Juurlink, David N; Dhalla, Irfan A
The use of opioids for chronic noncancer pain has increased dramatically over the past 25 years in North America and has been accompanied by a major increase in opioid addiction and overdose deaths. The increase in opioid prescribing is multifactorial and partly reflects concerns about the effectiveness and safety of alternative medications, particularly the nonsteroidal anti-inflammatory drugs. However, much of the rise in opioid prescribing reflects the assertion, widely communicated to physicians in the 1990s, that the risks of dependence and addiction during chronic opioid therapy were low, predictable, and could be minimized by the use of controlled-release opioid formulations. In this narrative review, we offer a critical appraisal of the publications most frequently cited as evidence that the risk of addiction during chronic opioid therapy is low. We conclude that very few well-designed studies support the notion that opioid addiction is rare during chronic opioid therapy and that none can be readily generalized to present-day practice. Despite serious methodological limitations, these studies have been repeatedly mischaracterized as showing that the risk of addiction during chronic opioid therapy is rare. These studies are countered by a larger, more rigorous and contemporary body of evidence demonstrating that dependence and addiction are relatively common consequences of chronic opioid therapy, occurring in up to one-third of patients in some series.
Russell K Portenoy
Full Text Available Long term administration of an opioid drug for chronic nonmalignant pain continues to be controversial, but is no longer uniformly rejected by pain specialists. This is true despite concerns that the regulatory agencies that oversee physician prescribing of opioid drugs continue to stigmatize the practice. The changing clinical perspective has been driven, in part, by widespread acknowledgement of the remarkably favourable outcomes achieved during opioid treatment of cancer pain. These outcomes contrast starkly with popular teaching about chronic opioid therapy and affirm the potential for prolonged efficacy, tolerable side effects, enhanced function associated with improved comfort and minimal risk of aberrant drug-related behaviours consistent with addiction. A large anecdotal experience in populations with nonmalignant pain suggests that these patients are more heterogeneous and that opioid therapy will greatly benefit some and will contribute to negative outcomes for others. The few controlled clinical trials that have been performed support the safety and efficacy of opioid therapy, but have been too limited to ensure generalization to the clinical setting. A critical review of the medical literature pertaining to chronic pain, opioid pharmacology and addiction medicine can clarify misconceptions about opioid therapy and provide a foundation for patient selection and drug administration. The available data support the view that opioids are no panacea for chronic pain, but should be considered in carefully selected patients using clinically derived guidelines that stress a structured approach and ongoing monitoring of efficacy, adverse effects, functional outcomes and the occurrence of aberrant drug-related behaviours.
Daum, Akiva M; Berkowitz, Oren; Renner, John A
Chronic pain is one of the most common complaints in the United States. Opioids have become a frequently prescribed treatment for patients with chronic nonmalignant pain. Concurrently, opioid use disorders have risen to epidemic levels. Studies investigating iatrogenic opioid addiction have been of limited quality. Aberrant drug-related behaviors may be warning signs of impending addiction. Proper screening and close monitoring are essential for managing patients on opioids for chronic nonmalignant pain.
Fleming, Sara; Rabago, David P; Mundt, Marlon P; Fleming, Michael F
Abstract Background Complementary and alternative medicine (CAM) is an increasingly common therapy used to treat chronic pain syndromes. However; there is limited information on the utilization and efficacy of CAM therapy in primary care patients receiving long-term opioid therapy. Method A survey of CAM therapy was conducted with a systematic sample of 908 primary care patients receiving opioids as a primary treatment method for chronic pain. Subjects completed a questionnaire designed to as...
Pearson, Amy CS; Moman, Rajat N; Moeschler, Susan M; Eldrige, Jason S; Hooten, W Michael
Introduction Many providers report lack of confidence in managing patients with chronic pain. Thus, the primary aim of this study was to investigate the associations of provider confidence in managing chronic pain with their practice behaviors and demographics. Materials and methods The primary outcome measure was the results of the Opioid Therapy Provider Survey, which was administered to clinicians attending a pain-focused continuing medical education conference. Nonparametric correlations were assessed using Spearman’s rho. Results Of the respondents, 55.0% were women, 92.8% were white, and 56.5% were physicians. Primary care providers accounted for 56.5% of the total respondents. The majority of respondents (60.8%) did not feel confident managing patients with chronic pain. Provider confidence in managing chronic pain was positively correlated with 1) following an opioid therapy protocol (P=0.001), 2) the perceived ability to identify patients at risk for opioid misuse (P=0.006), and 3) using a consistent practice-based approach to improve their comfort level with prescribing opioids (Pcorrelated with the perception that treating pain patients was a “problem in my practice” (P=0.005). Conclusion In this study, the majority of providers did not feel confident managing chronic pain. However, provider confidence was associated with a protocolized and consistent practice-based approach toward managing opioids and the perceived ability to identify patients at risk for opioid misuse. Future studies should investigate whether provider confidence is associated with measurable competence in managing chronic pain and explore approaches to enhance appropriate levels of confidence in caring for patients with chronic pain. PMID:28652805
Full Text Available Beginning in the late 1990s, a movement began within the pain management field focused upon the underutilization of opioids, thought to be a potentially safe and effective class of pain medication. Concern for addiction and misuse were present at the start of this shift within pain medicine, and an emphasis was placed on developing reliable and valid methods and measures of identifying those at risk for opioid misuse. Since that time, the evidence for the safety and effectiveness of chronic opioid therapy (COT has not been established. Rather, the harmful, dose-dependent deleterious effects have become clearer, including addiction, increased risk of injuries, respiratory depression, opioid induced hyperalgesia, and death. Still, many individuals on low doses of opioids for long periods of time appear to have good pain control and retain social and occupational functioning. Therefore, we propose that the question, “Who is at risk of opioid misuse?” should evolve to, “Who may benefit from COT?” in light of the current evidence.
Häuser, Winfried; Schug, Stephan; Furlan, Andrea D
A marked rise in opioid prescriptions for patients with chronic noncancer pain (CNCP) with a parallel increase in opioid abuse/misuse, and resulting deaths was noted in the Unites states in the past decade (opioid epidemic). In response, the US Center of Diseases Control (CDC) developed a guideline for prescribing of opioids for patients with CNCP. To assess (1) if there is an opioid epidemic in Australia, Canada, and Germany (2) to compare Australian, Canadian, German, and Center of Diseases Control guidelines recommendations for long-term opioid therapy for CNCP. National evidence-based guidelines and PubMed were searched for recommendations for opioid prescriptions for CNCP. There are signs of an opioid epidemic in Australia and Canada, but not in Germany. Guidelines in all 4 countries provide similar recommendations: opioids are not the first-line therapy for patients with CNCP; regular clinical assessments of benefits and harms are necessary; excessive doses should be avoided (recommended morphine equivalent daily doses range from 50 to 200 mg/d); stopping rules should be followed. All guidelines do not recommend the use of opioids in chronic pain conditions without an established nociceptive or neuropathic cause such as fibromyalgia and primary headache. Implementation of opioid prescribing guidelines should ensure that physicians prescribe opioids only for appropriate indications in limited doses for selected patients and advice patients on their safe use. These measures could contribute to reduce prescription opioid misuse/abuse and deaths.
Webster, Lynn; Gruener, Daniel; Kirby, Todd; Xiang, Qinfang; Tzanis, Evan; Finn, Andrew
Objective?Assess whether patients with chronic pain receiving 80 to 220?mg oral morphine sulfate equivalent of a full ?-opioid agonist could be transitioned to buccal buprenorphine at approximately 50% of their full dose without inducing opioid withdrawal or sacrificing analgesic efficacy. Methods.?A randomized, double-blind, double-dummy, active-controlled, two-period crossover study in adult patients receiving around-the-clock full opioid agonist therapy and confirmed to be opioid dependent...
Mundt Marlon P
Full Text Available Abstract Background Complementary and alternative medicine (CAM is an increasingly common therapy used to treat chronic pain syndromes. However; there is limited information on the utilization and efficacy of CAM therapy in primary care patients receiving long-term opioid therapy. Method A survey of CAM therapy was conducted with a systematic sample of 908 primary care patients receiving opioids as a primary treatment method for chronic pain. Subjects completed a questionnaire designed to assess utilization, efficacy and costs of CAM therapies in this population. Results Patients were treated for a variety of pain problems including low back pain (38.4%, headaches (9.9%, and knee pain (6.5%; the average duration of pain was 16 years. The median morphine equivalent opioid dose was 41 mg/day, and the mean dose was 92 mg/day. Forty-four percent of the sample reported CAM therapy use in the past 12 months. Therapies utilized included massage therapy (27.3%, n = 248, chiropractic treatment (17.8%, n = 162, acupuncture (7.6%, n = 69, yoga (6.1%, n = 55, herbs and supplements (6.8%, n = 62, and prolotherapy (5.9%, n = 54. CAM utilization was significantly related to age female gender, pain severity income pain diagnosis of neck and upper back pain, and illicit drug use. Medical insurance covered chiropractic treatment (81.8% and prolotherapy (87.7%, whereas patients primarily paid for other CAM therapies. Over half the sample reported that one or more of the CAM therapies were helpful. Conclusion This study suggests CAM therapy is widely used by patients receiving opioids for chronic pain. Whether opioids can be reduced by introducing such therapies remains to be studied.
Fleming, Sara; Rabago, David P; Mundt, Marlon P; Fleming, Michael F
Complementary and alternative medicine (CAM) is an increasingly common therapy used to treat chronic pain syndromes. However; there is limited information on the utilization and efficacy of CAM therapy in primary care patients receiving long-term opioid therapy. A survey of CAM therapy was conducted with a systematic sample of 908 primary care patients receiving opioids as a primary treatment method for chronic pain. Subjects completed a questionnaire designed to assess utilization, efficacy and costs of CAM therapies in this population. Patients were treated for a variety of pain problems including low back pain (38.4%), headaches (9.9%), and knee pain (6.5%); the average duration of pain was 16 years. The median morphine equivalent opioid dose was 41 mg/day, and the mean dose was 92 mg/day. Forty-four percent of the sample reported CAM therapy use in the past 12 months. Therapies utilized included massage therapy (27.3%, n = 248), chiropractic treatment (17.8%, n = 162), acupuncture (7.6%, n = 69), yoga (6.1%, n = 55), herbs and supplements (6.8%, n = 62), and prolotherapy (5.9%, n = 54). CAM utilization was significantly related to age female gender, pain severity income pain diagnosis of neck and upper back pain, and illicit drug use. Medical insurance covered chiropractic treatment (81.8%) and prolotherapy (87.7%), whereas patients primarily paid for other CAM therapies. Over half the sample reported that one or more of the CAM therapies were helpful. This study suggests CAM therapy is widely used by patients receiving opioids for chronic pain. Whether opioids can be reduced by introducing such therapies remains to be studied.
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1172] Impact of Approved Drug Labeling on Chronic Opioid Therapy; Public Hearing; Request for Comments AGENCY... impact the entire class of opioid drugs or a large subcategory thereof (e.g., ER/LA opioids), such as the...
pain and chronic pain associated with cancer and at the end of life. Although .... Opioid drugs are agonists that bind to endogenous opioid receptors and mimic ..... interstitial cystitis/painful bladder syndrome, chronic prostate pain, and irritable ...
Smallwood, Rachel F; Potter, Jennifer S; Robin, Donald A
Acceptance and Commitment Therapy (ACT) has been effectively utilized to treat both chronic pain and substance use disorder independently. Given these results and the vital need to treat the comorbidity of the two disorders, a pilot ACT treatment was implemented in individuals with comorbid chronic pain and opioid addiction. This pilot study supported using neurophysiology to characterize treatment effects and revealed that, following ACT, participants with this comorbidity exhibited reductions in brain activation due to painful stimulus and in connectivity at rest. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Tai, Betty; Saxon, Andrew J.; Ling, Walter
The “Medication-Assisted Therapy for Opioid Addiction” session was chaired by Dr. Betty Tai and had three presenters. The presenters (and their topics) were: Dr. Andrew J. Saxon (Methadone and Buprenorphine for Treatment of Opioid Addiction and HIV Risk Reduction), Dr. Walter Ling (Opioid Antagonist Treatment for Opioid Addiction), and Dr. Betty Tai (Chronic Care Model for Substance Use Disorder).
Reisfield, Gary M; Salazar, Elaine; Bertholf, Roger L
Urine drug testing (UDT) has become an essential feature of pain management, as physicians seek to verify adherence to prescribed opioid regimens and to detect the use of illicit or unauthorized licit drugs. Results of urine drug tests have important consequences in regard to therapeutic decisions and the trust between physician and patient. However, reliance on UDT to confirm adherence can be problematic if the results are not interpreted correctly, and evidence suggests that many physicians lack an adequate understanding of the complexities of UDT and the factors that can affect test results. These factors include metabolic conversion between drugs, genetic variations in drug metabolism, the sensitivity and specificity of the analytical method for a particular drug or metabolite, and the effects of intentional and unintentional interferants. In this review, we focus on the technical features and limitations of analytical methods used for detecting drugs or their metabolites in urine, the statistical constructs that are pertinent to ordering UDT and interpreting test results, and the application of these concepts to the clinical monitoring of patients maintained on chronic opioid therapy.
Faure, Delinger; Giniès, Patrick; Eiden, Céline; Portet, Laure; Peyrière, Hélène
The prescription of opioids for the treatment of chronic non-cancer pain (CNCP) is not recommended for all of them, and can expose the patients to a benefit/risk ratio unfavorable. The objective of this study was to evaluate the management of patients hospitalized at the centre for evaluation and treatment of pain for opioid withdrawal, their outcome during hospitalization. This is a retrospective descriptive study. The medical record of each patient was consulted to identify relevant data (demographics, treatments at the entrance and discharge of hospitalization, comorbidities, rating scale of pain). During the study period (3 years), 53 patients (64% of women), with a median age of 52 years, were included. Pain was mainly back pain and neck pain (52%). Morphine (43%) and fentanyl (42%) were the most frequently used opioids. At admission, 62% of patients had a depressive state. At hospital discharge, withdrawal was total in 18 patients (34%) and a total improvement of pain was observed for 19% of them. In this study, 57% of patients received, at admission to hospital, an opioid other than morphine in the treatment of CNCP. The management of pain offered by the pain clinic led to a total or partial opioid withdrawal in 94% of patients. © 2013 Société Française de Pharmacologie et de Thérapeutique.
Conclusion:. Implementation of opioid prescribing guidelines should ensure that physicians prescribe opioids only for appropriate indications in limited doses for selected patients and advice patients on their safe use. These measures could contribute to reduce prescription opioid misuse/abuse and deaths.
Salsitz, Edwin A
Over the past two decades, there has been a significant increase in the prescribing of opioids, with associated increases in opioid addiction and overdose deaths. This article reviews the evidence for the effectiveness and risk of developing an opioid use disorder (OUD) in those patients treated with chronic opioid therapy (COT) for chronic non-cancer pain (CNCP). Rates of development of OUD range from 0-50 %, and aberrant drug related behaviors (ADRBs) are reported to be 20 %. Health care providers must properly assess, screen, and carefully monitor patients on COT utilizing evidence-based tools.
Clark Michael E
Full Text Available Abstract Background Opioid prescribing for chronic pain is common and controversial, but recommended clinical practices are followed inconsistently in many clinical settings. Strategies for increasing adherence to clinical practice guideline recommendations are needed to increase effectiveness and reduce negative consequences of opioid prescribing in chronic pain patients. Methods Here we describe the process and outcomes of a project to operationalize the 2003 VA/DOD Clinical Practice Guideline for Opioid Therapy for Chronic Non-Cancer Pain into a computerized decision support system (DSS to encourage good opioid prescribing practices during primary care visits. We based the DSS on the existing ATHENA-DSS. We used an iterative process of design, testing, and revision of the DSS by a diverse team including guideline authors, medical informatics experts, clinical content experts, and end-users to convert the written clinical practice guideline into a computable algorithm to generate patient-specific recommendations for care based upon existing information in the electronic medical record (EMR, and a set of clinical tools. Results The iterative revision process identified numerous and varied problems with the initially designed system despite diverse expert participation in the design process. The process of operationalizing the guideline identified areas in which the guideline was vague, left decisions to clinical judgment, or required clarification of detail to insure safe clinical implementation. The revisions led to workable solutions to problems, defined the limits of the DSS and its utility in clinical practice, improved integration into clinical workflow, and improved the clarity and accuracy of system recommendations and tools. Conclusions Use of this iterative process led to development of a multifunctional DSS that met the approval of the clinical practice guideline authors, content experts, and clinicians involved in testing. The
Paul F. White
Full Text Available The use of opioid analgesics for postoperative pain management has contributed to the global opioid epidemic. It was recently reported that prescription opioid analgesic use often continued after major joint replacement surgery even though patients were no longer experiencing joint pain. The use of epidural local analgesia for perioperative pain management was not found to be protective against persistent opioid use in a large cohort of opioid-naïve patients undergoing abdominal surgery. In a retrospective study involving over 390,000 outpatients more than 66 years of age who underwent minor ambulatory surgery procedures, patients receiving a prescription opioid analgesic within 7 days of discharge were 44% more likely to continue using opioids 1 year after surgery. In a review of 11 million patients undergoing elective surgery from 2002 to 2011, both opioid overdoses and opioid dependence were found to be increasing over time. Opioid-dependent surgical patients were more likely to experience postoperative pulmonary complications, require longer hospital stays, and increase costs to the health-care system. The Centers for Disease Control and Prevention emphasized the importance of finding alternatives to opioid medication for treating pain. In the new clinical practice guidelines for back pain, the authors endorsed the use of non-pharmacologic therapies. However, one of the more widely used non-pharmacologic treatments for chronic pain (namely radiofrequency ablation therapy was recently reported to have no clinical benefit. Therefore, this clinical commentary will review evidence in the peer-reviewed literature supporting the use of electroanalgesia and laser therapies for treating acute pain, cervical (neck pain, low back pain, persistent post-surgical pain after spine surgery (“failed back syndrome”, major joint replacements, and abdominal surgery as well as other common chronic pain syndromes (for example, myofascial pain, peripheral
Rosenberg, Jack M; Bilka, Brandon M; Wilson, Sara M; Spevak, Christopher
The US Department of Veterans Affairs (VA) and US Department of Defense (DoD) revised the 2010 clinical practice guideline (CPG) for the management of opioid therapy for chronic pain, considering the specific needs of the VA and DoD and new evidence regarding prescribing opioid medication for non-end-of-life-related chronic pain. This paper summarizes the major recommendations and compares them with the US Centers for Disease Control and Prevention (CDC) guideline for prescribing opioids. This Opioid Therapy CPG was developed for VA-DoD service members, veterans, and their families. The VA/DoD Evidence-Based Practice Work Group convened a VA/DoD guideline renewal development effort and conformed to the guidelines established by the VA/DoD Joint Executive Council (JEC) and VA/DoD Health Executive Council (HEC). The panel developed questions, searched and evaluated the literature, developed recommendations using GRADE methodology, and developed algorithms. Passage of the CARA Act by Congress compelled consideration and comparison with the CDC opioid therapy guideline mid-development. There were 18 recommendations made. This article focuses on guideline development and key recommendations with CDC comparisons taken from four major areas, including: initiation and continuation of opioids;type, dose, follow-up, and taper of opioids;risk mitigation;acute pain. Guideline development and recommendations are presented. There was substantial overlap with the CDC opioid guideline. Additionally, there were items particularly relevant to the VA-DoD, including risk mitigation, suicide prevention, and preventing opioid use disorder in young patients. Our guideline highlights avoiding opioid therapy longer than 90 days as a critical juncture.
Yasin S AlMakadma
Full Text Available Background: In both developing and developed countries, chronic pain remains a real issue and a true disease that affects up to 42% of the population in some areas. Opioids are widely used for the management of chronic pain with variations in prescribing practices, indications and observed efficacy. Aim: to analyze trends in opioids prescribing and patient response in chronic non-cancer pain conditions. Methods: Retrospective study of 1500 casenotes of patients suffering variable non-cancer chronic pain conditions. Detailed review of those cases who were managed using opioids. Statistical analysis using "SOFA" software set. Results: The prevalence of opioids prescribing in patients suffering this condition was thus around 35% (n=526. Women older than 50 years were more likely than men to have a chronic pain condition and to be given opioid therapy for 1 year or more. Opioid efficacy on neuropathic and mixed types of pain was found to be significant with relatively low rate of drop-out and limited side-effects that are not life threatening. Overall, patients stopped or changed their opioid medication due to inefficacy in only 12.7% of cases. Conclusions: The simple fact of having pain is itself a source of self-reported disability regardless of the actual physiological or pathological mechanism. Policy makers should be aware of the huge impact of chronic pain disease and of its serious effects on social and economical well-being. In developing countries, chronic pain could represent a real challenge for all parties. Multimodal management, including opioids, appears crucial for the approach of this disease.
Carey, Evan P; Nolan, Charlotte; Kerns, Robert D; Ho, P Michael; Frank, Joseph W
Expert guidelines recommend non-pharmacologic treatments and non-opioid medications for chronic pain and recommend against initiating long-term opioid therapy (LTOT). We examined whether veterans with incident chronic pain receiving care at facilities with greater utilization of non-pharmacologic treatments and non-opioid medications are less likely to initiate LTOT. Retrospective cohort study PARTICIPANTS: Veterans receiving primary care from a Veterans Health Administration facility with incident chronic pain between 1/1/2010 and 12/31/2015 based on either of 2 criteria: (1) persistent moderate-to-severe patient-reported pain and (2) diagnoses "likely to represent" chronic pain. The independent variable was facility-level utilization of pain-related treatment modalities (non-pharmacologic, non-opioid medications, LTOT) in the prior calendar year. The dependent variable was patient-level initiation of LTOT (≥ 90 days within 365 days) in the subsequent year, adjusting for patient characteristics. Among 1,094,569 veterans with incident chronic pain from 2010 to 2015, there was wide facility-level variation in utilization of 10 pain-related treatment modalities, including initiation of LTOT (median, 16%; range, 5-32%). Veterans receiving care at facilities with greater utilization of non-pharmacologic treatments were less likely to initiate LTOT in the year following incident chronic pain. Conversely, veterans receiving care at facilities with greater non-opioid and opioid medication utilization were more likely to initiate LTOT; this association was strongest for past year facility-level LTOT initiation (adjusted rate ratio, 2.10; 95% confidence interval, 2.06-2.15, top vs. bottom quartile of facility-level LTOT initiation in prior calendar year). Facility-level utilization patterns of non-pharmacologic, non-opioid, and opioid treatments for chronic pain are associated with subsequent patient-level initiation of LTOT among veterans with incident chronic pain
Hayes, Corey J; Li, Xiaocong; Li, Chenghui; Shah, Anuj; Kathe, Niranjan; Bhandari, Naleen Raj; Payakachat, Nalin
Evaluate the association between opioid therapy and health-related quality of life (HRQoL) in participants with chronic, noncancer pain (CNCP). Medical Expenditure Panel Survey Longitudinal, Medical Conditions, and Prescription Files. Using a retrospective cohort study design, the Mental Health Component (MCS12) and Physical Health Component (PCS12) scores of the Short Form-12 Version 2 were assessed to measure mental and physical HRQoL. Chronic, noncancer pain participants were classified as chronic, nonchronic, and nonopioid users. One-to-one propensity score matching was employed to match chronic opioid users to nonchronic opioid users plus nonchronic opioid users and chronic opioid users to nonopioid users. A total of 5,876 participants were identified. After matching, PCS12 was not significantly different between nonchronic versus nonopioid users (LSM Diff = -0.98, 95% CI: -2.07, 0.10), chronic versus nonopioid users (LSM Diff = -2.24, 95% CI: -4.58, 0.10), or chronic versus nonchronic opioid users (LSM Diff = -2.23, 95% CI: -4.53, 0.05). Similarly, MCS12 was not significantly different between nonchronic versus nonopioid users (LSM Diff = 0.76, 95% CI: -0.46, 1.98), chronic versus nonopioid users (LSM Diff = 1.08, 95% CI: -1.26, 3.42), or chronic versus nonchronic opioid users (LSM Diff = -0.57, 95% CI: -2.90, 1.77). Clinicians should evaluate opioid use in participants with CNCP as opioid use is not correlated with better HRQoL. © Health Research and Educational Trust.
Trafton, Jodie; Martins, Susana; Michel, Martha; Lewis, Eleanor; Wang, Dan; Combs, Ann; Scates, Naquell; Tu, Samson; Goldstein, Mary K
To develop and evaluate a clinical decision support system (CDSS) named Assessment and Treatment in Healthcare: Evidenced-Based Automation (ATHENA)-Opioid Therapy, which encourages safe and effective use of opioid therapy for chronic, noncancer pain. CDSS development and iterative evaluation using the analysis, design, development, implementation, and evaluation process including simulation-based and in-clinic assessments of usability for providers followed by targeted system revisions. Volunteers provided detailed feedback to guide improvements in the graphical user interface, and content and design changes to increase clinical usefulness, understandability, clinical workflow fit, and ease of completing guideline recommended practices. Revisions based on feedback increased CDSS usability ratings over time. Practice concerns outside the scope of the CDSS were also identified. Usability testing optimized the CDSS to better address barriers such as lack of provider education, confusion in dosing calculations and titration schedules, access to relevant patient information, provider discontinuity, documentation, and access to validated assessment tools. It also highlighted barriers to good clinical practice that are difficult to address with CDSS technology in its current conceptualization. For example, clinicians indicated that constraints on time and competing priorities in primary care, discomfort in patient-provider communications, and lack of evidence to guide opioid prescribing decisions impeded their ability to provide effective, guideline-adherent pain management. Iterative testing was essential for designing a highly usable and acceptable CDSS; however, identified barriers may limit the impact of the ATHENA-Opioid Therapy system and other CDSS on clinical practices and outcomes unless CDSS are paired with parallel initiatives to address these issues.
Whitten, Stacey K; Stanik-Hutt, Julie
To enhance outcomes of patients with chronic noncancer pain (CNCP) treated with opioids in a primary care setting by implementing an evidence-based quality improvement project. The project consisted of the implementation of a 6-week cognitive behavioral therapy (CBT) program. Twenty-two patients with CNCP completed the program. Impact of the project was evaluated by comparing pre- and postintervention participant self-reports of mood on the Beck Depression Inventory and functional status on the Brief Pain Inventory and Short Form-36. Patient perception of treatment benefit was also measured using the Patient Global Impression of Change. Qualitative provider perceptions of the program were also collected. Paired t-test statistics were used to analyze the data. Mood (including negative attitude, performance difficulty, and physical complaints), and patient impression of treatment benefit improved significantly after CBT was added. Primary care providers reported that the CBT supported their overall management of these complex patients. The addition of a CBT program improved selected outcomes in this self-selected sample of patients with CNCP treated with opioids. ©2012 The Author(s) ©2012 American Association of Nurse Practitioners.
Weiss, Roger D; Potter, Jennifer Sharpe; Griffin, Margaret L; McHugh, R Kathryn; Haller, Deborah; Jacobs, Petra; Gardin, John; Fischer, Dan; Rosen, Kristen D
The number of individuals seeking treatment for prescription opioid dependence has increased dramatically, fostering a need for research on this population. The aim of this study was to examine reasons for prescription opioid use among 653 participants with and without chronic pain, enrolled in the Prescription Opioid Addiction Treatment Study, a randomized controlled trial of treatment for prescription opioid dependence. Participants identified initial and current reasons for opioid use. Participants with chronic pain were more likely to report pain as their primary initial reason for use; avoiding withdrawal was rated as the most important reason for current use in both groups. Participants with chronic pain rated using opioids to cope with physical pain as more important, and using opioids in response to social interactions and craving as less important, than those without chronic pain. Results highlight the importance of physical pain as a reason for opioid use among patients with chronic pain. Copyright © 2014 Elsevier Inc. All rights reserved.
Birke, H; Ekholm, Ola; Sjøgren, P
significantly associated with initiation of L-TOT in individuals with CNCP at baseline. During follow-up, L-TOT in CNCP patients increased the likelihood of negative changes in pain interference with work (OR 9.2; 95% CI 1.9-43.6) and in moderate activities (OR 3.7; 95% CI 1.1-12.6). The analysis of all......,145). A nationally representative subsample of individuals (n = 2015) completed the self-administered questionnaire in both 2000 and 2013. Collected information included chronic pain (≥6 months), health behaviour, self-rated health, pain interference with work activities and physical activities. Long-term users were...... individuals indicated a dose-response relationship between longer treatment duration and the risk of experiencing negative changes. CONCLUSIONS: Individuals on L-TOT seemed not to achieve the key goals of opioid therapy: pain relief, improved quality of life and functional capacity. SIGNIFICANCE: Long...
Marlowe, Karen F; Geiler, Richard
Pain continues to be a serious health care concern in the United States. Patients with chronic pain experience the impact of the disease throughout their lives including their social interactions, family relationships, and in many cases economic productivity. Multiple surveys have found that many pharmacists hold misconceptions regarding opioids, pain disease states, and their understandings of current regulations. Multiple barriers affect the ability of pharmacists to deliver care to patients' prescribed opioid therapy. Inadequate communication between health care professionals and patients is one of the hurdles, which prevents quality care. Increased communication between health care providers including access to health information is one step, which is crucial to improving provision of pharmacotherapy. Finally, the quality of educational opportunities relative to opioids and pain management specifically for pharmacists needs to be increased, and consideration needs to be given for making appropriate pain management education mandatory.
Full Text Available Abstract Background Due to tolerance development and adverse side effects, chronic pain patients frequently need to be switched to alternative opioid therapy Objective To assess the efficacy and tolerability of an alternative transdermally applied (TDS opioid in patients with chronic cancer pain receiving insufficient analgesia using their present treatment. Methods A total of 32 patients received alternative opioid therapy, 16 were switched from buprenorphine to fentanyl and 16 were switched from fentanyl to buprenorphine. The dosage used was 50% of that indicated in equipotency conversion tables. Pain relief was assessed at weekly intervals for the next 3 weeks Results Pain relief as assessed by VAS, PPI, and PRI significantly improved (p Conclusion Opioid switching at 50% of the calculated equianalgesic dose produced a significant reduction in pain levels and rescue medication. The incidence of side effects decreased and no new side effects were noted. Further studies are required to provide individualized treatment for patients according to their different types of cancer.
Højsted, J; Nielsen, P R; Kendall, S
Addiction is a feared complication of long-term opioid therapy for chronic pain patients. A screening tool to assess the potential risk of addiction may be helpful.......Addiction is a feared complication of long-term opioid therapy for chronic pain patients. A screening tool to assess the potential risk of addiction may be helpful....
Hah, Jennifer M; Bateman, Brian T; Ratliff, John; Curtin, Catherine; Sun, Eric
Physicians, policymakers, and researchers are increasingly focused on finding ways to decrease opioid use and overdose in the United States both of which have sharply increased over the past decade. While many efforts are focused on the management of chronic pain, the use of opioids in surgical patients presents a particularly challenging problem requiring clinicians to balance 2 competing interests: managing acute pain in the immediate postoperative period and minimizing the risks of persistent opioid use after the surgery. Finding ways to minimize this risk is particularly salient in light of a growing literature suggesting that postsurgical patients are at increased risk for chronic opioid use. The perioperative care team, including surgeons and anesthesiologists, is poised to develop clinical- and systems-based interventions aimed at providing pain relief in the immediate postoperative period while also reducing the risks of opioid use longer term. In this paper, we discuss the consequences of chronic opioid use after surgery and present an analysis of the extent to which surgery has been associated with chronic opioid use. We follow with a discussion of the risk factors that are associated with chronic opioid use after surgery and proceed with an analysis of the extent to which opioid-sparing perioperative interventions (eg, nerve blockade) have been shown to reduce the risk of chronic opioid use after surgery. We then conclude with a discussion of future research directions.
Højsted, Jette; Sjøgren, Per
To summarize and reflect over primarily recent epidemiological and randomized controlled trials in opioid-treated chronic nonmalignant pain patients, focusing on effects, side effects, risks and long-term consequences of the treatment. In the western world opioids are increasingly being used for long-term treatment of chronic nonmalignant pain. While the long-term benefits of opioids regarding pain relief, functional capacity and health-related quality of life still remain to be proven, studies are emerging that describe serious long-term consequences such as addiction, opioid-induced hyperalgesia, cognitive disorders, and suppression of the immune and reproductive systems. Much more research is needed concerning long-time effects and consequences of opioid therapy in chronic nonmalignant pain patients; however, some clear warning signals have been sent out within recent years.
Full Text Available It is well known that the mu-opioid receptor (MOR plays an important role in the rewarding properties of ethanol. However, it is less clear how chronic ethanol consumption affects MOR signaling. Here, we demonstrate that rats with prolonged voluntary ethanol consumption develop antinociceptive tolerance to opioids. Signaling through the MOR is controlled at many levels, including via the process of endocytosis. Importantly, agonists at the MOR that promote receptor endocytosis, such as the endogenous peptides enkephalin and β-endorphin, show a reduced propensity to promote antinociceptive tolerance than do agonists, like morphine, which do not promote receptor endocytosis. These observations led us to examine whether chronic ethanol consumption produced opioid tolerance by interfering with MOR endocytosis. Indeed, here we show that chronic ethanol consumption inhibits the endocytosis of MOR in response to opioid peptide. This loss of endocytosis was accompanied by a dramatic decrease in G protein coupled receptor kinase 2 (GRK2 protein levels after chronic drinking, suggesting that loss of this component of the trafficking machinery could be a mechanism by which endocytosis is lost. We also found that MOR coupling to G-protein was decreased in ethanol-drinking rats, providing a functional explanation for loss of opioid antinociception. Together, these results suggest that chronic ethanol drinking alters the ability of MOR to endocytose in response to opioid peptides, and consequently, promotes tolerance to the effects of opioids.
Højsted, Jette; Sjøgren, Per
, incidence and prevalence of addiction in opioid treated pain patients, screening tools for assessing opioid addiction in chronic pain patients and recommendations regarding addiction problems in national and international guidelines for opioid treatment in cancer patients and chronic non-malignant pain...... patients. The review indicates that the prevalence of addiction varied from 0% up to 50% in chronic non-malignant pain patients, and from 0% to 7.7% in cancer patients depending of the subpopulation studied and the criteria used. The risk of addiction has to be considered when initiating long-term opioid...... long-term opioid treatment, and specialised treatment facilities for pain management or addiction medicine should be consulted in these cases....
Højsted, Jette; Sjøgren, Per
, incidence and prevalence of addiction in opioid treated pain patients, screening tools for assessing opioid addiction in chronic pain patients and recommendations regarding addiction problems in national and international guidelines for opioid treatment in cancer patients and chronic non-malignant pain...... patients. The review indicates that the prevalence of addiction varied from 0% up to 50% in chronic non-malignant pain patients, and from 0% to 7.7% in cancer patients depending of the subpopulation studied and the criteria used. The risk of addiction has to be considered when initiating long-term opioid...... treatment as addiction may result in poor pain control. Several screening tools were identified, but only a few were thoroughly validated with respect to validity and reliability. Most of the identified guidelines mention addiction as a potential problem. The guidelines in cancer pain management...
Wilder, Christine M; Miller, Shannon C; Tiffany, Elizabeth; Winhusen, Theresa; Winstanley, Erin L; Stein, Michael D
Rising overdose fatalities among U.S. veterans suggest veterans taking prescription opioids may be at risk for overdose. However, it is unclear whether veterans prescribed chronic opioids are aware of this risk. The objective of this study was to identify risk factors and determine awareness of risk for opioid overdose in veterans treated with opioids for chronic pain, using veterans treated with methadone or buprenorphine for opioid use disorder as a high-risk comparator group. In the current study, 90 veterans on chronic opioid medication, for either opioid use disorder or pain management, completed a questionnaire assessing risk factors, knowledge, and self-estimate of risk for overdose. Nearly all veterans in both groups had multiple overdose risk factors, although individuals in the pain management group had on average a significantly lower total number of risk factors than did individuals in the opioid use disorder group (5.9 versus 8.5, p opioid overdose risk factors (12.1 versus 13.5, p opioid overdose risk factors. Our results suggest that veterans in both groups underestimated their risk for opioid overdose. Expansion of overdose education to include individuals on chronic opioids for pain management and a shift in educational approaches to overdose prevention may be indicated.
Kurita, G P; de Mattos Pimenta, C A; Braga, P E
The paucity of studies regarding cognitive function in patients with chronic pain, and growing evidence regarding the cognitive effects of pain and opioids on cognitive function prompted us to assess cognition via neuropsychological measurement in patients with chronic non-cancer pain treated...
Barth, Kelly S; Balliet, Wendy; Pelic, Christine M; Madan, Alok; Malcolm, Robert; Adams, David; Morgan, Katherine; Owczarski, Stefanie; Borckardt, Jeffrey J
The objective of this study is to assess clinical variables that may be associated with risk for opioid misuse in individuals with chronic pancreatitis. This study utilized a descriptive, quasi-experimental, cross sectional design. Three hundred seven individuals with nonalcoholic chronic pancreatitis engaged in chronic opioid therapy for pain presented to an outpatient specialty clinic at an academic medical center. Participants completed the Current Opioid Misuse Measure (COMM), Brief Pain Inventory (BPI), Short Form (SF)-12 Quality of Life Measure, Center for Epidemiological Studies 10-item Depression Scale (CESD), and a single item asking about current alcohol use. Mean scores on the CESD, COMM, BPI, SF-12, and factors associated with opioid misuse measures from regression analyses were the outcome measures. Mean scores on the CESD, COMM, BPI pain-on-average item, and the SF-12 physical and psychological quality of life factors (t scores) were 11.2 (standard deviation [SD] = 6.7), 8.5 (SD = 7.3), 4.8 (SD = 2.8), 39.7 (SD = 7.0), and 45 (SD = 9.0), respectively. Descriptive analyses revealed that 55% of participants scored above the clinical cutoff for depression on the CESD, and 39% scored above the cutoff for opioid misuse concerns on the COMM. Regression analyses identified several factors associated with higher opioid misuse measure scores, including increased depressive symptoms from the CESD (β = 0.38, P factors accounted for 37% of the variance in current opioid misuse scores. Depression, quality of life, pain intensity and alcohol use may be good candidate variables for prospective studies to determine clinical risk factors for opioid misuse among patients with pancreatitis. Wiley Periodicals, Inc.
Dennis, Brittany B; Bawor, Monica; Paul, James; Varenbut, Michael; Daiter, Jeff; Plater, Carolyn; Pare, Guillaume; Marsh, David C; Worster, Andrew; Desai, Dipika; Thabane, Lehana; Samaan, Zainab
The consequences of opioid relapse among patients being treated with opioid substitution treatment (OST) are serious and can result in abnormal cardiovascular function, overdose, and mortality. Chronic pain is a major risk factor for opioid relapse within the addiction treatment setting. There exist a number of opioid maintenance therapies including methadone, buprenorphine, naltrexone, and levomethadyl acetate (LAAM), of which the mediating effects of pain on treatment attrition, substance use behavior, and social functioning may differ across therapies. We aim to 1) evaluate the impact of pain on the treatment outcomes of addiction patients being managed with OST and 2) identify the most recently published opioid maintenance treatment guidelines from the United States, Canada, and the UK to determine how the evidence is being translated into clinical practice. The authors will search Medline, EMBASE, PubMed, PsycINFO, Web of Science, Cochrane Database of Systematic Reviews, ProQuest Dissertations and theses Database, Cochrane Central Register of Controlled Trials (CENTRAL), World Health Organization International Clinical Trials Registry Platform Search Portal, and the National Institutes for Health Clinical Trials Registry. We will search www. gov and the National Institute for Care and Excellence (NICE) databases to identify the most recently published OST guidelines. All screening and data extraction will be completed in duplicate. Provided the data are suitable, we will perform a multiple treatment comparison using Bayesian meta-analytic methods to produce summary statistics estimating the effect of chronic pain on all OSTs. Our primary outcome is substance use behavior, which includes opioid and non-opioid substance use. We will also evaluate secondary endpoints such as treatment retention, general physical health, intervention adherence, personal and social functioning, as well as psychiatric symptoms. This review will capture the experience of treatment
Gardner, Robert Andrew; Brewer, Kori L; Langston, Dennis B
Emergency department (ED) patients with chronic pain challenge providers to make quick and accurate assessments without an in-depth pain management consultation. Emergency physicians need reliable means to determine which patients may receive opioid therapy without exacerbating opioid use disorder (OUD). Eighty-nine ED patients with a chief complaint of chronic pain were enrolled. Researchers administered questionnaires and reviewed medical and state prescription monitoring database information. Participants were classified as either OUD or non-OUD. Statistical analysis included a bivariate analysis comparing differences between groups and multivariate logistic regression evaluating ORs. The 45 participants categorised as OUD had a higher proportion of documented or reported psychiatric diagnoses (p=0.049), preference of opioid treatment (p = 0.005), current oxycodone prescription (p = 0.043), borrowed pain medicine (p=0.004) and non-authorised dose increase (pOUD group to have an increased number of opioid prescriptions (p=0.005) and pills (p=0.010). Participants who borrowed pain medicine and engaged in non-authorised dose increase were 5.2 (p=0.025, 95% CI 1.24 to 21.9) and 6.1 times (p=0.001, 95% CI 1.55 to 24.1) more likely to have OUD, respectively. Major limitations of our study include a small sample size, self-reported measures and convenience sample which may introduce selection bias. Patients with chronic pain with OUD have distinguishable characteristics. Emergency physicians should consider such evidence-based variables prior to opioid therapy to ameliorate the opioid crisis and limit implicit bias. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Højsted, Jette; Ekholm, Kim Ola Michael; Kurita, Geana Paula
,281 individuals were analyzed through multiple logistic regression analyses to assess the association between chronic pain (lasting ⩾6 months), opioid use, health behavior, and body mass index. Six potential addictive behaviors were identified: daily smoking; high alcohol intake; illicit drug use in the past year...
Grosen, Kasper; Olesen, Anne E; Gram, Mikkel
of life after 14 days of opioid treatment. Secondary outcomes included patient's global impression of clinical change and side effects. Logistic regression models adjusted for age and sex were used to identify biomarkers predictive for successful treatment, defined as at least a 30% reduction in average.......03), relative delta (OR: 0.76; P = 0.03) and beta EEG activity (OR: 1.18; P = 0.04) induced by experimental cold pain. None of the study variables were related to improvement in quality of life. For the first time, individual pain processing characteristics have been linked to opioid response in a mixed chronic...
Højsted, Jette; Nielsen, Per Rotbøll; Guldstrand, Sally Kendall
Addiction is a feared consequence of long-term opioid treatment of chronic pain patients. The ICD-10 and DSM-IV diagnostic addiction criteria may not be appropriate in these patients. Therefore Portenoy's criteria (PC) were launched. The aim was to estimate the prevalence of addiction, to investi......Addiction is a feared consequence of long-term opioid treatment of chronic pain patients. The ICD-10 and DSM-IV diagnostic addiction criteria may not be appropriate in these patients. Therefore Portenoy's criteria (PC) were launched. The aim was to estimate the prevalence of addiction......, to investigate whether PC were applicable and to compare these criteria with the ICD-10 criteria. The study was cross-sectional and included 253 patients with chronic pain at a tertiary pain centre. Patients were screened for addiction by a physician and a nurse. The addiction prevalence was 14.4% according...... as addicted were treated with significantly higher opioid doses, drank more alcohol, smoked more tobacco, used benzodiazepines and had higher levels of depression. According to ICD-10 patients classified as addicted used higher doses of opioids, drank more alcohol and had higher scores of anxiety...
Elhwairis, Huda; Reznich, Christopher B
Chronic pain is common and can be devastating to the patient and challenging to the health care provider. Despite the importance of the topic, pain management curricula are incomplete in health professionals' training. We developed a longitudinal curriculum to teach therapy for chronic noncancer pain over four units and pilot-tested the teaching of one unit (opioids) to internal medicine residents. The educational strategies we used included didactic sessions, write-up of a management plan following a model, case discussions, and role-play group activities. We pilot-tested one unit (opioid therapy) in March 2008. We performed learner evaluations, using a pretest and posttest, a write-up plan following a model, and a learner knowledge questionnaire. Results showed significant improvement in knowledge. Residents found the sessions and educational strategy to be excellent and reported higher confidence levels in managing patients with chronic noncancer pain. This article demonstrates that multiple teaching modalities-including didactic lectures, case discussions, write-up of a management plan following a model, and role-play group activities-are effective methods of teaching internal medicine residents how to use opioids to manage chronic noncancer pain. Copyright © 2010 American Pain Society. Published by Elsevier Inc. All rights reserved.
Full Text Available Wojciech Leppert Chair and Department of Palliative Medicine, Poznan University of Medical Sciences, Poznan, Poland Abstract: Opioid-induced bowel dysfunction (OIBD comprises gastrointestinal (GI symptoms, including dry mouth, nausea, vomiting, gastric stasis, bloating, abdominal pain, and opioid-induced constipation, which significantly impair patients’ quality of life and may lead to undertreatment of pain. Traditional laxatives are often prescribed for OIBD symptoms, although they display limited efficacy and exert adverse effects. Other strategies include prokinetics and change of opioids or their administration route. However, these approaches do not address underlying causes of OIBD associated with opioid effects on mostly peripheral opioid receptors located in the GI tract. Targeted management of OIBD comprises purely peripherally acting opioid receptor antagonists and a combination of opioid receptor agonist and antagonist. Methylnaltrexone induces laxation in 50%–60% of patients with advanced diseases and OIBD who do not respond to traditional oral laxatives without inducing opioid withdrawal symptoms with similar response (45%–50% after an oral administration of naloxegol. A combination of prolonged-release oxycodone with prolonged-release naloxone (OXN in one tablet (a ratio of 2:1 provides analgesia with limited negative effect on the bowel function, as oxycodone displays high oral bioavailability and naloxone demonstrates local antagonist effect on opioid receptors in the GI tract and is totally inactivated in the liver. OXN in daily doses of up to 80 mg/40 mg provides equally effective analgesia with improved bowel function compared to oxycodone administered alone in patients with chronic non-malignant and cancer-related pain. OIBD is a common complication of long-term opioid therapy and may lead to quality of life deterioration and undertreatment of pain. Thus, a complex assessment and management that addresses underlying
O'Brien, T; Christrup, L L; Drewes, A M
rests with the primary care physician and other non-specialist opioid prescribers. There is much confusing and conflicting information available to non-specialist prescribers regarding opioid therapy and a great deal of unjustified fear is generated. Opioid therapy should only be initiated by competent...
Lloyd, Renae A; Hotham, Elizabeth; Hall, Catherine; Williams, Marie; Suppiah, Vijayaprakash
Opioids are one of the most commonly prescribed medicines for chronic pain. However, their use for chronic pain has been controversial. The objective of this literature review was to identify the role of genetic polymorphisms on patient treatment parameters (opioid dose requirements, response, and adverse effects) for opioids used in malignant and nonmalignant chronic pain. The opioids that this review focuses on are codeine, morphine, oxycodone, tramadol, and fentanyl. A literature search of databases Medline and Embase was carried out, and studies up to April 2016 were included in this review. Studies were included based on a combination of key words: chronic pain and related terms, pharmacogenetics and related terms, and opioids and related terms. Among the 1,408 individual papers retrieved from the search in Medline and Embase, 32 original articles were included in this review, with none related to codeine. The 32 papers reported various study designs, opioids, and polymorphisms being studied for associations with treatment outcomes. This literature review reveals that variants in ABCB1, OPRM1, and COMT have been replicated for opioid dosing and variants in ABCB1 have been replicated for both treatment response and adverse effects. Currently, there are few validated studies to form a strong evidence base to support pharmacogenomics testing when initiating opioid therapy. However, the field of pharmacogenomics in chronic pain is likely to expand over the coming years, with the increasing number of treatment options available and larger cohorts being assembled in order to identify true associations. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org
Adnan, Liyana Hazwani Mohd; Bakar, Nor Hidayah Abu; Mohamad, Nasir
Methadone is widely being used for opioid substitution therapy. However, the administration of methadone to opioid dependent individual is frequently accompanied by withdrawal syndrome and chemical dependency develops. Other than that, it is also difficult to retain patients in the treatment programme making their retention rates are decreasing over time. This article is written to higlights the potential use of prophetic medicines, Nigella sativa, as a supplement for opioid dependent receiving methadone. It focuses on the potential role of N. sativa and its major active compound, Thymoquinone (TQ) as a calcium channel blocking agent to reduce withdrawal syndrome and opioid dependency. PMID:25859295
Liyana Hazwani Mohd Adnan
Full Text Available Methadone is widely being used for opioid substitution therapy. However, the administration of methadone to opioid dependent individual is frequently accompanied by withdrawal syndrome and chemical dependency develops. Other than that, it is also difficult to retain patients in the treatment programme making their retention rates are decreasing over time. This article is written to higlights the potential use of prophetic medicines, Nigella sativa, as a supplement for opioid dependent receiving methadone. It focuses on the potential role of N. sativa and its major active compound, Thymoquinone (TQ as a calcium channel blocking agent to reduce withdrawal syndrome and opioid dependency.
Varma, Anjali; Sapra, Mamta; Iranmanesh, Ali
Objective The USA is in the midst of an opioid crisis. Understanding the impact of opioids and commonly used treatments for opioid dependence is essential for clinicians and researchers in order to educate and treat the nation's growing population with opioid use disorders. As a relatively new treatment for opioid dependence, buprenorphine is gaining popularity to the extent of becoming not only a preferred approach to the maintenance of opiate addiction, but also an option for chronic pain management. The purpose of this report is to review the available evidence on the endocrine effects of buprenorphine, particularly as it relates to the hypothalamic-pituitary-gonadal (HPG) axis, which is controversial and not fully defined. Method We conducted a Pubmed search (2000-2017) for human studies in the English language for articles that were available as full length regarding buprenorphine, endocrinopathy, hypogonadism, bone density, opioids. Case reports were also reviewed, although prospective studies and randomized controlled trials received more weight. Results Opioid induced hypogonadism is well established. Most studies report that buprenorphine being a partial agonist/antagonist may not be impacting the pituitary trophic hormones as much. There are reports of sexual dysfunction in subjects maintained on buprenorphine, some without hormonal correlation. Thus with the understanding that pertinent clinical studies are limited in number, varied in methodology, mostly cross sectional, predominantly in men and small number of participants, more research in this area is warranted. Conclusion Based on a comprehensive review of the available literature, we conclude that despite its increasing popularity, buprenorphine has not been adequately studied in respect to its long-term effects on the hypothalamic-pituitary-adrenal (HPA) axis. There is a great need for longitudinal systematic trials to define the potential buprenorphine-induced endocrine consequences.
Penney, Lauren S; Ritenbaugh, Cheryl; DeBar, Lynn L; Elder, Charles; Deyo, Richard A
Current literature describes the limits and pitfalls of using opioid pharmacotherapy for chronic pain and the importance of identifying alternatives. The objective of this study was to identify the practical issues patients and providers face when accessing alternatives to opioids, and how multiple parties view these issues. Qualitative data were gathered to evaluate the outcomes of acupuncture and chiropractic (A/C) services for chronic musculoskeletal pain (CMP) using structured interview guides among patients with CMP (n = 90) and primary care providers (PCPs) (n = 25) purposively sampled from a managed care health care system as well as from contracted community A/C providers (n = 14). Focus groups and interviews were conducted patients with CMP with varying histories of A/C use. Plan PCPs and contracted A/C providers took part in individual interviews. All participants were asked about their experiences managing chronic pain and experience with and/or attitudes about A/C treatment. Audio recordings were transcribed and thematically coded. A summarized version of the focus group/interview guides is included in the Additional file 1. We identified four themes around opioid use: (1) attitudes toward use of opioids to manage chronic pain; (2) the limited alternative options for chronic pain management; (3) the potential of A/C care as a tool to help manage pain; and (4) the complex system around chronic pain management. Despite widespread dissatisfaction with opioid medications for pain management, many practical barriers challenged access to other options. Most of the participants' perceived A/C care as helpful for short term pain relief. We identified that problems with timing, expectations, and plan coverage limited A/C care potential for pain relief treatment. These results suggest that education about realistic expectations for chronic pain management and therapy options, as well as making A/C care more easily accessible, might lead to more
Massaly, Nicolas; Morón, Jose A; Al-Hasani, Ream
Pain and stress are protective mechanisms essential in avoiding harmful or threatening stimuli and ensuring survival. Despite these beneficial roles, chronic exposure to either pain or stress can lead to maladaptive hormonal and neuronal modulations that can result in chronic pain and a wide spectrum of stress-related disorders including anxiety and depression. By inducing allostatic changes in the mesolimbic dopaminergic pathway, both chronic pain and stress disorders affect the rewarding values of both natural reinforcers, such as food or social interaction, and drugs of abuse. Despite opioids representing the best therapeutic strategy in pain conditions, they are often misused as a result of these allostatic changes induced by chronic pain and stress. The kappa opioid receptor (KOR) system is critically involved in these neuronal adaptations in part through its control of dopamine release in the nucleus accumbens. Therefore, it is likely that changes in the kappa opioid system following chronic exposure to pain and stress play a key role in increasing the misuse liability observed in pain patients treated with opioids. In this review, we will discuss how chronic pain and stress-induced pathologies can affect mesolimbic dopaminergic transmission, leading to increased abuse liability. We will also assess how the kappa opioid system may underlie these pathological changes.
Full Text Available Pain and stress are protective mechanisms essential in avoiding harmful or threatening stimuli and ensuring survival. Despite these beneficial roles, chronic exposure to either pain or stress can lead to maladaptive hormonal and neuronal modulations that can result in chronic pain and a wide spectrum of stress-related disorders including anxiety and depression. By inducing allostatic changes in the mesolimbic dopaminergic pathway, both chronic pain and stress disorders affect the rewarding values of both natural reinforcers, such as food or social interaction, and drugs of abuse. Despite opioids representing the best therapeutic strategy in acute pain conditions, they are often misused as a result of these allostatic changes induced by chronic pain and stress. The kappa opioid receptor system is critically involved in these neuronal adaptations in part through its control of dopamine release in the nucleus accumbens. Therefore, it is likely that changes in the kappa opioid system following chronic exposure to pain and stress play a key role in increasing the misuse liability observed in pain patients treated with opioids. In this review, we will discuss how chronic pain and stress-induced pathologies can affect mesolimbic dopaminergic transmission, leading to increased abuse liability. We will also assess how the kappa opioid system may underlie these pathological changes.
Xue Charlie CL
Full Text Available Abstract Background Chronic musculoskeletal pain is common and has been increasingly managed by opioid medications, of which the long-term efficacy is unknown. Furthermore, there is evidence that long-term use of opioids is associated with reduced pain control, declining physical function and quality of life, and could hinder the goals of integrated pain management. Electroacupuncture (EA has been shown to be effective in reducing postoperative opioid consumption. Limited evidence suggests that acupuncture could assist patients with chronic pain to reduce their requirements for opioids. The proposed research aims to assess if EA is an effective adjunct therapy to standard pain and medication management in reducing opioids use by patients with chronic musculoskeletal pain. Methods In this multicentre, randomised, sham-acupuncture controlled, three-arm clinical trial, 316 patients regularly taking opioids for pain control and meeting the defined selection criteria will be recruited from pain management centres and clinics of primary care providers in Victoria, Australia. After a four-week run-in period, the participants are randomly assigned to one of three treatment groups to receive EA, sham EA or no-EA with a ratio of 2:1:1. All participants receive routine pain medication management delivered and supervised by the trial medical doctors. Twelve sessions of semi-structured EA or sham EA treatment are delivered over 10 weeks. Upon completion of the acupuncture treatment period, there is a 12-week follow-up. In total, participants are involved in the trial for 26 weeks. Outcome measures of opioid and non-opioid medication consumption, pain scores and opioid-related adverse events are documented throughout the study. Quality of life, depression, function, and attitude to pain medications are also assessed. Discussion This randomised controlled trial will determine whether EA is of significant clinical value in assisting the management of
Bennett, Marsha; Bonanno, Laura; Kuhn, William
The objective of this systematic review is to examine the best available evidence on the clinical effectiveness of ketamine as an adjuvant to opioid-based therapy versus opioid-based therapy alone in decreasing perioperative pain associated with opioid tolerance in adult patients, aged 18-70 years, undergoing orthopedic surgical procedures.The following question guides the systematic review: does the administration of ketamine as an adjuvant to opioid-based therapy, compared to opioid-based therapy alone, improve perioperative pain relief in opioid-tolerant adult patients undergoing orthopedic surgical procedures?
Mammucari, M; Lazzari, M; Maggiori, E; Gafforio, P; Tufaro, G; Baffini, S; Maggiori, S; Palombo, E; de Meo, B; Sabato, A F
Informed consent is part of a process of communication useful to obtain an agreement (conscious, voluntary and free) between doctors and patients. Mesotherapy is based on the introduction of drugs by intradermal route in order to obtain a dose-sparing effect with respect to deeper administration. Opioids are the most appropriate therapy for patients who do not respond to other therapies. Proper communication between doctor and patient, including an explanation of the potential benefits, limitations and risks (even mild), is recommended both in clinical practice and research. Active participation of the patient has the advantage of better control of adverse events, both of mesotherapy and opioid-based therapy. This information-education process returns to the fundamental concept of "first do no harm" and set a "therapeutic partnership" with patients.
von Hippel, Courtney; Henry, Julie D; Terrett, Gill; Mercuri, Kimberly; McAlear, Karen; Rendell, Peter G
People with a history of substance abuse are subject to widespread stigmatization. It seems likely that this societal disapproval will result in feelings of stereotype threat, or the belief that one is the target of demeaning stereotypes. If so, stereotype threat has the potential to contribute to functional difficulties including poor social outcomes. Eighty drug users on opioid substitution therapy and 84 demographically matched controls completed measures of mental health and social function. The opioid substitution therapy group were additionally asked to complete a measure that focused on their feelings of stereotype threat in relation to their drug use history. Bivariate correlations and hierarchical regression analyses were conducted to establish the magnitude and specificity of the relationship between stereotype threat and social functioning. Relative to controls, the opioid substitution therapy group reported higher levels of negative affect and schizotypy, and poorer social functioning, with all three of these indices significantly correlated with their feelings of stereotype threat. The results also showed that stereotype threat contributed significant unique variance to social functioning in the opioid substitution therapy group, even after taking into account other background, clinical, and mental health variables. Social functioning is an important aspect of recovery, yet these data indicate that people with a history of drug abuse who believe they are the target of stereotypical attitudes have poorer social functioning. This relationship holds after controlling for the impact of other variables on social functioning, including mental health. The theoretical and practical implications of these findings are discussed. Concerns about being stereotyped can shape the social experiences of opioid substitution therapy patients. Opioid substitution therapy patients who feel negatively stereotyped experience greater social function deficits, and this
Opioid analgesics continue to be the mainstay of pharmacologic treatment of moderate to severe pain. Many patients, particularly those suffering from chronic pain, require chronic high-dose analgesic therapy. Achieving clinical efficacy and tolerability of such treatment regimens is hampered by the appearance of opioid-induced side effects such as tolerance, hyperalgesia and withdrawal syndrome. Among the therapeutic options to improve the opioid effectiveness, this current review focuses on strategies combining opioids to other drugs that can modulate opioid-mediated effects. We will discuss about experimental evidences reported for several potential opioid adjuvants, including N-methyl-D-aspartate receptor antagonists, 5-HT7 agonists, sigma-1 antagonists, I2-R ligands, cholecystokinin antagonists, neuropeptide FF-R antagonists and toll-like receptor 4 antagonists.
Paterson, Charlotte; Ledgerwood, Kay; Arnold, Carolyn; Hogg, Malcolm; Xue, Charlie; Zheng, Zhen
Opioids are increasingly prescribed for chronic noncancer pain across the developed world. Clinical guidelines for management of these patients focus on over-use. However, research into other types of long-term medication indicates that many patients minimize drug use whenever possible. To identify the varying influences on patients' decisions about their use of prescribed opioids and explore whether concepts of resistance and minimization of intake apply to these patients. A multiprofessional team performed a qualitative interview study using the constant-comparative method. Patient's decision making was explored in depth and with a thematic analysis utilizing a published "Model of medicine-taking." A purposive sample of 20 participants drawn from two pain clinics in Melbourne, Australia. The sample was biased toward patients interested in nonmedication pain management options. Patients' needs to obtain relief from severe pain, maintain function, and minimize side effects could lead to under-use as well as over-use of prescribed opioids. In keeping with the published Model of medicine-taking, resistance to taking opioids was a common and important influence on behavior. In the face of severe chronic pain, many participants used a variety of strategies to evaluate, avoid, reduce, self-regulate, and replace opioids. Furthermore, participants perceived a resistance to opioids within the system and among some healthcare professionals. This sometimes adversely affected their adherence. Both patients and doctors exhibit aspects of resistance to the use of prescribed opioids for chronic noncancer pain, suggesting that this shared concern could be the basis of a productive therapeutic alliance to improve communication and shared decision making. Clinical guidelines for opioids use for chronic noncancer pain focus on over-use. Our qualitative interview study found that many patients resisted and minimized the use of opioids. Using a published "Model of medicine-taking," we
Surjya Prasad Upadhyay
Full Text Available Many patients are admitted to the intensive care unit (ICU for acute intoxication, serious complication of overdose, or withdrawal symptoms of illicit drugs. An acute withdrawal of drugs with addiction potential is associated with a sympathetic overactivity leading to marked psychomimetic disturbances. Acute intoxication or withdrawal of such drugs is often associated with life-threatening complications which require ICU admission and necessitate prolonged sedative analgesic medications, weaning from which is often complicated by withdrawal and other psychomimetic symptoms. Dexmedetomidine, an alpha-2 (α2 agonist, has been used successfully to facilitate withdrawal and detoxification of various drugs and also to control delirium in ICU patients. Herein, we report a case of a chronic opioid abuse (heroin patient admitted with acute overdose complications leading to a prolonged ICU course requiring sedative-analgesic medication; the drug withdrawal-related symptoms further complicated the weaning process. Dexmedetomidine infusion was successfully used as a sedative-analgesic to control the withdrawal-related psychomimetic symptoms and to facilitate smooth detoxification and weaning from opioid and other sedatives.
Rocker, Graeme; Young, Joanne; Donahue, Margaret; Farquhar, Morag; Simpson, Catherine
A recent national practice guideline recommends the use of opioids for the treatment of refractory dyspnea in patients with advanced chronic obstructive pulmonary disease (COPD). We conducted two qualitative studies to explore the experiences of patients and family caregivers with opioids for refractory COPD-related dyspnea and the perspectives and attitudes of physicians toward opioids in this context. Patients (n = 8; 5 men, 3 women), their caregivers (n = 12; 5 men, 7 women) and physicians (n = 28, 17 men, 11 women) in Nova Scotia participated in the studies. Semistructured interviews were recorded, transcribed verbatim, coded conceptually and analyzed for emergent themes using interpretive description methodology. Patients reported that opioids provided a sense of calm and relief from severe dyspnea. Family caregivers felt that opioids helped patients to breathe more "normally," observed improvements in patients' symptoms of anxiety and depression, and experienced reductions in their own stress. Patients reported substantial improvements in their quality of life. All patients and family caregivers wanted opioid therapy to continue. Most physicians were reluctant to prescribe opioids for refractory dyspnea, describing a lack of related knowledge and experience, and fears related to the potential adverse effects and legal censure. Discrepancies between the positive experiences of patients and family caregivers with opioids and the reluctance of physicians to prescribe opioids for refractory dyspnea constitute an important gap in care. Bridging this gap will require initiatives to improve the uptake of practice guidelines and to increase confidence in prescribing opioids for dyspnea refractory to conventional treatment.
