MedicalResearch.com Interview with:
Alexander Egeberg, MD
Department of Cardiology
Herlev and Gentofte Hospital
Hellerup, Denmark
Medical Research: What is the background for this study? What are the main findings?
Dr. Egeberg: Psoriasis is a common chronic skin disease, with a strong inflammatory component. Within the last decade, our understanding of psoriasis have advanced significantly, and psoriasis is now widely regarded as a systemic disease, where the skin is a direct marker of disease activity. The inflammatory pathways in psoriasis have also been implicated in several central nervous system diseases such as depression, uveitis, and multiple sclerosis. Moreover, pain generation and sensitization can occur as a result of the pro-inflammatory mediators which are upregulated in psoriasis.
In the present study, we investigated the association between psoriasis and psoriatic arthritis, and the risk of new-onset migraine. The main finding was a psoriasis-severity dependent increased risk of new-onset migraine, and patients with severe skin psoriasis, and psoriatic arthritis appeared to have the highest risk.
MedicalResearch.com Interview with:
Prof. Dr. Holger Lode
Clinical Immunology, Pediatrics
University of Greifswald, Greifswald
Medical Research: What is the background for this study?
Response: Neuroblastoma is a cancer in childhood with one of the highest death rates. Standard treatment is already very intensive. It includes chemotherapy, surgery, radiation, high dose chemotherapy followed by autologous stem cell transplantation. However, the progress made in improving survival rates is still poor.
The use of an immune-modulatory treatment with a neuroblastoma specific monoclonal antibody ch14.18 (100 mg/m2 /cycle) in combination with cytokines and 13cis retinoic acid (13 cis RA) has shown benefit for patients with this disease [1]. This antibody targets ganglioside GD2 abundantly expressed on neuroblastoma with limited to no expression on healthy tissue. Low expression of GD2 on pain fibers is associated with an on-target side effect of the treatment, which is the induction of neuropathic pain. Approval of ch14.18 (dinutuximab) for the treatment of children with neuroblastoma has been provided by FDA.
In Europe, ch14.18 was not available for a long time. There were several reasons why the antibody in the US could not be given to children in Europe. Therefore a new development of this side of the Atlantic was initiated following the remanufacturing of the antibody in CHO cells [2] (dinutuximab beta) and was made available within clinical trials of the SIOPEN group. The SIOPEN group is a network of leading European pediatric oncology centers to improve outcome for children with neuroblastoma (http://www.siopen.org), similar to the COG (children`s oncology group in the USA; https://www.childrensoncologygroup.org).
Following the recloning procedure, ch14.18/CHO was first evaluated for safety in a Phase I study [3], which confirmed the tolerability and showed activity at a dosing regimen of 20 mg/m2 given by 8 hour infusions on 5 consecutive days. Dinutuximab beta is further developed by Apeiron Biologics.
The current way to apply 100 mg /m2 / cycle is by 4 short term infusions of 25 mg/m2/day each over 8 hrs on 4 consecutive days. The entire treatment consists of 5 cycles. The drawback is that STI is associated with a high amount of intravenous morphine required to make this treatment tolerable for patients. Also the rate of inflammatory side effects observed is substantial.
Clinical observation indicates that if patients treated by STI suffer from pain despite analgesic treatments, a decrease in speed of antibody infusion improves this on target toxicity. Therefore, we hypothesized that significant prolongation of the time of antibody infusion will improve tolerability of that treatment, but at the same time maintains clinical activity and efficacy in high risk neuroblastoma patients.
MedicalResearch.com Interview with:
Monika Goyal, MD
Pediatric emergency medicine
Children’s National Hospital
Washington, DC
Medical Research: What is the background for this study? What are the main findings?
Dr. Goyal: Appendicitis is a painful surgical condition and adequate analgesia, particularly with opioids, are considered one of the mainstays of management. We found that almost half of all children diagnosed with appendicitis did not receive any analgesia. Furthermore, among the patients that did receive analgesia, there were marked racial differences with black children having lower rates of opioid medication receipt than white children, even after we took pain scores or acuity level into account.
MedicalResearch.com Interview with:
Lynn Webster, M.D.
Vice President of Scientific Affairs
PRA Health Sciences
(lead study investigator, and former President of the American Academy of Pain Medicine)
Medical Research: What is the background for this study? What are the main advantages of the buccal film?
