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.
Von Korff, Michael; Walker, Rod L; Saunders, Kathleen; Shortreed, Susan M; Thakral, Manu; Parchman, Michael; Hansen, Ryan N; Ludman, Evette; Sherman, Karen J; Dublin, Sascha
No studies have assessed the comparative effectiveness of guideline-recommended interventions to reduce risk of prescription opioid use disorder among chronic opioid therapy (COT) patients. We compared the prevalence of prescription opioid use disorder among COT patients from intervention clinics that had implemented opioid dose and risk reduction initiatives for more than 4 years relative to control clinics that had not. After a healthcare system in Washington State implemented interventions to reduce opioid dose and risks, we surveyed 1588 adult primary care COT patients to compare the prevalence of prescription opioid use disorder among COT patients from the intervention and control clinics. Intervention clinics managed COT patients at lower COT doses and with more consistent use of risk reduction practices. Control clinics cared for similar COT patients but prescribed higher opioid doses and used COT risk reduction practices inconsistently. Prescription opioid use disorder was assessed with the Psychiatric Research Interview for Substance and Mental Disorders. The prevalence of prescription opioid use disorder was 21.5% (95% CI=18.9% to 24.4%) among COT patients in the intervention clinics and 23.9% (95% CI=20.5% to 27.6%) among COT patients in the control clinics. The adjusted relative risk of prescription opioid use disorder was 1.08 (95% CI=0.89, 1.32) among the control clinic patients relative to the intervention clinic patients. Long-term implementation of opioid dose and risk reduction initiatives was not associated with lower rates of prescription opioid use disorder among prevalent COT patients. Extreme caution should be exercised by clinicians considering COT for patients with chronic non-cancer pain until benefits of this treatment and attendant risks are clarified. Copyright © 2017 Elsevier B.V. All rights reserved.
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...
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...
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.
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.
Carroll, C Patrick; Lanzkron, Sophie; Haywood, Carlton; Kiley, Kasey; Pejsa, Megan; Moscou-Jackson, Gyasi; Haythornthwaite, Jennifer A; Campbell, Claudia M
Chronic opioid therapy (COT) for chronic non-cancer pain is frequently debated, and its effectiveness is unproven in sickle cell disease (SCD). The authors conducted a descriptive study among 83 adult SCD patients and compared the severity of disease and pain symptoms among those who were prescribed COT (n=29) with those who were not using COT. All patients completed baseline laboratory pain assessment and questionnaires between January 2010 and June 2014. Thereafter, participants recorded daily pain, crises, function, and healthcare utilization for 90 days using electronic diaries. Analyses were conducted shortly after the final diary data collection period. Patients on COT did not differ on age, sex, or measures of disease severity. However, patients on COT exhibited greater levels of clinical pain (particularly non-crisis); central sensitization; and depression and increased diary measures of pain severity, function, and healthcare utilization on crisis and non-crisis diary days, as well as a greater proportion of days in crisis. Including depressive symptoms in multivariate models did not change the associations between COT and pain, interference, central sensitization, or utilization. Additionally, participants not on COT displayed the expected positive relationship between central sensitization and clinical pain, whereas those on COT demonstrated no such relationship, despite having both higher central sensitization and higher clinical pain. Overall, the results point out a high symptom burden in SCD patients on COT, including those on high-dose COT, and suggest that nociceptive processing in SCD patients on COT differs from those who are not. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.
Holder, Renee M; Rhee, Diane
Opioid analgesics are frequently prescribed and play an important role in chronic pain management. Opioid-induced bowel dysfunction, which includes constipation, hardened stool, incomplete evacuation, gas, and nausea and vomiting, is the most common adverse event associated with opioid use. Mu-opioid receptors are specifically responsible for opioid-induced bowel dysfunction, resulting in reduced peristaltic and secretory actions. Agents that reverse these actions in the bowel without reversing pain control in the central nervous system may be preferred over traditional laxatives. The efficacy and safety of these agents in chronic noncancer pain were assessed from publications identified through Ovid and PubMed database searches. Trials that evaluated the safety and efficacy of oral agents for opioid-induced constipation or opioid-induced bowel dysfunction, excluding laxatives, were reviewed. Lubiprostone and naloxegol are approved in the United States by the Food and Drug Administration for use in opioid-induced constipation. Axelopran (TD-1211) and sustained-release naloxone have undergone phase 2 and phase 1 studies, respectively, for the same indication. Naloxegol and axelopran are peripherally acting μ-opioid receptor antagonists. Naloxone essentially functions as a peripherally acting μ-opioid receptor antagonist when administered orally in a sustained-release formulation. Lubiprostone is a locally acting chloride channel (CIC-2) activator that increases secretions and peristalsis. All agents increase spontaneous bowel movements and reduce other bowel symptoms compared with placebo in patients with noncancer pain who are chronic opioid users. The most common adverse events were gastrointestinal in nature, and none of the drugs were associated with severe adverse or cardiovascular events. Investigations comparing these agents to regimens using standard laxative and combination therapy and trials in special populations and patients with active cancer are
Knezevic, Nebojsa Nick; Khan, Omar M; Beiranvand, Afsaneh; Candido, Kenneth D
used. Our results showed that repeated UDT can improve compliance of patients on opioid medications and can improve overall pain management. We believe UDT testing should be used as an important adjunctive tool to help guide clinical decision-making regarding opioid therapy, potentially increasing future quality of care.Key words: Urine toxicology analysis, chronic pain, opioids, compliance, pain management, urine drug testing, urine drug screening.
Saunders, Kathleen; Von Korff, Michael; Campbell, Cynthia I.; Banta-Green, Caleb J.; Sullivan, Mark D.; Merrill, Joseph O.; Weisner, Constance
Taking opioids with other central nervous system (CNS) depressants can increase risk of oversedation and respiratory depression. We used telephone survey and electronic health care data to assess the prevalence of, and risk factors for, concurrent use of alcohol and/or sedatives among 1848 integrated care plan members who were prescribed chronic opioid therapy (COT) for chronic non-cancer pain. Concurrent sedative use was defined by receiving sedatives for 45+ days of the 90 days preceding the interview; concurrent alcohol use was defined by consuming 2+ drinks within 2 hours of taking an opioid in the prior 2 weeks. Some analyses were stratified by substance use disorder (SUD) history (alcohol or drug). Among subjects with no SUD history, 29% concurrently used sedatives vs. 39% of those with a SUD history. Rates of concurrent alcohol use were similar (12 to 13%) in the two substance use disorder strata. Predictors of concurrent sedative use included SUD history, female gender, depression, and taking opioids at higher doses and for more than one pain condition. Male gender was the only predictor of concurrent alcohol use. Concurrent use of CNS depressants was common among this sample of COT users regardless of substance use disorder status. PMID:22285611
LoCasale, Robert J; Datto, Catherine; Margolis, Mary Kay; Coyne, Karin S
Greater satisfaction with medication is associated with better adherence; however, specific to opioid-induced constipation (OIC), data on the relationship between medication satisfaction and efficacy are lacking. To understand satisfaction with therapy among patients with chronic noncancer pain and OIC. A prospective longitudinal study was conducted in the United States, Canada, Germany, and the United Kingdom using web-based patient surveys. Patients on daily opioid therapy for ≥ 74 weeks for the treatment of chronic noncancer pain with OIC were recruited from physician offices and completed a web-based survey at baseline and weeks 2, 4, 6, 8, 12, 16, 20, and 24. When completing each survey, patients selected the remedies used in the previous 2 weeks to relieve constipation; options included natural/behavioral therapies, over-the-counter (OTC) therapies, and prescription laxatives. Patients selected the amount of relief and satisfaction with each selected therapy. Descriptive statistics were calculated; Spearman's correlations were calculated for symptom relief and satisfaction. Mean age of the 489 patients who met the criteria for OIC and completed the baseline survey was 52.6 ± 11.6 years; 62% were female; 85% were white. Increasing levels of relief from constipation were associated with increasing levels of satisfaction for all agents; correlations were > 0.55 and statistically significant (P constipation was associated with increased satisfaction for all therapies, there remains a substantial number of patients who report satisfaction despite having only inadequate relief from OIC that merits further investigation.
Full Text Available Pamela B Landsman-Blumberg,1 Nathaniel Katz,2,3 Kavita Gajria,4 Anna O D’Souza,1 Sham L Chaudhari,1 Paul P Yeung,5 Richard White6 1Real-World Evidence, Xcenda LLC, Palm Harbor, FL, 2Analgesic Solutions, Natick, MA, 3Tufts University School of Medicine, Boston, MA, 4Global Health Economics Outcomes Research, Teva Pharmaceuticals, Inc., Frazer, PA, 5Migraine and Headache Clinical Development, Teva Pharmaceuticals, Inc., Frazer, PA, 6Neuroscience, Angarrack Value Solutions, West Chester, PA, USA Abstract: The study assessed 12-month chronic pain (CP-related health care utilization and costs among chronic noncancer pain (CNCP patients who initiated various long-term opioid treatments. Treatments included monotherapy with long-acting opioids (mono-LAOs, monotherapy with short-acting opioids (mono-SAOs, both LAOs and SAOs (combination, and opioid therapy initiated with SAO or LAO and switched to the other class (switch. Using MarketScan® claims databases (2006–2012, we identified CNCP patients with ≥90 days opioid supply after pain diagnosis and continuous enrollment 12 months before pain diagnosis (baseline period and 12 months after opioid start (post-index period. Outcomes included CP-related health care utilization and costs. Among CNCP patients (n=21,203, the cohort distribution was 74% mono-SAOs, 22% combination, 2% mono-LAOs, and 2% switch. During follow-up, the average daily morphine equivalent dose was highest in mono-LAO patients (96.4 mg compared with combination patients (89.8 mg, switch patients (64.3 mg, and mono-SAO patients (36.2 mg. After adjusting for baseline differences, the mono-LAO cohort had lower total CP-related costs ($4,933 compared with the mono-SAO ($8,604, switch ($10,470, and combination ($15,190 cohorts (all: P<0.05. Mono-LAO patients had greater CP-related prescription costs but lower medical costs than the other cohorts during the follow-up period, including lower CP-related hospitalizations (1% vs 11%–20
Chronic pain may have a significant impact on health-related quality of life and can be difficult to manage. In carefully selected patients, and as part of a comprehensive pain management strategy, opioid analgesia may help to achieve long-term pain control with a manageable side-effect profile and a low risk of serious ...
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.
Matteliano, Deborah; St Marie, Barbara J; Oliver, June; Coggins, Candace
Opioids represent a mainstay in the pharmacologic management of persistent pain. Although these drugs are intended to support improved comfort and function, the inherent risk of abuse or addiction must be considered in the delivery of care. The experience of living with persistent pain often includes depression, fear, loss, and anxiety, leading to feelings of hopelessness, helplessness, and spiritual crisis. Collectively, these factors represent an increased risk for all patients, particularly those with a history of substance abuse or addiction. This companion article to the American Society for Pain Management Nursing "Position Statement on Pain Management in Patients with Substance Use Disorders" (2012) focuses on the intersection of persistent pain, substance use disorder (SUD), and chronic opioid therapy and the clinical implications of monitoring adherence with safe use of opioids for those with persistent pain. This paper presents an approach to the comprehensive assessment of persons with persistent pain when receiving opioid therapy by presenting an expansion of the biopsychosocial model to include spiritual factors associated with pain and SUD, thus formulating a biopsychosocial-spiritual approach to mitigate risk. Key principles are provided for adherence monitoring using the biopsychosocial-spiritual assessment model developed by the authors as a means of promoting sensitive and respectful care. Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.
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
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.
Opioids are very useful medications to reduce suffering of cancer patients such as refractory pain and dyspnea. We physicians have to use opioids to have good management of pain and suffering associated with cancer including management of side effects caused by opioids. Opioids couple opioid receptors and affect several pharmacological effects. Other than analgesic effect, opioids have some side effects of constipation, nausea and vomiting, respiratory depression. In this chapter, I take important side effects of constipation, nausea and vomiting and respiratory depression. Next, serotonin syndrome caused by tramadol combined with anti-depressants is remarked as assignable syndrome. As advancing in chemotherapy for cancer treatment, cancer survivors live longer with opioid therapy. We have to pay attention to the side effects and another dysfunction caused by long use of opioids. It is important that we physician use opioids effectively to keep activity of daily living(ADL) of patients and families as team approach.
Birke, H.; Ekholm, O.; Sjøgren, P.
Background: Longitudinal population-based studies of long-term opioid therapy (L-TOT) in chronic non-cancer pain (CNCP) patients are sparse. Our study investigated incidence and predictors for initiating L-TOT and changes in self-rated health, pain interference and physical activities in long......-term opioid therapy does not seem to provide pain relief, improvement in HRQOL and physical capacity in CNCP patients in a general population.......,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...
Birke, H; Ekholm, Ola; Sjøgren, P
BACKGROUND: Longitudinal population-based studies of long-term opioid therapy (L-TOT) in chronic non-cancer pain (CNCP) patients are sparse. Our study investigated incidence and predictors for initiating L-TOT and changes in self-rated health, pain interference and physical activities in long......-term opioid therapy does not seem to provide pain relief, improvement in HRQOL and physical capacity in CNCP patients in a general population.......,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...
..., from 9 a.m. to 4 p.m. Submit electronic or written requests to make oral presentations and comments by... practices? b. Patient access to pain medication and patient pain control? c. Abuse and misuse of opioid... practices? b. Patient access to pain medication and patient pain control? c. Abuse and misuse of opioid...
Zgierska, Aleksandra E; Burzinski, Cindy A; Cox, Jennifer; Kloke, John; Stegner, Aaron; Cook, Dane B; Singles, Janice; Mirgain, Shilagh; Coe, Christopher L; Bačkonja, Miroslav
To assess benefits of mindfulness meditation and cognitive behavioral therapy (CBT)-based intervention for opioid-treated chronic low back pain (CLBP). 26-week parallel-arm pilot randomized controlled trial (Intervention and Usual Care versus Usual Care alone). Outpatient. Adults with CLBP, prescribed ≥30 mg/day of morphine-equivalent dose (MED) for at least 3 months. The intervention comprised eight weekly group sessions (meditation and CLBP-specific CBT components) and 30 minutes/day, 6 days/week of at-home practice. Outcome measures were collected at baseline, 8, and 26 weeks: primary-pain severity (Brief Pain Inventory) and function/disability (Oswestry Disability Index); secondary-pain acceptance, opioid dose, pain sensitivity to thermal stimuli, and serum pain-sensitive biomarkers (Interferon-γ; Tumor Necrosis Factor-α; Interleukins 1ß and 6; C-reactive Protein). Thirty-five (21 experimental, 14 control) participants were enrolled and completed the study. They were 51.8 ± 9.7 years old, 80% female, with severe CLBP-related disability (66.7 ± 11.4), moderate pain severity (5.8 ± 1.4), and taking 148.3 ± 129.2 mg/day of MED. Results of the intention-to-treat analysis showed that, compared with controls, the meditation-CBT group reduced pain severity ratings during the study (P = 0.045), with between-group difference in score change reaching 1 point at 26 weeks (95% Confidence Interval: 0.2,1.9; Cohen's d = 0.86), and decreased pain sensitivity to thermal stimuli (P meditation practice and the magnitude of intervention benefits. Meditation-CBT intervention reduced pain severity and sensitivity to experimental thermal pain stimuli in patients with opioid-treated CLBP. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org.
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.
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....
Ratuapli, Shiva K; Crowell, Michael D; DiBaise, John K; Vela, Marcelo F; Ramirez, Francisco C; Burdick, George E; Lacy, Brian E; Murray, Joseph A
Bowel dysfunction has been recognized as a predominant side effect of opioid use. Even though the effects of opioids on the stomach and small and large intestines have been well studied, there are limited data on opioid effects on esophageal function. The aim of this study was to compare esophageal pressure topography (EPT) of patients taking opioids at the time of the EPT (≤24 h) with chronic opioid users who were studied off opioid medications for at least 24 h using the Chicago classification v3.0. A retrospective review identified 121 chronic opioid users who completed EPT between March 2010 and August 2012. Demographic and manometric data were compared between the two groups using general linear models or χ(2). Of the 121 chronic opioid users, 66 were studied on opioid medications (≤24 h) and 55 were studied off opioid medications for at least 24 h. Esophagogastric junction (EGJ) outflow obstruction was significantly more prevalent in patients using opioids within 24 h compared with those who did not (27% vs. 7%, P=0.004). Mean 4 s integrated relaxation pressure was also significantly higher in patients studied on opioids (10.71 vs. 6.6 mm Hg, P=0.025). Resting lower esophageal sphincter pressures tended to be higher on opioids (31.61 vs. 26.98 mm Hg, P=0.25). Distal latency was significantly lower in patients studied on opioids (6.15 vs. 6.74 s, P=0.044). Opioid use within 24 h of EPT is associated with more frequent EGJ outflow obstruction and spastic peristalsis compared with when opioid use is stopped for at least 24 h before the study.