Brittany B. Dennis
Full Text Available Background While a number of pharmacological interventions exist for the treatment of opioid use disorder, evidence evaluating the effect of pain on substance use behavior, attrition rate, and physical or mental health among these therapies has not been well established. We aim to evaluate these effects using evidence gathered from a systematic review of studies evaluating chronic non-cancer pain (CNCP in patients with opioid use disorder. Methods We searched the Medline, EMBASE, PubMed, PsycINFO, Web of Science, Cochrane Database of Systematic Reviews, ProQuest Dissertations and theses Database, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform Search Portal, and National Institutes for Health Clinical Trials Registry databases to identify articles evaluating the impact of pain on addiction treatment outcomes for patients maintained on opioid agonist therapy. Results Upon screening 3,540 articles, 14 studies with a combined sample of 3,128 patients fulfilled the review inclusion criteria. Results from the meta-analysis suggest that pain has no effect on illicit opioid consumption [pooled odds ratio (pOR: 0.70, 95%CI 0.41–1.17; I 2 = 0.0] but a protective effect for reducing illicit non-opioid substance use (pOR: 0.57, 95%CI 0.41–0.79; I 2 = 0.0. Studies evaluating illicit opioid consumption using other measures demonstrate pain to increase the risk for opioid abuse. Pain is significantly associated with the presence of psychiatric disorders (pOR: 2.18; 95%CI 1.6, 2.9; I 2 = 0.0%. Conclusion CNCP may increase risk for continued opioid abuse and poor psychiatric functioning. Qualitative synthesis of the findings suggests that major methodological differences in the design and measurement of pain and treatment response outcomes are likely impacting the effect estimates.
Garland, Eric L; Froeliger, Brett; Zeidan, Fadel; Partin, Kaitlyn; Howard, Matthew O
Prescription opioid misuse and addiction among chronic pain patients are emerging public health concerns of considerable significance. Estimates suggest that more than 10% of chronic pain patients misuse opioid analgesics, and the number of fatalities related to nonmedical or inappropriate use of prescription opioids is climbing. Because the prevalence and adverse consequences of this threat are increasing, there is a pressing need for research that identifies the biobehavioral risk chain linking chronic pain, opioid analgesia, and addictive behaviors. To that end, the current manuscript draws upon current neuropsychopharmacologic research to provide a conceptual framework of the downward spiral leading to prescription opioid misuse and addiction among chronic pain patients receiving opioid analgesic pharmacotherapy. Addictive use of opioids is described as the outcome of a cycle initiated by chronic pain and negative affect and reinforced by opioidergic-dopamingeric interactions, leading to attentional hypervigilance for pain and drug cues, dysfunctional connectivity between self-referential and cognitive control networks in the brain, and allostatic dysregulation of stress and reward circuitry. Implications for clinical practice are discussed; multimodal, mindfulness-oriented treatment is introduced as a potentially effective approach to disrupting the downward spiral and facilitating recovery from chronic pain and opioid addiction. Copyright © 2013 Elsevier Ltd. All rights reserved.
Hansen, Carrinna; Abrahamsen, Bo
, socioeconomic and demographic characteristics. Data analysis is ongoing. Conclusions: It is expected that this study will serve as a significant supplement of existing knowledge in the area of opioid consumption among CNP patients in Denmark. In a future perspective of prevention and health promotion......Aims: 1) To determine the distribution and determinants of opioid use among chronic nonmalignant pain(CNP) patients. 2) To identify the patient, treatment and socioeconomic characteristics as determinants for potential risk groups. We hypothesized that CNP patient who use opioids for more than 1...... product using the ATC codes N02AA01-N02AX06. Patients were then classified as either opioid use for more than 1 year(group A), as opioid use for more than 6 months but less than 1 year(group B) and opioid use equal to or less than 6 months(group C). Results: The quantity of sold opioids has been...
Bates, John J
Opioid medication is the mainstay of therapy for severe acute and chronic pain. Unfortunately, the side effects of these medications can affect patient comfort and safety, thus limiting their proven therapeutic potential. Whereas the main analgesic effects of opioids are centrally mediated, many of the common side effects are mediated via peripheral receptors. Novel peripheral opioid antagonists have been recently introduced that can block the peripheral actions of opioids without affecting centrally mediated analgesia. We review the clinical and experimental evidence of their efficacy in ameliorating opioid side effects and consider what further information might be useful in defining their role. IMPLICATIONS: The major analgesic effects of opioid medication are mediated within the brain and spinal cord. Many of the side effects of opioids are caused by activation of receptors outside these areas. Recently developed peripherally restricted opioid antagonists have the ability to block many opioid side effects without affecting analgesia.
Ajo, Raquel; Segura, Ana; Inda, María-Del-Mar; Margarit, César; Ballester, Pura; Martínez, Emi; Ferrández, Guillermina; Sánchez-Barbie, Ángel; Peiró, Ana M
Chronic pain is associated with comorbidities that have an impact on the quality of life of patients and, among others, affect their sexual functioning. One of the most relevant side effects of opioid analgesics is erectile dysfunction (ED), due in part to the inhibition of the gonadal-pituitary-hypothalamic axis and the decline in testosterone levels. To evaluate ED and effectiveness of treatment in men with chronic pain treated with long-term opioids. Prospective observational study lasting 3 years, where the intensity of pain (visual analogue scale, 0-10cm), erectile function (IIEF-EF, range 1-30 points), quality of life (EQ-VAS, 0-100mm), quality of sexual life (MSLQ-QOL, 0-100 points), anxiety/depression (HAD, 0-21 points) and testosterone levels, was assessed in patients who reported sexual dysfunction (ED or libido modification). A 6-month follow-up was applied to each patient after administering the usual treatment in the Andrology Unit. The study was approved by the Clinical Research Ethics Committee and data were statistically analyzed with the GraphPad Prism 5 software. ED was observed in 27.6% of patients (n=105, 57±12.2 years, mean dose of morphine equivalent=107.1±107.9mg/day, 84.3% adjuvant analgesics). After 6 months, 42% of patients showed a significant improvement after being treated with iPDE5 (48.5%) and/or testosterone gel (81.8%), with a resolution rate of 31% (p=0.000). A positive correlation was observed between the improvement of IIEF and quality of sexual life (55.5±25.7 points, p=0.000), as well as anxiety (7.4±4.3 points, p=0.048). No significant changes were observed in the levels of testosterone, in the levels of pain nor in the quality of life, which remained moderate. Erectile function and quality of sexual life, as well as anxiety, improved in patients treated chronically with opioids after administering andrological treatment. The management of patients with pain should include a review of their sexual health history given the
Full Text Available Patients with chronic pain and depression are more likely to develop opioid abuse compared to patients without depression. It is not known if this association differs by pain location. We compared the strength of association between depression and opioid misuse in patients with chronic low back pain (CLBP vs. chronic pain of other location (CPOL. Chart abstracted data was obtained from 166 patients seeking care in a family medicine clinic. Depression was measured by the PHQ-9 and opioid misuse was measured using the Current Opioid Misuse Measure. Pain severity and interference questions came from the Brief Pain Inventory. Cross-tabulations were computed to measure the association between depression and opioid misuse stratified on pain location. Exploratory logistic regression modeled the association between depression and opioid misuse after adjusting for pain location and pain severity and interference. Depression was significantly associated with opioid misuse in CPOL but not in CLBP. Regression results indicate pain interference partly accounts for the depression–opioid misuse association. These preliminary results from a small patient sample suggest depression may co-occur with opioid misuse more often in CPOL than in CLBP. Further research is needed to compare this comorbidity in specific pain diagnoses such as arthritis, fibromyalgia and CLBP.
... Long-term daily use of opioids leads to physical dependence, which is not to be confused with addiction ... be screened and closely monitored. When people have physical dependence and the opioid use is stopped, withdrawal symptoms ...
Neumann, Anne M; Blondell, Richard D; Jaanimägi, Urmo; Giambrone, Amanda K; Homish, Gregory G; Lozano, Jacqueline R; Kowalik, Urszula; Azadfard, Mohammadreza
Patients with opioid addiction who receive prescription opioids for treatment of nonmalignant chronic pain present a therapeutic challenge. Fifty-four participants with chronic pain and opioid addiction were randomized to receive methadone or buprenorphine/naloxone. At the 6-month follow-up examination, 26 (48.1%) participants who remained in the study noted a 12.75% reduction in pain (P = 0.043), and no participants in the methadone group compared to 5 in the buprenorphine group reported illicit opioid use (P = 0.039). Other differences between the two conditions were not found. Long-term, low-dose methadone or buprenorphine/naloxone treatment produced analgesia in participants with chronic pain and opioid addiction.
Ekholm, Ola; Grønbaek, Morten; Peuckmann, Vera
The primary aim of this epidemiological study was to investigate associations between chronic non-cancer pain with or without opioid treatment and the alcohol and smoking behavior. The secondary aims were to investigate self-reported quality of life, sleeping problems, oral health and the use...... chronic/long-lasting pain lasting 6 months or more?' The question concerning alcohol intake assessed the frequency of alcohol intake and binge drinking. Smoking behavior assessed the daily number of cigarettes. Individuals reporting chronic pain were stratified into two groups (opioid users and non...... individuals. We found, that individuals suffering from chronic pain were less likely to drink alcohol. In opioid users alcohol consumption was further reduced. Cigarette smoking was significantly increased in individuals suffering from chronic pain and in opioid users smoking was further increased. Poor oral...
O'Brien, T; Christrup, L L; Drewes, A M
burdened by an unacceptable level of adverse effects, the overall management strategy must be reviewed and revised. No responsible clinician will wish to pursue a failed treatment strategy or persist with an ineffective and burdensome treatment. In a considered attempt to empower and inform non......Poorly controlled pain is a global public health issue. The personal, familial and societal costs are immeasurable. Only a minority of European patients have access to a comprehensive specialist pain clinic. More commonly the responsibility for chronic pain management and initiating opioid therapy...... years of clinical practice to produce these series of recommendations. Its success will be judged on the extent to which it contributes to an improved pain management experience for chronic pain patients across Europe. SIGNIFICANCE: This position paper provides expert recommendations for primary care...
Chu, Larry F; Rico, Tom; Cornell, Erika; Obasi, Hannah; Encisco, Ellen M; Vertelney, Haley; Gamble, Jamison G; Crawford, Clayton W; Sun, John; Clemenson, Anna; Erlendson, Matthew J; Okada, Robin; Carroll, Ian; Clark, J David
In this study, we investigated the co-administration of ondansetron with morphine, and whether it could prevent the development of physical dependence in patients taking opioids for the treatment of chronic pain. A total of 48 chronic back pain patients (N = 48) participated in this double-blinded, placebo-controlled, randomized study. Patients were titrated onto sustained-release oral morphine and randomized to take 8 mg ondansetron or placebo three times daily concurrently with morphine during the 30-day titration. Following titration, patients underwent Naloxone induced opioid withdrawal. Opioid withdrawal signs and symptoms were then assessed by a blinded research assistant (objective opioid withdrawal score: OOWS) and by the research participant (subjective opioid withdrawal score: SOWS). We observed clinically significant signs of naloxone-precipitated opioid withdrawal in all participants (ΔOOWS = 4.3 ± 2.4, p physical dependence in human subjects when co-administered with opioids, but found no difference in naloxone-precipitated opioid withdrawal scores between ondansetron and placebo treatment groups. These results suggest that further studies are needed to determine if 5HT 3 receptor antagonists are useful in preventing opioid physical dependence. Copyright © 2017 Elsevier B.V. All rights reserved.
Worley, Matthew J; Heinzerling, Keith G; Shoptaw, Steven; Ling, Walter
The combination of prescription opioid dependence and chronic pain is increasingly prevalent and hazardous to public health. Variability in pain may explain poor prescription opioid addiction treatment outcomes in persons with chronic pain. This study examined pain trajectories and pain volatility in patients with chronic pain receiving treatment for prescription opioid addiction. We conducted secondary analyses of adults with chronic pain (n = 149) who received buprenorphine/naloxone (BUP/NLX) and counseling for 12 weeks in an outpatient, multisite clinical trial. Good treatment outcome was defined as urine-verified abstinence from opioids at treatment endpoint (Week 12) and during at least 2 of the previous 3 weeks. Pain severity significantly declined over time during treatment (b = -0.36, p opioid dependence. Patients with greater volatility in subjective pain during treatment have increased risk of returning to opioid use by the conclusion of an intensive treatment with BUP/NLX and counseling. Future research should examine underlying mechanisms of pain volatility and identify related therapeutic targets to optimize interventions for prescription opioid addiction and co-occurring chronic pain. (PsycINFO Database Record (c) 2015 APA, all rights reserved).
Plesner, K; Jensen, H I; Højsted, J
doses than never smokers and former smokers not using nicotine. CONCLUSIONS: The study supports previous evidence that smoking is associated with chronic pain. Our data suggest that information about use of nicotine substitution in chronic non-malignant patients are relevant both in a clinical setting......BACKGROUND: Previous studies have demonstrated a positive association between smoking and addiction to opioids in patients with chronic non-malignant pain. This could be explained by a susceptibility in some patients to develop addiction. Another explanation could be that nicotine influences both...... pain and the opioid system. The objective of the study was to investigate whether smoking, former smoking ± nicotine use and nicotine dependence in patients with chronic non-malignant pain were associated with opioid use and addiction to opioids. METHODS: The study was a cross-sectional study carried...
Højsted, Jette; Nielsen, Per Rotbøll; Guldstrand, Sally Kendall
Addiction is a feared consequence of long-term opioid treatment of chronic pain patients. The ICD-10 and DSM-IV diagnostic addiction criteria may not be appropriate in these patients. Therefore Portenoy's criteria (PC) were launched. The aim was to estimate the prevalence of addiction......, to investigate whether PC were applicable and to compare these criteria with the ICD-10 criteria. The study was cross-sectional and included 253 patients with chronic pain at a tertiary pain centre. Patients were screened for addiction by a physician and a nurse. The addiction prevalence was 14.4% according...... to ICD-10 and 19.3% according to PC. A significant difference between the prevalence of addiction according to ICD-10 and to PC was found. The inter-rater reliability was 0.95 for ICD-10 and 0.93 for PC. The sensitivity of PC was 0.85 and the specificity was 0.96. According to PC patients classified...
Frank, Joseph W; Lovejoy, Travis I; Becker, William C; Morasco, Benjamin J; Koenig, Christopher J; Hoffecker, Lilian; Dischinger, Hannah R; Dobscha, Steven K; Krebs, Erin E
Expert guidelines recommend reducing or discontinuing long-term opioid therapy (LTOT) when risks outweigh benefits, but evidence on the effect of dose reduction on patient outcomes has not been systematically reviewed. To synthesize studies of the effectiveness of strategies to reduce or discontinue LTOT and patient outcomes after dose reduction among adults prescribed LTOT for chronic pain. MEDLINE, EMBASE, PsycINFO, CINAHL, and the Cochrane Library from inception through April 2017; reference lists; and expert contacts. Original research published in English that addressed dose reduction or discontinuation of LTOT for chronic pain. Two independent reviewers extracted data and assessed study quality using the U.S. Preventive Services Task Force quality rating criteria. All authors assessed evidence quality using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Prespecified patient outcomes were pain severity, function, quality of life, opioid withdrawal symptoms, substance use, and adverse events. Sixty-seven studies (11 randomized trials and 56 observational studies) examining 8 intervention categories, including interdisciplinary pain programs, buprenorphine-assisted dose reduction, and behavioral interventions, were found. Study quality was good for 3 studies, fair for 13 studies, and poor for 51 studies. Many studies reported dose reduction, but rates of opioid discontinuation ranged widely across interventions and the overall quality of evidence was very low. Among 40 studies examining patient outcomes after dose reduction (very low overall quality of evidence), improvement was reported in pain severity (8 of 8 fair-quality studies), function (5 of 5 fair-quality studies), and quality of life (3 of 3 fair-quality studies). Heterogeneous interventions and outcome measures; poor-quality studies with uncontrolled designs. Very low quality evidence suggests that several types of interventions may be effective to reduce or
Søndergaard, Jens; Christensen, Helene Nordahl; Ibsen, Rikke
-based cohort study including patients ≥18 years of age initiating ≥4 weeks opioid therapy (1998–2012) in Denmark. A measure of OIC was constructed based on data from Danish national health registries, and defined as ≥1 diagnosis of constipation, diverticulitis, mega colon, ileus/subileus, abdominal pain....../acute abdomen or haemorrhoids and/or ≥2 subsequent prescription issues of laxatives. Total healthcare resource utilization and costs (including pharmacy dispense, inpatient-, outpatient-, emergency room- and primary care) were estimated according to OIC status, opioid treatment dosage and length, gender, age...... characteristics of non-cancer OIC patients showed a higher frequency of strong opioid treatment (69% versus 41%), long-term opioid treatment (1189 days versus 584 days), advanced age (73 years versus 61 years), and cardiovascular disease (31% versus 19%) compared to those without OIC (P
Garland, Eric L; Hanley, Adam W; Bedford, Carter E; Zubieta, Jon-Kar; Howard, Matthew O; Nakamura, Yoshio; Donaldson, Gary W; Froeliger, Brett
A subset of chronic pain patients misuse prescription opioids as a means of regulating negative emotions. However, opioid misuse may result in deficits in emotion regulation strategies like reappraisal by virtue of the deleterious effects of chronic opioid exposure. The aim of this study was to characterize differences in reappraisal use among chronic pain patients at risk for opioid misuse and those who report taking opioids as prescribed. A sample of 127 pain patients receiving chronic opioid analgesic pharmacotherapy were classified as at risk for opioid misuse (n = 62) or taking opioids as prescribed (n = 65) using the Current Opioid Misuse Measure (COMM). The Emotion Regulation Questionnaire (ERQ) characterized use of emotion regulation strategies including reappraisal and expressive suppression. Participants also reported levels of opioid craving, emotional distress, and pain severity. Patients at risk for opioid misuse reported significantly less reappraisal use (M = 25.31, SD = 7.33) than those who reportedly took opioids as prescribed (M = 30.28, SD = 7.50), p<.001, but did differ with regard to suppression strategies. Reduced reappraisal use was associated with higher opioid craving and emotional distress that mediated the association between reappraisal deficits and opioid misuse risk. Further, there was a significant indirect effect of opioid misuse on emotional distress via reappraisal use. Opioid misuse risk was associated with reduced use of reappraisal, which in turn was associated with dysregulated negative emotions and increased appetitive drive towards consuming opioids. Studying individual differences in emotion regulation may yield efficacious intervention and prevention approaches to stem the rising tide of the prescription opioid crisis.
Full Text Available Igor Kissin Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Background: For the past 30 years, opioids have been used to treat chronic nonmalignant pain. This study tests the following hypotheses: (1 there is no strong evidence-based foundation for the conclusion that long-term opioid treatment of chronic nonmalignant pain is effective; and (2 the main problem associated with the safety of such treatment – assessment of the risk of addiction – has been neglected. Methods: Scientometric analysis of the articles representing clinical research in this area was performed to assess (1 the quality of presented evidence (type of study; and (2 the duration of the treatment phase. The sufficiency of representation of addiction was assessed by counting the number of articles that represent (1 editorials; (2 articles in the top specialty journals; and (3 articles with titles clearly indicating that the addiction-related safety is involved (topic-in-title articles. Results: Not a single randomized controlled trial with opioid treatment lasting >3 months was found. All studies with a duration of opioid treatment ≥6 months (n = 16 were conducted without a proper control group. Such studies cannot provide the consistent good-quality evidence necessary for a strong clinical recommendation. There were profound differences in the number of addiction articles related specifically to chronic nonmalignant pain patients and to opioid addiction in general. An inadequate number of chronic pain-related publications were observed with all three types of counted articles: editorials, articles in the top specialty journals, and topic-in-title articles. Conclusion: There is no strong evidence-based foundation for the conclusion that long-term opioid treatment of chronic nonmalignant pain is effective. The above identified signs indicating neglect of addiction associated with the
Feingold, Daniel; Goor-Aryeh, Itay; Bril, Silviu; Delayahu, Yael; Lev-Ran, Shaul
To assess prevalence rates and correlates of problematic use of prescription opioids and medicinal cannabis (MC) among patients receiving treatment for chronic pain. Cross-sectional study. Two leading pain clinics in Israel. Our sample included 888 individuals receiving treatment for chronic pain, of whom 99.4% received treatment with prescription opioids or MC. Problematic use of prescription opioids and MC was assessed using DSM-IV criteria, Portenoy’s Criteria (PC), and the Current Opioid Misuse Measure (COMM) questionnaire. Additional sociodemographic and clinical correlates of problematic use were also assessed. Among individuals treated with prescription opioids, prevalence of problematic use of opioids according to DSM-IV, PC, and COMM was 52.6%, 17.1%, and 28.7%, respectively. Among those treated with MC, prevalence of problematic use of cannabis according to DSM-IV and PC was 21.2% and 10.6%, respectively. Problematic use of opioids and cannabis was more common in individuals using medications for longer periods of time, reporting higher levels of depression and anxiety, and using alcohol or drugs. Problematic use of opioids was associated with higher self-reported levels of pain, and problematic use of cannabis was more common among individuals using larger amounts of MC. Problematic use of opioids is common among chronic pain patients treated with prescription opioids and is more prevalent than problematic use of cannabis among those receiving MC. Pain patients should be screened for risk factors for problematic use before initiating long-term treatment for pain-control.
Robert N. Jamison
Full Text Available Opioid analgesics provide effective treatment for noncancer pain, but many physicians have concerns about adverse effects, tolerance, and addiction. Misuse of opioids is prominent in patients with chronic back pain and early recognition of misuse risk could help physicians offer adequate patient care while implementing appropriate levels of monitoring to reduce aberrant drug-related behaviors. In this review, we discuss opioid abuse and misuse issues that often arise in the treatment of patients with chronic back pain and present an overview of assessment and treatment strategies that can be effective in improving compliance with the use of prescription opioids for pain. Many persons with chronic back pain have significant medical, psychiatric and substance use comorbidities that affect treatment decisions and a comprehensive evaluation that includes a detailed history, physical, and mental health evaluation is essential. Although there is no “gold standard” for opioid misuse risk assessment, several validated measures have been shown to be useful. Controlled substance agreements, regular urine drug screens, and interventions such as motivational counseling have been shown to help improve patient compliance with opioids and to minimize aberrant drug-related behavior. Finally, we discuss the future of abuse-deterrent opioids and other potential strategies for back pain management.
Becker, William C; Fenton, Brenda T; Brandt, Cynthia A; Doyle, Erin L; Francis, Joseph; Goulet, Joseph L; Moore, Brent A; Torrise, Virginia; Kerns, Robert D; Kreiner, Peter W
Opioid overdose and other related harms are a major source of morbidity and mortality among US Veterans, in part due to high-risk opioid prescribing. We sought to determine whether having multiple sources of payment for opioids-as a marker for out-of-system access-is associated with risky opioid therapy among veterans. Cross-sectional study examining the association between multiple sources of payment and risky opioid therapy among all individuals with Veterans Health Administration (VHA) payment for opioid analgesic prescriptions in Kentucky during fiscal year 2014-2015. Source of payment categories: (1) VHA only source of payment (sole source); (2) sources of payment were VHA and at least 1 cash payment [VHA+cash payment(s)] whether or not there was a third source of payment; and (3) at least one other noncash source: Medicare, Medicaid, or private insurance [VHA+noncash source(s)]. Our outcomes were 2 risky opioid therapies: combination opioid/benzodiazepine therapy and high-dose opioid therapy, defined as morphine equivalent daily dose ≥90 mg. Of the 14,795 individuals in the analytic sample, there were 81.9% in the sole source category, 6.6% in the VHA+cash payment(s) category, and 11.5% in the VHA+noncash source(s) category. In logistic regression, controlling for age and sex, persons with multiple payment sources had significantly higher odds of each risky opioid therapy, with those in the VHA+cash having significantly higher odds than those in the VHA+noncash source(s) group. Prescribers should examine the prescription monitoring program as multiple payment sources increase the odds of risky opioid therapy.
Eriksen, Jørgen; Sjøgren, Per; Bruera, Eduardo
-related quality of life (SF-36), use of the health care system, functional capabilities, satisfaction with medical pain treatment and regular or continuous use of medications. Participants reporting pain were divided into opioid and non-opioid users. The analyses were adjusted for age, gender, concomitant use...
Zaman, Tauheed; Rife, Tessa L; Batki, Steven L; Pennington, David L
Co-prescribing opioids and benzodiazepines increases overdose risk. A paucity of literature exists evaluating strategies to improve safety of co-prescribing. This study evaluated an electronic intervention to improve safety for patients co-prescribed chronic opioids for pain and benzodiazepines at 3 and 6 months. A prospective cohort study was conducted from December 2015 through May 2016 at San Francisco Veterans Affairs Health Care System. A clinical dashboard identified 145 eligible patients prescribed chronic opioids and benzodiazepines. Individualized taper and safety recommendations were communicated to prescribers via electronic medical record progress note and encrypted e-mail at baseline. Primary outcome was number of patients co-prescribed chronic opioids and benzodiazepines. Secondary outcomes included daily dose of opioids and benzodiazepines and number prescribed ≥100 mg morphine equivalent daily dose. Safety outcomes included number with opioid overdose education and naloxone distribution, annual urine drug screening, annual prescription drug monitoring program review, and signed opioid informed consent. Linear mixed models and generalized estimating equations were used to examine within-group change in outcomes between baseline and 3 and 6 months. Among the 145 patients, mean (standard deviation) age was 62 (11) years and 91.7% (133/145) were male. Number co-prescribed significantly decreased from 145/145 (100%) at baseline to 93/139 (67%) at 6-month follow-up (odds ratio [OR] = 0.53, 95% confidence interval [CI]: 0.34-0.81, P = .003). Mean opioid and benzodiazepine doses significantly decreased from 84.61 to 65.63 mg (95% CI: 8.32-27.86, P improve safety for patients co-prescribed chronic opioids for pain and benzodiazepines.
Bailey, Chris P; Husbands, Stephen M
Psychostimulant and opioid addiction are poorly treated. The majority of abstinent users relapse back to drug-taking within a year of abstinence, making 'anti-relapse' therapies the focus of much current research. There are two fundamental challenges to developing novel treatments for drug addiction. First, there are three key stimuli that precipitate relapse back to drug-taking: stress, presentation of drug-conditioned cue, taking a small dose of drug. The most successful novel treatment would be effective against all three stimuli. Second, a large number of drug users are poly-drug users: taking more than one drug of abuse at a time. The ideal anti-addiction treatment would, therefore, be effective against all classes of drugs of abuse. In this review, the authors discuss the clinical need and animal models used to uncover potential novel treatments. There is a very broad range of potential treatment approaches and targets currently being examined as potential anti-relapse therapies. These broadly fit into two categories: 'memory-based' and 'receptor-based' and the authors discuss the key targets here within. Opioid receptors and ligands have been widely studied, and research into how different opioid subtypes affect behaviours related to addiction (reward, dysphoria, motivation) suggests that they are tractable targets as anti-relapse treatments. Regarding opioid ligands as novel 'anti-relapse' medication targets, research suggests that a 'non-selective' approach to targeting opioid receptors will be the most effective.
Udi E Ghitza
Full Text Available Over the past two decades, a steeply growing number of persons with chronic non-cancer pain have been using opioid analgesics chronically to treat it, accompanied by a markedly increased prevalence of individuals with opioid-related misuse, opioid use disorders, emergency department visits, hospitalizations, admissions to drug treatment programs, and drug overdose deaths. This opioid misuse and overdose epidemic calls for well-designed randomized-controlled clinical trials into more skillful and appropriate pain management and for developing effective analgesics which have lower abuse liability and are protective against stress induced by chronic non-cancer pain. However, incomplete knowledge regarding effective approaches to treat various types of pain has been worsened by an under-appreciation of overlapping neurobiological mechanisms of stress, stress-induced relapse to opioid use, and chronic non-cancer pain in patients presenting for care for these conditions. This insufficient knowledge base has unfortunately encouraged common prescription of conveniently-available opioid pain-relieving drugs with abuse liability, as opposed to treating underlying problems using team-based multidisciplinary, patient-centered, collaborative-care approaches for addressing pain and co-occurring stress and risk for opioid use disorder. This paper reviews recent neurobiological findings regarding overlapping mechanisms of stress-induced relapse to opioid misuse and chronic non-cancer pain, and then discusses these in the context of key outstanding evidence gaps and clinical-treatment research directions which may be pursued to fill these gaps. Such research directions, if conducted through well-designed randomized controlled trials, may substantively inform clinical practice in general medical settings on how to effectively care for patients presenting with pain-related distress and these common co-occurring conditions.
Henry, Stephen G; Chen, Meng; Matthias, Marianne S; Bell, Robert A; Kravitz, Richard L
To describe the development and initial application of the Chronic Pain Coding System. Secondary analysis of data from a randomized clinical trial. Six primary care clinics in northern California. Forty-five primary care visits involving 33 clinicians and 45 patients on opioids for chronic noncancer pain. The authors developed a structured coding system to accurately and objectively characterize discussions about pain and opioids. Two coders applied the final system to visit transcripts. Intercoder agreement for major coding categories was moderate to substantial (kappa = 0.5-0.7). Mixed effects regression was used to test six hypotheses to assess preliminary construct validity. Greater baseline pain interference was associated with longer pain discussions (P = 0.007) and more patient requests for clinician action (P = 0.02) but not more frequent negative patient evaluations of pain (P = 0.15). Greater clinician-reported visit difficulty was associated with more frequent disagreements with clinician recommendations (P = 0.003) and longer discussions of opioid risks (P = 0.049) but not more frequent requests for clinician action (P = 0.11). Rates of agreement versus disagreement with patient requests and clinician recommendations were similar for opioid-related and non-opioid-related utterances. This coding system appears to be a reliable and valid tool for characterizing patient-clinician communication about opioids and chronic pain during clinic visits. Objective data on how patients and clinicians discuss chronic pain and opioids are necessary to identify communication patterns and strategies for improving the quality and productivity of discussions about chronic pain that may lead to more effective pain management and reduce inappropriate opioid prescribing. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: email@example.com.
Full Text Available We report a case of 42-year-old male patient with hypogonadotropic hypogonadism. He suffered from general fatigue and erectile dysfunction after the treatment with transdermal fentanyl for chronic pain by traffic injury. Endocrine examinations and hormone stimulating tests showed that he had hypogonadotropic hypogonadism. Brain magnetic resonance imaging (MRI showed no abnormal findings, and he had no past history of accounting for acquired hypogonadotropic hypogonadism. Therefore, his hypogonadism was diagnosed to be caused by opioid treatment. Although opioid-induced endocrine dysfunctions are not widely recognized, this case suggests that we should consider the possibility of endocrine dysfunctions in patients with opioid treatment.
Garland, Eric L; Riquino, Michael R; Priddy, Sarah E; Bryan, Craig J
Given that chronic pain patients experience significant rates of suicidal ideation and suicide attempts, access to prescription opioids compounds the risk of death by suicide. These patients may experience heightened opioid craving and exhibit increased cue-reactivity to stimuli associated with past opioid use when suicidal ideation produces negative affective states. Because both opioids and suicidal behavior are used to alleviate emotional and physical pain through a process of negative reinforcement, elucidating factors that mediate this association may yield insight into suicide risk among chronic pain patients. This study examined the relationship between suicidal ideation and opioid craving and cue-reactivity, and tested opioid self-medication as a mediator of associations between those factors after controlling for the impact of pain severity. A sample of 115 chronic pain patients provided demographic and clinical information on the Obsessive Compulsive Drug Use Scale, the Current Opioid Misuse Measure, and the Brief Pain Inventory before completing an opioid dot probe task in which heart rate variability was recorded. As hypothesized, suicidal ideation was positively correlated with subjective opioid craving and physiological cue-reactivity. Self-medication significantly mediated the association between suicidal ideation, craving, and cue-reactivity. As opioids relieve the emotional pain linked with suicidal thoughts, chronic pain patients with higher levels of suicidal ideation may experience more intense opioid craving and exhibit heightened physiological cue-reactivity when compared to patients with low levels of suicidal ideation.
Page, Julia; Traver, Robin; Patel, Sital; Saliba, Christopher
In 2016, the Oregon Health Authority and the Health Evidence Review Commission implemented guidance for Oregon Medicaid members who were taking opioids for chronic pain related to conditions of the back and spine. This guidance required that an individualized taper plan be developed and initiated by January 1, 2017, and a discontinuation date for all chronic opioid therapy of January 1, 2018. This program evaluated the effect of a proactive and voluntary health plan-driven opioid tapering program on morphine equivalent daily dose (MEDD) before the implementation of governmental guidance. Two mailings were sent to the providers of the targeted members with a variety of resources to facilitate an opioid taper. Pharmacy claims were analyzed to measure member opioid use, in the form of MEDD, after the provider outreach to be compared with their MEDDs before the outreach. A total of 113 members met the study inclusion criteria for the second provider outreach. Of the 19 members' providers who submitted responses via fax to the health plan in response to this outreach, 6 indicated they would initiate taper plans. Of the 6 members with taper plans, 5 had decreases in MEDD (3.6%, 4.5%, 42.9%, 45.5%, and 46.1%) after the 3-month data collection period, while the sixth member had no change in MEDD. Of the 113 members, 16 members (14.2%) had a decrease in MEDD; 23 members (20.4%) had no change in MEDD; and 72 members (63.7%) had an increase in MEDD. This study demonstrated that when a physician agrees to enroll patients in a health-plan driven clinical program it may result in decreased opioid use as referenced by MEDD. However, the results also showed the progressive nature of opioid use in this population. While these initial taper results were promising, a larger sample size and longer follow-up duration are needed to validate long-term adherence to an opioid tapering program and confirm that these results are attributable to the program and not other factors. This study
Ekaterina Leonidovna Zaytseva
Full Text Available Chronic wound in patients with diabetes mellitus (DM is one of the most urgent problems of modern diabetology and surgery. Numberof patients suffering from different types of chronic wounds follows increase in DM incidence. Vacuum therapy is a novel perspectivemethod of topical treatment for non-healing chronic wounds of various etiology. Current review addresses experimental and clinicalevidence for this method.
Svanberg, Anncarin; Birgegård, Gunnar; Ohrn, Kerstin
Mucositis is a major complication in myeloablative therapy, which often necessitates advanced pharmacological pain treatment, including i.v. opioids. Attempts to prevent oral mucositis have included oral cryotherapy, which has been shown to reduce mucositis, but there is a lack of knowledge concerning the effect of oral cryotherapy on opioid use by reducing the mucositis for patients treated with myeloablative therapy before bone marrow transplantation (BMT). The aim of the present study was to evaluate if oral cryotherapy could delay or alleviate the development of mucositis and thereby reduce the number of days with i.v. opioids among patients who receive myeloablative therapy before BMT. Eighty patients 18 years and older, scheduled for BMT, were included consecutively and randomised to oral cryotherapy or standard oral care. A stratified randomisation was used with regard to type of transplantation. Intensity of pain, severity of mucositis and use of opioids were recorded using pain visual analogue scale (VAS) scores, mucositis index scores and medical and nursing charts. This study showed that patients receiving oral cryotherapy had less pronounced mucositis and significantly fewer days with i.v. opioids than the control group. In the autologous setting, cryotherapy patients also needed significantly lower total dose of opioids. Oral cryotherapy is an effective and well-tolerated therapy to alleviate mucositis and consequently reduce the number of days with i.v. opioids among patients treated with myeloablative therapy before BMT.
How we frame our thoughts about chronic opioid therapy greatly influences our ability to practice patient-centered care. Even providers who strive to be non-judgmental may approach clinical decision-making about opioids by considering if the pain is real or they can trust the patient. Not only does this framework potentially lead to poor or unshared decision-making, it likely adds to provider and patient discomfort by placing the provider in the position of a police officer or judge. Similarly, providers often find themselves making deals with patients using a positional bargaining approach. Even if a compromise is reached, this framework can potentially inadvertently weaken the therapeutic relationship by encouraging the idea that the patient and provider have opposing goals. Reframing the issue can allow the provider to be in a more therapeutic role. As recommended in the APS/AAPM guidelines, providers should decide whether the benefits of opioid therapy are likely to outweigh the harms for a specific patient (or sometimes, for society) at a specific time. This paper discusses how providers can use a benefit-to-harm framework to make and communicate decisions about the initiation, continuation, and discontinuation of opioids for managing chronic non-malignant pain. Such an approach focuses decisions and discussions on judging the treatment, not the patient. It allows the provider and the patient to ally together and make shared decisions regarding a common goal. Moving to a risk-benefit framework may allow providers to provide more patient-centered care, while also increasing provider and patient comfort with adequately monitoring for harm. PMID:21539703
Ruiz Iban, Miguel Angel; Benavides, Javier; Forero, Juan Pablo; Bittelman, Sacha; Martinez, Rafael; Mite, Miguel Angel; Diaz Heredia, Jorge; Ulloa, Sergio; Lizárraga Ferrand, Mauro Marcelo
Osteoarthritis is the most common cause of arthritis and one of the main causes of chronic pain. Although opioids are frequently employed for chronic pain treatment, their usage for osteoarthritis pain remains controversial due to the associated adverse effects. Most guidelines reserve their use for refractory pain in patients with hip and knee osteoarthritis. The situation is even more complex in Latin America, where the prevalence of insufficient pain treatment is high because of the limited availability and use of strong opioids. Areas covered: In this article we review the epidemiology of osteoarthritis, its socioeconomic burden, its impact as a chronic pain cause and the pharmacological treatment options, giving emphasis to the role of strong opioids, their safety and efficacy, especially in Latin American countries, where restrictions regulate their usage. Expert commentary: Usage of strong opioids is safe and effective in the short-term management of osteoarthritis with moderate to severe pain, when other pharmacological treatments are inadequate and surgery is contraindicated, provided their use adheres to existing guidelines. Educational programs for patients and physicians and further research on treating chronic pain with opioids should be implemented to reduce adverse effects and improve care quality.
Guerrero-Alba, Raquel; Valdez-Morales, Eduardo E; Jimenez-Vargas, Nestor N; Lopez-Lopez, Cintya; Jaramillo-Polanco, Josue; Okamoto, Takanobu; Nasser, Yasmin; Bunnett, Nigel W; Lomax, Alan E; Vanner, Stephen J
Psychological stress accompanies chronic inflammatory diseases such as IBD, and stress hormones can exacerbate pain signalling. In contrast, the endogenous opioid system has an important analgesic action during chronic inflammation. This study examined the interaction of these pathways. Mouse nociceptive dorsal root ganglia (DRG) neurons were incubated with supernatants from segments of inflamed colon collected from patients with chronic UC and mice with dextran sodium sulfate (cDSS)-induced chronic colitis. Stress effects were studied by adding stress hormones (epinephrine and corticosterone) to dissociated neurons or by exposing cDSS mice to water avoidance stress. Changes in excitability of colonic DRG nociceptors were measured using patch clamp and Ca 2+ imaging techniques. Supernatants from patients with chronic UC and from colons of mice with chronic colitis caused a naloxone-sensitive inhibition of neuronal excitability and capsaicin-evoked Ca 2+ responses. Stress hormones decreased signalling induced by human and mouse supernatants. This effect resulted from stress hormones signalling directly to DRG neurons and indirectly through signalling to the immune system, leading to decreased opioid levels and increased acute inflammation. The net effect of stress was a change endogenous opioid signalling in DRG neurons from an inhibitory to an excitatory effect. This switch was associated with a change in G protein-coupled receptor excitatory signalling to a pathway sensitive to inhibitors of protein kinase A-protein, phospholipase C-protein and G protein βϒ subunits. Stress hormones block the inhibitory actions of endogenous opioids and can change the effect of opioid signalling in DRG neurons to excitation. Targeting these pathways may prevent heavy opioid use in IBD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Lara-Solares, Argelia; Aguayo Zamora, Carlos; Amescua García, César; Garcia, João Batista Santos; Berenguel Cook, María Del Rosario; Bonilla Sierra, Patricia; Campos Kraychete, Durval; Flores Cantisani, José Alberto; Guerrero, Carlos; Guillén Núñez, María Del Rocío; Hernández Castro, John Jairo; Hernández Ortíz, Andrés; Jreige Iskandar, Aziza; Lech, Osvandré; Macías Guerra, Jacqueline; Ramírez Samayoa, Gerardo; Rangel Morillo, Edwin; Rico Pazos, María Antonieta; Sempértegui Gallegos, Manuel
Latin-American experts in the use of opioids in patients with chronic nononcologic pain (CNOP) have updated existing recommendations to current Latin-American reality. Several key opinion leaders from Latin America participated in a face-to-face meeting in Guatemala (April 2015) to discuss the use of opioids in CNOP. Subgroups of experts worked on specific topics, reviewed the literature and shaped the final manuscript. The expert panel developed guidelines taking into consideration the utility of both opioid and nonopioid analgesics and factors pertaining to their efficacy, safety, adherence, administration and risks for abuse/addiction. Latin-American guidelines for the use of opioids in CNOP should improve pain relief and patients' quality of life by increasing access to these effective agents.
Marianne S Matthias; Donaldson, Melvin T; Jensen, Agnes C; Krebs, Erin E
Chronic musculoskeletal pain is a major public health problem. Although opioid prescribing for chronic pain has increased dramatically since the 1990s, this practice has come under scrutiny because of increases in opioid-related harms and lack of evidence for long-term effectiveness. The Strategies for Prescribing Analgesics Comparative Effectiveness (SPACE) trial was a pragmatic 12-month randomized trial comparing benefits and harms of opioid versus non-opioid medications for chronic musculoskeletal pain. The current qualitative study was designed to better understand trial results by exploring patients' experiences, including perceptions of medications, experiences with the intervention, and whether expectations were met. Thirty-four participants who were purposefully sampled based on treatment group and intervention response participated in semi-structured interviews. The constant comparison method guided analysis. Results revealed that participants often held strong beliefs about opioid medications, which sometimes changed during the trial as they gained experience with medications; participants described a wide variety of experiences with treatment effectiveness, regardless of study group or their response to the intervention; and participants highly valued the personalized pain care model used in SPACE. SPACE trial results indicated no advantage for opioid over non-opioid medications. Qualitative findings suggest that, for patients in both treatment groups, pre-existing expectations of medications and of anticipated improvement in pain shaped experiences with and responses to medications. In addition, the personalized pain care model was described as contributing to positive outcomes in both groups. Copyright © 2018. Published by Elsevier Inc.
Rose, Mark Edmund
Sharp increases in opioid prescriptions, and associated increases in overdose deaths in the 2000s, evoked widespread calls to change perceptions of opioid analgesics. Medical literature discussions of opioid analgesics began emphasizing patient and public health hazards. Repetitive exposure to this information may influence physician assumptions. While highly consequential to patients with pain whose function and quality of life may benefit from opioid analgesics, current assumptions about prescription opioid analgesics, including their role in the ongoing opioid overdose epidemic, have not been scrutinized. Information was obtained by searching PubMed, governmental agency websites, and conference proceedings. Opioid analgesic prescribing and associated overdose deaths both peaked around 2011 and are in long-term decline; the sharp overdose increase recorded in 2014 was driven by illicit fentanyl and heroin. Nonmethadone prescription opioid analgesic deaths, in the absence of co-ingested benzodiazepines, alcohol, or other central nervous system/respiratory depressants, are infrequent. Within five years of initial prescription opioid misuse, 3.6% initiate heroin use. The United States consumes 80% of the world opioid supply, but opioid access is nonexistent for 80% and severely restricted for 4.1% of the global population. Many current assumptions about opioid analgesics are ill-founded. Illicit fentanyl and heroin, not opioid prescribing, now fuel the current opioid overdose epidemic. National discussion has often neglected the potentially devastating effects of uncontrolled chronic pain. Opioid analgesic prescribing and related overdoses are in decline, at great cost to patients with pain who have benefited or may benefit from, but cannot access, opioid analgesic therapy.
Garland, Eric L
Prescription opioid misuse and addiction among chronic pain patients are problems of growing medical and social significance. Chronic pain patients often require intervention to improve their well-being and functioning, and yet, the most commonly available form of pharmacotherapy for chronic pain is centered on opioid analgesics--drugs that have high abuse liability. Consequently, health care and legal systems are often stymied in their attempts to intervene with individuals who suffer from both pain and addiction. As such, novel, nonpharmacologic interventions are needed to complement pharmacotherapy and interrupt the cycle of behavioral escalation. The purpose of this paper is to describe how the downward spiral of chronic pain and prescription opioid misuse may be targeted by one such intervention, Mindfulness-Oriented Recovery Enhancement (MORE), a new behavioral treatment that integrates elements from mindfulness training, cognitive-behavioral therapy, and positive psychology. The clinical outcomes and neurocognitive mechanisms of this intervention are reviewed with respect to their effects on the risk chain linking chronic pain and prescription opioid misuse. Future directions for clinical and pharmacologic research are discussed.
Alam, Asim; Juurlink, David N
The objectives for preparing this article were to review the historical context and epidemiology surrounding the North American prescription opioid crisis, to summarize the evidence regarding the benefits and harms of long-term opioid therapy for non-cancer pain, and to outline ways in which anesthesiologists may help ameliorate the problem. We searched PubMed, Google Scholar, and EMBASE™ for relevant articles using various search terms, including pain, opioid epidemic, history of opioid use, perioperative care, and addiction. Related citations were further explored and searched depending on the specific subtopic of interest. In the 1980s and early 1990s, opioids were infrequently used for the treatment of chronic pain. Thereafter, however, physicians were gradually inculcated with the message that long-term opioid therapy was a safe and effective treatment option for patients with chronic non-cancer pain. Pharmaceutical companies supported this growing movement and employed aggressive and sometimes misleading marketing strategies for new opioid formulations. As a result, the practice of prescribing opioids flourished in the late 1990s. The surge in prescribing opioids was accompanied by a marked increase in opioid-related morbidity and mortality. This change in practice transpired despite the absence of randomized trials showing clinically significant benefit from the long-term use of opioids. Subsequently, however, a large and growing body of evidence has emerged quantifying the harms associated with long-term opioid therapy. Anesthesiologists widely prescribe opioids for acute and chronic pain; yet, as a group, they may be largely unaware of the current state of this growing epidemic and what role they can play to rectify this problem. Anesthesiologists are well positioned to take a leadership role in the management of postoperative discharge opioid therapy in an effort to curb the overutilization of opioids. Furthermore, anesthesiologists who regularly
Krumova, Elena K; Bennemann, Philipp; Kindler, Doris; Schwarzer, Andreas; Zenz, Michael; Maier, Christoph
In specialized pain clinics there is an increasing number of patients with severe chronic noncancer pain (CNCP) despite long-term opioid medication. Few clinical studies show short-term pain relief after opioid withdrawal (OW). We have evaluated the relation between pain intensity after OW and long-term opioid nonuse. One hundred two consecutive patients with severe CNCP despite opioid medication (mean treatment duration, 43 mo) reported pain intensity (numerical rating scale, 0 to 10), Pain Disability Index, mood (CES-D), and quality of life (Short Form 36) before, shortly, and 12 to 24 months after inpatient OW. Total opioid withdrawal (n = 78) or significant dose reduction (DR; n = 24, mean reduction, 82%) was performed after individual decision. Opioid intake 12 to 24 months later, respectively dose increase ≥ 100% (DR group), was considered relapse. T tests, multivariable analysis of variance, logistic regression. After OW current pain intensity significantly decreased on an average by 41% (6.4 ± 2.4 vs. 3.8 ± 2.5), maximal and average pain by 18% and 24%, respectively. Twelve to 24 months later 42 patients (41%) relapsed (31 of the total opioid withdrawal group, 6 of the DR group, 5 lost). Patients without later relapse showed significantly lower pain scores than the later relapsed patients already shortly after OW (5.0 ± 2.2 vs. 5.9 ± 2.1) and 12 to 24 months later (5.5 ± 2.4 vs. 6.5 ± 2.0). There was a significant relation between relapse probability and pain intensity immediately after OW. In many patients with severe CNCP, despite opioid medication, sustainable pain relief can be achieved if OW is included in the rehabilitation program. Consequently, we recommend OW for opioid-resistant CNCP before any opioid escalation. Lower pain intensity shortly after OW may predict the long-term opioid nonuse probability.
Elliott, Jennifer A; Opper, Susan E; Agarwal, Sonali; Fibuch, Eugene E
Opioids are among the oldest known and most widely used analgesics. The application of opioids has expanded over the last few decades, especially in the treatment of chronic non-malignant pain. This upsurge in opioid use has been accompanied by the increasingly recognized occurrence of opioid-associated endocrinopathy. This may arise after exposure to enteral, parenteral, or neuraxial opioids. Opioid-associated endocrinopathy consists primarily of hypothalamic-pituitary-gonadal axis or hypothalamic-pituitary-adrenal axis dysfunction and may manifest with symptoms of hypogonadism, adrenal dysfunction, and other hormonal disturbances. Additionally, opioid related endocrine dysfunction may be coupled with such disorders as osteoporosis and mood disturbances including depression. Undesirable changes in pain sensitivity such as opioid-induced hyperalgesia, and reduced potency of opioid analgesia may also be potential consequences of chronic opioid consumption. Few studies to date have been able to establish what degree of opioid exposure, in terms of dose or duration of therapy, may predispose patients to opioid-associated endocrinopathy. This article will review the currently available literature concerning opioid-associated endocrinopathy and will provide recommendations for the evaluation, monitoring, and management of opioid-associated endocrinopathy and its other accompanying undesired effects.
Full Text Available Srinivas NalamachuInternational Clinical Research Institute and Pain Management Institute, Overland Park, KS, USAAbstract: Opioid rotation is a common and necessary clinical practice in the management of chronic non-cancer pain to improve therapeutic efficacy with the lowest opioid dose. When dose escalations fail to achieve adequate analgesia or are associated with intolerable side effects, a trial of a new opioid should be considered. Much of the scientific rationale of opioid rotation is based on the wide interindividual variability in sensitivity to opioid analgesics and the novel patient response observed when introducing an opioid-tolerant patient to a new opioid. This article discusses patient indicators for opioid rotation, the conversion process between opioid medications, and additional practical considerations for increasing the effectiveness of opioid therapy during a trial of a new opioid. A Patient vignette that demonstrates a step-wise approach to opioid rotation is also presented.Keywords: extended-release opioids, chronic pain, opioid rotation
Koblish, Michael; Carr, Richard; Siuda, Edward R; Rominger, David H; Gowen-MacDonald, William; Cowan, Conrad L; Crombie, Aimee L; Violin, Jonathan D; Lark, Michael W
Prescription opioids are a mainstay in the treatment of acute moderate to severe pain. However, chronic use leads to a host of adverse consequences including tolerance and opioid-induced hyperalgesia (OIH), leading to more complex treatment regimens and diminished patient compliance. Patients with OIH paradoxically experience exaggerated nociceptive responses instead of pain reduction after chronic opioid usage. The development of OIH and tolerance tend to occur simultaneously and, thus, present a challenge when studying the molecular mechanisms driving each phenomenon. We tested the hypothesis that a G protein-biased µ -opioid peptide receptor (MOPR) agonist would not induce symptoms of OIH, such as mechanical allodynia, following chronic administration. We observed that the development of opioid-induced mechanical allodynia (OIMA), a model of OIH, was absent in β -arrestin1 -/- and β -arrestin2 -/- mice in response to chronic administration of conventional opioids such as morphine, oxycodone and fentanyl, whereas tolerance developed independent of OIMA. In agreement with the β -arrestin knockout mouse studies, chronic administration of TRV0109101, a G protein-biased MOPR ligand and structural analog of oliceridine, did not promote the development of OIMA but did result in drug tolerance. Interestingly, following induction of OIMA by morphine or fentanyl, TRV0109101 was able to rapidly reverse allodynia. These observations establish a role for β -arrestins in the development of OIH, independent of tolerance, and suggest that the use of G protein-biased MOPR ligands, such as oliceridine and TRV0109101, may be an effective therapeutic avenue for managing chronic pain with reduced propensity for opioid-induced hyperalgesia. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.
Full Text Available Ish K Khanna, Sivaram PillarisettiNeuroPn Therapeutics, Alpharetta, GA, USAAbstract: Despite proven clinical utility, buprenorphine has not been used widely for the treatment of chronic pain. Questions about “ceiling effect” or bell-shaped curve observed for analgesia in preclinical studies and potential withdrawal issues on combining with marketed µ-agonists continue to hinder progress in expanding full potential of buprenorphine in the treatment of cancer and noncancer pain. Mounting evidence from clinical studies and conclusions drawn by a panel of experts strongly support superior safety and efficacy profile of buprenorphine vs marketed opioids. No ceiling on analgesic effect has been reported in clinical studies. The receptor pharmacology and pharmacokinetics profile of buprenorphine is complex but unique and contributes to its distinct safety and efficacy. The buprenorphine pharmacology also allows it to be combined with other µ-receptor opioids for additivity in efficacy. Transdermal delivery products of buprenorphine have been preferred choices for the management of pain but new delivery options are under investigation for the treatment of both opioid dependence and chronic pain.Keywords: buprenorphine, opioids, opioid dependence, partial agonist, hyperalgesia, neuropathic pain
Nielsen, Suzanne; Campbell, Gabrielle; Peacock, Amy; Smith, Kimberly; Bruno, Raimondo; Hall, Wayne; Cohen, Milton; Degenhardt, Louisa
Objective The aims of the present study were to describe the use, and barriers to the use, of non-medication pain therapies and to identify the demographic and clinical correlates of different non-opioid pain treatments. Methods The study was performed on a cohort (n=1514) of people prescribed pharmaceutical opioids for chronic non-cancer pain (CNCP). Participants reported lifetime and past month use of healthcare services, mental and physical health, pain characteristics, current oral morphine equivalent daily doses and financial and access barriers to healthcare services. Results Participants reported the use of non-opioid pain treatments, both before and after commencing opioid therapy. Services accessed most in the past month were complementary and alternative medicines (CAMs; 41%), physiotherapy (16%) and medical and/or pain specialists (15%). Higher opioid dose was associated with increased financial and access barriers to non-opioid treatment. Multivariate analyses indicated being younger, female and having private health insurance were the factors most commonly associated with accessing non-opioid treatments. Conclusions Patients on long-term opioid therapy report using multiple types of pain treatments. High rates of CAM use are concerning given limited evidence of efficacy for some therapies and the low-income status of most people with CNCP. Financial and insurance barriers highlight the importance of considering how different types of treatments are paid for and subsidised. What is known about the topic? Given concerns regarding long-term efficacy, adverse side-effects and risk of misuse and dependence, prescribing guidelines recommend caution in prescribing pharmaceutical opioids in cases of CNCP, typically advising a multidisciplinary approach to treatment. There is a range of evidence supporting different (non-drug) treatment approaches for CNCP to reduce pain severity and increase functioning. However, little is known about the non-opioid treatments
Reznikov, Igor; Pud, Dorit; Eisenberg, Elon
Previous research has reported on reduced paw withdrawal latencies to heat and mechanical stimuli after parenteral administration of opioids in animals and on increased pain sensitivity in humans subsequent to postoperative infusions of short-acting opioids or in drug addicts. The aim of the present study was to explore the possibility that oral opioid treated patients with cancer-related or chronic nonmalignant pain differ in their pain sensitivity from patients treated with non-opioid analgesics. The study population consisted of 224 patients, including 142 in the opioid-treated group and 82 in the non-opioid-treated group. Pain thresholds for punctuate measured by von Frey filaments (g), mechanical pressure measured by pressure algometer (mmHg), heat stimuli measured by quantitative sensory testing (degrees C), as well as suprathreshold tonic heat pain intensity (46.5 degrees C for 1 min) measured by 0-10 numerical pain scale (NPS) were obtained at a nonpainful site (thenar eminence) in all patients. No differences between the groups were found for gender, age, duration of pain, or duration of treatment (independent variables). No significant differences between the groups were found in punctuate (difference = 17.0 g (95% CI -8.8, 42.8), P = 0.19), pressure (2.2 mmHg (-28.7, 33.2), P = 0.89) and heat (-0.3 degrees C (-1.5, 0.9), P = 0.70) pain thresholds, or in suprathreshold heat pain intensity (difference between maximal pain intensities -0.4 NPS units (95% CI -1.2, 0.4), P = 0.31). Pearson correlations within the opioid-treated group failed to show significant relationships between any of the independent variables and the outcome measures. A further comparison of the outcomes between the 'weak' opioid-treated subgroup and the 'strong' opioid-treated subgroup again revealed insignificant results. These results suggest that the administration of 'commonly used' dosages of oral opioids does not result in abnormal pain sensitivity beyond that of patients
Krasnoperov, R A; Glumova, V A; Riashchikov, S N; Proshutina, N E
In adult rabbits stress was modelled by electrostimulation of the hypothalamus ventromedial nucleus (15-hour-long session during 30 days) and medulla's raphe big nucleus which is one of the central places of the opioid peptides synthesis was irritated. It is revealed, that under stress thyroid gland responds by serum T3 increase in comparison with control animals with statistically significant variability of the T4 profile. Chronicity of the emotional agitation involves destructive changes in the thyroid parenchyma the hurting effect of the negative emotional factor is expressed less during opioid peptides complex activation. It is suggested that there are its own stress-limiting mechanisms in thyroid gland.
Marino, Elise N; Rosen, Kristen D; Gutierrez, Antonio; Eckmann, Maxim; Ramamurthy, Somayaji; Potter, Jennifer Sharpe
Impulsivity and sensation seeking have been associated with substance use disorders, including opioid use disorders. This pilot study sought to examine whether impulsivity and sensation seeking, as measured by the Barratt Impulsiveness Scale (BIS) and Sensation Seeking Scale (SSS), were associated with opioid analgesic misuse risk in chronic, low-back pain patients prescribed opioid analgesics. Participants were 42 chronic, low-back pain patients enrolled in a larger study examining problematic opioid analgesic use. Impulsivity was assessed using the BIS, sensation seeking was measured using the SSS, and opioid analgesic misuse risk was assessed using the Current Opioid Misuse Measure (COMM). Significant bivariate associations were found between the COMM and the following predictor variables: age and the three BIS subscales: Attentional Impulsiveness, Non-planning Impulsiveness, and Motor Impulsiveness. Using a multivariate linear regression, after controlling for age, the BIS subscales accounted for 29.0% of the variance in the COMM. Attentional Impulsiveness was the only significant BIS subscale. These results suggest a potential relationship between impulsivity, but not sensation seeking, and risk for opioid analgesic misuse. Impulsivity is not a prominent trait observed in chronic pain patients; however, it may be an important risk factor for opioid analgesic misuse for a subset of individuals with chronic pain. As such, these findings suggest that additional exploration of this potential risk factor is warranted. Published by Elsevier Ltd.
Worley, Matthew J; Heinzerling, Keith G; Shoptaw, Steven; Ling, Walter
Buprenorphine-naloxone (BUP-NLX) can be used to manage prescription opioid addiction among persons with chronic pain, but post-treatment relapse is common and difficult to predict. This study estimated whether changes in pain over time and pain volatility during BUP-NLX maintenance would predict opioid use during the taper BUP-NLX taper. Secondary analysis of a multi-site clinical trial for prescription opioid addiction, using data obtained during a 12-week BUP-NLX stabilization and 4-week BUP-NLX taper. Community clinics affiliated with a national clinical trials network in 10 US cities. Subjects with chronic pain who entered the BUP-NLX taper phase (n = 125) with enrollment occurring from June 2006 to July 2009 (52% male, 88% Caucasian, 31% married). Outcomes were weekly biologically verified and self-reported opioid use from the 4-week taper phase. Predictors were estimates of baseline severity, rate of change and volatility in pain from weekly self-reports during the 12-week maintenance phase. Controlling for baseline pain and treatment condition, increased pain [odds ratio (OR) = 2.38, P = 0.02] and greater pain volatility (OR = 2.43, P = 0.04) predicted greater odds of positive opioid urine screen during BUP-NLX taper. Increased pain (IRR = 1.40, P = 0.04) and greater pain volatility [incidence-rate ratio (IRR) = 1.66, P = 0.009] also predicted greater frequency of self-reported opioid use. Adults with chronic pain receiving out-patient treatment with buprenorphine-naloxone (BUP-NLX) for prescription opioid addiction have an elevated risk for opioid use when tapering off maintenance treatment. Those with relative persistence in pain over time and greater volatility in pain during treatment are less likely to sustain abstinence during BUP-NLX taper. © 2017 Society for the Study of Addiction.
Higgins, C; Smith, B H; Matthews, K
The prevalence and incidence of chronic conditions, such as pain and opioid dependence, have implications for policy development, resource allocation, and healthcare delivery. The primary objective of the current review was to estimate the incidence of iatrogenic opioid dependence or abuse after treatment with opioid analgesics. Systematic electronic searches utilised six research databases (Embase, Medline, PubMed, Cinahl Plus, Web of Science, OpenGrey). A 'grey' literature search and a reference search of included articles were also undertaken. The PICOS framework was used to develop search strategies and the findings are reported in accordance with the PRISMA Statement. After eligibility reviews of 6164 articles, 12 studies (involving 310 408 participants) were retained for inclusion in the meta-analyses. A random effects model (DerSimonian-Laird method) generated a pooled incidence of opioid dependence or abuse of 4.7%. There was little within-study risk of bias and no significant publication bias; however, substantial heterogeneity was found among study effects (99.78%). Sensitivity analyses indicated that the diagnostic criteria selected for identifying opioid dependence or abuse (Diagnostic Statistical Manual (DSM-IV) vs International Classification of Diseases (ICD-9)) accounted for 20% and duration of exposure to opioid analgesics accounted for 18% of variance in study effects. Longer-term opioid analgesic exposure, and prescription of strong rather than weak opioids, were associated with a significantly lower incidence of opioid dependence or abuse. The incidence of iatrogenic opioid dependence or abuse was 4.7% of those prescribed opioids for pain. Further research is required to confirm the potential for our findings to inform prevention of this serious adverse event. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.
Katz, Nathaniel; Mazer, Norman A
Opioids have been used for medicinal and analgesic purposes for centuries. However, their negative effects on the endocrine system, which have been known for some times, are barely discussed in modern medicine. Therefore, we conducted a systematic review of the impact of opioids on the endocrine system. A review of the English language literature on preclinical and clinical studies of any type on the influence of opioids on the endocrine system was conducted. Preliminary recommendations for monitoring and managing these problems were provided. Long-term opioid therapy for either addiction or chronic pain often induces hypogonadism owing to central suppression of hypothalamic secretion of gonadotropin-releasing hormone. Symptoms of opioid-induced hypogonadism include loss of libido, infertility, fatigue, depression, anxiety, loss of muscle strength and mass, osteoporosis, and compression fractures in both men and women; impotence in men; and menstrual irregularities and galactorrhea in women. In view of the increased use of opioids for chronic pain, it has become increasingly important to monitor patients taking opioids and manage endocrine complications. Therefore, patients on opioid therapy should be routinely screened for such symptoms and for laboratory abnormalities in sex hormones. Opioid-induced hypogonadism seems to be a common complication of therapeutic or illicit opioid use. Patients on long-term opioid therapy should be prospectively monitored, and in cases of opioid-induced hypogonadism, we recommend nonopioid pain management, opioid rotation, or sex hormone supplementation after careful consideration of the risks and benefits.
