Author Interviews, Cost of Health Care, Emory, Infections, Pharmacology / 17.12.2015

[caption id="attachment_20151" align="alignleft" width="150"]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 Dr. Carlos del Rio[/caption] 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.
Annals Internal Medicine, Author Interviews, Diabetes, Pharmacology / 13.12.2015

[caption id="attachment_20071" align="alignleft" width="120"]Francesco Zaccardi, MD Diabetes Research Centre Leicester General Hospital, Leicester, United Kingdom Dr. Zaccardi[/caption] 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.
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.
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.
Author Interviews, Lancet, Multiple Sclerosis, Pharmacology, UCLA / 07.12.2015

[caption id="attachment_19869" align="alignleft" width="150"]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 Prof. Voskuhl[/caption] 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.
ADHD, Author Interviews, BMJ, Pharmacology / 26.11.2015

[caption id="attachment_19655" align="alignleft" width="160"]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 Dr. Storebø[/caption] 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.
Author Interviews, Pharmacology, Pulmonary Disease / 23.11.2015

[caption id="attachment_19554" align="alignleft" width="175"]Imre Noth, M.D. Professor of Medicine and Director of the Interstitial Lung Disease Programme The University of Chicago Imre Noth, M.D.[/caption] 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.
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.
Author Interviews, Personalized Medicine, Pharmacology / 16.11.2015

[caption id="attachment_19406" align="alignleft" width="85"]Diane Frenier Esq Reed Smith Corporate Partner Member of Corporate & Securities Group and Life Sciences Health Industry Group Diana Frenier[/caption] 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.
Author Interviews, Duke, JAMA, Pharmacology, Stroke / 10.11.2015

[caption id="attachment_19166" align="alignleft" width="137"]Ying Xian, PhD Assistant Professor of Medicine. Member in the Duke Clinical Research Institute Dr. Ying Xian[/caption] 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.
Author Interviews, Duke, Heart Disease, Pharmacology / 10.11.2015

[caption id="attachment_19231" align="alignleft" width="200"]Lauren Cooper, MD Fellow in Cardiovascular Diseases Duke University Medical Center Duke Clinical Research Institute Dr. Cooper[/caption] 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).
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.
Author Interviews, Heart Disease, Kidney Disease, Pharmacology / 08.11.2015

[caption id="attachment_19171" align="alignleft" width="158"]Frederic T. (Josh) Billings IV, MD, Msc Assistant Professor of Anesthesiology and Critical Care Medicine Vanderbilt University Medical Center Dr. Frederic T.Billings[/caption] 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.
Author Interviews, Cost of Health Care, JAMA, Pharmacology, Sloan Kettering / 04.11.2015

MedicalResearch.com Interview with: Dr. Elizabeth D. Kantor PhD MPH Assistant Attending Epidemiologist Memorial Sloan Kettering Cancer Center

Medical Research: What is the background for this study? What are the main findings? Dr. Kantor: We know that use of prescription drugs represents a major expenditure in the United States and research suggests that use of prescriptions has increased. However, much of what we know is derived from information on expenditures, is outdated, or is limited to certain populations, such as older adults or those with a given clinical condition. For example, a number of studies have looked at things like use of drugs used to control condition x among persons with condition x, but that doesn't tell us about use of that class of drugs in the population. It’s important that we continue to monitor use of prescription drugs in the population, as practice patterns are continually evolving as the population ages, the health needs of the population change, drugs enter/exit the market, scientific knowledge advances, and policies change. We therefore sought to create an updated comprehensive reference on prescription drug use among US adults using nationally representative data from the National Health And Nutrition Examination Survey, a continuous survey conducted by the Centers for Disease Control and Prevention. We examined trends in use of prescription drugs over 7 cycles, ranging from 1999-2000 to 2011-2012 (the sample size per cycle ranged from 4,861 to 6,212).Participants were asked about use of prescription medications over the prior 30 days, from which we were able to estimate the prevalence of use within each survey cycle. We then looked at trends in prescription drug use, both overall and within drug classes. In our study, we observed that use of any prescription medications increased over the study period, with 51% of adults reporting any prescription medication use in 1999-2000 and 59% reporting any use in 2011-2012. We also observed an increase in polypharmacy (or use of 5 or more prescription drugs) over the study period, with approximately 8% of adults reporting use of 5 or more drugs in 1999-2000, as compared to 15% in 2011-2012. Polypharmacy was much more common among older adults: 24% of adults ages 65 and older reported use of 5 or more drugs in 1999-2000 and 39% reported use of 5 or more drugs in 2011-2012. At first glance, one might take a look at these results and think that this is probably because the US population is aging and people tend to take more drugs as they age. But we found that the increase in overall prescription drug use and polypharmacy persisted even after accounting for the aging of the US population. This means that something else is driving the observed increase in use of prescription drugs. We also found that use of the majority of drug classes increased over the study period. For example, among commonly used drug classes, we observed marked increases in use of drugs taken to control high cholesterol, high blood pressure, and diabetes. We also observed marked increases in some less commonly used drug classes, such as muscle relaxants. Interestingly, if we look at the ten most commonly used drugs in 2011-2012, we can see that most are taken for conditions associated with cardiometabolic disease This raises the question of how much of this increase in prescription drug use may be attributable to overweight/obesity, as we know that the prevalence of obesity has increased among US adults.
Author Interviews, Brigham & Women's - Harvard, JAMA, McGill, Pharmacology / 04.11.2015