Characteristics of patients receiving long-term opioid therapy for chronic noncancer pain: a cross-sectional survey of patients attending the Pain Management Centre at Hamilton General Hospital, Hamilton, Ontario
Mahmood, Hamza; Maqbool, Bilal; Maqbool, Amna; Zahran, Ali; Alwosaibai, Adnan; Alshaqaq, Eshaq; Persaud, Nav; Cooper, Lynn; Carol, Angela; Sumpton, Janice; McGinnis, Erin; Rosenbaum, Daniel; Lidster, Natalie; Buckley, D. Norman
Background Characteristics of patients receiving long-term opioid therapy (≥ 6 months) for chronic noncancer pain are poorly understood. We conducted a cross-sectional survey of this patient population to explore demographic variables, pain relief, functional improvement, adverse effects and impressions of an educational pamphlet on long-term opioid therapy. Methods We invited 260 adult patients presenting to the Pain Management Centre at the Hamilton General Hospital, Hamilton, Ontario, with chronic noncancer pain to complete a 20-item survey. Patients who presented for procedures were not eligible for our study. We used adjusted logistic regression models to explore the association between higher morphine equivalent dose and pain relief, functional improvement, adverse events and employment. Results The survey was completed by 170 patients (a response rate of 65.4%). Most respondents (87.6%; 149 out of 170) were receiving long-term opioid therapy, and the median morphine equivalent dose was 180 mg daily (interquartile range 60−501). Most respondents reported at least modest (> 40%) opioid-specific pain relief (74.1%; 106 out of 143) and functional improvement (67.6%; 96 out of 142), and 46.5% (66 out of 142) reported troublesome adverse effects that they attributed to their opioid use. Most patients were receiving disability benefits (68.3%; 99 out of 145) and, among those respondents who were less than 65 years of age (90.3%; 131 out of 145), 10 (7.6%) were working full-time and 14 (10.7%) part-time. In our adjusted analyses, higher morphine equivalent dose was associated with greater self-reported functional improvement (odds ratio [OR] 1.45, 95% confidence interval [CI] 1.07−1.96) but not with pain relief (OR 1.38, 95% CI 1.00−1.89), troublesome adverse effects (OR 0.92, 95% CI 0.70−1.20) or employment (OR 0.80, 95% CI 0.56−1.15). Interpretation Most outpatients receiving long-term opioid therapy for chronic noncancer pain at a tertiary care
Højsted, Jette; Sjøgren, Per
Opioids have proven very useful for treatment of acute pain and cancer pain, and in the developed countries opioids are increasingly used for treatment of chronic non-malignant pain patients as well. This literature review aims at giving an overview of definitions, mechanisms, diagnostic criteria......, 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...
Ballantyne, Jane C
Opioid analgesics have been used increasingly over the past 20 years for the management of chronic non-cancer pain in the USA under the assumption that they were safe and effective when used as directed. The accuracy of that assumption has not been tested against accumulated evidence. The safety of opioids used on a long-term basis has not been tested in clinical trials. Epidemiologic evidence from examinations of such use in the general population indicates that the risk of overdose increases in a dose-response manner. Such evidence also suggests increased risk of fractures and acute myocardial infarctions among elderly users of opioids for chronic pain. Experimental evidence supports short-term use of opioids, but trials of long-term use for chronic pain have not been conducted. Epidemiologic evidence suggests that long-term use does not result in improvement in function or quality of life while being associated with significant dropout rates and a high prevalence of adverse drug effects. Substantial fractions of patients are not using opioid analgesics as directed, while millions of US residents are using them without a prescription for nonmedical reasons. A prudent treatment approach consistent with the available evidence would be to reserve chronic opioid therapy for serious pain-related problems for which the effectiveness of opioids has been demonstrated and for patients whose use as directed is assured through close monitoring and for whom an explicit, informed calculation has been made that the benefits of opioids outweigh the risks.
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...... with opioids....
Devulder, J.; Jacobs, A.; Richarz, U.; Wiggett, H.
Background There is little evidence that short-acting opioids as rescue medication for breakthrough pain is an optimal long-term treatment strategy in chronic non-malignant pain. We compared clinical studies of long-acting opioids that allowed short-acting opioid rescue medication with those that did not, to determine the impact of opioid rescue medication use on the analgesic efficacy and tolerability of chronic opioid therapy in patients with chronic non-malignant pain. Methods We searched MEDLINE (1950 to July 2006) and EMBASE (1974 to July 2006) using terms for chronic non-malignant pain and long-acting opioids. Independent review of the search results identified 48 studies that met the study selection criteria. The effect of opioid rescue medication on analgesic efficacy and the incidence of common opioid-related side-effects were analysed using meta-regression. Results After adjusting for potentially confounding variables (study design and type of opioid), the difference in analgesic efficacy between the ‘rescue’ and the ‘no rescue’ studies was not significant, with regression coefficients close to 0 and 95% confidence intervals that excluded an effect of more than 18 points on a 0–100 scale in each case. There was also no significant difference between the ‘rescue’ and the ‘no rescue’ studies for the incidence of nausea, constipation, or somnolence in both the unadjusted and the adjusted analyses. Conclusions We found no evidence that rescue medication with short-acting opioids for breakthrough pain affects analgesic efficacy of long-acting opioids or the incidence of common opioid-related side-effects among chronic non-malignant pain patients. PMID:19736216
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.
The use of opioid contracts, which often require patients to submit to random drug screens, have become widespread amongst physicians using opioids to treat chronic pain. The main purpose of the contract is to improve care through better adherence to opioid therapy but there is little evidence as to its efficacy. The author suggests the use of opioid contracts and random drug testing destroys patients' trust which impacts health outcomes, and that physicians' motivation for their use are concerns about prosecution, medication abuse and misuse, and addiction. Statistics are provided to counter fears, and evidence is offered suggesting opioid contracts are unenforceable and lack efficacy; random drug testing is often inconclusive, and a patient's trust improves adherence to treatment.
Kata, Vijay; Novitch, Matthew B; Jones, Mark R; Anyama, Best O; Helander, Erik M; Kaye, Alan D
The primary cause of overdose death in the United States is related to pharmaceutical opioids. A few particular populations that struggle with adverse outcomes related to opioid abuse are those in palliative care, those with chronic pain, and those receiving pain treatments secondary to cancer or chemotherapy. There have been massive efforts to decrease the use of opioid abuse in patient care in a gestalt manner, but palliative care provides unique challenges in applying these reduction tactics used by other specialties. We explore behavioral interventions, provider education, alternative pain management techniques, postmarketing surveillance, and abuse-deterrent formulas as emerging methods to counteract opioid abuse in these populations.
Jamison, Robert N; Mao, Jianren
Chronic pain is an international health issue of immense importance that is influenced by both physical and psychological factors. Opioids are useful in treating chronic pain but have accompanying complications. It is important for clinicians to understand the basics of opioid pharmacology, the benefits and adverse effects of opioids, and related problematic issues of tolerance, dependence, and opioid-induced hyperalgesia. In this article, the role of psychiatric comorbidity and the use of validated assessment tools to identify individuals who are at the greatest risk for opioid misuse are discussed. Additionally, interventional treatment strategies for patients with chronic pain who are at risk for opioid misuse are presented. Specific behavioral interventions designed to improve adherence with prescription opioids among persons treated for chronic pain, such as frequent monitoring, periodic urine screens, opioid therapy agreements, opioid checklists, and motivational counseling, are also reviewed. Use of state-sponsored prescription drug monitoring programs is also encouraged. Areas requiring additional investigation are identified, and the future role of abuse-deterrent opioids and innovative technology in addressing issues of opioid therapy and pain are presented. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
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...... of anxiolytics and antidepressants and pain intensity. Pain relief, quality of life and functional capacity among opioid users were compared with non-opioid users. Opioid usage was significantly associated with reporting of moderate/severe or very severe pain, poor self-rated health, not being engaged......The aim of the study was epidemiologically to evaluate the long-term effects of opioids on pain relief, quality of life and functional capacity in long-term/chronic non-cancer pain. The study was based on data from the 2000 Danish Health and Morbidity Survey. As part of a representative National...
Højsted, Jette; Ekholm, Ola; Kurita, Geana Paula
The growing body of research showing increased opioid use in patients with chronic pain coupled with concerns regarding addiction encouraged the development of this population-based study. The goal of the study was to investigate the co-occurrence of indicators of addictive behaviors in patients......,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......; obesity; long-term use of benzodiazepines; and long-term use of benzodiazepine-related drugs. At least 2 of the 6 addictive behaviors were observed in 22.6% of the long-term opioid users with chronic pain compared with 11.5% of the non-opioid users with chronic pain and 8.9% of the individuals without...
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...
Darnall, Beth D.; Stacey, Brett R.; Chou, Roger
Background Long-term opioid use has increased substantially over the past decade for U.S. women. Women are more likely than men to have a chronic pain condition, to be treated with opioids, and may receive higher doses. Prescribing trends persist despite limited evidence to support the long-term benefit of this pain treatment approach. Purpose To review the medical and psychological risks and consequences of long-term opioid therapy in women. Method Scientific literature containing relevant keywords and content were reviewed. Results and Conclusions Long-term opioid use exposes women to unique risks, including endocrinopathy, reduced fertility, neonatal risks, as well as greater risk for polypharmacy, cardiac risks, poisoning and unintentional overdose, among other risks. Risks for women appear to vary by age and psychosocial factors may be bidirectionally related to opioid use. Gaps in understanding and priorities for future research are highlighted. PMID:22905834
Birthi, Pravardhan; Nagar, Vittal R; Nickerson, Robert; Sloan, Paul A
Sexual dysfunction and Opioid-Induced Sexual Hormone Deficiency (OPISHD) have been associated with patients on long-term opioid pain therapy. There have been few comprehensive reviews to establish a relation between hypogonadism with chronic opioid pain management. The OPISHD is often not treated and literature guiding this topic is scarce. To investigate hypogonadism associated with long-term opioid therapy based on qualitative data analysis of the available literature. Systematic review. The review included relevant literature identified through searches of PubMed, Cochrane, Clinical Trials, US National Guideline Clearinghouse, and EMBASE, for the years 1960 to September 2013. The quality assessment and clinical relevance criteria used were the Cochrane Musculoskeletal Review Group Criteria for randomized control trials and the Newcastle-Ottawa Scale Criteria for observational studies. The level of evidence was classified as good, fair, and poor, based on the quality of evidence. The primary outcome measures were clinical symptoms and laboratory markers of hypogonadism. Secondary outcome measure was management of OPISHD. Thirty-one studies were identified, of which 14 studies met inclusion criteria. There were no randomized control trials and eight of 14 studies were of moderate quality. The remaining studies were of poor quality. Four studies report most patients on long-term oral opioid therapy have associated hypogonadism and three studies of patients receiving intrathecal opioid therapy suggest that hypogonadism is common. There is lack of high-quality studies to associate chronic opioid pain management with hypogonadism. At present, there is fair evidence to associate hypogonadism with chronic opioid pain management, and only limited evidence for treatment of OPISHD.
Turner Barbara J
Full Text Available Abstract Background The use of opioid medications as treatment for chronic non-cancer pain remains controversial. Little information is currently available regarding healthcare providers' attitudes and beliefs about this practice among older adults. This study aimed to describe primary care providers' experiences and attitudes towards, as well as perceived barriers and facilitators to prescribing opioids as a treatment for chronic pain among older adults. Methods Six focus groups were conducted with a total of 23 physicians and three nurse practitioners from two academically affiliated primary care practices and three community health centers located in New York City. Focus groups were audiotape recorded and transcribed. The data were analyzed using directed content analysis; NVivo software was used to assist in the quantification of identified themes. Results Most participants (96% employed opioids as therapy for some of their older patients with chronic pain, although not as first-line therapy. Providers cited multiple barriers, including fear of causing harm, the subjectivity of pain, lack of education, problems converting between opioids, and stigma. New barriers included patient/family member reluctance to try an opioid and concerns about opioid abuse by family members/caregivers. Studies confirming treatment benefit, validated tools for assessing risk and/or dosing for comorbidities, improved conversion methods, patient education, and peer support could facilitate opioid prescribing. Participants voiced greater comfort using opioids in the setting of delivering palliative or hospice care versus care of patients with chronic pain, and expressed substantial frustration managing chronic pain. Conclusions Providers perceive multiple barriers to prescribing opioids to older adults with chronic pain, and use these medications cautiously. Establishing the long-term safety and efficacy of these medications, generating improved prescribing methods
Spitz, Aerin; Moore, Alison A; Papaleontiou, Maria; Granieri, Evelyn; Turner, Barbara J; Reid, M Carrington
The use of opioid medications as treatment for chronic non-cancer pain remains controversial. Little information is currently available regarding healthcare providers' attitudes and beliefs about this practice among older adults. This study aimed to describe primary care providers' experiences and attitudes towards, as well as perceived barriers and facilitators to prescribing opioids as a treatment for chronic pain among older adults. Six focus groups were conducted with a total of 23 physicians and three nurse practitioners from two academically affiliated primary care practices and three community health centers located in New York City. Focus groups were audiotape recorded and transcribed. The data were analyzed using directed content analysis; NVivo software was used to assist in the quantification of identified themes. Most participants (96%) employed opioids as therapy for some of their older patients with chronic pain, although not as first-line therapy. Providers cited multiple barriers, including fear of causing harm, the subjectivity of pain, lack of education, problems converting between opioids, and stigma. New barriers included patient/family member reluctance to try an opioid and concerns about opioid abuse by family members/caregivers. Studies confirming treatment benefit, validated tools for assessing risk and/or dosing for comorbidities, improved conversion methods, patient education, and peer support could facilitate opioid prescribing. Participants voiced greater comfort using opioids in the setting of delivering palliative or hospice care versus care of patients with chronic pain, and expressed substantial frustration managing chronic pain. Providers perceive multiple barriers to prescribing opioids to older adults with chronic pain, and use these medications cautiously. Establishing the long-term safety and efficacy of these medications, generating improved prescribing methods, and implementing provider and patient educational interventions
Bruehl, Stephen; Apkarian, A. Vania; Ballantyne, Jane C.; Berger, Ann; Borsook, David; Chen, Wen G.; Farrar, John T.; Haythornthwaite, Jennifer A.; Horn, Susan D.; Iadarola, Michael J.; Inturrisi, Charles E.; Lao, Lixing; Mackey, Sean; Mao, Jianren; Sawczuk, Andrea; Uhl, George R.; Witter, James; Woolf, Clifford J.; Zubieta, Jon-Kar; Lin, Yu
Use of opioid analgesics for pain management has increased dramatically over the past decade, with corresponding increases in negative sequelae including overdose and death. There is currently no well-validated objective means of accurately identifying patients likely to experience good analgesia with low side effects and abuse risk prior to initiating opioid therapy. This paper discusses the concept of data-based personalized prescribing of opioid analgesics as a means to achieve this goal. Strengths, weaknesses, and potential synergism of traditional randomized placebo-controlled trial (RCT) and practice-based evidence (PBE) methodologies as means to acquire the clinical data necessary to develop validated personalized analgesic prescribing algorithms are overviewed. Several predictive factors that might be incorporated into such algorithms are briefly discussed, including genetic factors, differences in brain structure and function, differences in neurotransmitter pathways, and patient phenotypic variables such as negative affect, sex, and pain sensitivity. Currently available research is insufficient to inform development of quantitative analgesic prescribing algorithms. However, responder subtype analyses made practical by the large numbers of chronic pain patients in proposed collaborative PBE pain registries, in conjunction with follow-up validation RCTs, may eventually permit development of clinically useful analgesic prescribing algorithms. Perspective Current research is insufficient to base opioid analgesic prescribing on patient characteristics. Collaborative PBE studies in large, diverse pain patient samples in conjunction with follow-up RCTs may permit development of quantitative analgesic prescribing algorithms which could optimize opioid analgesic effectiveness, and mitigate risks of opioid-related abuse and mortality. PMID:23374939
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.
Eisenberg, Elon; Ståhl, Camilla; Drewes, Asbjørn M
The value of opioid pharmacotherapy in the management of chronic pancreatitis pain is described. The role of kappa receptor opioid agonists and specifically oxycodone as compared to other opioid agonists is discussed. Limitations in the published studies on this topic are delineated as are diffic......The value of opioid pharmacotherapy in the management of chronic pancreatitis pain is described. The role of kappa receptor opioid agonists and specifically oxycodone as compared to other opioid agonists is discussed. Limitations in the published studies on this topic are delineated...... as are difficulties in extrapolating form animal studies to clinical care. Udgivelsesdato: 2007-null...
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
Ismail, Ismaliza; Wahab, Suzaily; Sidi, Hatta; Das, Srijit; Lin, Loo Jiann; Razali, Rosdinom
Kratom (Mitragynaspeciosa), a natural existing plant found in South-East Asia, is tradi-tionally used as an herb to help to elevate a person's energy and also to treat numerous medical ailments. Other than the analgesic property, kratom has been used as an agent to overcome opioid withdrawal as it contains natural alkaloids, i.e. mitragynine, 7-hydroxymitragynine, and MGM-9, which has agonist affinity on the opioid receptors, including mu (μ) and kappa (κ). The role of neural reward pathway linked to μ-opioid receptors and both dopaminergic and GABA-ergic interneurons that express μ-opioid receptors were deliberated. However, kratom has been reported to be abused together with other illicit substances with high risk of potential addiction. There are also anecdotes of an adverse effect and toxicity of kratom, i.e. tremor, fatigue, seizure, and death. Different countries have distinctive regulation and policy on the plantation and use of this plant when most of the countries banned the use of it because of its addiction problems and side effects. The aim of this review is to highlight on the potential use of kratom, a unique 'herbs" as a substitution therapy for chronic pain and opioid addiction, based on the neurobiological perspective of pain and the underlying mechanism of actions of drug addiction. Copyright© Bentham Science Publishers; For any queries, please email at email@example.com.