Dr. Webster: Because of its partial agonist activity and high affinity for mu-opioid receptors, buprenorphine has the potential to precipitate withdrawal in patients who are already on mu-opioid full agonists. As a result, the current practice is to taper patients who are on around-the-clock (ATC) opioid therapy to a morphine sulfate equivalent (MSE) dose before switching to buprenorphine. But tapering can result in a loss of pain control for patients. For this study, we wanted to determine if patients on around-the-clock opioid full agonist therapy could be safely transitioned to buprenorphine HCl buccal film – an opioid partial agonist administered through the buccal mucosa – without the need for an opioid taper, and without inducing opioid withdrawal or sacrificing pain control. Buprenorphine HCl buccal film is the first pain product in development to combine the efficacy of buprenorphine with this unique delivery system, which allows for efficient and convenient delivery of buprenorphine into the bloodstream.
MedicalResearch.com Interview with:
Dr. Sebastiano Mercadante MD
Director, Anesthesia and Intensive Care Unit and Pain Relief and Palliative Care Unit
La Maddalena Cancer Center, Palermo, Italy
Medical Research: What is the background for this study? What are the main findings?
Dr. Mercadante: Breakthrough cancer pain (BTcP) has been defined as a transitory increase in pain intensity that occurs either spontaneously, or in relation to a specific predictable or unpredictable trigger, despite relatively stable and adequately controlled background (1). Breakthrough cancer pain is a common problem in patients with cancer and is associated with significant morbidity. In a recent report in which a pragmatic definition of breakthrough cancer pain was used (2), the prevalence of BTcP was 75% (3).
Oral morphine (OM) has been traditionally offered as a breakthrough cancer pain medication in doses of about 1/6 of the daily opioid regimen for years, although this approach has never been supported by any evidence. Different technologies have been developed to provide a rapid onset of effect with potent opioid drugs such as fentanyl (rapid onset opioids, ROOs) delivered by non-invasive routes. Fentanyl products have been shown to be significantly superior to oral opioids, but it has been suggested that the dose of fentanyl should be individually titrated in order to enable effective analgesia to be delivered while minimizing the risk of clinically significant adverse effects. The need of dose titration with rapid onset opioids has never been appropriately assessed and this statement is derived by a series of weaknesses of papers published for regulatory issues. Indeed, the only existing study comparing dose titration and proportional doses, reported that proportional doses of (Fentanyl buccal tablet) FBT are more effective and safe over dose titration method. NICE guidelines did not provide evidence for that, at least at certain time intervals after administration.
To scientifically compare rapid onset opioids and oral morphine, we used a similar approach and made a strict selection of patients, according to a more specific algorithm for a diagnosis o fbreakthrough cancer pain. Thus, patients were randomized to receive in a crossover design Fentanyl buccal tablet and oral morphine, both given in doses proportional to opioid daily doses, for the management of breakthrough cancer pain.
This comparative study has shown that, when giving the drugs for breakthrough cancer pain in doses proportional to the opioid regimen for background pain, Fentanyl was clearly superior for efficacy and rapidity in comparison with oral morphine. The analgesic effect was more intense either at 15 and 30 minutes after study medications were given. A larger number of episodes treated with Fentanyl buccal tablet presented a decrease in pain intensity of ≥33% and ≥50% in comparison with episodes treated with oral morphine, and a relevant difference in SPID30 was reported. Of interest, adverse effects commonly observed in patients receiving opioids were not severe and did not differ between the treatments, suggesting that the use of proportional doses of both drugs are safe, reflecting what is derived by the long-lasting experience with oral morphine.
MedicalResearch.com Interview with:
Dr Martin Hirsch
Clinical Research Fellow
Women’s Health Research Unit
Queen Mary University of London and
Dr Jenny Hole
Foundation Year 1 Doctor
Kettering University Hospital
MedicalResearch: What is the background for this study? What are the main findings?
Response: As doctors we see medicines being prescribed on a daily basis and the benefit but also harm that they can cause. We wanted to assess the role of non pharmaceutical interventions which can benefit patients with a low or minimal potential for harm. We all have an interest in music of different genres and we agreed that we didn’t know anybody who did not like music of one sort or another. On the basis that we all have gained pleasure from music, we wanted to see if this pleasurable experience at the time of a difficult and painful stimulus could reduce the problems encountered as people recover from surgery.
We searched all published medical literature and found 73 of the highest quality studies (randomised controlled trials) to compare and combine their findings in a meta-analysis. This technique aims to strengthen the validity by producing a combined result.