MedicalResearch.com Interview with: Tewodros Eguale, MD, PhD Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada Research Fellow in Medicine Brigham and Women's Hospital Medical Research: What is the background for this study? Dr. Eguale: Off-label prescribing is common and has been identified as a potentially important contributor to preventable adverse drug events (ADE). Significant deleterious effects were reported with off-label use of some drugs. Moreover, studies in children, where drugs are often used without sufficient scientific investigation, have shown that off-label uses increase the risk of ADE.  In adults, there has been no systematic investigation of the effects of off-label use in real world situation. The lack of knowledge is related to the methodological challenges of measuring off-label use and its effects; specifically the lack of link between prescribed drugs and their indication for use. The Medical Office of the XXI Century (MOXXI) electronic health record (EHR), developed by team of researchers at McGill University, facilitates the documentation of treatment indications, reasons for discontinuation of drug orders and adverse drug event. These new features provided the first opportunity to systematically monitor and evaluate off-label use and the occurrence of adverse drug events.  This study took advantage of the use of this new generation of software in a network of primary care practices to systematicaly evaluate the effect of off-label use on ADEs.
Antibiotic Resistance, Author Interviews, Dermatology, NYU/NYMC, Pharmacology / 30.10.2015

[caption id="attachment_18899" align="alignleft" width="185"]Arielle Nagler MD Instructor, Department of Ronald O. Perelman Department of Dermatology NYU Langone Medical Center Dr. Nagler[/caption] MedicalResearch.com Interview with: Arielle Nagler MD Instructor, Department of Ronald O. Perelman Department of Dermatology NYU Langone Medical Center Medical Research: What is the background for this study of acne patient who eventually require isotretinoin? Dr. Nagler: Isotretinoin is a highly effective medication for the treatment of severe acne. In fact, it is the only medication that has been shown to provide patients with a durable cure for acne. However, its use is limited by its known teratogenicity as well as controversies regarding its relationship with psychiatric disturbances and inflammatory bowel disease. For many patients, systemic antibiotics provide an effective treatment for inflammatory acne. However, antibiotics do not provide the long term clearance that isotretinoin provides. Moreover, antibiotics are getting increasing attention due to fears of emerging bacterial resistance. There has been a recent emphasis on limiting antibiotic use in acne. As a result, this study sought to understand antibiotic use patterns amongst patients who eventually received isotretinoin. 
Aging, Author Interviews, Cost of Health Care, Pharmacology / 26.10.2015