Jiang, Xueying; Orton, Margaret; Feng, Rui; Hossain, Erik; Malhotra, Neil R; Zager, Eric L; Liu, Renyu
The objective of this study is to investigate the prevalence and disparity of chronic opioid usage in surgical patients and the potential risk factors associated with chronic opioid usage. Chronic opioid usage is common in surgical patients; however, the characteristics of opioid usage in surgical patients is unclear. In this study, we hypothesize that the prevalence of chronic opioid usage in surgical patients is high, and that significant disparities may exist among different surgical populations. Data of opioid usage in outpatients among different surgical services were extracted from the electronic medical record database. Patient demographics, clinical characteristics of sex, age, race, body mass index (BMI), specialty visited, duration of opioid use, and opioid type were collected. Chronic opioid users were defined as patients who had been recorded as taking opioids for at least 90 days determined by the first and last visit dates under opioid usage during the investigation. There were 79,123 patients included in this study. The average prevalence is 9.2%, ranging from 4.4% to 23.8% among various specialties. The prevalence in orthopedics (23.8%), neurosurgery (18.7%), and gastrointestinal surgery (14.4%) ranked in the top three subspecialties. Major factors influencing chronic opioid use include age, Ethnicitiy, Subspecialtiy, and multiple specialty visits. Approximately 75% of chronic users took opioids that belong to the category II Drug Enforcement Administration classification. Overall prevalence of chronic opioid usage in surgical patients is high with widespread disparity among different sex, age, ethnicity, BMI, and subspecialty groups. Information obtained from this study provides clues to reduce chronic opioid usage in surgical patients.
Wasan, Ajay D.; Butler, Stephen F.; Budman, Simon H.; Fernandez, Kathrine; Weiss, Roger; Greenfield, Shelly; Jamison, Robert N.
Objective: To examine the relationship between the self-report of craving prescription medication and subsequent opioid misuse among chronic pain patients prescribed opioids for pain. Methods: Six hundred thirteen (613) patients taking opioid medication for chronic noncancer pain were asked how often they have felt a craving for their medication on a scale from 0 = never to 4= very often. All subjects completed a series of baseline questionnaires. After six months the subjects were administered a structured prescription drug use interview (Prescription Drug Use Questionnaire; PDUQ), and submitted a urine sample for toxicology assessment. Their treating physicians also completed a substance misuse behavior checklist (Prescription Opioid Therapy Questionnaire; POTQ). Results: Three hundred thirty-seven subjects (55.0%) reported that they never felt a craving for their medication, while 276 (45.0%) reported some degree of craving their medication (seldom to very often). Those who reported craving their medication were significantly more often male (p<0.01), unmarried (p<0.05), had lower scores on social desirability (p<0.001), and had been prescribed opioids for a longer time (p<0.05) than those who did not report craving medication. At 6-month follow-up, those who reported craving their medication showed higher scores on the PDUQ (p<0.001), had a higher incidence of physician-rated aberrant drug behavior on the POTQ (p<0.05), showed a higher frequency of abnormal urine toxicology screens (p<0.001) and more often had a positive Aberrant Drug Behavior Index (p<0.001). Discussion: These results suggest that self-reported craving is a potential marker for identification of those at risk for opioid medication misuse. PMID:19333168
Perhac J Stephen
Full Text Available Abstract Background Opioid misuse can complicate chronic pain management, and the non-medical use of opioids is a growing public health problem. The incidence and risk factors for opioid misuse in patients with chronic pain, however, have not been well characterized. We conducted a prospective cohort study to determine the one-year incidence and predictors of opioid misuse among patients enrolled in a chronic pain disease management program within an academic internal medicine practice. Methods One-hundred and ninety-six opioid-treated patients with chronic, non-cancer pain of at least three months duration were monitored for opioid misuse at pre-defined intervals. Opioid misuse was defined as: 1. Negative urine toxicological screen (UTS for prescribed opioids; 2. UTS positive for opioids or controlled substances not prescribed by our practice; 3. Evidence of procurement of opioids from multiple providers; 4. Diversion of opioids; 5. Prescription forgery; or 6. Stimulants (cocaine or amphetamines on UTS. Results The mean patient age was 52 years, 55% were male, and 75% were white. Sixty-two of 196 (32% patients committed opioid misuse. Detection of cocaine or amphetamines on UTS was the most common form of misuse (40.3% of misusers. In bivariate analysis, misusers were more likely than non-misusers to be younger (48 years vs 54 years, p Conclusion Opioid misuse occurred frequently in chronic pain patients in a pain management program within an academic primary care practice. Patients with a history of alcohol or cocaine abuse and alcohol or drug related convictions should be carefully evaluated and followed for signs of misuse if opioids are prescribed. Structured monitoring for opioid misuse can potentially ensure the appropriate use of opioids in chronic pain management and mitigate adverse public health effects of diversion.
Silverman, Sanford; Raffa, Robert B; Cataldo, Marc J; Kwarcinski, Monica; Ripa, Steven R
The buprenorphine transdermal system (BTDS) is approved in the US for the management of chronic pain. Due to its high affinity for μ-opioid receptors with a slow dissociation profile, buprenorphine may potentially displace or prevent the binding of competing μ-opioid-receptor agonists, including immediate-release (IR) opioids, in a dose-dependent manner. Health care professionals may assume that the use of IR opioids for supplemental analgesia during BTDS therapy is not acceptable. This post hoc analysis evaluated the use of IR opioids as supplemental analgesia during the management of moderate-severe chronic pain with BTDS at 52 US sites (BUP3015S, NCT01125917). Patients were categorized into IR-opioid and no-IR-opioid groups. At each visit of the extension phase, adverse events, concomitant medications, and information from the Brief Pain Inventory (BPI) were recorded. The most common supplemental IR opioids prescribed during BTDS treatment (n=354) were hydrocodone-acetaminophen and oxycodone-acetaminophen. The mean daily dose of IR opioids (morphine equivalents) for supplemental analgesia was 22 mg. At baseline, BPI - pain intensity and BPI - interference scores were higher for patients in the IR-opioid group. In both treatment groups, scores improved by week 4, and then were maintained throughout 6 months of the open-label extension trial. The incidence of treatment-emergent adverse events was similar in both groups. Patients who were prescribed IR opioids reported lower scores for BPI pain intensity and pain interference to levels similar to patients receiving BTDS without IR opioids, without increasing the rate or severity of treatment-emergent adverse events. Patients prescribed concomitant use of IR opioids with BTDS had greater treatment persistence. The results of this post hoc analysis provide support for the concomitant use of IR opioids for supplemental analgesia during the management of moderate-severe chronic pain with BTDS.
Daitch, Jonathan; Frey, Michael E; Silver, David; Mitnick, Carol; Daitch, Danielle; Pergolizzi, Joseph
Sublingual buprenorphine-naloxone (buprenorphine SL) is a preparation that is used to treat opioid dependence. In addition, the Drug Enforcement Administration (DEA) has acknowledged the legality of an off-label use to treat pain with a sublingual buprenorphine preparation. Buprenorphine SL is unique among the opioid class of analgesics; this compound has a high affinity for the mu-receptor, yet only partially activates it. Thus, buprenorphine SL can provide analgesia, yet minimize opioid side effects. Many patients on high doses of traditional opioid medication develop tolerance. Despite escalating medication dosage, a subset of patients had a paradoxical increase in pain, which has been characterized as opioid-induced hyperalgesia (OIH). Buprenorphine SL, on the other hand, may even be anti-hyperalgesic and may have utility in treating these challenging patients. To determine the effectiveness of converting patients from traditional full agonist opioid medication to sublingual buprenorphine, as well as to identify patient groups that are most likely to benefit from this therapy. Patients who underwent conversion either had developed tolerance with diminished analgesia or were experiencing side effects on their opioid medications. An observational report of outcomes assessment. An interventional pain management practice setting in the United States. Retrospective data from clinical records was compiled on 104 de-identified chronic pain patients whose personal information had been redacted (60 men and 44 women, aged 21-78) and who had previously been treated with opioid-agonist drugs; they were converted to buprenorphine SL in tablet form during the study. Chronic pain was defined as persistent pain for at least 6 months. Data collected from patient profiles included age, sex, diagnosis, medication history, pre-induction opioid intake, reason for detoxification, pre-induction Clinical Opiate Withdrawal Score (COWS), and if applicable, cause of buprenorphine SL
Full Text Available Aliza Z Weinrib,1,2 Lindsay C Burns,1,2 Alex Mu,1 Muhammad Abid Azam,1,2 Salima SJ Ladak,1 Karen McRae,1,3 Rita Katznelson,1,3 Saam Azargive,1 Cieran Tran,1 Joel Katz,1–3 Hance Clarke1,3 1Pain Research Unit, Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, 2Department of Psychology, York University, 3Department of Anesthesia, University of Toronto, Toronto, Ontario, Canada Abstract: In an era of growing concern about opioid prescribing, the postsurgical period remains a critical window with the risk of significant opioid dose escalation, particularly in patients with a history of chronic pain and presurgical opioid use. The purpose of this case report is to describe the multidisciplinary care of a complex, postsurgical pain patient by an innovative transitional pain service (TPS. A 59-year-old male with complex chronic pain, as well as escalating long-term opioid use, presented with a bleeding duodenal ulcer requiring emergency surgery. After surgery, the TPS provided integrated pharmacological and behavioral treatment, including buprenorphine combined with naloxone and acceptance and commitment therapy (ACT using the ACT Matrix. The result was dramatic pain reduction and improved functioning and quality of life after 40+ years of chronic pain, thus changing the pain trajectory of a chronic, complex, opioid-dependent patient. Keywords: transitional pain service, postsurgical pain, chronic pain, opioid dependence, opioid weaning, acceptance and commitment therapy
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
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
Sjøgren, Per; Grønbæk, Morten; Peuckmann, Vera
OBJECTIVES: The aims of this study were 2-fold: (1) to investigate the consequences of opioid use in individuals with chronic pain in the Danish population, and (2) to investigate the development of and recovery from chronic pain from 2000 to 2005. METHODS: Data derived from the Danish Health.......4%, respectively. Increasing age up to 64 years, short education, poor self-rated health, high body mass index, and physical strain at work were predictors of chronic pain. The odds of recovery from chronic pain were almost 4 times higher among individuals not using opioids compared with individuals using opioids....... In addition, use of strong opioids was associated with poor health-related quality of life. Furthermore, the results indicated that individuals with chronic pain using strong opioids pain had a higher risk of death than individuals without chronic pain (HR: 1.67; 95% CI: 1.03-2.70). However, this study cannot...
Plesner, K; Jensen, H I; Højsted, J
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...... as in the general population. The prevalence of patients using opioids was 54% and the prevalence of addiction to opioids was 6%. No significant differences in addiction were found between the different smoking groups, but smokers and former smokers using nicotine tended to use opioids more frequently and at higher...
Graczyk, Michał; Borkowska, Alina; Krajnik, Małgorzata
INTRODUCTION Opiophobia is deemed one of the key barriers in effective pain management. OBJECTIVES The study aimed to assess the overall perception of opioids in cancer patients treated for chronic pain, as well as to determine the nature of their most common related fears. PATIENTS AND METHODS The study included 100 palliative care patients who suffered from chronic cancer or noncancer pain. Initially, they had to complete a survey exploring their knowledge on analgesics and potential fear of using opioids. The second phase was based on in‑depth interviews with 10 palliative care patients suffering from cancer pain who were reluctant to use opioids. RESULTS Of the 100 patients, 43 expressed concerns over commencing the treatment with opioids. Fear was reported more often in patients already on strong opioids, who either overtly expressed it (group C) or not (group B), as compared with patients treated with weak opioids (group A) (50%, 48%, and 19% of groups C, B, and A, respectively). The main concerns were drug addiction, fear of death or dying, and undesirable side effects. A qualitative study revealed similar types of fear among patients expressing concerns prior to being put on strong opioids. CONCLUSIONS Opiophobia seems to be common among palliative care patients (up to 50%) treated with strong opioids. They mainly fear drug addiction, undesirable effects, and death or dying. Better awareness of patients' preconceptions about opioids may become instrumental to alleviating their suffering through enhanced pain management.
Nikulina, Valentina; Guarino, Honoria; Acosta, Michelle C; Marsch, Lisa A; Syckes, Cassandra; Moore, Sarah K; Portenoy, Russell K; Cruciani, Ricardo A; Turk, Dennis C; Rosenblum, Andrew
During long-term opioid therapy for chronic noncancer pain, monitoring medication adherence of patients with a history of aberrant opioid medication-taking behaviors (AMTB) is an essential practice. There is limited research, however, into the concordance among existing monitoring tools of self-report, physician report, and biofluid screening. This study examined associations among patient and provider assessments of AMTB and urine drug screening using data from a randomized trial of a cognitive-behavioral intervention designed to improve medication adherence and pain-related outcomes among 110 opioid-treated patients with chronic pain who screened positive for AMTB and were enrolled in a pain program. Providers completed the Aberrant Behavior Checklist (ABC) and patients completed the Current Opioid Misuse Measure (COMM) and the Chemical Coping Inventory (CCI). In multivariate analyses, ABC scores were compared with COMM and CCI scores, while controlling for demographics and established risk factors for AMTB, such as pain severity. Based on clinical cutoffs, 84% of patients reported clinically significant levels of AMTB and providers rated 36% of patients at elevated levels. Provider reports of AMTB were not correlated with COMM or CCI scores. However, the ABC ratings of experienced providers (nurse practitioners/attending physicians) were higher than those of less experienced providers (fellows) and were correlated with CCI scores and risk factors for AMTB. Associations between patient- and provider-reported AMTB and urine drug screening results were low and largely nonsignificant. In conclusion, concordance between patient and provider reports of AMTB among patients with chronic pain prescribed opioid medication varied by provider level of training.
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.
Sjøgren, Per; Grønbæk, Morten; Peuckmann, Vera Irina
The aims of this study were 2-fold: (1) to investigate the consequences of opioid use in individuals with chronic pain in the Danish population, and (2) to investigate the development of and recovery from chronic pain from 2000 to 2005.......The aims of this study were 2-fold: (1) to investigate the consequences of opioid use in individuals with chronic pain in the Danish population, and (2) to investigate the development of and recovery from chronic pain from 2000 to 2005....
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.
Grosen, Kasper; Olesen, Anne E; Gram, Mikkel
use for diverse types of chronic pain at five European centers. Quantitative sensory testing, electroencephalography (EEG) recordings, and assessment of pain catastrophizing were performed prior to treatment. The co-primary outcomes were change from baseline in ratings of chronic pain and quality...... 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...... pain intensity or an improvement in quality of life of at least 10 scale points. Fifty-nine patients (94%) completed the study. The mean age was 55 ± 16 years and 69% were females. Pain reduction was predicted by cold pain intensity (OR: 0.69; P = 0.01), pain catastrophizing (OR: 0.82; P = 0...
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...... treated pain patients and seems to be more sensitive and specific than ICD-10 criteria....
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.
Iyer, Shrividya; Davis, Keith L; Candrilli, Sean
The main objective of this study was to compare the opioid use patterns, resource utilization, and costs of patients on opioid therapy who have constipation with those who do not. Retrospective, observational matched cohort design Patients initiating opioid therapy between Jan. 1, 1999 and Dec. 31, 2005 were identified from a longitudinal insurance claims database. Patients had > or = 30 days of opioid use and continuous plan coverage for > or = 6 months before and > or = 12 months after their index date, defined as the date of the first pharmacy claim for an opioid. Constipation was defined as having one or more ICD-9 codes of 564.0 during the follow-up period. Patterns of opioid use and resource utilization were compared between patients with constipation and a demographically matched (1:1) cohort of opioid initiators without consti- pation using t-tests and Chi-square (chi2) tests. We identified 39,485 patients, of whom 2,519 (6.4%) had constipation. Most patients with constipation were female (66%) and > or = 45 years old (68%). Compared to controls, the constipation group had significantly higher rates of concurrent use of > or = 2 opioids (p < 0.0001), discontinuation, and switching between opioids. Patients with constipation had statistically significant higher hospital admissions, emergency room visits, home health services, nursing home care, physician office visits, other outpatient/ ancillary care, and laboratory tests. Patients with constipation had significantly higher mean all-cause costs for emergency, physician visits, nursing facility, home health, and prescription drug services compared to patients without constipation. Opioid-treated patients with constipation were found to have significant differences in opioid use patterns and significantly higher health care utilization and associated costs.
