Author Interviews, ENT, JAMA, Pain Research, Pediatrics, Surgical Research / 05.04.2019 Interview with: Gillian R. Diercks, MD, MPH Instructor in Otolaryngology, Harvard Medical School Department of Otolaryngology Massachusetts Eye and Ear Infirmary Boston, Massachusetts What is the background for this study? What are the main findings? Response: Pediatric tonsillectomy is a commonly performed procedure, representing the second most common ambulatory surgery performed on children in the United States, with over half a million children undergoing the surgery annually.  A major concern for surgeons, patients, and their families is the issue of postoperative pain control as pain can last up to 10-14 days after surgery, be quite severe, and result in readmission to the hospital or ED visits for medications and dehydration. In young children and children with sleep apnea we cannot safely administer narcotic pain medications at home.  This leaves limited options for pain control, including acetaminophen and ibuprofen.  However, there are concerns that ibuprofen could potentially increase bleeding risk after surgery because of its effects on platelet function in the blood.  At baseline, the risk of postoperative hemorrhage within the first two weeks after tonsillectomy is around 4.5%, with about 1-1.5% of children requiring a return to the operating room to control severe bleeding.  Our study set out to show that the risk of severe postoperative bleeding when ibuprofen is given for 9 days after tonsillectomy was not increased compared with the bleeding risk when acetaminophen was administered instead. Our study could not conclude that the risk of bleeding is no different when ibuprofen is used, and was suggestive that the bleeding risk may actually be higher. (more…)
Author Interviews, Inflammation, JAMA, Kidney Disease, Pain Research, Stanford / 16.02.2019 Interview with: Alan Nelson, MPAS, PhD Division of Primary Care and Population Health, Department of Medicine Stanford University School of Medicine Stanford, California What is the background for this study?   Response: The past research literature has provided relatively little information on the appropriate level of concern regarding non-steroidal anti-inflammatory drugs (NSAIDs) and kidney disease risk among younger, apparently healthy patients. Clinicians are generally most concerned about the effects of these medications on the kidneys among patients with existing renal impairment and persons at risk for it, especially older patients. Given that NSAID use appears to be high and rising in the US, we were interested in developing evidence on this topic in a population of working-age adults. (more…)
Author Interviews, C. difficile, Microbiome, Pain Research / 09.01.2019 Interview with: David M. Aronoff, MD, FIDSA, FAAM Professor & Addison B. Scoville Jr. Chair in Medicine Director, Division of Infectious Diseases Department of Medicine Vanderbilt University Medical Center What is the background for this study? Response: Clostridium difficile infection (CDI) is a major cause of antibiotic-associated colitis and diarrhea and a leading cause of hospital-acquired infection. It is caused by the toxin-producing, anaerobic, spore-forming bacterium Clostridium difficile. Antibiotic use is a major risk factor for CDI but epidemiological studies suggest that other factors, some modifiable, some not, can also increase the risk for CDI. Older age is an example of a non-modifiable risk factor for CDI. Some epidemiological studies suggested that taking the prostaglandin synthesis inhibiting drugs called non-steroidal anti-inflammatory drugs (NSAIDs) might also increase the risk for CDI. NSAIDs include medications such as ibuprofen, naproxen, indomethacin, and others. Because NSAID use is so common, if it is a risk factor for the acquisition of, or severity of, CDI, that would be important because that would be a modifiable risk factor. We therefore sought to determine the impact of NSAID exposure on CDI severity in a mouse model of antibiotic-associated CDI. We also sought evidence for possible mechanisms whereby NSAIDs might increase the risk for CDI. (more…)