MedicalResearch.com Interview with: Sue Dong, DrPH Data Center Director CPWR-The Center for Construction Research and Training Silver Spring, MD, 20910 Medical Research: What is the background for this study? What are the main findings? Response: The Center for Construction Research and Training (CPWR) is a nonprofit organization funded by NIOSH and several other federal government agencies. The aging workforce study is part of our NIOSH projects. According to our surveillance data (using the Current Population Survey), more than 30% of US workers were baby boomers in 2014, and about 63% of those baby boomers were aged 55 and up. Overall, the baby boomer generation is composed of 75 million Americans who have reached or will soon reach their retirement years. Despite the impending magnitude of societal disruption, information on health status among baby boomers and the potential burden faced by this cohort is still scarce. We hope this study can provide some needed information on the aging population in the US. To address this concern, we used data from the Health and Retirement Study (HRS). HRS is a national longitudinal survey of Americans aged 50 and over, which started in 1992. The baby boomer cohort (including Early Baby Boomers and Mid Baby Boomers who were born between 1948 and 1959) was added to the survey in recent years. HRS collects information on demographics, employment, health, health expenditures, etc. The rich information and relatively consistent survey instruments used over time allowed us to conduct this study. Medical Research: What are the main findings? Response: We estimated medical conditions and expenditures among the baby boomer cohort and compared them with the original HRS cohort (born between 1931 and 1941). We found that the baby boomers were more likely to report chronic conditions than the previous generation (HRS cohort) at similar ages. For example, at age 51-61, about 70% of the baby boomer cohort had at least one chronic condition, while 60% of the HRS cohort had at least one chronic condition. By detailed condition, 42.2% of baby boomers had high blood pressure, compared to 32.1% of the HRS cohort; 14.4% of the baby boomers had diabetes, nearly twice the proportion for the HRS cohort (7.8%). Overall, baby boomers had higher prevalence of chronic conditions for the nine conditions we measured compared to the HRS cohort at the same age. We also found that the baby boomers were more likely to be overweight compared to the previous generation. The prevalence of obesity was 37% among baby boomers, but it was 21.9% among the HRS cohort when they were at similar ages In terms of medical expenditures, the average out-of-pocket expenditure (OOPE) for the past two years for those aged 51-61 was $2,156 for the HRS cohort, but $3,118 for the baby boomers. Dollar value was adjusted to 2012 dollars for even comparison. The findings will be presented at the recent APHA annual conference in Chicago.
Author Interviews, Bipolar Disorder, Kidney Disease, Lancet, Mental Health Research, Pharmacology / 24.10.2015

MedicalResearch.com Interview with: Dr. Stefan Clos MSc Applied Health Statistics Psychiatrist Murray Royal Hospital Scotland UK Medical Research: What is the background for this study? Dr. Clos: For more than 40 years there has been a debate about the long-term effect of lithium maintenance therapy on renal function. There is a lack of good quality data from randomized clinical trials and two previous meta-analyses from 2010 and 2012 suggest that little evidence exists for a clinically significant reduction in renal function in most patients who are on lithium therapy. However, the two publications point out the poor quality of available study data, emphasising the need for large scale epidemiological studies that control for confounders. Several population-based studies have since attempted to address this problem, but had insufficient ability to adjust for confounders or had limitations because of inappropriate cross-sectional study design or did not include an appropriate comparator group. 
Author Interviews, CDC, JAMA, Opiods, Pharmacology / 16.10.2015

MedicalResearch.com Interview with: Beth Han, MD, PhD, MPH Substance Abuse and Mental Health Services Administration U.S. Department of Health and Human Services Rockville, Maryland Medical Research: What is the background for this study? What are the main findings? Dr. Han: Since 1999, the United States has experienced increases in negative consequences and deaths associated with nonmedical use of prescription opioids. During this period, emergency department visits and drug overdose deaths involving these drugs have increased rapidly. To fully understand the current status of this public health crisis and who is currently most affected, we conducted this study based on nationally representative U.S. surveillance data. Our main study findings include:
  • Among adults age 18 through 64 years, the prevalence of nonmedical use of prescription opioids decreased from 5.4 percent in 2003 to 4.9 percent in 2013, but the prevalence of prescription opioid use disorders increased from 0.6 percent in 2003 to 0.9 percent in 2013. The 12-month prevalence of high-frequency use (200 days or more) also increased from 0.3 percent in 2003 to 0.4 percent in 2013.
  • Mortality assessed by drug overdose death rates involving prescription opioids increased from 4.5 per 100,000 in 2003 to 7.8 per 100,000 in 2013. The average number of days of nonmedical use of prescription opioids increased from 2.1 in 2003 to 2.6 in 2013. The prevalence of having prescription opioid use disorders among nonmedical users increased to 15.7 percent in 2010, 16.1 percent in 2011, 17 percent in 2012, and 16.9 percent in 2013, from 12.7 percent in 2003.
Allergies, Author Interviews, CDC, Pharmacology, Vaccine Studies / 07.10.2015