Full Text Available Sanford Silverman,1,2 Robert B Raffa,3,4 Marc J Cataldo,5 Monica Kwarcinski,5 Steven R Ripa5 1Comprehensive Pain Medicine, Pompano Beach, 2Department of Integrated Medical Sciences, Charles E Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, 3Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, Philadelphia, PA, 4Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ, 5Purdue Pharma LP, Stamford, CT, US Background: The buprenorphine transdermal system (BTDS is approved in the US for the management of chronic pain. Due to its high affinity for μ-opioid receptors with a slow dissociation profile, buprenorphine may potentially displace or prevent the binding of competing μ-opioid-receptor agonists, including immediate-release (IR opioids, in a dose-dependent manner. Health care professionals may assume that the use of IR opioids for supplemental analgesia during BTDS therapy is not acceptable.Materials and methods: This post hoc analysis evaluated the use of IR opioids as supplemental analgesia during the management of moderate–severe chronic pain with BTDS at 52 US sites (BUP3015S, NCT01125917. Patients were categorized into IR-opioid and no-IR-opioid groups. At each visit of the extension phase, adverse events, concomitant medications, and information from the Brief Pain Inventory (BPI were recorded.Results: The most common supplemental IR opioids prescribed during BTDS treatment (n=354 were hydrocodone–acetaminophen and oxycodone–acetaminophen. The mean daily dose of IR opioids (morphine equivalents for supplemental analgesia was 22 mg. At baseline, BPI – pain intensity and BPI – interference scores were higher for patients in the IR-opioid group. In both treatment groups, scores improved by week 4, and then were maintained throughout 6 months of the open-label extension trial. The incidence of treatment-emergent adverse events was similar in
Ballantyne, Jane C
An overreliance on opioids has impacted all types of pain management, making it undoubtedly a root cause of the "epidemic" of prescription opioid abuse in the United States. Yet, an examination of the statistics that led the US Centers for Disease Control and Prevention to declare that prescription opioid abuse had reached epidemic levels shows that the abuse occurrences and deaths are arising outside the hospital or hospice setting, which strongly implicates the outpatient use of opioids to treat chronic pain. Such abuse and related deaths are occurring in chronic pain patients themselves and also through diversion. Overprescribing to outpatients has afforded distressed and vulnerable individuals access to these highly addictive drugs. The focus of this article is on what we have learned since opioid treatment of chronic pain was first popularized at the end of the 20th century and how this new information can guide chronic pain management in the future.
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
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.
Loijens, L.W.S.; Schouten, W.G.P.; Wiepkema, P.R.; Wiegant, V.M.
Opioid receptor densities were measured in the hippocampus of chronically stressed (tethered) pigs to study the involvement of endogenous opioid systems in stereotypy performance. Three groups of animals were housed tethered for 2 (n = 12), 5.5 (n = 12) and 8-9 months (n = 8), respectively, and the
Manchikanti, Laxmaiah; Kaye, Adam M; Knezevic, Nebojsa Nick; McAnally, Heath; Slavin, Konstantin; Trescot, Andrea M; Blank, Susan; Pampati, Vidyasagar; Abdi, Salahadin; Grider, Jay S; Kaye, Alan D; Manchikanti, Kavita N; Cordner, Harold; Gharibo, Christopher G; Harned, Michael E; Albers, Sheri L; Atluri, Sairam; Aydin, Steve M; Bakshi, Sanjay; Barkin, Robert L; Benyamin, Ramsin M; Boswell, Mark V; Buenaventura, Ricardo M; Calodney, Aaron K; Cedeno, David L; Datta, Sukdeb; Deer, Timothy R; Fellows, Bert; Galan, Vincent; Grami, Vahid; Hansen, Hans; Helm Ii, Standiford; Justiz, Rafael; Koyyalagunta, Dhanalakshmi; Malla, Yogesh; Navani, Annu; Nouri, Kent H; Pasupuleti, Ramarao; Sehgal, Nalini; Silverman, Sanford M; Simopoulos, Thomas T; Singh, Vijay; Solanki, Daneshvari R; Staats, Peter S; Vallejo, Ricardo; Wargo, Bradley W; Watanabe, Arthur; Hirsch, Joshua A
patient preferences, shared decision-making, and practice patterns with limited evidence, based on randomized controlled trials (RCTs) to improve pain and function in chronic non-cancer pain on a long-term basis. Consequently, chronic opioid therapy should be provided only to patients with proven medical necessity and stability with improvement in pain and function, independently or in conjunction with other modalities of treatments in low doses with appropriate adherence monitoring and understanding of adverse events.Key words: Chronic pain, persistent pain, non-cancer pain, controlled substances, substance abuse, prescription drug abuse, dependency, opioids, prescription monitoring, drug testing, adherence monitoring, diversionDisclaimer: The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."
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....
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...
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.......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....
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
Background and aim Opioid analgesics are often effective for pain management, but may cause constipation. The aim of this study was to determine healthcare resource use and costs in non-cancer and cancer patients with opioid-induced constipation (OIC). Methods This was a nationwide register......-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......, marital status, and comorbidities using Generalised Linear Model. Results We identified 97 169 eligible opioid users (77 568 non-cancer and 19 601 patients with a cancer diagnosis). Among non-cancer patients, 15% were classified with OIC, 10% had previous constipation, and 75% were without OIC. Patients...
Robertson, J A; Purple, R J; Cole, P; Zaiwalla, Z; Wulff, K; Pattinson, K T S
Poor sleep is an increasingly recognised problem with chronic pain and further increases the effect on daily function. To identify the relationship between chronic pain, opioid analgesia and sleep quality, this study investigated activity and sleep patterns in patients taking opioid and non-opioid analgesia for chronic back pain. Thirty-one participants (10 healthy controls, 21 patients with chronic pain: 6 on non-opioid medication; 15 on opioid medication) were assessed using actigraphy, polysomnography and questionnaires. Patients with chronic pain subjectively reported significant sleep and wake disturbances as shown by decreased overall sleep quality (Pittsburgh Sleep Quality Index, p 100 mg morphine-equivalent/day) demonstrated distinctly abnormal brain activity during sleep suggesting that polysomnography is necessary to detect sleep disturbance in this population in the absence of irregular rest-activity behaviour. Night-time sleep disturbance is common in individuals suffering from chronic pain and may be further exacerbated by opioid treatment. Considerations must be made regarding the appropriate use of combined actigraphy and miniaturised polysomnography for future population-based studies. © 2016 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists of Great Britain and Ireland.
Burns, Rachel M; Pacula, Rosalie L; Bauhoff, Sebastian; Gordon, Adam J; Hendrikson, Hollie; Leslie, Douglas L; Stein, Bradley D
State Medicaid policies play an important role in Medicaid enrollees' access to and use of opioid agonists, such as methadone and buprenorphine, in the treatment of opioid use disorders. Little information is available, however, regarding the evolution of state policies facilitating or hindering access to opioid agonists among Medicaid enrollees. During 2013-2014, we surveyed state Medicaid officials and other designated state substance abuse treatment specialists about their state's recent history of Medicaid coverage and policies pertaining to methadone and buprenorphine. We describe the evolution of such coverage and policies and present an overview of the Medicaid policy environment with respect to opioid agonist therapy from 2004 to 2013. Among our sample of 45 states with information on buprenorphine and methadone coverage, we found a gradual trend toward adoption of coverage for opioid agonist therapies in state Medicaid agencies. In 2013, only 11% of states in our sample (n = 5) had Medicaid policies that excluded coverage for methadone and buprenorphine, whereas 71% (n = 32) had adopted or maintained policies to cover both buprenorphine and methadone among Medicaid enrollees. We also noted an increase in policies over the time period that may have hindered access to buprenorphine and/or methadone. There appears to be a trend for states to enact policies increasing Medicaid coverage of opioid agonist therapies, while in recent years also enacting policies, such as prior authorization requirements, that potentially serve as barriers to opioid agonist therapy utilization. Greater empirical information about the potential benefits and potential unintended consequences of such policies can provide policymakers and others with a more informed understanding of their policy decisions.
Passik, Steven D; Webster, Lynn
Prescription opioid analgesics with a wide range of potencies are currently used for the treatment of chronic pain. Yet understanding the clinical relevance and therapeutic consequences of opioid potency remains ill defined. Both patients and clinicians alike have misperceptions about opioid potency, expecting that less-potent opioids will be less effective or fearing that more-potent opioids are more dangerous or more likely to be abused. In this review, common myths about the potency of opioid analgesics will be discussed. Clinicians should understand that pharmacologic potency per se does not necessarily imply more effective analgesia or higher abuse liability. Published dose conversion tables may not accurately calculate the dose for effective and safe rotation from one opioid to another in patients receiving long-term opioid therapy because they are based on limited data that may not apply to chronic pain. Differences in pharmacologic potency are largely accounted for by the actual doses prescribed, according to individualized patient need. Factors for achieving effective analgesia and reducing the risks involved with opioid use include careful medication selection based on patient characteristics, appropriate dosing titration and opioid rotation practices, knowledge of product formulation characteristics (eg, extended release, immediate release, and tamper-resistant features), and an awareness of differences in opioid pharmacokinetics and metabolism. Clinicians should remain vigilant in monitoring patients on any opioid medication, regardless of classification along the opioid potency continuum.
Leonard, James B; Nair, Vidya; Diaz, Christopher J; Penoyar, Jonathan B; Goode, Penelope A
Low dose naltrexone (LDN) has been evaluated in several small studies for the treatment of inflammatory conditions. It is thought to work through modulation of inflammatory mediators and upregulation of endogenous opioid receptors. This may hypersensitize patients to exogenous opioids. Drug-drug interaction screening tools built into electronic health records and other services identify the interaction as risk of opioid withdrawal rather than hypersensitivity. We present a case of a drug-drug interaction in a patient who was receiving LDN treatment of multiple sclerosis. The patient received a single dose of oxycodone 5mg that resulted in obtundation unresponsive to painful stimuli necessitating the administration of naloxone boluses and infusion along with admission to the intensive care unit for 1 night. The patient responded well to naloxone therapy. He was discharged in satisfactory condition. Copyright © 2017 Elsevier Inc. All rights reserved.
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.
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.
Full Text Available Opioid dependence, despite being the subject of significantpublic funding, remains a costly burden to Australian societyin human and economic terms. The most cost-effective publichealth strategy for managing opioid dependence is opioidsubstitution therapy (OST, primarily through the use ofmethadone or buprenorphine. Supervised dispensing of OSTfrom specialist clinics and community pharmacies plays acrucial role in enhancing compliance, monitoring treatmentand reducing diversion. Australia, compared with othercountries in the world, ranks very high in illicit opioid use;hence there is a great demand for OST.The utilisation of community pharmacies for stable patientshas many advantages. For public clinics, patient transfer tocommunity pharmacies relieves workload and costs, andincreases capacity for new OST patients. From a patient’sperspective, dosing at a pharmacy is more flexible andgenerally more preferable. Pharmacists stand to gain clientele,profit and receive small incentives from state governments inAustralia, for their services. Yet, many “unmet needs” existand there is a high demand for more involvement in OSTservice provision in community pharmacy in Australia.In the UK there has been a steady increase in communitypharmacy provision of OST, and pharmacists appear ready toprovide further healthcare services to these patients.The role of pharmacy in some countries in Europe, such asGermany, is less prominent due to their approach to harmminimisation and the complex, variable nature of OSTprovision across the European Union (EU. The provisionof OST by pharmacists in the USA on the other hand is oflesser frequency as the healthcare system in the USAencourages detoxification clinics to handle cases of illicitdrug addiction.At a time when harm minimisation strategies constitute atopic of considerable political and public interest, it isimportant to understand the scope and variability ofpharmacy involvement in drug policy in Australia
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.
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.
F. J. López-Pérez; E. Vicario-Sánchez; A. Mínguez-Martí; M. P. Ortega-García; A. Pastor-Clérigues; J. Sanfeliu-García
Objetivo: Analizar la mejoría clínica de los pacientes sometidos a cambio de opioide y describir el protocolo utilizado para el cambio. Método: Estudio observacional retrospectivo. Se seleccionaron pacientes sometidos a cambio de opioide en el periodo de estudio (18 meses). Fueron criterios para cambio de opioide: tratamiento con fármacos escalón 3 de la escalera de la OMS junto a coadyuvantes durante más de 6 meses y presentar una escala análogo visual del dolor de al menos 5, con o sin ...
Shanmugam, Victoria K.; Couch, Kara S.; McNish, Sean; Amdur, Richard L.
Opioids are routinely used analgesics in patients with chronic wounds; however the impact of opioid exposure on wound healing is poorly understood. The purpose of this study was to investigate the association between opioid exposure and wound outcome in the WE-HEAL study. This longitudinal observational study was conducted on 450 subjects enrolled in the WE-HEAL biorepository. Data were collected prospectively including baseline characteristics, pain score, longitudinal opioid exposure, and total wound surface area (tWSA). Data were analyzed using static multivariate models, fixed-effects mixed models, and time to event analysis. Using fixed-effects models, opioid dose was significantly associated with tWSA after accounting for the effects of pain score and baseline co-variates (pwound size. Patients with opioid dose >0 to wounds; however, the data presented suggest that opioid exposure is associated with reduced likelihood of healing in patients with chronic wounds. Whether this is a causal relationship will require further study. PMID:27865036
Jones, Jermaine D; Vogelman, Jonathan S; Luba, Rachel; Mumtaz, Mudassir; Comer, Sandra D
While research on the separate relationships between health-related quality of life (HRQOL) and chronic pain, and HRQOL and opioid abuse has been sparse, even less work has investigated the factors associated with HRQOL in individuals who have both chronic pain and meet criteria for opioid use disorder. The data presented in this analysis should allow a better understanding the factors important to quality of life among this dual-diagnosed population. Individuals with dual diagnoses of chronic pain and opioid use disorder were recruited for clinical research studies at Columbia University Medical Center. Participants (n = 47) completed inventories to assess pain (Brief Pain Inventory), opioid (ab)use, and depression (Beck Depression Inventory). Variable from these and other inventories, along with demographic factors (age, race, sex, pain severity, depressive symptoms, duration of opioid use, route of opioid use, amount of opioid use) were entered into a regression analysis in order to identify the strongest predictors of SF-36 Health Survey score. In the bivariate analysis we found that demographic and drug use variables were rarely associated with HRQOL. Typically, ratings of pain severity and pain interference were the best predictors. In the multivariate analysis, we found that across the several HRQOL dimensions greater Brief Pain Inventory (BPI) ratings of pain "interference" and Beck Depression Inventory (BDI) scores were consistently associated with lower HRQOL. These data suggest that insufficient pain management and depression are significant variables contributing to lower quality of life among individuals with chronic pain and opioid use disorder. (Am J Addict 2017;26:815-821). © 2017 American Academy of Addiction Psychiatry.
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
Gálvez, Rafael; Schäfer, Michael; Hans, Guy; Falke, Dietmar; Steigerwald, Ilona
This open-label, phase 3b study evaluated the effectiveness and tolerability of oral tapentadol prolonged release (PR; 50-250 mg twice daily [b.i.d.]) for managing severe, chronic low back pain in patients responding to World Health Organization (WHO) step III opioids but tolerating treatment poorly. Equianalgesic ratios for tapentadol to prior strong opioids were calculated. Patients rotated directly from prior WHO step III opioids to tapentadol. Patients received tapentadol PR (50-250 mg b.i.d.) during 5-week titration and 7-week maintenance periods. Tapentadol immediate release (IR) 50 mg (≤ twice/day, ≥ 4 h apart) was allowed (total daily dose of tapentadol PR and IR ≤ 500 mg/day). The primary endpoint was responder rate 1 at week 6 (percentage of patients with the same or less pain intensity [11-point numerical rating scale (NRS; 3-day average)] vs week -1). Responder rate 1 at week 6 (last observation carried forward [LOCF]) was 80.9% (76/94; P pain intensity and neuropathic pain symptoms were observed at weeks 6 and 12 with tapentadol PR (P comparable pain relief and improved tolerability versus prior strong opioids in patients with severe, chronic low back pain responding to WHO step III therapy. Conversion from strong opioids to tapentadol PR, with its two mechanisms of action, went smoothly considering overall effectiveness and tolerability outcomes. Equianalgesic ratios of tapentadol to oxycodone and other strong opioids were in line with other phase 3/3b studies.
Knight, Kelly R; Kushel, Margot; Chang, Jamie S; Zamora, Kara; Ceasar, Rachel; Hurstak, Emily; Miaskowski, Christine
There is growing concern among US-based clinicians, patients, policy makers, and in the media about the personal and community health risks associated with opioids. Perceptions about the efficacy and appropriateness of opioids for the management of chronic non-cancer pain (CNCP) have dramatically transformed in recent decades. Yet, there is very little social scientific research identifying the factors that have informed this transformation from the perspectives of prescribing clinicians. As part of an on-going ethnographic study of CNCP management among clinicians and their patients with co-occurring substance use, we interviewed 23 primary care clinicians who practice in safety-net clinical settings. In this paper, we describe the clinical and social influences informing three historic periods: (1) the escalation of opioid prescriptions for CNCP; (2) an interim period in which the efficacy of and risks associated with opioids were re-assessed; and (3) the current period of "opioid pharmacovigilance," characterized by the increased surveillance of opioid prescriptions. Clinicians reported that interpretations of the evidence-base in favor of and opposing opioid prescribing for CNCP evolved within a larger clinical-social context. Historically, pharmaceutical marketing efforts and clinicians' concerns about racialized healthcare disparities in pain treatment influenced opioid prescription decision-making. Clinicians emphasized how patients' medical complexity (e.g. multiple chronic health conditions) and structural vulnerability (e.g. poverty, community violence) impacted access to opioids within resource-limited healthcare settings. This clinical-social history of opioid prescribing practices helps to elucidate the ongoing challenges of CNCP treatment in the US healthcare safety net and lends needed specificity to the broader, nationwide conversation about opioids. Copyright © 2017 Elsevier Ltd. All rights reserved.