We found that using music before during or after surgery reduced pain, reduced the requirement for pain killers, reduced anxiety, and improved satisfaction.
MedicalResearch.com Interview with:
Richard L. Nahin, Ph.D., M.P.H
National Center for Complementary and Integrative Health
National Institutes of Health, Bethesda, Maryland
Medical Research: What is the background for this study?
Dr. Nahin: In 2011 the Institute of Medicine published a blueprint for transforming pain care in the United States. In this report the IOM noted the lack of a comprehensive picture of pain’s prevalence and severity in the U.S., and especially noted that lack of data examining racial and ethnic groups. The current analysis of data from the 2012 National Health Interview survey is a step toward addressing these deficiencies.
Medical Research: What are the main findings?
Dr. Nahin: The analyses found that an estimated 25.3 million adults (11.2 percent) had pain every day for the preceding 3 months. Nearly 40 million adults (17.6 percent) experience severe levels of pain. Those with severe pain are also likely to have worse health status. There were associations between pain severity and race, ethnicity, language preference, gender, and age. Women, older individuals, and non-Hispanics were more likely to report any pain, while Asians were less likely. Minorities who did not choose to be interviewed in English are markedly less likely to report pain.
MedicalResearch.com Interview with:
Edward W. Cowen, MD, MHSc
Dermatology Branch, Center for Cancer Research
National Cancer Institute
Bethesda, Maryland
Medical Research: What is the background for this study?
Dr. Cowen: Cutaneous leiomyomas are benign smooth muscle proliferations that are associated with pain that is typically not well-controlled by topical remedies or systemic pain medication. Hereditary leiomyomatosis and renal cell cancer is a rare syndrome in which patients may have dozens or even hundreds of these painful tumors. We sought to determine if botulinum toxin injected directly into leiomyomas may ameliorate discomfort and improve quality of life in patients who experience significant pain from cutaneous leiomyomas.
Medical Research: What are the main findings?
Dr. Cowen: In a double-blinded placebo-controlled study, we found that injection of botulinum toxin was associated with improved skin-related quality of life (p = 0.007) and decreased skin-specific pain (p = 0.048) on the Dermatology Life Quality Index. A trend for decreased pain (p = 0.06) by visual analog score was reported in the botulinum toxin treated group compared to the placebo group.
MedicalResearch.com Interview with:
Mark S. Wallace MD
Department of Anesthesiology
School of Medicine
University of California, San Diego, California
Medical Research: What is the background for this study? What are the main findings?
Dr. Wallace: The study was funded by the center for medicinal cannabis research at the University of California San Diego. The center was funded by the state of California. The center was the first to fund a series of double-blind randomized controlled trials with inhaled cannabis for neuropathic pain. My trial is the first in diabetic peripheral neuropathy pain which is one of the most prevalent pain syndromes in our society with limited treatments. We found a dose dependent reduction in pain. However there was also a dose dependent increase in euphoria and sedation which may limit clinical use. Effects on neurocognitive functioning were minimal.
MedicalResearch.com Interview with: Dr. Bahman Guyuron MD Cleveland and Lyndhurst, Ohio From the Department of Plastic Surgery, University Hospital Case Medical Center; and the American Migraine Center Medical Research: What is the background for this study? Dr. Guyuron: Through several studies including retrospective, prospective pilot, prospective randomized, prospective randomized study with sham surgery, prospective...
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.
MedicalResearch.com Interview with:
Harley Goldberg, DO
Physical Medicine and Rehabilitation
Kaiser Permanente
Medical Research: What is the background for this study? What are the main findings?
Dr. Goldberg: This is the first large-scale randomized, double-blind, placebo-controlled clinical trial of oral steroids for acute radiculopathy, commonly called sciatica, associated with a herniated lumbar disk.
Lumbar radiculopathy (or pain down the leg in a lumbar nerve root distribution) is a common source of pain and disability for many adults. It is thought that inflammation from a disk herniation is responsible for many of the symptoms, so giving a powerful anti-inflammatory, such as steroid medication, might help relieve sciatica symptoms quickly. Prior research has shown that lumbar diskectomy does not affect the one year outcome for most patients, and epidural steroid injections do not have strong support by clinical trials. If the use of epidural steroids injections is based on application of steroid anti-inflammatory to the affected nerve root(s), perhaps an oral steroid can have affect. Although oral steroids are used by many physicians and have been included in some clinical guidelines, no large-scale clinical trials of oral steroids for sciatica have been conducted before.