Vowles, Kevin E; McEntee, Mindy L; Julnes, Peter Siyahhan; Frohe, Tessa; Ney, John P; van der Goes, David N
Opioid use in chronic pain treatment is complex, as patients may derive both benefit and harm. Identification of individuals currently using opioids in a problematic way is important given the substantial recent increases in prescription rates and consequent increases in morbidity and mortality. The present review provides updated and expanded information regarding rates of problematic opioid use in chronic pain. Because previous reviews have indicated substantial variability in this literature, several steps were taken to enhance precision and utility. First, problematic use was coded using explicitly defined terms, referring to different patterns of use (ie, misuse, abuse, and addiction). Second, average prevalence rates were calculated and weighted by sample size and study quality. Third, the influence of differences in study methodology was examined. In total, data from 38 studies were included. Rates of problematic use were quite broad, ranging from addiction averaged between 8% and 12% (range, 95% CI: 3%-17%). Abuse was reported in only a single study. Only 1 difference emerged when study methods were examined, where rates of addiction were lower in studies that identified prevalence assessment as a primary, rather than secondary, objective. Although significant variability remains in this literature, this review provides guidance regarding possible average rates of opioid misuse and addiction and also highlights areas in need of further clarification.
Boscarino, Joseph A; Hoffman, Stuart N; Han, John J
Previously, we estimated the prevalence and risk factors for prescription opioid-use disorder among outpatients on opioid therapy using the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 and DSM-4 criteria. However, at the time, the DSM-5 criteria were not finalized. In the current study, we analyzed these data using the final DSM-5 criteria and compared these results. Using electronic records from a large US health care system, we identified outpatients receiving five or more prescription orders for opioid therapy in the past 12 months for noncancer pain (mean prescription orders =10.72; standard deviation =4.96). In 2008, we completed diagnostic interviews with 705 of these patients using the DSM-4 criteria. In the current study, we reassessed these results using the final DSM-5 criteria. The lifetime prevalence of DSM-5 opioid-use disorders using the final DSM-5 criteria was 58.7% for no or few symptoms (DSM-4 criteria indicated that the majority of patients with lifetime DSM-4 opioid dependence were now classified as having mild opioid-use disorder, based on the DSM-5 criteria (53.6%; 95% CI =44.1-62.8). In ordinal logistic regression predicting no/few, mild, moderate, and severe opioid-use disorder, the best predictors were age DSM-5 criteria, including the elimination of tolerance and withdrawal, inclusion of craving and abuse symptoms, and introduction of a new graded severity classification, the prevalence of opioid-use disorders has changed, while many of the DSM-4 risk factors for opioid dependence were similar. To our knowledge, this is one of the first studies to compare the final results for DSM-5 versus DSM-4 prescription opioid-use disorders among a high-risk patient population.
Conclusion: Serum prolactin concentration correlated negatively with male reproductive hormones and may play a major role in reproductive deficits associated with chronic use of PDE5 inhibitors and opioids.
Full Text Available Chronic pain is a major health concern that affects millions of people. There are no adequate long-term therapies for chronic pain sufferers, leading to significant cost for both society and the individual. The most commonly used therapy for chronic pain is the application of opioid analgesics and nonsteroidal anti-inflammatory drugs, but these drugs can lead to addiction and may cause side effects. Further studies of the mechanisms of chronic pain have opened the way for development of new treatment strategies, one of which is gene therapy. The key to gene therapy is selecting safe and highly efficient gene delivery systems that can deliver therapeutic genes to overexpress or suppress relevant targets in specific cell types. Here we review several promising viral vectors that could be applied in gene transfer for the treatment of chronic pain and further discuss the possible mechanisms of genes of interest that could be delivered with viral vectors for the treatment of chronic pain.
Malone Robert M
Full Text Available Abstract Background Chronic non-cancer pain is a common problem that is often accompanied by psychiatric comorbidity and disability. The effectiveness of a multi-disciplinary pain management program was tested in a 3 month before and after trial. Methods Providers in an academic general medicine clinic referred patients with chronic non-cancer pain for participation in a program that combined the skills of internists, clinical pharmacists, and a psychiatrist. Patients were either receiving opioids or being considered for opioid therapy. The intervention consisted of structured clinical assessments, monthly follow-up, pain contracts, medication titration, and psychiatric consultation. Pain, mood, and function were assessed at baseline and 3 months using the Brief Pain Inventory (BPI, the Center for Epidemiological Studies-Depression Scale scale (CESD and the Pain Disability Index (PDI. Patients were monitored for substance misuse. Results Eighty-five patients were enrolled. Mean age was 51 years, 60% were male, 78% were Caucasian, and 93% were receiving opioids. Baseline average pain was 6.5 on an 11 point scale. The average CESD score was 24.0, and the mean PDI score was 47.0. Sixty-three patients (73% completed 3 month follow-up. Fifteen withdrew from the program after identification of substance misuse. Among those completing 3 month follow-up, the average pain score improved to 5.5 (p = 0.003. The mean PDI score improved to 39.3 (p Conclusions A primary care disease management program improved pain, depression, and disability scores over three months in a cohort of opioid-treated patients with chronic non-cancer pain. Substance misuse and depression were common, and many patients who had substance misuse identified left the program when they were no longer prescribed opioids. Effective care of patients with chronic pain should include rigorous assessment and treatment of these comorbid disorders and intensive efforts to insure follow up.
Bruehl, Stephen; Burns, John W.; Gupta, Rajnish; Buvanendran, Asokumar; Chont, Melissa; Schuster, Erik; France, Christopher R.
Background and Objectives Factors underlying differential responsiveness to opioid analgesic medications used in chronic pain management are poorly understood. We tested whether individual differences in endogenous opioid inhibition of chronic low back pain were associated with magnitude of acute reductions in back pain ratings following morphine administration. Methods In randomized, counterbalanced order over three sessions, 50 chronic low back pain patients received intravenous naloxone (8mg), morphine (0.08 mg/kg), or placebo. Back pain intensity was rated pre-drug and again after peak drug activity was achieved using the McGill Pain Questionnaire-Short Form (Sensory and Affective subscales, VAS intensity measure). Opioid blockade effect measures to index degree of endogenous opioid inhibition of back pain intensity were derived as the difference between pre-to post-drug changes in pain intensity across placebo and naloxone conditions, with similar morphine responsiveness measures derived across placebo and morphine conditions. Results Morphine significantly reduced back pain compared to placebo (MPQ-Sensory, VAS; P effects of opioid blockade on back pain intensity. However, individual differences in opioid blockade effects were significantly associated with degree of acute morphine-related reductions in back pain on all measures, even after controlling for effects of age, sex, and chronic pain duration (P morphine. Conclusions Morphine appears to provide better acute relief of chronic back pain in individuals with lower natural opioidergic inhibition of chronic pain intensity. Possible implications for personalized medicine are discussed. PMID:24553304
Blum, Kenneth; Gold, Mark S; Jacobs, William; McCall, William Vaughn; Febo, Marcelo; Baron, David; Dushaj, Kristina; Demetrovics, Zsolt; Badgaiyan, Rajendra D
This review begins with a comprehensive history of opioid dependence and treatment in the United States. The focus is an evidence-based treatment model for opioid/opiate dependent individuals. The role of reward genetic polymorphisms and the epigenetic modifications that lead to vulnerability to use and misuse of opiates/opioid to treat pain are reviewed. The neurochemical mechanisms of acute opiate withdrawal and opiate/opioid reward mechanisms are explored with a goal of identifying specific treatment targets. Alterations in functional brain connectivity based on neurobiological mechanisms in heroin dependence and abstinence are also reviewed. A new clinical model an alternative to merely blocking acute withdrawal symptoms as identified in the DSM -5 is proposed. Genetic diagnosis at the onset of detoxification, to determine risk stratification, and identify polymorphic gene targets for pharmaceutical and nutraceutical interventions, followed by the simultaneous initiation of Medication Assisted Therapy (MAT), to enable psychological extinction, and steady pro-dopaminergic therapy with the goal of developing "dopamine homeostasis" is recommended. The objective of these interventions is to prevent future relapse by treating all "Reward Deficiency Syndrome" (RDS) behaviors and eventually make an addiction-free life possible .
Nielsen, Suzanne; Peacock, Amy; Lintzeris, Nicholas; Bruno, Raimondo; Larance, Briony; Degenhardt, Louisa
Take-home naloxone (THN) is recommended in response to pharmaceutical opioid-related mortality. Some health professionals are reluctant to discuss THN for fear of causing offense. The aims of this study were to assess knowledge of opioid overdose and attitudes toward THN for opioid overdose reversal in people with chronic noncancer pain (CNCP). Prospective cohort study. Australia, September to October 2015. A subset of participants (N = 208) from a cohort of people prescribed restricted opioids for CNCP. Questions added in the two-year telephone interviews examined knowledge of overdose symptoms and attitudes toward community supply of naloxone. Associations with overdose risk factors and naloxone supply eligibility criteria with attitudes toward naloxone were explored. Fourteen percent reported ever experiencing opioid overdose symptoms. Participants correctly identified fewer than half of the overdose signs and symptoms. After receiving information on naloxone, most participants (60%), thought it was a "good" or "very good" idea. Few participants reported that they would be "a little" (N = 21, 10%) or "very" offended (N = 7, 3%) if their opioid prescriber offered them naloxone. Positive attitudes toward THN were associated with male gender (odds ratio [OR] = 1.96, 95% confidence interval [CI] = 1.09-3.50), past year cannabis use (OR = 2.52, 95% CI = 1.03-6.16), and past year nicotine use (OR = 2.11, 95% CI = 1.14-3.91). Most participants had positive attitudes toward THN but low knowledge about opioid overdose symptoms. Strategies for educating patients and their caregivers on opioid toxicity are needed. THN may be best targeted toward those with risk factors in terms of overdose prevention and acceptability.
Feingold, Daniel; Brill, Silviu; Goor-Aryeh, Itay; Delayahu, Yael; Lev-Ran, Shaul
High rates of depression and anxiety have been consistently reported among patients suffering from chronic pain. Prescription opioids are one of the most common modalities for pharmacological treatment of pain, however in recent years medical marijuana(MM) has been increasingly used for pain control in the US and in several countries worldwide. The aim of this study was to compare levels of depression and anxiety among pain patients receiving prescription opioids and MM. Participants were patients suffering from chronic pain treated with prescription opioids (OP,N=474), MM (N=329) or both (OPMM,N=77). Depression and anxiety were assessed using the depression module of the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder scale (GAD-7). Prevalence of depression among patients in the OP, MM and OPMM groups was 57.1%, 22.3% and 51.4%, respectively and rates of anxiety were 48.4%, 21.5% and 38.7%, respectively. After controlling for confounders, patients in the OP group were significantly more likely to screen positive for depression (Adjusted Odds Ratio(AOR)=6.18;95%CI=4.12-9.338) and anxiety(AOR=4.12;CI=3.84-5.71)) compared to those in the MM group. Individuals in the OPMM group were more prone for depression (AOR for depression=3.34;CI=1.52-7.34)) compared to those in the MM group. Cross-sectional study, restricting inference of causality. Levels of depression and anxiety are higher among chronic pain patients receiving prescription opioids compared to those receiving MM. Findings should be taken into consideration when deciding on the most appropriate treatment modality for chronic pain, particularly among those at risk for depression and anxiety. Copyright © 2017 Elsevier B.V. All rights reserved.
Hoban, B; Larance, B; Gisev, N; Nielsen, S; Cohen, M; Bruno, R; Shand, F; Lintzeris, N; Hall, W; Farrell, M; Degenhardt, L
The regular use of simple analgesics in addition to opioids such as paracetamol (or acetaminophen) is recommended for persistent pain to enhance analgesia. Few studies have examined the frequency and doses of paracetamol among people with chronic non-cancer pain including use above the recommended maximum daily dose. To assess (i) the prevalence of paracetamol use among people with chronic non-cancer pain prescribed opioids, (ii) assess the prevalence of paracetamol use above the recommended maximum daily dose and (iii) assess correlates of people who used paracetamol above the recommended maximum daily dose including: age, gender, income, education, pain severity and interference, use of paracetamol/opioid combination analgesics, total opioid dose, depression, anxiety, pain self-efficacy or comorbid substance use, among people prescribed opioids for chronic non-cancer pain. This study draws on baseline data collected for the Pain and Opioids IN Treatment (POINT) study and utilises data from 962 interviews and medication diaries. The POINT study is national prospective cohort of people with chronic non-cancer pain prescribed opioids. Participants were recruited from randomly selected pharmacies across Australia. Sixty-three per cent of the participants had used paracetamol in the past week (95% CI = 59.7-65.8). Among the paracetamol users 22% (95% CI = 19.3-24.6) had used paracetamol/opioid combination analgesics and 4.8% (95% CI = 3.6-6.3) had used paracetamol above the recommended maximum daily dose (i.e. > 4000 mg/day). Following binomial logistic regression (χ(2) = 25.98, df = 10, p = 0.004), people who had taken above the recommended maximum daily dose were less likely to have low income (AOR = 0.52, 95% CI = 0.27-0.99), more likely to use paracetamol/opioid combination analgesics (AOR = 2.01, 95% CI = 1.02-3.98) and more likely to take a higher opioid dose (AOR = 1.00, 95% CI = 1.00-1.01). The majority of people with chronic non-cancer pain prescribed
Sohler, Nancy L; Starrels, Joanna L; Khalid, Laila; Bachhuber, Marcus A; Arnsten, Julia H; Nahvi, Shadi; Jost, John; Cunningham, Chinazo O
Chronic pain is common in the United States and prescribed opioid analgesics use for noncancer pain has increased dramatically in the past two decades, possibly accounting for the current opioid addiction epidemic. Co-morbid drug use in those prescribed opioid analgesics is common, but there are few data on polysubstance use patterns. We explored patterns of use of cigarette, alcohol, and illicit drugs in HIV-infected people with chronic pain who were prescribed opioid analgesics. We conducted a secondary data analysis of screening interviews conducted as part of a parent randomized trial of financial incentives to improve HIV outcomes among drug users. In a convenience sample of people with HIV and chronic pain, we collected self-report data on demographic characteristics; pain; patterns of opioid analgesic use (both prescribed and illicit); cigarette, alcohol, and illicit drug use (including cannabis, heroin, and cocaine) within the past 30 days; and current treatment for drug use and HIV. Almost half of the sample of people with HIV and chronic pain reported current prescribed opioid analgesic use (N = 372, 47.1%). Illicit drug use was common (N = 505, 63.9%), and cannabis was the most commonly used illicit substance (N = 311, 39.4%). In multivariate analyses, only cannabis use was significantly associated with lower odds of prescribed opioid analgesic use (adjusted odds ratio = 0.57; 95% confidence interval: 0.38-0.87). Conclusions/Importance: Our data suggest that new medical cannabis legislation might reduce the need for opioid analgesics for pain management, which could help to address adverse events associated with opioid analgesic use.
Staahl, Camilla; Dimcevski, Georg; Andersen, Søren Due
and morphine on experimental pain in patients with pain caused by chronic pancreatitis. MATERIAL AND METHODS: Ten patients took part in this blinded, cross-over study. The analgesic effects of morphine (30 mg, oral), oxycodone (15 mg, oral) and placebo were tested against multimodal (mechanical, thermal...
Full Text Available Joseph A Boscarino,1 Stuart N Hoffman,1 John J Han2 1Center for Health Research, 2Department of Pain Medicine, Geisinger Clinic, Danville, PA, USAAims: Previously, we estimated the prevalence and risk factors for prescription opioid-use disorder among outpatients on opioid therapy using the Diagnostic and Statistical Manual of Mental Disorders (DSM-5 and DSM-4 criteria. However, at the time, the DSM-5 criteria were not finalized. In the current study, we analyzed these data using the final DSM-5 criteria and compared these results.Methods: Using electronic records from a large US health care system, we identified outpatients receiving five or more prescription orders for opioid therapy in the past 12 months for noncancer pain (mean prescription orders =10.72; standard deviation =4.96. In 2008, we completed diagnostic interviews with 705 of these patients using the DSM-4 criteria. In the current study, we reassessed these results using the final DSM-5 criteria.Results: The lifetime prevalence of DSM-5 opioid-use disorders using the final DSM-5 criteria was 58.7% for no or few symptoms (<2, 28.1% for mild symptoms (2–3, 9.7% for moderate symptoms (4–5, and 3.5% for severe symptoms (six or more. Thus, the lifetime prevalence of “any” prescription opioid-use disorder in this cohort was 41.3% (95% confidence interval [CI] =37.6–45.0. A comparison to the DSM-4 criteria indicated that the majority of patients with lifetime DSM-4 opioid dependence were now classified as having mild opioid-use disorder, based on the DSM-5 criteria (53.6%; 95% CI =44.1–62.8. In ordinal logistic regression predicting no/few, mild, moderate, and severe opioid-use disorder, the best predictors were age <65 years, current pain impairment, trouble sleeping, suicidal thoughts, anxiety disorders, illicit drug use, and history of substance abuse treatment.Conclusion: Given the final DSM-5 criteria, including the elimination of tolerance and withdrawal, inclusion of
Full Text Available Lynn R Webster,1 Darren M Brenner,2 Andrew C Barrett,3 Craig Paterson,3 Enoch Bortey,3 William P Forbes3 1PRA Health Sciences, Salt Lake City, UT, 2Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 3Salix, a Division of Valeant Pharmaceuticals North America LLC, Bridgewater, NJ, USA Background: Subcutaneous methylnaltrexone is efficacious and well tolerated for opioid-induced constipation (OIC but may theoretically disrupt opioid-mediated analgesia. Methods: Opioid use, pain intensity, and opioid withdrawal (Objective Opioid Withdrawal Scale [OOWS] and Subjective Opiate Withdrawal Scale [SOWS] scores were reported in a randomized, double-blind trial with an open-label extension (RCT and an open-label trial (OLT evaluating safety in adults with chronic noncancer pain. In the RCT, patients taking ≥50 mg of oral morphine equivalents daily with <3 rescue-free bowel movements weekly received methylnaltrexone 12 mg once daily (n=150, every other day (n=148, or placebo (n=162 for 4 weeks, followed by open-label methylnaltrexone 12 mg (as needed [prn]; n=364 for 8 weeks. In the OLT, patients (n=1,034 on stable opioid doses with OIC received methylnaltrexone 12 mg prn for up to 48 weeks. Results: Minimal fluctuations of median morphine equivalent dose from baseline (BL were observed in the RCT double-blind period (BL, 154.8–161.0 mg/d; range, 137.1–168.0 mg/d, RCT open-label period (BL, 156.3–174.6; range, 144.0–180.0 and OLT (BL, 120 mg/d; range, 117.3–121.1 mg/d. No significant change from BL in pain intensity score occurred in any group at weeks 2 or 4 (both P≥0.1 of the RCT double-blind period, and scores remained stable during the open-label period and in the OLT (mean change, —0.2 to 0.1. Changes from BL in OOWS and SOWS scores during the double-blind period were not significantly impacted by methylnaltrexone exposure at weeks 2 or 4 (P>0.05 for all. Conclusion: Methylnaltrexone did not affect
Idrisov, Bulat; Murphy, Sean M; Morrill, Tyler; Saadoun, Mayada; Lunze, Karsten; Shepard, Donald
Opioid agonist therapy using methadone, an effective treatment of opioid use disorders (OUD) for people who inject drugs (PWID), is recommended by the World Health Organization as essential to curtail the growing HIV epidemic. Yet, despite increasing prevalence of OUD and HIV, methadone therapy has not yet been implemented in Russia. The aim of this modeling study was to estimate the cost-effectiveness of methadone therapy for Russian adults with a diagnosed OUD. We modeled the projected program implementation costs and estimated disability-adjusted life years (DALYs) averted over a 10-year period, associated with the provision of methadone therapy for a hypothetical, unreplenished cohort of Russian adults with an OUD (n = 249,000), in comparison to the current therapies at existing addiction treatment facilities. Our model compared four distinct scenarios of treatment coverage in the cohort ranging from 3.1 to 55%. Providing methadone therapy to as few as 3.1% of adults with an OUD amounted to an estimated almost 50,000 DALYs averted over 10 years at a cost of just over USD 17 million. Further expanding service coverage to 55% resulted in an estimated almost 900,000 DALYs averted, at a cost of about USD 308 million. Our study indicated that implementing opioid agonist therapy with methadone to treat OUD at existing facilities in Russia is highly cost-effective.
Senn, Oliver; Seidenberg, André; Rosemann, Thomas
Injection drug users are at high risk for chronic hepatitis C virus infection (CHC). Opioid maintenance treatment (OMT) offers a unique opportunity to screen for CHC. This study proposed the hypothesis that a general practitioner (GP) with special interest in addiction medicine can achieve CHC screening rates comparable to specialized centres and aimed to investigate determinants for a successful CHC case finding in a primary care setting. Retrospective medical record analysis of 387 patients who received opioid maintenance therapy between 1 January 2002 and 31 May 2008 in a general practice in Zurich, Switzerland. Successful CHC assessment was defined as performance of hepatitis C virus (HCV) serology with consecutive polymerase chain reaction-based RNA and genotype recordings. The association between screening success and patient characteristics was assessed using multiple logistic regression. findings: Median (interquartile range) age and duration of OMT of the 387 (268 males) patients was 38.5 (33.6-44.5) years and 34 (11.3-68.0) months, respectively. Fourteen patients (3.6%) denied HCV testing and informed consent about screening was missing in 13 patients (3.4%). In 327 of 360 patients (90.8%) with informed consent a successful CHC assessment has been performed. Screening for HCV antibodies was positive in 136 cases (41.6%) and in 86 of them (63.2%) a CHC was present. The duration of OMT was an independent determinant of a successful CHC assessment. In addicted patients a high CHC assessment rate in a primary care setting in Switzerland is feasible and opioid substitution provides an optimal framework.
Elena Elizabeth Bagley
Full Text Available Opioids are intensely addictive, and cessation of their chronic use is associated with a highly aversive withdrawal syndrome. A cellular hallmark of withdrawal is an opioid sensitive protein kinase A-dependent increase in GABA transporter-1 (GAT-1 currents in periaqueductal gray (PAG neurons. Elevated GAT-1 activity directly increases GABAergic neuronal excitability and synaptic GABA release, which will enhance GABAergic inhibition of PAG output neurons. This reduced activity of PAG output neurons to several brain regions, including the hypothalamus and medulla, contributes to many of the PAG-mediated signs of opioid withdrawal. The GABAB receptor agonist baclofen reduces some of the PAG mediated signs of opioid withdrawal. Like the opioid receptors the GABAB receptor is a Gi/Go coupled G-protein coupled receptor. This suggests it could be modulating GAT-1 activity in PAG neurons through its inhibition of the adenylyl cyclase/protein kinase A pathway. Opioid modulation of the GAT-1 activity can be detected by changes in the reversal potential of opioid membrane currents. We found that when opioids are reducing the GAT-1 cation conductance and increasing the GIRK conductance the opioid agonist reversal potential is much more negative than Ek. Using this approach for GABAB receptors we show that the GABAB receptor agonist, baclofen, does not couple to inhibition of GAT-1 currents during opioid withdrawal. It is possible this differential signaling of the two Gi/Go coupled G-protein coupled receptors is due to the strong compartmentalization of the GABAB receptor that does not favor signaling to the adenylyl cyclase/protein kinase A/GAT-1 pathway. This highlights the importance of studying the effects of G-protein coupled receptors in native tissue with endogenous G-protein coupled receptors and the full complement of relevant proteins and signaling molecules. This study suggests that baclofen reduces opioid withdrawal symptoms through a non-GAT-1
Boscarino, Joseph A; Hoffman, Stuart N; Han, John J
Aims Previously, we estimated the prevalence and risk factors for prescription opioid-use disorder among outpatients on opioid therapy using the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 and DSM-4 criteria. However, at the time, the DSM-5 criteria were not finalized. In the current study, we analyzed these data using the final DSM-5 criteria and compared these results. Methods Using electronic records from a large US health care system, we identified outpatients receiving five or more prescription orders for opioid therapy in the past 12 months for noncancer pain (mean prescription orders =10.72; standard deviation =4.96). In 2008, we completed diagnostic interviews with 705 of these patients using the DSM-4 criteria. In the current study, we reassessed these results using the final DSM-5 criteria. Results The lifetime prevalence of DSM-5 opioid-use disorders using the final DSM-5 criteria was 58.7% for no or few symptoms (DSM-5 criteria (53.6%; 95% CI =44.1–62.8). In ordinal logistic regression predicting no/few, mild, moderate, and severe opioid-use disorder, the best predictors were age DSM-5 criteria, including the elimination of tolerance and withdrawal, inclusion of craving and abuse symptoms, and introduction of a new graded severity classification, the prevalence of opioid-use disorders has changed, while many of the DSM-4 risk factors for opioid dependence were similar. To our knowledge, this is one of the first studies to compare the final results for DSM-5 versus DSM-4 prescription opioid-use disorders among a high-risk patient population. PMID:26316838
Oliva, Elizabeth M; Trafton, Jodie A; Harris, Alex H S; Gordon, Adam J
Opioid agonist therapy (OAT) through addiction specialty clinic settings (clinic-based OAT) using methadone or buprenorphine or office-based settings using buprenorphine (office-based OAT) is an evidence-based treatment for opioid dependence. The low number of clinic-based OATs available to veterans (N = 53) presents a barrier to OAT access; thus, the expansion in office-based OAT has been encouraged. To examine trends in office-based OAT utilization over time and whether availability of office-based OAT improved the proportion of veterans with opioid use disorders treated with OAT. We examined Veterans Health Administration (VHA) administrative data for evidence of buprenorphine prescribing and clinic-based OAT clinic stops from October 2003 through September 2010 [fiscal years (FY) 2004-2010]. The number of patients receiving buprenorphine increased from 300 at 27 facilities in FY2004 to 6147 at 118 facilities in FY2010. During this time, the number of patients diagnosed with an opioid use disorder increased by 45%; however, the proportion of opioid use disorder patients receiving OAT remained relatively stable, ranging from 25% to 27%. Office-based OAT utilization and the number of opioid use disorder veterans treated with OAT are increasing at the same rate over time, suggesting that office-based OAT is being used to meet the growing need for OAT care. Although office-based OAT is increasingly being used within the VHA and may be one way the VHA is keeping up with the demand for OAT, more research is needed to understand how to engage a greater proportion of opioid use disorder patients in treatment.
Hooten, W Michael; Warner, David O
The objectives of this randomized, single-blinded, placebo-controlled pilot trial were to investigate the effects of varenicline on opioid withdrawal among chronic pain patients undergoing opioid detoxification in an interdisciplinary pain program and the feasibility of varenicline use in this population. Twenty-one patients were recruited (varenicline=10, placebo=11), and 7 patients in the varenicline and 11 in the placebo group completed the study. Opioid withdrawal was quantified using the Clinical Opiate Withdrawal Scale, and varenicline-related adverse effects were assessed. Opioid withdrawal scores tended to decrease over the course of opioid tapering in those receiving varenicline and increase in those receiving placebo. Varenicline was well-tolerated in this population, with no adverse drug effects (including nausea) observed and no effect on improvements in pain severity and depression. This randomized pilot study provides preliminary data for future trials of varenicline in opioid-dependent adults with chronic pain undergoing medically directed opioid detoxification. Copyright © 2014 Elsevier Ltd. All rights reserved.
Saloner, Brendan; Stoller, Kenneth B; Barry, Colleen L
This study examined differences in opioid agonist therapy (OAT) utilization among Medicaid-enrolled adults receiving public-sector opioid use disorder treatment in states with Medicaid coverage of methadone maintenance, states with block grant funding only, and states without public coverage of methadone. Person-level treatment admission data, which included information on reason for treatment and use of OAT from 36 states were linked to state-level Medicaid policies collected in a 50-state survey. Probabilities of OAT use among Medicaid enrollees in opioid addiction treatment were calculated, with adjustment for demographic characteristics and patterns of substance use. In adjusted analysis, 45.0% of Medicaid-enrolled individuals in opioid addiction treatment in states with Medicaid coverage for methadone maintenance used OAT, compared with 30.1% in states with block grant coverage only and 17.0% in states with no coverage. Differences were widest in nonintensive outpatient settings. Medicaid methadone maintenance coverage is critical for encouraging OAT among individuals with opioid use disorders.
Roth, Craig S; Burgess, Diana J
To determine if a pilot phase workshop influenced residents' beliefs and concerns about using opioids for chronic noncancer pain. Pre- and post-survey questionnaire. University residency program. Seventy-two Medicine and Medicine-Pediatrics residents. Participation in a 4-hour workshop based on adult learning theory. Residents' pre- and post-workshop concerns, feelings, and beliefs about the efficacy and safety of opioids for chronic noncancer pain (low back pain), and barriers to prescribing them (paired t-tests). On a scale of 1 = least to 10 = most, residents' concerns about addiction risk from opioids in patients with chronic noncancer pain dropped significantly (P changes were observed regarding concerns about abuse (5.61 to 3.92), side effects (4.88 to 2.88), limiting use of other treatments (5.41 to 3.60), sanctioning (State Board; 4.27 to 3.71; Legal 4.22 to 3.43), and drawing criticism from attending staff (4.50 to 2.77), with P beliefs about efficacy and safety of opioids for chronic noncancer pain increased (Pre 4.96 to Post 7.40), and they were more comfortable prescribing them (4.30 to 6.82), with P beliefs and concerns about using opioids for chronic noncancer pain changed after participating in a 4-hour interactive workshop.
Cepeda, M Soledad; Carr, Daniel B; Sarquis, Tony; Miranda, Nelcy; Garcia, Ricardo J; Zarate, Camilo
A growing multibillion dollar industry markets magnetic necklaces, bracelets, bands, insoles, back braces, mattresses, etc., for pain relief, although there is little evidence for their efficacy. We sought to evaluate the effect of magnetic therapy on pain intensity and opioid requirements in patients with postoperative pain. We designed a randomized, double-blind, controlled trial. One-hundred-sixty-five patients older than 12 yr of age were randomized to magnetic (n = 81) or sham therapy (n = 84) upon reporting moderate-to-severe pain in the postanesthesia care unit. Devices were placed over the surgical incision and left in place for 2 h. Patients rated their pain intensity on a 0-10 scale every 10 min and received incremental doses of morphine until pain intensity was Magnetic therapy lacks efficacy in controlling acute postoperative pain intensity levels or opioid requirements and should not be recommended for pain relief in this setting.
Marvel, Richard P
Chronic pelvic pain(CPP) is a common condition in women that can have a devastating effect on quality of life. Some of the most severe forms of CPP are related to peripheral nerve injuries causing persistent neuropathic pain. This is a case of a young woman with severe opioid dependent chronic pelvic and right groin pain due to obturator neuralgia. She had failed a multitude of treatments including multiple medications, manual physical therapy, nerve blocks, surgical neurolysis and spinal cord stimulation without significant benefit. She underwent a trial of peripheral neuromodulation of the obturator nerve with laparoscopic placement of a quadripolar lead. During the 6-day trial she had almost complete relief of her pain; therefore, she underwent permanent implantation of an intermittent pulse generator. Over the next 6 months she was completely weaned completely off her chronic opioids. At 23 months post implantation, she had essentially no pain and is no longer on any analgesic, antidepressant or membrane stabilizing medications. Peripheral Neuromodulation has the potential to alleviate pain and significantly improve quality of life in women with longstanding neuropathic chronic pelvic pain who have failed multimodal conservative therapy. Copyright © 2018. Published by Elsevier Inc.
Nielsen, Rikke Vibeke; Fomsgaard, Jonna Storm; Siegel, Hanna; Martusevicius, Robertas; Nikolajsen, Lone; Dahl, Jørgen Berg; Mathiesen, Ole
Perioperative handling of surgical patients with opioid dependency represents an important clinical problem. Animal studies suggest that ketamine attenuates central sensitization and hyperalgesia and thereby reduces postoperative opioid tolerance. We hypothesized that intraoperative ketamine would reduce immediate postoperative opioid consumption compared with placebo in chronic pain patients with opioid dependency undergoing lumbar spinal fusion surgery. Primary outcome was morphine consumption 0 to 24 hours postoperatively. Secondary outcomes were acute pain at rest and during mobilization 2 to 24 hours postoperatively (visual analogue scale), adverse events, and persistent pain 6 months postoperatively. One hundred fifty patients were randomly assigned to intraoperative S-ketamine bolus 0.5 mg/kg and infusion 0.25 mg·kg·h or placebo. Postoperatively, patients received their usual opioids, paracetamol and IV patient-controlled analgesia with morphine. In the final analyses, 147 patients were included. Patient-controlled analgesia IV morphine consumption 0 to 24 hours postoperatively was significantly reduced in the ketamine group compared with the placebo group: 79 (47) vs 121 (53) mg IV, mean difference 42 mg (95% confidence interval -59 to -25), P ketamine group 6 and 24 hours postoperatively. There were no significant differences regarding acute pain, nausea, vomiting, hallucinations, or nightmares. Back pain at 6 months postoperatively compared with preoperative pain was significantly more improved in the ketamine group compared with the placebo group, P = 0.005. In conclusion, intraoperative ketamine significantly reduced morphine consumption 0 to 24 hours after lumbar fusion surgery in opioid-dependent patients. The trend regarding less persistent pain 6 months postoperatively needs further investigation.
... therapy in a primary care setting struggles with opioid addiction. 4,5,6 Once addicted, it can be ... of drug overdose deaths involving methadone and other opioid analgesics in West Virginia. Addiction 2009;104(9):1541-8. Dunn KM, Saunders ...
Larance, Briony; Bruno, Raimondo; Lintzeris, Nicholas; Degenhardt, Louisa; Black, Emma; Brown, Amanda; Nielsen, Suzanne; Dunlop, Adrian; Holland, Rohan; Cohen, Milton; Mattick, Richard P
Early identification of problems is essential in minimising the unintended consequences of opioid therapy. This study aimed to develop a brief scale that identifies and quantifies recent aberrant behaviour among diverse patient populations receiving long-term opioid treatment. 40 scale items were generated via literature review and expert panel (N=19) and tested in surveys of: (i) N=41 key experts, and (ii) N=426 patients prescribed opioids >3 months (222 pain patients and 204 opioid substitution therapy (OST) patients). We employed item and scale psychometrics (exploratory factor analyses, confirmatory factor analyses and item-response theory statistics) to refine items to a brief scale. Following removal of problematic items (poor retest-reliability or wording, semantic redundancy, differential item functioning, collinearity or rarity) iterative factor analytic procedures identified a 10-item unifactorial scale with good model fit in the total sample (N=426; CFI=0.981, TLI=0.975, RMSEA=0.057), and among pain (CFI=0.969, TLI=0.960, RMSEA=0.062) and OST subgroups (CFI=0.989, TFI=0.986, RMSEA=0.051). The 10 items provided good discrimination between groups, demonstrated acceptable test-retest reliability (ICC 0.80, 95% CI 0.60-0.89; Cronbach's alpha=0.89), were moderately correlated with related constructs, including opioid dependence (SDS), depression and stress (DASS subscales) and Social Relationships and Environment domains of the WHO-QoL, and had strong face validity among advising clinicians. The Opioid-Related Behaviours In Treatment (ORBIT) scale is brief, reliable and validated for use in diverse patient groups receiving opioids. The ORBIT has potential applications as a checklist to prompt clinical discussions and as a tool to quantify aberrant behaviour and assess change over time. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Carmody, J; Cooper, K
Chronic nociception has been studied in male mice by means of the formalin test in which forelimb motor behaviour is scored after subcutaneous formalin injection. The rating remained above 2.0 for 30 min after the injection (scale range 0-3). The magnitude of the nociception has been compared with that reported in other animal types. Mice are more sensitive than rats, cats and monkeys. The stress of a swim of 3 min has been found to reduce nociception by up to 25%. This analgesia is wholly opioid in nature, being abolished by a moderate dose of naloxone (1 mg/kg).
Vrancken, A. F. J. E.; van Schaik, I. N.; Hughes, R. A. C.; Notermans, N. C.
BACKGROUND: Chronic idiopathic axonal polyneuropathy is an insidiously progressive sensory or sensorimotor polyneuropathy that affects elderly people. Although severe disability or handicap does not occur, it reduces quality of life. OBJECTIVES: To assess whether drug therapy for chronic idiopathic
Robert B Coambs
Full Text Available BACKGROUND: Many physicians are overly cautious about prescribing opioids for chronic pain because of fears of iatrogenic addiction. However, in patients with chronic pain, addiction to opioid analgesics is exceedingly rare when there is no prior history of alcohol or drug abuse.
McHugh, R Kathryn; Votaw, Victoria R; Barlow, David H; Fitzmaurice, Garrett M; Greenfield, Shelly F; Weiss, Roger D
Opioid use disorder is a highly disabling psychiatric disorder, and is associated with both significant functional disruption and risk for negative health outcomes such as infectious disease and fatal overdose. Even among those who receive evidence-based pharmacotherapy for opioid use disorder, many drop out of treatment or relapse, highlighting the importance of novel treatment strategies for this population. Over 60% of those with opioid use disorder also meet diagnostic criteria for an anxiety disorder; however, efficacious treatments for this common co-occurrence have not be established. This manuscript describes the rationale and methods for a behavioral treatment development study designed to develop and test an integrated cognitive-behavioral therapy for those with co-occurring opioid use disorder and anxiety disorders. The aims of the study are (1) to develop and pilot test a new manualized cognitive behavioral therapy for co-occurring opioid use disorder and anxiety disorders, (2) to test the efficacy of this treatment relative to an active comparison treatment that targets opioid use disorder alone, and (3) to investigate the role of stress reactivity in both prognosis and recovery from opioid use disorder and anxiety disorders. Our overarching aim is to investigate whether this new treatment improves both anxiety and opioid use disorder outcomes relative to standard treatment. Identifying optimal treatment strategies for this population are needed to improve outcomes among those with this highly disabling and life-threatening disorder. Copyright © 2017 Elsevier Inc. All rights reserved.
Wirz, Stefan; Klaschik, Eberhard
This study assessed the efficacy of laxative use for treatment of constipation in patients receiving opioid therapy, with special attention to polyethylene glycol 3350/electrolyte solution (PEG-ES). Computerized data from 206 patients were analyzed using descriptive statistics. Subgroups were analyzed using confirmatory statistics. Constipation occurred in 42.7 percent of patients. Laxatives were administered to 74.3 percent of these patients using a standardized step scheme, with good results in 78.4 percent. As a therapy for constipation, the combined administration of PEG-ES, sodium picosulphate, and liquid paraffin proved most effective, although statistical analysis yielded no significance. Early use of PEG-ES using a step scheme holds promise for treatment of opioid-related constipation in palliative care patients, although further investigation is warranted.
Nielsen, Rikke Vibeke; Fomsgaard, Jonna Storm; Siegel, Hanna
Perioperative handling of surgical patients with opioid dependency represents an important clinical problem. Animal studies suggest that ketamine attenuates central sensitization and hyperalgesia and thereby reduces postoperative opioid tolerance. We hypothesized that intraoperative ketamine would...... to 24 hours postoperatively (visual analogue scale), adverse events, and persistent pain 6 months postoperatively. One hundred fifty patients were randomly assigned to intraoperative S-ketamine bolus 0.5 mg/kg and infusion 0.25 mg·kg·h or placebo. Postoperatively, patients received their usual opioids......, paracetamol and IV patient-controlled analgesia with morphine. In the final analyses, 147 patients were included. Patient-controlled analgesia IV morphine consumption 0 to 24 hours postoperatively was significantly reduced in the ketamine group compared with the placebo group: 79 (47) vs 121 (53) mg IV, mean...
Neal, C P; Dennison, A R; Garcea, G
valid surgical option for the treatment of pain. Though previously dismissed as a valid treatment due to the resultant brittle diabetes, the advent of islet cell autotransplantation has enabled this procedure to produce excellent long-term results in relation to pain, endocrine status and quality of life. Given these excellent short- and long-term results of surgical therapy for chronic pancreatitis, and the poor symptom control provided by conservative and endoscopic treatment (coupled to near inevitable progression to exocrine and endocrine failure), it is likely that future years will see a further shift towards the earlier and more frequent surgical treatment of chronic pancreatitis. Furthermore, the expansion of islet cell autotransplantation to a wider range of pancreatic resections has the potential to even further improve the outcomes of surgical treatment for this problematic yet increasingly common disease.
Roux, Perrine; Sullivan, Maria A; Cohen, Julien; Fugon, Lionel; Jones, Jermaine D; Vosburg, Suzanne K; Cooper, Ziva D; Manubay, Jeanne M; Mogali, Shanthi; Comer, Sandra D
Few studies have examined abuse of prescription opioids among individuals with chronic pain under buprenorphine/naloxone (Bup/Nx) maintenance. The current 7-week inpatient study assessed oral oxycodone self-administration by patients with chronic pain who had a history of opioid abuse. Participants (n=25) were transitioned from their preadmission prescribed opioid to Bup/Nx. All of the participants were tested under each of the sublingual Bup/Nx maintenance doses (2/0.5, 8/2 or 16/4 mg) in random order. During each maintenance period, participants could self-administer oxycodone orally (0, 10, 20, 40 or 60 mg prescription opioids) or receive money during laboratory sessions. Drug choice (percentage) was the primary dependent variable. Subjective ratings of clinical pain and withdrawal symptoms also were measured. Mann-Whitney tests compared percentage of drug choice for each active oxycodone dose to placebo. Logistic regression analyses identified correlates of oxycodone preference, defined as 60% or greater choice of oxycodone compared to money. Pain was significantly reduced while participants were maintained on Bup/Nx compared to preadmission ratings. No differences in percentage drug choice were observed between the active oxycodone doses and placebo under each Bup/Nx maintenance dose. However, factors associated with oxycodone preference were lower Bup/Nx maintenance dose, more withdrawal symptoms and more pain. These data suggest that Bup/Nx was effective in reducing pain and supplemental oxycodone use. Importantly, adequate management of pain and withdrawal symptoms by Bup/Nx may reduce oxycodone preference in this population. Published by Elsevier B.V.
Transdermal buprenorphine, opioid rotation to sublingual buprenorphine, and the avoidance of precipitated withdrawal: a review of the literature and demonstration in three chronic pain patients treated with butrans.
Kornfeld, Howard; Reetz, Heidi
Buprenorphine is an opioid, used in the United States and abroad for both analgesia and addiction, with unique opioid receptor binding properties. There are several pharmacological features of buprenorphine that make it an emerging option for the long-term treatment of chronic pain-its respiratory suppression ceiling effect, its efficacy in neuropathic pain and hyperalgesic states, and its decreased suppression of the immune and endocrine systems compared with other long-acting opioids. Previous studies have shown that high-dose sublingual buprenorphine is an effective treatment of chronic pain patients not responding to other opioids. Guidelines for the introduction of sublingual buprenorphine, termed buprenorphine induction, include an opioid-free "withdrawal" period of 12-48 hours to avoid an anticipated and accelerated opioid withdrawal, a syndrome described in this article as precipitated withdrawal. The requirement of a period of opioid abstinence before buprenorphine use may present a significant barrier to its adoption for chronic pain. We present a case series of a novel method of sublingual buprenorphine introduction without an induction period, using the recently Food and Drug Administration-approved low-dose transdermal buprenorphine (Butrans; Purdue Pharma L.P.) as a bridge medication. In these cases, buprenorphine was started in opioid-dependent chronic noncancer pain patients who had taken short-acting opioid medications within hours of the initiation of the rotation. This method avoids the painful abstinence period and did not result in precipitated withdrawal or other significant adverse effects.
Chronic pain and its associated syndrome have become increasingly prevalent in primary care. With the increase in narcotic use and subsequent adverse events, primary care physicians often seek safer alternatives to treating this condition. Prescribing narcotics necessitates using methods to screen for high abuse risk and protect against misuse. With the understanding of how chronic pain is related to mental illnesses such as depression and posttraumatic stress disorder, mindfulness techniques and behavioral therapy can be used to help decrease the dependence on dangerous opioid medications and help patients understand, accept, and cope with their chronic pain. Copyright © 2016 Elsevier Inc. All rights reserved.
Olesen, Søren S; Poulsen, Jakob Lykke; Broberg, Marie C H; Madzak, Adnan; Drewes, Asbjørn M
Chronic pancreatitis (CP) is a complex and debilitating disease with high resource utilisation. Prospective data on hospital admission rates and associated risk factors are scarce. We investigated hospitalisation rates, causes of hospitalisations and associated risk factors in CP outpatients. This was a prospective cohort study comprising 170 patients with CP. The primary outcome was time to first pancreatitis related hospitalisation and secondary outcomes were the annual hospitalisation frequency (hospitalisation burden) and causes of hospitalisations. A number of clinical and demographic parameters, including pain pattern and severity, opioid use and parameters related to the nutritional state, were analysed for their association with hospitalisation rates. Of the 170 patients, 57 (33.5%) were hospitalised during the follow-up period (median 11.4 months [IQR 3.8-26.4]). The cumulative hospitalisation incidence was 7.6% (95% CI; 4.5-12.2) after 30 days and 28.8% (95% CI; 22.2-35.7) after 1 year. Eighteen of the hospitalised patients (32%) had three or more admissions per year. High dose opioid treatment (>100 mg per day) (Hazard Ratio 3.1 [95% CI; 1.1-8.5]; P = 0.03) and hypoalbuminemia (risk factors for hospitalisation. The most frequent causes of hospitalisations were pain exacerbation (40%) and common bile duct stenosis (28%). One-third of CP outpatients account for the majority of hospital admissions and associated risk factors are high dose opioid treatment and hypoalbuminemia. This information should be implemented in outpatient monitoring strategies to identify risk patients and improve treatment. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.
Renner, F.; Arntz, A.; Leeuw, I.; Huibers, M.J.H.
Schema therapy (ST) is an integrative treatment approach to chronic lifelong problems with an established effectiveness for treating personality disorders. This article describes the adaptation of ST to chronic depression by reviewing the literature on the underlying risk factors to chronic
Maslov, L. N.; Naryzhnaya, N. V.; Prokudina, E. S.; Kolář, František; Gorbunov, A. S.; Zhang, Y.; Wang, H.; Tsibulnikov, S.Yu.; Portnichenko, A. G.; Lasukova, T. V.; Lishmanov, Yu. B.
Roč. 42, č. 5 (2015), s. 496-501 ISSN 1440-1681 R&D Projects: GA ČR(CZ) GAP303/12/1162 Institutional support: RVO:67985823 Keywords : cardioprotection * chronic hypoxia * ischaemia/reperfusion * mitochondrial function * opioid receptors Subject RIV: ED - Physiology Impact factor: 2.004, year: 2015
Tsui, Judith I; Evans, Jennifer L; Lum, Paula J; Hahn, Judith A; Page, Kimberly
Injection drug use is the primary mode of transmission for hepatitis C virus (HCV) infection. Prior studies suggest opioid agonist therapy may reduce the incidence of HCV infection among injection drug users; however, little is known about the effects of this therapy in younger users. To evaluate whether opioid agonist therapy was associated with a lower incidence of HCV infection in a cohort of young adult injection drug users. Observational cohort study conducted from January 3, 2000, through August 21, 2013, with quarterly interviews and blood sampling. We recruited young adult (younger than 30 years) injection drug users who were negative for anti-HCV antibody and/or HCV RNA. Substance use treatment within the past 3 months, including non-opioid agonist forms of treatment, opioid agonist (methadone hydrochloride or buprenorphine hydrochloride) detoxification or maintenance therapy, or no treatment. Incident HCV infection documented with a new positive result for HCV RNA and/or HCV antibodies. Cumulative incidence rates (95% CI) of HCV infection were calculated assuming a Poisson distribution. Cox proportional hazards regression models were fit adjusting for age, sex, race, years of injection drug use, homelessness, and incarceration. Baseline characteristics of the sample (n = 552) included median age of 23 (interquartile range, 20-26) years; 31.9% female; 73.1% white; 39.7% who did not graduate from high school; and 69.2% who were homeless. During the observation period of 680 person-years, 171 incident cases of HCV infection occurred (incidence rate, 25.1 [95% CI, 21.6-29.2] per 100 person-years). The rate ratio was significantly lower for participants who reported recent maintenance opioid agonist therapy (0.31 [95% CI, 0.14-0.65]; P = .001) but not for those who reported recent non-opioid agonist forms of treatment (0.63 [95% CI, 0.37-1.08]; P = .09) or opioid agonist detoxification (1.45 [95% CI, 0.80-2.69]; P = .23). After adjustment for
Yoon, Jin H; Lane, Scott D; Weaver, Michael F
Practitioners are highly likely to encounter patients with concurrent use of nicotine products and opioid analgesics. Smokers present with more severe and extended chronic pain outcomes and have a higher frequency of prescription opioid use. Current tobacco smoking is a strong predictor of risk for nonmedical use of prescription opioids. Opioid and nicotinic-cholinergic neurotransmitter systems interact in important ways to modulate opioid and nicotine effects: dopamine release induced by nicotine is dependent on facilitation by the opioid system, and the nicotinic-acetylcholine system modulates self-administration of several classes of abused drugs-including opioids. Nicotine can serve as a prime for the use of other drugs, which in the case of the opioid system may be bidirectional. Opioids and compounds in tobacco, including nicotine, are metabolized by the cytochrome P450 enzyme system, but the metabolism of opioids and tobacco products can be complicated. Accordingly, drug interactions are possible but not always clear. Because of these issues, asking about nicotine use in patients taking opioids for pain is recommended. When assessing patient tobacco use, practitioners should also obtain information on products other than cigarettes, such as cigars, pipes, smokeless tobacco, and electronic nicotine delivery systems (ENDS, or e-cigarettes). There are multiple forms of behavioral therapy and pharmacotherapy available to assist patients with smoking cessation, and opioid agonist maintenance and pain clinics represent underutilized opportunities for nicotine intervention programs.
Conclusion: This nationwide survey described the concurrent pain intensity, daily function, and various adverse effects by long-term opioids among 210 monitored outpatients with chronic noncancer pain in Taiwan. More efforts are suggested to reduce opioid prescriptions in the 30% of patients exceeding daily watchful dose.
Sun, Eric C; Bateman, Brian T; Memtsoudis, Stavros G; Neuman, Mark D; Mariano, Edward R; Baker, Laurence C
Total knee arthroplasty (TKA) is associated with high rates of prolonged opioid use after surgery (10%-34%). By decreasing opioid use in the immediate postoperative period, perioperative nerve blockade has been hypothesized to decrease the risk of persistent opioid use. Using health care utilization data, we constructed a sample of 120,080 patients undergoing TKA between 2002 and 2012 and used billing data to identify the utilization of peripheral or neuraxial blockade. We then used a multivariable logistic regression to estimate the association between nerve blockade and the risk of chronic opioid use, defined as having filled ≥10 prescriptions or ≥120 days' supply for an opioid in the first postsurgical year. Our analyses were adjusted for an extensive set of potential confounding variables, including medical comorbidities, previous opioid use, and previous use of other medications. We did not find an association between nerve blockade and the risk of postsurgical chronic opioid use across any of these 3 groups: adjusted relative risk (ARR) 0.984 for patients opioid-naïve in the year before surgery (98.3% confidence interval [CI], 0.870-1.12, P = .794), ARR 1.02 for intermittent opioid users (98.3% CI, 0.948-1.09, P = .617), and ARR 0.986 (98.3% CI, 0.963-1.01, P = .257) for chronic opioid users. Similar results held for alternative measures of postsurgical opioid use. Although the use of perioperative nerve blockade for TKA may improve short-term outcomes, the analyzed types of blocks do not appear to decrease the risk of persistent opioid use in the longer term.
Full Text Available Stress increases the risk of drug abuse, causes relapse to drug seeking, and potentiates the rewarding properties of both nicotine and cocaine. Understanding the mechanisms by which stress regulates the rewarding properties of drugs of abuse provides valuable insight into potential treatments for drug abuse. Prior reports have demonstrated that stress causes dynorphin release, activating kappa-opioid receptors (KOR in monoamine circuits resulting in both potentiation and reinstatement of cocaine and nicotine conditioned place preference. Here we report that kappa-opioid dependent reinstatement of cocaine and nicotine place preference is reduced when the mice are exposed to a randomized chronic mild stress regime prior to training in a conditioned place preference-reinstatement paradigm. The chronic mild stress schedule involves seven different stressors (removal of nesting for 24hr, 5min forced swim stress at 15°C, 8hr food and water deprivation, damp bedding overnight, white noise, cage tilt and disrupted home cage lighting rotated over a three-week period. This response is KOR-selective, because chronic mild stress does not protect against cocaine or nicotine drug-primed reinstatement. This protection from reinstatement is also observed following sub-chronic social defeat stress, where each mouse is placed in an aggressor mouse home cage for a period of 20 min over five days. In contrast, a single acute stressor resulted in a potentiation of KOR-induced reinstatement, similarly to previously reported. Prior studies have shown that stress alters sensitivity to opioids and prior stress can influence the pharmacodynamics of the opioid receptor system. Together, these findings suggest that exposure to different forms of stress may cause a dysregulation of kappa opioid circuitry and that changes resulting from mild stress can have protective and adaptive effects against drug relapse.
Franklyn, Alexandra M; Eibl, Joseph K; Gauthier, Graham J; Marsh, David C
With the Canadian government legalizing cannabis in the year 2018, the potential harms to certain populations-including those with opioid use disorder-must be investigated. Cannabis is one of the most commonly used substances by patients who are engaged in medication-assisted treatment for opioid use disorder, the effects of which are largely unknown. In this study, we examine the impact of baseline and ongoing cannabis use, and whether these are impacted differentially by gender. We conducted a retrospective cohort study using anonymized electronic medical records from 58 clinics offering opioid agonist therapy in Ontario, Canada. One-year treatment retention was the primary outcome of interest and was measured for patients who did and did not have a cannabis positive urine sample in their first month of treatment, and as a function of the proportion of cannabis-positive urine samples throughout treatment. Our cohort consisted of 644 patients, 328 of which were considered baseline cannabis users and 256 considered heavy users. Patients with baseline cannabis use and heavy cannabis use were at increased risk of dropout (38.9% and 48.1%, respectively). When evaluating these trends by gender, only female baseline users and male heavy users are at increased risk of premature dropout. Both baseline and heavy cannabis use are predictive of decreased treatment retention, and differences do exist between genders. With cannabis being legalized in the near future, physicians should closely monitor cannabis-using patients and provide education surrounding the potential harms of using cannabis while receiving treatment for opioid use disorder.
Hser, Yih-Ing; Mooney, Larissa J; Saxon, Andrew J; Miotto, Karen; Bell, Douglas S; Huang, David
To examine the prevalence of comorbid chronic pain among patients with opioid use disorder (OUD) and to compare other comorbidities (substance use disorder (SUD), mental health disorders, health/disease conditions) among patients in four categories: no chronic pain (No Pain), OUD prior to pain (OUD First), OUD and pain at the same time (Same Time), or pain condition prior to OUD (Pain First). Using an electronic health record (EHR) database from 2006-2015, the study assessed 5307 adult patients with OUD in a large healthcare system; 35.6% were No Pain, 9.7% were OUD First, 14.9% were Same Time, and 39.8% were Pain First. Most OUD patients (64.4%) had chronic pain conditions, and among them 61.8% had chronic pain before their first OUD diagnosis. Other SUDs occurred more frequently among OUD First patients than among other groups in terms of alcohol (33.4% vs. 25.4% for No Pain, 20.7% for Same Time, and 20.3% for Pain First), cocaine (19.0%, vs. 13.8%, 9.4%, 7.1%), and alcohol or drug-induced disorders. OUD First patients also had the highest rates of HIV (4.7%) and hepatitis C virus (HCV; 28.2%) among the four groups. Pain First patients had the highest rates of mental disorder (81.7%), heart disease (72.0%), respiratory disease (68.4%), sleep disorder (41.8%), cancer (23.4%), and diabetes (19.3%). The alarming high rates of chronic pain conditions occurring before OUD and the associated severe mental health and physical health conditions require better models of assessment and coordinated care plans to address these complex medical conditions. Copyright © 2017 Elsevier Inc. All rights reserved.
Kater, Arnon P.; van Oers, Marinus H. J.; Kipps, Thomas J.
Although chemotherapy can induce complete responses in patients with chronic lymphocytic leukemia (CLL), it is not considered curative. Treated patients generally develop recurrent disease requiring additional therapy, which can cause worsening immune dysfunction, myelosuppression, and selection for
Addiction to opioids, or opioid dependence, encompasses the biopsychosocial dysfunction seen in illicit heroin injectors, as well as aberrant behaviours in patients prescribed opioids for chronic nonmalignant pain. To outline the management of opioid dependence using opioid pharmacotherapy as part of a comprehensive chronic illness management strategy. The same principles and skills general practitioners employ in chronic illness management underpin the care of patients with opioid dependence. Opioid pharmacotherapy, with the substitution medications methadone and buprenorphine, is an effective management of opioid dependence. Training and regulatory requirements for prescribing opioid pharmacotherapies vary between jurisdictions, but this treatment should be within the scope of most Australian GPs.
Full Text Available Aim. To examine medical practices and training needs of Québec family physicians with respect to pain management and opioid prescription for chronic noncancer pain (CNCP. Methodology. An online survey was carried out in 2016. Results. Of 636 respondents (43.0% men; 54.3% ≥ 50 years old, 15.2% and 70.9% felt very or somewhat confident that they could properly prescribe opioids for CNCP. Concerns related to abuse (72.5% strongly/somewhat agree, dependence (73.2%, and lack of support (75.4% were the main barriers reported. Only 19.7% always/often screened their patients for risks of abuse and dependence using a screening tool. About two-thirds of participants (65.7% had recently (last five years taken part in continuing education programs on opioid use for CNCP and 73.4% on CNCP management. Patient evaluation and differential diagnoses of chronic pain syndromes were rated as a top priority for further training. Conclusions. This study provides insights into Québec family physicians’ concerns, practices, and needs with respect to the management of CNCP. Physicians’ difficulties around the application of strategies to mitigate the problem of opioid abuse and addiction are worrying. The need to better train physicians in the field of pain and addiction cannot be emphasized enough.
Weiner, Scott G; Yannopoulos, Paul F; Lu, Chao
To determine if an opioid prescribing guideline poster, meant to be posted in an emergency department (ED) triage area, would deter patients with chronic pain from seeking care. We prospectively enrolled patients presenting to a chronic craniofacial pain clinic affiliated with an urban academic Level I trauma center. Patients were surveyed with a close-ended, structured questionnaire. Included patients were aged 18 and older with pain lasting 12 weeks or longer. Patients were shown a sample pain poster. The primary outcome was determination if such a poster would prevent the patient from staying to receive care in the ED. One hundred patients were surveyed. Most patients (77%) reported having been a patient in the ED in the past, and of these, 23% reported visiting the ED for worsening of chronic pain. After being shown the poster, 97% believed the recommendations in the poster were reasonable and 97% thought that the poster should be displayed in the ED. Seven patients (7%) reported that seeing the poster in the ED waiting room or triage area would intimidate them, and two patients within this group (2% of total sample) reported that it would prevent them from staying to get care. The vast majority of patients with chronic pain in this cohort believes that a pain guideline poster is reasonable and should be posted in the ED. However, a small percentage of patients reported that they would feel intimidated by such a poster and that it would prevent them from staying to get care, a result meant to inform hospitals and policy-makers deciding if such posters should be displayed. Wiley Periodicals, Inc.
Bagley, Elena E; Chieng, Billy C H; Christie, MacDonald J; Connor, Mark
The midbrain periaqueductal gray (PAG) is a major site of opioid analgesic action, and a significant site of cellular adaptations to chronic morphine treatment (CMT). We examined mu-opioid receptor (MOP) regulation of voltage-gated calcium channel currents (I(Ca)) and G-protein-activated K channel currents (GIRK) in PAG neurons from CMT mice. Mice were injected s.c. with 300 mg kg(-1) of morphine base in a slow release emulsion three times over 5 days, or with emulsion alone (vehicles). This protocol produced significant tolerance to the antinociceptive effects of morphine in a test of thermal nociception. Voltage clamp recordings were made of I(Ca) in acutely isolated PAG neurons and GIRK in PAG slices. The MOP agonist DAMGO (Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol enkephalin) inhibited I(Ca) in neurons from CMT mice (230 nM) with a similar potency to vehicle (150 nM), but with a reduced maximal effectiveness (37% inhibition in vehicle neurons, 27% in CMT neurons). Inhibition of I(Ca) by the GABA(B) agonist baclofen was not altered by CMT. Met-enkephalin-activated GIRK currents recorded in PAG slices were significantly smaller in neurons from CMT mice than vehicles, while GIRK currents activated by baclofen were unaltered. These data demonstrate that CMT-induced antinociceptive tolerance is accompanied by homologous reduction in the effectiveness of MOP agonists to inhibit I(Ca) and activate GIRK. Thus, a reduction in MOP number and/or functional coupling to G proteins accompanies the characteristic cellular adaptations to CMT previously described in PAG neurons.
Lalanne, L; Ayranci, G; Filliol, D; Gavériaux-Ruff, C; Befort, K; Kieffer, B L; Lutz, P-E
Addiction is a chronic brain disorder that progressively invades all aspects of personal life. Accordingly, addiction to opiates severely impairs interpersonal relationships, and the resulting social isolation strongly contributes to the severity and chronicity of the disease. Uncovering new therapeutic strategies that address this aspect of addiction is therefore of great clinical relevance. We recently established a mouse model of heroin addiction in which, following chronic heroin exposure, 'abstinent' mice progressively develop a strong and long-lasting social avoidance phenotype. Here, we explored and compared the efficacy of two pharmacological interventions in this mouse model. Because clinical studies indicate some efficacy of antidepressants on emotional dysfunction associated with addiction, we first used a chronic 4-week treatment with the serotonergic antidepressant fluoxetine, as a reference. In addition, considering prodepressant effects recently associated with kappa opioid receptor signaling, we also investigated the kappa opioid receptor antagonist norbinaltorphimine (norBNI). Finally, we assessed whether fluoxetine and norBNI could reverse abstinence-induced social avoidance after it has established. Altogether, our results show that two interspaced norBNI administrations are sufficient both to prevent and to reverse social impairment in heroin abstinent animals. Therefore, kappa opioid receptor antagonism may represent a useful approach to alleviate social dysfunction in addicted individuals. © 2016 Society for the Study of Addiction.