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.
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.
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.
van Ojik, Annette L.; Jansen, Paul A. F.; Brouwers, Jacobus R. B. J.; van Roon, Eric N.
In the treatment of chronic malignant and non-malignant pain, opioids are used as strong analgesics. Frail elderly patients often have multiple comorbidities and use multiple medicines, leading to an increased risk of clinically relevant drug-drug and drug-disease interactions. Age-related changes
Gauntlett-Gilbert, Jeremy; Gavriloff, Dimitri; Brook, Peter
Opioid prescription for noncancer pain is increasing in Europe and the United States. Research and guidance have focused on the potential for dependency and medical side effects with high doses. In contrast, benzodiazepines have received little attention in the chronic pain literature, despite evidence for dependency and cognitive impairment in long-term use. We aimed to examine the relationship between these classes of medication use, mood, and functioning. This cross-sectional study included patients (N=229) with disabling chronic pain who were about to start intensive pain rehabilitation. They completed self-report measures of mood, functioning, and responses to pain. We examined each patient's medication use and calculated a single morphine equivalent (ME) dose per person, and a similar diazepam equivalent (DE) dose. We examined the relationship between drug dose, mood, and functioning. Higher DE doses were associated with worse outcomes in most domains. Higher ME doses were more narrowly associated with worse functioning. There was no evidence for any benefit of these drugs; higher doses were not associated with less pain, fear, or disability. Higher ME doses were not more problematic, contrary to our predictions. The combination of opioids and benzodiazepines was associated with particularly poor outcomes for mood. This study is the first to examine both opioid and benzodiazepine use together in chronic pain. We found the anticipated negative effects of opioid medication, and particularly consistent associations between benzodiazepine use and poor well-being. Future guidance on chronic pain prescription should focus on restricting benzodiazepine use.
O'Brien, T; Christrup, L L; Drewes, A M
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 therap...
scavenging system of plasma and liver and heart pathology in adolescence heroin users; Vopr. Med. Khim. 45 501–506. Poppers P J 1980 Hepatic drug metabolism and anesthesia;. Anaesthesist 29 55–58. Portenoy K R and Foley K M 1986 Chronic use of opioid analgesics in non-malignant pain: Report of 38 cases; Pain.
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
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.
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...... of different health care providers. The Danish health survey of 2005 was based on a region-stratified random sample of 10.916 individuals. Data were collected via personal interviews and self-administrated questionnaires. Respondents suffering from chronic pain were identified through the question 'Do you have...... 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...
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
Full Text Available Over 50% of HIV-1/AIDS patients suffer chronic pain. Currently, opioids are the cornerstone medications for treating severe pain in these patients. Ironically, emerging clinical data indicates that repeated use of opiate pain medicines might in fact heighten the chronic pain states in HIV patients. Both laboratory-based and clinical studies strongly suggest that opioids exacerbate the detrimental effects of HIV-1 infection on the nervous system, both on neurons and glia. The combination of opioids and HIV-1 infection may promote the damage of neurons, including those in the pain sensory and transmission pathway, by activating both caspase-dependent and caspase-independent pro-apoptotic pathways. In addition, the opiate-HIV-1 interaction may also cause widespread disturbance of glial function and elicit glial-derived pro-inflammatory responses that dysregulate neuronal function. The deregulation of neuron-glia cross-talk that occurs with the combination of HIV-1 and opioids appears to play an important role in the development of the pathological pain state. In this article, we wish to provide an overview of the potential molecular and cellular mechanisms by which opioids may interact with HIV-1 to cause neurological problems, especially in the context of HIV-associated pathological pain. Elucidating the underlying mechanisms will help researchers and clinicians to understand how chronic use of opioids for analgesia enhances HIV-associated pain. It will also assist in optimizing therapeutic approaches to prevent or minimize this significant side effect of opiate analgesics in pain management for HIV patients.
Barry, Declan T; Cutter, Christopher J; Beitel, Mark; Kerns, Robert D; Liong, Christopher; Schottenfeld, Richard S
Psychiatric comorbidities complicate treatment of patients with chronic pain and opioid use disorder, but the prevalence of specific comorbid psychiatric disorders in this population has not been systematically investigated. 170 consecutive participants entering a treatment research program for co-occurring chronic pain and opioid use disorder between March 2009 and July 2013 were evaluated with the Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID-I/P) and the Diagnostic Interview for DSM-IV Personality Disorders (DIPD-IV). The prevalence of any lifetime (and current) comorbid Axis I disorder was 91% (75%); 52% met criteria for lifetime anxiety disorder (48% current), 57% for lifetime mood disorder (48% current), and 78% for lifetime nonopioid substance use disorder (34% current). Common current anxiety diagnoses were posttraumatic stress disorder (21%), generalized anxiety disorder (16%), and panic disorder without agoraphobia (16%). Common current mood diagnoses were major depressive disorder (40%) and dysthymia (11%). A majority of patients had a personality disorder (52%). High rates and persistence of co-occurring psychiatric disorders, including anxiety or mood disorders, may explain in part the difficulty providers have treating patients with co-occurring opioid use disorder and chronic pain and suggest possible targets for improving treatment. ClinicalTrials.gov identifiers: buprenorphine/naloxone treatment (NCT00634803), opioid treatment program-based methadone maintenance treatment (NCT00727675). © Copyright 2016 Physicians Postgraduate Press, Inc.
Maslov, L. N.; Naryzhnaya, N. V.; Tsibulnikov, S.Yu.; Kolář, František; Zhang, Y.; Wang, H.; Gusakova, A. M.; Lishmanov, Yu. B.
Roč. 93, 9-11 (2013), s. 373-379 ISSN 0024-3205 R&D Projects: GA ČR(CZ) GAP303/12/1162 Institutional support: RVO:67985823 Keywords : chronic hypoxia * myocardial infarction * cardioprotection * opioid peptides * opioid receptors Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.296, year: 2013
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.
Young, Neil; Silverman, Daniel; Bradford, Heather; Finkelstein, Jeffrey
Despite a range of therapeutic options for treating acute migraine headaches, the use of opioids is still reported to be common practice. This study describes treatment practices in regards to migraines in the ED. It characterizes the prevalence of opioid orders during visits in three different settings, an academic medical center, a non-academic urban ED, and a community ED. Fourteen months of consecutive migraine visits were identified. All medications ordered were separated into first-line and rescue medications. Number of visits, length of stay, door to provider time, and total provider time were compared. A total of 1222 visits were identified. Opioids were ordered in 35.8% of these visits. By facility, opioids were ordered in 12.3% of academic medical center visits, 40.9% of urban ED visits, and 68.6% of community ED visits. This ranged from 6.9% of first-line therapies in the academic center to 69.9% of rescue therapies in the community ED. Of those who received opioids, 36.0% versus 25.1% required rescue medications. Patients who received opioids had more repeat visits, 1.79 versus 1.30. The academic center and urban ED both found greater than 30% decrease in length of stay in visits where opioids were not given. In the face of evidence against opioids for migraines, over one third of patients received them. There was a higher prevalence in the community setting. There were no significant benefits in overall throughput time, however, opioid visits required more rescue medications, increased length of stay, and resulted in more repeat visits. Copyright © 2017 Elsevier Inc. All rights reserved.
Henry, Stephen G; Bell, Robert A; Fenton, Joshua J; Kravitz, Richard L
Patients and physicians report that communication about chronic pain and opioids is often challenging, but there is little empirical research on whether patient-physician communication about pain affects patient and physician visit experience. This study video recorded 86 primary care visits involving 49 physicians and 86 patients taking long-term opioids for chronic musculoskeletal pain, systematically coded all pain-related utterances during these visits using a custom-designed coding system, and administered previsit and postvisit questionnaires. Multiple regression was used to identify communication behaviors and patient characteristics associated with patients' ratings of their visit experience, physicians' ratings of visit difficulty, or both. After adjusting for covariates, 2 communication variables-patient-physician disagreement and patient requests for opioid dose increases-were each significantly associated with both worse ratings of patient experience and greater physician-reported visit difficulty. Patient desire for increased pain medicine was also significantly positively associated with both worse ratings of patient experience and greater physician-reported visit difficulty. Greater pain severity and more patient questions were each significantly associated with greater physician-reported visit difficulty, but not with patient experience. The association between patient requests for opioids and patient experience ratings was wholly driven by 2 visits involving intense conflict with patients demanding opioids. Patient-physician communication during visits is associated with patient and physician ratings of visit experience. Training programs focused on imparting communication skills that assist physicians in negotiating disagreements about pain management, including responding to patient requests for more opioids, likely have potential to improve visit experience ratings for both patients and physicians.
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.
Grande, Lucinda A; Thompson, Ellen Campbell; Au, Margaret A; Sawyer, Devin; Baldwin, Laura-Mae; Rosenblatt, Roger
Problem drug-related behavior (PDB) among patients on chronic opioid therapy may reflect an opioid use disorder. This study assessed PDB prevalence and the relationship between PDB and ongoing prescription of opioids at a primary care clinic that implemented a multifaceted opioid management program. A chart review of patients in a chronic opioid registry assessed prevalence of different types of PDB over 2 years, and whether opioids were prescribed during the last 3 months of the 2-year study period among patients with different levels of PDB. Among 233 registry patients, 84.1% exhibited PDB; 45.5% exhibited ≥3 types of PDB. At the end of 2 years, most registry patients were still prescribed opioids, though patients with ≥3 types of PDB were less likely than those without PDB to be prescribed opioids (62.3% vs. 78.4%, P = 0.016). PDB was pervasive in this population of patients on chronic opioid therapy. Those with the most PDB, and thus with the greatest likelihood of opioid use disorder and its social and medical consequences, were the least likely to be prescribed opioids by the clinic after 2 years. Given the rising rates of illicit opioid use in the U.S., it is important that clinics work closely with their patients who display PDB, systematically assess them for opioid use disorder, and offer evidence-based treatment. © Copyright 2016 by the American Board of Family Medicine.
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.
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.
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.
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.
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 .
Ringwalt, Chris; Gugelmann, Hallam; Garrettson, Mariana; Dasgupta, Nabarun; Chung, Arlene E; Proescholdbell, Scott K; Skinner, Asheley Cockrell
Despite >20 years of studies investigating the characteristics of patients seeking or receiving opioid analgesics, research characterizing factors associated with physicians' opioid prescribing practices has been inconclusive, and the role of practitioner specialty in opioid prescribing practices remains largely unknown. To examine the relationships between physicians' and other providers' primary specialties and their opioid prescribing practices among patients with chronic noncancer pain (CNCP). Prescriptions for opioids filled by 81,459 Medicaid patients with CNCP in North Carolina (USA), 18 to 64 years of age, enrolled at any point during a one-year study period were examined. χ2 statistics were used to examine bivariate differences in prescribing practices according to specialty. For multivariable analyses, maximum-likelihood logistic regression models were used to examine the effect of specialty on prescribing practices, controlling for patients' pain diagnoses and demographic characteristics. Of prescriptions filled by patients with CNCP, who constituted 6.4% of the total sample of 1.28 million individuals, 12.0% were for opioids. General practitioner⁄family medicine specialists and internists were least likely to prescribe opioids, and orthopedists were most likely. Across specialties, men were more likely to receive opioids than women, as were white individuals relative to other races⁄ethnicities. In multivariate analyses, all specialties except internal medicine had higher odds of prescribing an opioid than general practitioners: orthopedists, OR 7.1 (95% CI 6.7 to 7.5); dentists, OR 3.5 (95% CI 3.3 to 3.6); and emergency medicine physicians, OR 2.7 (95% CI 2.6 to 2.8). Significant differences in opioid prescribing practices across prescriber specialties may be reflective of differing norms concerning the appropriateness of opioids for the control of chronic pain. If so, sharing these norms across specialties may improve the care of patients with
Merlin, Jessica S; Young, Sarah R; Azari, Soraya; Becker, William C; Liebschutz, Jane M; Pomeranz, Jamie; Roy, Payel; Saini, Shalini; Starrels, Joanna L; Edelman, E Jennifer
Given the sharp rise in opioid prescribing and heightened recognition of opioid addiction and overdose, opioid safety has become a priority. Clinical guidelines on long-term opioid therapy (LTOT) for chronic pain consistently recommend routine monitoring and screening for problematic behaviours. Yet, there is no consensus definition regarding what constitutes a problematic behaviour, and recommendations for appropriate management to inform front-line providers, researchers and policymakers are lacking. This creates a barrier to effective guideline implementation. Thus, our objective is to present the protocol for a Delphi study designed to: (1) elicit expert opinion to identify the most important problematic behaviours seen in clinical practice and (2) develop consensus on how these behaviours should be managed in the context of routine clinical care. We will include clinical experts, defined as individuals who provide direct patient care to adults with chronic pain who are on LTOT in an ambulatory setting, and for whom opioid prescribing for chronic non-malignant pain is an area of expertise. The Delphi study will be conducted online in 4 consecutive rounds. Participants will be asked to list problematic behaviours and identify which behaviours are most common and challenging. They will then describe how they would manage the most frequently occurring common and challenging behaviours, rating the importance of each management strategy. Qualitative analysis will be used to categorise behaviours and management strategies, and consensus will be based on a definition established a priori. This study has been approved by the Institutional Review Board (IRB) of the University of Alabama at Birmingham (UAB). This study will generate Delphi-based expert consensus on the management of problematic behaviours that arise in individuals on LTOT, which we will publish and disseminate to appropriate professional societies. Ultimately, our findings will provide guidance to front
[Opioids in chronic noncancer pain-are opioids superior to nonopioid analgesics? A systematic review and meta-analysis of efficacy, tolerability and safety in randomized head-to-head comparisons of opioids versus nonopioid analgesics of at least four week's duration].
Welsch, P; Sommer, C; Schiltenwolf, M; Häuser, W
Some leading German pain medicine experts postulate that there is a type of chronic non-cancer pain (CNCP) with an opioid requirement. We tested whether opioids are superior to nonopioid analgesics in the management of CNCP in studies of at least 4 week's duration. We screened MEDLINE, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) up until October 2013, as well as the reference sections of original studies and systematic reviews of randomised controlled trials (RCTs) of opioids in CNCP. We included double-blind RTCs comparing opioids to nonopioid analgesics of at least 4 week's duration. Relative risks differences (RD) of categorical data and standardized mean differences (SMD) of continuous variables were calculated using a random effects model. We included 10 RCTs with 3046 participants. Median study duration was 6 weeks (range 4-12 weeks). Five studies compared tramadol with nonsteroidal anti-inflammatory drugs (NSAIDs) in osteoarthritis pain and one trial compared tramadol to flupirtine in low back pain. Morphine was compared to antidepressants (two studies), an anticonvulsant (one study) and an antiarrhythmic (one study) in different neuropathic pain syndromes. There was no significant difference between opioids and nonopioid analgesics in pain reduction (SMD 0.03 [95 % confidence interval, CI - 0.18, 0.24]; p = 0.76). Nonopioid analgesics were superior to opioids in improving physical function (SMD 0.17 [95 % CI 0.02, 0.32]; p = 0.03). Patients dropped out due to adverse events more frequently with opioids than with nonopioid analgesics (RD 0.09 [95 % CI 0.06, 0.13]; p opioids and nonopioid analgesics in terms of serious adverse events or dropout rates due to lack of efficacy. Nonopioid analgesics are superior to opioids in terms of improvement of physical function and tolerability in short-term (4-12 weeks) therapy of neuropathic, low back and osteoarthritis pain. Our results do not support the
Nosyk, Bohdan; Guh, Daphne P; Bansback, Nicholas J; Oviedo-Joekes, Eugenia; Brissette, Suzanne; Marsh, David C; Meikleham, Evan; Schechter, Martin T; Anis, Aslam H
Although diacetylmorphine has been proven to be more effective than methadone maintenance treatment for opioid dependence, its direct costs are higher. We compared the cost-effectiveness of diacetylmorphine and methadone maintenance treatment for chronic opioid dependence refractory to treatment. We constructed a semi-Markov cohort model using data from the North American Opiate Medication Initiative trial, supplemented with administrative data for the province of British Columbia and other published data, to capture the chronic, recurrent nature of opioid dependence. We calculated incremental cost-effectiveness ratios to compare diacetylmorphine and methadone over 1-, 5-, 10-year and lifetime horizons. Diacetylmorphine was found to be a dominant strategy over methadone maintenance treatment in each of the time horizons. Over a lifetime horizon, our model showed that people receiving methadone gained 7.46 discounted quality-adjusted life-years (QALYs) on average (95% credibility interval [CI] 6.91-8.01) and generated a societal cost of $1.14 million (95% CI $736,800-$1.78 million). Those who received diacetylmorphine gained 7.92 discounted QALYs on average (95% CI 7.32-8.53) and generated a societal cost of $1.10 million (95% CI $724,100-$1.71 million). Cost savings in the diacetylmorphine cohort were realized primarily because of reductions in the costs related to criminal activity. Probabilistic sensitivity analysis showed that the probability of diacetylmorphine being cost-effective at a willingness-to-pay threshold of $0 per QALY gained was 76%; the probability was 95% at a threshold of $100,000 per QALY gained. Results were confirmed over a range of sensitivity analyses. Using mathematical modelling to extrapolate results from the North American Opiate Medication Initiative, we found that diacetylmorphine may be more effective and less costly than methadone among people with chronic opioid dependence refractory to treatment.