MedicalResearch.com Interview with: Michael M. McNeil, MD, MPH Centers for Disease Control and Prevention Atlanta, GA Medical Research: What is the background for this study? What are the main findings? Dr. McNeil : Anaphylaxis is an uncommon potentially life-threatening allergic reaction which can occur immediately (usually within minutes) after exposures to food, drugs, venom and vaccines. More than 100 million people in the U.S. receive vaccinations each year. Most vaccines have the potential to trigger anaphylaxis, but the rates at which it occurs after vaccination are not well known. The CDC study examined data from the Vaccine Safety Datalink (VSD), a collaborative project between CDC and 9 integrated healthcare organizations, which contains vaccination records on more than 9 million patients. The study sought to determine the rates of anaphylaxis after all vaccines combined and some individual vaccines including seasonal influenza vaccines given to children and adults.  Patients studied received vaccinations between January 1, 2009 – December 31, 2011.  Electronic medical record data was screened for patients with specific diagnostic codes for anaphylaxis or who had received epinephrine prescriptions as a treatment for potential anaphylaxis. Researchers were able to look at data from 25,173,965 vaccinations during 17,606,500 visits to healthcare providers. The researchers identified 33 confirmed vaccine-triggered anaphylaxis cases that occurred after more than 25 million vaccine doses. The rate of anaphylaxis was calculated at 1.31 per million doses for all vaccines, and 1.35 per million for seasonal inactivated influenza vaccines. Patients ranged in age from 4 to 65 with a median age of 17. None of the patients with anaphylaxis were below the age of 4 years old. Only one of the 33 patients was hospitalized, and none died as a result of anaphylaxis. A majority (85%) of the case-patients had pre-existing atopic disease including previous anaphylaxis, asthma, and allergies.
Author Interviews, Opiods, Pediatrics, Pharmacology / 29.09.2015

Shannon M. Monnat, PhD Assistant Professor of Rural Sociology, Demography, and Sociology Department of Agricultural Economics, Sociology, and Education The Pennsylvania State University University Park, PA 16802MedicalResearch.com Interview with: Shannon M. Monnat, PhD Assistant Professor of Rural Sociology, Demography, and Sociology Department of Agricultural Economics, Sociology, and Education The Pennsylvania State University University Park, PA 16802  Medical Research: What is the background for this study? What are the main findings? Dr. Monnat: Given concurrent rapid increases in opioid prescribing and adolescent prescription opioid misuse since the 1990s and historical problems with opioid abuse in rural areas, we were interested in whether adolescents in rural areas were more likely to abuse prescription opioids than their peers in urban areas. Adolescence is a really crucial time to study substance abuse disorders because most abuse begins during adolescence, and individuals who begin use before age 18 are more likely to develop a long-term disorder as an adult compared to those who first try a substance later in life. The active ingredient in prescription opioids and heroin is the same. Prescription opioids are highly addictive and can be dangerous if utilized incorrectly. Prescription opioid abuse is currently responsible for over 16,000 deaths in the US annually and has an estimated annual cost of nearly $56 billion dollars. Therefore, it is correctly viewed as a major public health problem. We found that teens living in rural areas are more likely to abuse prescription opioids compared to teens living in large urban areas. Several important factors increased rural teens’ risk of abusing prescription opioids, including that they are more likely to rely on emergency department treatment than their urban peers, they have less risky attitudes and perceptions about substance abuse than their urban peers, and they are less likely to be exposed to drug/alcohol prevention messages outside of the school environment than their urban peers. Rural teens are also buffered by several factors that help to reduce opioid abuse, including stronger religious beliefs, less depression, less peer substance abuse, and less access to illicit drugs. If not for these protective factors, the current epidemic we see in rural areas could be even worse. We also found that both rural and urban adolescents were most likely to report obtaining the prescriptions they abused from friends or family. However, rural adolescents were less likely than urban adolescents to obtain the pills this way. Rural adolescents were more likely than urban adolescents to report getting the pills they abuse directly from physicians. 
Author Interviews, Blood Pressure - Hypertension, Compliance, Pharmacology / 31.08.2015