Full Text Available Jeffrey Scott Andrews,1 Ning Wu,2 Shih-Yin Chen,2 Xia Yu,2 Xiaomei Peng,1 Diego Novick1 1Global Health Outcomes, Eli Lilly and Company, Indianapolis, IN, USA; 2Evidera, Lexington, MA, USA Abstract: To describe the use of pain medications in patients with chronic low back pain (CLBP after initiating duloxetine or standard of care (SOC [muscle relaxants, gabapentin, pregabalin, venlafaxine, and tricyclic antidepressants] for pain management, pharmacy and medical claims from Surveillance Data, Inc (SDI Health were analyzed. Adult patients with CLBP who initiated duloxetine or SOC between November 2010 and April 2011 were identified. Treatment initiation was defined as no pill coverage for duloxetine or SOC in the previous 90 days. Included patients had no opioid use in the 90 days before initiation. Propensity score matching was used to select patients with similar baseline demographic and clinical characteristics for duloxetine and SOC cohorts. Compliance with index medication was assessed via medication possession ratio (MPR and proportion of days covered (PDC for 6 months after initiation. The proportion of patients receiving opioids and days on opioids after index date were assessed, and regression models were estimated to compare opioid use between cohorts. A total of 766 patients initiated duloxetine and 6,206 patients initiated SOC. After matching, 743 patients were selected for the duloxetine (mean age 57 years; female 74% and SOC (mean age 57 years; female 75% cohorts, respectively. Of the duloxetine cohort, 92% started on or below recommended daily dose (≤60 mg. The duloxetine cohort had significantly higher MPR (0.78 versus [vs] 0.60 and PDC (0.50 vs 0.31, were less likely to use opioids (45% vs 61%, and had fewer days on opioids (median 0 vs 7 days than the SOC cohort (all P < 0.001. After adjusting for demographic and clinical characteristics, the duloxetine cohort initiated opioids later than the SOC cohort (hazard ratio 0.77, 95
Imani, Saeed; Atef Vahid, Mohammad Kazem; Gharraee, Banafsheh; Noroozi, Alireza; Habibi, Mojtaba; Bowen, Sarah
This study investigated the effectiveness of mindfulness-based group therapy (MBGT) compared to the usual opioid dependence treatment (TAU).Thirty outpatients meeting the DSM-IV-TR criteria for opioid dependence from Iranian National Center for Addiction Studies (INCAS) were randomly assigned into experimental (Mindfulness-Based Group Therapy) and control groups (the Usual Treatment).The experimental group undertook eight weeks of intervention, but the control group received the usual treatment according to the INCAS program. The Five Factor Mindfulness Questionnaire (FFMQ) and the Addiction Sevier Index (ASI) were administered at pre-treatment and post-treatment assessment periods. Thirteen patients from the experimental group and 15 from the control group completed post-test assessments. The results of MANCOVA revealed an increase in mean scores in observing, describing, acting with awareness, non-judging, non-reacting, and decrease in mean scores of alcohol and opium in MBGT patient group. The effectiveness of MBGT, compared to the usual treatment, was discussed in this paper as a selective protocol in the health care setting for substance use disorders.
Full Text Available Objective: This study investigated the effectiveness of mindfulness-based group therapy (MBGT compared to the usual opioid dependence treatment (TAU.Thirty outpatients meeting the DSM-IV-TR criteria for opioid dependence from Iranian National Center for Addiction Studies (INCAS were randomly assigned into experimental (Mindfulness-Based Group Therapy and control groups (the Usual Treatment.The experimental group undertook eight weeks of intervention, but the control group received the usual treatment according to the INCAS program. Methods:The Five Factor Mindfulness Questionnaire (FFMQ and the Addiction Sevier Index (ASI were administered at pre-treatment and post-treatment assessment periods. Thirteen patients from the experimental group and 15 from the control group completed post-test assessments. Results:The results of MANCOVA revealed an increase in mean scores in observing, describing, acting with awareness, non-judging, non-reacting, and decrease in mean scores of alcohol and opium in MBGT patient group. Conclusion:The effectiveness of MBGT, compared to the usual treatment, was discussed in this paper as a selective protocol in the health care setting for substance use disorders.
Full Text Available OBJECTIVE: To report long term experience (1997-2009 of intrathecal (IT therapy for chronic non-cancer pain in the context of our team's increasing emphasis on active management. DESIGN: Descriptive case series. SETTING: Australian tertiary multidisciplinary pain center, Hunter Integrated Pain Service (HIPS. INTERVENTION: This case series reports the changing use of IT implanted drug delivery systems (IDDSs for chronic non-cancer pain over 13 years. Initially IT therapy was used selectively following multidisciplinary assessment and double blind IT trial. Typical therapy combined opioid with clonidine. Multidimensional management was offered. Treatment strategy changed in 2003 due to HIPS experience of limited therapeutic gains and equivocal support for IT therapy in the literature. Subsequently IT therapy was no longer initiated for non-cancer pain and those on established regimes were encouraged to shift to oral/transdermal opioids with greater emphasis on active management. Patient education and consultation were key elements. Where IT cessation was elective gradual dose reduction commenced as an outpatient. In elective and urgent cases ketamine infusion and oral clonidine were used during hospital admissions to cover the switch to oral/transdermal opioids. Over the study period transition occurred to a broader management framework in which IT therapy for chronic non-cancer pain was no longer supported by HIPS. RESULTS: 25 patients were managed using IDDSs; 8 implanted by HIPS and 17 by other teams. Dose escalation and adverse effects were common. 24 of 25 patients ceased IT therapy; 7 (29% with urgent IDDS related complications, 16 (67% electively and 1 due to an unrelated death. The remaining patient returned to her original team to continue IT therapy. One post-explantation patient transferred to another team to recommence IT therapy. The remainder were successfully maintained on oral/transdermal opioids combined with active management.
Trenkwalder, Claudia; Zieglgänsberger, Walter; Ahmedzai, Sam H; Högl, Birgit
Opioid receptor agonists are known to relieve restless legs syndrome (RLS) symptoms, including both sensory and motor events, as well as improving sleep. The mechanisms of action of opioids in RLS are still a matter of speculation. The mechanisms by which endogenous opioids contribute to the pathophysiology of this polygenetic disorder, in which there are a number of variants, including developmental factors, remains unknown. A summary of the cellular mode of action of morphine and its (partial) antagonist naloxone via α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and the involvement of dendritic spine activation is described. By targeting pain and its consequences, opioids are the first-line treatment in many diseases and conditions with both acute and chronic pain and have thus been used in both acute and chronic pain conditions over the last 40 years. Addiction, dependence, and tolerability of opioids show a wide variability interindividually, as the response to opioids is influenced by a complex combination of genetic, molecular, and phenotypic factors. Although several trials have now addressed opioid treatment in RLS, hyperalgesia as a complication of long-term opioid treatment, or opioid-opioid interaction have not received much attention so far. Therapeutic opioids may act not only on opioid receptors but also via histamine or N-methyl-d-aspartate (NMDA) receptors. In patients with RLS, one of the few studies investigating opioid bindings found that possible brain regions involved in the severity of RLS symptoms are similar to those known to be involved in chronic pain, such as the medial pain system (medial thalamus, amygdala, caudate nucleus, anterior cingulate gyrus, insular cortex, and orbitofrontal cortex). The results of this diprenorphine positron emission tomography study suggested that the more severe the RLS, the greater the release of endogenous opioids. Since 1993, when the first small controlled study was performed with
Sutter, Mary Beth; Leeman, Lawrence; Hsi, Andrew
Neonatal opioid withdrawal syndrome is common due to the current opioid addiction epidemic. Infants born to women covertly abusing prescription opioids may not be identified as at risk until withdrawal signs present. Buprenorphine is a newer treatment for maternal opioid addiction and appears to result in a milder withdrawal syndrome than methadone. Initial treatment is with nonpharmacological measures including decreasing stimuli, however pharmacological treatment is commonly required. Opioid monotherapy is preferred, with phenobarbital or clonidine uncommonly needed as adjunctive therapy. Rooming-in and breastfeeding may decease the severity of withdrawal. Limited evidence is available regarding long-term effects of perinatal opioid exposure. Copyright © 2014 Elsevier Inc. All rights reserved.
Filges, Trine; Knudsen, Anne-Sofie Due; Svendsen, Majken
), Multidimensional Family Therapy (MDFT), and Psychoeducational Therapy (PET)). RESULTS Our main objective was to evaluate the current evidence on the effect of CBT on abstinence and drug use reduction for young people in outpatient treatment for non-opioid drug use. Seven randomised trials, involving 953......, and PET ) with respect to reduction in young people’s drug use. The evidence drawn from this systematic review is based on seven included studies analysed in two separate analyses, depending on whether the intervention was CBT with an add-on component such as motivational interviewing (four studies......) or CBT without an add-on component (three studies). The seven studies are very different in terms of their findings regarding the effects of CBT interventions compared to other interventions (ACRA, CBOP (+ACC), DHPE, FFT, IT, MDFT, and PET ) on young people’s drug use. Therefore, the overall conclusion...
Chronic pain is a significant health-care problem. This review aims to critically analyse occupational therapy services for people with chronic pain and identify significant factors influencing the future development of occupational therapy services for people with chronic pain.
Ling, Walter; Mooney, Larissa; Hillhouse, Maureen
Prescription opioid misuse in the USA has increased over threefold since 1990 to epidemic proportions, with substantial increases in prescription opioid use also reported in other countries, such as Australia and New Zealand. The broad availability of prescription pain medications, coupled with public misconceptions about their safety and addictive potential, have contributed to the recent surge in non-medical use of prescription opioids and corresponding increases in treatment admissions for problems related to opioid misuse. Given competing pressures faced by physicians to both diagnose and treat pain syndromes and identify individuals at risk for addictive disorders, the use of opioids in the treatment of pain poses a significant clinical challenge. This paper reviews the interaction between pain and opioid addiction with a focus on clinical management issues, including risk factors for opioid dependence in patients with chronic pain and the use of assessment tools to identify and monitor at-risk individuals. Treatment options for opioid dependence and pain are reviewed, including the use of the partial µ agonist buprenorphine in the management of concurrent pain and opioid addiction. Physicians should strive to find a reasonable balance between minimising potential adverse effects of opioid medications without diminishing legitimate access to opioids for analgesia. The article discusses the need to identify methods for minimising risks and negative consequences associated with opioid analgesics and poses research directions, including the development of abuse-deterrent opioid formulations, genetic risk factors for opioid dependence and opioid-induced hyperalgesia as a potential target for medication therapy. © 2011 Australasian Professional Society on Alcohol and other Drugs.
Eibl, Joseph K; Gauthier, Graham; Pellegrini, David; Daiter, Jeffery; Varenbut, Michael; Hogenbirk, John C; Marsh, David C
Opioid use disorder has been declared a public health crisis across North America and opioid agonist therapy (OAT) is the standard of care for these patients. Despite the increasing adoption of telemedicine as a delivery method for OAT, its effectiveness has not yet been evaluated against traditional in-person treatment. This study compared treatment outcomes for in-person versus telemedicine-delivered OAT. We conducted a non-randomized cohort comparison study using an administrative database for patients who commenced OAT between 2011 and 2012 across 58 clinic sites in the province of Ontario, Canada. Patients were stratified by primary treatment modality as being: in-person (telemedicine), mixed (25-75% by telemedicine), or via telemedicine (>75% appointments by telemedicine). The primary outcome was continuous retention in treatment as defined by one year of uninterrupted therapy, based on pharmacy dosing records. A total of 3733 OAT initiating patients were identified. Patients treated via telemedicine were more likely to be retained in therapy than patients treated in-person (n=1590; aOR=1.27; 95% CI 1.14-1.41; pTelemedicine patients demonstrated a retention rate of 50% at one year whereas in-person patients were retained at a rate of 39%. The mixed group also had higher likelihood of retention than the in-person group (n=418; aOR=1.26; 95% CI 1.08-1.47; p=0.001) and had a retention rate of 47% at one year. Telemedicine may be an effective alternative to delivering in person OAT, and it has the potential to expand access to care in rural, remote, and urban regions. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.
Burns, John W; Bruehl, Stephen; France, Christopher R; Schuster, Erik; Orlowska, Daria; Chont, Melissa; Gupta, Rajnish K; Buvanendran, Asokumar
Long-term use of opioid analgesics may be ineffective or associated with significant negative side effects for some people. At present, there is no sound method of identifying optimal opioid candidates. Individuals with chronic low back pain (n = 89) and healthy control individuals (n = 102) underwent ischemic pain induction with placebo, opioid blockade (naloxone), and morphine in counterbalanced order. They completed the Spielberger Anger-Out subscale. Endogenous opioid function × Anger-out × Pain status (chronic pain, healthy control) interactions were tested for morphine responses to ischemic threshold, tolerance, and pain intensity (McGill Sensory and Affective subscales) and side effects. For individuals with chronic pain and healthy control participants, those with low endogenous opioid function and low anger-out scores exhibited the largest morphine analgesic responses, whereas those with high anger-out and low endogenous opioid function showed relatively weaker morphine analgesic responses. Further, individuals with chronic pain with low endogenous opioid function and low anger-out scores also reported the fewest negative effects to morphine, whereas those with low endogenous opioid function and high anger-out reported the most. Findings point toward individuals with chronic pain who may strike a favorable balance of good analgesia with few side effects, as well as those who have an unfavorable balance of poor analgesia and many side effects. We sought to identify optimal candidates for opioid pain management. Low back pain patients who express anger and also have deficient endogenous opioid function may be poor candidates for opioid therapy. In contrast, low back patients who tend not to express anger and who also have deficient endogenous opioid function may make optimal candidates for opioid therapy. Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.
Klinger, Regine; Kothe, Ralph; Schmitz, Julia; Kamping, Sandra; Flor, Herta
This study tested the experimental placebo effect in a group of chronic pain patients. Forty-eight patients having chronic back pain participated in a randomized clinical trial that tested the efficacy of a sham opioid solution (NaCl) compared with an alleged neutral, completely inactive solution (NaCl). We shaped the placebo effect by 2 interventions: verbal instruction and conditioning. The patients were either told that the "solution reduces pain and improves physical capacity" or the "solution is neutral, a placebo." Half of each group was additionally conditioned (coupling solution with reduced experimental pain), yielding 4 subgroups with 12 participants each. Outcome measures were as follows: the patients' clinical back pain ratings and acute pain ratings (both examined by numerical rating scale 0-10) and self-rated functional capacity (0%-100%; time required for the exercise). Expected pain relief before and after solution intake was also assessed. The inactive solution (NaCl), when presented as an effective treatment (sham "opioid" solution), induced placebo analgesia as evident in lower ratings of the patients' clinical back pain (F(3.12,144.21) = 25.05, P pain ratings (F(1.99,87.40) = 18.12, P pain expectations, and they were maintained in both sham opioid groups. The results suggest that it may be clinically useful to explicitly integrate placebo analgesia responses into pain management.
Amie L. Severino
Full Text Available Prescription opioid misuse is an ongoing and escalating epidemic. Although these pharmacological agents are highly effective analgesics prescribed for different types of pain, opioids also induce euphoria, leading to increasing diversion and misuse. Opioid use and related mortalities have developed in spite of initial claims that OxyContin, one of the first opioids prescribed in the USA, was not addictive in the presence of pain. These claims allayed the fears of clinicians and contributed to an increase in the number of prescriptions, quantity of drugs manufactured, and the unforeseen diversion of these drugs for non-medical uses. Understanding the history of opioid drug development, the widespread marketing campaign for opioids, the immense financial incentive behind the treatment of pain, and vulnerable socioeconomic and physical demographics for opioid misuse give perspective on the current epidemic as an American-born problem that has expanded to global significance. In light of the current worldwide opioid epidemic, it is imperative that novel opioids are developed to treat pain without inducing the euphoria that fosters physical dependence and addiction. We describe insights from preclinical findings on the properties of opioid drugs that offer insights into improving abuse-deterrent formulations. One finding is that the ability of some agonists to activate one pathway over another, or agonist bias, can predict whether several novel opioid compounds bear promise in treating pain without causing reward among other off-target effects. In addition, we outline how the pharmacokinetic profile of each opioid contributes to their potential for misuse and discuss the emergence of mixed agonists as a promising pipeline of opioid-based analgesics. These insights from preclinical findings can be used to more effectively identify opioids that treat pain without causing physical dependence and subsequent opioid abuse.
Severino, Amie L.; Shadfar, Arash; Hakimian, Joshua K.; Crane, Oliver; Singh, Ganeev; Heinzerling, Keith; Walwyn, Wendy M.
Prescription opioid misuse is an ongoing and escalating epidemic. Although these pharmacological agents are highly effective analgesics prescribed for different types of pain, opioids also induce euphoria, leading to increasing diversion and misuse. Opioid use and related mortalities have developed in spite of initial claims that OxyContin, one of the first opioids prescribed in the USA, was not addictive in the presence of pain. These claims allayed the fears of clinicians and contributed to an increase in the number of prescriptions, quantity of drugs manufactured, and the unforeseen diversion of these drugs for non-medical uses. Understanding the history of opioid drug development, the widespread marketing campaign for opioids, the immense financial incentive behind the treatment of pain, and vulnerable socioeconomic and physical demographics for opioid misuse give perspective on the current epidemic as an American-born problem that has expanded to global significance. In light of the current worldwide opioid epidemic, it is imperative that novel opioids are developed to treat pain without inducing the euphoria that fosters physical dependence and addiction. We describe insights from preclinical findings on the properties of opioid drugs that offer insights into improving abuse-deterrent formulations. One finding is that the ability of some agonists to activate one pathway over another, or agonist bias, can predict whether several novel opioid compounds bear promise in treating pain without causing reward among other off-target effects. In addition, we outline how the pharmacokinetic profile of each opioid contributes to their potential for misuse and discuss the emergence of mixed agonists as a promising pipeline of opioid-based analgesics. These insights from preclinical findings can be used to more effectively identify opioids that treat pain without causing physical dependence and subsequent opioid abuse. PMID:29740351
Krantz, Mori J; Mehler, Philip S
Almost 3 million Americans have abused heroin. The most effective treatment for this concerning epidemic is opioid replacement therapy. Although, from a historical perspective, acceptance of this therapy has been slow, growing evidence supports its efficacy. There are 3 approved medications for opioid maintenance therapy: methadone hydrochloride, levomethadyl acetate, and buprenorphine hydrochloride. Each has unique characteristics that determine its suitability for an individual patient. Cardiac arrhythmias have been reported with methadone and levomethadyl, but not with buprenorphine. Due to concerns about cardiac risk, levomethadyl use has declined and the product may ultimately be discontinued. These recent safety concerns, specifics about opioid detoxification and maintenance, and new federal initiatives were studied. Opioid detoxification has a role in both preventing acute withdrawal and maintaining long-term abstinence. Although only a minority of eligible patients are engaged in treatment, opioid maintenance therapy appears to offer the greatest public health benefits. There is growing interest in expanding treatment into primary care, allowing opioid addiction to be managed like other chronic illnesses. This model has gained wide acceptance in Europe and is now being implemented in the United States. The recent Drug Addiction Treatment Act enables qualified physicians to treat opioid-dependent patients with buprenorphine in an office-based setting. Mainstreaming opioid addiction treatment has many advantages; its success will depend on resolution of ethical and delivery system issues as well as improved and expanded training of physicians in addiction medicine.
Raghu S Thota
Full Text Available Introduction: Under treatment of pain is a recognized global issue. Opioid analgesic medication is the mainstay of treatment in cancer patients as per the World Health Organization (WHO pain relief ladder, yet 50% of cancer patients worldwide do not receive adequate pain relief or are undertreated. Aim: The aim of this study was to audit the ongoing opioid-prescribing practices in our tertiary cancer pain clinic during January-June 2010. Materials& Methods: The prescribed type of opioid, dose, dosing interval, and laxatives details were analyzed. Results: Five hundred pain files were reviewed and 435 were found complete for audit. Three hundred forty-eight (80% patients were prescribed opioids. Two hundred fifty-nine (74.4% received weak opioids while 118 (33.9% received strong opioids. A total of 195 (45% patients had moderate and 184 (42% had severe pain. Ninety-three (26.7% patients received morphine; however, only 31.5% (58 of 184 in severe pain received morphine as per the WHO pain ladder. Only 73 of 93 (78.4% patients received an adequate dose of morphine with an adequate dosing interval and only 27 (29% were prescribed laxatives with morphine. Conclusion: This study shows that the under treatment of pain and under dosing of opioids coupled with improper side effect management are major issues.
This review article addresses the question of whether biomarker-guided therapy is ready for clinical implementation in chronic heart failure. The most well-known biomarkers in heart failure are natriuretic peptides, namely B-type natriuretic peptide (BNP) and N-terminal pro-BNP. They are well-established in the diagnostic process of acute heart failure and prediction of disease prognosis. They may also be helpful in screening patients at risk of developing heart failure. Although studied by 11 small- to medium-scale trials resulting in several positive meta-analyses, it is less well-established whether natriuretic peptides are also helpful for guiding chronic heart failure therapy. This uncertainty is expressed by differences in European and American guideline recommendations. In addition to reviewing the evidence surrounding the use of natriuretic peptides to guide chronic heart failure therapy, this article gives an overview of the shortcomings of the trials, how the results may be interpreted and the future directions necessary to fill the current gaps in knowledge. Therapy guidance in chronic heart failure using other biomarkers has not been prospectively tested to date. Emerging biomarkers, such as galectin-3 and soluble ST2, might be useful in this regard, as suggested by several post-hoc analyses. PMID:28785440
Birke, H; Kurita, G P; Sjøgren, P
of benzodiazepine (BZD)/BZD-related drugs in the Danish population. METHODS: Data from the cross-sectional national representative Danish Health and Morbidity Surveys (2000, 2005, 2010, and 2013) were combined with The Danish National Prescription Registry at an individual level. The study populations varied...... prevalence of opioid use from 4.1% to 5.7% among CNCP individuals. Higher CNCP prevalence was related to female gender, no cohabitation partner, short education, non-Western origin, and overweight/obesity. In addition, women with CNCP, especially >65 years, became more frequent users of opioids and used...... higher doses than men. Concurrent use of BZD/BZD-related drugs decreased (13%) from 2010 to 2013, still one-third of long-term opioid user were co-medicated with these drugs. CONCLUSIONS: The use of opioids has increased in Denmark, especially among elderly women. The concurrent use of BZD...
Burgos, Jose Luis; Cepeda, Javier A; Kahn, James G; Mittal, Maria Luisa; Meza, Emilio; Lazos, Raúl Rafael Palacios; Vargas, Psyché Calderón; Vickerman, Peter; Strathdee, Steffanie A; Martin, Natasha K
Mexico recently enacted drug policy reform to decriminalize possession of small amounts of illicit drugs and mandated that police refer identified substance users to drug treatment. However, the economic implications of drug treatment expansion are uncertain. We estimated the costs of opioid substitution therapy (OST) provision in Tijuana, Mexico, where opioid use and HIV are major public health concerns. We adopted an economic health care provider perspective and applied an ingredients-based micro-costing approach to quantify the average monthly cost of OST (methadone maintenance) provision at two providers (one private and one public) in Tijuana, Mexico. Costs were divided by type of input (capital, recurrent personnel and non-personnel). We defined "delivery cost" as all costs except for the methadone and compared total cost by type of methadone (powdered form or capsule). Cost data were obtained from interviews with senior staff and review of expenditure reports. Service provision data were obtained from activity logs and senior staff interviews. Outcomes were cost per OST contact and cost per person month of OST. We additionally collected information on patient charges for OST provision from published rates. The total cost per OST contact at the private and public sites was $3.12 and $5.90, respectively, corresponding to $95 and $179 per person month of OST. The costs of methadone delivery per OST contact were similar at both sites ($2.78 private and $3.46 public). However, cost of the methadone itself varied substantially ($0.34 per 80 mg dose [powder] at the private site and $2.44 per dose [capsule] at the public site). Patients were charged $1.93-$2.66 per methadone dose. The cost of OST provision in Mexico is consistent with other upper-middle income settings. However, evidenced-based (OST) drug treatment facilities in Mexico are still unaffordable to most people who inject drugs.
Degenhardt, Louisa; Lintzeris, Nicholas; Campbell, Gabrielle; Bruno, Raimondo; Cohen, Milton; Farrell, Michael; Hall, Wayne D
There is increasing debate about cannabis use for medical purposes, including for symptomatic treatment of chronic pain. We investigated patterns and correlates of cannabis use in a large community sample of people who had been prescribed opioids for chronic non-cancer pain. The POINT study included 1514 people in Australia who had been prescribed pharmaceutical opioids for chronic non-cancer pain. Data on cannabis use, ICD-10 cannabis use disorder and cannabis use for pain were collected. We explored associations between demographic, pain and other patient characteristics and cannabis use for pain. One in six (16%) had used cannabis for pain relief, 6% in the previous month. A quarter reported that they would use it for pain relief if they had access. Those using cannabis for pain on average were younger, reported greater pain severity, greater interference from and poorer coping with pain, and more days out of role in the past year. They had been prescribed opioids for longer, were on higher opioid doses, and were more likely to be non-adherent with their opioid use. Those using cannabis for pain had higher pain interference after controlling for reported pain severity. Almost half (43%) of the sample had ever used cannabis for recreational purposes, and 12% of the entire cohort met criteria for an ICD-10 cannabis use disorder. Cannabis use for pain relief purposes appears common among people living with chronic non-cancer pain, and users report greater pain relief in combination with opioids than when opioids are used alone. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Lin, Tso-Chou; Ger, Luo-Ping; Pergolizzi, Joseph V; Raffa, Robert B; Wang, Ju-O; Ho, Shung-Tai
Prescribing opioids for chronic noncancer pain has been strictly regulated for two decades in Taiwan. The aim of this study was to survey the patients' perspectives and potential drawbacks following long-term use of opioids. An observational cross-sectional survey using the Taiwanese version of Brief Pain Inventory was conducted among outpatients with chronic noncancer pain registered by the Taiwan Food and Drug Administration. Patients were also asked about their sexual behavior, depression, opioid misuse behaviors, and use of complementary and alternative medicine. For 210 of 328 outpatients (64.0%), the median pain duration was 96 months and opioid treatment duration was 57 months. The median morphine equivalent dose was 150 mg/d, with 30.5% of patients exceeding the daily watchful dose, defined as 200 mg of morphine equivalent dose. Pain reduction after taking opioids was ∼50% in the past week. The top three diagnoses were chronic pancreatitis, spinal cord injury, and neuralgia. The leading side effects were constipation (46.7%), and decreased sexual desire (69.5%) and satisfaction (57.9%). Depression was currently diagnosed in 55.2% of patients. Twenty patients (9.5%) displayed at least one aberrant behavior in the past month. Only 76 (36.2%) patients had ever received nerve block procedures, and 118 (56.2%) tried complementary and alternative medicine. This nationwide survey described the concurrent pain intensity, daily function, and various adverse effects by long-term opioids among 210 monitored outpatients with chronic noncancer pain in Taiwan. More efforts are suggested to reduce opioid prescriptions in the 30% of patients exceeding daily watchful dose. Copyright © 2016. Published by Elsevier B.V.
Opioids and the management of chronic severe pain in the elderly: consensus statement of an International Expert Panel with focus on the six clinically most often used World Health Organization Step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone).
Pergolizzi, Joseph; Böger, Rainer H; Budd, Keith; Dahan, Albert; Erdine, Serdar; Hans, Guy; Kress, Hans-Georg; Langford, Richard; Likar, Rudolf; Raffa, Robert B; Sacerdote, Paola
SUMMARY OF CONSENSUS: 1. The use of opioids in cancer pain: The criteria for selecting analgesics for pain treatment in the elderly include, but are not limited to, overall efficacy, overall side-effect profile, onset of action, drug interactions, abuse potential, and practical issues, such as cost and availability of the drug, as well as the severity and type of pain (nociceptive, acute/chronic, etc.). At any given time, the order of choice in the decision-making process can change. This consensus is based on evidence-based literature (extended data are not included and chronic, extended-release opioids are not covered). There are various driving factors relating to prescribing medication, including availability of the compound and cost, which may, at times, be the main driving factor. The transdermal formulation of buprenorphine is available in most European countries, particularly those with high opioid usage, with the exception of France; however, the availability of the sublingual formulation of buprenorphine in Europe is limited, as it is marketed in only a few countries, including Germany and Belgium. The opioid patch is experimental at present in U.S.A. and the sublingual formulation has dispensing restrictions, therefore, its use is limited. It is evident that the population pyramid is upturned. Globally, there is going to be an older population that needs to be cared for in the future. This older population has expectations in life, in that a retiree is no longer an individual who decreases their lifestyle activities. The "baby-boomers" in their 60s and 70s are "baby zoomers"; they want to have a functional active lifestyle. They are willing to make trade-offs regarding treatment choices and understand that they may experience pain, providing that can have increased quality of life and functionality. Therefore, comorbidities--including cancer and noncancer pain, osteoarthritis, rheumatoid arthritis, and postherpetic neuralgia--and patient functional
Jagannath, Soumya; Garg, Pramod Kumar
Chronic pancreatitis (CP) is a progressive inflammatory disease of the pancreas. The currently available treatment of CP is aimed at controlling symptoms and managing complications. Unfortunately, no specific treatment is available to halt the progression of the disease process because the pathophysiological perturbations in CP are not well understood. In this review, we discuss various therapeutic targets and investigational agents acting on these targets. Among these, therapies modulating immune cells and those acting on pancreatic stellate cells appear promising and may translate into clinical benefit in near future. However, these experimental therapies are mostly in animal models and they do not recapitulate all aspects of human disease. Still they may be beneficial in developing effective therapeutic modalities to curb inflammation in chronic pancreatitis.
Full Text Available Drug addiction requires associative learning processes that critically involve hippocampal circuits, including the opioid system. We recently found that acute and chronic stress, important regulators of addictive processes, affect hippocampal opioid levels and mu opioid receptor trafficking in a sexually dimorphic manner. Here, we examined whether acute and chronic stress similarly alters the levels and trafficking of hippocampal delta opioid receptors (DORs. Immediately after acute immobilization stress (AIS or one-day after chronic immobilization stress (CIS, the brains of adult female and male rats were perfusion-fixed with aldehydes. The CA3b region and the dentate hilus of the dorsal hippocampus were quantitatively analyzed by light microscopy using DOR immunoperoxidase or dual label electron microscopy for DOR using silver intensified immunogold particles (SIG and GABA using immunoperoxidase. At baseline, females compared to males had more DORs near the plasmalemma of pyramidal cell dendrites and about 3 times more DOR-labeled CA3 dendritic spines contacted by mossy fibers. In AIS females, near-plasmalemmal DOR-SIGs decreased in GABAergic hilar dendrites. However, in AIS males, near-plasmalemmal DOR-SIGs increased in CA3 pyramidal cell and hilar GABAergic dendrites and the percentage of CA3 dendritic spines contacted by mossy fibers increased to about half that seen in unstressed females. Conversely, after CIS, near-plasmalemmal DOR-SIGs increased in hilar GABA-labeled dendrites of females whereas in males plasmalemmal DOR-SIGs decreased in CA3 pyramidal cell dendrites and near-plasmalemmal DOR-SIGs decreased hilar GABA-labeled dendrites. As CIS in females, but not males, redistributed DOR-SIGs near the plasmalemmal of hilar GABAergic dendrites, a subsequent experiment examined the acute affect of oxycodone on the redistribution of DOR-SIGs in a separate cohort of CIS females. Plasmalemmal DOR-SIGs were significantly elevated on hilar
Griffin, Aaron S; Cabot, Peter; Wallwork, Ben; Panizza, Ben
The use of alternative medicine in chronic rhinosinusitis (CRS) continues to increase in popularity, for the most part without meeting the burden of being based on sound clinical evidence. New and emerging treatments, both natural and developed, are numerous, and it remains a challenge for otolaryngologists as well as general practitioners to keep up to date with these therapies and their efficacy. In this systematic review, we discuss a number of alternative therapies for CRS, their proposed physiologic mechanisms, and evidence supporting their use. This analysis is based on our review of the English-language literature on alternative therapies for CRS (we did not include any therapies that are already recommended by accepted professional bodies). Data collection was performed using the PubMed database (not restricted to MEDLINE due to the nature of the subject matter), the Cochrane databases, and bibliography searches. We found that while many of the alternative therapies we reviewed might have a firm basis in science, they lack any clinical evidence to support their use specifically for CRS. Some emerging therapies, such as therapeutic ultrasonography and phonophoresis, show some promise, based on a growing body of positive evidence. In addition, the use of baby shampoo, thyme honey, and bromelain additives to saline lavage in CRS are all supported by clinical evidence, as is Sinupret, an oral preparation that contains echinacea. However, higher levels of evidence gleaned from large, well-designed, prospective, randomized, controlled trials are needed before any of these therapies can be recommended.
Khryanin, A A; Reshetnikov, O V
The article discusses the possible etiological factors in the development of chronic bacterial prostatitis. The authors presented a comparative long-term analysis of morbidity from non-viral sexually transmitted infections (STIs) in Russia. Against the background of general decline in STIs incidence, a significant percentage of them is made up by urogenital trichomoniasis. The findings substantiated the advantages of combination therapy (ornidazole and ofloxacin) for bacterial urinary tract infections.
Kowalczyk, Lukasz M; Draganov, Peter V
Chronic pancreatitis (CP) can cause failure of both the exocrine and endocrine portions of the gland. Pain is the most recalcitrant clinical complaint in CP. Generally, conservative measures are first attempted to manage pain. These include cessation of alcohol use and smoking, enzyme replacement therapy, and finally, opioid analgesia. Endoscopy can be employed to treat the pain and complications due to CP. The results of the only two prospective randomized controlled trials suggest that surgery has a more durable effect than endoscopic therapy in controlling pain. Both trials suffer from severe limitations, however, and endoscopy remains the preferred approach for many patients because of its minimally invasive nature. Endoscopic ultrasound celiac plexus block has limited value in helping to control pain. More randomized trials are needed, along with further technologic innovation to improve the current treatment modalities. When considering interventional therapy for a patient with CP, a tailored and multidisciplinary therapeutic approach should be taken.
Kul'chavenya, E V; Shevchenko, S Yu; Brizhatyuk, E V
Chronic prostatitis is a prevalent urologic disease, but treatment outcomes are not always satisfactory. As a rule, chronic prostatitis results in chronic pelvic pain syndrome, significantly reducing the patient's quality of life. Open pilot prospective non-comparative study was conducted to test the effectiveness of extracorporeal shock wave therapy (ESWT) using Aries (Dornier) machine in patients with chronic prostatitis (CP) of IIIb category. A total of 27 patients underwent ESWL as monotherapy, 2 times a week for a course of 6 sessions. Exposure settings: 5-6 energy level (by sensation), the frequency of 5 Hz, 2000 pulses per session; each patient received a total energy up to 12000 mJ. per procedure. Treatment results were evaluated using NIH-CPSI (National Institute of Health Chronic Prostatitis Symptom Index) upon completing the 3 week course of 6 treatments and at 1 month after ESWT. Immediately after the ESWT course positive trend was not significant: pain index decreased from 9.1 to 7.9, urinary symptom score remained almost unchanged (4.2 at baseline, 4.1 after treatment), quality of life index also showed a slight improvement, dropping from 7.2 points to 6.0. Total NIH-CPSI score decreased from 20.5 to 18.0. One month post-treatment pain significantly decreased to 3.2 points, the urinary symptom score fell to 2.7 points, the average quality of life score was 3.9 points. ESWT, performed on Aries (Dornier) machine, is highly effective as monotherapy in patients with category IIIb chronic prostatitis.
A. A. Shmonin
Full Text Available Chronic cerebrovascular attack (CCVA is a brain lesion caused by vascular factors. CCVA appears as cognitive impairments (CIs, affective (emotional disorders and focal syndromes. Treatment for CCVA requires a comprehensive approach. Effective combination therapy for CCVA involves secondary prevention of stroke and CIs; treatment of CIs; treatment of depression and other affective disorders; and neuroprotective therapy. Basic therapy for CCVA includes modification of risk factors, antihypertensive, hypolipidemic, and antithrombotic therapies. Central acetylcholinesterase inhibitors (galantamine, rivastigmine, donepezil and a reversible NMDA receptor blocker (memantine are symptomatically used at a stage of vascular and mixed dementia. There are no unique guidelines for the therapy of mild and moderate vascular nondementia-related CIs. Drug use, based on the neurochemical mechanisms underlying the development of vascular CIs, is substantiated. When choosing psychotropic agents, it is necessary to take into account the causes and clinical manifestations of neuromediator deficiency. Antidepressants are used as essential drugs. Neuroleptics and tranquilizers are additionally administered in complex-pattern syndromes, such as depression with marked anxiety. Prescription of neuroprotectors may be effective in treating both stroke and CCVA. These medicaments are most effective when a damaging factor acts, i.e. neuroprotectors should be given in a risk situation and to reduce damage. Citicoline is one of the most test drugs in a group of neuroprotectors.
Webster, Lynn R
Opioid analgesics are recognized as a legitimate medical therapy for selected patients with severe chronic pain that does not respond to other therapies. However, opioids are associated with risks for patients and society that include misuse, abuse, diversion, addiction, and overdose deaths. Therapeutic success depends on proper candidate selection, assessment before administering opioid therapy, and close monitoring throughout the course of treatment. Risk assessment and prevention include knowledge of patient factors that may contribute to misuse, abuse, addiction, suicide, and respiratory depression. Risk factors for opioid misuse or addiction include past or current substance abuse, untreated psychiatric disorders, younger age, and social or family environments that encourage misuse. Opioid mortality prevalence is higher in people who are middle aged and have substance abuse and psychiatric comorbidities. Suicides are probably undercounted or frequently misclassified in reports of opioid-related poisoning deaths. Greater understanding and better assessment are needed of the risk associated with suicide risk in patients with pain. Clinical tools and an evolving evidence base are available to assist clinicians with identifying patients whose risk factors put them at risk for adverse outcomes with opioids.
Diego J. Maselli
Full Text Available The management of patients with chronic respiratory diseases affected by difficult to treat infections has become a challenge in clinical practice. Conditions such as cystic fibrosis (CF and non-CF bronchiectasis require extensive treatment strategies to deal with multidrug resistant pathogens that include Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus aureus, Burkholderia species and non-tuberculous Mycobacteria (NTM. These challenges prompted scientists to deliver antimicrobial agents through the pulmonary system by using inhaled, aerosolized or nebulized antibiotics. Subsequent research advances focused on the development of antibiotic agents able to achieve high tissue concentrations capable of reducing the bacterial load of difficult-to-treat organisms in hosts with chronic respiratory conditions. In this review, we focus on the evidence regarding the use of antibiotic therapies administered through the respiratory system via inhalation, nebulization or aerosolization, specifically in patients with chronic respiratory diseases that include CF, non-CF bronchiectasis and NTM. However, further research is required to address the potential benefits, mechanisms of action and applications of inhaled antibiotics for the management of difficult-to-treat infections in patients with chronic respiratory diseases.
Hunold, Katherine M; Smith, Samantha A; Platts-Mills, Timothy F
Constipation is a common and potentially serious side effect of oral opioids. Accordingly, most clinical guidelines suggest routine use of laxatives to prevent opioid-induced constipation. The objective was to characterize emergency provider prescribing of laxatives to prevent constipation among adults initiating outpatient opioid treatment. National Hospital Ambulatory Medical Care Survey (NHAMCS) data from 2010 were analyzed. Among visits by individuals aged 18 years and older discharged from the emergency department (ED) with opioid prescriptions, the authors estimated the survey-weighted proportion of visits in which laxatives were also prescribed. A subgroup analysis was conducted for individuals aged 65 years and older, as the potential risks associated with opioid-induced constipation are greater among older individuals. To examine a group expected to be prescribed laxative medication and confirm that NHAMCS captures prescriptions for these medications, the authors estimated the proportion of visits by individuals discharged with prescriptions for laxatives among those who presented with constipation. Among visits in 2010 by adults aged 18 years and older discharged from the ED with opioid prescriptions, 0.9% (95% confidence interval [CI] = 0.7% to 1.3%, estimated total n = 191,203 out of 21,075,050) received prescriptions for laxatives. Among the subset of visits by adults aged 65 years and older, 1.0% (95% CI = 0.5% to 2.0%, estimated total n = 18,681 out of 1,904,411) received prescriptions for laxatives. In comparison, among visits by individuals aged 18 years and older with constipation as a reason for visit, 42% received prescriptions for laxatives. In this nationally representative sample, laxatives were not routinely prescribed to adults discharged from the ED with prescriptions for opioid pain medications. Routine prescribing of laxatives for ED visits may improve the safety and effectiveness of outpatient opioid pain management. © 2015 by the
Filges, Trine; Andersen, Ditte; Jørgensen, Anne-Marie Klint
The main aim of this review is to evaluate the current evidence on the effects of FFT on drug abuse reduction for young people in treatment for non-opioid drug use.......The main aim of this review is to evaluate the current evidence on the effects of FFT on drug abuse reduction for young people in treatment for non-opioid drug use....
Feldmann, C; Ertl, G; Angermann, C E
The rising prevalence and increasing disease-related costs render chronic heart failure a rapidly growing socioeconomic challenge. The concerted action of guideline-adjusted therapy and holistic patient care is essential to achieve improvements in mortality, morbidity, functional status and quality of life of patients with symptomatic heart failure. Holistic care strategies comprise consideration of comorbidities and individual needs, lifestyle recommendations and multidisciplinary management programs for high-risk symptomatic patients in addition to basic medication and surgical therapies. For optimal patient care and coaching, seamless interaction is required between in-hospital treatment and outpatient facilities. Moreover, the palliative needs of heart failure patients need to be considered, a topic that is currently not receiving enough attention.
M. P. Martínez-Montiel
Full Text Available Crohn's disease (CD and ulcerative colitis (UC make up the so-called chronic inflammatory bowel disease (IBD. Advances in the understanding of IBD pathophysiologic mechanisms in the last few years have allowed the development of novel therapies such as biologic therapies, which at least theoretically represent a more specific management of this disease with fewer side effects. Currently, the only effective and widely accepted biologic therapy for the treatment of intraluminal, fistulizing CD, both for remission induction and maintenance, is infliximab. The role of other monoclonal antibodies such as adalimumab is not clearly established. It could be deemed an alternative for patients with allergic reactions to infliximab, and for those with lost response because of anti-infliximab antibody development. However, relevant issues such as dosage and administration regimen remain to be established. Anti-integrin α4 therapies, despite encouraging results in phase-3 studies, are still unavailable, as their marketing authorization was held back in view of a number of reports regarding progressive multifocal leukoencephalopathy cases. Immunostimulating therapy may be highly relevant in the near future, as it represents a novel strategy against disease with the inclusion of granulocyte-monocyte colony-stimulating factors. Regarding ulcerative colitis, results from the ACT-1 and ACT-2 studies showed that infliximab is also useful for the management of serious UC flare-ups not responding to standard treatment, which will lead to a revision of therapeutic algorithms, where this drug should be given preference before intravenous cyclosporine. In the next few years, the role of anti-CD3 drugs (vilisilizumab, T-cell inhibiting therapies, and epithelial repair and healing stimulating factors will be established.
Full Text Available Introduction: People with chronic opioid use disorder often present to treatment with individual and structural vulnerabilities and remain at risk of reporting adverse health outcomes. This risk is greatly compounded by tobacco smoking, which is highly prevalent among people with chronic opioid use disorder. Despite the known burden of tobacco smoking on health, the relationship between nicotine dependence and health has not been studied among those receiving injectable opioid agonist treatment. As such, the present study aims to explore the association between nicotine dependence and physical health among participants of the Study to Assess Longer-Term Opioid Medication Effectiveness (SALOME at baseline and six-months. Methods: SALOME was a double-blind phase III clinical trial testing the non-inferiority of injectable hydromorphone to injectable diacetylmorphine for chronic opioid use disorder. Participants reporting tobacco smoking were included in a linear regression analysis of physical health at baseline (before receiving treatment and at six-months. Results: At baseline, nicotine dependence score, lifetime history of emotional, physical, or sexual abuse and prior month safe injection site access were independently and significantly associated with physical health. At six-months nicotine dependence score was the only variable that maintained this significant and independent association with physical health. Conclusions: Findings indicate that after six-months, the injectable treatment effectively brought equity to patients' physical health status, yet the association with nicotine dependence remained. Findings could inform whether the provision of treatment for nicotine dependence should be made a priority in settings where injectable opioid agonist treatment is delivered to achieve improvements in overall physical health in this population.
Kato, Kengo; Matsuura, Kazuto; Zenda, Sadamoto
Appropriate supportive care is essential for intensive chemoradiation therapy (CRT), and pain management is an important supportive care for CRT for head and neck cancer. We developed an opioid-based pain control program for head and neck cancer patients undergoing CRT, and assessed its efficacy and safety. 110 head and neck cancer patients undergoing platinum-based concomitant CRT were enrolled from 10 cancer centers or university hospitals. Their pain caused by CRT was managed with a four-step opioid-based pain control program, and adverse events and usage of opioid were analyzed. 101 suitable cases of 110 patients were analyzed. 53% of cases suffered grade 3-4 mucositis. The rate of completion of radiotherapy was 99% and the rate of unplanned breaks in radiotherapy was 13%. The usage rate of opioid was 83% and the rate of compliance with the pain control program was 92%. The median maximum quantity of morphine used per day was 35 mg. No patient had to stop the opioid program or radiotherapy due to adverse effects of opioids. An opioid-based pain control program for head and neck cancer patients undergoing CRT achieves a high completion rate of radiation. (author)
Besson, J; Beck, T; Wiesbeck, G; Hämmig, R; Kuntz, A; Abid, S; Stohler, R
Switzerland's drug policy model has always been unique and progressive, but there is a need to reassess this system in a rapidly changing world. The IMPROVE study was conducted to gain understanding of the attitudes and beliefs towards opioid maintenance therapy (OMT) in Switzerland with regards to quality and access to treatment. To obtain a "real-world" view on OMT, the study approached its goals from two different angles: from the perspectives of the OMT patients and of the physicians who treat patients with maintenance therapy. The IMPROVE study collected a large body of data on OMT in Switzerland. This paper presents a small subset of the dataset, focusing on the research design and methodology, the profile of the participants and the responses to several key questions addressed by the questionnaires. IMPROVE was an observational, questionnaire-based cross-sectional study on OMT conducted in Switzerland. Respondents consisted of OMT patients and treating physicians from various regions of the country. Data were collected using questionnaires in German and French. Physicians were interviewed by phone with a computer-based questionnaire. Patients self-completed a paper-based questionnaire at the physicians' offices or OMT treatment centres. A total of 200 physicians and 207 patients participated in the study. Liquid methadone and methadone tablets or capsules were the medications most commonly prescribed by physicians (60% and 20% of patient load, respectively) whereas buprenorphine use was less frequent. Patients (88%) and physicians (83%) were generally satisfied with the OMT currently offered. The current political framework and lack of training or information were cited as determining factors that deter physicians from engaging in OMT. About 31% of OMT physicians interviewed were ≥60 years old, indicating an ageing population. Diversion and misuse were considered a significant problem in Switzerland by 45% of the physicians. The subset of IMPROVE data
... easily result in intoxication. The provider prescribes a sleep medicine (sedative) in addition to the opioid. The provider ... an opioid with certain other drugs, such as sleep medicines or alcohol Taking the opioid in ways not ...
Pivec, Robert; Minshall, Michael E; Mistry, Jaydev B; Chughtai, Morad; Elmallah, Randa K; Mont, Michael A
Chronic low back pain (CLBP) may be treated without opioids through the use of transcutaneous electrical nerve stimulation (TENS). However, no study has evaluated its clinical effect and economic impact as measured by opioid utilization and costs. The purpose of this study was to evaluate patients who were given TENS for CLBP compared to a matched group without TENS at one-year follow-up, to determine differences between opioid consumption. Opioid utilization and costs in patients who did and did not receive TENS were extracted from a Medicare supplemental administrative claims database. Patients were selected if they had at least two ICD-9-CM coded claims for low back pain in a three-month period and were then propensity score matched at a 1:1 ratio between patients who received TENS and those who did not. There were 22,913 patients in each group who had a minimum follow-up of one year. There were no significant demographic or comorbidity differences with the exception that TENS patients had more episodes of back pain. Significantly fewer patients in the TENS group required opioids at final follow-up (57.7 vs. 60.3%). TENS patients also had significantly fewer annual per-patient opioid costs compared to non-TENS patients ($169 vs. $192). There were significantly lower event rates in TENS patients compared to non-TENS patients when measured by opioid utilization (characterized by frequency of prescription refills) (3.82 vs. 4.08, respectively) or pharmacy utilization (31.67 vs. 32.25). The TENS group also demonstrated a significantly lower cost of these utilization events ($44 vs. $49) and avoided more opioid events (20.4 events fewer per 100 patients annually). Treatment of CLBP with TENS demonstrated significantly fewer patients requiring opioids, fewer events where a patient required an opioid prescription, and lower per-patient costs. Since TENS is both non-invasive and a non-narcotic, it may potentially allow physicians to be more aggressive in treating CLBP
Full Text Available In this review, we discuss advances in acute pain management, including the recent report of the joint American Pain Society and American Academy of Pain Medicine task force on the classification of acute pain, the role of psychosocial factors, multimodal pain management, new non-opioid therapy, and the effect of the “opioid epidemic”. In this regard, we propose that a fundamental principle in acute pain management is identifying patients who are most at risk and providing an “opioid free anesthesia and postoperative analgesia”. This can be achieved by using a multimodal approach that includes regional anesthesia and minimizing the dose and the duration of opioid prescription. This allows prescribing medications that work through different mechanisms. We shall also look at the recent pharmacologic and treatment advances made in acute pain and regional anesthesia.
O uso de opióides no tratamento da dor crônica não oncológica: o papel da metadona El uso de opioides en el tratamiento del dolor crónico no oncológica: el papel de la metadona Opioids for treating non malignant chronic pain: the role of methadone
potential, mainly those refractory to conventional therapy. Morphine is the standard opioid, but other alternatives may be used such as oxycodone, hydromorphone or fentanyl. Methadone is a synthetic opioid, initially used to prevent withdrawal syndrome in addicted patients, which may be an important alternative for treating non-malignant chronic pain, especially neuropathic pain. CONCLUSIONS: Although the growing knowledge on the use of opioids for treating non-malignant chronic pain, new better controlled studies are still needed to allow a more scientific discussion about this subject. Oral methadone is cost-effective and an effective alternative for a better pain control in certain patients.
Chiauzzi, Emil; Trudeau, Kimberlee J.; Zacharoff, Kevin; Bond, Kathleen
Introduction: Primary care physicians (PCPs) treat a high proportion of chronic pain patients but often lack training about how to assess and address issues associated with prescribing opioids when they are an appropriate component of therapy. The result may be that they may avoid treating these patients, which can lead to an undertreatment of…
Kenworthy, James; Yi, Yunni; Wright, Antony; Brown, Jim; Maria Madrigal, Ana; Dunlop, William C N
This study investigated the cost-effectiveness of buprenorphine maintenance treatment (BMT) and methadone maintenance treatment (MMT) vs no opioid substitution therapy (OST) for the treatment of opioid use disorder, from the UK National Health Service (NHS)/personal social services (PSS) and societal perspectives over 1 year. Cost-effectiveness of OST vs no OST was evaluated by first replicating and then expanding an existing UK health technology assessment model. The expanded model included the impact of OST on infection rates of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection. Versus no OST, incremental cost-effectiveness ratios (ICERs) for BMT and MMT were £13,923 and £14,206 per quality-adjusted life year (QALY), respectively, from a NHS/PSS perspective. When total costs (NHS/PSS and societal) are considered, there are substantial savings associated with adopting OST; these savings are in excess of £14,032 for BMT vs no OST and £17,174 for MMT vs no OST over 1 year. This is primarily driven by a reduction in victim costs. OST treatment also impacted other aspects of criminality and healthcare resource use. The model's 1-year timeframe means long-term costs and benefits, and the influence of changes over time are not captured. OST can be considered cost-effective vs no OST from the UK NHS/PSS perspective, with a cost per QALY well below the UK's willingness-to-pay threshold. There were only small differences between BMT and MMT. The availability of two or more cost-effective options is beneficial to retaining patients in OST programs. From a societal perspective, OST is estimated to save over £14,032 and £17,174 per year for BMT and MMT vs no OST, respectively, due to savings in victim costs. Further work is required to fully quantify the clinical and health economic impacts of different OST formulations and their societal impact over the long-term.
O'Neill, Aimee; Moss, Hilary
This paper describes a community art therapy group for people living with chronic pain. Nine adults were offered 12 weekly group art therapy sessions that included art therapy activities such as guided imagery focusing on body scans followed by art responses and artistic expressions of the pain experience. This pilot group art therapy program is…
Filges, Trine; Rasmussen, Pernille; Andersen, Ditte
The main objectives of this review are to evaluate the current evidence on the effects of MDFT on drug abuse reduction for young people (aged 11-21 years) in treatment for non-opioid drug abuse, and if possible to examine moderators of drug abuse reduction effects, specifically analysing whether...
van Middelkoop, Marienke; Rubinstein, Sidney M; Verhagen, Arianne P; Ostelo, Raymond W; Koes, Bart W; van Tulder, Maurits W
Exercise therapy is the most widely used type of conservative treatment for low back pain. Systematic reviews have shown that exercise therapy is effective for chronic but not for acute low back pain. During the past 5 years, many additional trials have been published on chronic low back pain. This
Huffman, Kelly L; Shella, Elizabeth R; Sweis, Giries; Griffith, Sandra D; Scheman, Judith; Covington, Edward C
Limited research examines the risk of therapeutic opioid addiction (TOA) in patients with chronic noncancer pain. This study examined TOA among 199 patients undergoing long-term opioid therapy at the time of admission to a pain rehabilitation program. It was hypothesized that nonopioid substance use disorders and opioid dosage would predict TOA. Daily mean opioid dose was 132.85 mg ± 175.39. Patients with nonopioid substance use disorders had 28 times the odds (odds ratio [OR] = 28.58; 95% confidence interval [CI] = 10.86, 75.27) of having TOA. Each 50-mg increase in opioid dose nearly doubled the odds of TOA (OR = 1.73; 95% CI = 1.29, 2.32). A 100-mg increase was associated with a 3-fold increase in odds (OR = 3.00; 95% CI = 1.67, 5.41). Receiver operating characteristic analysis revealed that opioid dose was a moderately accurate predictor (area under the curve = .75; 95% CI = .68, .82) of TOA. The sensitivity (.70) and specificity (.68) of opioid dose in predicting TOA was maximized at 76.10 mg; in addition, 46.00 mg yielded 80% sensitivity in identifying TOA. These results underscore the importance of obtaining a substance use history prior to prescribing and suggest a low screening threshold for TOA in patients who use opioids in the absence of improvement in pain or functional impairment. This article examines TOA in patients with chronic noncancer pain undergoing long-term opioid therapy. Results suggest that patients should be screened for nonopioid substance use disorders prior to prescribing. In the absence of improvement in pain or function, there is a low threshold (∼50 mg daily opioid dose) for addiction screening. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.
Full Text Available Antiviral therapy is the most important treatment for chronic hepatitis C. This paper reviews the progress in antiviral treatment over recent years, including the combination therapy with polyethylene glycol-Interferon (PEG-IFN and ribavirin (RBV, specific target therapy, and gene therapy. The paper believes that the anti-hepatitis C virus treatment needs more effective drug combination therapies, shorter courses, less side effect, higher drug resistance threshold, etc.
Burgess, Diana J; Phelan, Sean; Workman, Michael; Hagel, Emily; Nelson, David B; Fu, Steven S; Widome, Rachel; van Ryn, Michelle
To test the hypothesis that racial biases in opioid prescribing would be more likely under high levels of cognitive load, defined as the amount of mental activity imposed on working memory, which may come from environmental factors such as stressful conditions, chaotic workplace, staffing insufficiency, and competing demands, one's own psychological or physiological state, as well as from demands inherent in the task at hand. Two (patient race: White vs Black) by two (cognitive load: low vs high) between-subjects factorial design. Ninety-eight primary care physicians from the Veterans Affairs Healthcare System. Web-based experimental study. Physicians were randomly assigned to read vignettes about either a Black or White patient, under low vs high cognitive load, and to indicate their likelihood of prescribing opioids. High cognitive load was induced by having physicians perform a concurrent task under time pressure. There was a three-way interaction between patient race, cognitive load, and physician gender on prescribing decisions (P = 0.034). Hypotheses were partially confirmed. Male physicians were less likely to prescribe opioids for Black than White patients under high cognitive load (12.5% vs 30.0%) and were more likely to prescribe opioids for Black than White patients under low cognitive load (30.8% vs 10.5%). By contrast, female physicians were more likely to prescribe opioids for Black than White patients in both conditions, with greater racial differences under high (39.1% vs 15.8%) vs low cognitive load (28.6% vs 21.7%). Physician gender affected the way in which patient race and cognitive load influenced decisions to prescribe opioids for chronic pain. Future research is needed to further explore the potential effects of physician gender on racial biases in pain treatment, and the effects of physician cognitive load on pain treatment. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
Despite complex treatment schedules for cancer, the occurrence of resistances and relapses is a major concern in oncology. Hence, novel treatment options are needed. In this thesis, different approaches using radioimmunotherapy and the opioid D,L-methadone alone or in combination with doxorubicin were analyzed regarding their cytotoxic potential and the triggered signalling pathways in sensitive and resistant leukaemia and non-Hodgkin lymphoma (NHL). The radioimmunoconjugates [Bi-213]anti-CD33 and [Bi-213]anti-CD20 for treatment of acute myeloid leukaemia (AML) or NHL, respectively, were applied exemplary for the use of targeted alpha-therapies (TAT). Depending on the analyzed cell lines, the used activity concentrations and specific activities (MBq/μg antibody) apoptosis was induced abrogating radio- and chemo-cross-resistances specifically. The cell death was caspase-dependent activating the mitochondrial pathway and was executed by downregulation of the anti-apoptotic proteins XIAP and Bcl-xL. D,L-Methadone induces apoptosis in vitro and in vivo in opioid-receptor (OR) expressing cells depending on the OR density and the used concentrations. Resistances could be overcome and proliferation was inhibited. In combination with doxorubicin, a synergistic effect regarding cytotoxicity in ex vivo patient cells and cell lines was observed. This effect depends on the increase of doxorubicin uptake co-administering D,L-methadone whereas doxorubicin enhances OR expression. The activation of OR leads to the downregulation of cAMP playing a pivotal role in apoptosis induction. In vivo, the therapeutic potential of D,L-methadone alone or in combination with doxorubicin could be proven as mice transplanted with human T-ALL-cells could be identified as tumour free. In summary, these studies show that TAT using [Bi-213]anti-CD33 and [Bi-213]anti-CD20 as well as the opioid D,L-methadone harbour the potential to optimize conventional treatment modalities for leukaemia and NHL.
Thomas, Donna-Ann; Maslin, Benjamin; Legler, Aron; Springer, Erin; Asgerally, Abbas; Vadivelu, Nalini
There is increasing interest in the use of complimentary and alternative medicine (CAM) for the treatment of chronic pain. This review examines alternative and complimentary therapies, which can be incorporated as part of a biopsychosocial approach in the treatment of chronic pain syndromes. In the present investigation, literature from articles indexed on PubMed was evaluated including topics of alternative therapies, complimentary therapies, pain psychology, biofeedback therapy, physical exercise therapies, acupuncture, natural and herbal supplements, whole-body cryotherapy, and smartphone technologies in the treatment of chronic pain syndromes. This review highlights the key role of psychology in the treatment of chronic pain. Cognitive behavior therapy appears to be the most impactful while biofeedback therapy has also been shown to be effective for chronic pain. Exercise therapy has been shown to be effective in short-, intermediate-, and long-term pain states. When compared to that in sham controls, acupuncture has shown some benefit for neck pain immediately after the procedure and in the short term and improvement has also been demonstrated in the treatment of headaches. The role of smartphones and whole-body cryotherapy are new modalities and further studies are needed. Recent literature suggests that several alternate therapies could play a role in the treatment of chronic pain, supporting the biopsychosocial model in the treatment of pain states.
Wells, Audrey M; Ridener, Elysia; Bourbonais, Clinton A; Kim, Woori; Pantazopoulos, Harry; Carroll, F Ivy; Kim, Kwang-Soo; Cohen, Bruce M; Carlezon, William A
Stress plays a critical role in the neurobiology of mood and anxiety disorders. Sleep and circadian rhythms are affected in many of these conditions. Here we examined the effects of chronic social defeat stress (CSDS), an ethological form of stress, on sleep and circadian rhythms. We exposed male mice implanted with wireless telemetry transmitters to a 10 day CSDS regimen known to produce anhedonia (a depressive-like effect) and social avoidance (an anxiety-like effect). EEG, EMG, body temperature, and locomotor activity data were collected continuously during the CSDS regimen and a 5 day recovery period. CSDS affected numerous endpoints, including paradoxical sleep (PS) and slow-wave sleep (SWS), as well as the circadian rhythmicity of body temperature and locomotor activity. The magnitude of the effects increased with repeated stress, and some changes (PS bouts, SWS time, body temperature, locomotor activity) persisted after the CSDS regimen had ended. CSDS also altered mRNA levels of the circadian rhythm-related gene mPer2 within brain areas that regulate motivation and emotion. Administration of the κ-opioid receptor (KOR) antagonist JDTic (30 mg/kg, i.p.) before CSDS reduced stress effects on both sleep and circadian rhythms, or hastened their recovery, and attenuated changes in mPer2 Our findings show that CSDS produces persistent disruptions in sleep and circadian rhythmicity, mimicking attributes of stress-related conditions as they appear in humans. The ability of KOR antagonists to mitigate these disruptions is consistent with previously reported antistress effects. Studying homologous endpoints across species may facilitate the development of improved treatments for psychiatric illness. SIGNIFICANCE STATEMENT Stress plays a critical role in the neurobiology of mood and anxiety disorders. We show that chronic social defeat stress in mice produces progressive alterations in sleep and circadian rhythms that resemble features of depression as it appears in
Bachireddy, Chethan; Bazazi, Alexander R; Kavasery, Ravi; Govindasamy, Sumathi; Kamarulzaman, Adeeba; Altice, Frederick L
Pre-incarceration HIV transmission behaviors and current attitudes toward opioid substitution therapy (OST) among HIV-infected male prisoners in Malaysia have important implications for secondary HIV prevention efforts. In June 2007, 102 HIV-infected male prisoners within 6 months of community-release were anonymously surveyed in Kota Bharu, Malaysia. Nearly all subjects (95%) met criteria for opioid dependence. Overall, 66% of participants reported sharing needles, and 37% reported unprotected sex in the 30 days prior to incarceration. During this period, 77% reported injection drug use, with 71% injecting daily and 65% injecting more than one substance. Injection of buprenorphine (28%), benzodiazepines (28%) and methamphetamines (49%) was reported. Nearly all (97%) of those reporting unprotected sex did so with someone not known to be HIV-infected. While 51% believed that opioid substitution therapy (OST) would be helpful, only 33% believed they needed it to prevent relapse after prison release. Most participants (70%) expressed interest in learning more about OST. Those reporting the highest injection risks were more likely to believe OST would be helpful (pMalaysia is crucial to reduce community HIV transmission after release. Effectively reducing HIV risk associated with opioid injection will require OST expansion, including social marketing to improve its acceptability and careful monitoring. Access to sterile injection equipment, particularly for non-opioid injectors, and behavioral interventions that reduce sexual risk will also be required. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Zekry, Olfat; Gibson, Stephen B; Aggarwal, Arun
This study was designed to describe the efficacy and toxicity of subcutaneous ketamine infusions and sublingual ketamine lozenges for the treatment of chronic nonmalignant pain. Data were collected prospectively on 70 subjects managed in an academic, tertiary care hospital between 2007 and 2012 who received between 3 and 7 days of subanesthetic, subcutaneous ketamine infusion. Data were analyzed for efficacy, adverse effects, and reduction in use of opioid medication. We also analyzed whether subsequent treatment with sublingual ketamine lozenges resulted in longer-term efficacy of the beneficial effects of the initial ketamine infusion. There was a significant reduction in pain intensity measured by numerical rating scale (NRS) from mean of 6.38 before ketamine to 4.60 after ketamine (P ketamine infusion from a mean morphine equivalent dose (MMED) of 216 mg/day before ketamine to 89 mg/day after ketamine (P ketamine infusion was 59%. No subjects increased their use of opioids during their hospitalization for the ketamine infusion. A small proportion of subjects who responded to the infusion were continued on ketamine lozenges. This group was followed for between 3 months and 2 years. The use of ketamine lozenges after the infusion resulted in 31% of these subjects being able to cease their use of opioids compared with only 6% who did not receive ketamine lozenges. Eleven percent of subjects who received lozenges subsequently increased their opioid usage. Adverse effects were fairly common, but only mild, with 46% of patients experiencing light-headedness and dizziness, 25% tiredness and sedation, 12% headaches, 12% hallucinations, and 8% vivid dreams. Adverse effects were easily managed by reducing the rate of the ketamine infusion. The administration of subanesthetic, subcutaneous ketamine infusion was well tolerated, with mostly mild adverse effects and no serious adverse effects. The infusion provided significant pain relief in subjects who had failed a wide
Rutledge, Thomas; Atkinson, J Hampton; Holloway, Rachael; Chircop-Rollick, Tatiana; D'Andrea, John; Garfin, Steven R; Patel, Shetal; Penzien, Donald B; Wallace, Mark; Weickgenant, Anne L; Slater, Mark
This study evaluated a nurse-delivered, telehealth intervention of cognitive behavioral therapy versus supportive psychotherapy for chronic back pain. Participants (N=61) had chronic back pain (pain "daily" ≥ 6 months at an intensity ≥4/10 scale) and were randomized to an 8-week, 12-session, Cognitive Behavioral Therapy (CBT) or to Supportive Care (SC) matched for frequency, format, and time, with each treatment delivered by a primary care nurse. The primary outcome was the Roland Morris Disability Questionnaire (RMDQ). Secondary outcomes included the Numerical Rating Scale (NRS) and the Patient Global Impressions Scale (CGI). CBT participants (n=30) showed significant improvements on the RMDQ (means=11.4[5.9] vs. 9.4[6.1] at baseline and post-treatment, respectively, p.10). The results suggest that telehealth, nurse-delivered CBT and SC treatments for chronic back pain can offer significant and relatively comparable benefits. ClinicalTrials.gov: NCT00608530. This article describes the benefits of training primary care nurses to deliver evidence-based behavioral therapies for low back pain. Due to the high prevalence of chronic pain and the growing emphasis on non-opioid therapies, training nurses to provide behavior therapies could be a cost-effective way to improve pain management. Copyright © 2018. Published by Elsevier Inc.