Pade, Patricia A; Cardon, Karen E; Hoffman, Richard M; Geppert, Cynthia M A
Abuse of opioids has become a public health crisis. The historic separation between the addiction and pain communities and a lack of training in medical education have made treatment difficult to provide, especially in primary care. The Co-occurring Disorders Clinic (COD) was established to treat patients with co-morbid chronic pain and addiction. This retrospective chart review reports results of a quality improvement project using buprenorphine/naloxone to treat co-occurring chronic non-cancer pain (CNCP) and opioid dependence in a primary care setting. Data were collected for 143 patients who were induced with buprenorphine/naloxone (BUP/NLX) between June 2009 and November 2011. Ninety-three patients (65%) continued to be maintained on the medication and seven completed treatment and were no longer taking any opioid (5%). Pain scores showed a modest, but statistically significant improvement on BUP/NLX, which was contrary to our expectations and may be an important factor in treatment retention for this challenging population. Published by Elsevier Inc.
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
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
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.
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.
Full Text Available Abstract Background Little data exist on how opioid doses vary with the length of exposure among chronic opioid users. Methods To characterize the change in the dosage of opioids over time, a retrospective cohort study using the PharMetrics database for the years 1999 through 2008 was conducted. Individuals exposed to opioids in 2000 who had 2 opioid dispensings at least 6 months apart and were opioid naive (did not receive any opioid 6 month before their exposure in 2000 were included. The date of the first dispensing in 2000 was defined as the index date and the dispensing had to be for a strong and full agonist opioid. All opioid doses were converted to oral morphine equivalent doses. Exposure was classified as continuous or intermittent. Mean, median, interquartile range, and 95th percentile of opioid dose over 6-month periods, as well as the percentage of subjects who ever received a high or very high opioid dose, were calculated. Results Among the 48,986 subjects, the mean age was 44.5 years and 54.5% were women. Intermittent exposure was observed in 99% of subjects; continuous exposure was observed in 1% of subjects. The mean duration of exposure for the subjects who were continuously exposed to opioids was 477 days. In subjects with no cancer diagnosis who were continuously exposed to opioids, the mean, 25th, 50th, and 75th percentile of dose was stable during the first 2 years of use, but the 95th percentile increased. Seven percent of them were exposed to doses of 180 mg or more of morphine at some point. Conclusions Dose escalation is uncommon in subjects with intermittent exposure to opioids. For subjects with continuous exposure to opioids who have cancer, doses rise substantially with time. For those without cancer, doses remain relatively stable for the first 2 years of use, but subsequently increase. Seven percent of subjects with no cancer diagnosis will be exposed to daily doses of 180 mg or more of morphine equivalent at some
Staahl, Camilla; Dimcevski, Georg; Andersen, Søren Due
in the oesophagus than placebo (F=8.6, popioids and placebo in any tissue studied. CONCLUSIONS: Oxycodone was a stronger analgesic than morphine in several pain modalities in the skin, muscle and oesophagus.......OBJECTIVE: Animal experiments and clinical observations have indicated a different working profile of oxycodone compared to morphine, and it has previously been shown that oxycodone attenuates visceral pain better than morphine. The objective of this study was to test the effects of oxycodone...... 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...
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
Krebs, Erin E; Gravely, Amy; Nugent, Sean; Jensen, Agnes C; DeRonne, Beth; Goldsmith, Elizabeth S; Kroenke, Kurt; Bair, Matthew J; Noorbaloochi, Siamak
Limited evidence is available regarding long-term outcomes of opioids compared with nonopioid medications for chronic pain. To compare opioid vs nonopioid medications over 12 months on pain-related function, pain intensity, and adverse effects. Pragmatic, 12-month, randomized trial with masked outcome assessment. Patients were recruited from Veterans Affairs primary care clinics from June 2013 through December 2015; follow-up was completed December 2016. Eligible patients had moderate to severe chronic back pain or hip or knee osteoarthritis pain despite analgesic use. Of 265 patients enrolled, 25 withdrew prior to randomization and 240 were randomized. Both interventions (opioid and nonopioid medication therapy) followed a treat-to-target strategy aiming for improved pain and function. Each intervention had its own prescribing strategy that included multiple medication options in 3 steps. In the opioid group, the first step was immediate-release morphine, oxycodone, or hydrocodone/acetaminophen. For the nonopioid group, the first step was acetaminophen (paracetamol) or a nonsteroidal anti-inflammatory drug. Medications were changed, added, or adjusted within the assigned treatment group according to individual patient response. The primary outcome was pain-related function (Brief Pain Inventory [BPI] interference scale) over 12 months and the main secondary outcome was pain intensity (BPI severity scale). For both BPI scales (range, 0-10; higher scores = worse function or pain intensity), a 1-point improvement was clinically important. The primary adverse outcome was medication-related symptoms (patient-reported checklist; range, 0-19). Among 240 randomized patients (mean age, 58.3 years; women, 32 [13.0%]), 234 (97.5%) completed the trial. Groups did not significantly differ on pain-related function over 12 months (overall P = .58); mean 12-month BPI interference was 3.4 for the opioid group and 3.3 for the nonopioid group (difference, 0.1 [95% CI, -0
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.
Yuan, Fang; Li, Hong-Wei; Song, Shi-Jun; Teng, Xu; Ma, Hui-Jie; Guo, Zan; Zhang, Yi; Zhou, Zhao-Nian
The present study was designed to investigate the role of opioid receptors in the vasorelaxation effect of chronic intermittent hypobaric hypoxia (CIHH) in thoracic aorta rings and the underlying mechanism in rats. Adult male Sprague-Dawley (SD) rats were randomly divided into 2 groups: CIHH treatment group and control group. The rats in CIHH group were exposed to hypoxia in a hypobaric chamber (simulated 5 000 m altitude) for 28 days, 6 h per day. The rats in control group were kept in the same environment as CIHH rats except no hypoxia exposure. The relaxation of thoracic aorta rings was recorded by organ bath perfusion technique, and expression of opioid receptors was measured by Western blot. Results are shown as follows. (1) The acetylcholine (ACh)-induced endothelium-dependent relaxation of thoracic aorta in CIHH rats was increased obviously in a concentration-dependent manner compared with that in control rats (P ACh-induced relaxation in CIHH rats was abolished by naloxone, a non-specific opioid receptor blocker (P ACh-induced vasorelaxation of thoracic aorta through KATP channel pathways.
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.
Coloma-Carmona, A; Carballo, J L; Rodríguez-Marín, J; Pérez-Carbonell, A
To analyse the prevalence in the use and dependence on opioid drugs in the Spanish population with chronic pain and evaluate the differences according to sex. The demographic variables, opioid treatment characteristics and use of other substances were assessed in 229 users of opioid drugs. A descriptive bivariate analysis of the data was performed. Forty-six percent of the patients met the criteria of dependence on opioid drugs (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition [DSM-IV-TR]). Alcohol and cannabis consumption was greater in the men. The rates of dependence on the use of opioid drugs were significantly higher in the extended treatments. Planning for treatments with opioids and strategies for preventing inappropriate use should not depend on the patient's sex. We need further studies on the medical and psychological variables related to the use of and dependence on opioids. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.
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.
Lindstrøm, Maia; Saidj, Madina; Kowalski, Krystyna
people who misuse non-opioid drugs. FBT is a manual-based family therapy approach. The program is behavior and skill-oriented. It is concerned with identifying psychological and situational stimuli and triggers presumed to be directly related to the youth’s drug use, and skills training to improve self......BACKGROUND Youth drug use is a severe problem worldwide, and the use of cannabis, amphetamine ecstasy and cocaine, referred to as non-opioid drugs, are strongly associated with a range of health and social problems. This review focuses on Family Behavior Therapy (FBT) as a treatment for young...... language nor date restrictions were applied to the searches. SELECTION CRITERIA Studies eligible for inclusion in the review are required to meet several eligibility criteria. Studies must: • have involved a manual-based FBT treatment for young people aged 11-21 years enrolled in outpatient treatment...
Niikura, Keiichi; Narita, Minoru; Butelman, Eduardo R; Kreek, Mary Jeanne; Suzuki, Tsutomu
Although morphine and other mu-opioid agonists are the main analgesics for severe pain, these compounds have potential for abuse and/or addiction. This has complicated the use of mu-agonists in the treatment of chronic pain. However, clinical studies show that when mu-agonist analgesics are appropriately used to control pain, actual abuse or addiction does not usually occur, although some risk factors that increase vulnerability need to be considered, including genetic variation. We review recent findings on molecular adaptations in sustained pain models, and propose how these adaptations (including sustained release of the endogenous mu-agonist beta-endorphin) can result in decreased abuse potential of mu-agonists in chronic pain states. We also review data on particular gene polymorphisms (e.g. in the mu-receptor gene) that could also influence the relative abuse potential of mu-agonists in clinical pain populations. Copyright 2010 Elsevier Ltd. 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
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...
Surbhi, Satya; Graetz, Ilana; Wan, Jim Y; Gatwood, Justin; Bailey, James E
Nonadherence to essential chronic medications has been identified as a potential driver of high health care costs in superutilizers of inpatient services. Few studies, however, have documented the levels of nonadherence and factors associated with nonadherence in this high-cost, vulnerable population. To examine the factors associated with nonadherence to essential chronic medications, with special emphasis on mental illness and use of opioid medications. This study was a retrospective panel analysis of 2-year baseline data for Medicare Part D beneficiaries eligible for the SafeMed care transitions program in Memphis, Tennessee, from February 2013 to December 2014. The 2-year baseline data for each patient were divided into four, 6-month patient periods. The study included Medicare superutilizers (defined as patients with ≥ 3 hospitalizations or ≥ 2 hospitalizations with ≥ 2 emergency visits in 6 months) with continuous Part D coverage who had filled at least 1 drug class used to treat hypertension, diabetes mellitus, congestive heart failure, coronary artery disease, or chronic lung disease. The outcome included medication nonadherence assessed using proportion of days covered (PDC), with PDC mental illness (defined as a diagnosis of depression or anxiety or ≥ 1 anxiolytic or antidepressant fill) and opioid medication fills assessed in each 6-month period. Pooled observations from the four 6-month periods were used for multivariable analyses using the patient periods as the unit of analysis. A random effects model with robust standard errors and a binary distribution were used to examine associations between independent variables (time invariant and time variant factors) and medication nonadherence. The model included lagged effects of time variant factors measured in each period. Overall nonadherence to essential chronic medications ranged from 39.3% to 58.4%, with the highest for chronic lung disease medications (49.1%-64.4%). Factors associated with
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.
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
Amabile, Celene M; Bowman, Bill J
To evaluate pharmaceutical and pharmacotherapeutic differences in oral opioid modified-release products used in the management of chronic pain. Searches of MEDLINE (1966-May 2006) and an extensive review of peer reviewed journals were conducted using the key search terms opioid, morphine, hydromorphone, and oxycodone. Supplemental information was gathered through the American Pain Society, and limited but relevant information was obtained from manufacturers' labeling. All articles identified from the data sources were evaluated. Information deemed relevant was included for this review if it introduced new or well supported concepts or clarified clinical practice issues. The recognition and treatment of pain has become a major focus of healthcare professionals. The Joint Commission on Accreditation of Healthcare Organizations mandates compliance with recommended standards, outcome measures, and other initiatives. A general review of pain management and pharmacokinetic parameters are included. Oral modified-release products have enabled patients to better maintain pain control due to convenient dosing intervals and sustained blood concentrations. The differences between available oral modified-release products are half-life, cost, and formulation (excipients and drug-release properties).
agility, suggesting that the decrease in voluntary exercise is due to loss of motivation or pain amplification rather than physical disability . We... disability 15 Sep 2016 - 14 Sep 2017 15. SUBJECT TERMS chronic pain, opioid analgesics, non-opioid analgesics, toll-like receptor 4, return to duty 16...of the project? 1. Define whether deleterious effects of opioids extend beyond neuropathic pain to other indices of disability . Determine
Vargovich, Alison M; McNeil, Daniel W; Foley, Kimberly P; Sperry, Jeannie
The misuse and abuse of opioids has increased across the United States in recent years, associated with a rise in opioid-related overdose deaths. Physicians report having difficulty discerning substance abuse or drug diversion, which can lead to over- or under-prescribing of opioids and poor pain management. Additionally, research suggests that patient characteristics (eg, sex, ethnicity/race, age) may unduly influence the pain management decisions of health care providers. This investigation aimed to assist in physicians' prescribing decisions and reduce prescribing bias through the assistance of mental health professionals. This study utilized 151 chronic pain patients being considered for chronic opioid therapy to determine if a psychological opioid-risk evaluation influenced physicians' opioid prescribing. The evaluation resulted in an opioid-risk level (ie, low, moderate, high) being assigned to each patient representing their potential risk for misusing or abusing opioid medication. A record review was conducted on each patient, abstracting information about opioid prescribing, and several other factors, which were included in logistic regression analyses. Risk status and substance abuse history significantly predicted opioid prescribing, with a lower risk status associated with greater likelihood of opioid prescribing and those with a history of substance abuse being less likely to be prescribed an opioid; however, substance abuse did not significantly improve the overall model and was removed. Demographic variables were not significant predictors of prescribing contrary to findings in other studies. These findings suggest that providing physicians with additional information about their patients' opioid abuse potential aids in prescribing decisions and may reduce prescribing bias based on demographic factors.
Filges, Trine; Knudsen, Anne-Sofie Due; Svendsen, Majken
BACKGROUND Youth drug use is a severe problem worldwide. This review focuses on Cognitive-Behavioural Therapy (CBT) as a treatment for young people who misuse non-opioid drugs, such as cannabis, amphetamines, ecstasy and cocaine, which are strongly associated with a range of health and social...... problems. CBT is an individualized and multicomponent intervention that combines behavioural and cognitive therapy. While behavioural therapy mainly focuses on external settings and observable behaviour, cognitive therapy is concerned with internal cognitive processes. The primary focus of CBT is to reduce...... literature databases, citations in other reviews and in the included primary studies, hand searches of relevant journals, and Internet searches using Google. We also corresponded with researchers in the CBT field. No language or date restrictions were applied to the searches. SELECTION CRITERIA Studies were...
Chang, Ku-Lang; Fillingim, Roger; Hurley, Robert W; Schmidt, Siegfried
Nonpharmacologic therapies have become a vital part of managing chronic pain (CP). Although these can be used as stand-alone therapies, nonpharmacologic treatments often are used to augment and complement pharmacologic treatments (ie, multimodal therapy). Nonpharmacologic approaches can be classified as behavioral, cognitive, integrative, and physical therapies. Core principles in developing a treatment plan are explaining the nature of the CP condition, setting appropriate goals, and developing a comprehensive treatment approach and plan for adherence. Clinicians should become familiar with these interventions so that they can offer patients flexibility in the pain management approach. Effective noninvasive treatment modalities for CP include behavioral therapy for short-term pain relief; cognitive behavioral therapy for reducing long-term pain and disability; hypnosis as adjunctive therapy; guided imagery, diaphragmatic breathing, and muscle relaxation, especially for cancer-related pain; mindfulness-based stress reduction for patients with chronic low back pain; acupuncture for multiple pain conditions; combination manipulation, manual therapy, endurance exercise, stretching, and strengthening for chronic neck pain; animal-assisted therapy; and S-adenosyl-L-methionine for joint pain. Guidelines for use of these treatment modalities are based on expert panel recommendations in combination with data from randomized controlled trials. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.
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.
Ho, K.Y.; Chua, N.H.; George, J.M.; Yeo, S.N.; Main, N.B.; Choo, C.Y.; Tan, J.W.; Tan, K.H.; Ng, B.Y.
INTRODUCTION: While opioids are effective in carefully selected patients with chronic non-cancer pain (CNCP), they are associated with potential risks. Therefore, treatment recommendations for the safe and effective use of opioids in this patient population are needed. MATERIALS AND METHODS: A
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.
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.
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.
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.