Dr M Lobo PhD FRCP Director Barts BP Centre of Excellence Consultant Physician and Hon Senior Lecturer NIHR Barts Cardiovascular Biomedical Research Unit William Harvey Research Institute, London MedicalResearch.com Interview with: Dr M Lobo PhD FRCP Director Barts BP Centre of Excellence Consultant Physician and Hon Senior Lecturer NIHR Barts Cardiovascular Biomedical Research Unit William Harvey Research Institute, London Medical Research: What hypothesis did you set out to investigate and why? Dr. Lobo: We investigated the clinical utility of a novel treatment algorithm for multi-drug intolerant patients with hypertension who are at very high risk of cardiovascular disease due to uncontrolled blood pressure and inability to take conventional (guideline-based) antihypertensive regiments. These patients are often poorly managed by primary care physicians (or specialists such as cardiologists) because there has been little interest/research in medication intolerance. There has however been a major focus on drug non-adherence as a cause of failure to control hypertension - we believe that a key cause of non-adherence is medication intolerance which patients do not always volunteer. Medical Research: What is the report's ultimate take-away message? Dr. Lobo: Our novel stepwise algorithm was successful in managing uncontrolled hypertension in the majority of patients without needing an increase in their medicines burden. The message therefore is that patients who do not tolerate their antihypertensives do not have to put up with side effects and resultant poor quality of life as we have demonstrated that there are ways to get around medication intolerances.
Author Interviews, JAMA, Opiods, Pharmacology / 21.08.2015

Lainie Rutkow, JD, PhD, MPH Associate Professor Department of Health Policy and Management Johns Hopkins Bloomberg School of Public HealMedicalResearch.com Interview with: Lainie Rutkow, JD, PhD, MPH Associate Professor Department of Health Policy and Management Johns Hopkins Bloomberg School of Public Health  Medical Research: What is the background for this study? What are the main findings? Dr. Rutkow: Rates of prescription drug diversion and misuse, as well as overdose deaths, have increased throughout the United States. CDC estimates that each day, 44 people die from a prescription drug overdose. In the mid-2000s, Florida was viewed as the epicenter of this epidemic, with prescription drug overdose deaths increasing more than 80% from 2003 to 2009. In response, Florida enacted several laws to mitigate prescription drug abuse and diversion. Its pill mill law required pain management clinics to register with the state and prohibited physician dispensing of certain drugs. Florida’s Prescription Drug Monitoring Program (PDMP) collects data about dispensing of prescription drugs and can be accessed by physicians and pharmacists. Little is known about how these laws have affected prescribing of opioids. We applied comparative interrupted time series analyses to pharmacy claims data to examine four outcomes related to opioid prescribing in Florida, with Georgia as a comparison state. We found that in the first year of implementation, Florida’s Prescription Drug Monitoring Program and pill mill law were associated with modest reductions in prescription opioid volume, prescriptions written, and the dose per prescription. These declines were statistically significant among the highest volume prescribers and patients at baseline.
Author Interviews, Cost of Health Care, Infections, JAMA, Pharmacology / 19.08.2015

Jerome A. Leis, MD MSc FRCPC Division of Infectious Diseases, Sunnybrook Health Sciences Centre Physician Lead, Antimicrobial Stewardship Team Faculty Quality Improvement Advisor, Centre for QuIPS Assistant Professor, Department of Medicine, University of Toronto Sunnybrook Health Sciences Centre Toronto, OntarioMedicalResearch.com Interview with: Jerome A. Leis, MD MSc FRCPC Division of Infectious Diseases Sunnybrook Health Sciences Centre Physician Lead, Antimicrobial Stewardship Team Faculty Quality Improvement Advisor, Centre for QuIPS Assistant Professor, Department of Medicine University of Toronto Sunnybrook Health Sciences Centre Toronto, Ontario Medical Research: What is the background for this study? What are the main findings? Dr. Leis: We know that urinary tract infections are frequently diagnosed among general medicine patients who lack symptoms of this infection.  We wondered whether urinalysis ordering practices in the Emergency Department influence diagnosis and treatment for urinary tract infection among these asymptomatic patients.  We found that over half of patients admitted to the general medicine service underwent a urinalysis in the Emergency Department of which over 80% lacked a clinical indication for this test.  Urinalysis results among these asymptomatic patients did influence diagnosis as patients with incidental positive results were more likely to undergo urine cultures and treatment with antibiotics for urinary tract infection.  The study suggests that unnecessary urinalysis ordering contributes to over-diagnosis and treatment of urinary tract infection among patients admitted to general medicine service.
Author Interviews, Emergency Care, FDA, Opiods, Pharmacology / 15.07.2015