Hirchak, Katherine A; Murphy, Sean M
Opioid misuse is a large public health problem in the United States. Residents of rural areas and American Indian (AI) reservation/trust lands represent traditionally underserved populations with regard to substance-use disorder therapy. Assess differences in the number of opioid agonist therapy (OAT) facilities and physicians with Drug Addiction Treatment Act (DATA) waivers for rural versus urban, and AI reservation/trust land versus non-AI reservation/trust land areas in Washington State. The unit of analysis was the ZIP code. The dependent variables were the number of OAT facilities and DATA-waivered physicians in a region per 10,000 residents aged 18-64 in a ZIP code. A region was defined as a ZIP code and its contiguous ZIP codes. The independent variables were binary measures of whether a ZIP code was classified as rural versus urban, or AI reservation/trust land versus non-AI reservation/trust land. Zero-inflated negative binomial regressions with robust standard errors were estimated. The number of OAT clinics in a region per 10,000 ZIP-code residents was significantly lower in rural versus urban areas (P = .002). This did not differ significantly between AI reservation/trust land and non-AI reservation/trust land areas (P = .79). DATA-waivered physicians in a region per 10,000 ZIP-code residents was not significantly different between rural and urban (P = .08), or AI reservation/trust land versus non-AI reservation/trust land areas (P = .21). It appears that the potential for Washington State residents of rural and AI reservation areas to receive OAT is similar to that of residents outside of those areas; however, difficulties in accessing therapy may remain, highlighting the importance of expanding health care insurance and providing support for DATA-waivered physicians. © 2016 National Rural Health Association.
Bachhuber, Marcus A; Mehta, Pooja K; Faherty, Laura J; Saloner, Brendan
Opioid agonist therapy (OAT) is the standard of care for pregnant women with opioid use disorder (OUD). Medicaid coverage policies may strongly influence OAT use in this group. To examine the association between Medicaid coverage of methadone maintenance and planned use of OAT in the publicly funded treatment system. Retrospective cross-sectional analysis of treatment admissions in 30 states extracted from the Treatment Episode Data Set (2013 and 2014). Medicaid-insured pregnant women with OUD (n=3354 treatment admissions). The main outcome measure was planned use of OAT on admission. The main exposure was state Medicaid coverage of methadone maintenance. Using multivariable logistic regression models adjusting for sociodemographic, substance use, and treatment characteristics, we compared the probability of planned OAT use in states with Medicaid coverage of methadone maintenance versus states without coverage. A total of 71% of pregnant women admitted to OUD treatment were 18-29 years old, 85% were white non-Hispanic, and 56% used heroin. Overall, 74% of admissions occurred in the 18 states with Medicaid coverage of methadone maintenance and 53% of admissions involved planned use of OAT. Compared with states without Medicaid coverage of methadone maintenance, admissions in states with coverage were significantly more likely to involve planned OAT use (adjusted difference: 32.9 percentage points, 95% confidence interval, 19.2-46.7). Including methadone maintenance in the Medicaid benefit is essential to increasing OAT among pregnant women with OUD and should be considered a key policy strategy to enhance outcomes for mothers and newborns.
Bojko, Martha J; Mazhnaya, Alyona; Makarenko, Iuliia; Marcus, Ruthanne; Dvoriak, Sergii; Islam, Zahedul; Altice, Frederick L
Opioid substitution therapy (OST) is an evidence-based HIV prevention strategy for people who inject drugs (PWIDs). Yet, only 2.7% of Ukraine's estimated 310,000 PWIDs receive it despite free treatment since 2004. The multi-level barriers to entering OST among opioid dependent PWIDs have not been examined in Ukraine. A multi-year mixed methods implementation science project included focus group discussions with 199 PWIDs in 5 major Ukrainian cities in 2013 covering drug treatment attitudes and beliefs and knowledge of and experiences with OST. Data were transcribed, translated into English and coded. Coded segments related to OST access, entry, knowledge, beliefs and attitudes were analyzed among 41 PWIDs who were eligible for but had never received OST. A number of programmatic and structural barriers were mentioned by participants as barriers to entry to OST, including compulsory drug user registration, waiting lists, and limited number of treatment slots. Participants also voiced strong negative attitudes and beliefs about OST, especially methadone. Their perceptions about methadone's side effects as well as the stigma of being a methadone client were expressed as obstacles to treatment. Despite expressed interest in treatment, Ukrainian OST-naïve PWIDs evade OST for reasons that can be addressed through changes in program-level and governmental policies and social-marketing campaigns. Voiced OST barriers can effectively inform public health and policy directives related to HIV prevention and treatment in Ukraine to improve evidence-based treatment access and availability.
Polonsky, Maxim; Azbel, Lyuba; Wickersham, Jeffrey A; Taxman, Faye S; Grishaev, Evgeny; Dvoryak, Sergey; Altice, Frederick L
Ukraine is experiencing one of the most volatile HIV epidemics globally, fueled primarily by people who inject drugs (PWIDs), and a parallel incarceration epidemic. Opioid substitution therapy (OST) is internationally recognized as one of the most effective forms of treatment for opioid dependence and is among the most effective HIV prevention strategies available, yet efforts to adopt it in Ukraine's Criminal Justice System (CJS) have been thwarted. To understand the reluctance of the Ukrainian CJS to adopt OST despite the overwhelming evidence pointing to its health benefits and improved criminal justice outcomes, we conducted the first survey of Ukrainian prison administrative, medical and custodial staff (N=243) attitudes towards addiction in general, OST, and people living with HIV/AIDS (PLWHA) in representative regions of Ukraine. Results revealed that Ukrainian CJS workers' attitudes toward OST, PLWHA, and drug addiction were universally negative, but differed substantially along geographic and occupational lines. Whereas geographic and cultural proximity to the European Union drove positive attitudes in the west, in the southern region we observed an identifiability effect, as workers who worked directly with prisoners held the most positive attitudes. We also found that knowledge mediated the effect of drug intolerance on OST attitudes. In Ukraine, adoption of OST is more influenced by myths, biases and ideological prejudices than by existing scientific evidence. By elucidating existing attitudes among CJS personnel, this study will help to direct subsequent interventions to address the barriers to implementing evidence-based HIV prevention treatments. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Cushman, Phoebe A; Liebschutz, Jane M; Hodgkin, Joseph G; Shanahan, Christopher W; White, Julie L; Hardesty, Ilana; Alford, Daniel P
In 2012, the US Food and Drug Administration (FDA) responded to the opioid crisis with a Risk Evaluation and Mitigation Strategy, requiring manufacturers of extended-release/long-acting opioids to fund continuing medical education based on the "FDA Blueprint for Prescriber Education." Topics in the Blueprint are "Assessing Patients for Treatment," "Initiating Therapy, Modifying Dosing, and Discontinuing Use," "Managing Therapy," "Counseling Patients and Caregivers about Safe Use," "General Drug Information," and "Specific Drug Information." Based on the FDA Blueprint, Boston University School of Medicine's "Safe and Competent Opioid Prescribing Education" (SCOPE of Pain) offers live trainings for physicians and other prescribers. During trainings, participants submit written questions about the curriculum and/or their clinical experiences. The objective was to compare themes that arose from questions asked by SCOPE of Pain participants with content of the FDA Blueprint in order to evaluate how well the Blueprint answers prescribers' concerns. The authors conducted qualitative analyses of all 1309 questions submitted by participants in 29 trainings across 16 states from May 2013 to May 2015, using conventional content analysis to code the questions. Themes that emerged from participants' questions were then compared with the Blueprint. Most themes fell into the topic categories of the Blueprint. Five main themes diverged: Participants sought information on (1) safe alternatives to opioids, (2) overcoming barriers to safe opioid prescribing, (3) government regulations of opioid prescribing, (4) the role of marijuana in opioid prescribing, and (5) maintaining a positive provider-patient relationship while prescribing opioids. In addition to learning the mechanics of safe opioid prescribing, providers want to understand government regulations and effective patient communication skills. Aware of the limitations of opioids in managing chronic pain, providers seek advice
A multicenter, primary-care-based, open-label study to assess the success of converting opioid-experienced patients with chronic moderate-to-severe pain to morphine sulfate and naltrexone hydrochloride extended-release capsules using a standardized conversion guide.
Setnik, Beatrice; Roland, Carl L; Sommerville, Kenneth W; Pixton, Glenn C; Berke, Robert; Calkins, Anne; Goli, Veeraindar
To evaluate the conversion of opioid-experienced patients with chronic moderate-to-severe pain to extended-release morphine sulfate with sequestered naltrexone hydrochloride (MSN) using a standardized conversion guide. This open-label, single-arm study was conducted in 157 primary care centers in the United States. A total of 684 opioid-experienced adults with chronic moderate-to-severe pain were converted to oral administration of MSN from transdermal fentanyl and oral formulations of hydrocodone, hydromorphone, methadone, oxycodone, oxymorphone, and other morphine products using a standardized conversion guide. The primary endpoint was the percentage of patients achieving a stable MSN dose within a 6-week titration phase. Secondary endpoints included duration of time to stable dose, number of titration steps, safety and efficacy measures, and investigator assessment of conversion guide utility. Of the 684 patients, 51.3% were converted to a stable dose of MSN (95% confidence interval: 47.5%, 55.1%). The mean (standard deviation) number of days to stable dose was 20 (8.94), and number of titration steps to stable dose was 2.4 (1.37). The majority of adverse events were mild/moderate and consistent with opioid therapy. Mean pain scores at stable dose decreased from baseline. Investigators were generally satisfied with the conversion guide and, in 94% of cases, reported they would use it again. Conversion to MSN treatment using the standardized MSN conversion guide was an attainable goal in approximately half of the population of opioid-experienced patients with chronic moderate-to-severe pain. Investigators found the guide to be a useful tool to assist conversion of opioid-experienced patients to MSN.
Starrels, Joanna L; Peyser, Deena; Haughton, Lorlette; Fox, Aaron; Merlin, Jessica S; Arnsten, Julia H; Cunningham, Chinazo O
Human immunodeficiency virus (HIV)-infected patients have a high prevalence of chronic pain and opioid use, making HIV care a critical setting for improving the safety of opioid prescribing. Little is known about HIV treatment providers' perspectives about opioid prescribing to patients with chronic pain. The authors administered a questionnaire and conducted semistructured telephone interviews with 18 HIV treatment providers (infectious disease specialists, general internists, family medicine physicians, nurse practitioners, and physician assistants) in Bronx, NY. Open-ended interview questions focused on providers' experiences, beliefs, and attitudes about opioid prescribing and about the use of guideline-based opioid prescribing practices (conservative prescribing, and monitoring for and responding to misuse). Transcripts were thematically analyzed using a modified grounded theory approach. Eighteen HIV treatment providers included 13 physicians, four nurse practitioners, and one physician assistant. They were 62% female, 56% white, and practiced as HIV treatment providers for a mean of 14.6 years. Most reported always or almost always using opioid treatment agreements (56%) and urine drug testing (61%) with their patients on long-term opioid therapy. HIV treatment providers tended to view opioid prescribing for chronic pain within the "HIV paradigm," a set of priorities and principles defined by three key themes: (1) primacy of HIV goals, (2) familiarity with substance use, and (3) the clinician as ally. The HIV paradigm sometimes supported, and sometimes conflicted with, guideline-based opioid prescribing practices. For HIV treatment providers, perceived alignment with the HIV paradigm determined whether and how guideline-based opioid prescribing practices were adopted. For example, the primacy of HIV goals superseded conservative opioid prescribing when providers prescribed opioids with the goal of retaining patients in HIV care. These findings highlight
Chen, Kelly Yan; Chen, Lucy; Mao, Jianren
Buprenorphine-naloxone (bup/nal in 4:1 ratio; Suboxone; Reckitt Benckiser Pharmaceuticals Incorporation, Richmond, VA) is approved by the Food and Drug Administration for outpatient office-based addiction treatment. In the past few years, bup/nal has been increasingly prescribed off-label for chronic pain management. The current data suggest that bup/nal may provide pain relief in patients with chronic pain with opioid dependence or addiction. However, the unique pharmacological profile of bup/nal confers it to be a weak analgesic that is unlikely to provide adequate pain relief for patients without opioid dependence or addiction. Possible mechanisms of pain relief by bup/nal therapy in opioid-dependent patients with chronic pain may include reversal of opioid-induced hyperalgesia and improvement in opioid tolerance and addiction. Additional studies are needed to assess the implication of bup/nal therapy in clinical anesthesia and perioperative pain management.
Wachholtz, Amy; Gonzalez, Gerardo
Medication assisted treatment for opioid dependence alters the pain experience. This study will evaluate changes pain sensitivity and tolerance with opioid treatments; and duration of this effect after treatment cessation. 120 Individuals with chronic pain were recruited in 4 groups (N = 30): 1-methadone for opioid addiction; 2-buprenorphine for opioid addiction; 3-history of opioid maintenance treatment for opioid addiction but with prolonged abstinence (M = 121 weeks; SD = 23.3); and 4-opioid naïve controls. Participants completed a psychological assessment and a cold water task including, time to first pain (sensitivity) and time to stopping the pain task (tolerance). Data analysis used survival analyses. A Kaplan-Meier-Cox survival analysis showed group differences for both pain sensitivity (log rank = 15.50; p opioid maintenance resulted in differing pain sensitivity compared to opioid naïve (p's opioid maintenance compared to active methadone patients (p opioid naïve control group participants (p's opioid abstinence increased (R = .37; p opioid maintenance, there appears to be long-term differences in pain sensitivity that do not resolve with discontinuation of opioid maintenance. Although pain sensitivity does not change, pain tolerance does improve after opioid maintenance cessation. Implications for treating co-morbid opioid addiction and pain (acute and chronic) are discussed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Full Text Available The South-East Asia Region contains an estimated 400,000-500,000 people who inject drugs (PWID. HIV prevalence among PWID is commonly 20% or higher in Indonesia, Thailand, Myanmar and some regions of India. Opioid substitution therapy (OST is an important HIV prevention intervention in this part of the world. However, key challenges and barriers to scale up of OST exist, including: pervasive stigma and discrimination towards PWID; criminalisation of drug use overshadowing a public health response; lack of political will and national commitment; low financial investment; focus towards traditional treatment models of detoxification and rehabilitation; inadequate dosing of OST; and poor monitoring and evaluation of programmes. Our review of local evidence highlights that OST can be successful within the Asian context. Such evidence should be utilised more widely to advocate for policy change and increased political commitment to ensure OST reaches substantially more drug users.
Lindstrøm, Maia; Saidj, Madina; Kowalski, Krystyna
-control. FBT is designed to accommodate diverse populations of youth with a variety of behavioral, cultural and individual preferences. FBT incorporates behavioral theory (reduction of undesired behavior by manipulating external reinforcement), structural family theory (in which the structure of the family...... for non-opioid drug use; • have used experimental, quasi-experimental or non-randomized controlled designs; • have reported at least one eligible outcome variable measuring abstinence, reduction of drug use, family functioning, education or vocational involvement, retention, risk behavior or any other...
Ashburn, Michael A; Levine, Rachel L
The objective of this project was to develop core competencies for education on opioids and addiction to be used in all Pennsylvania medical schools. The Pennsylvania Physician General created a task force that was responsible for the creation of the core competencies. A literature review was completed, and a survey of graduating medical students was conducted. The task force then developed, reviewed, and approved the core competencies. The competencies were grouped into nine domains: understanding core aspects of addiction; patient screening for substance use disorder; proper referral for specialty evaluation and treatment of substance use disorder; proper patient assessment when treating pain; proper use of multimodal treatment options when treating acute pain; proper use of opioids for the treatment of acute pain (after consideration of alternatives); the role of opioids in the treatment of chronic noncancer pain; patient risk assessment related to the use of opioids to treat chronic noncancer pain, including the assessment for substance use disorder or increased risk for aberrant drug-related behavior; and the process for patient education, initiation of treatment, careful patient monitoring, and discontinuation of therapy when using opioids to treat chronic noncancer pain. Specific competencies were developed for each domain. These competencies will be incorporated into the educational process at all Pennsylvania medical schools. It is hoped that these curriculum changes will improve student knowledge and attitudes in these areas, thus improving patient outcomes. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org
Tabuchi, Yukiko; Yasuda, Tetsuyuki; Kaneto, Hideaki; Kitamura, Tetsuhiro; Kozawa, Junji; Otsuki, Michio; Imagawa, Akihisa; Nakae, Aya; Matsuda, Youichi; Uematsu, Hironobu; Mashimo, Takashi; Shibata, Masahiko; Shimomura, Iichiro
We report a case of 42-year-old male patient with hypogonadotropic hypogonadism. He suffered from general fatigue and erectile dysfunction after the treatment with transdermal fentanyl for chronic pain by traffic injury. Endocrine examinations and hormone stimulating tests showed that he had hypogonadotropic hypogonadism. Brain magnetic resonance imaging (MRI) showed no abnormal findings, and he had no past history of accounting for acquired hypogonadotropic hypogonadism. Therefore, his hypog...
Bell, Timothy; Annunziata, Kathy; Leslie, John B
To characterize the impact of opioid-induced constipation (OIC) on healthcare resource use, work productivity, and health-related quality of life (HRQOL) in patients receiving chronic opioid therapy. Data were collected via Internet questionnaires during the international National Health and Wellness Survey (NHWS) 2004 from individuals aged > or = 18 years who reported taking opioids for > or = 6 months. Healthcare resource utilization, Work Productivity, and Activity Impairment, and Short-Form 8 (SF-8) questionnaire responses were compared between those who did or did not report OIC. Data were available from 2,430 individuals receiving opioids, of whom 359 reported OIC. Participants with OIC reported significantly more physician visits (mean difference 3.84 visits; p hospitalization were observed. Respondents with OIC also reported significantly greater time missed from work, impairment while working, overall work impairment, and activity impairment (p constipation in patients receiving chronic opioid therapy.
Jones, E. A.; Dekker, L. R.
Findings consistent with the hypothesis that increased central opioidergic tone contributes to the pruritus of cholestasis provide a rationale for treating this form of pruritus with opiate antagonists. However, initiation of therapy with an opiate antagonist in a cholestatic patient may precipitate
Bauer, Brent A; Tilburt, Jon C; Sood, Amit; Li, Guang-Xi; Wang, Shi-Han
Pain afflflicts over 50 million people in the US, with 30.7% US adults suffering with chronic pain. Despite advances in therapies, many patients will continue to deal with ongoing symptoms that are not fully addressed by the best conventional medicine has to offer them. The patients frequently turn to therapies outside the usual purview of conventional medicine (herbs, acupuncture, meditation, etc.) called complementary and alternative medicine (CAM). Academic and governmental groups are also starting to incorporate CAM recommendations into chronic pain management strategies. Thus, for any physician who care for patients with chronic pain, having some familiarity with these therapies-including risks and benefits-will be key to helping guide patients in making evidence-based, well informed decisions about whether or not to use such therapies. On the other hand, if a CAM therapy has evidence of both safety and efficacy then not making it available to a patient who is suffering does not meet the need of the patient. We summarize the current evidence of a wide variety of CAM modalities that have potential for helping patients with chronic pain in this article. The triad of chronic pain symptoms, ready access to information on the internet, and growing patient empowerment suggest that CAM therapies will remain a consistent part of the healthcare of patients dealing with chronic pain.
Manjiani, Deepak; Paul, D Baby; Kunnumpurath, Sreekumar; Kaye, Alan David; Vadivelu, Nalini
Pain can significantly influence an individual's health status and can have serious negative consequences: poor nutrition, decreased appetite, abnormal sleep patterns, fatigue, and impairment of daily living activities. Pain can cause psychological impairment and decrease healing and recovery from injuries and illness. A hallmark of many chronic conditions, pain affects more patients' lives than diabetes mellitus, heart disease, and cancer combined. However, many chronic sufferers do not have access to effective pain management for a variety of reasons, including limited access, restrictions, and personal and cultural biases. This review summarizes issues of access, distribution, and cultural bias with regard to opioid agents and seeks to clarify the challenges related to opioid delivery. The considerable negative physical and mental consequences of chronic pain are discussed for the general and palliative care population. Opioids are an effective treatment for various intractable painful conditions, but problems in global opioid access for safe and rational use in pain management contribute to unnecessary suffering. These problems persist despite increased understanding in recent years of the pathophysiology of pain. Comprehensive guidelines for goal-directed and patient-friendly chronic opiate therapy will potentially enhance the outlook for future chronic pain management. The improvement of pain education in undergraduate and postgraduate training will benefit patients and clinicians. The promise of new medications, along with the utilization of multimodal approaches, has the potential to provide effective pain relief to future generations of sufferers.
Full Text Available Autologous serum therapy is a promising therapy for treatment resistant urticaria. This is useful in developing countries as this is economical option. Minimum instruments like centrifuge, syringe and needles are required for the procedure.
Cassano, Nicoletta; Tessari, Gianpaolo; Vena, Gino A; Girolomoni, Giampiero
Chronic pruritus is a major and distressing symptom of many cutaneous and systemic diseases and can significantly impair the patient's quality of life. Pruritus perception is the final result of a complex network involving dedicated nerve pathways and brain areas, and an increasing number of peripheral and central mediators are thought to be involved. Itch is associated with most cutaneous disorders and, in these circumstances, its management overlaps with that of the skin disease. Itch can also occur without associated skin diseases or primary skin lesions, but only with nonspecific lesions secondary to rubbing or scratching. Chronic itch with no or minimal skin changes can be secondary to important diseases, such as neurologic disorders, chronic renal failure, cholestasis, systemic infections, malignancies, and endocrine disorders, and may also result from exposure to some drugs. The search for the cause of pruritus usually requires a meticulous step-by-step assessment involving careful history taking as well as clinical examination and laboratory investigations. Few evidence-based treatments for pruritus are available. Topical therapy, oral histamine H(1) receptor antagonists, and phototherapy with UV radiation can target pruritus elicitation in the skin, whereas antiepileptic drugs, opioid receptor antagonists, and antidepressants can block signal processing in the CNS.
Lenard, N R; Zheng, H; Berthoud, H-R
To test the hypothesis that micro-opioid receptor signaling in the nucleus accumbens contributes to hedonic (over)eating and obesity. To investigate the effects of chronic micro-opioid antagonism in the nucleus accumbens core or shell on intake of a palatable diet, and the development of diet-induced obesity in rats. Chronic blockade of micro-opioid receptor signaling in the nucleus accumbens core or shell was achieved by means of repeated injections (every 4-5 days) of the irreversible receptor antagonist beta-funaltrexamine (BFNA) over 3-5 weeks. The diet consisted of either a choice of high-fat chow, chocolate-flavored Ensure and regular chow (each nutritionally complete) or regular chow only. Intake of each food item, body weight and body fat mass were monitored throughout the study. The BFNA injections aimed at either the core or shell of the nucleus accumbens resulted in significantly attenuated intake of palatable diet, body weight gain and fat accretion, compared with vehicle control injections. The injection of BFNA in the core did not significantly change these parameters in chow-fed control rats. The injection of BFNA in the core and shell differentially affected intake of the two palatable food items: in the core, BFNA significantly reduced the intake of high-fat, but not of Ensure, whereas in the shell, it significantly reduced the intake of Ensure, but not of high-fat, compared with vehicle treatment. Endogenous micro-opioid receptor signaling in the nucleus accumbens core and shell is necessary for palatable diet-induced hyperphagia and obesity to fully develop in rats. Sweet and non-sweet fatty foods may be differentially processed in subcomponents of the ventral striatum.
van Koppen, A.N.
Chronic kidney disease (CKD) may lead to end-stage renal failure, requiring renal replacement strategies. Development of new therapies to reduce progression of CKD is therefore a major global public health target. The aim of this thesis was to investigate whether cell-based therapies have the
Alyn, Jody H.; Becker, Lee A.
Assessed the effectiveness of feminist therapy with 28 chronically disturbed female clients enrolled in a partial hospitalization program. Significant improvement in self-esteem, and significant increase in sexual knowledge, were produced for participants in the feminist therapy groups. No changes were produced on the Attitudes Toward Women Scale.…
Hsu, Eric S
Chronic pain is usually managed by various pharmacotherapies after exhausting the conservative modalities such as over-the-counter choices. The goal of this review is to investigate current state of opioids and non-opioid medication overuse that includes NSAIDs, skeletal muscle relaxants, antidepressants, membrane stabilization agents, and benzodiazepine. How to minimize medication overuse and achieve better outcome in chronic pain management? Although antidepressants and membrane stabilization agents contribute to the crucial components for neuromodulation, opioids were frequently designated as a rescue remedy in chronic pain since adjunct analgesics usually do not provide instantaneous relief. The updated CDC guideline for prescribing opioids has gained widespread attention via media exposure. Both patients and prescribers are alerted to respond to the opioid epidemic and numerous complications. However, there has been overuse of non-opioid adjunct analgesics that caused significant adverse effects in addition to concurrent opioid consumption. It is a common practice to extrapolate the WHO three-step analgesic ladder for cancer pain to apply in non-cancer pain that emphasizes solely on pharmacologic therapy which may result in overuse and escalation of opioids in non-cancer pain. There has been promising progress in non-pharmacologic therapies such as biofeedback, complementary, and alternative medicine to facilitate pain control instead of dependency on pharmacologic therapies. This review article presents the current state of medication overuse in chronic pain and proposes precaution to balance the risk and benefit ratio. It may serve as a premier for future study on clinical pathway for comprehensive chronic pain management and reduce medication overuse.
Full Text Available Evidence suggests that recurrent nocturnal hypoxemia may affect pain response and/or the sensitivity to opioid analgesia. We tested the hypothesis that nocturnal hypoxemia, quantified by sleep time spent at an arterial saturation (SaO2 < 90% and minimum nocturnal SaO2 on polysomnography, are associated with decreased pain and reduced opioid consumption during the initial 72 postoperative hours in patients having laparoscopic bariatric surgery.With Institutional Review Board approval, we examined the records of all patients who underwent laparoscopic bariatric surgery between 2004 and 2010 and had an available nocturnal polysomnography study. We assessed the relationships between the time-weighted average of pain score and total opioid consumption during the initial 72 postoperative hours, and: (a the percentage of total sleep time spent at SaO2 < 90%, (b the minimum nocturnal SaO2, and (c the number of apnea/hypopnea episodes per hour of sleep. We used multivariable regression models to adjust for both clinical and sleep-related confounders.Two hundred eighteen patients were included in the analysis. Percentage of total sleep time spent at SaO2 < 90% was inversely associated with total postoperative opioid consumption; a 5-%- absolute increase in the former would relatively decrease median opioid consumption by 16% (98.75% CI: 2% to 28%, P = 0.006. However, the percentage of total sleep time spent at SaO2 < 90% was not associated with pain. The minimum nocturnal SaO2 was associated neither with total postoperative opioid consumption nor with pain. In addition, neither pain nor total opioid consumption was significantly associated with the number of apnea/hypopnea episodes per hour of sleep.Preoperative nocturnal intermittent hypoxia may enhance sensitivity to opioids.
Shaparin, Naum; Mehta, Neel; Kunkel, Frank; Stripp, Richard; Borg, Damon; Kolb, Elizabeth
Interpretation limitations of urine drug testing and the invasiveness of blood toxicology have motivated the desire for the development of simpler methods to assess biologically active drug levels on an individualized patient basis. Oral fluid is a matrix well-suited for the challenge because collections are based on simple noninvasive procedures and drug concentrations better correlate to blood drug levels as oral fluid is a filtrate of the blood. Well-established pharmacokinetic models were utilized to generate oral fluid steady state concentration ranges to assess the interpretive value of the alternative matrix to monitor steady state plasma oxycodone levels. Paired oral fluid and plasma samples were collected from patients chronically prescribed oxycodone and quantitatively analyzed by liquid chromatography tandem mass spectrometry. Steady state plasma concentration ranges were calculated for each donor and converted to an equivalent range in oral fluid. Measured plasma and oral fluid oxycodone concentrations were compared with respective matrix-matched steady state ranges, using each plasma steady state classification as the control. A high degree of correlation was observed between matrices when classifying donors according to expected steady state oxycodone concentration. Agreement between plasma and oral fluid steady state classifications was observed in 75.6% of paired samples. This study supports novel application of basic pharmacokinetic knowledge to the pain management industry, simplifying and improving individualized drug monitoring and risk assessment through the use of oral fluid drug testing. Many benefits of established therapeutic drug monitoring in plasma can be realized in oral fluid for patients chronically prescribed oxycodone at steady state. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: email@example.com
Polackwich, A S; Shoskes, D A
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), also known as NIH Category III Prostatitis is a highly prevalent syndrome with significant impact on quality of life. As a heterogeneous syndrome, there exists no 'one size fits all' therapy with level 1 evidence to guide therapy. This often leads to a nihilistic approach to patients and clinical outcomes are poor. In this review, we examine the evidence for CP/CPPS therapies and discuss our technique of clinical phenotyping combined with multimodal therapy. Review of Medline articles with terms 'non-bacterial prostatitis', 'abacterial prostatitis' and 'chronic pelvic pain syndrome'. Many individual therapies have been evaluated in the treatment of CP/CPPS; antibiotics, anti-inflammatory medications (including bioflavonoids), neuromodulators, alpha blockers, pelvic floor physical therapy and cognitive behavior therapy. Each of these has been found to have varying success in alleviating symptoms. UPOINT is a system of clinical phenotyping for CP/CPPS patients that has 6 defined domains, which guide multimodal therapy. It has been validated to correlate with symptom burden and therapy guided by UPOINT leads to significant symptom improvement in 75-84% of patients based on three independent studies. CP/CPPS is a heterogeneous condition and, much like with prostate cancer, optimal therapy can only be achieved by classifying patients into clinically meaningful phenotypic groups (much like TNM) and letting the phenotype drive therapy.
Full Text Available Hypercapnic respiratory failure is a frequently encountered medical emergency. Two common causes are acute exacerbations of chronic obstructive pulmonary disease (COPD and as a side effect of opioids. The two causes may coexist leading to diagnostic confusion and consequent delay in optimal management. We report a case of what was initially thought to be an exacerbation of COPD. The patient failed to improve with treatment as expected which led to the empirical administration of naloxone resulting in a dramatic reversal of her respiratory failure. The patient was subsequently discovered to be taking regular dihydrocodeine for chronic back pain.
Schiltenwolf, Marcus; Akbar, Michael; Neubauer, Eva; Gantz, Simone; Flor, Herta; Hug, Andreas; Wang, Haili
Little is known about the affected cognitive problems in chronic low back pain patients. For this patient cohort research mostly focused on memory of pain, rather than cognitive difficulties related to pain. Chronic pain may be associated with specific (yet undefined) cognitive deficits that affect everyday behaviour. We set out to compare the cognitive function of patients with chronic low back pain (cLBP) in the course of multidisciplinary pain treatments before and after therapy. Thirty-three patients with cLBP and 25 healthy controls between 20 and 70 years were recruited into the study. The inclusion criteria for patients were: (1) a history of at least 12 weeks of chronic myofascial low back pain without radicular pain sensation before enrolment; (2) grade II and higher chronicity according to von Korff; (3) no opioid medication. The patients recruited had a mean pain duration of 7.13±7.16 years and reported a mean pain intensity of 6.62±2.04 (visual analogue score, VAS). Their mean back function according to the Funktionsfragebogen Hannover (FFbH, a questionnaire comparable with the Health Assessment Questionnaire) was 52.39±20.23%. At three time points (before therapy, 3 weeks and 6 months after therapy) the study subjects were assessed prospectively with a battery of visual memory tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). These included choice reaction time (CRT), pattern recognition memory (PRM) and spatial span (SSP). In parallel, the Trail-Making Test (TMT-A, TMT-B) and the Wechsler Adult Intelligence Scale (WAIS-III) were used to evaluate intelligence and cognitive flexibility. At the beginning of MDPT (T1), it took patients with cLBP significantly longer than HC to complete TMT-A (38.29±19.99s vs 30.25±14.19s, p=0.047) and TMT-B (72.10±26.98s vs 55.99±22.14s, p=0.034). There were no significant differences between patients and HC in CRT, PRM and SSP. Three weeks (T2) and 6 months (T3) after MDPT, TMT
Warendorf, Janna; Vrancken, Alexander F.J.E.; van Schaik, Ivo N.; Hughes, Richard A.C.; Notermans, Nicolette C.
Background: Chronic idiopathic axonal polyneuropathy (CIAP) is an insidiously progressive sensory or sensorimotor polyneuropathy that affects elderly people. Although severe disability or handicap does not occur, CIAP reduces quality of life. CIAP is diagnosed in 10% to 25% of people referred for
Warendorf, Janna; Vrancken, Alexander F. J. E.; van Schaik, Ivo N.; Hughes, Richard A. C.; Notermans, Nicolette C.
Chronic idiopathic axonal polyneuropathy (CIAP) is an insidiously progressive sensory or sensorimotor polyneuropathy that affects elderly people. Although severe disability or handicap does not occur, CIAP reduces quality of life. CIAP is diagnosed in 10% to 25% of people referred for evaluation of
Quinn, Christopher; Chandler, Clint; Moraska, Albert
Objectives. The effect of massage therapy on chronic nonmigraine headache was investigated. Methods. Chronic tension headache sufferers received structured massage therapy treatment directed toward neck and shoulder muscles. Headache frequency, duration, and intensity were recorded and compared with baseline measures. Results. Compared with baseline values, headache frequency was significantly reduced within the first week of the massage protocol. The reduction of headache frequency continued for the remainder of the study (P = .009). The duration of headaches tended to decrease during the massage treatment period (P = .058). Headache intensity was unaffected by massage (P = .19). Conclusions. The muscle-specific massage therapy technique used in this study has the potential to be a functional, nonpharmacological intervention for reducing the incidence of chronic tension headache. PMID:12356617
Gimbel, Joseph; Spierings, Egilius L H; Katz, Nathaniel; Xiang, Qinfang; Tzanis, Evan; Finn, Andrew
A buccal film of buprenorphine (BBUP) was evaluated for safety and efficacy in a multicenter, double-blind, placebo-controlled, enriched-enrollment, randomized-withdrawal study in opioid-experienced patients (30 to ≤160 mg/d morphine sulfate equivalent) with moderate to severe chronic low back pain taking around-the-clock opioid analgesics. Patients' opioid doses were tapered to ≤30 mg morphine sulfate equivalent before open-label titration with BBUP (range, 150-900 μg every 12 hours). Patients who responded (received adequate analgesia that was generally well tolerated for 14 days) were randomized to receive buprenorphine (n = 254) or placebo (n = 257) buccal film. The primary efficacy variable was the change from baseline to week 12 of double-blind treatment in mean average daily pain-intensity scores using a rating scale of 0 (no pain) to 10 (worst pain imaginable). In the intent-to-treat population, mean pain scores were 6.7 after opioid taper and declined to 2.8 after the BBUP titration period. After randomization, mean pain scores were lower in the BBUP group than in the placebo group; the difference between groups in the mean change from baseline to week 12 was -0.98 (95% CI, -1.32 to -0.64; P opioid-experienced patients taking around-the-clock opioid treatment for chronic low back pain.
Bilevicius, Elena; Sommer, Jordana L; Asmundson, Gordon J G; El-Gabalawy, Renée
Chronic pain conditions and posttraumatic stress disorder (PTSD) commonly co-occur and are associated with opioid use disorder (OUD). The aims of this paper were to identify prevalence estimates of OUD among individuals with and without PTSD and assess independent and combined contributions of PTSD and chronic pain conditions on OUD in a nationally representative sample. Data were extracted from 36,309 individuals from the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions. Past-year PTSD and OUD were assessed using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-5 edition. Respondents reported physician-confirmed, past-year chronic pain conditions, categorized into musculoskeletal pain (e.g., arthritis), digestive pain (e.g., pancreatitis), and nerve pain (e.g., reflex sympathetic dystrophy). We examined the weighted prevalence of OUD among those with and without PTSD. Multiple logistic regressions examined the association between PTSD and chronic pain conditions on OUD. The prevalence of OUD was higher among those with PTSD than those without. Comorbid PTSD/musculoskeletal pain and PTSD/nerve pain conditions were associated with increased odds of OUD, compared to those with neither PTSD nor chronic pain conditions. Digestive pain conditions were not associated with OUD. Comorbid PTSD/musculoskeletal pain conditions demonstrated an additive relationship on OUD compared to musculoskeletal pain conditions and PTSD alone. Results reveal that musculoskeletal pain and nerve pain conditions are associated with increased odds of OUD, but only musculoskeletal pain conditions display an additive relationship on OUD when combined with PTSD. These findings have implications for opioid management and screening among those with comorbid conditions. Copyright © 2018 Elsevier B.V. All rights reserved.
When assessing women with chronic vulvar pain, women's health physical therapists search for comorbid mechanical components (including musculoskeletal, fascial, and visceral) and other disorders that may contribute to or be caused by chronic vulvar pain (CVP). Pelvic floor hypertonicity is a key perpetuating factor for CVP. Comprehensive physical therapy evaluation and suggested physical therapy interventions are described. Anatomy of the pelvis, common evaluative findings, and specifics for pelvic floor muscle rehabilitation are presented. Normalization of pelvic floor muscle function contributes to the reduction of CVP. Successful treatment includes the identification and treatment of co-existing physical abnormalities throughout the trunk and pelvis. © 2010 Wiley Periodicals, Inc.
Sinozić, Tamara; Kovacević, Jadranka
Carboxytherapy is a supportive method in chronic wound treatment conducted by cutaneous and subcutaneous injection of medical carbon dioxide (CO2). The primary effect of the injected CO2 is the correction of tissue hypoxia due to the Bohr effect. With its effects on endothelial growth factors, it stimulates neoangiogenesis and fibroblast collagen synthesis consequently leading to better wound healing. Carboxytherapy is used in many areas from chronic wound treatment, peripheral venous and arterial diseases, dermatological diseases, to cosmetic medicine. It is minimally invasive, patients take it well, it is economically acceptable, and it can be conducted in outpatient conditions by properly trained doctors. The application of new technologic innovations in the healing processes, education and teamwork combined with developed holistic individual approach ensure good cooperation and mutual doctor-patient communication, enhance patient care and improve their quality of life.
A multicenter, primary-care-based, open-label study to assess the success of converting opioid-experienced patients with chronic moderate-to-severe pain to morphine sulfate and naltrexone hydrochloride extended-release capsules using a standardized conversion guide
Full Text Available Beatrice Setnik,1 Carl L Roland,1 Kenneth W Sommerville,1,2 Glenn C Pixton,1 Robert Berke,3,4 Anne Calkins,5 Veeraindar Goli1,2 1Pfizer Inc, 2Duke University Medical Center, Durham, NC, USA; 3Family Health Medical Services PLLC, Mayville, 4Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, 5New York Spine & Wellness Center, Syracuse, NY, USA Objective: To evaluate the conversion of opioid-experienced patients with chronic moderate-to-severe pain to extended-release morphine sulfate with sequestered naltrexone hydrochloride (MSN using a standardized conversion guide. Methods: This open-label, single-arm study was conducted in 157 primary care centers in the United States. A total of 684 opioid-experienced adults with chronic moderate-to-severe pain were converted to oral administration of MSN from transdermal fentanyl and oral formulations of hydrocodone, hydromorphone, methadone, oxycodone, oxymorphone, and other morphine products using a standardized conversion guide. The primary endpoint was the percentage of patients achieving a stable MSN dose within a 6-week titration phase. Secondary endpoints included duration of time to stable dose, number of titration steps, safety and efficacy measures, and investigator assessment of conversion guide utility. Results: Of the 684 patients, 51.3% were converted to a stable dose of MSN (95% confidence interval: 47.5%, 55.1%. The mean (standard deviation number of days to stable dose was 20 (8.94, and number of titration steps to stable dose was 2.4 (1.37. The majority of adverse events were mild/moderate and consistent with opioid therapy. Mean pain scores at stable dose decreased from baseline. Investigators were generally satisfied with the conversion guide and, in 94% of cases, reported they would use it again. Conclusion: Conversion to MSN treatment using the standardized MSN conversion guide was an attainable goal in approximately half of the population of
patients with COPD require pharmacological therapy. ... pulmonary dysfunction. Clearly the patient's tolerance to the various drugs will influence the choice of long-term maintenance treatment. The other important factor in the .... blocking cervical immune responses might leave her less protected against other infections.
Müller, Jana; Schmidt, Daniel; Kollan, Christian; Lehmann, Marc; Bremer, Viviane; Zimmermann, Ruth
In Germany, medical care of prisoners is completely separated from extramural health care. The extent and quality of medical care among prisoners in Germany are therefore largely unknown. We performed a secondary data analysis of pharmacy sales data for tuberculosis (TB), HIV, hepatitis C (HCV) and opioid substitution treatment (OST) delivered to prisons in 11 federal states (FS) in Germany between 01/2012 and 03/2013. The aims of this study were to assess (i) the treatment availability for the selected diseases and OST in German prisons, (ii) the proportion of prisoners treated per FS and overall for TB, HIV, HCV and OST during the study period. Substances unique to or typically used for the treatment of each disease were defined as marker substances with defined daily doses (DDD). For each marker substance we assessed the cumulative number of DDD, the average daily number of DDD (DDD d ) and average treatment prevalence per day in percent (adTP). Accordingly, the DDD d represents one person treated per day and the adTP means the proportion of prisoners treated per day. We compared the adTP of the diseases with previously measured prevalences. We obtained data from pharmacies supplying prisons in 11 of 16 German FS. Of the included prisons, 41% were supplied with medicines for TB, 71% for HIV and 58% for HCV and OST. Twice as many delivered marker substances for TB were indicated for the continuation phase and chemoprevention than the intensive phase. The HIV adTP ranged from 0.06% to 0.94%, HCV adTP ranged from 0.03% to 0.59% and OST adTP ranged from 0% to 7.90%. The overall adTP for the respective treatment was 0.39% for HIV, 0.12% for HCV and 2.18% for OST. According to our findings treatment rates for TB were consistent with the expected TB prevalence, at least in Berlin. HIV treatment seems to be offered to an adequate proportion of estimated infected prisoners. In contrast, the HCV treatment prevalence was low. High variation among FS in provision of all
Xu, Changqing; Fitting, Sylvia
Due to combined antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) is considered a chronic disease with high prevalence of mild forms of neurocognitive impairments, also referred to as HIV-associated neurocognitive disorders (HAND). Although opiate drug use can exacerbate HIV-1 Tat-induced neuronal damage, it remains unknown how and to what extent opioids interact with Tat on the GABAergic system. We conducted whole-cell recordings in mouse striatal slices and examined...
Full Text Available Current biological treatments for non-healing wounds aim to address the common deviations in healing mechanisms, mainly inflammation, inadequate angiogenesis and reduced synthesis of extracellular matrix. In this context, regenerative medicine strategies, i.e., platelet rich plasmas and mesenchymal stromal cell products, may form part of adjuvant interventions in an integral patient management. We synthesized the clinical experience on ulcer management using these two categories of biological adjuvants. The results of ten controlled trials that are included in this systematic review favor the use of mesenchymal stromal cell based-adjuvants for impaired wound healing, but the number and quality of studies is moderate-low and are complicated by the diversity of biological products. Regarding platelet-derived products, 18 controlled studies investigated their efficacy in chronic wounds in the lower limb, but the heterogeneity of products and protocols hinders clinically meaningful quantitative synthesis. Most patients were diabetic, emphasizing an unmet medical need in this condition. Overall, there is not sufficient evidence to inform routine care, and further clinical research is necessary to realize the full potential of adjuvant regenerative medicine strategies in the management of chronic leg ulcers.
Filges, Trine; Jørgensen, Anne-Marie Klint
Objectives: This review evaluates the evidence on the effects of cognitive–behavioral therapy (CBT) on drug use reduction for young people in treatment for nonopioid drug use. Method: We followed Campbell Collaboration guidelines to conduct a systematic review of randomized and nonrandomized trials...
Cronin-Fenton, Deirdre P; Heide-Jørgensen, Uffe; Ahern, Thomas P
BACKGROUND: Opioids may alter immune function, thereby potentially affecting cancer recurrence. The authors investigated the association between postdiagnosis opioid use and breast cancer recurrence. METHODS: Patients with incident, early stage breast cancer who were diagnosed during 1996 through...... 2008 in Denmark were identified from the Danish Breast Cancer Cooperative Group Registry. Opioid prescriptions were ascertained from the Danish National Prescription Registry. Follow-up began on the date of primary surgery for breast cancer and continued until breast cancer recurrence, death......, emigration, 10 years, or July 31, 2013, whichever occurred first. Cox regression models were used to compute hazard ratios and 95% confidence intervals associating breast cancer recurrence with opioid prescription use overall and by opioid type and strength, immunosuppressive effect, chronic use (≥6 months...
P'yanzina, A V
The aim of the study was to elaborate the methodology of magnetic therapy for complex treatment of chronic periodontal disease (CPD). The study included 60 patients aged 35 to 65 years with moderate CPD divided in 2 groups. Patients in group 1 (controls) received impulse carbonate irrigation for 12 min №10, group 2 additionally received magnetic therapy for 5 min №10 in maxillary and mandibular areas. periodontal and rheological indices proved magnetic therapy to be useful tool for eradication of inflammation, periodontal tissue functional recovery and stabilization.
Rheumatoid arthritis (RA) is a relatively common disease that is characterized by chronic inflammation of joints. The research as described in this thesis focused on the question of whether adoptive cellular therapy is effective in a mouse model of RA. The most generally known type of adoptive
de Bruijne, J.
Hepatitis C virus (HCV) infection was discovered in the late 1980s. Since then, tremendous progress has been made in understanding the pathophysiology of HCV infection together with the development of improved therapies for patients with chronic hepatitis C. The main focus of this thesis was to
Vlakhov, N.; Parusheva, D.; Vankova, V.
β-therapy with 32 P was provided to 22 chronic eczema patients. A dose of 25 Gy given in 5 sessions resulted in a cure of 19 patients within 3 years of follow-up. Hyperpigmentation of the skin was noted in 2 patients
van der Harst, Pim; Boehm, Michael; van Gilst, Wiek H.; van Veldhuisen, Dirk J.
Both primary and secondary prevention studies have provided a wealth of evidence that statin therapy effectively reduces cardiovascular events. However, this general statement on the efficacy and safety of statin treatment has not been validated in patients with chronic heart failure (CHF).
A. L. Poznyak
Full Text Available Present material of problem question therapy chronic trichomoniasis. Study clinical and bacteriological effectiveness basic etiotropic preparation and their combination, used in treatment patients trichomoniasis. Found that the combined application antiprotozoal drugs have a more pronounced effect on kills T. vaginalis and shortens the rehabilitation of the patient.
Nakamura, Takashi; Ebihara, Satoru; Ohkuni, Ikuko; Izukura, Hideaki; Harada, Takashi; Ushigome, Nobuyuki; Ohshiro, Toshio; Musha, Yoshiro; Takahashi, Hiroshi; Tsuchiya, Kazuaki; Kubota, Ayako
Chronic knee joint pain is one of the most frequent complaints which is seen in the outpatient clinic in our medical institute. In previous studies we have reported the benefits of low level laser therapy (LLLT) for chronic pain in the shoulder joints, elbow, hand, finger and the lower back. The present study is a report on the effects of LLLT for chronic knee joint pain. Over the past 5 years, 35 subjects visited the outpatient clinic with complaints of chronic knee joint pain caused by the knee osteoarthritis-induced degenerative meniscal tear. They received low level laser therapy. A 1000 mW semi-conductor laser device was used to deliver 20.1 J/cm(2) per point in continuous wave at 830nm, and four points were irradiated per session (1 treatment) twice a week for 4 weeks. A visual analogue scale (VAS) was used to determine the effects of LLLT for the chronic pain and after the end of the treatment regimen a significant improvement was observed (pknee joint range of motion. Discussions with the patients revealed that it was important for them to learn how to avoid postures that would cause them knee pain in everyday life in order to have continuous benefits from the treatment. The present study demonstrated that 830 nm LLLT was an effective form of treatment for chronic knee pain caused by knee osteoarthritis. Patients were advised to undertake training involving gentle flexion and extension of the knee.
Atalay, Nilgun Simsir; Sahin, Fusun; Atalay, Ali; Akkaya, Nuray
The aim of this prospective study was to evaluate the effects of neural therapy, and physical therapy on level of pain, disability, quality of life, and psychological status in patients with chronic low back pain. Patients admitted to the physical therapy and rehabilitation outpatient clinic with the complaint of low back pain of at least 3 months duration. Group 1 (n=27), physical therapy (PT, hotpack, ultrasound, TENS 15 sessions), group 2 (n=33), neural therapy (NT, 1:1 mixture of 20 mg/mL...
Platt, Lucy; Minozzi, Silvia; Reed, Jennifer; Vickerman, Peter; Hagan, Holly; French, Clare; Jordan, Ashly; Degenhardt, Louisa; Hope, Vivian; Hutchinson, Sharon; Maher, Lisa; Palmateer, Norah; Taylor, Avril; Bruneau, Julie; Hickman, Matthew
Background Needle syringe programmes and opioid substitution therapy for preventing hepatitis C transmission in people who inject drugs Needle syringe programmes (NSP) and opioid substitution therapy (OST) are the primary interventions to reduce hepatitis C (HCV) transmission in people who inject drugs. There is good evidence for the effectiveness of NSP and OST in reducing injecting risk behaviour and increasing evidence for the effectiveness of OST and NSP in reducing HIV acquisition risk, but the evidence on the effectiveness of NSP and OST for preventing HCV acquisition is weak. Objectives To assess the effects of needle syringe programmes and opioid substitution therapy, alone or in combination, for preventing acquisition of HCV in people who inject drugs. Search methods We searched the Cochrane Drug and Alcohol Register, CENTRAL, the Cochrane Database of Systematic Reviews (CDSR), the Database of Abstracts of Reviews of Effects (DARE), the Health Technology Assessment Database (HTA), the NHS Economic Evaluation Database (NHSEED), MEDLINE, Embase, PsycINFO, Global Health, CINAHL, and the Web of Science up to 16 November 2015. We updated this search in March 2017, but we have not incorporated these results into the review yet. Where observational studies did not report any outcome measure, we asked authors to provide unpublished data. We searched publications of key international agencies and conference abstracts. We reviewed reference lists of all included articles and topic-related systematic reviews for eligible papers. Selection criteria We included prospective and retrospective cohort studies, cross-sectional surveys, case-control studies and randomised controlled trials that measured exposure to NSP and/or OST against no intervention or a reduced exposure and reported HCV incidence as an outcome in people who inject drugs. We defined interventions as current OST (within previous 6 months), lifetime use of OST and high NSP coverage (regular attendance at
Angeles, Danilyn M; Ashwal, Stephen; Wycliffe, Nathaniel D; Ebner, Charlotte; Fayard, Elba; Sowers, Lawrence; Holshouser, Barbara A
To examine the effects of opioid and tissue-damaging procedures (TDPs) [i.e. procedures performed in the neonatal intensive care unit (NICU) known to result in pain, stress, and tissue damage] on brain metabolites, we reviewed the medical records of 28 asphyxiated term neonates (eight opioid-treated, 20 non-opioid treated) who had undergone magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) within the first month of life as well as eight newborns with no clinical findings of asphyxial injury. We found that lower creatine (Cr), myoinositol (Ins), and N-acetylaspartate (NAA)/choline (Cho) (p OGM) NAA/Cr was decreased (p = 0.03) and lactate (Lac) was present in a significantly higher amount (40%; p = 0.03) in non-opioid-treated neonates compared with opioid-treated neonates. Compared with controls, untreated neonates showed larger changes in more metabolites in basal ganglia (BG), thalami (TH), and OGM with greater significance than treated neonates. Our data suggest that TDPs affect spectral metabolites and that opioids do not cause harm in asphyxiated term neonates exposed to repetitive TDPs in the first 2-4 DOL and may provide a degree of neuroprotection.
Kimer, Nina; Dahl, Emilie Kristine; Gluud, Lise Lotte
To determine whether antiviral therapy reduces the risk of developing hepatocellular carcinoma (HCC) in chronic hepatitis C.......To determine whether antiviral therapy reduces the risk of developing hepatocellular carcinoma (HCC) in chronic hepatitis C....
Weinman, Bernard; And Others
It is concluded that systematic desensitization or relaxation therapy is not effective in inducing assertive behavior in the male chronic schizophrenic. The treatment of choice for the older chronic male schizophrenic remains socioenvironmental therapy. (Author)
Sklar, C.A. [Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Constine, L.S. [Univ. of Rochester Medical Center, Rochester, NY (United States)
A variety of neuroendocrine disturbances are observed following treatment with external radiation therapy when the hypothalamic-pituitary axis (HPA) is included in the treatment field. Radiation-induced abnormalities are generally dose dependent and may develop many years after irradiation. Growth hormone deficiency and premature sexual development can occur following doses as low as 18 Gy fractionated radiation and are the most common neuroendocrine problems noted in children. Deficiency of gonadotropins, thyroid stimulating hormone, and adrenocorticotropin are seen primarily in individuals treated with > 40 Gy HPA irradiation. Hyperprolactinemia can be seen following high-dose radiotherapy (>40 Gy), especially among young women. Most neuroendocrine disturbances that develop as a result of HPA irradiation are treatable; patients at risk require long-term endocrine follow-up. 23 refs., 6 figs., 2 tabs.
Labuz, Dominika; Celik, Melih Ö; Zimmer, Andreas; Machelska, Halina
Neuropathic pain often results from peripheral nerve damage, which can involve immune response. Local leukocyte-derived opioid peptides or exogenous opioid agonists inhibit neuropathy-induced mechanical hypersensitivity in animal models. Since neuropathic pain can also be augmented by heat, in this study we investigated the role of opioids in the modulation of neuropathy-evoked heat hypersensitivity. We used a chronic constriction injury of the sciatic nerve in wild-type and opioid peptide-knockout mice, and tested opioid effects in heat and mechanical hypersensitivity using Hargreaves and von Frey tests, respectively. We found that although perineural exogenous opioid agonists, including peptidergic ligands, were effective, the endogenous opioid peptides β-endorphin, Met-enkephalin and dynorphin A did not alleviate heat hypersensitivity. Specifically, corticotropin-releasing factor, an agent triggering opioid peptide secretion from leukocytes, applied perineurally did not attenuate heat hypersensitivity in wild-type mice. Exogenous opioids, also shown to release opioid peptides via activation of leukocyte opioid receptors, were equally analgesic in wild-type and opioid peptide-knockout mice, indicating that endogenous opioids do not contribute to exogenous opioid analgesia in heat hypersensitivity. Furthermore, exogenously applied opioid peptides were ineffective as well. Conversely, opioid peptides relieved mechanical hypersensitivity. Thus, both opioid type and sensory modality may determine the outcome of neuropathic pain treatment.
Farr, Alex; Kiss, Herbert; Hagmann, Michael; Holzer, Iris; Kueronya, Verena; Husslein, Peter W; Petricevic, Ljubomir
Vaginal infections are a risk factor for preterm delivery. In this study, we sought to evaluate the vaginal flora of pregnant women receiving opioid maintenance therapy (OMT) in comparison to non-dependent, non-maintained controls. A total of 3763 women with singleton pregnancies who underwent routine screening for asymptomatic vaginal infections between 10 + 0 and 16 + 0 gestational weeks were examined. Vaginal smears were Gram-stained, and microscopically evaluated for bacterial vaginosis, candidiasis, and trichomoniasis. In a retrospective manner, data of 132 women receiving OMT (cases) were matched for age, ethnicity, parity, education, previous preterm delivery, and smoking status to the data of 3631 controls. The vaginal flora at antenatal screening served as the primary outcome measure. Secondary outcome measures were gestational age and birth weight. In the OMT group, 62/132 (47 %) pregnant women received methadone, 39/132 (29.5 %) buprenorphine, and 31/132 (23.5 %) slow-release oral morphine. Normal or intermediate flora was found in 72/132 OMT women (54.5 %) and 2865/3631 controls [78.9 %; OR 0.49 (95 % CI, 0.33-0.71); p Candidiasis occurred more frequently in OMT women than in controls [OR 2.11 (95 % CI, 1.26-3.27); p candidiasis) and trichomoniasis. Compared to infants of the control group, those of women with OMT had a lower mean birth weight [MD -165.3 g (95 % CI, -283.6 to -46.9); p = 0.006]. Pregnant women with OMT are at risk for asymptomatic vaginal infections. As recurrent candidiasis is associated with preterm delivery, the vulnerability of this patient population should lead to consequent antenatal infection screening at early gestation.
Full Text Available Michael J Brennan The Pain Center of Fairfield, Fairfield, CT, USA Abstract: Chronic pain is largely underdiagnosed, often undertreated, and expected to increase as the American population ages. Many patients with chronic pain require long-term treatment with analgesic medications, and pain management may involve use of prescription opioids for patients whose pain is inadequately controlled through other therapies. Yet because of the potential for abuse and addiction, many clinicians hesitate to treat their patients with pain with potentially beneficial agents. Finding the right opioid for the right patient is the first – often complicated – step. Ensuring that patients continue to properly use the medication while achieving therapeutic analgesic effects is the long-term goal. Combined with careful patient selection and ongoing monitoring, new formulations using extended-release technologies incorporating tamper-resistant features may help combat the growing risk of abuse or misuse, which will hopefully reduce individual suffering and the societal burden of chronic pain. The objective of this manuscript is to provide an update on extended-release opioids and to provide clinicians with a greater understanding of which patients might benefit from these new opioid formulations and how to integrate the recommended monitoring for abuse potential into clinical practice. Keywords: chronic pain, opioid analgesics, extended release, abuse prevention
Full Text Available Martin E Hale,1 Srinivas R Nalamachu,2 Arif Khan,3 Michael Kutch4,* 1Gold Coast Research, LLC, Weston, FL, USA; 2International Clinical Research Institute, Overland Park, KS, USA; 3MedNorthwest Clinical Research Center, Bellevue, WA, USA; Duke University Medical Center, Durham, NC, USA; 4Applied Clinical Intelligence, LLC, Bala Cynwyd, PA, USA *Affiliation at the time this work was completed. Michael Kutch is currently affiliated with Cytel Inc, Chesterbrook, PA, USA Purpose: To describe the efficacy and safety of hydromorphone extended-release tablets (OROS hydromorphone ER during dose conversion and titration. Patients and methods: A total of 459 opioid-tolerant adults with chronic moderate to severe low back pain participated in an open-label, 2- to 4-week conversion/titration phase of a double-blind, placebo-controlled, randomized withdrawal trial, conducted at 70 centers in the United States. Patients were converted to once-daily OROS hydromorphone ER at 75% of the equianalgesic dose of their prior total daily opioid dose (5:1 conversion ratio, and titrated as frequently as every 3 days to a maximum dose of 64 mg/day. The primary outcome measure was change in pain intensity numeric rating scale; additional assessments included the Patient Global Assessment and the Roland–Morris Disability Questionnaire scores. Safety assessments were performed at each visit and consisted of recording and monitoring all adverse events (AEs and serious AEs. Results: Mean (standard deviation final daily dose of OROS hydromorphone ER was 37.5 (17.8 mg. Mean (standard error of the mean [SEM] numeric rating scale scores decreased from 6.6 (0.1 at screening to 4.3 (0.1 at the final titration visit (mean [SEM] change, -2.3 [0.1], representing a 34.8% reduction. Mean (SEM change in Patient Global Assessment was -0.6 (0.1, and mean change (SEM in the Roland–Morris Disability Questionnaire was -2.8 (0.3. Patients achieving a stable dose showed greater improvement
Ugur, Muzeyyen; Kaya, Egemen; Gozen, Oguz; Koylu, Ersin O; Kanit, Lutfiye; Keser, Aysegul; Balkan, Burcu
Delta and kappa opioid receptors (DOR and KOR, respectively) and their endogenous ligands, proenkephalin (PENK) and prodynorphin (PDYN)-derived opioid peptides are proposed as important mediators of nicotine reward. This study investigated the regulatory effect of chronic nicotine treatment on the gene expression of DOR, KOR, PENK and PDYN in the mesocorticolimbic system. Three groups of rats were injected subcutaneously with nicotine at doses of 0.2, 0.4, or 0.6 mg/kg/day for 6 days. Rats were decapitated 1 hr after the last dose on day six, as this timing coincides with increased dopamine release in the mesocorticolimbic system. mRNA levels in the ventral tegmental area (VTA), lateral hypothalamic area (LHA), amygdala (AMG), dorsal striatum (DST), nucleus accumbens, and medial prefrontal cortex were measured by quantitative real-time PCR. Our results showed that nicotine upregulated DOR mRNA in the VTA at all of the doses employed, in the AMG at the 0.4 and 0.6 mg/kg doses, and in the DST at the 0.4 mg/kg dose. Conversely, PDYN mRNA was reduced in the LHA with 0.6 mg/kg nicotine and in the AMG with 0.4 mg/kg nicotine. KOR mRNA was also decreased in the DST with 0.6 mg/kg nicotine. Nicotine did not regulate PENK mRNA in any brain region studied. © 2017 Wiley Periodicals, Inc.
Schmahl, W.; Miaskowski, U. (Department of Pathology, Gesellschaft fuer Strahlen-und Umweltforschung mbh Muechen, Neuherberg (West Germany))
We recently reported that in rats prenatally x-irradiated on gestation day 14 with 1 Gy, postnatal chronic application of the opioid antagonist naltrexone (Nx) led to a remarkable growth spurt of the microencephalic brain. In the present study we present histological and autoradiographic results found in the subependymal layer (SEL) of the forebrain lateral ventricles. Nx led to an intermittent augmentation of the mitotic index of the x-irradiated brains within a postnatal observation period of 24 weeks. The most conspicuous finding was transient hyperplasia of the SEL at 4-6 weeks of age which occurred in close proximity to an intact ependymal lining. Districts of the lateral ventricles which were denuded from ependyme and where the rest of the ependymal layer (EL) was dislocated peripherally showed upon Nx treatment a long-lasting SEL hyperplasia with a tendency towards dysplasia. These results revealed that repair proliferation of embryotoxic x-irradiation is normally under strong control by the opioid system. If that system, which exerts a suppressing effect upon glial growth, is blocked by Nx, prominent hyperplastic reactions occur which may be useful for repairing the lesion pattern.