Treatment guidelines discourage long-term opioid treatment for patients with chronic pain and major depression, but this treatment occurs commonly, producing higher daily doses, longer duration, and more adverse events. Review of prospective cohort, retrospective cohort, and other observational studies of the relation between depression and opioid use, abuse, and addiction. Depressed patients initiate opioid therapy slightly more often than non-depressed patients, but are twice as likely to transition to long-term use. This adverse selection of high-risk patients with depression into long-term high-dose opioid therapy appears to be a process of self-selection. Opioids may be used by patients with chronic pain and depression to compensate for a reduced endogenous opioid response to stressors. Depressed patients appear to continue opioid use at lower pain intensity levels and higher levels of physical function than do non-depressed patients. In studies that carefully control for confounding by indication, it has been shown that long-term opioid therapy increases the risk of incident, recurrent and treatment-resistant depression. Depressed patients tend to overuse opioids because they use them to treat insomnia and stress. Depression also appears to increase the risk of abuse or non-medical use of prescription opioids among adults and adolescents. This increased rate of non-medical opioid use may be the path through which depression increases the risk of Opioid Use Disorder among patients with chronic pain. It is not possible to understand long-term opioid therapy for chronic pain without understanding the close and multifaceted relationship of this therapy with depression.
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.
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.
... Injury Violence Prevention WISQARS (Injury & Death Data) Prescription Opioids Recommend on Facebook Tweet Share Compartir Prescription opioids ... Problem Risk Factors Addiction and Overdose About Prescription Opioids Side Effects In addition to the serious risks ...
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.
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.
Treatment of chronic hepatitis B remains a clinical challenge. Long-term viral suppression is a major goal of antiviral therapy to improve the clinical outcome of the patients. Antiviral treatment of chronic hepatitis B relies currently on immune modulators such as interferon alpha and its pegylated form, and viral polymerase inhibitors. Because of the slow kinetics of viral clearance and the spontaneous viral genome variability, viral mutants resistant to nucleoside analogs may be selected. ...
Offending, custody and opioid substitution therapy treatment utilisation among opioid-dependent people in contact with the criminal justice system: comparison of Indigenous and non-Indigenous Australians.
Gisev, Natasa; Gibson, Amy; Larney, Sarah; Kimber, Jo; Williams, Megan; Clifford, Anton; Doyle, Michael; Burns, Lucy; Butler, Tony; Weatherburn, Don J; Degenhardt, Louisa
Although Indigenous Australians are over-represented among heroin users, there has been no study examining offending, time in custody, and opioid substitution therapy (OST) treatment utilisation among Indigenous opioid-dependent (including heroin) people at the population level, nor comparing these to non-Indigenous opioid-dependent people. The aims of this study were to compare the nature and types of charges, time in custody and OST treatment utilisation between opioid-dependent Indigenous and non-Indigenous Australians in contact with the criminal justice system. This was a population-based, retrospective data linkage study using records of OST entrants in New South Wales, Australia (1985-2010), court appearances (1993-2011) and custody episodes (2000-2012). Charge rates per 100 person-years were compared between Indigenous and non-Indigenous Australians by sex, age and calendar year. Statistical comparisons were made for variables describing the cumulative time and percentage of follow-up time spent in custody, as well as characteristics of OST initiation and overall OST treatment utilisation. Of the 34,962 people in the cohort, 6,830 (19.5%) were Indigenous and 28,132 (80.5%) non-Indigenous. Among the 6,830 Indigenous people, 4,615 (67.6%) were male and 2,215 (32.4%) female. The median number of charges per person against Indigenous people (25, IQR 31) was significantly greater than non-Indigenous people (9, IQR 16) (p Indigenous people were charged with 33.2% of the total number of charges against the cohort and 44.0% of all violent offences. The median percentage of follow-up time that Indigenous males and females spent in custody was twice that of non-Indigenous males (21.7% vs. 10.1%, p Indigenous people who first commenced OST in prison (30.2%) was three times that of non-Indigenous people (11.2%) (p Indigenous males spent less time in OST compared to non-Indigenous males (median percentage of follow-up time in treatment: 40.5% vs. 43.1%, p Indigenous
The main histopathologic finding was vacuolization in tubular cells in morphine and tramadol groups. Our findings pointed out the risk of increased lipid peroxidation, hepatic and renal damage due to long term use of opioids, especially morphine. Although opioids are reported to be effective in pain management, their toxic ...
Birke, H; Kurita, G P; Sjøgren, P
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...
Marco, A; López-Burgos, A; García-Marcos, L; Gallego, C; Antón, J J; Errasti, A
Agonist therapy (OAT) programs in combination with a psychosocial approach are the most effective way to prevent relapse in opioid-dependent patients. These programs reduce morbidity and risk behaviours for HIV transmission and other infections, improve quality of life and retention in treatment, and have a positive impact on antisocial behaviour. They are therefore very useful for prisoners with a history of opiate use. OATs based on buprenorphine/naloxone (B/N), along with others using methadone, are currently available in Spain. Diversified treatment offers an alternative treatment for opioid dependence that is more personalized and tailored to the patient's characteristics. As regards effectiveness, both drugs are very similar, but B/N shows a better safety profile and fewer drug-drug interactions and can be dispensed in pharmacies once the patient is released, which can assist with the patient' social reintegration. B/N treatment is more expensive than methadone. It is advisable to have different modes of OAT. These should be prescribed according to the characteristics and needs of each case, without incarceration impeding the right to drug treatment, which should be similar to that performed outside prison.
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.
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
Guise, Andy; Seguin, Maureen; Mburu, Gitau; McLean, Susie; Grenfell, Pippa; Islam, Zahed; Filippovych, Sergii; Assan, Happy; Low, Andrea; Vickerman, Peter; Rhodes, Tim
People who use drugs in many contexts have limited access to opioid substitution therapy and HIV care. Service integration is one strategy identified to support increased access. We reviewed and synthesized literature exploring client and provider experiences of integrated opioid substitution therapy and HIV care to identify acceptable approaches to care delivery. We systematically reviewed qualitative literature. We searched nine bibliographic databases, supplemented by manual searches of reference lists of articles from the database search, relevant journals, conferences, key organizations and consultation with experts. Thematic synthesis was used to develop descriptive themes in client and provider experiences. The search yielded 11 articles for inclusion, along with 8 expert and policy reports. We identify five descriptive themes: the convenience and comprehensive nature of co-located care, contrasting care philosophies and their role in shaping integration, the limits to disclosure and communication between clients and providers, opioid substitution therapy enabling HIV care access and engagement, and health system challenges to delivering integrated services. The discussion explores how integrated opioid substitution therapy and HIV care needs to adapt to specific social conditions, rather than following universal approaches. We identify priorities for future research. Acceptable integrated opioid substitution therapy and HIV care for people who use drugs and providers is most likely through co-located care and relies upon attention to stigma, supportive relationships and client centred cultures of delivery. Further research is needed to understand experiences of integrated care, particularly delivery in low and middle income settings and models of care focused on community and non-clinic based delivery.
Rasu, Rafia S; Vossen, Rachel K; Knell, Maureen E
Chronic pain affects over 100 million adults in the United States, yet continues to be difficult to treat. Concerns continue to mount over the use of opioids to treat noncancer chronic pain (NCCP). Guidelines support the use of adjuvant medications as one of the preferred options for treating chronic pain over opioids. To examine reported usage of adjuvants in the treatment of chronic pain via the National Ambulatory Medical Care Survey (NAMCS). A retrospective, cross-sectional study evaluating reported usage of adjuvant pain medications for the treatment of NCCP was conducted using NAMCS data from 2000 to 2007. Weighted samples were analyzed with regard to several patient variables. Logistic regression models provided 95% confidence intervals and an adjusted odds ratio to determine statistically significant differences in reported usage for the evaluated patient variables. In total, 244,797,406 weighted visits were included for analysis. The analysis showed an almost 2-fold increase in adjuvant use during the study period. Statistically significant differences were identified for several factors evaluated. Younger age, female sex, care from a nonprimary care physician, comorbidities with pain, and >5 current medications were associated with higher rates adjuvant therapy use. Overall adjuvant usage dramatically increased during the study period. Analysis of data demonstrated adjuvant use in chronic pain varied based patient-specific characteristics. These results may allow clinicians, policy makers, and medical educators to identify potential gaps in adjuvant use in certain populations and target areas for clinical, populations-based, and educational improvements in managing NCCP.
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.
Full Text Available Chronic constipation, an ancient disease, is prevalent, and costly in the general population. Complementary and alternative therapies are frequently used for constipation. This review introduces various methods of complementary and alternative therapies, including acupuncture, moxibustion, massage, and herbal medicine. Efficacy, safety, influence factors, sham control design, and mechanisms of these therapies are discussed and evaluated. Acupuncture or electroacupuncture was found to be most commonly used for constipation among these complementary and alternative therapies, followed by herbal medicine. Although only a small number of clinical studies are flawless, our review of the literature seems to suggest that acupuncture or electroacupuncture and herbal medicine are effective in treating constipation, whereas findings on massage and moxibustion are inconclusive. More well-designed clinical trials are needed to improve and prove the efficacy of the complementary and alternative therapies for constipation; mechanistic studies that would lead to wide spread use and improvement of the methods are also discussed in this review.
Hoell, Imke; Amanzada, Ahmad; Degner, Detlef; Havemann-Reinecke, Ursula
The majority of opioid dependent patients suffer from various psychiatric and somatic comorbid diseases like mood and anxiety disorders, psychotic diseases, personality disorders, HIV infection, Hepatitis B and C. If medical treatment is needed, grouping active substances to FDA Pregnancy Categories (A, B, C, D or X) may be helpful. The majority of substances reported here only fulfill the FDA-categories C or D, which means that they could have teratogenic effects, but with probably different rank order. First of all, referring to mood, personality and anxiety disorders, the focus should be laid on non-pharmacological treatment by offering psychotherapeutic and supporting psychosocial interventions to the patients. However, opioid dependent pregnant patients who suffer from severe diseases such as psychosis, bipolar affective disorder or severe depression, may need psychoactive medication like antipsychotics, antidepressants or mood stabilizers to prevent them from harm caused by psychotic ideas and actions and/or suicidality. However these medications may comprise fetal risks, especially when taken together, and therefore should only be used when benefit and risks are considered together with patients and their relatives. It is important to avoid acute or renewed psychiatric decompensation. We present the current differentiated knowledge for therapy of opioid dependent patients with antipsychotics, antidepressants (e.g. higher fetal risk in case of treatment with fluoxetine and paroxetine) or mood stabilizers. All of them should only be used after considering benefit and risks. During pregnancy, there should not be switched between different antidepressant drugs. Referring mood stabilizers, the intake of valproic acid should be avoided in pregnancy or at least, dosage should be kept as low as possible since severe teratogenetic effects are known. In addition the specific drug treatment of HIV and hepatitis B during pregnancy is described. During childbirth HIV
Højsted, J; Nielsen, P R; Eriksen, Jacob Gram
Breakthrough pain (BTP) has not formerly been discussed as such in chronic non-malignant pain patients referred to pain centres and clinics. The purpose of the study was to investigate the prevalence, characteristics and mechanisms of BTP in opioid-treated chronic non-malignant pain patients...... referred to a pain centre and to assess the short-term effects of pain treatment....
Full Text Available Pain is a common symptom in orthopedic patients, but is managed sub-optimally, partly due to scarce opioid use in severe cases. The aim of the Orthopedic Instant Pain Survey (POIS was to evaluate changes in pain management in Italian orthopedic practice 2 years after a legislative change (Law 38/2010 simplifying opioid access for pain control. A web-based survey on the knowledge of this law and trends observed in clinical practice for severe pain treatment was administered to 143 Italian orthopedic specialists. In total, 101 (70% respondents showed a high level of knowledge. Nevertheless, 54.5% stated that they do not use opioids for severe osteo-articular pain management. Main barriers to opioid use are fear of adverse events (61.4%, especially nausea/vomiting and constipation, and patient resistance (29.7%. A modest knowledge of pain classification was also demonstrated. Opioid use remains very limited in Italian orthopedic practice. Physicians’ fear of side effects showed poor knowledge of strategies for effective management of opioid-related adverse events, such as combined oral prolonged-release oxycodone/naloxone. Continuing educational programs could improve delivery of evidence-based pain management.
Fanelli, Guido; Cherubino, Paolo; Compagnone, Christian
Pain is a common symptom in orthopedic patients, but is managed sub-optimally, partly due to scarce opioid use in severe cases. The aim of the Orthopedic Instant Pain Survey (POIS) was to evaluate changes in pain management in Italian orthopedic practice 2 years after a legislative change (Law 38/2010) simplifying opioid access for pain control. A web-based survey on the knowledge of this law and trends observed in clinical practice for severe pain treatment was administered to 143 Italian orthopedic specialists. In total, 101 (70%) respondents showed a high level of knowledge. Nevertheless, 54.5% stated that they do not use opioids for severe osteo-articular pain management. Main barriers to opioid use are fear of adverse events (61.4%), especially nausea/vomiting and constipation, and patient resistance (29.7%). A modest knowledge of pain classification was also demonstrated. Opioid use remains very limited in Italian orthopedic practice. Physicians’ fear of side effects showed poor knowledge of strategies for effective management of opioid-related adverse events, such as combined oral prolonged-release oxycodone/naloxone. Continuing educational programs could improve delivery of evidence-based pain management. PMID:25002934
Jiang, Yongliang; He, Xiaofen; Yin, Xiaohu; Shen, Yafang; Fang, Jianqiao
To observe the analgesic effect of electroacupuncture (EA) on collagen-induced arthritis (CIA) rats and its regulating effect on inflammation reaction and the endogenous opioid system of synovial tissues. Methods A total of 30 healthy male Wistar rats were randomly divided into a control group, a model group and an EA group, 10 rats in each one. The chronic pain model of CIA rats was made by cattle type-II collagen in the model group and EA group. Rats in the EA group were treated with EA at "Zusanli" (ST 36) and "Kunlun" (BL 60) for 30 min from 16th day after model establishment, once a day for consecutive 10 days. Rats in the control group did not receive any treatment. Rats in the model group were treated with fixation as the EA group. Threshold of pain, arthritis index, paw swelling were measured before model establishment and 16 d, 20 d, 23 d and 25 d after model establishment. The levels of beta-endorphin (β-END), met-enkephalin (met-ENK), dynorphin A (Dyn A) were measured by radioimmunoassay; the mRNA expressions of mu opioid receptor (MOR), kappa opioid receptor (KOR) and delta opioid receptor (DOR) in synovial tissues of CIA rats were detected by I quantitative polymerase chain reaction (qPCR). Compared with the control group, threshold of pain was reduced (all Ppain was increased in the EA group (all Ppain of CIA rats is superior, which is likely to be related with effects of EA on anti-inflammation and up-regulation of synovial tissue β-END and MOR, KOR, DOR.
... These medications can be given during or after menopause. Hormone Therapy to Prevent Chronic Conditions Many women take ... a recommendation. Click Here to Learn More About Menopause and Hormone Therapy Postmenopausal Hormone Therapy: Information for the Public ( ...
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.
Rosa, Palomba; Federica, Miralto; Annamaria, Vinciguerra; Fabiana, Salvato; Anna, Vaccarella
The aim of this study is the analysis of the beneficial impact of using opioid receptor antagonist associated to opioid analgesic on the quality of life in patients suffering from chronic non-cancer pain. We recruited 60 patients suffering from osteo-articular diseases who were randomized into two groups of treatment. The group A was treated with the association of opioid receptor antagonist and opioid agonist, represented by Oxycodone. The group B was treated with the opioid analgesics Oxycodone, transdermal Fentanil, and Hidromorphone, without the opioid antagonist. The end-points assessed were the duration of titration, the average reached dosage, the duration of the stability of dosage and the opioid-induced constipation (OIC) using the BFI.
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
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.
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
Rauck, Richard L; Potts, Jeffrey; Xiang, Qinfang; Tzanis, Evan; Finn, Andrew
Buprenorphine HCl buccal film has been developed for treating chronic pain utilizing BioErodible MucoAdhesive (BEMA(®)) delivery technology. Buccal buprenorphine (BBUP; Belbuca(TM), Endo Pharmaceuticals) was evaluated for the management of moderate to severe chronic low back pain (CLBP) requiring around-the-clock analgesia in a multicenter, double-blind, placebo-controlled, enriched-enrollment, randomized-withdrawal study in opioid-naive patients. Patients (n = 749) were titrated to a dose of BBUP (range, 150-450 µg every 12 h) that was generally well tolerated and provided adequate analgesia for ≥14 days, and then randomized to BBUP (n = 229) or placebo (n = 232), respectively. The primary efficacy variable was the change from baseline to week 12 of double-blind treatment in the mean of daily average pain intensity scores (numeric rating scale from 0 [no pain] to 10 [worst pain imaginable]). Patients were experiencing moderate to severe pain at study entry: mean (SD) = 7.15 (1.05). Following titration, pain was reduced to the mild range; 2.81 (1.07). After randomization, mean (SD) pain scores increased from baseline to week 12 more with placebo (1.59 [2.04]) versus BBUP: (0.94 [1.85]) with a significant between-group difference (-0.67 [95% CI: -1.07 to -0.26]; p = 0.0012). A significantly larger percentage of patients receiving BBUP versus placebo had ≥30% pain reduction (63% vs 47%; p = 0.0012). During double-blind treatment, the most frequent adverse events (AEs) with BBUP were nausea (10%), constipation (4%) and vomiting (4%). The most common AEs with placebo were nausea (7%), upper respiratory tract infection (4%), headache (3%) and diarrhea (3%). These findings demonstrate the efficacy and tolerability of BBUP among opioid-naive patients requiring around-the-clock opioid treatment for CLBP.