Author Interviews, Infections, Pain Research, PLoS, Urinary Tract Infections / 17.05.2018 Interview with: Ingvild Vik MD Doctoral Research Fellow Department of General Practice Institute of Health and Society - UiO University of Oslo, Norway What is the background for this study? Response: Uncomplicated urinary tract infection (UTI) is the most common bacterial infection in women. It is painful and troublesome, and even though it is often self-limiting most women who see a doctor will be prescribed an antibiotic, as antibiotics provide quick symptom relief.  Antibiotic resistance is a growing, serious public health problem. Antibiotic use is the main contributor to antibiotic resistance, and to stop the rapid development it is crucial that we reduce unnecessary use of antibiotics. Antibiotics can cause unpleasant and potentially severe side effects, so avoiding unnecessary use is also beneficial for the individual patient. A small German trial published in 2010 by Bleidorn et al. suggested that ibuprofen was non-inferior to the antibiotic ciprofloxacin in achieving symptomatic cure in uncomplicated UTI. This inspired us to conduct a larger trial to compare the anti-inflammatory drug ibuprofen to antibiotics in the treatment of uncomplicated UTI.  (more…)
Author Interviews, Dental Research, Pain Research, University of Pittsburgh / 03.05.2018 Interview with: “Dental Exam” by 807th Medical Command (Deployment Support) is licensed under CC BY 2.0Paul A. Moore, DMD, PhD, MPH School of Dental Medicine University of Pittsburgh What is the background for this study? What are the main findings? Response: Effective pain management is a priority in dental practice. Government and private agencies highlight the need to provide optimal pain relief, balancing potential benefits and harms of both opioid and nonopioid analgesic agents. The purpose of our study is to summarize the available evidence on the benefits and harms of analgesic agents, focusing on preexisting systematic reviews. We found combinations of ibuprofen and acetaminophen as having the highest association with treatment benefit in adult patients and the highest proportion of adult patients who experienced maximum pain relief. Diflunisal, acetaminophen, and oxycodone were found to have the longest duration of action in adult patients. Medication and medication combinations that included opioids were among those associated most frequently with acute adverse events in both child and adult-aged patient populations. (more…)
Author Interviews, Orthopedics, Pain Research, Rheumatology / 02.05.2018 Interview with: “dog” by Neil Mullins is licensed under CC BY 2.0Deborah S. Cummins, PhD Director, Research, Quality and Scientific Affairs American Academy of Orthopaedic Surgeons On behalf of the researchers: David Jevsevar, MD, MBA; Gregory A. Brown, MD, PHD, and Deborah S. Cummins, PhD What is the background for this study? What are the main findings? Response: It is estimated that individuals have a 45% risk of developing knee osteoarthritis (OA) in their lifetime. As a result of the shifting demographics of the US, where an increasing percentage of the population is older than 65, the burden of knee OA will continue to increase. To help deal with this burden, effective nonsurgical treatments are needed to manage knee OA symptoms associated with pain and function before surgical intervention becomes necessary. To determine which non-surgical options are best, we performed a network meta-analysis exploring mixed treatment comparisons for nonsurgical treatment of knee osteoarthritis in order to effectively rank the various nonsurgical treatment options from best to worst. Our network meta-analysis suggests that the single most effective nonsurgical treatment for improving knee function is function is naproxen, followed by diclofenac, celecoxib, and ibuprofen. When considering pain and function together, our data suggest that naproxen is the most effective treatment followed by IA corticosteroid injection. The single most effective short-term (4-6 weeks) treatment for decreasing pain is intra-articular (IA) corticosteroid injection, followed by ibuprofen, IA platelet rich plasma, and naproxen. Additionally, intra-articular hyaluronic acid injections never achieved a rank in the top five treatments for pain, function, or combined pain and function. An analysis of 12 articles also found that HA is not significantly different than IA placebo in effect. (more…)
Author Interviews, Pharmacology / 26.01.2018 Interview with: “#Headache situation #ibuprofen” by Khairil Zhafri is licensed under CC BY 2.0David Kaufman, ScD Director, Slone Epidemiology Center, Boston Universit Professor of Epidemiolog Boston University School of Public Health What is the background for this study?   Response: Ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most-used medicines in the US, but, if too much is taken, can cause harm. This was an internet-based diary study.  1326 individuals who reported taking an ibuprofen medication in the preceding month completed a daily diary of their NSAID use for one week.  The daily dosage ingested was computed from the diary, which allowed us to determine whether a user exceed the recommended daily maximum dose. (more…)