Schmahl, W.; Miaskowski, U.
We recently reported that in rats prenatally x-irradiated on gestation day 14 with 1 Gy, postnatal chronic application of the opioid antagonist naltrexone (Nx) led to a remarkable growth spurt of the microencephalic brain. In the present study we present histological and autoradiographic results found in the subependymal layer (SEL) of the forebrain lateral ventricles. Nx led to an intermittent augmentation of the mitotic index of the x-irradiated brains within a postnatal observation period of 24 weeks. The most conspicuous finding was transient hyperplasia of the SEL at 4-6 weeks of age which occurred in close proximity to an intact ependymal lining. Districts of the lateral ventricles which were denuded from ependyme and where the rest of the ependymal layer (EL) was dislocated peripherally showed upon Nx treatment a long-lasting SEL hyperplasia with a tendency towards dysplasia. These results revealed that repair proliferation of embryotoxic x-irradiation is normally under strong control by the opioid system. If that system, which exerts a suppressing effect upon glial growth, is blocked by Nx, prominent hyperplastic reactions occur which may be useful for repairing the lesion pattern
Marc A. Lazzaro
Full Text Available Recent reports have emerged suggesting that multiple sclerosis (MS may be due to abnormal venous outflow from the central nervous system, termed Chronic Cerebrospinal Venous Insufficiency (CCSVI. These reports have generated strong interest and controversy over the prospect of a treatable cause of this chronic debilitating disease. This review aims to describe the proposed association between CCSVI and MS, summarize the current data, and discuss the role of endovascular therapy and the need for rigorous randomized clinical trials to evaluate this association and treatment.
Drug addiction is a chronic brain disorder leading to complex adaptive changes within the brain reward circuits. Several neurotransmitters, including the endogenous opioid system are involved in these changes. The opioid system plays a pivotal role in different aspects of addiction. Thus, opioid receptors and endogenous opioid peptides are largely distributed in the mesolimbic system and modulate dopaminergic activity within the reward circuits. Opioid receptors and peptides are selectively involved in several components of the addictive processes induced by opioids, cannabinoids, psychostimulants, alcohol and nicotine. This review is focused on the contribution of each component of the endogenous opioid system in the addictive properties of the different drugs of abuse. Copyright 2010 Elsevier Masson SAS. All rights reserved.
... breathing rate nausea, vomiting constipation physical agitation poor decision making abandoning responsibilities slurred speech sleeping more or less than normal mood swings euphoria (feeling high) irritability depression lowered motivation anxiety attacks. Symptoms of opioid overdose An overdose ...
... Updated: 03/10/2016 Medications to Treat OPIOID ADDICTION Methadone Naltrexone Buprenorphine Related SAMHSA Resources Behavioral Health ... Systems Integration Health Disparities Health Financing Health Information Technology HIV, AIDS, and Viral Hepatitis Homelessness and Housing ...
Weeks, William B; Goertz, Christine M
The purpose of this study was to determine whether the per-capita supply of doctors of chiropractic (DCs) or Medicare spending on chiropractic care was associated with opioid use among younger, disabled Medicare beneficiaries. Using 2011 data, at the hospital referral region level, we correlated the per-capita supply of DCs and spending on chiropractic manipulative therapy (CMT) with several measures of per-capita opioid use by younger, disabled Medicare beneficiaries. Per-capita supply of DCs and spending on CMT were strongly inversely correlated with the percentage of younger Medicare beneficiaries who had at least 1, as well as with 6 or more, opioid prescription fills. Neither measure was correlated with mean daily morphine equivalents per opioid user or per chronic opioid user. A higher per-capita supply of DCs and Medicare spending on CMT were inversely associated with younger, disabled Medicare beneficiaries obtaining an opioid prescription. However, neither measure was associated with opioid dosage among patients who obtained opioid prescriptions. Copyright © 2016. Published by Elsevier Inc.
Esquibel, Angela Y; Borkan, Jeffrey
Use of chronic opioid therapy (COT) for chronic noncancer pain has dramatically increased in the United States. Patients seek compassionate care and relief while physicians struggle to manage patients' pain effectively without doing harm. This study explores the narratives of chronic noncancer pain patients receiving chronic opioid therapy and those of their physicians to better understand the effects of COT on the doctor-patient relationship. A mixed method study was conducted that included in-depth interviews and qualitative analysis of 21 paired patients with chronic pain and their physicians in the following groups: patients, physicians, and patient-physician pairs. Findings revealed that patients' narratives focus on suffering from chronic pain, with emphasis on the role of opioid therapy for pain relief, and physicians' narratives describe the challenges of treating patients with chronic pain on COT. Results elucidate the perceptions of ideal vs difficult patients and show that divergent patterns surrounding the consequences, utility, and goals of COT can negatively affect the doctor-patient relationship. The use of paired interviews through a narrative lens in this exploratory study offers a novel and informative approach for clinical practice and research. The findings have significant implications for improving doctor-patient communication and health outcomes by encouraging shared decision making and goal-directed health care encounters for physicians and patients with chronic pain on COT. This study found patterns of understanding pain, opioid pain medications, and the doctor-patient relationship for patients with chronic pain and their physicians using a narrative lens. Thematic findings in this exploratory study, which include a portrayal of collaborative vs conflictual relationships, suggest areas of future intervention and investigation. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Sara, A S; Gottfried, M R
Benign intraductal papilloma is a rare lesion in the male breast. The authors report the occurrence of an intraductal papilloma in a male with more than a ten-year history of phenothiazine therapy (Mellaril and Prolixin). Phenothiazines have been demonstrated to cause elevated serum prolactin levels. The literature regarding the relationship between prolactin and mammary tumors in rodents and in humans remains controversial. The occurrence of this rare male breast tumor in the setting of chronic phenothiazine therapy raises further questions as to the role of prolactin in the development of mammary tumors.
Full Text Available Prescription opioid use is highly associated with risk of opioid-related death, with 1 of every 550 chronic opioid users dying within approximately 2.5 years of their first opioid prescription. Although gabapentin is widely perceived as safe, drug-induced respiratory depression has been described when gabapentin is used alone or in combination with other medications. Because gabapentin and opioids are both commonly prescribed for pain, the likelihood of co-prescription is high. However, no published studies have examined whether concomitant gabapentin therapy is associated with an increased risk of accidental opioid-related death in patients receiving opioids. The objective of this study was to investigate whether co-prescription of opioids and gabapentin is associated with an increased risk of accidental opioid-related mortality.We conducted a population-based nested case-control study among opioid users who were residents of Ontario, Canada, between August 1, 1997, and December 31, 2013, using administrative databases. Cases, defined as opioid users who died of an opioid-related cause, were matched with up to 4 controls who also used opioids on age, sex, year of index date, history of chronic kidney disease, and a disease risk index. After matching, we included 1,256 cases and 4,619 controls. The primary exposure was concomitant gabapentin use in the 120 days preceding the index date. A secondary analysis characterized gabapentin dose as low (<900 mg daily, moderate (900 to 1,799 mg daily, or high (≥1,800 mg daily. A sensitivity analysis examined the effect of concomitant nonsteroidal anti-inflammatory drug (NSAID use in the preceding 120 days. Overall, 12.3% of cases (155 of 1,256 and 6.8% of controls (313 of 4,619 were prescribed gabapentin in the prior 120 days. After multivariable adjustment, co-prescription of opioids and gabapentin was associated with a significantly increased odds of opioid-related death (odds ratio [OR] 1.99, 95% CI
Carpenter, Kenneth M; Jiang, Huiping; Sullivan, Maria A; Bisaga, Adam; Comer, Sandra D; Raby, Wilfrid Noel; Brooks, Adam C; Nunes, Edward V
This study investigated the process of change by modeling transitions among four clinical states encountered in 64 detoxified opiate-dependent individuals treated with daily oral naltrexone: no opiate use, blocked opiate use (i.e., opiate use while adhering to oral naltrexone), unblocked opiate use (i.e., opiate use after having discontinued oral naltrexone), and treatment dropout. The effects of baseline characteristics and two psychosocial interventions of differing intensity, behavioral naltrexone therapy (BNT) and compliance enhancement (CE), on these transitions were studied. Participants using greater quantities of opiates were more likely than other participants to be retained in BNT relative to CE. Markov modeling indicated a transition from abstinence to treatment dropout was approximately 3.56 times greater among participants in CE relative to participants in BNT, indicating the more comprehensive psychosocial intervention kept participants engaged in treatment longer. Transitions to stopping treatment were more likely to occur after unblocked opiate use in both treatments. Continued opiate use while being blocked accounted for a relatively low proportion of transitions to abstinence and may have more deleterious effects later in a treatment episode. (PsycINFO Database Record (c) 2009 APA, all rights reserved).
Harvey, Allison G; Dong, Lu; Bélanger, Lynda; Morin, Charles M
To examine the mediators and the potential of treatment matching to improve outcome for cognitive behavior therapy (CBT) for insomnia. Participants were 188 adults (117 women; Mage = 47.4 years, SD = 12.6) meeting the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; text rev.; DSM-IV-TR; American Psychiatric Association [APA], 2000) diagnostic criteria for chronic insomnia (Mduration: 14.5 years, SD: 12.8). Participants were randomized to behavior therapy (BT; n = 63), cognitive therapy (CT; n = 65), or CBT (n = 60). The outcome measure was the Insomnia Severity Index (ISI). Hypothesized BT mediators were sleep-incompatible behaviors, bedtime variability (BTv), risetime variability (RTv) and time in bed (TIB). Hypothesized CT mediators were worry, unhelpful beliefs, and monitoring for sleep-related threat. The behavioral processes mediated outcome for BT but not CT. The cognitive processes mediated outcome in both BT and CT. The subgroup scoring high on both behavioral and cognitive processes had a marginally significant better outcome if they received CBT relative to BT or CT. The subgroup scoring relatively high on behavioral but low on cognitive processes and received BT or CBT did not differ from those who received CT. The subgroup scoring relatively high on cognitive but low on behavioral processes and received CT or CBT did not differ from those who received BT. The behavioral mediators were specific to BT relative to CT. The cognitive mediators were significant for both BT and CT outcomes. Patients exhibiting high levels of both behavioral and cognitive processes achieve better outcome if they receive CBT relative to BT or CT alone. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Igic, M; Kesic, L; Lekovic, V; Apostolovic, M; Mihailovic, D; Kostadinovic, L; Milasin, J
The purpose of this study was to determine the level of gingival inflammation and the prevalence of periodontopathogenic microorganisms in adolescents with chronic gingivitis, as well as to compare the effectiveness of two approaches in gingivitis treatment-basic therapy alone and basic therapy + adjunctive low-level laser therapy (LLLT). After periodontal evaluation, the content of gingival pockets of 140 adolescents with gingivitis was analyzed by multiplex PCR for the presence of P. gingivalis, A. actinomycetemcomitans, T. forsythensis and P. intermedia. Subsequent to bacteria detection, the examinees were divided into two groups with homogenous clinical and microbiological characteristics. Group A was subjected to basic gingivitis therapy, and group B underwent basic therapy along with adjunctive LLLT. A statistically significant difference between the values of plaque-index (PI) and sulcus bleeding index (SBI) before and after therapy was confirmed in both groups (pgingivitis should be regarded as a sign for dentists to foster more effective oral health programs. LLLT appears to be beneficial as adjuvant to basic therapy.
Sadeghi, Mostafa; Yekta, Reza Atef; Azimaraghi, Omid; Barzin, Gilda; Movafegh, Ali
The primary outcome of this study was to evaluate the effect of adding sufentanil to hyperbaric bupivacaine on duration of sensory blockade of spinal anesthesia in chronic opioid users in comparison with non-addicts. Sixty patients scheduled for orthopedic surgery under spinal anesthesia were allocated into four groups: group 1 (no history of opium use who received intrathecal hyperbaric bupivacaine along with 1mL saline as placebo); group 2 (no history of opium use who received intrathecal bupivacaine along with 1mL sufentanil [5μg]); group 3 (positive history of opium use who received intrathecal bupivacaine along with 1mL saline as placebo) and group 4 (positive history of opium use who received intrathecal bupivacaine along with 1mL sufentanil [5μg]). The onset time and duration of sensory and motor blockade were measured. The duration of sensory blockade in group 3 was 120±23.1min which was significantly less than other groups (G1=148±28.7, G2=144±26.4, G4=139±24.7, p=0.007). The duration of motor blockade in group 3 was 145±30.0min which was significantly less than other groups (G1=164±36.0, G2=174±26.8, G4=174±24.9, p=0.03). Addition of 5μg intrathecal sufentanil to hyperbaric bupivacaine in chronic opioid users lengthened the sensory and motor duration of blockade to be equivalent to blockade measured in non-addicts. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.
Full Text Available The research goal is to determine the clinical and pathogenetic efficacy of Cycloferon liniment in the combined therapy in patients with herpetic stomatitis accompanied by chronic tonsillitis. Materials and methods: Medical examination and treatment of 60 patients have been carried out. The marker of endogenous intoxication, infectious severity and immunity has been investigated. Results. It has been established that use of Cycloferon liniment in the combined therapy in patients with herpetic stomatitis accompanied by chronic tonsillitis has allowed to decrease infectious severity in par-odontal recess and evidence of local inflammation, to normalize immunity indices and reduce the level of endogenous intoxication that has been liable for acceleration of recuperation processes and lowering of frequency of stomatitis recurrences. Conclusion. The clinical efficacy of Cycloferon liniment in the therapy in patients with herpetic stomatitis accompanied by chronic tonsillitis conditioned by the decreasing of activity of local inflammatory process according to the reducing of level pro-inflammatory cytokines, infectious burden of the mouth cavity, endogenous intoxication
Hale, Martin E; Nalamachu, Srinivas R; Khan, Arif; Kutch, Michael
Purpose To describe the efficacy and safety of hydromorphone extended-release tablets (OROS hydromorphone ER) during dose conversion and titration. Patients and methods A total of 459 opioid-tolerant adults with chronic moderate to severe low back pain participated in an open-label, 2- to 4-week conversion/titration phase of a double-blind, placebo-controlled, randomized withdrawal trial, conducted at 70 centers in the United States. Patients were converted to once-daily OROS hydromorphone ER at 75% of the equianalgesic dose of their prior total daily opioid dose (5:1 conversion ratio), and titrated as frequently as every 3 days to a maximum dose of 64 mg/day. The primary outcome measure was change in pain intensity numeric rating scale; additional assessments included the Patient Global Assessment and the Roland–Morris Disability Questionnaire scores. Safety assessments were performed at each visit and consisted of recording and monitoring all adverse events (AEs) and serious AEs. Results Mean (standard deviation) final daily dose of OROS hydromorphone ER was 37.5 (17.8) mg. Mean (standard error of the mean [SEM]) numeric rating scale scores decreased from 6.6 (0.1) at screening to 4.3 (0.1) at the final titration visit (mean [SEM] change, −2.3 [0.1], representing a 34.8% reduction). Mean (SEM) change in Patient Global Assessment was −0.6 (0.1), and mean change (SEM) in the Roland–Morris Disability Questionnaire was −2.8 (0.3). Patients achieving a stable dose showed greater improvement than patients who discontinued during titration for each of these measures (P < 0.001). Almost 80% of patients achieving a stable dose (213/268) had a ≥30% reduction in pain. Commonly reported AEs were constipation (15.4%), nausea (11.9%), somnolence (8.7%), headache (7.8%), and vomiting (6.5%); 13.0% discontinued from the study due to AEs. Conclusion The majority of opioid-tolerant patients with chronic low back pain were successfully converted to effective doses of
Arai, Tsutomu; Kashimoto, Yuji; Ukyo, Yoshifumi; Tominaga, Yushin; Imanaka, Keiichiro
To evaluate the efficacy and safety of fentanyl 1 day patch in opioid-naïve patients with non-cancer chronic pain insufficiently relieved by non-opioid analgesics. Two phase III placebo-controlled, double-blind, group-comparison, randomized withdrawal studies were conducted in patients with osteoarthritis and/or low back pain (N01 study) and post-herpetic neuralgia, complex regional pain syndrome, or chronic postoperative pain (N02) in Japan. Both studies consisted of period I (10-29 days of titration, fentanyl 12.5-50.0 µg/h) and period II (12 weeks double-blind). N01, NCT01008618; N02, NCT01008553 MAIN OUTCOME MEASURES: The primary endpoint was the number of days until study discontinuation due to insufficient pain relief in period II, and secondary endpoints included pain scored on visual analog scale (VAS), subject's overall assessment, the number of rescue dose, brief pain inventory short form score, score on short-form 36-item health survey version 2.0, physician's overall assessment, and assessment of adverse events. Of the 218 (N01) and 258 (N02) subjects who entered period I, 150 and 163 subjects entered period II, respectively. In the N01 study, the between-group difference was significant in the VAS score (95% CI: 7.3 [1.1, 13.5] mm, P = 0.0215) but not in the primary endpoint (P = 0.0846, log-rank test). In the N02 study, both primary efficacy (P = 0.0003) and VAS (8.7 [2.4, 15.0] mm, P = 0.0071) results showed that fentanyl was more effective than placebo. The major adverse events were nervous system and gastrointestinal disorders typically associated with opioid analgesic use. The incidence of adverse events in the fentanyl group was 68.5% to 85.7%. Although the primary efficacy results showed significant effects of fentanyl in the N02 but not the N01 study, overall results showed that fentanyl 1 day patch is effective and well tolerated.
There seems to be a strong cultural expectation among patients for effective pain relief. As a result, physicians often find themselves trying to bridge the gap between the chronic pain patient's expectations and harsh biomedical reality. The typology of Emanuel and Emanuel of four models for the patient-physician relationship is used in this article as a conceptual tool to examine the possible roles of physicians in the context of chronic noncancer pain. Their typology is reconceptualized as a "pathway" along which the physician is able to walk more or less far, starting from the "information" end of the path. The other end of the pathway is "caring deliberation." I then propose that, in pain medicine today, consumerism is a powerful incentive for physicians to stay at the information end of the spectrum. Against this background, I discuss the current opioid epidemic in the United States and the need for what has been called a new medical professionalism. I conclude by challenging educators involved in pain medicine continuing professional development to not only design adequate biomedical-educational programs, but also consider issues like professionalism, personal development, critical self-reflection, and the ethics of engaging in caring deliberation with chronic pain patients.
Staal, J Bart; de Bie, Rob; de Vet, Henrica Cw; Hildebrandt, Jan; Nelemans, Patty
The effectiveness of injection therapy for low-back pain is still debatable. Heterogeneity of target tissue, pharmacological agent and dosage generally found in randomized controlled trials (RCTs) points to the need for clinically valid comparisons in a literature synthesis. To determine if injection therapy is more effective than placebo or other treatments for patients with subacute or chronic low-back pain. We updated the search of the earlier systematic review and searched the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE databases from January 1999 to March 2007 for relevant trials reported in English, French, German, Dutch and Nordic languages. We also screened references from trials identified. RCTs on the effects of injection therapy involving epidural, facet or local sites for subacute or chronic low-back pain were included. Studies which compared the effects of intradiscal injections, prolotherapy or Ozone therapy with other treatments, were excluded unless injection therapy with another pharmaceutical agent (no placebo treatment) was part of one of the treatment arms. Studies about injections in sacroiliac joints and studies evaluating the effects of epidural steroids for radicular pain were also excluded. Two review authors independently assessed the quality of the trials. If study data were clinically and statistically too heterogeneous to perform a meta-analysis, we used a best evidence synthesis to summarize the results. The evidence was classified into five levels (strong, moderate, limited, conflicting or no evidence), taking into account the methodological quality of the studies. 18 trials (1179 participants) were included in this updated review. The injection sites varied from epidural sites and facet joints (i.e. intra-articular injections, peri-articular injections and nerve blocks) to local sites (i.e. tender- and trigger points). The drugs that were studied consisted of corticosteroids, local anesthetics and a variety of
Baxter, Mary Frances; Newman, Robin; Longpré, Sheila M; Polo, Katie M
Improved medical care has resulted in a documented increase in cancer survivors in the United States. Cancer survivors face challenges in participation across all facets of life as a result of the cancer and subsequent cancer treatments. Long-term and late-term sequelae can result in impairments in neurological systems, decreased stamina, loss of range of motion, and changes in sensation and cognition. These impairments are often long lasting, which categorizes cancer survivorship as a chronic condition. This categorization presents treatment challenges, especially in creating rehabilitation and habilitation service options that support cancer survivors. Occupational therapy provides a unique focus that can benefit cancer survivors as they face limitations in participation in all aspects of daily living. Research, advocacy, and education efforts are needed to focus on the specific rehabilitation and habilitation needs of cancer survivors to increase access to occupational therapy's distinct value. Copyright © 2017 by the American Occupational Therapy Association, Inc.
Valenza, Marta; Butelman, Eduardo R; Kreek, Mary Jeanne
The recruitment of the stress circuitry contributes to a shift from positive to negative reinforcement mechanisms sustaining long-term cocaine addiction. The kappa opioid receptor (KOPr) signaling is upregulated by stress and chronic cocaine exposure. While KOPr agonists induce anhedonia and dysphoria, KOPr antagonists display antidepressant and anxiolytic properties. Most of the knowledge on KOPr antagonism is based on drugs with unusual pharmacokinetic and pharmacodynamic properties, complicating interpretation of results. Here we characterized in vivo behavioral and neuroendocrine effects of the novel relatively short-acting KOPr antagonist LY2444296. To date, no study has investigated whether systemic KOPr blockade reduced anxiety-like and depressive-like behaviors in animals previously exposed to chronic extended access cocaine self-administration. We tested the effect of LY2444296 in blocking KOPr-mediated aversive and neuroendocrine effects. Then, we tested acute systemic LY2444296 in reducing anxiety- and depression-like behaviors, as well as releasing the stress hormone corticosterone (CORT), observed after chronic extended access (18 h/day for 14 days) cocaine self-administration. LY2444296 blocked U69,593-induced place aversion and -reduced motor activity as well as U69,593-induced release of serum CORT, confirming its major site of action, without exerting an effect per se. Acute systemic administration of LY2444296 reduced anxiety-like and depressive-like behaviors, as well as CORT release, in rats tested after chronic extended access cocaine self-administration, but not in cocaine-naïve rats. Results suggest that acute blockade of KOPr by a relatively short-acting antagonist produces therapeutic-like effects selectively in rats with a history of chronic extended access cocaine self-administration.
Tasić, J; Milenović, M; Drasković, S; Vukicević, T; Macukanović, L; Kitić, Lj; Bakić, M
Basic principles in the therapy of chronic idiopathic thrombocytopenic purpura are glucocorticoides and splenectomy. Other measures: Intravenous high doses gamma globulin therapy, attenuated androgenes, immunosupresive drugs and plasmaferesis are less effective. During the period of 1989-1992 we treated 34 patients. From 34 patients, 23 were women and 11 were men. We treated patients primarily by prednisolon approximaly for 2 - 4 weeks. Rarely we use doses of 3 mg/kg per day for short periods of time (5 to 10 days) or "pulse therapy" of 500 mg per day. Those doses may be effective in elevating platelet count if the response is poor. If response occurs, high dosages of steroides should be tareped to determine the amount that will maintain the platelet count in the range of 30x10(9)/l to 50x10(9)/l (to minimaze the toxic sade effects of steroides). If steroides are ineffective, we perform splenectomy. From 34 treated patients by glucocorticoides, in 16 we got remission and in 11 partial response. We discussed in detailes relationship duration of treatment with glucocorticoides and level of platelets, and also correlation duration of treatment with prognosis. From 6 splenectomized patients 3 were successful. In two patients we applied intravenous gamma globulin therapy and attenuated androgen successfuly. In one patients therapy with gamma globulin, immunosupresive drugs, androgen and other measures was ineffective. In one patients without splenectomy we administrated successfuly gamma globulin therapy and androgen for peroid of two years.
Michael A. Ueberall
Full Text Available Objective. To describe physicians’ daily life experience with WHO-step III opioids in the treatment of chronic (low back pain (CLBP. Methods. Post hoc analysis of data from a cross-sectional online survey with 4.283 Germany physicians. Results. With a reported median use in 17% of affected patients, WHO-step III opioids play a minor role in treatment of CLBP in daily practice associated with a broad spectrum of positive and negative effects. If prescribed, potent opioids were reported to show clinically relevant effects (such as ≥50% pain relief in approximately 3 of 4 patients (median 72%. Analgesic effects reported are frequently related with adverse events (AEs. Only 20% of patients were reported to remain free of any AE. Most frequently reported AE was constipation (50%, also graded highest for AE-related daily life restrictions (median 46%. Specific AE countermeasures were reported to be necessary in approximately half of patients (median 45%; nevertheless AE-related premature discontinuation rates reported were high (median 22%. Fentanyl/morphine were the most/least prevalently prescribed potent opioids mentioned (median 20 versus 8%. Conclusion. Overall, use of WHO-step III opioids for CLBP is low. AEs, especially constipation, are commonly reported and interfere significantly with analgesic effects in daily practice. Nevertheless, beneficial effects outweigh related AEs in most patients with CLBP.
Kligler, Benjamin; Nielsen, Arya; Kohrherr, Corinne; Schmid, Tracy; Waltermaurer, Eve; Perez, Elidania; Merrell, Woodson
This project was designed to test the feasibility and effectiveness of acupuncture therapy given in a group setting for chronic pain. Nonrandomized, repeated measures quasi-experimental trial. Care was delivered in a primary care clinic waiting area after clinic hours. Included were primary care patients (≥18 years old) with chronic pain of the neck, back, shoulder, or osteoarthritis of any site of at least three months' duration. Subjects received eight weekly acupuncture therapy sessions in a group setting. Acupuncture therapy included a combination of palpation, acupuncture needling, Tui na, Gua sha, and auricular treatment. Baseline pain levels were established in a two- to four-week run-in; assessment of the intervention impact on pain intensity, mood, and functional status were made at the end of the treatment period (eight weeks) and 16 weeks after completion of intervention (24 weeks). Of the total 113 participants recruited for the trial, 96 completed the 24-week protocol. We found a statistically and clinically significant decrease in pain severity, pain interference, and depression in our study population. There were no serious adverse events. Acupuncture therapy offered in the group setting was effective in reducing pain severity, pain interference, and depression in patients with chronic neck, back, or shoulder pain or osteoarthritis. Benefit persisted through the 24-week measure despite no additional treatment. This finding has potentially important implications for improving access to effective acupuncture treatment for patients with limited financial resources. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org
Ramdurg, Santosh; Ambekar, Atul; Lal, Rakesh
People suffering from substance dependence suffer from various sexual dysfunctions and are at risk for indulging in various high-risk sexual behaviors and thus are vulnerable to acquire various infections such as HIV/AIDS and other sexually transmitted infections. The aim of the study was to evaluate the correlation between sexual dysfunction and high-risk sexual behavior in opioid-dependent men receiving buprenorphine and naltrexone maintenance therapy. Semi-structured questionnaire, brief male sexual functioning inventory and HIV-risk taking behavior scale was administered to a sample of 60 sexually active men, receiving buprenorphine (n = 30) and naltrexone (n = 30) maintenance therapy for opioid dependence. The main outcomes are correlation between severity of sexual dysfunction and HIV-risk taking behavior. The study results showed 83% of the men on buprenorphine and 90% on naltrexone reported at least one of the sexual dysfunction symptoms. There was a negative correlation between sexual dysfunction and HIV-risk taking behavior that suggest severe the dysfunction, higher the risk taking behavior. Significant correlation was present with overall sexual dysfunction and HIV-risk taking behavior (P = 0.028 and in naltrexone receiving group premature ejaculation versus HIV-risk taking behavior however, (P = 0.022, P sexual dysfunctions and HIV-risk taking behavior, which has clinical implication. Future research should explore this further using biochemical analyses.
Full Text Available Objective. To investigate the effects of Chinese herbal therapy on chronic tension-type headache. Method. 132 patients with chronic tension-type headache were enrolled in the study. All patients filled in headache questionnaire at baseline phase and 4, 8, and 12 weeks after baseline. As an alternative therapeutic method, the patients were orally administrated Chinese herbal concoction for ten days. Therapeutic effects were evaluated during 12 weeks of followup. Result. In the primary outcome analysis, mean headache scores were significantly lower in the group. Scores fell by 25%–40% during 12 weeks of followup. Patients fared significantly well for most secondary outcome measures. From baseline to 4–12 weeks of followup, the number of days with headache decreased by 6.8–9.5 days. Duration of each attack also significantly (P < 0.05 shortened from 5.3 hours at 4 weeks to 4.9 hours after 8 weeks of followup. Days with medication per four weeks at followup were lower than those at the baseline. The differences were significant (P < 0.05, 0.01 for all end points. Days with medication fell by 56.6% at 12 weeks. Conclusion. The study has provided evidence that Chinese herbal therapy can be clinically useful for the treatment of chronic tension-type headache.
Mlachkova, Antoaneta M; Popova, Christina L
Chronic periodontitis is defined as an inflammatory disease of the supporting tissues of teeth caused by microorganisms in the dental biofilm, resulting in progressive destruction of the periodontal ligament and alveolar bone with pocket formation and gingival recession. Treatment of chronic periodontitis aims at arresting the inflammation and stopping the loss of attachment by removal and control of the supra- and subgingival biofilm and establishing a local environment and microflora compatible with periodontal health. The AIM of this study was to evaluate the effectiveness of non-surgical therapy (scaling and root planning) in the treatment of moderate chronic periodontitis. The study included 30 patients aged between 33 and 75 years, of which 46.7% women and 53.3% men, diagnosed with moderate and, at some sites, severe periodontitis. They were treated with non-surgical periodontal therapy methods (scaling and root planning and curettage if indicated). Additionally, chemical plaque control with rinse water containing chlorhexidine was applied. The diagnostic and reassessment procedures included measuring the periodontal indices of 601 periodontal units before and after the therapy. The indices measured were the papillary bleeding index (PBI), the hygiene index (HI), the probing pocket depth (PPD) and the clinical attachment level (CAL). Significant reduction of plaque and gingival inflammation was found in all treated patients; we also found a statistically significant reduction of periodontal pockets with clinically measured depth 5 mm did not show statistically significant lower incidence rates probably due to the initially small percentage of deep pockets in the patients studied. There was a statistically significant reduction of all sites with attachment loss, the highest significance found at sites where the attachment loss was greater than 5 mm. The results of the study suggest that nonsurgical periodontal therapy is effective in managing the moderate
Full Text Available In chronic hypersensitivity pneumonitis (CHP, lack of improvement or declining lung function may prompt use of immunosuppressive therapy. We hypothesised that use of azathioprine or mycophenolate mofetil with prednisone reduces adverse events and lung function decline, and improves transplant-free survival. Patients with CHP were identified. Demographic features, pulmonary function tests, incidence of treatment-emergent adverse events (TEAEs and transplant-free survival were characterised, compared and analysed between patients stratified by immunosuppressive therapy. A multicentre comparison was performed across four independent tertiary medical centres. Among 131 CHP patients at the University of Chicago medical centre (Chicago, IL, USA, 93 (71% received immunosuppressive therapy, and had worse baseline forced vital capacity (FVC and diffusing capacity, and increased mortality compared with those who did not. Compared to patients treated with prednisone alone, TEAEs were 54% less frequent with azathioprine therapy (p=0.04 and 66% less frequent with mycophenolate mofetil (p=0.002. FVC decline and survival were similar between treatment groups. Analyses of datasets from four external tertiary medical centres confirmed these findings. CHP patients who did not receive immunosuppressive therapy had better survival than those who did. Use of mycophenolate mofetil or azathioprine was associated with a decreased incidence of TEAEs, and no difference in lung function decline or survival when compared with prednisone alone. Early transition to mycophenolate mofetil or azathioprine may be an appropriate therapeutic approach in CHP, but more studies are needed.
Polese, Lino; Marini, Lucia; Rizzato, Roberto; Picardi, Edgardo; Merigliano, Stefano
The purpose of this study is to determine the effectiveness of endoscopic diode laser therapy in patients presenting rectal bleeding due to chronic radiation proctitis (CRP). A retrospective analysis of CRP patients who underwent diode laser therapy in a single institution between 2010 and 2016 was carried out. The patients were treated by non-contact fibers without sedation in an outpatient setting. Fourteen patients (median age 77, range 73-87 years) diagnosed with CRP who had undergone high-dose radiotherapy for prostatic cancer and who presented with rectal bleeding were included. Six required blood transfusions. Antiplatelet (three patients) and anticoagulant (two patients) therapy was not suspended during the treatments. The patients underwent a median of two sessions; overall, a mean of 1684 J of laser energy per session was used. Bleeding was resolved in 10/14 (71%) patients, and other two patients showed improvement (93%). Only one patient, who did not complete the treatment, required blood transfusions after laser therapy; no complications were noted during or after the procedures. Study findings demonstrated that endoscopic non-contact diode laser treatment is safe and effective in CRP patients, even in those receiving antiplatelet and/or anticoagulant therapy.
Bundi, R S; Scott, J S; Halnan, K E [Institute of Radiotherapeutics, Glasgow (UK)
The majority of cases reported in the literature of leukemia following treatment of thyroid disease (thyrotoxicosis and carcinoma) are of acute variety. A description is given of the development of chronic myeloid leukemia in a case of carcinoma of the thyroid treated with radioiodine and megavoltage X-ray therapy. The case history contains details of radioiodine and X-ray doses administered over the years 1961 to 1972 to a male patient, on whom a right hemithyroidectomy was carried out in 1960. The results of blood counts are also recorded for the period up to 1973. The patient died, at 57, in 1974. A total of 860 mCi of /sup 131/I was administered and the first abnormal blood count was noted two months after the last therapeutic dose. Estimates have been made of blood and thyroid doses from /sup 131/I. There has been only one other report in the literature of the development of chronic myeloid leukemia following radioiodine therapy for carcinoma of the thyroid, and although the leukemogenic hazard of /sup 131/I cannot be ruled out for this patient, it is possible that the development of leukemia was coincidental rather than due to the radioiodine therapy.
Fernandes, Ancilla W.; Kern, David M.; Datto, Catherine; Chen, Yen-Wen; McLeskey, Charles; Tunceli, Ozgur
-related costs per patient totaled $4646 (total average plan-paid costs, $4424; total patient-paid costs, $222). Conclusions Patients using opioids with newly diagnosed constipation had significantly greater healthcare utilization and costs than patients without constipation; these costs accounted for approximately 16% of the total healthcare costs per patient during the 12-month study period. Recognition and effective treatment of opioid-induced constipation may decrease healthcare utilization for patients with chronic noncancer pain and may reduce the economic burden of pain therapy. PMID:27606040
Abdullah Sulieman Terkawi
Conclusion: Our study highlighted the high burden of chronic pain after therapy for major head and neck tumors. We identified demographic and clinical factors that are associated with the presence of chronic pain. Further studies are required to better understand the risk factors to implement strategies to prevent, alleviate, and treat chronic pain associated with major head and neck tumor therapies.
Furlan, Andrea D; Reardon, Rhoda; Salach, Lena
The Opioid Manager is designed to be used as a point-of-care tool for providers prescribing opioids for chronic noncancer pain. It condenses the key elements from the Canadian Opioid Guideline and can be used as a chart insert. The Opioid Manager has been validated and is available for download from the Guideline's Web site http://nationalpaincentre.mcmaster.ca/opioidmanager/. The Opioid Manager is divided into the following four parts: A) before you write the first script, B) initiation trial, C) maintenance and monitoring, and D) when is it time to decrease the dose or stop the opioid completely? The Opioid Manager has been downloaded by 1,432 users: 47 percent family physicians, 18 percent pharmacists, 13 percent other physicians, and 22 percent miscellaneous. To show how to use the Opioid Manager, the authors created a 10-minute video that is available on the Internet. The Opioid Manager is being translated to French, Spanish, Portuguese, and Farsi.
Although chronic myeloid leukemia (CML) was probably first described in the early nineteenth century, there was little progress in understanding its biology until the discovery of the Philadelphia (Ph) chromosome in 1960. Subsequent important landmarks were the recognition that the Ph chromosome results from a t(9;22) translocation and subsequently of BCR-ABL fusion gene. Between 1980 and 2000, allo grafting, despite the risks of morbidity and mortality, was the recommended initial treatment for younger patients with HLA-matched donors. Therapy has now been „revolutionized“ by the introduction on imatinib mesylate (IM), the original Abl tyrosine kinase inhibitor (TKI) which was used first in the clinic in 1998. This paper will attempt to define approaches to management of the newly diagnosed patient with CML in chronic phase that are favored in 2012, but it is most probable these recommendations will need to be updated as further experience in gained with the use of TKI. (author)
Full Text Available Nutrition is an important health element for elderly people and influence aging process. Malnutrition prevalence is increasing in this population. Chronic Obstructive Pulmonary Disease (COPD is one of the chronic diseases in elderly that is related to malnutrition. The association between malnutrition and pulmonary disease (including COPD has been known for a long time. Malnutrition has negative impacts on pulmonary structure, elasticity, and function, strength and endurance of respiratory muscles, pulmonary immunity defense mechanism, and breath control. Inversely, pulmonary disease (including COPD will increase energy need and may reduce dietary intake. Nutrition intervention in COPD patient is intended for regulating anorexia, improving pulmonary function, and controlling weight loss. Nutrient requirements will be calculated according to the results of nutrition assessment. This article will discuss about nutrition therapy in elderly with COPD. It describes respiratory system in aging, association COPD and nutrition, and nutrition assessment, as well as nutrition intervention in elderly people with COPD.
Full Text Available Christopher A Latz,1 Kellie R Brown,2 Ruth L Bush11Texas A&M Health Science Center College of Medicine, Bryan, TX, USA; 2Medical College of Wisconsin, Milwaukee, WI, USAAbstract: Compression therapy has been the mainstay for the treatment of lower extremity edema, venous insufficiency, and particularly, venous ulcerative disease. Though modern surgical treatments exist, none are completely effective without good compressive options to allow for decreased swelling and better oxygenation of damaged tissues. This review article will describe the pathophysiology and presentation of lower extremity venous ulcerations, as well as current options for compression therapy. The benefits, along with the major pitfall of nonadherence, will also be discussed.Keywords: venous disease, chronic venous insufficiency, venous ulceration
Full Text Available Background/Aim. Virological testing is considered to be essential in the management of hepatitis C virus (HCV infection in order to diagnose infection, and, most importantly, as a quide for treatment decisions and assess the virological response to antiviral therapy. The aim of this study was to determine the rate of a sustained virological response (SVR and various factors associated with response rates in chronic hepatitis C infected patients treated with pegiinterferon alpha (PEGINF and ribavirin (RBV combination therapy. Methods. A total of 34 patients, treated with PEG-IFN and RBV were studied. Serum HCV-RNA was measured before the treatment, 12 weeks following the start of the therapy and 6 weeks after the treatment cessation. SVR was defined as undetectable serum HCV-RNA 6 months of post-treatment follow-up, virologic relapse (VR as relapse of HCV-RNA during the post-treatment follow-up. Serum HCV-RNA was measured with the Cobas Amplicor test. Results. At the end of post-treatment follow-up 19 (55.8% patients demonstrated a SVR. The majority of the patients were genotype 1 (27, and the other were genotype 3 (5 patients and genotype 4 (2 patients. There was VR in 6 patients 6 months after the therapy. In 9 patients HCV-RNA was positive after 12 weeks. Conclusion. We demonstrated that patients with chronic HCV infection can be successfully treated with combination of PEG-INF and RBV. This result emphasizes also that post-treatment follow-up to identify patients with SVR or VR could be important.
In this issue of the Hastings Center Report, Joshua Rager and Peter Schwartz suggest using opioid treatment agreements as public health monitoring tools to inform patients about "the requirements entailed by undergoing opioid therapy," rather than as contractual agreements to alter patients' individual behavior or to benefit them directly. Because Rager and Schwartz's argument presents suspected OTA violations as a justification to stop providing opioids yet does not highlight the broader epistemic and systemic context within which clinicians prescribe these medications, their proposal may perpetuate a climate of distrust and stigmatization without correcting systemic factors that may have placed patients and others at risk in the first place. Given the context of epistemic uncertainty regarding opioid safety and efficacy, insufficient training for opioid prescribers, and inadequate patient education, I propose replacing OTAs, which have a narrow focus on patient behaviors, with opioid treatment plans, which would promote mutual, collaborative, and shared decision-making on the most appropriate pain management program. An OTP can be ethically justified as a tool to prevent and treat iatrogenic addiction under a specific paradigm-one that adopts a default position of professional epistemic humility and holds all collaborative parties accountable in chronic pain management. © 2017 The Hastings Center.
Full Text Available The article grounds the application of the spasmolytic therapy in complex treatment of chronic constipations among children by the example of hyoscine butylbromide (buscopan, boehringer ingelheim pharma, germany. favourable impact of the medication on the motoraevacuation function of the large intestine has been proved both clinically and by means of functional and ultrasonic methods of the large intestine examination. Good tolerance of the medication allows for its application in pediatric practice.Key words: children, chronic constipation, diagnostics, treatment, hyoscine butylbromide.
Hirchak, Katherine A.; Murphy, Sean M.
Background Opioid misuse is a large public health problem in the United States. Residents of rural areas and American Indian (AI) reservation/trust lands represent traditionally underserved populations with regard to substance-use-disorder therapy. Purpose Assess differences in the number of opioid agonist therapy (OAT) facilities and physicians with Drug Addiction Treatment Act (DATA) waivers for rural versus urban, and AI reservation/trust land versus non-AI reservation/trust land areas in Washington State. Methods The unit of analysis was the zip code. The dependent variables were the number of OAT facilities and DATA-waivered physicians in a region per 10,000 residents aged 18–64 in a zip code. A region was defined as a zip code and its contiguous zip codes. The independent variables were binary measures of whether a zip code was classified as rural versus urban, or AI reservation/trust land versus non-AI reservation/trust land. Zero-inflated negative binomial regressions with robust standard errors were estimated. Results The number of OAT clinics in a region per 10,000 zip-code residents was significantly lower in rural versus urban areas (P = .002). This did not differ significantly between AI reservation/trust land and non-AI reservation/trust land areas (P = .79). DATA-waivered physicians in a region per 10,000 zip-code residents was not significantly different between rural and urban (P = .08), or AI reservation/trust land versus non-AI reservation/trust land areas (P = .21). Conclusions It appears that the potential for Washington State residents of rural and AI reservation areas to receive OAT is similar to that of residents outside of those areas; however, difficulties in accessing therapy may remain, highlighting the importance of expanding health care insurance and providing support for DATA-waivered physicians. PMID:26987797
M. T. Baedilova
Full Text Available The study included 84 children aged 12—16 years with chronic fatigue syndrome in the presence of mitral valve prolapse (MVP, who were treated with L-carnitine (Elcar 30% and Coenzyme Q10 (Kudevita. L-carnitine is involved in metabolic processes as a carrier of long-chain fatty acids from the cytoplasm to the mitochondria to produce ATP and acetyl-CoA. Coenzyme Q10 stimulates tissue respiration (aerobic processes and participates in electron transfer in the mitochondrial electron transport chain. The clinical efficacy of energy-rich drugs was investigated before and after their treatment. The therapy was based on the data of an investigation by M. Trivellato et al. on carnitine deficiency and on those of our trials: the children with MVP were observed to have a significant increase in malondialdehyde levels and conjugated diene oxidation indices, which underlie mitochondrial insufficiency. The investigation indicated that prior to their treatment 100% of the children had been observed to have fatigue after exercise, as well as headache, memory and attention focusing impairments, and idiopathic hypersomnia, 34% of the patients complained of palpitation, and 43% had stabbing cardialgia. Three months later, the children who had received combined energy-rich therapy were noted to have a pronounced positive effect: 82% of them had no clinical symptoms of chronic fatigue.
Hirakawa, Koichi; Abe, Koichiro; Ayabe, Yoshiharu; Nishimura, Masao [Ageo Central General Hospital, Saitama (Japan)
Amiodarone is an amphiphilic, iodinated, benzofuran derivative that is known to be effective for refractory ventricular tachyarrhythmia. Amiodarone also is known to cause a variety of side effects, related to its accumulation in multiple organs. The deposition of amiodarone and its metabolite, desethylamiodarone (DA), in liver elevates liver function tests and increases liver attenuation on computed tomography (CT). Although several groups have reported increased liver attenuation in patients receiving chronic amiodarone therapy, there is still no clear statistically significant relationship between liver CT attenuation and the cumulative dose of amiodarone, or between plasma levels of amiodarone and DA. CT scans were originally performed for the evaluation of pulmonary fibrosis in 13 patients (7 men and 6 women; mean age, 69.9 years, range 35 to 86 years) receiving chronic amiodarone therapy. Liver CT attenuation tended to increase in these patients. We found no significant correlation between liver CT attenuation and the cumulative dose of amiodarone. However, the CT attenuation of the liver was correlated significantly with the plasma level of amiodarone and DA. It was also suggested that liver CT scan is a useful means of evaluating the plasma levels of amiodarone and DA, and for estimating their deposition in liver. (author)
Hirakawa, Koichi; Abe, Koichiro; Ayabe, Yoshiharu; Nishimura, Masao
Amiodarone is an amphiphilic, iodinated, benzofuran derivative that is known to be effective for refractory ventricular tachyarrhythmia. Amiodarone also is known to cause a variety of side effects, related to its accumulation in multiple organs. The deposition of amiodarone and its metabolite, desethylamiodarone (DA), in liver elevates liver function tests and increases liver attenuation on computed tomography (CT). Although several groups have reported increased liver attenuation in patients receiving chronic amiodarone therapy, there is still no clear statistically significant relationship between liver CT attenuation and the cumulative dose of amiodarone, or between plasma levels of amiodarone and DA. CT scans were originally performed for the evaluation of pulmonary fibrosis in 13 patients (7 men and 6 women; mean age, 69.9 years, range 35 to 86 years) receiving chronic amiodarone therapy. Liver CT attenuation tended to increase in these patients. We found no significant correlation between liver CT attenuation and the cumulative dose of amiodarone. However, the CT attenuation of the liver was correlated significantly with the plasma level of amiodarone and DA. It was also suggested that liver CT scan is a useful means of evaluating the plasma levels of amiodarone and DA, and for estimating their deposition in liver. (author)
therapy (52.2 ± 4.9%, massage (50.8 ± 4.8%, chiropractic manipulation (69.1 ± 10.4% and acupuncture treatment (50 ± 11.6%. All patients used NSAIDs, with the average duration of therapy 24.2 ± 11.9 months, and the average effectiveness 61.6 ± 2.8%. These patients used compounding topical creams for 7.5 ± 2.3 months on average with effectiveness of 41.1 ± 3.5%. None of the patients used opioids. Majority of them - 72.8% never missed any day of work while 8.6% missed 10-30 days, and only 4.3% missed more than 30 days of work even though 79.6% patients had an active type of job (walking, bending, heavy lifting, etc. Discussion: Administration of opioids, epidural steroid injection, facet joint block in the treatment of chronic low back pain became extremly frequent in the USA in the last 15 years. Multimodal therapy approach of back pain is the main characteristic of the treatment strategies in the USA. Opposite to the USA, European strategy concern non-invasive, non-pharmacologic and pharmacologic approaches. Conclusion: Results of this study showed higher utilization of pharmacologic and non-pharmacological therapies in patients with chronic low back pain prior to opioids and interventional procedures than in the USA.
Dennis, Brittany B; Roshanov, Pavel S; Bawor, Monica; Paul, James; Varenbut, Michael; Daiter, Jeff; Plater, Carolyn; Pare, Guillame; Marsh, David C; Worster, Andrew; Desai, Dipika; Thabane, Lehana; Samaan, Zainab
Chronic pain is implicated as a risk factor for illicit opioid use among patients with opioid addiction treated with methadone. However, there exists conflicting evidence that supports and refutes this claim. These discrepancies may stem from the large variability in pain measurement reported across studies. We aim to determine the clinical and demographic characteristics of patients reporting pain and evaluate the prognostic value of different pain classification measures in a sample of opioid addiction patients. Multi-center prospective cohort study. Methadone maintenance treatment facilities for managing patients with opioid addiction. This study includes participants from the Genetics of Opioid Addiction (GENOA) prospective cohort study. We assessed the prognostic value of different pain measures for predicting opioid relapse. Pain measures include the Brief Pain Inventory (BPI) and patients' response to a direct pain question all study participants were asked from the GENOA case report form (CRF) "are you currently experiencing or have been diagnosed with chronic pain?" Performance characteristics of the GENOA CRF pain measure was estimated with sensitivity and specificity using the BPI as the gold standard reference. Prognostic value was assessed using pain classification as the primary independent variable in an adjusted analysis using 1) the percentage of positive opioid urine screens and 2) high-risk opioid use (= 50% positive opioid urine screens) as the dependent variables in a linear and logistic regression analyses, respectively. Among participants eligible for inclusion (n = 444) the BPI was found to be highly sensitive, classifying a large number of GENOA participants with pain (n = 281 of the 297 classified with pain, 94.6%) in comparison to the GENOA CRF (n = 154 of 297 classified with pain, 51.8%). Participants concordantly classified as having pain according to the GENOA CRF and BPI were found to have an estimated 7.79% increase in positive
Full Text Available Hitomi Sano,1 Sachio Kouraba,2 Rei Ogawa11Department of Plastic, Reconstructive, and Aesthetic Surgery, Nippon Medical School, Tokyo, Japan; 2Sapporo Wound Care and Anti-Aging Laboratory, Sapporo, JapanAbstract: Chronic leg ulcers are a significant health care concern. Although deep wounds are usually treated by flap transfers, the operation is invasive and associates with serious complications. Skin grafts may be a less invasive means of covering wounds. However, skin grafts cannot survive on deep defects unless high-quality granulation tissue can first be generated in the defects. Technologies that generate high-quality granulation tissue are needed. One possibility is to use wound care matrices, which are bioengineered skin and soft tissue substitutes. Because they all support the healing process by providing a premade extracellular matrix material, these matrices can be termed “extracellular matrix replacement therapies”. The matrix promotes wound healing by acting as a scaffold for regeneration, attracting host cytokines to the wound, stimulating wound epithelialization and angiogenesis, and providing the wound bed with bioactive components. This therapy has lasting benefits as it not only helps large skin defects to be closed with thin skin grafts or patch grafts but also restores cosmetic appearance and proper function. In particular, since it acts as a layer that slides over the subcutaneous fascia, it provides skin elasticity, tear resistance, and texture. Several therapies and products employing wound care matrices for wound management have been developed recently. Some of these can be applied in combination with negative pressure wound therapy or beneficial materials that promote wound healing and can be incorporated into the matrix. To date, the clinical studies on these approaches suggest that wound care matrices promote spontaneous wound healing or can be used to facilitate skin grafting, thereby avoiding the need to use
Fisher, Deborah; Grap, Mary Jo; Younger, Janet B; Ameringer, Suzanne; Elswick, R K
The purpose of this study was to, in a pediatric population, describe the frequency of opioid withdrawal signs and symptoms and to identify factors associated with these opioid withdrawal signs and symptoms. Opioids are used routinely in the pediatric intensive care population for analgesia, sedation, blunting of physiologic responses to stress, and safety. In children, physical dependence may occur in as little as 2-3 days of continuous opioid therapy. Once the child no longer needs the opioid, the medications are reduced over time. A prospective, descriptive study was conducted. The sample of 26 was drawn from all patients, ages 2 weeks to 21 years admitted to the Children's Hospital of Richmond pediatric intensive care unit (PICU) and who have received continuous infusion or scheduled opioids for at least 5 days. Data collected included: opioid withdrawal score (WAT-1), opioid taper rate (total dose of opioid per day in morphine equivalents per kilogram [MEK]), pretaper peak MEK, pretaper cumulative MEK, number of days of opioid exposure prior to taper, and age. Out of 26 enrolled participants, only 9 (45%) had opioid withdrawal on any given day. In addition, there was limited variability in WAT-1 scores. The most common symptoms notes were diarrhea, vomit, sweat, and fever. For optimal opioid withdrawal assessments, clinicians should use a validated instrument such as the WAT-1 to measure for signs and symptoms of opioid withdrawal. Further research is indicated to examine risk factors for opioid withdrawal in children. Copyright © 2013 Elsevier Inc. All rights reserved.
Randesi, Matthew; van den Brink, Wim; Levran, Orna; Blanken, Peter; Butelman, Eduardo R; Yuferov, Vadim; da Rosa, Joel Correa; Ott, Jurg; van Ree, Jan M; Kreek, Mary Jeanne
BACKGROUND: Heroin addiction is a chronic, relapsing brain disease. Genetic factors are involved in the development of drug addiction. The aim of this study was to determine whether specific variants in genes of the opioid system are associated with non-dependent opioid use and heroin dependence.
Randesi, Matthew; van den Brink, Wim; Levran, Orna; Blanken, Peter; Butelman, Eduardo R.; Yuferov, Vadim; da Rosa, Joel Correa; Ott, Jurg; van Ree, Jan M.; Kreek, Mary Jeanne
Heroin addiction is a chronic, relapsing brain disease. Genetic factors are involved in the development of drug addiction. The aim of this study was to determine whether specific variants in genes of the opioid system are associated with non-dependent opioid use and heroin dependence. Genetic
Full Text Available Severe forms of chronic kidney disease can lead to a critical, end-stage condition, requiring renal replacement therapy, which may involve a form of dialysis or renal transplantation. Identification and characterization of novel markers and/or targets of therapy that could be applied in these critically ill patients remains the focus of the current research in the field of critical care medicine and has been the objective of our studies for some years past. To this end, we used models of renal vascular disease, Ang II, L-NAME or mice overexpressing renin, treated with AT1 antagonists at different stages of progression, to create cohorts of animals during progression, reversal or escape from therapy. Transcriptomic analysis and comparisons were performed and genes were selected according to the following criteria: a not previously described in the kidney, b highly upregulated during progression and returning to the normal levels during reversal, and c producing proteins that are either circulating or membrane receptors.
Heiskanen, Tarja; Langel, Kaarina; Gunnar, Teemu; Lillsunde, Pirjo; Kalso, Eija A
Measuring opioid concentrations in pain treatment is warranted in situations where optimal opioid analgesia is difficult to reach. To assess the usefulness of oral fluid (OFL) as an alternative to plasma in opioid concentration monitoring in cancer patients on chronic opioid therapy. We collected OFL and plasma samples from 64 cancer patients on controlled-release (CR) oral morphine, CR oral oxycodone, or transdermal (TD) fentanyl for pain. Samples were obtained on up to five separate days. A total of 213 OFL and plasma samples were evaluable. All patients had detectable amounts of the CR or TD opioid in both plasma and OFL samples. The plasma concentrations of oxycodone and fentanyl (determination coefficient R(2) = 0.628 and 0.700, respectively), but not morphine (R(2) = 0.292), were moderately well correlated to the daily opioid doses. In contrast to morphine and fentanyl (mean OFL/plasma ratio 2.0 and 3.0, respectively), the OFL oxycodone concentrations were significantly higher than the respective plasma concentrations (mean OFL/plasma ratio 14.9). An active transporter could explain the much higher OFL vs. plasma concentrations of oxycodone compared with morphine and fentanyl. OFL analysis is well suited for detecting the studied opioids. For morphine and fentanyl, an approximation of the plasma opioid concentrations is obtainable, whereas for oxycodone, the OFL/plasma concentration relationship is too variable for reliable approximation results. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.
Jamie H. Rose
Full Text Available The development of pharmacotherapeutics that reduce relapse to alcohol drinking in patients with alcohol dependence is of considerable research interest. Preclinical data support a role for nucleus accumbens (NAc κ opioid receptors (KOR in chronic intermittent ethanol (CIE exposure-induced increases in ethanol intake. Nalmefene, a high-affinity KOR partial agonist, reduces drinking in at-risk patients and relapse drinking in rodents, potentially due to its effects on NAc KORs. However, the effects of nalmefene on accumbal dopamine transmission and KOR function are poorly understood. We investigated the effects of nalmefene on dopamine transmission and KORs using fast scan cyclic voltammetry in NAc brain slices from male C57BL/6J mice following five weeks of CIE or air exposure. Nalmefene concentration-dependently reduced dopamine release similarly in air and CIE groups, suggesting that dynorphin tone may not be present in brain slices. Further, nalmefene attenuated dopamine uptake rates to a greater extent in brain slices from CIE-exposed mice, suggesting that dopamine transporter-KOR interactions may be fundamentally altered following CIE. Additionally, nalmefene reversed the dopamine-decreasing effects of a maximal concentration of a KOR agonist selectively in brain slices of CIE-exposed mice. It is possible that nalmefene may attenuate withdrawal-induced increases in ethanol consumption by modulation of dopamine transmission through KORs.
Rose, Jamie H.; Karkhanis, Anushree N.; Steiniger-Brach, Björn; Jones, Sara R.
The development of pharmacotherapeutics that reduce relapse to alcohol drinking in patients with alcohol dependence is of considerable research interest. Preclinical data support a role for nucleus accumbens (NAc) κ opioid receptors (KOR) in chronic intermittent ethanol (CIE) exposure-induced increases in ethanol intake. Nalmefene, a high-affinity KOR partial agonist, reduces drinking in at-risk patients and relapse drinking in rodents, potentially due to its effects on NAc KORs. However, the effects of nalmefene on accumbal dopamine transmission and KOR function are poorly understood. We investigated the effects of nalmefene on dopamine transmission and KORs using fast scan cyclic voltammetry in NAc brain slices from male C57BL/6J mice following five weeks of CIE or air exposure. Nalmefene concentration-dependently reduced dopamine release similarly in air and CIE groups, suggesting that dynorphin tone may not be present in brain slices. Further, nalmefene attenuated dopamine uptake rates to a greater extent in brain slices from CIE-exposed mice, suggesting that dopamine transporter-KOR interactions may be fundamentally altered following CIE. Additionally, nalmefene reversed the dopamine-decreasing effects of a maximal concentration of a KOR agonist selectively in brain slices of CIE-exposed mice. It is possible that nalmefene may attenuate withdrawal-induced increases in ethanol consumption by modulation of dopamine transmission through KORs. PMID:27472317
Full Text Available Introduction: People suffering from substance dependence suffer from various sexual dysfunctions and are at risk for indulging in various high-risk sexual behaviors and thus are vulnerable to acquire various infections such as HIV/AIDS and other sexually transmitted infections. AIM: The aim of the study was to evaluate the correlation between sexual dysfunction and high-risk sexual behavior in opioid-dependent men receiving buprenorphine and naltrexone maintenance therapy. Materials and Methods: Semi-structured questionnaire, brief male sexual functioning inventory and HIV-risk taking behavior scale was administered to a sample of 60 sexually active men, receiving buprenorphine (n = 30 and naltrexone (n = 30 maintenance therapy for opioid dependence. Results: The main outcomes are correlation between severity of sexual dysfunction and HIV-risk taking behavior. The study results showed 83% of the men on buprenorphine and 90% on naltrexone reported at least one of the sexual dysfunction symptoms. There was a negative correlation between sexual dysfunction and HIV-risk taking behavior that suggest severe the dysfunction, higher the risk taking behavior. Significant correlation was present with overall sexual dysfunction and HIV-risk taking behavior (P = 0.028 and in naltrexone receiving group premature ejaculation versus HIV-risk taking behavior however, (P = 0.022, P < 0.05 there were no significant differences among both the groups except above findings. Conclusion: Conclusion was treatment is associated with sexual dysfunctions and HIV-risk taking behavior, which has clinical implication. Future research should explore this further using biochemical analyses.
Zharov, Vladimir P.
According to the world statistics, from 30 to 60 percent of elderly male population suffer from chronic prostatitis in different countries. This disease has a number of consequences such as urino-genital inflammation, dysuria, perineal pain, reduction in the physiological activity of smooth muscles, blockage of the anus passages with micro-organism vital activity products, appearance of stagnant zones and low blood circulation complicated by disorders of the sexual function. Most of these features make it difficult to use standard drug therapies with antibiotics or immunocorrectors. For that reason, the objective of this study is to develop and to investigate a novel combined electrolaser therapy which improves drug delivery in the prostate gland and simultaneously provides an independent physiotherapeutic effect. The main feature of this therapy is the utilization of two diode lasers emitting in the red (0.67 micrometer, 10 mW) and in the infrared (0.85 micrometer, 1 W) spectrum ranges in combination with transurethral electrostimulation. An electrolaser catheter containing both hollow cylindrical electrodes and an axial optical fiber to deliver laser radiation was brought along the urethra to the seminal vesicles. The red laser in combination with a photosensitizer ('Photosens,' Russia) was used to realize the antibacterial treatment of the urethra. The infrared laser was employed to heat the prostate gland and to stimulate the blood perfusion without thermal damage of tissues. The laser heating of the prostate at a local tissue temperature of 41 degrees Celsius in combination with the electrostimulation provided approximately a 4.5-fold increase in the blood flow. The realization of an additional mode of photovacuum therapy inside the urethra together with the electrostimulation made it possible to 'clean' the anus passages and to improve the DNA diagnosis reliability in respect of the urogenital infectious remainder. The clinical data obtained in 980 patients
ElMouedden, M.; Meert, T.F.
