 Celsius). Yet, guidelines on the management of community acquired influenza infection in humans is to rest, maintain hydration and to take antipyretics such as paracetamol on the basis that this may help and is unlikely to cause harm. We undertook this study to see whether using regular paracetamol during influenza infection might be harmful, as it may allow the influenza virus to replicate more readily, and increase and/or prolong symptoms. To the best of our knowledge, this is the first randomised controlled trial comparing the effects of regular paracetamol (1gram four times daily for five days) versus placebo in human adults infected with influenza. We found that there was no difference in influenza viral loads, temperature or influenza symptoms between the regular paracetamol group and placebo group. (more…)
Author Interviews, Melanoma, Pharmacology / 07.12.2015

MedicalResearch.com Interview with: Jeff Legos Senior Vice President Global Program Head Novartis Oncology Medical Research: What is the background for this study? What are the main findings? Response: Melanoma is the most serious form of skin cancer, and in recent years, research has discovered that melanoma is a diverse disease. In metastatic melanoma, approximately half of all patients have a mutation in the BRAF gene, and genetic testing can identify whether BRAF mutations are present in a tumor. Identifying a mutation can help doctors determine the appropriate treatment to treat BRAF-positive melanoma. Since January 2014, the combination of Tafinlar + Mekinist has been approved for use in the US in patients with BRAF V600E/K mutation-positive unresectable or metastatic melanoma as detected by an FDA-approved test. The combination was initially approved based on Phase II data through the FDA’s Accelerated Approval program and reviewed under a priority review designation. The approval was contingent on the results of the Phase III COMBI-d study, which was designed to evaluate the clinical benefit of the combination in patients with unresectable or metastatic melanoma with a BRAF V600E/K mutation. The regular approval is based on survival data from two Phase III studies: COMBI-d and COMBI-v. These studies showed that Tafinlar + Mekinist demonstrated statistically significant overall survival (OS) and progression-free survival (PFS) compared with dabrafenib or vemurafenib, in patients with BRAF V600E/K mutation-positive unresectable or metastatic melanoma. In addition, combination use of Tafinlar + Mekinist in patients with unresectable or metastatic melanoma who have a BRAF V600 mutation is approved in the EU, Australia, Canada and additional countries. (more…)
Author Interviews, Lancet, Multiple Sclerosis, Pharmacology, UCLA / 07.12.2015

MedicalResearch.com Interview with: Professor Rhonda Voskuhl, M.D. Jack H. Skirball Chair in MS Research Director of the UCLA MS Program David Geffen School of Medicine University of California, Los Angeles Medical Research: What is the background for this study? What are the main findings? Dr. Voskuhl: It had been known for decades that relapses were reduced during pregnancy in women with Multiple Sclerosis (MS), psoriasis and rheumatoid arthritis. We viewed this as a major clue to help find new disease modifying treatments. Focusing on MS, we investigated treatment with estriol, an estrogen that is made by the fetus/placenta during pregnancy. Preclinical studies and a pilot clinical trial at UCLA showed good results leading to the current Phase 2 clinical trial at 16 sites across the U.S. It showed that treatment with estriol pills compared to placebo pills, each in combination with standard of care (glatirmar acetate) injections, reduced relapses by one third to one half over and above standard of care treatment. (more…)
ADHD, Author Interviews, BMJ, Pharmacology / 26.11.2015

MedicalResearch.com Interview with: Dr. Ole Jakob Storebø Region Zealand, Child and Adolescent Psychiatric Department, Roskilde Region Zealand Psychiatry Psychiatric Research Unit, Slagelse University of Southern Denmark Department of Psychology Faculty of Health Science, Odense Denmark Medical Research: What is the background for this study? What are the main findings? Dr. Storebø: Despite widespread use of methylphenidate for the treatment of children and adolescents with attention deficit hyperactivity disorder (ADHD), a comprehensive systematic review of its benefits and harms has not yet been conducted. Over the past 15 years, several reviews investigating the efficacy of methylphenidate for ADHD (with or without meta-analyses) have been published. Each of these reviews, however, has several shortcomings and these are described in detail in the review. The most important concerns are that none of these reviews are based on a pre-published protocol, and most assessed neither the risk of bias (systematic errors) of included trials nor adverse events. Moreover, none of these reviews considered the risk of random errors. Therefore, their interpretation of findings is unlikely to have taken into account the poor reporting of adverse events, the impact of combining data from small trial samples, or the impact of risk of bias on their analyses; information about adverse events is also missing from several RCTs. Because of this it is our opinion that these previous reviews might have overestimated the true treatment effect. We found that Methylphenidate may improve ADHD symptoms, general behaviour and quality of life in children and adolescents aged 18 years and younger with ADHD. We rated the evidence to be of very low quality and, as a result, we cannot be certain about the magnitude of the effects from the meta-analyses. The evidence is limited by serious risk of bias in the included trials, under-reporting of relevant outcome data, and a high level of statistical variation between the results. We found no evidence for serious adverse events, but a lot of non-serious adverse events. Most of these are well known but the number of adverse events might even be higher than the number we found due to underreporting of adverse events. We know very little about the long term effects or harms as most of the trials in our review did not measure outcomes beyond 6 months. The risk of rare, serious adverse events seem low over the short duration of follow-up of the trials that reported on harms, but in general there was inadequate reporting of adverse events in many trials. (more…)
Author Interviews, Pharmacology, Pulmonary Disease / 23.11.2015

