Author Interviews, Pediatrics, Pharmacology / 29.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23896" align="alignleft" width="145"]Jonathan Slaughter, MD, MPH Assistant Professor of Pediatrics Center for Perinatal Research Nationwide Children's Hospital/The Ohio State University Columbus, OH 43205 Dr. Jonathan Slaughter[/caption] 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.
Author Interviews, Diabetes, Pharmacology / 21.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23655" align="alignleft" width="148"]Pedro L. Herrera, PhD Professor Dept. Genetic Medicine & Development, room #F09.2770 Faculty of Medicine, University of Geneva Geneva, Switzerland Dr. Pedro Herrera[/caption] 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.
Author Interviews, Diabetes, Pharmacology / 12.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23375" align="alignleft" width="117"]Christopher Sorli, MD SUSTAIN 1 investigator and Chair of the Department of Diabetes, Endocrinology and Metabolism Billings Clinic, Billings, Montana Dr. Christopher Sorli[/caption] 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.
Author Interviews, Bone Density, Endocrinology, Hip Fractures, Pharmacology / 08.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23284" align="alignleft" width="151"]Bente Langdahl Professor, Consultant, PhD, DMSc Department of Endocrinology and Internal Medicine THG Aarhus University Hospital Aarhus Denmark Dr. Bente Langdahl[/caption] 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).
Author Interviews, NEJM, Pharmacology / 18.03.2016

MedicalResearch.com Interview with: [caption id="attachment_22771" align="alignleft" width="159"]Prof. Bruce Guthrie Primary Care Medicine and Honorary Consultant NHS Fife University of Dundee Dundee, Scotland Prof. Bruce Guthrie[/caption] 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.
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.
Author Interviews, Heart Disease, Lipids, Pharmacology, University of Pennsylvania / 03.03.2016

MedicalResearch.com Interview with: [caption id="attachment_22305" align="alignleft" width="111"]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 Dr. Richard Dunbar[/caption] 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 [caption id="attachment_22306" align="alignleft" width="90"]Dr. Harsh Goel WellSpan Academic Hospitalists Department of Medicine, York Hospital, PA Dr. Harsh Goel[/caption] 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.
Author Interviews, Diabetes, JAMA, Pharmacology / 01.03.2016

MedicalResearch.com Interview with: [caption id="attachment_22181" align="alignleft" width="200"]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 Dr. John Buse[/caption] 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.
Author Interviews, Heart Disease, NEJM, Pharmacology / 25.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22006" align="alignleft" width="120"]Professor Paul Myles MBBS, MPH, MD, FCARCSI, FANZCA, FRCA Director, Dept of Anaesthesia and Perioperative Medicine Alfred Hospital and Monash University, Melbourne, Australia Prof. Paul Myles[/caption] 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.
Author Interviews, Heart Disease, JAMA, Kidney Disease, Pharmacology / 24.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21970" align="alignleft" width="158"]Frederic T. Billings Dr. Frederic T.Billings[/caption] 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.
Annals Internal Medicine, Author Interviews, Emergency Care, Gout, Pharmacology / 23.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21670" align="alignleft" width="120"]Professor Timothy H Rainer MD MBBCh Director, Accident & Emergency Medicine Academic Unit The Chinese University of Hong Kong Prof. Timothy Rainer[/caption] 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.
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.
Author Interviews, Critical Care - Intensive Care - ICUs, Pharmacology / 17.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21673" align="alignleft" width="200"]Professor Chris Thiemermann Centre for Trauma Sciences Queen Mary University of London Prof. Chris Thiemermann[/caption] 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.
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
Author Interviews, Epilepsy, Lancet, Pharmacology / 15.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21621" align="alignleft" width="160"]Dr. Michael Privitera MD Professor of the Department of Neurology and director of the Epilepsy Center University of Cincinnati Neuroscience Institute Dr. Michael Privitera[/caption] 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.
Author Interviews, Heart Disease, Pharmacology / 12.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21364" align="alignleft" width="113"]Giuseppe Biondi-Zoccai MD Department of Medico-Surgical Sciences and Biotechnologies Sapienza University of Rome Corso della Repubblica Latina, Italy Dr. Biondi-Zoccai[/caption] 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.
Author Interviews, Cancer Research, Heart Disease, JAMA, Pharmacology / 06.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21344" align="alignleft" width="200"]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) Dr. Jonathan Douxfils[/caption] 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.
Author Interviews, BMJ, Mental Health Research, Pediatrics, Pharmacology / 29.01.2016