Chronic pain resulting from metastasis into skeleton of certain neoplastic diseases remains poorly understood and relatively resistant to analgesic treatment. Opioids are the principal axis in drug therapy for this type of pain, especially at the end stage of cancer. Our aim was to examine whether,
Anderson, Rachel I; Lopez, Marcelo F; Becker, Howard C
Our laboratory has previously demonstrated that daily forced swim stress (FSS) prior to ethanol drinking sessions facilitates enhanced ethanol consumption in mice with a history of chronic intermittent ethanol (CIE) vapor exposure without altering ethanol intake in air-exposed controls. Because both stress and chronic ethanol exposure have been shown to activate the dynorphin/kappa opioid receptor (KOR) system, the present study was designed to explore a potential role for KORs in modulating stress effects on ethanol consumption in the CIE model of dependence and relapse drinking. After stable baseline ethanol intake was established in adult male C57BL/6J mice, subjects received chronic intermittent exposure (16 h/day × 4 days/week) to ethanol vapor (CIE group) or air (CTL group). Weekly cycles of inhalation exposure were alternated with 5-day limited access drinking tests (1 h access to 15% ethanol). Experiment 1 compared effects of daily FSS and KOR activation on ethanol consumption. CIE and CTL mice were either exposed to FSS (10 min), the KOR agonist U50,488 (5 mg/kg), or a vehicle injection (non-stressed condition) prior to each daily drinking session during test weeks. FSS selectively increased drinking in CIE mice. U50,488 mimicked this effect in CIE mice, but also increased drinking in CTL mice. Experiment 2 assessed effects of KOR blockade on stress-induced drinking in CIE and CTL mice. Stressed and non-stressed mice were administered the short-acting KOR antagonist LY2444296 (0 or 5 mg/kg) 30 min prior to each drinking session during test weeks. FSS selectively increased ethanol consumption in CIE mice, an effect that was abolished by LY2444296 pretreatment. In Experiment 3, CIE and CTL mice were administered one of four doses of U50,488 (0, 1.25, 2.5, 5.0 mg/kg) 1 h prior to each daily drinking test (in lieu of FSS). All doses of U50,488 increased ethanol consumption in both CIE and CTL mice. The U50,488-induced increase in drinking was blocked by LY
Rachel Ivy Anderson
Full Text Available Our laboratory has previously demonstrated that daily forced swim stress (FSS prior to ethanol drinking sessions facilitates enhanced ethanol consumption in mice with a history of chronic intermittent ethanol (CIE vapor exposure without altering ethanol intake in air-exposed controls. Because both stress and chronic ethanol exposure have been shown to activate the dynorphin/kappa opioid receptor (KOR system, the present study was designed to explore a potential role for KORs in modulating stress effects on ethanol consumption in the CIE model of dependence and relapse drinking. After stable baseline ethanol intake was established in adult male C57BL/6J mice, subjects received chronic intermittent exposure (16 hr/day x 4 days/week to ethanol vapor (CIE group or air (CTL group. Weekly cycles of inhalation exposure were alternated with 5-day limited access drinking tests (1 hour access to 15% ethanol. Experiment 1 compared effects of daily FSS and KOR activation on ethanol consumption. CIE and CTL mice were either exposed to FSS (10 min, the KOR agonist U50,488 (5 mg/kg, or a vehicle injection (non-stressed condition prior to each daily drinking session during test weeks. FSS selectively increased drinking in CIE mice. U50,488 mimicked this effect in CIE mice, but also increased drinking in CTL mice. Experiment 2 assessed effects of KOR blockade on stress-induced drinking in CIE and CTL mice. Stressed and non-stressed mice were administered the short-acting KOR antagonist LY2444296 (0 or 5 mg/kg 30 min prior to each drinking session during test weeks. FSS selectively increased ethanol consumption in CIE mice, an effect that was abolished by LY2444296 pretreatment. In Experiment 3, CIE and CTL mice were administered one of four doses of U50,488 (0,1.25, 2.5, 5.0 mg/kg one hour prior to each daily drinking test (in lieu of FSS. All doses of U50,488 increased ethanol consumption in both CIE and CTL mice. The U50,488-induced increase in drinking was
Full Text Available Background: The aim of periodontal treatment is to provide healthy and functional dentition for the whole life.Cases Report: A 42 year old female with sever chronic periodontitis, treated medically and surgically, is reported. She initially received antibiotic, Scaling and root planning in addition to oral hygiene instruction. After four weeks, periodontal Surgery, root canal Therapy, extraction of excess tooth and restoration of some teeth were performed, because of remaining residual pockets, and bone loss, flap Surgery and Access flap, with papilla preservation flap method, also modified Widmann flap, were done. After one month, favorable clinical improvement was obtained.Conclusion: It can be concluded that high oral hygiene level in accompanied with Suitable medical and surgical treatment, enhanced the success of periodontal treatment outcomes even in sever disease.
Hussain, S.; Kayani, A.M.; Munir, R.
Objective: Systolic heart failure is a chronic condition with significant morbidity and mortality. Evidence based optimal medical therapy (OMT) has been shown to reduce mortality. Underuse of OMT due to multiple reasons has been a consistent problem. The study objective was to audit the use of OMT in patients with heart Failure. Study Design: Descriptive study. Place and Duration of study: This audit was carried out in AFIC-NIHD from April 2011- February 2012. Material and Methods: Seventy consecutive stage D heart failure patients were included in the study. The patients were assessed clinically by a cardiologist and all previous documentations, referral letters, prescriptions, and purchase receipts were reviewed. To identify any other medication patients might have been taking (which did not appear on the prescriptions) patients were asked to identify common medicine packs. The patients underwent a detailed clinical evaluation including history, physical examination. Relevant investigations were done. ACCF/AHA (American College of Cardiology Foundation / American Heart Association) and ESC (European Society of Cardiology) guidelines for the diagnosis and treatment of acute and chronic heart failure were taken as standard of care. Results: In our audit we found that a large proportion of patients who were at high risk as per the Seattle Heart Failure Model (SHFM) were not on OMT, only 4.3% of the patients were on beta blockers that have been shown to improve mortality in the large randomized clinical trials, 64.3% were not taking any beta blockers where as 55.7% were not on ACE inhibitors and adding the OMT greatly reduced their mortality risk. Conclusions: We concluded that a large proportion of patients were not on OMT despite not having any contraindication to such therapy. This deprives them of significant survival benefit. (author)
Schranz, Dietmar; Voelkel, Norbert F
Major advances in chronic heart failure (cHF) therapy have been achieved and documented in adult patients, while research regarding the mechanisms and therapy of cHF in children has lagged behind. Based on receptor physiological studies and pharmacological knowledge, treatment with specific ß1-adrenergic receptor blocker (ARB), tissue angiotensin-converting enzyme inhibitor (ACE-I), and mineralocorticoid antagonists have to be recommended in children despite lack of sufficient data derived from prospective randomized studies. At our institution, bisoprolol, lisinopril, and spironolactone have been firmly established to treat systolic cHF, hypoplastic left heart syndrome (HLHS) following hybrid approach and congenital left-right shunt diseases, latest in patients where surgery has to be delayed. Chronic therapy with long-acting diuretics and fluid restriction are not advocated because short-term effects are achieved at the expense of further neuro-humoral stimulation. It remains unclear why diuretics are recommended although evidence-based studies, documenting long-term benefit, are missing. However, that is true for all currently used drugs for pediatric cHF. This review focuses on the prevailing "nihilism" of cHF therapy in children with the goal to encourage physicians to treat pediatric cHF with a rationally designed therapy, which combines available agents that have been shown to improve survival in adult patients with cHF. Because of the lack of clinical trials, which generate the needed evidence, surrogate variables like heart and respiratory rate, weight gain, image-derived data, and biomarkers should be monitored and used instead. The recommended pharmacological therapy for systolic heart failure is also provided as the basis for utilizing reversible pulmonary arterial banding (PAB) as a novel strategy in young children with dilative cardiomyopathy (DCM) with preserved right ventricular function. • Heart failure (HF) in children is a serious public
Tsui, Judith I.; Herman, Debra S.; Kettavong, Malyna; Alford, Daniel; Anderson, Bradley J.; Stein, Michael D.
This study determined the frequency of reporting being introduced to opioids by a physician among opioid dependent patients. Cross-sectional analyses were performed using baseline data from a cohort of opioid addicts seeking treatment with buprenorphine. The primary outcome was response to the question: “Who introduced you to opiates?” Covariates included sociodemographics, depression, pain, current and prior substance use. Of 140 participants, 29% reported that they had been introduced to opioids by a physician. Of those who were introduced to opioids by a physician, all indicated that they had initially used opioids for pain, versus only 11% of those who did not report being introduced to opioids by a physician (p<0.01). There was no difference in current pain (78% vs. 85%, p=0.29), however participants who were introduced to opioids by a physician were more likely to have chronic pain (63% vs. 43%, p=0.04). A substantial proportion of individuals with opioid dependence seeking treatment may have been introduced to opioids by a physician. PMID:20727704
Kuba, Katharina; Weißflog, Gregor
Acceptance and Commitment Therapy (ACT) is an intervention representing a transdiagnostic and contextual approach that assumes that psychological suffering is caused by experiential avoidance. The primary intention of ACT is not to eliminate symptoms and to treat mental disorders. Instead, ACT aims to increase psychological flexibility, i. e. to broaden the repertoire of cognitions and behaviors when facing inner and outer aversive events or experiences. Psychological flexibility can be enhanced by working with the 6 core components of the ACT model. Experience-focused methods like metaphors and exercises for acceptance play a crucial role in the therapeutic work. In short, with ACT patients can learn: ▪ that rigid and inflexible attempts to fight aversive experience are problematic ▪ a mindful experience of inner and outer experience ▪ to differentiate between unchangeable and changeable events (acceptance) ▪ to identify values or respectively life goals and to behave in a way that is consistent with them (commitment)The therapeutic focus of ACT is to create a balance between acceptance and behavioral change consistent with chosen values. Chronic diseases are often associated with aversive inner and outer experiences. A growing number of studies support the efficacy of ACT. There is evidence that ACT can increase psychological flexibility and potentially also lead to better self-management within the context of chronic somatic diseases. © Georg Thieme Verlag KG Stuttgart · New York.
Venzin, C; Ohlerth, S; Koch, D; Spreng, D
A 15-month-old, spayed female, Bernese mountain dog was presented to the Institute of Small Animal Surgery at the University of Zurich because of chronic left forelimb lameness. The referring veterinarian diagnosed pain in the left shoulder region and had treated the dog with systemic non-steroidal anti-inflammatory drugs and restricted exercise for a two-week period. The follow-up examination revealed only minimal improvement and therefore, the dog was referred for further diagnostic evaluation. Chronic bicipital tenosynovitis and tendinitis of the infraspinatus muscle was diagnosed based on survey radiographs, arthrography, ultrasound, computed tomography (CT), and synovial fluid cytology. The dog underwent three sessions of extracorporeal shockwave therapy and substantial clinical improvement was observed. On follow-up examinations, only mild left forelimb lameness was evident following exercise, and changes in the intertubercular groove and at the supraglenoid tuberosity appeared less active on radiographs and CT. However, six months following treatment, mild degenerative joint disease was apparent.
Full Text Available Prescription opioid drug abuse has reached epidemic proportions. Individuals with chronic pain represent a large population at considerable risk of abusing opioids. The Opioid Abuse Risk Screener was developed as a comprehensive self-administered measure of potential risk that includes a wide range of critical elements noted in the literature to be relevant to opioid risk. The creation, refinement, and preliminary modeling of the item pool, establishment of preliminary concurrent validity, and the determination of the factor structure are presented. The initial development and validation of the Opioid Abuse Risk Screener shows promise for effective risk stratification.
Atalay, Nilgun Simsir; Sahin, Fusun; Atalay, Ali; Akkaya, Nuray
The aim of this prospective study was to evaluate the effects of neural therapy, and physical therapy on level of pain, disability, quality of life, and psychological status in patients with chronic low back pain. Patients admitted to the physical therapy and rehabilitation outpatient clinic with the complaint of low back pain of at least 3 months duration. Group 1 (n=27), physical therapy (PT, hotpack, ultrasound, TENS 15 sessions), group 2 (n=33), neural therapy (NT, 1:1 mixture of 20 mg/mL Lidocaine HCl (Jetokain simplex®) and saline for 5 sessions. For pain, Visual Analogue Scale (VAS), for disability Roland Morris Disability Questionnaire (RMDQ), for quality-of-life Nottingham-Health-Profile (NHP), for depression, and anxiety, Hospital Anxiety-Depression Scale (HADS) were used before and after the treatment. Mean age was 47.3±11.32 years, symptom time was 13.78±11.98 months. There were no differences for demographic variables between groups. Significant improvements were detected for VAS, RMDQ, NHP-Pain, NHP-Physical activity, HADS for both of two groups after treatment. In addition to these findings, significant improvements were found for NHP-Energy, NHP-Social isolation in NT group. The differences of pre- and post-treatment values of parameters were evaluated for each group. Although there were no differences for VAS, NHP-sleep, NHP-Emotional reaction, HADS between groups, RMDQ, NHP-Pain, NHP-Physical activity, NHP-Social isolation were higher in NT than PT before treatment, the improvements for these parameters were better in NT than PT. In conclusion both of NT and PT are effective on pain, function, quality of life, anxiety, and depression in patients with chronic low back pain.
Safley, Rebecca R; Swietlikowski, Jamie
Opioid dependence is an epidemic in the United States, and the percentage of pregnant women who are opioid dependent has increased dramatically in the last decade. Pain management, already a concern for intrapartum and postpartum care, is complicated in the context of opioid dependence. This clinical review surveys the literature on pain management in opioid-dependent pregnant women to summarize current consensus and evidence to guide clinical practice. Points of consensus for pain management in opioid-dependent pregnant women include continual opioid maintenance therapy throughout the pregnancy and the postpartum period; adequate management of acute pain; the contraindication of opioid agonist-antagonists for pain management; and the need for interdisciplinary teams using a multimodal approach to provide optimal care to opioid-dependent pregnant women.
Zanzi, I.; Roginsky, M.S.; Rosen, A.; Cohn, S.H.
The technique of in vivo total body neutron activation analysis was used to measure total body calcium (TBCa), a sensitive and precise index of skeletal mass, expressed as the Ca ratio (TBCa observed/TBCa predicted). 23 unselected, ambulatory, noninstitutionalized, adult epileptic patients under long-term anticonvulsant therapy were studied. Ca ratio was normal in 20 of the patients, low in only 2 and borderline in 1 patient. Plasma alkaline phosphatase values were elevated in half the subjects. Plasma Ca (uncorrected) was in the normal range in all. Serum 25-hydroxvitamin D (25-OHD) was low in 67% of the subjects, but only 1 patient had a value below 5 ng/ml. There was no correlation between the Ca ratio and the alkaline phosphatase or 25-OHD values. No radiographic or other evidences of osteomalacia were observed. This study does not support the notion of a prevalence of osteopenia in ambulatory, noninstitutionalized, adult epileptic patients receiving chronic anticonvulsant therapy in this geographical area despite the frequent findings of biochemical abnormalities.
Furia, John P
High-energy extracorporeal shock wave therapy has been shown to be an effective treatment for chronic insertional Achilles tendinopathy. The results of high-energy shock wave therapy for chronic noninsertional Achilles tendinopathy have not been determined. Shock wave therapy is an effective treatment for noninsertional Achilles tendinopathy. Case control study; Level of evidence, 3. Thirty-four patients with chronic noninsertional Achilles tendinopathy were treated with a single dose of high-energy shock wave therapy (shock wave therapy group; 3000 shocks; 0.21 mJ/mm(2); total energy flux density, 604 mJ/mm(2)). Thirty-four patients with chronic noninsertional Achilles tendinopathy were treated not with shock wave therapy but with additional forms of nonoperative therapy (control group). All shock wave therapy procedures were performed using regional anesthesia. Evaluation was by change in visual analog score and by Roles and Maudsley score. One month, 3 months, and 12 months after treatment, the mean visual analog scores for the control and shock wave therapy groups were 8.4 and 4.4 (P wave therapy and control groups were 12 and 0 (P wave therapy group than in the control group (P wave therapy is an effective treatment for chronic noninsertional Achilles tendinopathy.
Full Text Available To examine the impact of national clinical practice guidelines and provincial drug policy interventions on prevalence of high-dose opioid prescribing and rates of hospitalization for opioid toxicity.Interventional time-series analysis.Ontario, Canada, from 2003 to 2014.Ontario Drug Benefit (ODB beneficiaries aged 15 to 64 years from 2003 to 2014.Publication of Canadian clinical practice guidelines for use of opioids in chronic non-cancer pain (May 2010 and implementation of Ontario's Narcotics Safety and Awareness Act (NSAA; November 2011.Three outcomes were explored: the rate of opioid use among ODB beneficiaries, the prevalence of opioid prescriptions exceeding 200 mg and 400 mg morphine equivalents per day, and rates of opioid-related emergency department visits and hospital admissions.Over the 12 year study period, the rate of opioid use declined 15.2%, from 2764 to 2342 users per 10,000 ODB eligible persons. The rate of opioid use was significantly impacted by the Canadian clinical practice guidelines (p-value = .03 which led to a decline in use, but no impact was observed by the enactment of the NSAA (p-value = .43. Among opioid users, the prevalence of high-dose prescribing doubled (from 4.2% to 8.7% over the study period. By 2014, 40.9% of recipients of long-acting opioids exceeded daily doses of 200 mg morphine or equivalent, including 55.8% of long-acting oxycodone users and 76.3% of transdermal fentanyl users. Moreover, in the last period, 18.7% of long-acting opioid users exceeded daily doses of 400 mg morphine or equivalent. Rates of opioid-related emergency department visits and hospital admissions increased 55.0% over the study period from 9.0 to 14.0 per 10,000 ODB beneficiaries from 2003 to 2013. This rate was not significantly impacted by the Canadian clinical practice guidelines (p-value = .68 or enactment of the NSAA (p-value = .59.Although the Canadian clinical practice guidelines for use of opioids in chronic non
Full Text Available Background: The regenerative potential of brain has led to emerging therapies that can cure clinico-motor deficits after neurological diseases. Bone marrow mononuclear cell therapy is a great hope to mankind as these cells are feasible, multipotent and aid in neurofunctional gains in Stroke patients. Aims: This study evaluates safety, feasibility and efficacy of autologous mononuclear (MNC stem cell transplantation in patients with chronic ischemic stroke (CIS using clinical scores and functional imaging (fMRI and DTI. Design: Non randomised controlled observational study Study: Twenty four (n=24 CIS patients were recruited with the inclusion criteria as: 3 months–2years of stroke onset, hand muscle power (MRC grade at least 2; Brunnstrom stage of recovery: II-IV; NIHSS of 4-15, comprehendible. Fugl Meyer, modified Barthel Index (mBI and functional imaging parameters were used for assessment at baseline, 8 weeks and at 24 weeks. Twelve patients were administered with mean 54.6 million cells intravenously followed by 8 weeks of physiotherapy. Twelve patients served as controls. All patients were followed up at 24 weeks. Outcomes: The laboratory and radiological outcome measures were within normal limits in MNC group. Only mBI showed statistically significant improvement at 24 weeks (p<0.05 whereas the mean FM, MRC, Ashworth tone scores in the MNC group were high as compared to control group. There was an increased number of cluster activation of Brodmann areas BA 4, BA 6 post stem cell infusion compared to controls indicating neural plasticity. Cell therapy is safe and feasible which may facilitate restoration of function in CIS.
Full Text Available Immunomodulatory therapy is an important part of treating patients with chronic tonsillitis caused by β-hemolytic streptococcus group A, on the background of antibiotic therapy it allows us to achieve a more effective elimination of the pathogen. Administration of Imupret in the comprehensive treatment for exacerbation of chronic tonsillitis of streptococcal origin leads to the rapid disappearance of clinical manifestations of the disease, high frequency of pathogen elimination, reduces the incidence of chronic tonsillitis exacerbations.
Larance, Briony; Dietze, Paul; Ali, Robert; Lintzeris, Nicholas; White, Nancy; Jenkinson, Rebecca; Degenhardt, Louisa
Buprenorphine-naloxone (BNX) film for opioid dependence treatment was introduced in Australia in 2011. A key difference in State policy approaches saw transfer from BNX tablets to BNX film mandated in South Australia (SA) with New South Wales (NSW) and Victoria (VIC) having less stringent policies. This study examined (i) how initiations and transfers were implemented, (ii) the profile and predictors of adverse effects as self-reported by BNX film clients, and (iii) dosing issues. Survey of 334 buprenorphine (BPN), BNX tablet and BNX film clients and semi-structured interviews with 39 key experts (KEs) in 2012. Comparisons are made between clients interviewed in SA versus NSW and VIC combined. Among the 180 current BNX film clients, 23% started treatment on BNX film, 18% requested a transfer to BNX film and 59% (n = 106) reported their clinic/prescriber recommended transfer to BNX film. Among clients who were offered but refused a transfer to BNX film (n = 66), the most common reason was 'I am happy with my current treatment and do not see a reason to change' (53%). Some opioid substitution therapy clients and KE viewed transfers as 'forced' (i.e. no choice of buprenorphine formulation). Multivariable regression showed residing in SA (vs. NSW/VIC) and a shorter length of current treatment episode were associated with more BNX film-attributed adverse effects but clinic/prescriber-recommended transfer was not. The introduction of BNX film in Australia varied across States. A perception of restricted choice in medication may have undermined initial acceptance in SA. © 2015 Australasian Professional Society on Alcohol and other Drugs.
Bojko, Martha J; Mazhnaya, Alyona; Marcus, Ruthanne; Makarenko, Iuliia; Islam, Zahedul; Filippovych, Sergey; Dvoriak, Sergii; Altice, Frederick L
Opioid agonist therapies (OAT) to treat opioid addiction in people who inject drugs (PWID) began in Ukraine in 2004. Scale-up of OAT, however, has been hampered by both low enrollment and high attrition. To better understand the factors influencing OAT retention among PWID in Ukraine, qualitative data from 199 PWIDs were collected during 25 focus groups conducted in five Ukrainian cities from February to April 2013. The experiences of PWID who were currently or previously on OAT or currently trying to access OAT were analyzed to identify entry and retention barriers encountered. Transcribed data were analyzed using a grounded theory approach. Individual beliefs about OAT, particularly misaligned treatment goals between clients and providers, influenced PWID's treatment seeking behaviors. Multiple programmatic and structural issues, including inconvenient hours and treatment site locations, complicated dosing regimens, inflexible medication dispensing guidelines, and mistreatment by clinic and medical staff also strongly influenced OAT retention. Findings suggest the need for both programmatic and policy-level structural changes such as revising legal regulations covering OAT dispensing, formalizing prescription dosing policies and making OAT more available through other sites, including primary care settings as a way to improve treatment retention. Quality improvement interventions that target treatment settings could also be deployed to overcome healthcare delivery barriers. Additional patient education and medical professional development around establishing realistic treatment goals as well as community awareness campaigns that address the myths and fears associated with OAT can be leveraged to overcome individual, family and community-level barriers. Copyright © 2016 Elsevier Inc. All rights reserved.
Full Text Available Due to combined antiretroviral therapy (cART, human immunodeficiency virus type 1 (HIV-1 is considered a chronic disease with high prevalence of mild forms of neurocognitive impairments, also referred to as HIV-associated neurocognitive disorders (HAND. Although opiate drug use can exacerbate HIV-1 Tat-induced neuronal damage, it remains unknown how and to what extent opioids interact with Tat on the GABAergic system. We conducted whole-cell recordings in mouse striatal slices and examined the effects of HIV-1 Tat in the presence and absence of morphine (1 μM and damgo (1 μM on GABAergic neurotransmission. Results indicated a decrease in the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs and miniature IPSCs (mIPSCs by Tat (5 – 50 nM in a concentration-dependent manner. The significant Tat-induced decrease in IPSCs was abolished when removing extracellular and/or intracellular calcium. Treatment with morphine or damgo alone significantly decreased the frequency, but not amplitude of IPSCs. Interestingly, morphine but not damgo indicated an additional downregulation of the mean frequency of mIPSCs in combination with Tat. Pretreatment with naloxone (1 μM and CTAP (1 μM prevented the Tat-induced decrease in sIPSCs frequency but only naloxone prevented the combined Tat and morphine effect on mIPSCs frequency. Results indicate a Tat- or opioid-induced decrease in GABAergic neurotransmission via µ-opioid receptors with combined Tat and morphine effects involving additional opioid receptor-related mechanisms. Exploring the interactions between Tat and opioids on the GABAergic system may help to guide future research on HAND in the context of opiate drug use.
Kunnumpurath, Sreekumar; Julien, Natasha; Kodumudi, Gopal; Kunnumpurath, Anamika; Kodumudi, Vijay; Vadivelu, Nalini
The goal of this review is to evaluate the global supply and demand of opioids used for pain management and discuss how it relates to the utilization of opioids around the world. The purpose of the review is also to determine the factors that contribute to inappropriate pain management. The total global production of opium for opioid manufacturing is enough to supply the growing global demands. However, licit opioids are only consumed by 20% of the world population. Most people throughout the world had no access to opioid analgesics for pain relief in case of need. Opioid misuse and abuse is not only a phenomena plague by the USA but globally across many countries. Many countries have a lack of availability of opioids, contributing factors being strict government regulations limiting access, lack of knowledge of the efficacy of opioid analgesics in treating acute and chronic pain and palliative care, and the stigma that opioids are highly addictive. For the countries in which opioids are readily available and prescribed heavily, diversion, misuse, abuse, and the resurgence of heroin have become problems leading to morbidity and mortality. It is pertinent to find a balance between having opioids accessible to patients in need, with ensuring that opioids are regulated along with other illicit drugs to decrease abuse potential.
Cogan, Jennifer; Lalumière, Geneviève; Vargas-Schaffer, Grisell; Deschamps, Alain; Yegin, Zeynep
Recent meta-analyses have concluded that low-dose intravenous ketamine infusions (LDKIs) during the postoperative period may help to decrease acute and chronic postoperative pain after major surgery. This study aims to evaluate the level of pain at least 3 months after surgery for patients treated with a postoperative LDKI versus patients who were not treated with a postoperative LDKI. Administrative and Ethics Board approval were obtained for this study. We performed a retrospective chart review for all patients receiving LDKI, and equal number of age-, sex-, and surgery-matched patients who did not receive LDKI. Low-dose ketamine was prepared using 100 mg of ketamine in 100 ml of normal saline and run between 50 and 200 mcg/kg/h. We reviewed 115 patients with LDKI and 115 without LDKI. The average age was 63.1 years, 73% of the patients were men and sex was evenly distributed between LDKI and non-LDKI. The average duration of the ketamine infusions was 26.8 h with the average dose being 169.9 mg. At an average of 9 months after surgery, 42% of the ketamine group and 38% of the nonketamine group stated that they had had pain on discharge. Of these patients, 30% of the ketamine group and 26% of the nonketamine group still had pain at the time of the phone call. Women in both groups had more acute and chronic pain than men. These results show that LDKI does not promote a decrease in long-term postoperative pain.
Modesto-Lowe, Vania; Girard, Lisa; Chaplin, Margaret
Although cancer elicits an array of physical and emotional symptoms, pain is often identified as the most distressing. Cancer pain may result from the primary tumor, metastasis, surgery, radiation, chemotherapy, or medical comorbidities. Although treatment with opioid analgesics is accepted as appropriate therapy for cancer-related pain, under treatment may persist among certain patients. Opioid-addicted individuals represent a challenging and heterogeneous population to treat. Addiction is linked to psychopathology and antisocial behaviors (eg, lying) which often complicate evaluation. Chronic exposure to opioids may lead to physiologic dependence and its correlates, tolerance and hyperalgesia. Given the variability and subjectivity of the cancer pain experience, there are no objective measures which capture the adequacy of pain control. Thus, when faced with complaints of uncontrolled pain, clinicians must consider a differential diagnosis of tolerance, disease progression, addiction, pseudoaddiction, chemical coping, or even criminal behavior. This article explores the cognitive, behavioral, and physiological correlates of opioid addiction that may impact cancer pain management. It also discusses risk reduction strategies for opioid misuse and research directions that may lead to improved clinical outcomes in these patients.
Opioid Addiction; Opioid Abuse, Continuous Use; Opioid Use; Opioid-Related Disorders; Paternal Pheromone Deficiency; Opioid Dependence; Opioid Abuse; Opioid-use Disorder; Opioid Intoxication; Opioid Abuse, Episodic
Giannitrapani, Karleen F; Ahluwalia, Sangeeta C; McCaa, Matthew; Pisciotta, Maura; Dobscha, Steven; Lorenz, Karl A
Opioid prescribing for chronic pain, including the potential for over-reliance and misuse, is a public health concern. In the context of Veterans Administration (VA) primary care team-based pain management, we aimed to understand providers' perceptions of barriers to reducing opioid use and improving the use of nonpharmacologic pain management therapies (NPTs) for chronic pain. A semistructured interview elucidated provider experiences with assessing and managing pain. Emergent themes were mapped to known dimensions of VA primary care access. Informants included 60 primary care providers, registered nurses, licensed practical nurses, clerks, psychologists, and social workers at two VA Medical Centers. Nine multidisciplinary focus groups. Provider perceptions of barriers to reducing opioids and improving use of NPTs for patients with chronic pain clustered around availability and access. Barriers to NPT access included the following subthemes: geographical (patient distance from service), financial (out-of-pocket cost to patient), temporal (treatment time delays), cultural (belief that NPTs increased provider workload, perception of insufficient training on NPTs, perceptions of patient resistance to change, confrontation avoidance, and insufficient leadership support), and digital (measure used for pain assessment, older patients hesitant to use technology, providers overwhelmed by information). Decreasing reliance on opioids for chronic pain requires a commitment to local availability and provider-facing strategies that increase efficacy in prescribing NPTs. Policies and interventions for decreasing utilization of opioids and increasing use of NPTs should comprehensively consider access barriers. 2017 American Academy of Pain Medicine. This work is written by US Government employees and is in the public domain in the US.
Anand, Kanwaljeet J S; Willson, Douglas F; Berger, John; Harrison, Rick; Meert, Kathleen L; Zimmerman, Jerry; Carcillo, Joseph; Newth, Christopher J L; Prodhan, Parthak; Dean, J Michael; Nicholson, Carol
After prolonged opioid exposure, children develop opioid-induced hyperalgesia, tolerance, and withdrawal. Strategies for prevention and management should be based on the mechanisms of opioid tolerance and withdrawal. Relevant manuscripts published in the English language were searched in Medline by using search terms "opioid," "opiate," "sedation," "analgesia," "child," "infant-newborn," "tolerance," "dependency," "withdrawal," "analgesic," "receptor," and "individual opioid drugs." Clinical and preclinical studies were reviewed for data synthesis. Mechanisms of opioid-induced hyperalgesia and tolerance suggest important drug- and patient-related risk factors that lead to tolerance and withdrawal. Opioid tolerance occurs earlier in the younger age groups, develops commonly during critical illness, and results more frequently from prolonged intravenous infusions of short-acting opioids. Treatment options include slowly tapering opioid doses, switching to longer-acting opioids, or specifically treating the symptoms of opioid withdrawal. Novel therapies may also include blocking the mechanisms of opioid tolerance, which would enhance the safety and effectiveness of opioid analgesia. Opioid tolerance and withdrawal occur frequently in critically ill children. Novel insights into opioid receptor physiology and cellular biochemical changes will inform scientific approaches for the use of opioid analgesia and the prevention of opioid tolerance and withdrawal.
Linares, Oscar A; Linares, Annemarie L
We implemented a pharmacokinetics-based mathematical modeling technique using algebra to assist prescribers with point-of-care opioid dosing. We call this technique computational opioid prescribing (COP). Because population pharmacokinetic parameter values are needed to estimate drug dosing regimen designs for individual patients using COP, and those values are not readily available to prescribers because they exist scattered in the vast pharmacology literature, we estimated the population pharmacokinetic parameter values for 12 commonly prescribed opioids from various sources using the bootstrap resampling technique. Our results show that opioid dosing regimen design, evaluation, and modification is feasible using COP. We conclude that COP is a new technique for the quantitative assessment of opioid dosing regimen design evaluation and adjustment, which may help prescribers to manage acute and chronic pain at the point-of-care. Potential benefits include opioid dose optimization and minimization of adverse opioid drug events, leading to potential improvement in patient treatment outcomes and safety.
Full Text Available Chronic pancreatitis (CP, a disease of varied etiology can, from the endoscopists perspective present as ductal strictures, stones, ductal leaks and fluid collections, biliary strictures or duodenal narrowing. This article deals with role of ERCP in the management of CP associated strictures and calculi. ERCP has a limited role in the diagnosis CP, though we feel that it is better at identifying small ductal calculi or leaks as compared to MRCP. Major and minor papilla sphincterotomy gives relief from pain in patients with mild or moderate ductal changes. Pancreatic ductal strictures are best managed by stenting. Use of multiple plastic stents (8.5-11Fr diameter gives relief from pain in 84% and strictures resolution in 95% on follow up of over 3 years. CP associated CBD strictures are also managed by placement of multiple stents. Covered SEMS are increasingly being used in these strictures. Surgery is often the best option for CP associated CBD strictures which recur after adequate endotherapy. ESWL is the standard of therapy for pancreatic ductal calculi which are large, as seen in the tropics and the non alcoholic form of CP. Our experience has shown complete or partial clearance with ESWL in over 90% of patients with large PD calculi. Good pain relief was seen in both on short and long term follow up. In selected patients of CP, ERCP and endotherapy should be offered as first line of treatment, as the results are comparable to surgery. Prior endotherapy also does not interfere with subsequent surgical procedures.
Scudla, V; Adam, Z; Scudlová, M
The article deals with contemporary views on anaemia associated with chronic diseases. The authors present the definition of this nosological unit, draw attention to its high incidence in clinical practice and fact that it is frequently mistaken for iron deficiency anaemia. The authors submit a review of the most frequent diseases which cause the development of this type of anaemia and analyze the role of activation of the system of cellular immunity, the monocyte-macrophage system, agents of the cytokine network in inhibition of proliferation and differentiation of erythroid precursors, reduced production of endogenous erythropoietin with a reduced sensitivity of erythroid progenitor cells to its action and impaired iron homeostasis and inhibition of its reutilization. Special attention is devoted to diagnostic and differential diagnostic criteria in relation to other types of anaemia caused by impaired haeme synthesis and some secondary multifactorially conditioned types of anaemia. More detailed attention is paid to the diagnostic value of evaluating serum levels of soluble transferrin receptors and explanation of the asset of calculation of the transferrin receptor/ferririn index as a sensitive indicator of latent sideropenia as well as the Fe-absorption test using low oral iron doses. Part of the paper is also an account of contemporary possibilities of treatment including the use of the recombinant form of human erythropoietin, and attention is drawn to the unsuitability and pitfalls of iron therapy in this type of anaemia.
Karaoglan, Murat; Demirci, Fikret; Coskun, Yavuz; Karaoglan, Ilkay; Bayraktaroglu, Ziya; Okan, Vahap; Karsligil, Tekin
PURPOSE: The aim of this study is to investigate the effects of HBsAg vaccine and levamisole on virological indicators in naive patients suffering from chronic hepatitis B (CHB) and in healthy carriers of hepatitis B. METHOD: Vaccination and treatment with levamisole were applied to 93 minor patients in total, 43 of them inactive CHB carriers and 50 patients suffering from CHB. RESULTS: 15 (30%) of 50 patients who had high ALT values in the beginning of the study had normal values after treatment. In nine (12%) patients, posttreatment ALT values were higher than pretreatment values, and six (10%) patients showed HBV-DNA loss. In spite of the presence of 50 (54%) HBeAg-positive patients before treatment, 17 (34%) patients proved to be HBeAg-negative after treatment. HBeAg sero-conversion was seen in 10 (20%) cases. In two (2%) patients, HBsAg sero-conversion occurred. CONCLUSION: It was found that treatment with levamisole and vaccine had positive effects on CHB patients and healthy carriers with respect to HBV DNA loss, HBeAg sero-conversion and ALT normalization. The viral load increases and ALT increases that occurred in certain cases were thought to be related to the early immune response. It was determined that combined levamisole and vaccine therapy had no additional positive effect. PMID:16708498
Zhou, Kehua; Jia, Peng; Bhargava, Swati; Zhang, Yong; Reza, Taslima; Peng, Yuan Bo; Wang, Gary G
Opioid use disorder (OUD) refers to a maladaptive pattern of opioid use leading to clinically significant impairment or distress. OUD causes, and vice versa, misuses and abuse of opioid medications. Clinicians face daily challenges to treat patients with prescription opioid use disorder. An evidence-based management for people who are already addicted to opioids has been identified as the national priority in the US; however, options are limited in clinical practices. In this study, we aimed to explore the success rate and important adjuvant medications in the medication assisted treatment with temporary use of methadone for opioid discontinuation in patients with prescription OUD. This is a retrospective chart review performed at a private physician office for physical medicine and rehabilitation. We reviewed all medical records dated between December 1st, 2011 and August 30th, 2016. The initial evaluation of the included patients (N=140) was completed between December 1st, 2011 and December 31st, 2014. They all have concumittant prescription OUD and chronic non-cancer pain. The patients (87 female and 53 male) were 46.7±12.7 years old, and had a history of opioid use of 7.7±6.1 years. All patients received the comprehensive opioid taper treatments (including interventional pain management techniques, psychotherapy, acupuncture, physical modalities and exercises, and adjuvant medications) on top of the medication assisted treatment using methadone (transient use). Opioid tapering was considered successful when no opioid medication was used in the last patient visit. The 140 patients had pain of 9.6±8.4 years with 8/10 intensity before treatment which decreased after treatment in all comparisons (pOUD. For patients with OUD, indefinite opioid maintenance treatment may not be necessary. Considering the ethical values of autonomy, nonmaleficence, and beneficence, clinicians should provide patients with OUD the option of opioid tapering. Copyright © 2017
When intrathecal and epidural opioids are administered, pruritus occurs as an unwanted and troublesome side effect. The reported incidence varies between 30% and 100%. The exact mechanisms of neuraxial opioid-induced pruritus remain unclear. Postulated mechanisms include the presence of an "itch center" in the central nervous system, medullary dorsal horn activation, and antagonism of inhibitory transmitters. The treatment of intrathecal opioid-induced pruritus remains a challenge. Many pharmacological therapies, including antihistamines, 5-HT(3)-receptor antagonists, opiate-antagonists, propofol, nonsteroid antiinflammatory drugs, and droperidol, have been studied. In this review, we will summarize pathophysiological and pharmacological advances that will improve understanding and ultimately the management of this troublesome problem.
Aspegren, Oskar P.; Åstrand, Ramona; Lundgren, Maria I.
Chronic subdural hematoma (CSDH) is a common disease among the elderly and with increasing incidence we have chosen to focus on associations between development and recurrence of CSDH and anticoagulation and/or antiplatelet agent therapy.......Chronic subdural hematoma (CSDH) is a common disease among the elderly and with increasing incidence we have chosen to focus on associations between development and recurrence of CSDH and anticoagulation and/or antiplatelet agent therapy....
Thiele, Maja; Gluud, Lise Lotte; Dahl, Emilie K
The effect of antiviral therapy on clinical outcomes in chronic hepatitis B virus (HBV) is not established. We aimed to assess the effects of interferon and/or nucleos(t)ide analogues versus placebo or no intervention on prevention of hepatocellular carcinoma (HCC) and mortality in chronic HBV....
Jeppesen, S M; Yderstraede, K B; Rasmussen, B S B
OBJECTIVE: To investigate the efficacy of extracorporeal shockwave therapy (ESWT) on healing chronic diabetic foot ulcers (DFU). METHOD: Patients with chronic DFUs were randomised (1:1) to receive a series of six ESWT treatments over 3 weeks in combination with standard care or standard care alone...
Kristensen, Søren Lund; Fosbøl, Emil L; Kamper, Anne-Lise
PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with severe renal complications, including acute renal failure, reduced glomerular filtration rate and interstitial nephritis. Caution against NSAIDs is therefore recommended in advanced chronic kidney disease. In this study......, we examined NSAID use, aetiology and comorbidity among a national cohort of patients before the initiation of chronic renal replacement therapy (RRT). METHODS: Patients initiated on chronic RRT in the period 1997-2006 were identified in the Danish National Registry on Regular Dialysis...
Moessner, J. [Medizinische Klinik und Poliklinik 2, Zentrum fuer Innere Medizin, Univ. Leipzig (Germany)
The incidence of chronic pancreatitis is increasing in industrialized countries due to the steady increase of alcohol abuse. The pathogenesis of this disease is still incompletely understood. A cure is not possible. The knowledge of the patients history and a thorough clinical investigation together with the availability of a wide array of laboratory tests and imaging procedures enable the physician to characterize the stage of the disease. Exact knowledge of the present pancreatic morphology, potential complications of the disease, and knowledge about the present exocrine and endocrine function capacity are prerequisites for adequate therapeutic decision making. The therapeutic possibilities include termination of alcohol abuse, various options of treatment of pain according to the various pathogenetic possibilities leading to pain, pancreatic digestive enzyme supplementation, treatment of diabetes, and either endoscopic or surgical treatments of complications of the disease. (orig.) [Deutsch] Die Inzidenz der chronischen Pankreatitis nimmt in den Industrienationen aufgrund der Zunahme des Alkoholabusus an Haeufigkeit zu. Die Diagnose der chronischen Pankreatitis wird oft spaet gestellt. Eine Heilung ist noch nicht moeglich. Eine detailierte Anamnese, Beurteilung der Klinik, Laborparameter, Pankreasfunktionsanalysen und eine ganze Palette unterschiedlicher bildgebender Verfahren ermoeglichen eine Charakterisierung des jeweiligen Krankheitszustandes. Dies ist die Voraussetzung zur differenzierten Einleitung einer medikamentoesen und/oder interventionellen endoskopischen und/oder chirurgischen Therapie. Wie bei jedem nicht heilbaren chronischen Krankheitsbild ist eine stadiengerechte Therapie erforderlich. (orig.)
Chronic Right-Sided Heart Failure; Pulmonary Arterial Hypertension; Pulmonary Hypertension, Primary, 2; Pulmonary Hypertension, Primary, 3; Pulmonary Hypertension, Primary, 4; Cardiomyopathy Right Ventricular
An overview is given on the current classification, description and treatment of chronic pain with causally relevant psychological factors. It is based on the "practice guidelines on somatoform disorders" and on a thematically related meta-analysis. The classificatory problems, especially of the demarcation of somatoform and other chronic pain, are presented. Additional descriptive dimensions of the relevant psychosocial factors are: pain description, other organically unexplained pain- and non-pain-symptoms, anxiety and depression, disease conviction and illness behaviour, personality and childhood abuse. A modified psychotherapy for (somatoform) chronic pain is outlined. Finally, this aetiologically oriented psychosomatic-psychiatric approach is compared to psychological coping models for chronic pain.
Shah, Drishti; Anupindi, Vamshi Ruthwik; Vaidya, Varun
Chronic back pain is an extremely common health problem. The largest category for pain therapy costs includes nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids. However, there has been limited evidence outlining their effectiveness in terms of quality of life for the treatment of chronic back pain. The authors performed a comparative pharmacoeconomic analysis of chronic back pain patients using NSAIDs versus those using opioids alone or combination opioid analgesics. This pharmacoeconomic evaluation was conducted using the Medical Expenditure Panel Survey (MEPS). Adults ≥18 years with chronic back pain diagnosis were included in the study. Individuals using opioids were matched in 1:1 ratio with those using only NSAIDs using propensity scores. All direct medical costs were included, and utility scores from Short Form 6D (SF-6D) were used to calculate QALYs (quality-adjusted life years). Monte Carlo probabilistic simulation technique was employed to determine the cost-effectiveness acceptability curve. After matching, there were 1109 patients in each cohort. The total mean annual cost was found to be $6137.41 for NSAIDs and $8982.28 for opioids. The mean utility gain for NSAIDs was found to be 0.661, whereas for opioids it was 0.633. Probabilistic sensitivity analysis showed that at all willingness-to-pay thresholds, the probability of NSAIDs being cost-effective was higher than the probability of the opioids being cost-effective. The authors found NSAIDs to be a dominant strategy as compared with opioids. Considering the higher cost associated with opioids/combination opioid analgesics, it might be cost-effective if they are used in patients who did not respond to the NSAIDs.
Juul, A; Pedersen, A T
Cancer patients with chronic pain and obstetric patients have participated in clinical trials of the analgesic effects of endogenous opioids. It is possible to achieve adequate relief of pain in these patients following epidural or intrathecal administration of endogenous opioids. Further investi...
García, César Amescua; Santos Garcia, Joao Batista; Rosario Berenguel Cook, María Del; Colimon, Frantz; Flores Cantisani, José Alberto; Guerrero, Carlos; Rocío Guillén Núnez, María Del; Hernández Castro, John Jairo; Kraychete, Durval Campos; Lara-Solares, Argelia; Lech, Osvandré; Rico Pazos, María Antonieta; Gallegos, Manuel Sempértegui; Marcondes, Lizandra Pattaro
Pain is highly prevalent among the adult Latin American population. However, many patients with moderate to severe pain do not have access to effective pain management with opioids due to limited access to healthcare, overuse of nonopioid analgesics, regulatory barriers and lack of appropriate information about opioids. There is scarce training on use of opioids among physicians and other healthcare providers, which leads to misconceptions, mainly related to a fear of prescribing opioids. Although opioids are safe and effective drugs for the treatment of moderate to severe chronic pain, the use of opioids in Latin American nations is clearly below standards compared with developed countries.
Takkenberg, R. B.; Weegink, C. J.; Zaaijer, H. L.; Reesink, H. W.
Chronic hepatitis B affects approximately 400 million people in the world with a substantial disease burden like liver cirrhosis and hepatocellular carcinoma (HCC). Treatment for chronic hepatitis B has improved dramatically in the last decade, resulting in more patients achieving a state of
Burke, Susan G.
Presents current research on chronic fatigue syndrome, which currently afflicts mostly females between ages of 25 and 55. Notes that, because depression is common symptom of chronic fatigue syndrome, mental health practitioners are often involved with victims and must formulate appropriate treatment strategy that considers physiological,…
Univaldo Etsuo Sagae
Full Text Available PURPOSE: The purpose of this study was to evaluate the effect of physical therapy in women diagnosed with chronic constipation using functional training of the pelvic floor (biofeedback. PATIENTS AND METHODS: From March 2009 to March 2010, 67 women with chronic constipation were prospectively evaluated. The patients were evaluated and the constipation score proposed by Agachan et al. was applied. Then, they were sent to biofeedback. These patients were divided into 2 groups: with anismus (group I: mean age of 46.90 years old and without anismus (group II: mean age of 44.89 years old and diagnosed by anorectal electromanometry. The treatment was performed with different exercises for each group, associated with some hygieno-dietetic directions. At the end of treatment, the constipation score was reapplied. RESULTS: Pre-biofeedback constipation score in group I was 15.04 (standard deviation - SD=2.48 and post-biofeedback constipation score was 3.39 (SD=1.62 (pOBJETIVO: Este trabalho objetivou avaliar o efeito do tratamento fisioterapêutico, em mulheres diagnosticadas com constipação crônica, utilizando treinamento funcional do assoalho pélvico (biofeedback. CASUÍSTICA E MÉTODO: No período de março de 2009 a março de 2010, foram avaliadas, prospectivamente, 67 mulheres com constipação intestinal. As pacientes foram avaliadas e o escore de constipação, proposto por Agachan et al., foi aplicado; então, foram encaminhadas ao biofeedback. Essas pacientes foram divididas em 2 grupos: com anismus (56 pacientes do grupo I: média de idade 46,90 anos e sem anismus (11 pacientes do grupo II: média de idade 44,89 anos, diagnosticadas pela eletromanometria anorretal. Para o tratamento, foram estipulados exercícios diferentes para cada grupo, associados com orientações higienodietéticas. Ao fim do tratamento, foi reaplicado o escore de constipação. RESULTADOS: O escore de constipação do grupo I, na avaliação pré-biofeedback, foi 15
Coluzzi, Flaminia; Bifulco, Francesca; Cuomo, Arturo; Dauri, Mario; Leonardi, Claudio; Melotti, Rita Maria; Natoli, Silvia; Romualdi, Patrizia; Savoia, Gennaro; Corcione, Antonio
The increasing number of opioid users among chronic pain patients, and opioid abusers among the general population, makes perioperative pain management challenging for health care professionals. Anesthesiologists, surgeons, and nurses should be familiar with some pharmacological phenomena which are typical of opioid users and abusers, such as tolerance, physical dependence, hyperalgesia, and addiction. Inadequate pain management is very common in these patients, due to common prejudices and fears. The target of preoperative evaluation is to identify comorbidities and risk factors and recognize signs and symptoms of opioid abuse and opioid withdrawal. Clinicians are encouraged to plan perioperative pain medications and to refer these patients to psychiatrists and addiction specialists for their evaluation. The aim of this review was to give practical suggestions for perioperative management of surgical opioid-tolerant patients, together with schemes of opioid conversion for chronic pain patients assuming oral or transdermal opioids, and patients under maintenance programs with methadone, buprenorphine, or naltrexone. PMID:28919771
Littlejohn, Geoffrey O; Guymer, Emma K; Ngian, Gene-Siew
The use of opioids for chronic pain has increased significantly due to a combination of the high patient burden of pain and the more widespread availability of a range of long-acting opioid preparations. This increased opioid use has translated into the care of many patients with fibromyalgia. The pain mechanism in fibromyalgia is complex but does not seem to involve disturbance of opioid analgesic functions. Hence, there is general concern about the harms in the absence of benefits of opioids in this setting. There is no evidence that pure opioids are effective in fibromyalgia but there is some evidence that opioids with additional actions on the norepinephrine-related pain modulatory pathways, such as tramadol, can be clinically useful in some patients. Novel actions of low-dose opioid antagonists may lead to better understanding of the role of opioid function in fibromyalgia.
Hser, Yih-Ing; Evans, Elizabeth; Grella, Christine; Ling, Walter; Anglin, Douglas
McKenna, L.; Marks, E. M.; Hallsworth, C. A.; Schaette, R.
BACKGROUND: Tinnitus is experienced by up to 15% of the population and can lead to significant disability and distress. There is rarely a medical or surgical target and psychological therapies are recommended. We investigated whether mindfulness-based cognitive therapy (MBCT) could offer an effective new therapy for tinnitus. METHODS: This single-site randomized controlled trial compared MBCT to intensive relaxation training (RT) for chronic, distressing tinnitus in adults. Both treatments in...
E. V. Esaulenko
Full Text Available Patients with chronic virus hepatitis (32 patients, 13 with chronic hepatitis B and 19 with chronic hepatitis C ages from 20 to 72 with elevated levels of bilirubin and active alanine aminotransferase, aspartate aminotransferase, gamma- glutamyl transpeptidase, received ursodeoxycholic acid (Urdoxa over the course of 12 weeks. During therapy alanine aminotransferase, aspartate aminotransferase, bilirubin and gamma-glutamyl transpeptidase levels decreased. Urdoxa demonstrated good tolerance, efficacy and no visible side effects. Thus, Urdoxa could be used in treatment of chronic viral hepatitis with cytolytic and cholestatic syndromes.
Ringbaek, T.; Lange, P.; Mogensen, T.
Acute exacerbation of COPD is a major cause of hospitalisation in Denmark. Most of the patients require supplemental oxygen in the acute phase and some patients continue oxygen therapy at home after discharge. In this paper we discuss the physiological mechanisms of respiratory failure seen...... in acute exacerbations of COPD. The principles for oxygen therapy in the acute phase are described and recommendations for oxygen therapy are suggested Udgivelsesdato: 2008/5/5...
Design and implementation of a factorial randomized controlled trial of methadone maintenance therapy and an evidence-based behavioral intervention for incarcerated people living with HIV and opioid dependence in Malaysia.
Bazazi, Alexander R; Wickersham, Jeffrey A; Wegman, Martin P; Culbert, Gabriel J; Pillai, Veena; Shrestha, Roman; Al-Darraji, Haider; Copenhaver, Michael M; Kamarulzaman, Adeeba; Altice, Frederick L
Incarcerated people living with HIV and opioid dependence face enormous challenges to accessing evidence-based treatment during incarceration and after release into the community, placing them at risk of poor HIV treatment outcomes, relapse to opioid use and accompanying HIV transmission risk behaviors. Here we describe in detail the design and implementation of Project Harapan, a prospective clinical trial conducted among people living with HIV and opioid dependence who transitioned from prison to the community in Malaysia from 2010 to 2014. This trial involved 2 interventions: within-prison initiation of methadone maintenance therapy and an evidence-based behavioral intervention adapted to the Malaysian context (the Holistic Health Recovery Program for Malaysia, HHRP-M). Individuals were recruited and received the interventions while incarcerated and were followed for 12months after release to assess post-release HIV transmission risk behaviors and a range of other health-related outcomes. Project Harapan was designed as a fully randomized 2×2 factorial trial where individuals would be allocated in equal proportions to methadone maintenance therapy and HHRP-M, methadone maintenance therapy alone, HHRP-M alone, or control. Partway through study implementation, allocation to methadone maintenance therapy was changed from randomization to participant choice; randomization to HHRP-M continued throughout. We describe the justification for this study; the development and implementation of these interventions; changes to the protocol; and screening, enrollment, treatment receipt, and retention of study participants. Logistical, ethical, and analytic issues associated with the implementation of this study are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.
Akbarali, Hamid I; Dewey, William L
The prevailing opioid crisis has necessitated the need to understand mechanisms leading to addiction and tolerance, the major contributors to overdose and death and to develop strategies for developing drugs for pain treatment that lack abuse liability and side-effects. Opioids are commonly used for treatment of pain and symptoms of inflammatory bowel disease. The significant effect of opioids in the gut, both acute and chronic, includes persistent constipation and paradoxically may also worsen pain symptoms. Recent work has suggested a significant role of the gastrointestinal microbiome in behavioral responses to opioids, including the development of tolerance to its pain-relieving effects. In this review, we present current concepts of gut-brain interaction in analgesic tolerance to opioids and suggest that peripheral mechanisms emanating from the gut can profoundly affect central control of opioid function. Copyright © 2017 Elsevier Ltd. All rights reserved.
Bhalla, Shaifali; Andurkar, Shridhar V; Gulati, Anil
Morphine and oxycodone are potent opioid analgesics most commonly used for the management of moderate to severe acute and chronic pain. Their clinical utility is limited by undesired side effects like analgesic tolerance, dependence, and withdrawal. We have previously demonstrated that endothelin-A (ETA) receptor antagonists potentiate opioid analgesia and eliminate analgesic tolerance. Mechanistically, G proteins and regulatory proteins such as β-arrestins have shown to play an important role in mediating opioid tolerance, dependence, and withdrawal. Recently, the involvement of central ET mechanisms in opioid withdrawal was investigated. ETA receptor antagonist was shown to block majority of the signs and symptoms associated with opioid withdrawal. This review focuses on ET as one of the potential novel strategies to manage the challenge of opioid withdrawal. An overview of additional players in this process (G proteins and β-arrestin2), and the possible therapeutic implications of these findings are presented. Copyright © 2016 Elsevier Inc. All rights reserved.
Shen, Y X; Guo, S J; Wu, Y F
Chronic periodontitis is a progressive, infectious inflammation disease, caused by the dysbiosis of oral resident flora, leading to the destruction of periodontium. The onset of pathogenic microorganisms is the etiological factor of periodontitis, while the immuno-inflammatory response affects the progression of the disease. Under chronic periodontitis, oxidative stress occurs when excessive reactive oxygen species are produced and exceed the compensative capacity of the organism. Oxidative stress leads to the destruction of periodontium, in a direct way(damaging the biomolecule) or an indirect way(enhancing the produce of inflammatory cytokine and destructive enzymes). Therefore, as the antagonist of the reactive oxygen species, antioxidants may be helpful to treat the chronic periodontitis. This paper reviewed relevant literatures about the destructive role of excessive reactive oxygen species and protective role of antioxidants in chronic periodontitis.
Miller, R.J.; Chang, K.-J.
A radioreceptor assay is described for assaying opioid drugs in biological fluids. The method enables the assay of total opioid activity, being specific for opioids as a class but lacking specificity within the class. A radio-iodinated opioid and the liquid test sample are incubated with an opiate receptor material. The percentage inhibition of the binding of the radio-iodinated compound to the opiate receptor is calculated and the opioid activity of the test liquid determined from a standard curve. Examples of preparing radio-iodinated opioids and assaying opioid activity are given. A test kit for the assay is described. Compared to other methods, this assay is cheap, easy and rapid. (U.K.)
Kutsa, Oksana; Marcus, Ruthanne; Bojko, Martha J; Zelenev, Alexei; Mazhnaya, Alyona; Dvoriak, Sergii; Filippovych, Sergii; Altice, Frederick L
Ukraine's volatile HIV epidemic, one of the largest in Eastern Europe and Central Asia, remains concentrated in people who inject drugs (PWID). HIV prevalence is high (21.3% to 41.8%) among the estimated 310,000 PWID. Opioid agonist therapy (OAT) is the most cost-effective HIV prevention strategy there, yet OAT services are hampered by negative attitudes and frequent harassment of OAT clients and site personnel by law enforcement. This paper examines the various types of police violence that Ukrainian PWID experience and factors associated with the different types of violence, as well as the possible implications of police harassment on OAT retention. In 2014 to 2015, we conducted a cross-sectional survey in five Ukrainian cities with 1613 PWID currently, previously and never on OAT, using a combination of respondent-driven sampling, as well as random sampling. We analysed correlates of police violence by multiple factors, including by gender, and their effects on duration of OAT retention. Self-reported physical and sexual violence by police were the two primary outcomes, while retention on OAT was used as a secondary outcome. Overall, 1033 (64.0%) PWID reported being physically assaulted by police, which was positively correlated with currently or previously being on OAT (69.1% vs. 60.2%; pmen experiencing significantly more physical violence, while women experienced more sexual violence (65.9% vs. 42.6%; psexual assault by police and fewer non-fatal overdoses. Police violence is a frequent experience among PWID in Ukraine, particularly for those accessing OAT, an evidence-based primary and secondary HIV prevention strategy. Police violence experiences, however, were different for men and women, and interventions with police that address these sexual differences and focus on non-violent interactions with PWID to improve access and retention on OAT are crucial for improving HIV prevention and treatment goals for Ukraine.
Vuoristo-Myllys, Salla; Lahti, Jari; Alho, Hannu; Julkunen, Juhani
This study investigated predictors of dropout in an outpatient treatment program for problem drinking that included individual cognitive-behavioral therapy combined with naltrexone. Specifically, we investigated whether sociodemographic factors, severity of alcohol dependence, history of problem drinking, or intensity of alcohol craving assessed at the beginning of the treatment predicted dropout from an outpatient program among a sample of 372 patients (65% male). We also investigated whether the effectiveness of the treatment (the change in alcohol consumption and symptoms of alcohol craving) or adherence to naltrexone was related to dropout. Predictors of dropout were investigated using an analysis of covariance with the number of attended treatment sessions as an independent variable. Our results demonstrated that the treatment entry factors predictive of dropout were younger age, lower severity of alcohol dependence, better ability to resist and control alcohol use, and lower obsession with alcohol. In addition, those who dropped out were more likely to begin the program by abstaining from alcohol and had lower adherence to naltrexone use than those who completed the program. The length of stay for treatment was not related to change in alcohol consumption. Patients with less severe alcohol-related problems may lack motivation for treatment, specifically cognitive-behavioral therapy and naltrexone. These patients may benefit more from less intensive treatments.
Full Text Available Guido Fanelli,1 Andrea Fanelli2 1Anesthesia and Intensive Care Unit, University of Parma, Parma, 2Anesthesia and Intensive Care Unit, Policlinico S Orsola-Malpighi, Bologna, Italy Abstract: Chronic pain is a highly disabling condition, which can significantly reduce patients’ quality of life. Prevalence of moderate and severe chronic pain is high in the general population, and it increases significantly in patients with advanced cancer and older than 65 years. Guidelines for the management of chronic pain recommend opioids for the treatment of moderate-to-severe pain in patients whose pain is not responsive to initial therapies with paracetamol and/or nonsteroidal anti-inflammatory drugs. Despite their analgesic efficacy being well recognized, adverse events can affect daily functioning and patient quality of life. Opioid-induced constipation (OIC occurs in 40% of opioid-treated patients. Laxatives are the most common drugs used to prevent and treat OIC. Laxatives do not address the underlying mechanisms of OIC; for this reason, they are not really effective in OIC treatment. Naloxone is an opioid receptor antagonist with low systemic bioavailability. When administered orally, naloxone antagonizes the opioid receptors in the gut wall, while its extensive first-pass hepatic metabolism ensures the lack of antagonist influence on the central-mediated analgesic effect of the opioids. A prolonged-release formulation consisting of oxycodone and naloxone in a 2:1 ratio was developed trying to reduce the incidence of OIC maintaining the analgesic effect compared with use of the sole oxycodone. This review includes evidence related to use of oxycodone and naloxone in the long-term management of chronic non-cancer pain and OIC. Keywords: chronic pain, opioid-induced constipation, opioids, oxycodone–naloxone
Luo, Qing; Deng, Jie; Xu, Rui; Zuo, Kejun; Li, Huabin; Shi, Jianbo
To evaluate the efficacy of clarithromycin (CAM) treatment in adult Chinese patients suffering from chronic rhinosinusitis with nasal polyps (CRSwNP) or without nasal polyps (CRSsNP). A prospective, open and self-controlled clinical trial on patients with CRS was conducted. Fifty patients met inclusion criteria. Of 50 patients, there were 33 patients with CRSsNP and 17 patients with CRSwNP. CAM was administered at 250 mg/d and the duration of administration was 12 weeks. Outcome measures included assessments of visual analogue scale (VAS), the sino-nasal outcome test-20(SNOT-20), the medical outcomes study short-form 36 items(SF-36), Lund-Kennedy endoscopy score, and Lund-Mackay computed tomography score. Before starting the treatment, 2 months after treatment and at the end of treatment, each patient had to complete all the measures except Lund-Mackay computed tomography score, which was only conducted before and after treatment. In order to evaluate the safety of CAM, liver function and renal function in all patients were detected before and after treatment. SPSS 16.0 software was used to analyze the data. Forty-five patients completed 3 months follow-up and 5 patients withdrew due to different reasons. The results were as follows: (1) Thirty-three patients with CRSsNP's VAS scores of four time point were 5.81 ± 1.69, 3.76 ± 1.94, 2.98 ± 1.95, 2.06 ± 2.13, respectively, there were statistically significant improvements in turn (t values were 5.910, 8.090, 8.932, all P 0.05). Endoscopy score of four time point were 10.65 ± 1.77, 9.35 ± 1.93, 8.65 ± 2.76, 8.47 ± 2.76, respectively, there were statistically significant improvements in turn(t values were 4.068, 4.863, 5.156, all P CAM treatment, 1 patient reported a tolerable headache and weakness and 1 patient had abdominal pain after two months treatment, all the symptoms disappeared while they were asked to stop the drug. Liver function and renal function were detected in 40 patients, the differences
Fikowski, Jill; Marchand, Kirsten; Palis, Heather; Oviedo-Joekes, Eugenia
Uncovering patterns of drug use and treatment access is essential to improving treatment for opioid dependence. The life history calendar (LHC) could be a valuable instrument for capturing time-sensitive data on lifetime patterns of drug use and addiction treatment. This study describes the methodology applied when collecting data using the LHC in a sample of individuals with long-term opioid dependence and aims to identify specific factors that impact the feasibility of administering the LHC interview. In this study, the LHC allowed important events such as births, intimate relationships, housing, or incarcerations to become reference points for recalling details surrounding drug use and treatment access. The paper concludes that the administration of the LHC was a resource-intensive process and required special attention to interviewer training and experience with the study population. These factors should be considered and integrated into study plans by researchers using the LHC in addiction research.
Zhou, Dongkai; Wang, Weilin; Cheng, Xiaofei; Wei, Jianfeng; Zheng, Shusen
Chronic pancreatitis is a progressive, inflammatory disease of pancreas characterized by significant abdominal pain, malabsorption, and diabetes mellitus. Antioxidant therapy has been proposed as an effective treatment for painful chronic pancreatitis. We performed a meta-analysis of trials in which antioxidant therapy was compared with placebo in chronic pancreatitis. We searched six databases to identify relevant trials. Results are expressed as risk ratio (RR) or standardized mean difference (SMD) with accompanying 95% confidence intervals (CI). The meta-analysis was performed with the fixed-effects model or random-effects model according to heterogeneity. Eight studies including 573 patients met the inclusion criteria. A meta-analysis of these studies revealed that the intervention of antioxidants was associated with a significant increase in patients with pain relief (RR, 2.15; 95% CI, 1.72-2.69; P chronic pancreatitis patients (SMD: -0.41; 95% CI: -0.83 to -0.10; P = 0.0005). Additionally, antioxidants may cause some adverse reactions (RR, 4.22; 95% CI: 2.17-8.20; P pathophysiology of chronic pancreatitis, and administration of antioxidants to patients with painful chronic pancreatitis is effective in relieving pain. Antioxidant supplements may be advocated as one medical therapy for chronic pancreatitis patients with low antioxidant capacity in their blood. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Argstatter, Heike; Grapp, Miriam; Plinkert, Peter K; Bolay, Hans Volker
Musical training positively influences the cortical plasticity of the brain and has proven to be effective in treating chronic tinnitus. A neuro-music therapy concept, the "Heidelberg Neuro-Music Therapy" treatment was developed and evaluated. A prospective, cross-sectional design was used. N = 135 patients (mean age 47 years) with chronic, tonal tinnitus attended a standardized protocol for Neuro-Music Therapy (either "standard therapy" ST or "compact therapy" CT). The results were compared to a cognitive behavioral placebo music therapy procedure (PT). Tinnitus distress was assessed using the German version of the Tinnitus-Questionnaire (TQ) at admission, at discharge and six months after therapy. Changes were assessed statistically and by means of clinical significance. TQ scores significantly improved - independent of group allocation. But more than 80% of the music therapy patients (both ST and CT) revealed a reliable improvement ("responder") compared to 44% in the PT group. Therapy impact seems to be lasting since TQ scores remained stable until follow-up at six months. The "Heidelberg Neuro-Music Therapy" is a method with fast onset and long lasting effect for patients with "tonal" tinnitus. A number of potential working factors accounting for the treatment success are highlighted.