MedicalResearch.com Interview with: Imre Noth, M.D. Professor of Medicine and Director of the Interstitial Lung Disease Programme The University of Chicago Medical Research: What is the background for this study? What are the main findings? Dr. Noth: In 2014, OFEV® (nintedanib) became one of the first FDA-approved drug treatments for idiopathic pulmonary fibrosis (IPF), a rare and serious lung disease that causes permanent scarring of the lungs. In this post-marketing surveillance study in the United States, treatment with OFEV in the real-world clinical setting showed a safety profile consistent with that observed in clinical trials supporting its approval by the FDA. Post-marketing surveillance of the safety and tolerability of OFEV in the United States has been collected in the Boehringer Ingelheim drug safety and reporting database since OFEV was first approved on October 15, 2014. Until May 31, 2015, 3,838 people were treated with OFEV for a length of time ranging from 14 to 265 days (on average 88 days).  The most frequently reported side effects were gastrointestinal in nature and included diarrhea, nausea, vomiting and decreased appetite. Diarrhea was the most frequently reported individual side effect, occurring at a similar frequency to that observed in the clinical trials supporting approval. No new safety concerns were identified. (more…)
Annals Internal Medicine, Asthma, Author Interviews, Pharmacology / 16.11.2015

MedicalResearch.com Interview with: Michael Miligkos, MD, MS Laboratory of Biomathematics, University of Thessaly School of Medicine Larissa, Greece Medical Research: What is the background for this study? What are the main findings? Dr. Miligkos: Asthma is one of the most common chronic diseases with and has considerable social and economic burdens. Although inhaled corticosteroids constitute the current gold standard of maintenance treatment, leukotriene-receptor antagonists (LTRAs) have the advantages of oral once- or twice- daily dosing and, apparent avoidance of the adverse effects associated with long-term corticosteroid therapy. In addition, their mechanisms of action theoretically predicts a good response in patients with specific asthma “phenotypes”. This systematic review investigated the use of all marketed LTRAs in usual licensed doses as asthma controller medications compared with placebo and found that administration of a LTRA to adults and adolescents with asthma significantly reduced the risk for an exacerbation. In trials of LTRA monotherapy, LTRAs significantly improved asthma control compared with placebo, whereas only some measures of asthma control were significantly improved in trials of LTRAs used as add-on use therapy to ICSs. (more…)
Author Interviews, Personalized Medicine, Pharmacology / 16.11.2015

MedicalResearch.com Interview with: Diane Frenier Esq Reed Smith Corporate Partner Member of Corporate & Securities Group and Life Sciences Health Industry Group Background: Diane Frenier Esq discusses the M&A boom in the pharmaceutical and retail drug industry including a the "global study of 100 senior executives at life sciences companies by global law firm Reed Smith, in partnership with Mergermarket, reveals that 94% are planning to make an acquisition in the next year”. Medical Research: What are the main drivers behind the pursuit of cross-border life sciences deals? Ms Frenier: I think companies are trying to strengthen their capabilities in areas that are a core focus for them (e.g., in certain therapeutic areas, or for orphan drugs), and that includes adding products in those core focus areas and, in some cases, broadening geographically so they can market products in those core focus areas on a more global basis.  This will allow them to use their resources more efficiently and take advantage of saving from reducing redundancies. (more…)
Author Interviews, Duke, JAMA, Pharmacology, Stroke / 10.11.2015