Our study found that among patients with acute radiculopathy associated with a herniated lumbar disk, a short course of oral steroids resulted in only modest improvement in function and no significant improvement in pain.
MedicalResearch.com Interview with:
Hassan R. Mir, MD, MBA
Associate professor of Orthopaedics and Rehabilitation
Vanderbilt Orthopaedic Institute and
and
Dr. Brent J. Morris, M.D.
Shoulder and Elbow Surgery Fellowship
Texas Orthopaedic Hospital University of Texas Houston Health Science Center,
Houston, Texas
Medical Research: What is the background for this study? What are the main findings?
Dr. Mir: The past few decades have seen an alarming rise in opioid use in the United States, and the negative consequences are dramatically increasing. The US represents less than 5% of the world's population, yet consumes 80% of the global opioid supply. Management of pain is an important part of patient care, however, the increased usage of opioids for the treatment of pain has led to several unanticipated aftereffects for individual patients and for society at large.
Orthopaedic surgeons are the third highest prescribers of opioid prescriptions among physicians in the United States. Orthopaedic patients can experience a tremendous amount of pain with acute injuries and chronic conditions, and the treatment plan may involve opioid prescriptions for relief of discomfort. A significant number of orthopaedic patients and their families are at risk for repercussions from opioid use. We must work together to decrease the use of opioids for musculoskeletal pain.
Clinicians should aim to control pain and improve patient satisfaction while avoiding overprescribing opioids. A comprehensive strategy of risk assessment is needed to identify patients who may be at risk for opioid abuse. Objective measures including patient history, recognition of aberrant behavior, urine drug testing, state prescription drug–monitoring programs, and opioid risk-assessment screening tools may be necessary in select cases.
MedicalResearch.com Interview with:
Gustavo C Machado, PhD student
The George Institute for Global Health, Sydney Medical School
University of Sydney Sydney Australia
(Editor’s note: Paracetamol isalso known as acetaminophen)
MedicalResearch: What is the background for this study? What are the main findings?
Response: Back pain and osteoarthritis are the two major musculoskeletal conditions affecting people worldwide, and paracetamol is the most used over the counter medicine to treat these conditions. Recent debates on the efficacy and safety of paracetamol prompted us to conduct a systematic review of literature on the efficacy of this medication. In our study we included all available clinical trials that compared paracetamol to placebo, and our conclusions are based on data from more than 5,300 patients with low back pain and hip or knee osteoarthritis. We found that paracetamol is ineffective for low back pain and provides small and not clinically important benefits to patients with osteoarthritis.
MedicalResearch.com Interview with:
Jeffrey (Jerry) G. Jarvik MD MPH
Professor, Radiology, Neurological Surgery and Health Services
Adjunct Professor, Pharmacy and Orthopedics & Sports Medicine
Director, Comparative Effectiveness, Cost and Outcomes Research Center University of Washington Seattle, WA
Medical Research: What is the background for this study?
Dr. Jarvik: When I arrived at the Univ of WA over 20 years ago, my mentor, Rick Deyo, had just finished leading a project that was responsible for developing one of the first set of guidelines for the diagnosis and treatment of acute low back pain. These guidelines, published in a booklet by AHRQ (then called AHCPR), recommended that patients with acute low back pain not undergo imaging for 4-6 weeks unless a red flag was present. One of the exceptions was that patients older than 50 could get imaged immediately, the rationale being that older adults had a higher prevalence of potentially serious conditions such as cancer, infections, etc, that would justify the early imaging. As a practicing neuroradiologist, it was clear that a potential problem with this strategy is that the prevalence of age-related changes, which may or may not be related to back pain, also increases with age. So earlier imaging of older adults would almost certainly reveal findings, and these could easily start a series of unfortunate events leading to potentially poor outcomes and more healthcare resource use. Thus this policy of early imaging of older adults didn’t entirely make sense.
About 5 years ago, these guidelines hit home when I developed acute low back pain and since I was over 50 (barely) my doctor recommended that I get an imaging study. Being a knowledgeable patient and having a reasonable doctor, we mutually agreed not to get the study. I improved but that wasn’t the end of it. When we had the chance to apply for one of the CHOICE ARRA awards funded by AHRQ, we made answering this question of early imaging in older adults one of our primary goals.
