Addiction, Author Interviews, CDC, Opiods, Pain Research / 27.08.2016
Illicitly-Manufactured Fentanyl Contributing To Increasing Numbers of Heroin Deaths
MedicalResearch.com Interview with:
John Halpin, MD, MPH, Medical officer
Prescription Drug Overdose Epidemiology and Surveillance Team
CDC Injury Center
MedicalReseach.com editor’s note: Dr. Halpern discusses the CDC alert of August 25, 2016 regarding the increase in fentanyl-related unintentional overdose fatalities in multiple states.
MedicalResearch.com: What is the background for this alert?
Response: The current health alert is an update to a previous alert in October, 2015 from CDC which described the geographic spread of states in which forensic labs were increasingly detecting fentanyl in the drug submissions that they receive from law enforcement, and how many of these same states were beginning to report fentanyl-related overdose deaths by their departments of public health.
Further investigation by CDC and DEA have revealed that the great majority of fentanyl now present in the illicit drugs market is clandestinely-produced, and most commonly mixed with and sold as heroin, and is responsible for the great majority of fentanyl-related overdose deaths. Indications at the time of that alert pointed to a likely continuous rise in the supply of illicitly-manufactured fentanyl, and the potential for increasing numbers of fentanyl-related overdose deaths, particularly among those who use heroin.
Dr. Alan Fayaz[/caption]
Dr Alan Fayaz
MA MBBS MRCP FRCA FFPMRCA
Consultant in Anaesthesia and Pain Medicine
University College London Hospital NHS Foundation Trust
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Fayaz: Despite fairly well established negative consequences of chronic pain (social, psychological, biological) very little is known about the burden of chronic pain in the United Kingdom. For example healthcare costs relating to chronic pain in the USA outstrip those of Cancer and Cardiovascular disease, and yet the profile of chronic pain (as disease in its own right) is not nearly as well established as either of those conditions. Surprisingly, prior to our study, there was little consensus regarding the prevalence of chronic pain in the UK. The purpose of our review was to synthesise existing data on the prevalence of various chronic pain phenotypes, in the United Kingdom, in order to produce accurate and contemporary national estimates.
Dr. Gretchen Tietjen[/caption]
Dr. Gretchen Tietjen MD
Professor and Chair of Neurology
Director of UTMC Headache Treatment and Research Program
Director of the UTMC Stroke Program
MedicalResearch.com: What is the background for this study?
Dr. Tietjen : C-reactive protein (CRP) is a well-established biomarker of inflammation. Elevated levels of CRP predict future cardiovascular events, such as myocardial infarction (heart attack) and stroke. Evidence linking higher CRP levels with migraine is limited and results from large population-based studies are conflicting. The National Health and Nutrition Examination Survey (NHANES) data for children and adolescents linked elevated CRP to headache, particularly in girls, and the Women’s Health Study showed an association of CRP with migraine in women over 45 years of age. In the Reykjavik study, CRP levels in persons with migraine were similar to levels in those without migraine. The aim of our study was to examine the relationship of CRP and migraine in a large population-based sample of over 9,000 young adults (24 to 32 years old) from The National Longitudinal Study of Adolescent to Adult Health (Add Health).
Dr. Vincent Chung[/caption]
Dr Vincent Chung
Assistant Professor, Jockey Club School of Public Health and Primary Care
Associate Director (Education), Hong Kong Institute of Integrative Medicine
Registered Chinese Medicine Practitioner
The Chinese University of Hong Kong
MedicalResearch.com: What is the background for this study?
Response: Primary carpal tunnel syndrome (CTS) is one of the most common forms of peripheral entrapment neuropathy. It is a major cause of disability on the upper extremity incurring considerable limitation on daily activities among patients. Currently, there is no consensus on appropriate treatment for patients with chronic (≥6 months) mild to moderate symptoms [Archives of physical medicine and rehabilitation. 2014;95(12):2253-63].
Electroacupuncture is a common technique for managing pain and neuropathy in Chinese medicine. Current CTS treatment guidelines from the UK National Institute for Health and Care Excellence (NICE), American Academy of Orthopaedic Surgeons (AAOS) and the American College of Occupational and Environmental Medicine (ACOEM) made no specific recommendations for or against electroacupuncture.