MedicalResearch.com Interview with: Ying Xian, PhD Assistant Professor of Medicine. Member in the Duke Clinical Research Institute Medical Research: What is the background for this study? What are the main findings? Dr. Xian: Intravenous tissue plasminogen activator (tPA) is the only FDA approved medical therapy to reduce disability and improve outcomes for patients with acute ischemic stroke. But treatment with tPA also carries the risk of symptomatic intracranial hemorrhage (sICH), which is often fatal. Nearly half of ischemic stroke patients are taking antiplatelet drugs such as aspirin and/or clopidogrel prior to stroke. We found these patients had higher risk for sICH when treated with tPA. But the risk is relatively small. For every 147 patients on aspirin treated with tPA, only 1 more symptomatic intracranial hemorrhage as compared with those treated with tPA without prior antiplatelet therapy. The risk is slightly higher among those on dual antiplatelet therapy of aspirin and clopidogrel (number needed to harm 60). Despite the higher bleeding risk, patients treated with tPA on prior antiplatelet therapy appeared to have better functional outcomes in terms of ambulatory status and modified Rankin scale than those not on prior antiplatelet therapy. Therefore, overall the benefits of thrombolytic therapy may outweigh the risks. (more…)
Author Interviews, Duke, Heart Disease, Pharmacology / 10.11.2015

MedicalResearch.com Interview with: Lauren Cooper, MD Fellow in Cardiovascular Diseases Duke University Medical Center Duke Clinical Research Institute Medical Research: What is the background for this study? What are the main findings? Dr. Cooper: Heart failure guidelines recommend routine monitoring of serum potassium and renal function in patients treated with a mineralocorticoid receptor antagonist (MRA). Specific monitoring recommendations include: within 2-3 days of initiation of the drug, again at 7 days, monthly for at least 3 months, then every 3 months thereafter. However, no large studies had evaluated compliance with these safety recommendations in routine clinical practice. Using Medicare claims data from 2011, we evaluated monitoring of serum creatinine and potassium levels among patients with heart failure initiated on an MRA. After MRA initiation, rates of guideline-recommended laboratory monitoring of creatinine and potassium were low. Of 10,443 Medicare beneficiaries included in this study, 91.6% received pre-initiation testing; however, only 13.3% received appropriate testing in the first 10 days after drug initiation and 29.9% received appropriate testing in the first 3 months. Only 7.2% of patients received guideline-recommended laboratory monitoring both before and after MRA initiation. Chronic kidney disease was associated with a greater likelihood of appropriate testing (relative risk, 1.83; 95% CI, 1.58-2.13), as was concomitant diuretic use (relative risk, 1.78; 95% CI, 1.44-2.21). (more…)
Author Interviews, Heart Disease, Pharmacology / 10.11.2015

Josep Rodés-Cabau, MD Director, Catheterization and Interventional Laboratories Quebec Heart and Lung Institute Professor, Faculty of Medicine, Laval University Quebec City, Quebec, CanadaMedicalResearch.com Interview with: Josep Rodés-Cabau, MD Director, Catheterization and Interventional Laboratories Quebec Heart and Lung Institute Professor, Faculty of Medicine, Laval University Quebec City, Quebec, Canada Medical Research: What is the background for this study? What are the main findings? Dr. Rodés-Cabau: The occurrence of new-onset migraine attacks has been reported in about 15% of patients following transcatheter atrial septal defect (ASD) closure. Prior observational studies suggested a reduction of migraine headache post-ASD closure with the use of clopidogrel on top of aspirin. Our study (the prospective randomized CANOA trial) showed that the use of clopidogrel (in addition to aspirin) following transcatheter ASD closure was associated with a significant reduction in the occurrence and number of new-onset migraine attacks within the 3 months following the procedure. Also, among patients with migraine attacks, those receiving clopidogrel therapy experience less-severe migraine attacks. (more…)
Author Interviews, Heart Disease, Kidney Disease, Pharmacology / 08.11.2015

MedicalResearch.com Interview with: Frederic T. (Josh) Billings IV, MD, Msc Assistant Professor of Anesthesiology and Critical Care Medicine Vanderbilt University Medical Center  Medical Research: What is the background for this study? What are the main findings? Dr. Billings: Acute kidney injury (AKI) following cardiac surgery is common (affects 20-30% of patients), and even mild forms of AKI are independently associated with a five-fold increase in death. Statins, commonly prescribed to reduce cholesterol concentrations and cardiovascular disease, affect several mechanisms underlying surgical AKI. Observational studies comparing rates of AKI between statin users and non-users have yielded inconsistent results and don’t assess the effect of statin use during the surgical period. In a double blind, placebo-controlled, randomized clinical trial of 653 cardiac surgery patients, we found that high-dose atorvastatin given prior to surgery, the day of surgery and daily postoperatively did not affect AKI. In fact, among statin-naïve patients with pre-existing kidney disease, rates of AKI were higher in those randomized to atorvastatin compared to those randomized to placebo. In patients who were using statins prior to the study, rates of AKI were similar between those randomized to atorvastatin and those randomized to placebo (short-term withdrawal), regardless of baseline kidney function. Safety markers of muscle and liver toxicity were not affected by statin treatment. (more…)