MedicalResearch.com Interview with:
Matthew J. Bair, MD, MS
Research Service, Veterans Affairs Health Services Research and Development, Center for Health Information and Communication
Richard L. Roudebush Veterans Affairs Medical Center,
Department of Medicine, Indiana University School of Medicine, Health Services Research, Regenstrief Institute, Inc, Indianapolis, Indiana
MedicalResearch.com: What is the background for this study?
Dr. Bair: Despite the prevalence and functional, psychological, and economic impact of chronic pain, there have been few intervention studies to treat chronic pain in Veterans.
MedicalResearch.com: What are the main findings?
Dr. Bair: A stepped-care intervention that combined analgesics, self-management strategies, and brief cognitive behavioral therapy resulted in statistically significant reductions in pain-related disability, pain interference, and pain severity in Veterans with chronic musculoskeletal pain.
MedicalResearch.com Interview with:
Prof. Dr. med. Andreas Michalsen
Stiftungsprofessur für klinische Naturheilkunde
Institut für Sozialmedizin, Epidemiologie und
Gesundheitsökonomie
Charité - Universitätsmedizin Berlin
Immanuel Krankenhaus Berlin
Medical Research: What is the background for this study? What are the main findings?
Response: Chronic neck and back pain is an increasing health care problem in Europe and the U.S.
Chronic neck pain is associated with distress and there is a need to evaluate methods of stress reduction in the management of chronic neck pain. The main findings of this trial were, that an 8-week meditation program teaching a traditional meditation technique, Jyoti meditation, leads to significant pain relief and reduced pain-related bothersomeness.
MedicalResearch.com Interview with: Anne-Marie Schjerning Olsen, MD, PhD Department of Cardiology Gentofte Hospital, University of Copenhagen Denmark MedicalResearch.com: What is the background for this study? Dr. Olsen: The question addressed in the study was: Do people who have had a myocardial infarction (heart attack) and are who taking drugs (known as antithrombotics) to reduce their risk...
MedicalResearch.com Interview with:
Dan White PT , ScD, Msc
University of Delaware
Medical Research: What is the background for this study? What are the main findings?
Dr. White: We know that diet and exercise are beneficial to reduce knee pain, however it is not known whether diet and exercise can actually prevent the development of knee pain in people at high risk. We found that an intensive program of diet and exercise had a small but statistically significant protective effect with preventing the development of knee pain in overweight and obese people with diabetes.
MedicalResearch.com Interview with:
John N. Mafi, M.D.
Fellow, Harvard Combined Program in General Medicine
Beth Israel Deaconess Medical Center
Brookline, MA 02446
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Mafi: Headache costs our healthcare system over 30 billion dollars annually. Clinical guidelines recommend conservative treatments for uncomplicated headache, such as counseling on dietary trigger avoidance. The Choosing Wisely Campaign of the American Board of Internal Medicine has in turn identified advanced imaging (e.g. CT or MRI) and opioid or barbiturate medications as low value treatments in the management of headache. In this context we used a nationally representative database to evaluate trends in physician practice patterns on headache management. We found a doubling in use of advanced imaging, referrals to other physicians and no change in opioid/barbiturate medications, although these continued to be used at high rates (18%). We also found a decline in life-style modification counseling, meant to prevent headaches from starting.
MedicalResearch.com Interview with:
Sandra Goldsmith, MA, MS, RD
Director of Public and Patient Education at Hospital for Special Surgery
New York City.
Medical Research: What is the background for this study? What are the main findings?
Response: Almost 50 million adults in the United States suffer from some form of musculoskeletal disorder, which can affect their mobility and quality of life. Osteoarthritis (OA) is the leading cause of disability in the U.S. and affects more than 70 percent of adults between the ages of 55 and 78. Research has shown that there is a connection between being physically active and maintaining joint health, pain relief and improved quality of life. This study attempts to support the efficacy of Hospital for Special Surgery’s hospital-based exercise programs in increasing physical activity and improving quality of life through pain relief and improved stiffness, fatigue and balance in the older adult community.
This study found that after taking the exercise classes, fewer participants reported experiencing a high level of muscle/joint pain from their condition (56 percent before the program started vs. 47 percent after completing the program). The study also reported improved quality of life, as evidenced by statistically significant reductions in how much their pain interfered with their general activities, ability to walk, mood, sleep and enjoyment of life. In addition, 83 percent of participants indicated a reduction in stiffness; 82 percent said they felt their balance improved; and 67 percent said they experienced less fatigue as a result of taking part in the program. Health outcomes were also related to the type of exercise class participants chose, with the greatest reduction in muscle/joint pain reported by those who took t’ai chi.