MedicalResearch.com Interview with: [caption id="attachment_21081" align="alignleft" width="92"]Tarang Sharma, PhD candidate Nordic Cochrane Centre, Rigshospitalet University of Copenhagen, Faculty of Health and Medical Sciences, Denmark Tarang Sharma[/caption] 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.
Author Interviews, BMJ, Cancer Research, Heart Disease, Pharmacology / 24.01.2016

More on Heart Disease on MedicalResearch.com [caption id="attachment_20895" align="alignleft" width="104"]Prof. Ian Wong Prof. Ian Wong[/caption] 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.

Asthma, Author Interviews, Lancet, Pharmacology / 20.01.2016

[caption id="attachment_19464" align="alignleft" width="133"]Professor of Pediatrics Hans Bisgaard, MD, DMSc Copenhagen Prospective Studies on Asthma in Childhood Herlev and Gentofte Hospital, University of Copenhagen, Denmark. Prof. Bisgaard[/caption] 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.
Author Interviews, Diabetes, JAMA, Mental Health Research, Pediatrics, Pharmacology / 20.01.2016

[caption id="attachment_20681" align="alignleft" width="210"]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, USA Medical Director, Recognition and Prevention (RAP) Program The Zucker Hillside Hospital, Department of Psychiatry Dr. Christoph Correll[/caption] 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.
Author Interviews, Brigham & Women's - Harvard, Pancreatic, Pharmacology, PLoS / 15.01.2016

More on Pancreatic Cancer on MedicalResearch.com [caption id="attachment_20661" align="alignleft" width="200"]Dai Fukumura, M.D., Ph.D. Edwin L. Steele Laboratory Department of Radiation Oncology Massachusetts General Hospital Harvard Medical School Dr. Dai Fukumura[/caption] 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.
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.
Author Interviews, Blood Clots, Endocrinology, Hormone Therapy, Pharmacology / 07.01.2016

[caption id="attachment_20473" align="alignleft" width="160"]Ida Martinelli MD, PhD A Bianchi Bonomi Hemophilia and Thrombosis Center Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan, Italy Dr. Martinelli[/caption] 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.
Author Interviews, BMJ, Brigham & Women's - Harvard, OBGYNE, Pharmacology / 07.01.2016

[caption id="attachment_20419" align="alignleft" width="100"]Brittany M. Charlton, ScD Instructor Boston Children's Hospital and Harvard Medical School Researcher, Harvard Chan School Department of Epidemiology Boston, MA 02115 Dr. Charlton[/caption] 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.
Author Interviews, Depression, OBGYNE, Pharmacology / 06.01.2016

[caption id="attachment_20443" align="alignleft" width="187"]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 Dr. Anick Bérard[/caption] 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.
Author Interviews, Pharmacology / 04.01.2016

[caption id="attachment_20424" align="alignleft" width="155"]Prof. Daniel F. Klessig Boyce Thompson Institute for Plant Research, Department of Plant Pathology and Plant-Microbe Biology Cornell University, Ithaca, New York Dr. Klessig[/caption] 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.
Author Interviews, Autism, Pediatrics, Pharmacology / 02.01.2016

[caption id="attachment_20374" align="alignleft" width="156"]Diane C. Chugani, PhD Director, Nemours Neuroscience Research Nemours—AI DuPont Hospital for Children Wilmington, DE 19803 Dr. Chugani[/caption] 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.
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.