Author Interviews, Heart Disease, Pharmacology / 20.03.2017 Interview with: Kathrine Bach Søndergaard MD, Research Fellow Gentofte University Hospital Department of Cardiology Hellerup What is the background for this study? Response: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used and have in previous studies been associated with an increased risk of cardiovascular adverse events, such as myocardial infarction and heart failure. Cardiac arrest is the ultimate adverse event; however, no research exists of the association between cardiac arrest and use of NSAIDs, which we aimed to assess in this study. (more…)
Author Interviews, BMJ, Pain Research, Pharmacology / 07.02.2017 Interview with: Dr. Gustavo Machado BPhty (Hons) Cert.MDT The George Institute for Global Health Sydney Medical School, University of Sydney Sydney, New South Wales, Australia What is the background for this study? What are the main findings? Response: People with back pain are usually told by their health care practitioners to take analgesic medications to relieve their pain. But our previous research published in the BMJ showed that paracetamol does not have a measurable impact on patient’s symptoms. This resulted in recent changes in guidelines' recommendations. The 2017 National Institute for Health and Care Excellence (NICE) guidelines/UK no longer recommend paracetamol as a stand-alone intervention for back pain. So now non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as the analgesic of first choice. However, our results show that compared to placebo, commonly used NSAIDs, such as Ibuprofen (e.g. Nurofen) and Diclofenac (e.g. Voltaren), provide only small benefits for people with back pain while increasing the risk of gastrointestinal adverse effects by 2.5 times. (more…)
Author Interviews, JAMA, Kidney Disease, Pediatrics / 05.01.2017 Interview with: Jonathan Slaughter, MD, MPH Assistant Professor of Pediatrics Center for Perinatal Research Nationwide Children's Hospital/The Ohio State University Columbus, OH 43205 What are the main findings? Response: The ductus arteriosus, a fetal blood vessel that limits blood flow through the lungs, normally closes shortly after birth. However, the ductus often remains open in premature infants, leading to patent ductus arteriosus (PDA). Infants with PDA are more likely to die or develop bronchopulmonary dysplasia (BPD), the major chronic lung disease of preterm infants. Nonsteroidal Anti-inflammatory Drug (NSAID) treatment has been shown to close PDAs in preterm infants and NSAID treatment of PDA is common. However, it has never been shown that PDA closure with NSAIDs leads to decreased mortality or improved long-term respiratory outcomes. NSAID closure of PDA has become increasingly controversial in recent years since NSAID treatment has been associated with acute renal injury. Also, these medications are expensive, with the usual three-dose treatment course costing well over $1000 per patient. Due to these controversies, the likelihood of a preterm infant with PDA being treated with NSAIDs varies by clinician and institution and has decreased over time. Meta-analyses of randomized trials that investigated NSAID (indomethacin and/or ibuprofen) treatment for PDA closure in preterm infants did not show a benefit. However, they were principally designed only to study whether the ductus itself closed following treatment and not to determine if there was an improvement in mortality risk or in respiratory outcomes following NSAID treatment. Given the difficulty of conducting randomized trials in preterm infants and the urgent need for practicing clinician's to know whether treatment of PDA in all preterm infants is beneficial, we used a study design that incorporated the naturally occurring practice variation in NSAID treatment for PDA as a mechanism to reduce the risk of biases that are commonly found in non-randomized investigations. This is based on the premise that if NSAID treatment for PDA in preterm infants is truly effective, we should expect to see improved mortality and respiratory outcomes in instances when clinician preference-based NSAID administration rates are higher. (more…)
Author Interviews, Cancer Research, JNCI / 20.12.2016 Interview with: Theodore Brasky, PhD The Ohio State University Comprehensive Cancer Center What is the background for this study? What are the main findings? Response: There is a significant amount of data to suggest that long-term, regular use of nonsteroidal anti-inflammatory drugs (NSAIDS; examples include aspirin and ibuprofen) are associated with reduced risks of several cancers. Although the data across studies are inconsistent, one such candidate is endometrial cancer, which is the most common gynecologic cancer. There is good evidence that the use of these medications is associated with improved prognosis among patients diagnosed with colon cancer. Despite the importance of inflammation in endometrial cancer progression, very few have examined whether use of NSAIDs is associated with risk of death or recurrence from the disease. The study we published is the first of its kind to examine NSAID use comprehensively and in a study of over 4,000 patients. (more…)