Dr. Robert Levenson[/caption]
Robert W. Levenson, Ph.D.
Professor, Department of Psychology
Director, Institute of Personality
and Social Research (IPSR)
University of California
Berkeley, CA
MedicalResearch.com: What is the background for this study?
Dr. Levenson: This study comes from a 20-year longitudinal study of Bay Area married couples that we began in the late 1980s. The main purpose of the study was to understand the emotional qualities of successful marriages. Couples came to our laboratory every five years so that we could get a snapshot of the way they interacted with each. We also measured their psychological and physical health. This new paper connects the emotional behaviors we observed when couples discussed a problem in their marriage at the start of the study with the kinds of illnesses they developed over the ensuing decades.
Dr. Richard Mangano[/caption]
Richard M. Mangano, PhD
Chief Scientific Officer at Relmada Therapeutics
Dr. Mangano has extensive experience leading global R&D programs in both large and small pharmaceutical companies including positions in discovery and clinical research at Hoffmann-La Roche, Lederle Laboratories, Wyeth Research and Adolor Corporation. He served as acting Therapeutic Area Director for Neuroscience at Wyeth before joining Adolor as Vice President of Clinical Research and Development. Dr. Mangano’s expertise includes multiple IND/CTC submissions and NDA/MAA approvals in psychiatry, neurology and gastrointestinal therapeutic areas. Dr. Mangano is also an adjunct professor in the Department of Pharmacology and Physiology at the Drexel University School of Medicine. He lectures in the Drug Discovery and Development Program and in the Psychiatry Department’s Resident Training Program. He has authored 30 peer reviewed publications and over 120 abstracts and presentations. Dr. Mangano holds a B.S degree in Chemistry from Iona College and a PhD degree in Biochemistry from Fordham University. Prior to joining the pharmaceutical industry, he was a research faculty member of the Maryland Psychiatric Research Institute at the University of Maryland School of Medicine.
Dr. Mangano discusses the opioid addiction and the development of abuse-resistant medications.
MedicalResearch.com: What is the background for the development of abuse-resistant medications? How extensive is the problem of opioid addiction?
Dr. Mangano: Recognizing the growing incidence of opioid abuse, misuse, and overdose in the United States, pharmaceutical companies, with the guidance of the FDA, are developing products that can mitigate abuse, while recognizing the importance of maintaining the availability of opioid analgesics for the millions of patients in this country who suffer from pain.
Approximately two million people in the U.S. are addicted to opioids. The market for products that treat opioid dependence has grown significantly due to the rapidly escalating problem of prescription opioid misuse and abuse, a recent resurgence of heroin use, and the growing number of physicians treating opioid dependence.
One of our product candidates, REL-1028 (BuTab), is a proprietary formulation of buprenorphine designed to treat both opioid addiction and moderate to severe chronic pain. Although there is the potential for addiction to buprenorphine, the risk is lower because it is a “partial agonist” of the mu opioid receptor compared with “full agonist” opioids like heroin, morphine, oxycodone, and hydrocodone. As a result, products containing buprenorphine, such as BuTab, should have reduced risk of abuse and physical dependence and would be controlled in Schedule III of the Controlled Substances Act (as opposed to the more restrictive Schedule II). We are also considering a formulation that would include an opioid antagonist that would not interfere with analgesia when taken orally as prescribed but would block the action of buprenorphine if it were to be inhaled or injected.
Dr. Dominik Mischkowski[/caption]
Dominik Mischkowski, co-author of the study
Former Ph.D. student at Ohio State
Now at the National Institutes of Health
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Mischkowski: We tested in two double blind experiments whether the popular physical painkiller acetaminophen reduces empathy for the pain of other people. In the first experiment (N=80), participants completed measures of empathy (i.e., perceived pain and personal distress) while reading hypothetical about the physical and social mishaps of other people. We found that acetaminophen reduced empathy for pain in these scenarios. In Study 2 (N=114), we replicated and extending these findings, showing that acetaminophen also decreased empathy (i.e., perceived pain, personal distress, and empathic concern) for another study participant experiencing ostracism or painful noise blasts. Furthermore, noise unpleasantness accounted for the effect of acetaminophen on empathy for noise pain.