MedicalResearch.com Interview with: Christopher M. Jones, Pharm D., M.P.H Senior advisor, Office of Public Health Strategy and Analysis Office of the Commissioner, Food and Drug Administration Medical Research: What is the background for this study? Dr. Jones: Opioid analgesics and benzodiazepines are the two most common drug classes involved in prescription drug overdose deaths. In 2010, 75% of prescription drug overdose deaths involved opioid analgesics and 29% involved benzodiazepines. Opioid analgesics and benzodiazepines are also the most common drugs associated with emergency department visits due to nonmedical use of prescription drugs. Combined opioid and benzodiazepine use has been suggested as a risk factor for overdose death. Opioids and benzodiazepines have complex drug interactions and in combination can result in synergistic respiratory depression, but the exact mechanisms by which benzodiazepines worsen opioid-related respiratory depression are not fully understood. Widespread co-use of benzodiazepines and opioids has been documented in both chronic pain and addiction treatment settings. Studies suggest that among patients who receive long-term opioids for chronic non-cancer pain, 40% or more also use benzodiazepines. Among patients who abuse opioids, benzodiazepine abuse also is prevalent, and co-users report using benzodiazepines to enhance opioid intoxication. This study builds on the prior literature by analyzing trends on how the combined use of opioids and benzodiazepines in the U.S. contributes to the serious adverse outcomes of nonmedical use–related ED visits and drug overdose deaths. A better understanding of the consequences of co-use of these medications will help identify at-risk populations, inform prevention efforts, and improve the risk–benefit balance of these medications. Medical Research: What are the main findings? Dr. Jones: From 2004 to 2011, the rate of nonmedical use–related Emergency Department visits involving both opioid analgesics and benzodiazepines increased from 11.0 to 34.2 per 100,000 population. During the same period, drug overdose deaths involving both drugs increased from 0.6 to 1.7 per 100,000. Statistically significant increases in Emergency Department visits occurred among males and females, non-Hispanic whites, non-Hispanic blacks, and Hispanics, and all age groups except 12–17-year-olds. For overdose deaths, statistically significant increases were seen in males and female, all three race/ethnicity groups, and all age groups except 12–17-year-olds. Benzodiazepine involvement in opioid analgesic overdose deaths increased each year, increasing from 18% of opioid analgesic overdose deaths in 2004 to 31% in 2011.
Author Interviews, Cost of Health Care, OBGYNE, Pharmacology / 14.07.2015

Nora V. Becker MD/PhD candidate Department of Health Care Management and Economics Wharton School, University of Pennsylvania, in Philadelphia. MedicalResearch.com Interview with: Nora V. Becker MD/PhD candidate Department of Health Care Management and Economics Wharton School, University of Pennsylvania, in Philadelphia. Medical Research: What is the background for this study? What are the main findings? Response: The Affordable Care Act mandates that private health insurance plans cover prescription contraceptives with no consumer cost sharing. The positive financial impact of this new provision on consumers who purchase contraceptives could be substantial, but it has not yet been estimated. Using a large administrative claims data set from a national insurer, we estimated out-of-pocket spending before and after the mandate. We found that mean and median per prescription out-of-pocket expenses have decreased for almost all reversible contraceptive methods on the market. The average percentages of out-of-pocket spending for oral contraceptive pill prescriptions and intrauterine device (IUD) insertions by women using those methods both dropped by 20 percentage points after implementation of the ACA mandate. We estimated average out-of-pocket savings per contraceptive user to be $248 for the IUD and $255 annually for the oral contraceptive pill.
Author Interviews, Neurological Disorders, NYU/NYMC, Opiods, Pain Research, Pharmacology / 25.06.2015