Full Text Available Objective: Quality of life has recently been recognized as an important goal of health care in psychiatry. In this study quality of life of chronic psychiatric patients was evaluated after psychosocial occupational therapy interventions. Materials & Methods: This study is interventional and quasi experimental. Twoenty four chronic mental patients who had refered to SINA Daily Center as intervention group and fifty chronic mental patients as control group were selected by simle and convenient sampling. The instrument was Wisconsin Quality of Life Client Questionnaire that included 8 subscales. Occupational therapy services consisting group therapy, activity therapy and art therapy, according to center’ plane, were performed during 3 months (2 times in week, 90 minutes in each session for intervention group. Independent T test & Paired T test were used for data analysis. Results: There was no significant difference between two groups in parts of QOL before intervention, but after intervention, significant differences were observed in mean scores of satisfaction level, occupational activities, psychological well–being, physical health and total quality o life (P<0.001, also social relation (P=0.005 and economic situation (P=0.003.There was no significant difference between two group in symptoms (P=0.277 and activity of daily living (P=0.020 after intervention. Conclusion: Psychosocial occupational therapy services are effective on satisfaction level and quality of life of chronic psychiatric patients.
Full Text Available Background: Methadone Maintenance Therapy (MMT is the most important treatment for opioid -dependency recurrence. The aim of this study was to compare the craving level in opioid-dependent individuals and people under methadone maintenance therapy. Methods: In this case – control study, 120 men with opioid dependency were selected through cluster sampling method. They were divided into two groups, 60 people in opioid-dependent group and 60 people in MMT group. Both groups were matched for age, sex, marital status, education, duration of opioid dependency and method of consumption. Then, they completed INCAS Substance Abuse Profile (ISAP, opiate withdrawal symptoms checklist, self–report of craving, Desire for Drug Questionnaire (DDQ, Obsessive Compulsive Drug Use Scale (OCDUS and visual cue-induced craving questionnaire. Data were analyzed by SPSS 15 using t-test and ANOVA. Results: Mean craving for drug significantly was lower in MMT group comparing opioid-dependent group (P<0.01. Conclusion: Methadone Maintenance Therapy decreased the craving for drugs and substances This can have an important role in relapse prevention.
Overdose related to prescription opioids has become an epidemic. This podcast discusses the risks of this type of drug sometimes used to treat pain, and how to protect yourself. . Created: 4/19/2016 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP). Date Released: 4/19/2016.
Benjamin Arthurs, MD; Kathy Wunderle, MD; Maylee Hsu, MD; Suil Kim, MD, PhD
We report a case of invasive pulmonary aspergillosis in a patient taking ibrutinib, a Bruton's tyrosine kinase inhibitor used to treat refractory chronic lymphocytic leukemia. We hypothesize that ibrutinib promoted this infection by suppressing innate immune responses against Aspergillus. Clinicians should be aware of potential Aspergillus infections in patients treated with this drug.
Benjamin Arthurs, MD
Full Text Available We report a case of invasive pulmonary aspergillosis in a patient taking ibrutinib, a Bruton's tyrosine kinase inhibitor used to treat refractory chronic lymphocytic leukemia. We hypothesize that ibrutinib promoted this infection by suppressing innate immune responses against Aspergillus. Clinicians should be aware of potential Aspergillus infections in patients treated with this drug.
Arthurs, Benjamin; Wunderle, Kathy; Hsu, Maylee; Kim, Suil
We report a case of invasive pulmonary aspergillosis in a patient taking ibrutinib, a Bruton's tyrosine kinase inhibitor used to treat refractory chronic lymphocytic leukemia. We hypothesize that ibrutinib promoted this infection by suppressing innate immune responses against Aspergillus . Clinicians should be aware of potential Aspergillus infections in patients treated with this drug.
Marcella, Stefanie; Welsh, Belinda; Foley, Peter
A 38-year-old woman developed clinical, biochemical, radiological and histopathological evidence of cutaneous and pulmonary sarcoidosis 5 months after commencing adalimumab for chronic plaque psoriasis. Signs and symptoms resolved within 3 months of cessation of adalimumab. © 2010 The Authors. Australasian Journal of Dermatology © 2010 The Australasian College of Dermatologists.
Full Text Available Clinical and pharmacological characteristics of nootropics — one of the most productive groups of neuropsychotropic drugs, are considered. Classification of nootropics based on the main mechanism of action is constructed. The examples of clinical use of drugs in patients with chronic cerebral ischemia are presented.
Chekman, I.S.; Belenichev, I.F.; Demchenko, A.V.; Bobrova, V.I.; Kucherenko, L.I.; Gorchakova, N.A.; Bukhtiyarova, N.V.
Clinical and pharmacological characteristics of nootropics — one of the most productive groups of neuropsychotropic drugs, are considered. Classification of nootropics based on the main mechanism of action is constructed. The examples of clinical use of drugs in patients with chronic cerebral ischemia are presented.
Ordzhonikidze, N V; Filimonov, V G; Klimenko, P A; Kondrikov, N I; Akin'shina, V S; Berlin, Iu V
A new pathogenetically based non-medicamentous method for correction of uteroplacental bloodflow disturbances has been developed on the model of chronic placental insufficiency in rats. A single 5 min laser-magnetic exposure on day 21 of normal pregnancy resulted in a vasodilating effect with reduction of the peripheral resistance in the uterine horn vessels and with improvement of their blood supply. A new LAMA laser magneto-therapeutic device was employed. Daily 5 min sessions of laser magnetic therapy administered to rats with chronic placental insufficiency from pregnancy days 15-16 to 21 normalized uterine horn contractility and resulted in positive morphofunctional changes in the components of the uterine horns and placenta, being associated with a noticeable improvement of fetal functions. Hence, laser magnetic therapy may be regarded as an effective non-drug method for therapy of chronic placental insufficiency.
Leathern, L L
Opioid drugs influence various behavioural parameters including locomotor activity in experimental animals. The interaction between the opioid and dopaminergic systems is one possible explanation for the effect of opioid drugs on locomotor activity. In this study behavioural and biochemical assays were done to investigate the interaction between the opioid and dopaminergic systems. Behavioural studies were done by measurement of locomotor activity (LA) of rats after acute or chronic pretreatment with opioid andor dopaminergic drugs. Biochemical studies were in the form of radioligand binding assays, the effect on the number (Bmax) and affinity (K/sub D/) of receptors was measured after chronic pretreatment with opioid andor dopaminergic drugs. The opioid drugs used are morphine, nalbuphine and naloxone. Dopaminergic drugs used included: agonists-apomorphine and piribedil; antagonists-pimozide, haloperidol, chlorpromazine. In the acute situation increased LA was obtained with morphine and the DA agonists. A correlation between the behavioural and biochemical assays was found. Chronic pretreatment with morphine enhanced apomorphine induced LA, this supersensitivity was also measured as an increased receptor density (Bmax) of D2 receptors in the striatum. Chronic morphine pretreatment caused a decrease in morphine induced LA, while this subsensitivity was not apparent in the ligand binding assays - where no change in receptor number was observed. Chronic naloxone pretreatment enhanced morphine induced LA, as well as increased the Bmax of opioid receptors in the whole brain. It is concluded that an interaction between the opioid and dopaminergic systems does exist, and may account for the mechanism of action of the opioids.
Leece, Pamela; Buchman, Daniel Z; Hamilton, Michael; Timmings, Caitlyn; Shantharam, Yalnee; Moore, Julia; Furlan, Andrea D
Introduction In North America, drug overdose deaths are reaching unprecedented levels, largely driven by increasing prescription opioid-related deaths. Despite the development of several opioid guidelines, prescribing behaviours still contribute to poor patient outcomes and societal harm. Factors at the provider and system level may hinder or facilitate the application of evidence-based guidelines; interventions designed to address such factors are needed. Methods and analysis Using implementation science and behaviour change theory, we have planned the development and evaluation of a comprehensive Opioid Self-Assessment Package, designed to increase adherence to the Canadian Opioid Guideline among family physicians. The intervention uses practical educational and self-assessment tools to provide prescribers with feedback on their current knowledge and practices, and resources to improve their practice. The evaluation approach uses a pretest and post-test design and includes both quantitative and qualitative methods at baseline and 6 months. We will recruit a purposive sample of approximately 10 family physicians in Ontario from diverse practice settings, who currently treat patients with long-term opioid therapy for chronic pain. Quantitative data will be analysed using basic descriptive statistics, and qualitative data will be analysed using the Framework Method. Ethics and dissemination The University Health Network Research Ethics Board approved this study. Dissemination plan includes publications, conference presentations and brief stakeholder reports. This evidence-informed, theory-driven intervention has implications for national application of opioid quality improvement tools in primary care settings. We are engaging experts and end users in advisory and stakeholder roles throughout our project to increase its national relevance, application and sustainability. The performance measures could be used as the basis for health system quality improvement
Herath, Samantha C; Poole, Phillippa
There has been renewal of interest in the use of prophylactic antibiotics to reduce the frequency of exacerbations and improve quality of life in chronic obstructive pulmonary disease (COPD). To determine whether or not regular treatment of COPD patients with prophylactic antibiotics reduces exacerbations or affects quality of life. We searched the Cochrane Airways Group Trials Register and bibliographies of relevant studies. The latest literature search was August 2013. Randomised controlled trials (RCTs) that compared prophylactic antibiotics with placebo in patients with COPD. We used the standard methods of The Cochrane Collaboration. Data were extracted and analysed by two independent review authors. Seven RCTs involving 3170 patients were included in this systematic review. All studies were published between 2001 and 2011. Five studies were of continuous antibiotics and two studies were of intermittent antibiotic prophylaxis (termed 'pulsed' for this review). The antibiotics investigated were azithromycin, erythromycin, clarithromycin and moxifloxacin. Azithromycin, erythromycin and clarithromycin are macrolides while moxifloxacin is a fourth-generation synthetic fluoroquinolone antibacterial agent. The study duration varied from three months to 36 months and all used intention-to-treat analysis. Most of the results were of moderate quality. The risk of bias of the included studies was generally low, and we did not downgrade the quality of evidence for risk of bias.The trials recruited participants with a mean age of 66 years and with at least a moderate severity of COPD. Three trials included participants with frequent exacerbations and two trials recruited participants requiring systemic steroids or antibiotics, or both, or who were at the end stage of their disease and required oxygen.The primary outcomes for this review were the number of exacerbations and quality of life.With use of continuous prophylactic antibiotics the number of patients experiencing
Full Text Available Background. It has been established that many patients with chronic hepatitis C have elevated serum iron, feritin levels and iron deposits in the liver. Therefore, the liver damage due to hepatitis C virus may be aggravated with iron overload. In many studies higher levels of iron in the blood and the liver were connected with the decreased response to interferon-alfa therapy for chronic viral hepatitis C. Recent introduction of pegylated interferons plus ribavirin has improved the therapeutic response, so it is now possible to cure more than 50% of the patients. Case report. Three patients with chronic hepatitis C and iron overload were presented. Iron reduction therapy using phlebotomy or eritrocytapheresis with plasmapheresis was done at different times in regard to specific antiviral therapy or as a sole therapy. Conclusion. It has been shown that iron reduction, sole or combined with antiviral therapy, led to the deacreased aminotransferase serum activity and might have slow down the evolution of chronic hepatitis C viral infection.
O. M. Drapkina
Full Text Available The theory of chronic hyperactivation of neurohormonal systems, in particular, sympathoadrenal and renin-angiotensin-aldosterone, is the basis of modern concepts of the pathogenesis of heart failure. The medicinal blocking of these two systems has proved to be effective in the treatment of heart failure with reduced ejection fraction (<40%. Antagonists of mineralocorticoid receptors, along with angiotensin-converting enzyme inhibitors and beta-blockers, are neurohumoral modulators. They are used to treat patients with heart failure with reduced ejection fraction. The prescription of mineralocorticoid receptor antagonists in clinical practice remains insufficient despite their high efficacy. Demonstration of the site of mineralocorticoid receptor antagonists in the complex treatment of a patient with chronic heart failure and diabetes type 2 is the goal of this article.
Venzin, Claudio; Ohlerth, Stefanie; Koch, D; Spreng, D
A 15-month-old, spayed female, Bernese mountain dog was presented to the Institute of Small Animal Surgery at the University of Zurich because of chronic left forelimb lameness. The referring veterinarian diagnosed pain in the left shoulder region and had treated the dog with systemic non-steroidal anti-inflammatory drugs and restricted exercise for a two-week period. The follow-up examination revealed only minimal improvement and therefore, the dog was referred for further diagnostic evaluat...
Sindermann, J R; Klotz, S; Rahbar, K; Hoffmeier, A; Drees, G
The German Disease Management Guideline "Chronic Heart Failure" intends to guide physicians working in the field of diagnosis and treatment of heart failure. The guideline provides a tool on the background of evidence based medicine. The following short review wants to give insights into the role of some surgical treatment options to improve heart failure, such as revascularization, ventricular reconstruction and aneurysmectomy, mitral valve reconstruction, ventricular assist devices and heart transplantation. (c) Georg Thieme Verlag KG Stuttgart-New York.
Siebenhuener, Klarissa; Eschmann, Emmanuel; Kienast, Alexander; Schneider, Dominik; Minder, Christoph E.; Saller, Reinhard; Zimmerli, Lukas; Blaser, Jürg; Battegay, Edouard
Background Chronic pain is common in multimorbid patients. However, little is known about the implications of chronic pain and analgesic treatment on multimorbid patients. This study aimed to assess chronic pain therapy with regard to the interaction potential in a sample of inpatients with multiple chronic conditions. Methods and Findings We conducted a retrospective study with all multimorbid inpatients aged ≥18 years admitted to the Department of Internal Medicine of University Hospital Zurich in 2011 (n = 1,039 patients). Data were extracted from the electronic health records and reviewed. We identified 433 hospitalizations of patients with chronic pain and analyzed their combinations of chronic conditions (multimorbidity). We then classified all analgesic prescriptions according to the World Health Organization (WHO) analgesic ladder. Furthermore, we used a Swiss drug-drug interactions knowledge base to identify potential interactions between opioids and other drug classes, in particular coanalgesics and other concomitant drugs. Chronic pain was present in 38% of patients with multimorbidity. On average, patients with chronic pain were aged 65.7 years and had a mean number of 6.6 diagnoses. Hypertension was the most common chronic condition. Chronic back pain was the most common painful condition. Almost 90% of patients were exposed to polypharmacotherapy. Of the chronic pain patients, 71.1% received opioids for moderate to severe pain, 43.4% received coanalgesics. We identified 3,186 potential drug-drug interactions, with 17% classified between analgesics (without coanalgesics). Conclusions Analgesic drugs-related DDIs, in particular opioids, in multimorbid patients are often complex and difficult to assess by using DDI knowledge bases alone. Drug-multimorbidity interactions are not sufficiently investigated and understood. Today, the scientific literature is scarce for chronic pain in combination with multiple coexisting medical conditions and medication
... and gallbladder disease. It also can increase the risk of dementia and urinary incontinence. The Task Force found that taking estrogen alone ... has important potential harms. It can increase the risk of stroke, blood clots, gallbladder disease, and urinary ... a fracture Combined Hormone Therapy ...
QIN Yuan; ZHANG Ying; ZHAO Jieru
More than 20% of chronic hepatitis C (CHC) patients receiving the antiviral therapy with interferonα(IFNα) experience depression, and fluoxetine is often used to alleviate this symptom. Fluoxetine has anti-inflammatory properties and can change the synthesis of liver lipids, but its influence on antiviral therapy for CHC and related mechanism remain unknown. Recent studies show that fluoxetine can inhibit hepatitis C virus (HCV) infection and reduce the production of reactive oxygen species (...
Pizzolato, N.; Valenti, D.; Spagnolo, B.; Persano Adorno, D.
A simulative study of cancer growth dynamics in patients affected by Chronic Myeloid Leukemia (CML), under the effect of a targeted dose dependent continuous or pulsed therapy, is presented. We have developed a model for the dynamics of CML in which the stochastic evolution of white blood cell populations are simulated by adopting a Monte Carlo approach. Several scenarios in the evolutionary dynamics of white blood cells, as a consequence of the efficacy of the different modelled therapies, pulsed or continuous, are described. The best results, in terms of a permanent disappearance of the leukemic phenotype, are achieved with a continuous therapy and higher dosage. However, our findings demonstrate that an intermittent therapy could represent a valid choice in patients with high risk of toxicity, when a long-term therapy is considered. A suitably tuned pulsed therapy can enhance the treatment efficacy and reduce the percentage of patients developing resistance. (authors)
Nevitt, Benjamin N; Robinson, Narda; Kratz, Gail; Johnston, Matthew S
Management of trauma-induced chronic torticollis in raptors has historically been challenging. Euthanasia is common in affected birds because of their inability to maintain normal cervical position, although they may be able to function normally. To assess effectiveness of physical therapy of the neck and head as an adjunct treatment for this condition, a case-control study was done in raptors admitted to the Rocky Mountain Raptor Program from 2003 to 2010. Eleven cases were identified with a diagnosis of chronic torticollis resulting from traumatic brain injury. Five cases were treated with physical therapy of the head and neck, and 6 control cases did not receive any physical therapy for the torticollis. Of the control cases, 0 of 6 had resolution of the torticollis, 0 of 6 were released, and 5 of 6 were euthanatized. Of the treated cases, 4 of 5 had complete resolution of the torticollis and 5 of 5 were released. Resolution of torticollis differed significantly between cases receiving physical therapy and controls. These results indicate that physical therapy should be used as an adjunctive therapy in cases of chronic torticollis induced by trauma in raptors because it results in better resolution of the torticollis and increased likelihood of release.
Rupasinghe, Sukitha Namal; Siriwardena, Ajith K
Micronutrient antioxidant therapy did not relieve pain in a European randomized trial of patients with chronic pancreatitis without malnutrition. However, intervention was undertaken only for 6 months leaving unanswered the question of whether long-term antioxidant therapy may modulate chronic pancreatitis. The aim of this study is to assess the outcome of long-term use of micronutrient antioxidant therapy in patients with chronic pancreatitis. This is a single center clinical cohort report of patients with chronic pancreatitis prescribed micronutrient antioxidant therapy and followed for up to 10 years. Data were collected on demographic detail, clinic pain assessment, insulin requirements, interventions and outcome. A group of 30 patients with a diagnosis of chronic pancreatitis constitute the study population. Median age at time of diagnosis was 40 years (range 14-66); 19 (63%) were male and the median duration of symptoms was 2 years (range 0-18). Alcohol was the dominant cause in 22 (73%) patients and 16 (53%) patients were Cambridge stage 1. Twenty-four (80%) patients had pain at presentation. During antioxidant treatment of 4 years (range 1-10), pain decreased but the proportion with abdominal pain compared to those who were pain-free remained constant (P=0.16; two-way ANOVA with Bonferroni correction). There was a significant increase in requirement for insulin (P=0.028) with time together with use of both endoscopic and surgical interventions. This is the first study to report long-term disease-specific outcome in patients with chronic pancreatitis prescribed micronutrient antioxidant therapy. There appears to be no effect of intervention on outcome.
Højsted, Jette; Kurita, Geana Paula; Kendall, Sally
Opioids constitute the basis for pharmacological treatment of moderate to severe pain in cancer pain and non-cancer pain patients. Their action is mediated by the activation of opioid receptors, which integrates the pain modulation system with other effects in the central nervous system including...... groups: no effects or worsening of cognitive function in cancer pain patients and no effect or improvements in the chronic non-cancer pain patients, however, due to methodological limitations and a huge variety of designs definite conclusions are difficult to draw from the studies. In studies of higher...
Full Text Available Ashley Brenton,1 Steven Richeimer,2,3 Maneesh Sharma,4 Chee Lee,1 Svetlana Kantorovich,1 John Blanchard,1 Brian Meshkin1 1Proove Biosciences, Irvine, CA, 2Keck school of Medicine, University of Southern California, Los Angeles, CA, 3Departments of Anesthesiology and Psychiatry, University of Southern California, Los Angeles, CA, 4Interventional Pain Institute, Baltimore, MD, USA Background: Opioid abuse in chronic pain patients is a major public health issue, with rapidly increasing addiction rates and deaths from unintentional overdose more than quadrupling since 1999. Purpose: This study seeks to determine the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm incorporating phenotypic risk factors and neuroscience-associated single-nucleotide polymorphisms (SNPs. Patients and methods: The Proove Opioid Risk (POR algorithm determines the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm incorporating phenotypic risk factors and neuroscience-associated SNPs. In a validation study with 258 subjects with diagnosed opioid use disorder (OUD and 650 controls who reported using opioids, the POR successfully categorized patients at high and moderate risks of opioid misuse or abuse with 95.7% sensitivity. Regardless of changes in the prevalence of opioid misuse or abuse, the sensitivity of POR remained >95%. Conclusion: The POR correctly stratifies patients into low-, moderate-, and high-risk categories to appropriately identify patients at need for additional guidance, monitoring, or treatment changes. Keywords: opioid use disorder, addiction, personalized medicine, pharmacogenetics, genetic testing, predictive algorithm
Ay, Yilmaz; Karapinar, Tuba H; Oymak, Yesim; Toret, Ersin; Demirag, Bengu; Ince, Dilek; Ozcan, Esin; Moueminoglou, Nergial; Koker, Sultan A; Vergin, Canan
Immune thrombocytopenic purpura (ITP) results from accelerated platelet destruction mediated by autoantibodies to platelet glycoproteins. Some patients with chronic ITP are refractory to all therapies [steroids, intravenous immunoglobulin (IVIG), anti-D and immunosuppresive drugs] and have chronic low platelet counts and episodic bleeding. We retrospectively evaluated the efficacy and safety of rituximab treatment and splenectomy in paediatric patients diagnosed with chronic and refractory ITP who were unresponsive to steroids, IVIG, cyclosporine and mycophenolate mofetil. Records of patients with chronic and refractory ITP in 459 patients with primary ITP who were followed up in our hospital from January 2005 to December 2014 were reviewed. Fifteen of patients received rituximab and/or applied splenectomy. Fifteen chronic ITP patients (10 boys, five girls) with a mean age of 10 years were enrolled in the study. Two of these patients were suffering from Evans syndrome. The median time since diagnosis of ITP was 10 years. The median follow-up duration after starting Rituximab and splenectomy were 13 and 9.5 months, respectively.None of the seven patients who were treated with rituximab achieved a response. A splenectomy was performed in six of the seven patients who had been treated with rituximab. Complete and partial responses were achieved in 67 and 33% of the patients, respectively. We evaluated the clinical characteristics and responses of chronic ITP patients who did not receive rituximab therapy and underwent a splenectomy. The success rate was 100% in the eight patients with chronic and refractory ITP. Rituximab therapy might not be beneficial for some children with severe chronic ITP who are refractory to standard agents. A splenectomy might be useful and preferable to rituximab.
Frankenstein, Lutz; Zugck, Christian; Schellberg, Dieter; Nelles, Manfred; Froehlich, Hanna; Katus, Hugo; Remppis, Andrew
Like aldosterone escape to ACE-inhibitors, adrenergic escape (AE) to beta-blockers appears conceivable in chronic heart failure (CHF), as generalized systemic neurohumoral activation has been described as the pathophysiological basis of this syndrome. The aim of this study was to examine the prevalence and prognostic value of AE with respect to different beta-blocker agents and doses. This was a prospective, observational study of 415 patients with systolic CHF receiving chronic stable beta-blocker therapy. AE was defined by norepinephrine levels above the upper limit of normal. Irrespective of the individual beta-blocker agents used and the dose equivalent taken, the prevalence of AE was 31-39%. Norepinephrine levels neither correlated with heart rate (r=0.02; 95% CI: -0.08-0.11; P=0.74) nor were they related to underlying rhythm (P=0.09) or the individual beta-blocker agent used (P=0.87). The presence of AE was a strong and independent indicator of mortality (adjusted HR: 1.915; 95% CI: 1.387-2.645; chi2: 15.60). We verified the presence of AE in CHF patients on chronic stable beta-blocker therapy, irrespective of the individual beta-blocker agent and the dose equivalent. As AE might indicate therapeutic failure, the determination of AE could help to identify those patients with CHF that might benefit from more aggressive treatment modalities. Heart rate, however, is not a surrogate for adrenergic escape.
Hayes, Corey J; Hudson, Teresa J; Phillips, Martha M; Bursac, Zoran; Williams, James S; Austin, Mark A; Edlund, Mark J; Martin, Bradley C
Our aim is to determine if propoxyphene withdrawal from the US market was associated with opioid continuation, continued chronic opioid use, and secondary propoxyphene-related adverse events (emergency department visits, opioid-related events, and acetaminophen toxicity). Medical service use and pharmacy data from 19/11/08 to 19/11/11 were collected from the national Veterans Healthcare Administration healthcare databases. A quasi-experimental pre-post retrospective cohort design utilizing a historical comparison group provided the study framework. Logistic regression controlling for baseline covariates was used to estimate the effect of propoxyphene withdrawal. There were 24,328 subjects (policy affected n = 10,747; comparison n = 13,581) meeting inclusion criteria. In the policy-affected cohort, 10.6% of users ceased using opioids, and 26.6% stopped chronic opioid use compared with 3.8% and 13.5% in the historical comparison cohort, respectively. Those in the policy-affected cohort were 2.7 (95%CI: 2.5-2.8) and 3.2 (95%CI: 2.9-3.6) times more likely than those in the historical comparison cohort to discontinue chronic opioid and any opioid use, respectively. Changes in adverse events and Emergency Department (ED) visits were not different between policy-affected and historical comparison cohorts (p > 0.05). The withdrawal of propoxyphene-containing products resulted in rapid and virtually complete elimination in propoxyphene prescribing in the veterans population; however, nearly 90% of regular users of propoxyphene switched to an alternate opioid, and three quarters continued to use opioids chronically. Copyright © 2015 John Wiley & Sons, Ltd.
Schultze, J.; Reinke, C.; Kimmig, B.; Frese, K.A.
Background: The treatment results of symptomatic radiation therapy of the Eustachian tube in chronic otitis media had to be evaluated retrospectively. Patients and Methods: Between 1980 and 1997, 66 patients were referred for therapy. The median age was 58 years. In the clinical presentation, all the patients had a hearing impairment, 35 patients complained of pain, 21 had otorrhea. In their history, 20 patients indicated chronic recurrent infections. The complaints lasted for 4.7 years in the median, primary conservative (adstringentia, antibiotics) and surgical treatment (paracentesis, tympanic tubule, tympanoplastic) did not lead to lasting cure. In 40 of 66 patients, finally radiation therapy was done of both Eustachian tubes. With opposed fields and cobalt-60 photons a total dose of 6 Gy at single doses of 1 Gy, three times a week, was applied. Under the causes for exclusion of radiation therapy were non-acceptance of the patients (nine), prior radiation therapies (six) or spontaneous improvement after initial presentation in our department. The treatment results were evaluated by interviews of the patients and regular otorhinolaryngological examinations. Results: There were no side effects noticed. 28 of 40 (70%) patients reported a significant improvement that could be verified by objective otorhinolaryngological examinations. In the group of 26 nonirradiated patients, 22 could be interviewed indicating in 16 cases (72%) that the complaints were unchanged and chronic otitis media was lasting. In a subgroup analysis concerning the duration of otitis media radiation therapy proved more effective in an acute and subacute stadium of disease of up to 5 years duration, while the patients resistant to radiation therapy were entirely in a chronic stage of disease exceeding 5 years duration. (orig.) [de
Full Text Available Objective: To compare pre- and post-therapy symptom scores reported on the National Institute of Health Chronic Prostatitis Symptom Index (NIHCPSI after trans-rectal antibiotic injections therapy for men suffering from chronic prostatitis. Materials and methods: Retrospective analysis of NIHCPSI symptom scores obtained from chart reviews of 77 treated males suffering from chronic prostatitis before and after trans rectal injections for the treatment of chronic prostatitis. Results: Most patients reported a 40% to 60% improvement in symptom scores. In subgroups comparing scores in patients with less than 5 injections, the improvement was less than in patients who received 10 or more injections. Patients’ responses after a shorter (3 months follow up showed better pain scores than patient’s scores after longer, over one-year or more, follow- up periods. Conclusion: Our findings show that direct antibiotic injection for chronic prostatitis is a viable addition to standard therapies. Improvements in symptom scores are long lasting. Discomfort is minimal and side effects are rare and avoidable
Full Text Available Chronic kidney disease has direct implications in nutritional status, causing anorexia and muscular catabolism. These situations are frequent in kidney renal replacement therapy in which nutritional disorders and inflammatory mechanisms associated with therapy often lead to the development of protein-energy wasting. Nutrition therapy has shown an adequate therapeutic strategy to prevent and treat metabolic alterations, reducing surgical and nutritional complication risks in kidney transplantation patients. The current case reports nutritional intervention on a continuous ambulatory peritoneal dialysis patient who was subsequently prescribed to automatic peritoneal dialysis and, finally, kidney transplant from a living donor.
Jadhav, Tanya; Bhat, K Mahalinga; Bhat, G Subraya; Varghese, Jothi M
Gingival enlargement, also synonymous with the terms gingival hyperplasia or hypertrophy, is defined as an abnormal overgrowth of gingival tissues. A case of a 19-year-old male presenting with maxillary and mandibular chronic inflammatory gingival enlargement associated with prolonged orthodontic therapy is reported here. Surgical therapy was carried out to provide a good aesthetic outcome. No recurrence was reported at the end of 1 year. The importance of patient motivation and compliance during and after therapy as a critical factor in the success of treatment has also been highlighted through this case report.
Dignam, Jade; Copland, David; O'Brien, Kate; Burfein, Penni; Khan, Asaduzzaman; Rodriguez, Amy D.
Purpose: The relationship between cognitive abilities and aphasia rehabilitation outcomes is complex and remains poorly understood. This study investigated the influence of language and cognitive abilities on anomia therapy outcomes in adults with aphasia. Method: Thirty-four adults with chronic aphasia participated in Aphasia Language Impairment…
Geraets, J.J.; Goossens, M.E.J.B.; Bruijn, C.P. de; Groot, I.J.M. de; Koke, A.J.; Pelt, R.A.; Heijden, G. van der; Dinant, G.J.; Heuvel, W.J.A. van den
OBJECTIVES: The present study evaluated the cost-effectiveness of a behavioral graded exercise therapy (GET) program compared with usual care (UC) in terms of the performance of daily activities by patients with chronic shoulder complaints in primary care. METHODS: A total of 176 patients were
Wong, Daniel F. K.; Ip, Priscilla S. Y.; Lee, Kim Man
This pilot study attempted to examine the effectiveness of a brief cognitive behavioural therapy (CBT) psychoeducational group for Chinese people with chronic illness in Hong Kong. It adopted a single group design, and 52 participants joined the group. A questionnaire with three outcome measures, measuring general mental health, quality of life…
de Lange, Floris P.; Koers, Anda; Kalkman, Joke S.; Bleijenberg, Gijs; Hagoort, Peter; van der Meer, Jos W. M.; Toni, Ivan
Chronic fatigue syndrome (CFS) is a disabling disorder, characterized by persistent or relapsing fatigue. Recent studies have detected a decrease in cortical grey matter volume in patients with CFS, but it is unclear whether this cerebral atrophy constitutes a cause or a consequence of the disease. Cognitive behavioural therapy (CBT) is an…
Heins, M.J.; Knoop, H.; Lobbestael, J.; Bleijenberg, G.
Objective: To examine the relationship between a history of childhood maltreatment and the treatment response to cognitive behavior therapy for chronic fatigue syndrome (CFS). Methods: A cohort study in a tertiary care clinic with a referred sample of 216 adult patients meeting the Centers for
Shaplygin, L V; Begaev, A I; V'iushina, V V
The examination of the patients exposed to physical factors (magnetotherapy, laser therapy and thermotherapy) has demonstrated that Intramag unit with attachments Intraterm and LAST-02 for local physiotherapy is effective in patients with chronic prostatitis and can be used in urological hospitals and outpatient clinics.
The paper summarizes the latest evidence on the treatment of musculoskeletal conditions (with special focus on chronic LBP) by using acupuncture and bee venom therapy (BVT). Methodology: The overview is based on English-language studies and articles found by searches of Medline over more than last 10 years.
Valmaggia, Lucia R.; Tabraham, Paul; Morris, Eric; Bourrian, Theo K.
Since the early 1990s, cognitive behavioral therapy (CBT) has been increasingly used as an adjunctive treatment for psychotic disorders. This paper describes the CBT of three cases, each at a different stage of psycholic disorder: at-risk mental state, first-episode psychosis, and chronic psychotic
Achhra, Amit C; Nugent, Melinda; Mocroft, Amanda
Chronic kidney disease (CKD) has emerged as an important health concern in HIV-positive individuals. Preventing long-term kidney toxicity from an antiretroviral therapy is therefore critical. Selected antiretroviral agents, especially tenofovir disoproxil fumarate (TDF) and some ritonavir-boosted...
Miyamura, Satoshi; Tsuji, Shigeyoshi; Iwai, Takao; Hamada, Masayuki
Vacuum-assisted wound closure (VAC) is useful for difficult wound beds, although sites where bleeding or infection is expected are usually regarded as problematic for this therapy. This report outlines the treatment of chronic tibial osteomyelitis (Cierny- Mader type III) due to mixed infection with Nocardia spp and Bacteroi- des fragilis by postoperative VAC therapy direct to the medullary cavity, followed by wound coverage with a gastrocnemius myocutaneous skin flap. A 64-year-old man developed chronic left tibial os- teomyelitis after a work injury. The nonviable tissues were debrided, including a sequestrum. Nocardia spp and B. fragilis were isolated from surgical bone specimens, and chronic tibial osteomyelitis due to mixed infection was diagnosed. Postoperatively, VAC therapy was performed directly to the open medullary cavity of the tibia and sub- sequently covered the residual soft tissue defect with a gastrocnemius myocutaneous flap. The authors could not find any English literature on VAC therapy direct to the medullary cavity combined with transplantation of a myocutaneous flap for osteomyelitis. Nocardia spp can cause a variety of infections, among which osteomyelitis occupies a relatively small percentage. This case raises the possibil- ity of treating chronic tibial osteomyelitis caused by mixed infection with Nocardia spp and B. fragilis by applying postoperative VAC ther- apy directly to the medullary cavity and covering the residual wound with a gastrocnemius myocutaneous flap.
Rudmik, Luke; Hoy, Monica; Schlosser, Rodney J; Harvey, Richard J; Welch, Kevin C; Lund, Valerie; Smith, Timothy L
Topical therapies have become an integral component in the management plan for chronic rhinosinusitis (CRS). Several topical therapy strategies have been evaluated, but a formal comprehensive evaluation of the evidence has never been performed. The purpose of this article is to provide an evidence-based approach for the utilization of topical therapies in the management of CRS. A systematic review of the literature was performed and the guidelines for development of an evidence-based review with recommendations were followed. Study inclusion criteria were: adult population >18 years old; chronic rhinosinusitis (CRS) based on published diagnostic criteria; and clearly defined primary clinical end-point. We focused on reporting higher-quality studies (level 2b or higher), but reported on lower-level studies if the topic contained insufficient evidence. We excluded drug-eluting spacer and stent therapy from this review. This review identified and evaluated the literature on 5 topical therapy strategies for CRS: saline irrigation, topical steroid, topical antibiotic, topical antifungal, and topical alternatives (surfactant, manuka honey, and xylitol irrigations). Based on the available evidence, sinonasal saline irrigation and standard topical nasal steroid therapy are recommended in the topical treatment of CRS. Nonstandard (off-label) topical sinonasal steroid therapies can be an option for managing CRS. The evidence recommends against the use of topical antifungal therapy and topical antibiotic therapy delivered using nebulized and spray techniques in routine cases of CRS. There is insufficient clinical research to provide recommendations for alternative therapies or topical antibiotic therapy delivered using other delivery methods (eg, irrigations). © 2013 ARS-AAOA, LLC.
Aneni, Ehimen C; Escolar, Esteban; Lamas, Gervasio A
Over the last few decades, there has been a growing body of epidemiologic evidence linking chronic toxic metal exposure to cardiovascular disease-related morbidity and mortality. The recent and unexpectedly positive findings from a randomized, double-blind, multicenter trial of metal chelation for the secondary prevention of atherosclerotic cardiovascular disease (Trial to Assess Chelation Therapy (TACT)) have focused the discussion on the role of chronic exposure to toxic metals in the development and propagation of cardiovascular disease and the role of toxic metal chelation therapy in the secondary prevention of cardiovascular disease. This review summarizes the most recent evidence linking chronic toxic metal exposure to cardiovascular disease and examines the findings of TACT.
Pleyer, Christopher; Wiestner, Adrian; Sun, Clare
Ibrutinib and idelalisib are kinase inhibitors that have revolutionized the treatment of chronic lymphocytic leukemia (CLL). Capable of inducing durable remissions, these agents also modulate the immune system. Both ibrutinib and idelalisib abrogate the tumor-supporting microenvironment by disrupting cell-cell interactions, modulating the T-cell compartment, and altering the cytokine milieu. Ibrutinib also partially restores T-cell and myeloid defects associated with CLL. In contrast, immune-related adverse effects, including pneumonitis, colitis, hepatotoxicity, and infections are of particular concern with idelalisib. While opportunistic infections and viral reactivations occur with both ibrutinib and idelalisib, these complications are less common and less severe with ibrutinib, especially when used as monotherapy without additional immunosuppressive agents. This review discusses the impact of ibrutinib and idelalisib on the immune system, including infectious and auto-immune complications as well as their specific effects on the B-cell, T-cell, and myeloid compartment.
The incidence of chronic pancreatitis is increasing in industrialized countries due to the steady increase of alcohol abuse. The pathogenesis of this disease is still incompletely understood. A cure is not possible. The knowledge of the patients history and a thorough clinical investigation together with the availability of a wide array of laboratory tests and imaging procedures enable the physician to characterize the stage of the disease. Exact knowledge of the present pancreatic morphology, potential complications of the disease, and knowledge about the present exocrine and endocrine function capacity are prerequisites for adequate therapeutic decision making. The therapeutic possibilities include termination of alcohol abuse, various options of treatment of pain according to the various pathogenetic possibilities leading to pain, pancreatic digestive enzyme supplementation, treatment of diabetes, and either endoscopic or surgical treatments of complications of the disease. (orig.) [de
Jones, A; Rowe, B H
This study had two objectives: (1) to examine the effects of bronchopulmonary hygiene physical therapy on patients with chronic obstructive pulmonary disease and bronchiectasis; (2) to determine any differences between manual and mechanical techniques for bronchopulmonary hygiene physical therapy. The study design was a systematic review of the literature that used an exhaustive search for trials and review methods prescribed by the Cochrane Collaboration. Randomized controlled trials examined patient groups, interventions, and dependent variables. Patients included those with chronic obstructive pulmonary diseases (emphysema or chronic bronchitis) or bronchiectasis. Any of the following interventions or combinations thereof were included: manual interventions, such as postural drainage, chest percussion, vibration, chest shaking, directed coughing, or forced exhalation technique. Controls of the study were as follows: no intervention; placebo; coughing; and mechanical interventions, such as mechanical vibration. The search identified 99 potential trials; inclusion or exclusion analysis left 7, which examined a total of 126 patients. Mean score on trial quality was 1.4 (5 = greatest). Three separate trials (N = 51) found statistically significant effects for bronchopulmonary hygiene physical therapy on sputum production and radioaerosol clearance. No trials (N = 126) found statistically significant effects on pulmonary function variables or differences between manual and mechanical techniques. Considering the small sizes, low quality, and mixed results from the trials, the research on bronchopulmonary hygiene physical therapy is inconclusive. There is a need for adequately sized, high-quality, randomized controlled trials with uniform patient populations to examine the effects of bronchopulmonary hygiene physical therapy.
Drewes, Asbjørn; Jensen, Rasmus D.; Nielsen, Lecia M.
to morphine. Although this approach is recognized as cost-effective in most cases there is solid evidence that, on an individual patient basis, opioids are not all equal. Therefore it is important to have an armamentarium of strong analgesics in clinical practice to ensure a personalized approach in patients...... who do not respond to standard treatment. In this review we highlight differences between opioids in human studies from a pharmacological, experimental, clinical and health economics point of view. We provide evidence that individuals respond differently to opioids, and that general differences......Clinical studies comparing the response and side effects of various opioids have not been able to show robust differences between drugs. Hence, recommendations of the regulatory authorities have been driven by costs with a general tendency in many countries to restrict physician's use of opioids...
Full Text Available The insufficient pain relief provided by current pharmacotherapy for chronic neuropathic pain is a serious medical problem. The enhanced glutamate signaling via NMDA receptors appears to be one of the key events in the development of chronic pain. Although effective, clinical use of systemic NMDA antagonists is limited by adverse effects such as hallucinations and motor dysfunction. Opioids are also potent analgesics but their chronic use is accompanied by tolerance and risk of addiction. However, combination of NMDA antagonists and opioids seems to provide a stable pain relieve at subthreshold doses of both substances, eliminating development of side effects. Our previous research showed that combined delivery of NMDA antagonist Serine histrogranin (SHG and endomorphin1 (EM1 leads to attenuation of acute and chronic pain. The aim of this study was to design and evaluate an analgesic potency of the gene construct encoding SHG and EM1. Constructs with 1SHG copy in combination with EM1, 1SHG/EM1, and 6SHG/EM1 were intraspinally injected to animals with peripheral nerve injury-induced pain (chronic constriction injury, CCI or spinal cord injury induced pain (clip compression model, SCI and tactile and cold allodynia were evaluated. AAV2/8 particles were used for gene delivery. The results demonstrated 6SHG/EM1 as the most efficient for alleviation of pain-related behavior. The effect was observed up to 8 weeks in SCI animals, suggesting the lack of tolerance of possible synergistic effect between SHG and EM1. Intrathecal injection of SHG antibody or naloxone attenuated the analgesic effect in treated animals. Biochemical and histochemical evaluation confirmed the presence of both peptides in the spinal tissue. The results of this study showed that the injection of AAV vectors encoding combined SHG/EM constructs can provide long term attenuation of pain without overt adverse side effects. This approach may provide better treatment options for
Zviagin, A A; Nikolaenko, E A
The efficiency of transcutaneous magneto-laser treatment as a component of combined therapy of chronic gastritis in children and adolescents (aged 5-17 years) was compared with that of pharmacotherapy and low-intensity laser therapy. The patients were allocated to three groups of 25 persons each. Patients of group 1 were given only drug therapy, those in group 2 were treated with pharmaceuticals and low-intensity laser therapy. The patients comprising group 3 were subjected to the action of magneto-laser radiation. Magneto-laser therapy was shown to result in a significantly more expressed improvement of clinical and morphological characteristics of the patients compared with pharmacotherapy alone. There was no significant difference between effects of magneto-laser and low-intensity laser radiation.
Filimonov, R M; Musaeva, O M
Primary chronic gastroduodenitis (PCG) is one of the most frequent diseases of the gastrointestinal tract. Timely and efficient treatment of patients with PCG promotes ulcer prevention. In this connection, an urgent problem of restorative medicine is to develop medical programs with active introduction of pharmacophysiotherapeutic complexes, in particular, laser therapy and anti-secretory preparation (famotidine) that increase therapeutic efficacy of treatment of this disease. To this end, we give results of treatment of 50 patients with primary chronic gastroduodenitis (26 having undergone laser therapy only, and 24 having had a combination of laser therapy and famotidine), which demonstrated that the complex action method has a more adequate effect on pathogenetic components in this disease than monotherapy.
Full Text Available Objectives: The objective of this work was to compare the efficacy of Maitland mobilization and conventional physical therapy on pain response, range of motion (ROM and functional ability in patients with chronic low back pain due to lumbar spondylosis. Methods: A total sample of 30 subjects (40–70 years of age with complaints of slow insidious onset of low back pain (LBP, with or without radiation not less than three months duration and decrease ROM were randomly assigned to: group-I, Maitland mobilization and lumbar stabilization exercises; group-II conventional physical therapy (traction, strengthening, stretching exercises. and outcomes were assessed for dependent variables. Results: There is statically a significant difference between pre and post measurement readings with time (p = 0.00 and between groups (p < 0.05 with respect to pain and function, but, with respect to ROM readings, showed statistical significance with time (p = 0.00 and no significance between groups (p > 0.05, indicating manual therapy group-I is improving faster and better than conventional physical therapy group-II. Conclusion: Our results showed that manual therapy interventions are more effective in managing low back pain, and function and range of motion of the lumbar spine than conventional physical therapy treatment.
The therapeutic action of opioid analgesics is compromised by peripheral adverse effects among which opioid-induced constipation (OIC) is the most disabling, with a prevalence reported to vary between 15 and 90 %. Although OIC is usually treated with laxatives, there is insufficient clinical evidence that laxatives are efficacious in this indication. In contrast, there is ample evidence from double- blind, randomized and placebo-controlled trials that peripheral opioid receptor antagonists (PORAs) counteract OIC. This specific treatment modality is currently based on subcutaneous methylnaltrexone for the interruption of OIC in patients with advanced illness, and a fixed combination of oral prolonged-release naloxone with prolonged-release oxycodone for the prevention of OIC in the treatment of non-cancer and cancer pain. Both drugs counteract OIC while the analgesic effect of opioids remains unabated. The clinical studies show that more than 50 % of the patients with constipation under opioid therapy may benefit from the use of PORAs, while PORA-resistant patients are likely to suffer from non-opioid-induced constipation, the prevalence of which increases with age. While the addition of naloxone to oxycodone seems to act by preventing OIC, the intermittent dosing of methylnaltrexone every other day seems to stimulate defaecation by provoking an intestinal withdrawal response. The availability of PORAs provides a novel opportunity to specifically control OIC and other peripheral adverse effects of opioid analgesics (e.g., urinary retention and pruritus). The continuous dosing of a PORA has the advantage of few adverse effects, while intermittent dosing of a PORA can be associated with abdominal cramp-like pain.
Full Text Available Objective: To explore the mechanism of Smilax China (Chinese spelling: Jingangteng Capsules and Azithromycin combined therapy for chronic annexitis, and offer help to patients with chronic annexitis on relevant clinical therapies. Methods: A total of 170 cases of patients with chronic annexitis were selected from the gynecological department in our hospital, and randomly divided to be the combination therapy group and the control group by digital table, 85 cases for each group. Patients in control group were treated with Azithromycin. Patients in combination therapy group were treated by giving Smilax China capsules based on the Azithromycin treatment. Relevant indexes of lymphocyte subsets (CD3+ , CD4+ , CD8+ and CD4+ /CD8+ , cytokines (TNF-α, IL-2, IL-6 and IL-10 and hemorheology (blood viscosity, plasma viscosity, hematocrit, red blood cell aggregation index in patients of the two groups were detected before and after treatment. Results: Before treatment, no statistical significance found on the differences of lymphocyte subsets, cytokines and hemorheology between the two groups of patients (P>0.05; After treatment received on the two groups of patients, indexes of CD3+ , CD4+ and CD4+ /CD8+ were dramatically increased, CD8+ , cytokines (TNF-α, IL-2, IL-6 and IL-10 and hemorheology in the combination therapy group were significantly decreased compared with patients in the control group; Statistical significance existed in differences between the two groups (P<0.05. Conclusions: Patients who received Azithromycin therapy added with Smilax China capsules concurrently could be significantly improved levels of lymphocyte subsets, cytokines and hemorheology index. It is of clinical importance for treatment of patients with chronic annexitis.
Richer, Nadia; Marchand, Andrée-Anne; Descarreaux, Martin
The purpose of this pilot study was to evaluate the feasibility and efficacy of adding cryostimulation to manual therapy in patients with chronic lateral epicondylitis. The control group (n = 19) was treated with manual therapy consisting of soft-tissue therapy and radial head mobilizations. The experimental group (n = 18) received cryostimulation in addition to manual therapy care similar to that for the control group. Both protocols consisted of 8 treatments over a 4-week period. Outcome measures included pain intensity (visual analog scale), pain-free grip strength (handheld dynamometer), and functional index (Patient-Rated Tennis Elbow Evaluation questionnaire). Assessments were performed at baseline, postintervention, and 3-month follow-up. Adherence and dropout rates were also considered. Both groups exhibited significant improvements in pain intensity and functional index at postintervention assessments, which were maintained at follow-up. All participants attended the prescribed number of treatments, but 27% were lost at follow-up. Minor adverse events were reported after cryostimulation in 4 cases. This study indicated that it is feasible to complete a clinical trial evaluating the efficacy of adding cryostimulation to manual therapy in patients with chronic lateral epicondylitis. On the basis of these preliminary data, the combination of cryostimulation and manual therapy care did not provide any additional benefits in both the short term and the long term. Manual myofascial point treatment and mobilization techniques yielded positive outcomes in chronic lateral epicondylitis. Further studies should focus on the sole therapeutic effect of cryostimulation in both patients with acute and those with chronic conditions.
Jones, A P; Rowe, B H
Bronchopulmonary hygiene physical therapy is a form of chest physical therapy including chest percussion and postural drainage to remove lung secretions. These are applied commonly to patients with both acute and chronic airway diseases. Despite controversies in the literature regarding its efficacy, it remains in use in a variety of clinical settings. The various forms of this therapy are labour intensive and need to be evaluated. The objective of this review was to assess the effects of bronchial hygiene physical therapy in people with chronic obstructive pulmonary disease and bronchiectasis. We searched the Cochrane Airways Group trials register and reference lists of articles up to July 1997. We also wrote to study authors. Randomised trials in which postural drainage, chest percussion, vibration, chest shaking, directed coughing or forced exhalation technique was compared to other drainage or breathing techniques, placebo or no treatment. Two reviewers applied the inclusion and exclusion criteria on masked publications independently. They assessed the trial quality independently. Only data from the first arm of crossover trials were included. The seven included trials involved six comparisons and a total of 126 people. The trials were small and not generally of high quality. The results could not be combined as trials addressed different patient groups and outcomes. In most comparisons, bronchial hygiene physical therapy produced no significant effects on pulmonary function, apart from clearing sputum in chronic obstructive pulmonary disease and in bronchiectasis. There is not enough evidence to support or refute the use of bronchial hygiene physical therapy in people with chronic obstructive pulmonary disease and bronchiectasis.
Jones, Arthur P; Rowe, Brian H
Bronchopulmonary hygiene physical therapy is a form of chest physical therapy including chest percussion and postural drainage to remove lung secretions. These are applied commonly to patients with both acute and chronic airway diseases. Despite controversies in the literature regarding its efficacy, it remains in use in a variety of clinical settings. The various forms of this therapy are labour intensive and need to be evaluated. The objective of this review was to assess the effects of bronchial hygiene physical therapy in people with chronic obstructive pulmonary disease and bronchiectasis. We searched the Cochrane Airways Group trials register and reference lists of articles up to January 2007. We also wrote to study authors. Randomised trials in which postural drainage, chest percussion, vibration, chest shaking, directed coughing or forced exhalation technique was compared to other drainage or breathing techniques, placebo or no treatment. Two reviewers applied the inclusion and exclusion criteria on masked publications independently. They assessed the trial quality independently. Only data from the first arm of crossover trials were included. The seven included trials involved six comparisons and a total of 126 people. The trials were small and not generally of high quality. The results could not be combined as trials addressed different patient groups and outcomes. In most comparisons, bronchial hygiene physical therapy produced no significant effects on pulmonary function, apart from clearing sputum in chronic obstructive pulmonary disease and in bronchiectasis. An update search carried out in January 2007 did not identify any new studies for inclusion. There is not enough evidence to support or refute the use of bronchial hygiene physical therapy in people with chronic obstructive pulmonary disease and bronchiectasis.
Jackson, Leanne K; Imam, Syed N; Braun, Ursula K
Opioid analgesia is a mainstay of the treatment of cancer pain. Treatment of pain in patients with cancer with an ongoing substance abuse disorder can be difficult. We report the ethical challenges of treating a patient with cancer with a concomitant substance abuse disorder in an outpatient palliative care setting. We present an analysis of ethical considerations for the palliative care physician and strategies to aid in the successful treatment of such patients. We argue that there are select patients with cancer for whom exclusion from treatment with opioid therapy is warranted if their health is endangered by prescription of these medications.
While the evidence for urine drug testing for patients on chronic opioid therapy is weak, the guidelines created by numerous medical societies and state and federal regulatory agencies recommend that it be included as one of the tools used to monitor patients for compliance with chronic opioid therapy. To get the most comprehensive results, clinicians should order both an immunoassay screen and confirmatory urine drug test. The immunoassay screen, which can be performed as an in-office point-of-care test or as a laboratory-based test, is a cheap and convenient study to order. Limitations of an immunoassay screen, however, include having a high threshold of detectability and only providing qualitative information about a select number of drug classes. Because of these restrictions, clinicians should understand that immunoassay screens have high false-positive and false-negative rates. Despite these limitations, though, the results can assist the clinician with making preliminary treatment decisions. In comparison, a confirmatory urine drug test, which can only be performed as a laboratory-based test, has a lower threshold of detectability and provides both qualitative and quantitative information. A urine drug test's greater degree of specificity allows for a relatively low false-negative and false-positive rate in contrast to an immunoassay screen. Like any other diagnostic test, an immunoassay screen and a confirmatory urine drug test both possess limitations. Clinicians must keep this in mind when interpreting an unexpected test result and consult with their laboratory when in doubt about the meaning of the test result to avoid making erroneous decisions that negatively impact both the patient and clinician.
Parkar, S.R.; Seethalakshmi, R; Adarkar, S; Kharawala, S
Seven patients with opioid dependence admitted in the de-addiction centre for detoxification developed convulsions and delirium during the withdrawal phase. After ruling out all other possible causes of these complications, opioid withdrawal seemed to emerge as the most likely explanation. The unpredictability of the course of opioid dependence and withdrawal needs to be considered when treating patients with opioid dependence.
Studies on the optimization of leukemia and non-Hodgkin lymphoma therapies using opioids, chemotherapy and radioimmunotherapy; Studien zur Optimierung von Leukaemie- und non-Hodgkin-Lymphom-Therapien durch den Einsatz von Opioiden, Chemotherapeutika und Radioimmuntherapien
Despite complex treatment schedules for cancer, the occurrence of resistances and relapses is a major concern in oncology. Hence, novel treatment options are needed. In this thesis, different approaches using radioimmunotherapy and the opioid D,L-methadone alone or in combination with doxorubicin were analyzed regarding their cytotoxic potential and the triggered signalling pathways in sensitive and resistant leukaemia and non-Hodgkin lymphoma (NHL). The radioimmunoconjugates [Bi-213]anti-CD33 and [Bi-213]anti-CD20 for treatment of acute myeloid leukaemia (AML) or NHL, respectively, were applied exemplary for the use of targeted alpha-therapies (TAT). Depending on the analyzed cell lines, the used activity concentrations and specific activities (MBq/μg antibody) apoptosis was induced abrogating radio- and chemo-cross-resistances specifically. The cell death was caspase-dependent activating the mitochondrial pathway and was executed by downregulation of the anti-apoptotic proteins XIAP and Bcl-xL. D,L-Methadone induces apoptosis in vitro and in vivo in opioid-receptor (OR) expressing cells depending on the OR density and the used concentrations. Resistances could be overcome and proliferation was inhibited. In combination with doxorubicin, a synergistic effect regarding cytotoxicity in ex vivo patient cells and cell lines was observed. This effect depends on the increase of doxorubicin uptake co-administering D,L-methadone whereas doxorubicin enhances OR expression. The activation of OR leads to the downregulation of cAMP playing a pivotal role in apoptosis induction. In vivo, the therapeutic potential of D,L-methadone alone or in combination with doxorubicin could be proven as mice transplanted with human T-ALL-cells could be identified as tumour free. In summary, these studies show that TAT using [Bi-213]anti-CD33 and [Bi-213]anti-CD20 as well as the opioid D,L-methadone harbour the potential to optimize conventional treatment modalities for leukaemia and NHL.
Full Text Available The impact of the prescription opioid public health crisis has been illustrated by the dramatic increase in opioid-related deaths in North America. We aimed to identify patterns and characteristics amongst opioid-users whose cause of death was related to opioid toxicity.This was a population-based study of Ontarians between the years 2006 and 2008. All drug-related deaths which occurred during this time frame were reviewed at the Office of the Chief Coroner of Ontario, and opioid-related deaths were identified. Medical, toxicology, pathology, and police reports were comprehensively reviewed. Narratives, semi-quantitative, and quantitative variables were extracted, tabulated, and analyzed.Out of 2330 drug-related deaths in Ontario, 58% were attributed either in whole or in part, to opioids (n = 1359. Oxycodone was involved in approximately one-third of all opioid-related deaths. At least 7% of the entire cohort used opioids that were prescribed for friends and/or family, 19% inappropriately self-administered opioids (injection, inhalation, chewed patch, 3% were recently released from jail, and 5% had been switched from one opioid to another near the time of death. Accidental deaths were significantly associated with personal history of substance abuse, enrollment in methadone maintenance programs, cirrhosis, hepatitis, and cocaine use. Suicides were significantly associated with mental illness, previous suicide attempts, chronic pain, and a history of cancer.These results identify novel, susceptible groups of opioid-users whose cause of death was related to opioids in Ontario and provide the first evidence to assist in quantifying the contribution of opioid misuse and diversion amongst opioid-related mortality in Canada. Multifaceted prevention strategies need to be developed based on subpopulations of opioid users.
Full Text Available Jeffrey A GudinEnglewood Hospital and Medical Center, Englewood, NJ, USAAbstract: Prescriptions for opioid analgesics to manage moderate-to-severe chronic noncancer pain have increased markedly over the last decade, as have postmarketing reports of adverse events associated with opioids. As an unintentional consequence of greater prescription opioid utilization, there has been the parallel increase in misuse, abuse, and overdose, which are serious risks associated with all opioid analgesics. In response to these concerns, the Food and Drug Administration announced the requirement for a class-wide Risk Evaluation and Mitigation Strategy (REMS for long-acting and extended-release (ER opioid analgesics in April 2011. An understanding of the details of this REMS will be of particular importance to primary care providers. The class-wide REMS is focused on educating health care providers and patients on appropriate prescribing and safe use of ER opioids. Support from primary care will be necessary for the success of this REMS, as these clinicians are the predominant providers of care and the main prescribers of opioid analgesics for patients with chronic pain. Although currently voluntary, future policy will likely dictate that providers undergo mandatory training to continue prescribing medications within this class. This article outlines the elements of the class-wide REMS for ER opioids and clarifies the impact on primary care providers with regard to training, patient education, and clinical practice.Keywords: long-acting opioid, extended-release opioid, risk, REMS, FDA, primary care
Łoniewski, Igor; Wesson, Donald E
Kidney injury in chronic kidney disease (CKD) is likely multifactorial, but recent data support that a component is mediated by mechanisms used by the kidney to increase acidification in response to an acid challenge to systemic acid-base status. If so, systemic alkalization might attenuate this acid-induced component of kidney injury. An acid challenge to systemic acid-base status increases nephron acidification through increased production of endothelin, aldosterone, and angiotensin II, each of which can contribute to kidney inflammation and fibrosis that characterizes CKD. Systemic alkalization that ameliorates an acid challenge might attenuate the contributions of angiotensin II, endothelin, and aldosterone to kidney injury. Some small clinical studies support the efficacy of alkalization in attenuating kidney injury and slowing glomerular filtration rate decline in CKD. This review focuses on the potential that orally administered NaHCO₃ prevents CKD progression and additionally addresses its mechanism of action, side effects, possible complications, dosage, interaction, galenic form description, and contraindications. Current National Kidney Foundation guidelines recommend oral alkali, including NaHCO₃(-), in CKD patients with serum HCO₃(-) <22 mmol/l. Although oral alkali can be provided by other medications and by base-inducing dietary constituents, oral NaHCO₃ will be the focus of this review because of its relative safety and apparent efficacy, and its comparatively low cost.
Willich Stefan N
Full Text Available Abstract Background Many patients with chronic diseases use complementary therapies, often provided by their physicians. In Germany, several physician-provided complementary therapies have been reimbursed by health insurance companies as part of health benefit programs. In most of these therapies, the patient has a predominantly passive role. In eurythmy therapy, however, patients actively exercise specific movements with the hands, the feet or the whole body. The purpose of this study was to describe clinical outcomes in patients practising eurythmy therapy exercises for chronic diseases. Methods In conjunction with a health benefit program, 419 outpatients from 94 medical practices in Germany, referred to 118 eurythmy therapists, participated in a prospective cohort study. Main outcomes were disease severity (Disease and Symptom Scores, physicians' and patients' assessment on numerical rating scales 0–10 and quality of life (adults: SF-36, children aged 8–16: KINDL, children 1–7: KITA. Disease Score was documented after 0, 6 and 12 months, other outcomes after 0, 3, 6, 12, 18, 24, and (SF-36 and Symptom Score 48 months. Results Most common indications were mental disorders (31.7% of patients; primarily depression, fatigue, and childhood emotional disorder and musculoskeletal diseases (23.4%. Median disease duration at baseline was 3.0 years (interquartile range 1.0–8.5. Median number of eurythmy therapy sessions was 12 (interquartile range 10–19, median therapy duration was 119 days (84–188. All outcomes improved significantly between baseline and all subsequent follow-ups (exceptions: KITA Psychosoma in first three months and KINDL. Improvements from baseline to 12 months were: Disease Score from mean (standard deviation 6.65 (1.81 to 3.19 (2.27 (p Adverse reactions to eurythmy therapy occurred in 3.1% (13/419 of patients. No patient stopped eurythmy therapy due to adverse reactions. Conclusion Patients practising eurythmy therapy
Full Text Available Background. Patients treated with interferon (IFN based therapies may develop exacerbation of autoimmune disease. We herein present the case of a 53-year-old female patient who developed celiac disease (CD as a result of triple therapy (interferon, ribavirin, and boceprevir for chronic HCV. Case. 53-year-old Caucasian female with past medical history of IV drug abuse was referred for abnormal LFTs. Laboratory data showed HCV RNA of 4,515,392 IU/mL, HCV genotype 1a, with normal LFTs. She was treated with 4 weeks of pegylated interferon alfa-2a plus ribavirin, followed by triple therapy using boceprevir for a total of 28 weeks. Approximately 4 weeks after initiation of triple therapy patient developed loose nonbloody bowel movements and was also found to have anemia. Biopsies from first and second portions of the duodenum were consistent with CD. The patient was treated with a gluten-free diet. Her intestinal symptoms improved and the hemoglobin returned to normal. Conclusion. Chronic HCV patients being treated with interferon alfa can develop celiac disease during or after therapy. For patients with positive autoantibodies, all-oral-IFN-free regimens should be considered. Celiac disease should be considered in patients who develop CD-like symptoms while on and shortly after cessation of interferon alfa therapy.