Dr. Hui-Lin Pan[/caption]
Hui-Lin Pan, MD, PhD
Helen T. Hawkins Distinguished Professor
and Deputy Division Head for Research
Division of Anesthesiology and Critical Care, Unit 110
The University of Texas MD Anderson Cancer Center
Houston, TX
MedicalResearch.com: What is the background for this study?
Dr. Hui-Lin Pan: Chronic nerve pain caused by damage to the peripheral nerve is a debilitating health problem and remains very difficult to treat. Sensory neurons in the spinal cord are normally inhibited by inhibitory neurotransmitters (GABA and glycine) to regulate transmission of painful information. A major feature of nerve injury-induced chronic pain is reduced spinal cord inhibition, resulting from diminished activity of a chloride transporter called KCC2. In this study, we investigated whether increasing KCC2 expression at the spinal level using a lentiviral vector can restore KCC2 activity, thereby reducing chronic nerve pain.
Dr. Martin[/caption]
MedicalResearch.com Interview with:
Dr. Vincent Martin, MD
Professor of Internal Medicine
University of Cincinnati College of Medicine
Cincinnati OH
Medical Research: What is the background for this study? What are the main findings?
Dr. Martin: Past studies have found that the perimenopause is associated with an increased prevalence of migraine headache, but there have been no studies to determine if the frequency of migraine attacks is increased during this time period. In our study we reported that high frequency headache (≥10 days per month with headache) was increased by 62% during perimenopause (irregular menstrual cycles) as compared to premenopause (regular menstrual cycles). We later divided the perimenopause into early and late stages. During the early perimenopause women experience irregular menstrual bleeding while during the late perimenopause women begin skipping menstrual periods for 2-11 months. Of the two stages the late perimenopause in particular had the greatest likelihood for high frequency headache increasing its risk by 86%. This could suggest that low estrogen and progesterone levels, which occur when menstrual periods are skipped, might account for the increased probability of headache attacks in women with migraine.
The common belief in the medical field is that migraine attacks improve in women during menopause. To the contrary we found that high frequency migraine increased by 76% during menopause compared to premenopause. This indicates that a subgroup of women with frequent headaches tend to worsen with menopause. The increased probability of high frequency headache appeared to be secondary to an increased intake of pain medications occurring during this time period, which could result in “rebound headaches”. Rebound headaches occur from overuse of pain medications.
Acupuncture Presure[/caption]
MedicalResearch.com Interview with:
Carolyn Ee, MBBS
Department of General Practice
University of Melbourne
Carlton, Victoria, Australia
Medical Research: What is the background for this study? What are the main findings?
Response: Hot flushes affect up to 90% of women during the menopause and beyond, and women are turning to complementary therapies. Our randomised sham-controlled trial found no difference between real and sham acupuncture (given with a blunt needle) for hot flushes, with both groups improving by around 40% at the end of treatment.
Prof. Guy Boeckxstaens[/caption]
MedicalResearch.com Interview with:
Daniel Steffens, Ph.D.
The George Institute for Global Health
The University of Sydney
Medical Research: What is the background for this study?
Dr. Steffens: Back pain is a leading cause of disease burden globally. At present, a variety of interventions, such as getting a 
Dr. LaRochelle[/caption]
MedicalResearch.com Interview with:
Marc R. Larochelle, MD, MPH
Assistant Professor of Medicine
Boston Medical Center
Boston, MA
Medical Research: What is the background for this study? What are the main findings?
Dr. Larochelle: More than 16 thousand people in the United States die from prescription opioid overdose each year. However, morbidity extends well beyond fatal overdose - nearly half a million emergency department visits each year are related to prescription opioid-related harms. Emergency department visits for misuse of opioids represent an opportunity to identify and intervene on opioid use disorders, particularly for patients who receive prescriptions for opioids to treat pain. We examined a cohort of nearly 3000 commercially insured individuals prescribed opioids for chronic pain who were treated for a nonfatal opioid overdose in an emergency department or inpatient setting. We were interested in examining rates of continued prescribing after the overdose and the association of that prescribing with risk of repeated overdose. We found that 91% of individuals received another prescription for opioids after the overdose. Those continuing to receive 