Author Interviews, FASEB, Heart Disease, Imperial College, Pain Research, Pharmacology / 17.10.2016 Interview with: Dr Nicholas Kirkby BHF Intermediate Fellow | Vascular Biology National Heart & Lung Institute | Imperial College London London What is the background for this study? What are the main findings? Response: We know drugs like ibuprofen, called ‘non-steroidal anti-inflammatory drugs’ cause an increase in the risk of heart attacks. These side effects cause very real concerns for the many millions of people who rely on them. They are also the reason why there are no new drugs in this class and why they have been withdrawn (2011) for use as a preventative treatment for colon cancer. Previous research from our group suggests that L-arginine supplements may prevent the cardiovascular side effects caused by these drugs. Our findings here suggest that a particular formulations of ibuprofen, called ibuprofen arginate, which is already available in many parts of the world, can act like an L-arginine supplement and that this could potentially protect the cardiovascular system. (more…)
Author Interviews, Cancer Research, Dermatology / 06.10.2015

Nirmala Pandeya, PhD Post Doctoral Research Fellow Faculty of Medicine and Biomedical Sciences, School of Public Health Herston campus The University of Interview with: Nirmala Pandeya, PhD Post Doctoral Research Fellow Faculty of Medicine and Biomedical Sciences, School of Public Health Herston campus The University of Queensland Medical Research: What is the background for this study? Dr. Pandeya: Basal cell carcinoma (BCC) is the most common cancer. Although BCC is curable and has low mortality, its high occurrence in the population causes significant healthcare and financial burdens to the community. Hence exploring preventive strategies for this cancer is important in reducing the burden. To date few chemopreventives for BCC have been identified. In many cancer cells, inflammatory biomarkers such as cyclooxygenase-2 (COX-2) and its product prostaglandin E2 are increased and basal cell carcinoma is no exception. Anti-inflammatory drugs, suppressing COX-2 activity, have been shown to reduce the risk of various cancers including squamous cell carcinoma of the skin, so they also have a potential to prevent BCC. But to date research evidence on the benefit of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) on basal cell carcinoma has been inconsistent. So we reviewed and synthesized all published epidemiological studies on NSAIDs and BCC to combine results and estimate the overall pooled effect. Medical Research: What are the main findings? Dr. Pandeya: After thorough evaluation, we identified eleven studies that were relevant and pooling showed a 10% reduction in risk of BCC among those using any kind of NSAIDs. Aspirin and non-aspirin NSAIDs analysed separately suggested a reduced risk of basal cell carcinoma, but were not statistically significant likely due to lack of power. Our research found strongest risk reduction of BCC by the use of NSAIDs among those with either a history of skin cancers or high prevalence of actinic keratosis. (more…)
Author Interviews, Pain Research / 07.08.2015 Interview with: Jane Marjoribanks Obstetrics and Gynaecology University of Auckland, National Women's Hospital, Auckland, New Zealand MedicalResearch: What is the background for this study? Response: This study is a systematic review of all randomised evidence published up to January 2015 on the effectiveness and safety of non-steroidal inflamatory drugs (NSAIDs) used to treat primary dysmenorrhoea (period pain). It includes 80 randomised controlled trials (total 5820 participants), which compare 20 different NSAIDs versus placebo, other NSAIDs or paracetamol. The review was prepared by researchers from the Cochrane Collaboration, which is a global independent network of contributors (37,000 from more than 130 countries) who gather and summarize the best evidence from research to produce credible, accessible health information that is free from commercial sponsorship and other conflicts of interest. (more…)