Dr. Mia T. Minen, MD, MPH Director, Headache Services at NYU Langone Medical Center Assistant professor, Department of Neurology MedicalResearch.com Interview with: Dr. Mia T. Minen, MD, MPH Director, Headache Services NYU Langone Medical Center Assistant professor, Department of Neurology   Medical Research: What is the background for this study? What are the main findings? Dr. Minen: We conducted a survey on opioid and barbiturate use among patients visiting a headache center to find out which medications they were receiving for treatment. There’s limited evidence that long-term use of these medications can help treat headaches or migraines, and even short-term use in small quantities can cause medication overuse headache. It is important to determine which providers start these medications so that educational interventions can be tailored to these physician specialties to try to prevent situations such as incorrect prescribing practices and medication overuse. In this sample of patients from a specialty headache center, approximately 20 percent of patients -- or 1 in 5 -- were using opioids or barbiturates, and about half had been prescribed these medications at some point in the past for their headaches. These findings show that opioids and barbiturates are commonly prescribed to patients with headaches. While two-thirds of patients found opioids or barbiturates helpful, many did not like them, were limited by side effects or did not find them to be helpful. Emergency department physicians were reported to be the most frequent first prescribers of opioids and general neurologists were the most frequent prescribers of barbiturate-containing medications. Primary care physicians were also identified as frequent first prescribers of these medications.
Author Interviews, Erectile Dysfunction, JAMA, Melanoma, NYU/NYMC, Pharmacology / 24.06.2015

Dr. Stacy Loeb, MD, MScDepartment of Urology, Population Health, and Laura and Isaac Perlmutter Cancer CenterNew York University, New York MedicalResearch.com Interview with: Dr. Stacy Loeb, MD, MSc Department of Urology, Population Health, and Laura and Isaac Perlmutter Cancer Center New York University, New York Medical Research: What is the background for this study? Dr. Loeb: A paper published last year suggested a relationship between use of (Viagra) and melanoma.  That study had only 142 cases of melanoma, and of these men 14 had used sildenafil.  This study got a lot of publicity leading numerous patients to express concern over whether erectile dysfunction drugs could cause melanoma. Our goal was to look more closely at this issue in a larger population from Sweden (including 4065 melanoma cases of whom 435 used any type of erectile dysfunction drug- Viagra, as well as Levitra and Cialis).  Sweden has a national health system so we were able to access prescription records for men across the entire country, which we linked to the national registries for melanoma and basal cell skin cancer.  
Author Interviews, Depression, Diabetes, Heart Disease, Pharmacology, Women's Heart Health / 08.06.2015

Dr. Karin Rådholm MD Ph.D. Division of Community Medicine, Primary Care, Department of Medicine and Health Sciences, Faculty of Health Sciences, Linköping University, Department of Local Care West, County Council of Östergötland, Linköping, SwedenMedicalResearch.com Interview with Dr. Karin Rådholm MD Ph.D. student Division of Community Medicine, Primary Care, Department of Medicine and Health Sciences, Faculty of Health Sciences, Linköping University Department of Local Care West, County Council of Östergötland, Linköping, Sweden MedicalResearch: What is the background for this study? Dr. Rådholm: Psychosocial risk factors and depressive disorders often co-occur with general medical comorbidities, such as myocardial infarction. Depression is more common in patients with diabetes than in patients without diabetes. About 10-30% of patients with diabetes have a comorbid depressive disorder, which is double the estimated prevalence of depression in individuals without diabetes. There is an association between comorbid depressive symptoms and diabetes complications. This is believed to be mainly due to poor adherence to treatment recommendations and diabetes self-management activities, but could also possibly be due to biological and behavioural causes that could predispose for both metabolic and affective disorders. The general risk of myocardial infarction is strongly dependent on age and sex, where men have an earlier disease onset compared to women. In the general population women are at much lower risk for ischemic heart disease mortality than men are. However, women with diabetes are at especially high risk for coronary heart disease, relatively more so than men with type 2 diabetes, meaning that the impact of diabetes on the risk of coronary death is significantly greater for women than men. The age- and gender-specific risk for myocardial infarction due to diabetes with coexistent depression has not previously been described. Data on all dispensed drug prescriptions in Sweden are available in the Swedish Prescribed Drug Register and all myocardial infarctions are registered in the Myocardial Infarction Statistics. These registers are population-based and have a total national coverage and high validity, which has been previously shown. Prescribed and dispensed antidiabetics and antidepressants were used as markers of disease. Our objective was to prospectively explore the gender- and age-specific risk of first myocardial infarction in people treated with antidiabetic and/or antidepressant drugs compared to participants with no pharmaceutical treatment for diabetes or depression in a nationwide register study.