Author Interviews, BMJ, Clots - Coagulation / 17.07.2015 Interview with: Byung-Joo Park, MD, MPH, PhD Professor Department of Preventive Medicine Seoul National University College of Medicine Medical Research: What is the background for this study? What are the main findings? Response: Antidepressants and NSAIDs are each thought to increase the risk of abnormal bleeding.  However, previous studies found neither antidepressants nor NSAIDs alone to be associated with an increased risk of intracranial haemorrhage.  Our research found that combined use of NSADIs in antidepressant users showed the increased relative risk of intracranial haemorrhage risk within the initial 30-days of combined use. (more…)
Author Interviews, Cancer Research, Nature / 19.12.2014

Dr Catherine Olsen  |  Senior Research Officer QIMR Berghofer Medical Research Institute Royal Brisbane Hospital, QLD Interview with: Dr Catherine Olsen  |  Senior Research Officer QIMR Berghofer Medical Research Institute Royal Brisbane Hospital, QLD 4029 Medical Research: What is the background for this study? What are the main findings? Response: Squamous cell carcinomas (SCCs)are the second most common skin cancer occurring in white skinned populations. They cause significant morbidity as they can invade local structures (often the nose or ears) and they also have the potential to metastasize although most are successfully treated before any spread occurs. They are also very expensive cancers to treat because they are so common, posing a significant burden on health care budgets. NSAIDS have been shown to be protective for other cancers (e.g. colorectal and oesophageal cancer). This prompted use to evaluate all of the available evidence on NSAIDs use and SCC by conducting a systematic review and meta-analysis of the association. (more…)
Author Interviews, Heart Disease, Imperial College, JACC / 13.12.2014 Interview with: Dr. Jane A. Mitchell National Heart and Lung Institute Imperial College, London, UK Medical Research: What is the background for this study? What are the main findings? Dr. Mitchell: Anti-inflammatory drugs (NSAIDs) work by inhibiting the enzyme COX-2. COX-2 selective anti-inflammatory drugs, like Vioxx, were introduced to reduce gastrointestinal side effects associated with these drugs. However, COX-2 inhibitors as well as most older NSAIDs are associated with increased risk of heart attacks although the precise mechanisms underlying these side effects are not completely understood. The main findings of this study are: 1) COX-2 is highly expressed in the kidney where its genetic deletion leads to changes in more than 1000 genes. 2) Analysis of these genes revealed changes in 2-3 specific genes that regulate levels of ADMA, an endogenous inhibitor of the nitric oxide released by vessels, that can be reversed by giving more of the substrate for NO, L-arginine. 3) Further studies showed that ADMA was indeed increased in the plasma of mice where COX-2 gene was knocked out or in normal mice given a COX-2 inhibitor. 4) In mice where COX-2 was knocked out the release of nitric oxide from vessels was reduced and this could be reversed by supply L-arginine. 5) ADMA was also increased in human volunteers taking a COX-2 inhibitor (more…)
AHA Journals, Author Interviews, Global Health, Heart Disease / 10.07.2014

Anthony Bavry, MD MPH Interventional Cardiology, North Florida/South Georgia Veterans Health System Associate Professor of Medicine, University of Florida Gainesville, FL Interview with: Anthony Bavry, MD MPH Interventional Cardiology, North Florida/South Georgia Veterans Health System Associate Professor of Medicine, University of Florida Gainesville, FL 32610 Medical Research: What are the main findings of the study? Dr. Bavry: 1) Among post-menopausal women, the regular use of NSAIDs was associated with an increased risk of cardiovascular death, myocardial infarction, or stroke. 2) Cardiovascular risk was observed among users of celecoxib, naproxen, but not ibuprofen. (more…)
Author Interviews, CMAJ, OBGYNE / 10.02.2014 Interview with: Dr. Sharon Daniel MD, MPH Physician, Intern in pediatrics at Soroka Medical Center, Beer-Sheva, Israel PhD Candidate and Prof. Amalia Levy (MPH, PhD Epidemiologist, Head of the Department of Public Health Principle Investigator. Ben-Gurion University of the Negev in Beer-Sheva, Israel, What are the main findings of the study? Answer: We tested the risk for miscarriage following the use of NSAIDs (ibuprofen, diclofenac, naproxen, indomethacin, etodolac) on the first trimester of pregnancy. We did not find increased risk among women who took those drugs during the first trimester of pregnancy, although we did find increased risk after the use of indomethacin. We found higher risk after the use of specific NSAIDs (Celecoxib, Rofecoxib, Etoricoxib) which are usually used to treat inflammatory diseases, only the exposure group was very small. (more…)