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.
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.
care system. The combination of opioids and benzodiazepines poses numerous safety risks for the patient including respiratory su ppression...short-acting, receive chronic opioid therapy (>90 days): 2.39 Cl[2.24, 256], and also have been prescribed an antidepressant : 2.07 Cl [1 .89, 2.28
Behbahan, Iman Saramipoor; Keating, Armand; Gale, Robert Peter
Chronic heart failure is a leading cause of death. The demand for new therapies and the potential regenerative capacity of bone marrow-derived cells has led to numerous clinical trials. We critically discuss current knowledge of the biology and clinical application of bone marrow cells. It appears unlikely that bone marrow cells can develop into functional cardiomyocyte after infusion but may have favorable paracrine effects. Most, but not all, clinical trials report a modest short- but not long-term benefit of infusing bone marrow-derived cells. Effect size appears to correlate with stringency of study-design: the most stringent trials report the smallest effect-sizes. We conclude there may be short- but not substantial long-term benefit of infusing bone marrow-derived cells into persons with chronic heart failure and any benefit observed is unlikely to result from trans-differentiation of bone marrow-derived cells into functioning cardiomyocytes. © 2015 AlphaMed Press.
A multicenter, primary care-based, open-label study to identify behaviors related to prescription opioid misuse, abuse, and diversion in opioid-experienced patients with chronic moderate-to-severe pain.
Setnik, Beatrice; Roland, Carl L; Sommerville, Kenneth W; Pixton, Glenn C; Berke, Robert; Calkins, Anne; Goli, Veeraindar
To compare the investigator assessment of patient risk for prescription opioid misuse, abuse, and diversion with patient self-reports of these activities in a population with chronic pain. As a secondary objective of an open-label, multicenter, primary care-based clinical study to evaluate the success of converting opioid-experienced patients with chronic pain to morphine sulfate with sequestered naltrexone hydrochloride, risk for misuse, abuse, and diversion was assessed using two nonvalidated questionnaires: one was completed by the investigator and another by the patient (Self-Reported Misuse, Abuse, and Diversion [SR-MAD]). In addition, the validated Current Opioid Misuse Measure (COMM) test and urine drug test were used. Of the 684 patients assessed by the investigators, 537 returned the self-assessment, SR-MAD. Most patients were assigned by the investigator as low risk for misuse (84.2%), abuse (89.3%), and diversion (94.3%). Of the patients who returned SR-MAD, 60% indicated having taken more opioids than prescribed and 10.9% reported chewing or crushing their opioids in the past. Of the patients who completed COMM, 40.6% were deemed as having aberrant behaviors. COMM results correlated with the risk levels from the investigator assessment. One-third of patients (33.8%) had at least one abnormal urine drug test result. More research is needed to better understand the gap between the investigator assessment of potential risk for misuse, abuse, and diversion and the actual extent of these behaviors among patients with chronic pain.
Seltenhammer, Monika H; Marchart, Katharina; Paula, Pia; Kordina, Nicole; Klupp, Nikolaus; Schneider, Barbara; Fitzl, Christine; Risser, Daniele U
Aims The main intention of this retrospective study was to investigate whether chronic illicit drug abuse, especially the intravenous use of opioids (heroin), could potentially trigger the development of myocardial fibrosis in drug addicts. Design A retrospective case–control study was performed using myocardial tissue samples from both drug-related deaths (DRD) with verifiable opioid abuse and non-drug-related deaths in the same age group. Setting Department of Forensic Medicine, Medical University of Vienna, Austria (1993–94). Participants Myocardial specimens were retrieved from 76 deceased intravenous opioid users and compared to those of 23 deceased non-drug users. Measurements Drug quantification was carried out using the enzyme-multiplied immunoassay technique (EMIT), followed by [gas chromatography–mass spectrometry (GC–MS), MAT 112®], and analysed using the Integrator 3390A by Hewlett Packard® and LABCOM.1 computer (MSS-G.G.). The amount of fibrous connective tissue (FCT) in the myocardium was determined by using the morphometric software LUCIA Net version 1.16.2©, Laboratory Imaging, with NIS Elements 3.0®. Findings Drug analysis revealed that 67.11% were polydrug users and the same proportion was classified as heroin addicts (6-monoacetylmorphine, 6-MAM)—32.89% were users of pure heroin. In 76.32% of DRD cases, codeine was detected. Only 2.63% consumed cocaine. The mean morphine concentrations were 389.03 ng/g in the cerebellum and 275.52 ng/g in the medulla oblongata, respectively. Morphometric analysis exhibited a strong correlation between DRD and myocardial fibrosis. The mean proportion of FCT content in the drug group was 7.6 ± 2.9% (females: 6.30 ± 2.19%; males: 7.91 ± 3.01%) in contrast to 5.2 ± 1.7% (females: 4.45 ± 1.23%; males: 5.50 ± 1.78%) in the control group, indicating a significant difference (P = 0.0012), and a significant difference in the amount of FCT between females and males (P = 0.0383). There was no significant
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.
Bhan, Ishir; Thadhani, Ravi
Vitamin D has played a central role in the nephrologist's armamentarium, with active vitamin D analogues enjoying broad use for treatment of secondary hyperparathyroidism. Increasing data are now coming to light about the broader biological actions of vitamin D, including wide-ranging effects in several endocrine pathways, cardiovascular disease, infectious disease, and even the progression of chronic kidney disease (CKD). As additional agents are emerging to help with control of metabolic bone disease, these nontraditional pathways of vitamin D action will become increasingly important to consider when formulating a treatment plan. Although the only approved use for vitamin D analogues in CKD is the treatment of secondary hyperparathyroidism, well-conducted clinical trials may soon broaden the scope of this therapy. This article reviews the role of vitamin D therapy in CKD and looks to the answers that future research may bring.
Bautista, Christopher A; Iosif, Ana-Maria; Wilsey, Barth L; Melnikow, Joy A; Crichlow, Althea; Henry, Stephen G
To examine encounter-level factors associated with opioid dose increases during patients' first year on opioid therapy for chronic pain. Case-control study analyzing all opioid prescriptions for patients with chronic pain during their first year after opioid initiation. Cases were patients who experienced an overall dose escalation of ≥ 30 mg morphine equivalents over the 1-year period; controls did not experience overall dose escalation. Main measures were encounter type, opioid dose change, documented prescribing rationale, documentation of guideline-concordant opioid-prescribing practices. Two coders reviewed all encounters associated with opioid prescriptions. Analysis of factors associated with dose increases and provider documentation of prescribing rationale was conducted using multiple logistic regression. There were 674 encounters coded for 66 patients (22 cases, 44 controls). Fifty-three percent of opioid prescriptions were associated with telephone encounters; 13% were associated with e-mail encounters. No prescribing rationale was documented for 43% of all opioid prescriptions and 25% of dose increases. Likelihood of dose increase and documentation of prescribing rationale did not significantly differ for cases versus controls. Compared with face-to-face encounters, dose increases were significantly less likely for telephone (OR 0.18, 95% CI 0.11-0.28) and e-mail (OR 0.23, 95% CI 0.12-0.47) encounters; documentation of prescribing rationale was significantly more likely for e-mail (OR 5.06, 95% CI 1.87-13.72) and less likely for telephone (OR 0.30, 95% CI 0.18-0.51) encounters. Most opioid prescriptions were written without face-to-face encounters. One quarter of dose increases contained no documented prescribing rationale. Documented encounter-level factors were not significantly associated with overall opioid dose escalation. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org
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.
Gomes, Tara; Juurlink, David N; Antoniou, Tony; Mamdani, Muhammad M; Paterson, J Michael; van den Brink, Wim
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 (opioids and gabapentin was associated with a significantly increased odds of opioid-related death (odds ratio [OR] 1.99, 95% CI 1.61 to 2.47, p opioid prescription alone. In the dose-response analysis, moderate-dose (OR 2.05, 95% CI 1.46 to 2.87, p opioid-related death relative to no concomitant gabapentin use. As expected, we found no significant association between co-prescription of opioids and NSAIDs and opioid-related death (OR 1.11, 95% CI 0.98 to 1.27, p = 0.113; aOR 1.14, 95% CI 0.98 to 1.32, p = 0.083). In an
Mukandavire, Christinah; Low, Andrea; Mburu, Gitau; Trickey, Adam; May, Margaret T; Davies, Charlotte F; French, Clare E; Looker, Katharine J; Rhodes, Tim; Platt, Lucy; Guise, Andy; Hickman, Matthew; Vickerman, Peter
A recent meta-analysis suggested that opioid substitution therapy (OST) increased uptake of antiretroviral treatment (ART) and HIV viral suppression. We modelled whether OST could improve the HIV prevention benefit achieved by ART among people who inject drugs (PWID). We modelled how introducing OST could improve the coverage of ART across a PWID population for different baseline ART coverage levels. Using existing data on how yearly HIV-transmission risk is related to HIV plasma viral load, changes in the level of viral suppression across the population were used to project the relative reduction in yearly HIV-transmission risk achieved by ART, with or without OST, compared with if there was no ART - defined here as the prevention effectiveness of ART. Owing to OST use increasing the chance of being on ART and achieving viral suppression if on ART, the prevention effectiveness of ART for PWID on OST (compared with PWID not on OST) increases by 44, 31, or 20% for a low (20%), moderate (40%), or high (60%) baseline ART coverage, respectively. Improvements in the population-level prevention effectiveness of ART are also achieved across all PWID, compared with if OST was not introduced. For instance, if OST is introduced at 40% coverage, the population-level prevention effectiveness of ART could increase by 27, 20, or 13% for a low (20%), moderate (40%), or high (60%) baseline ART coverage, respectively. OST could improve the HIV prevention benefit of ART; supporting strategies that aim to concurrently scale-up OST with ART.
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....
A multicenter, primary care-based, open-label study to identify behaviors related to prescription opioid misuse, abuse, and diversion in opioid-experienced patients with chronic moderate-to-severe pain
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, 3Family Health Medical Services PLLC, Mayville, NY, 4Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, NY, 5New York Spine & Wellness Center, Syracuse, NY, USA Objective: To compare the investigator assessment of patient risk for prescription opioid misuse, abuse, and diversion with patient self-reports of these activities in a population with chronic pain. Methods: As a secondary objective of an open-label, multicenter, primary care-based clinical study to evaluate the success of converting opioid-experienced patients with chronic pain to morphine sulfate with sequestered naltrexone hydrochloride, risk for misuse, abuse, and diversion was assessed using two nonvalidated questionnaires: one was completed by the investigator and another by the patient (Self-Reported Misuse, Abuse, and Diversion [SR-MAD]. In addition, the validated Current Opioid Misuse Measure (COMM test and urine drug test were used. Results: Of the 684 patients assessed by the investigators, 537 returned the self-assessment, SR-MAD. Most patients were assigned by the investigator as low risk for misuse (84.2%, abuse (89.3%, and diversion (94.3%. Of the patients who returned SR-MAD, 60% indicated having taken more opioids than prescribed and 10.9% reported chewing or crushing their opioids in the past. Of the patients who completed COMM, 40.6% were deemed as having aberrant behaviors. COMM results correlated with the risk levels from the investigator assessment. One-third of patients (33.8% had at least one abnormal urine drug test result. Conclusion: More research is needed to better understand the gap between the investigator assessment of potential risk for misuse, abuse, and diversion and the actual extent of these behaviors among patients with
Full Text Available Background and aims: Depression and anxiety are commonly reported among patients in opioid maintenance treatment (OMT. The aim of the present study was to describe aspects of prescription of antidepresant drug therapy among patients on OMT. Our research questions were: 1 What is the prevalence of antidepressant use according to age and gender? 2 Which antidepressants are used? 3 How are antidepressants used in terms of reimbursement codes, dispensed dose and duration of therapy?Methods: Pharmacoepidemiological data were retrieved from the complete national Norwegian Prescription Database which contains information on all prescription drugs (such as Anatomical Theraputical Chemical (ATC-code, Defined Daily Dose (DDDs, dispensed at pharmacies to individual patients. Norwegian OMT-patients (N=4374, 3035 men and 1339 women who received methadone mixture, buprenorphine capsules or combined buprenorphine-naloxone capsules for at least 6 months in 2009 were included. Prevalence of antidepressant use in the studied patients was measured in terms of retrieval of prescriptions.Results: During 2009 21.7% of the studied patients filled at least one prescription for an antidepressant drugs (men: 21.2%; women: 22.9%. The subgroup of antidepressants most frequently dispensed was selective serotonin reuptake inhibitors (SSRIs (33%, followed by the sedative antidepressants mianserin and mirtazapin (22% and tricyclic antidepressants (TCAs (20%. Except for TCAs, prescriptions of all antidepressant subgroups were reimbursed for either anxiety or depression in 90% of the cases. Overall, 46.9% of the antidepressant users were prescribed antidepressants in the category < 1 DDD per day and/or treatment < 3 months, with no gender difference.Conclusions: About one out of five OMT-patients filled a prescription for an antidepressant drug in 2009. Above 90% had their prescriptions reimbursed for either depression or anxiety. Use at low doses and/or sporadic use among half
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…
Crain, Stanley M; Shen, Ke-Fei
Low-dose naloxone-precipitated withdrawal hyperalgesia is a reliable indicator of physical dependence after chronic morphine treatment. A remarkably similar long-lasting (>3-4 h) hyperalgesia is evoked by injection of a low dose of naloxone (10 microg/kg, s.c.) in naïve mice after acute pretreatment with the glycolipid, GM1 ganglioside (1 mg/kg) (measured by warm-water-immersion tail-flick assays). GM1 treatment markedly increases the efficacy of excitatory Gs-coupled opioid receptor signaling in nociceptive neurons. Co-treatment with an ultra-low-dose (0.1 ng/kg, s.c.) of the broad-spectrum opioid receptor antagonist, naltrexone or the selective kappa opioid receptor antagonist, nor-binaltorphimine, blocks naloxone-evoked hyperalgesia in GM1-pretreated naïve mice and unmasks prominent, long-lasting (>4 h) inhibitory opioid receptor-mediated analgesia. This unmasked analgesia can be rapidly blocked by injection after 1-2 h of a high dose of naltrexone (10 mg/kg) or nor-binaltorphimine (0.1 mg/kg). Because no exogenous opioid is administered to GM1-treated mice, we suggest that naloxone may evoke hyperalgesia by inducing release of endogenous bimodally acting opioid agonists from neurons in nociceptive networks by antagonizing putative presynaptic inhibitory opioid autoreceptors that "gate" the release of endogenous opioids. In the absence of exogenous opioids, the specific pharmacological manipulations utilized in our tail-flick assays on GM1-treated mice provide a novel bioassay to detect the release of endogenous bimodally acting (excitatory/inhibitory) opioid agonists. Because mu excitatory opioid receptor signaling is blocked by ultra-low doses of naloxone, the higher doses of naloxone that evoke hyperalgesia in GM1-treated mice cannot be mediated by activation of mu opioid receptors. Co-treatment with ultra-low-dose naltrexone or nor-binaltorphimine may selectively block signaling by endogenous GM1-sensitized excitatory kappa opioid receptors, unmasking
Lin, Hsien-Chang; Wang, Zhi; Boyd, Carol; Simoni-Wastila, Linda; Buu, Anne
State-level prescription drug monitoring programs (PDMPs) have been implemented in most states. PDMPs enable registered prescribers to obtain real-time information on patients' prescription history to reduce non-medical use of controlled drugs. This study examined whether PDMP implementation and different levels of PDMP requirements were associated with physicians' patterns of prescribing opioid analgesics for patients with non-cancer chronic pain. This is a secondary analysis study using cross-sectional national data. Patients with non-cancer chronic pain from the 2012 National Ambulatory Medical Care Survey were included (weighted N=81,018,131; unweighted N=3295). Heckman two-step selection procedure employing two logistic regressions was used to explore the associations between PDMP requirements and physicians' prescribing behaviors, controlling for physician characteristics, patient characteristics, physician-healthcare system interaction, and physician-patient relationship, guided by the Eisenberg's model of physician decision making. State PDMP implementation status and requirement levels were not associated with physician opioid prescribing for non-cancer chronic pain treatment (p's ranged 0.30-0.32). Patients with Medicare coverage were more likely to be prescribed opioid analgesics than those with private health insurance (OR=1.55, pprescription opioids. Copyright © 2017 Elsevier Ltd. All rights reserved.
Brunet, Laurence; Napravnik, Sonia; Heine, Amy D; Leone, Peter A; Eron, Joseph J
Longitudinal opioid prescription use is unknown among HIV-infected patients. Group-based trajectory modeling followed by multinomial logistic regression was used to identify distinct trajectories and their association with baseline characteristics among 1239 HIV-infected UNC CFAR HIV Clinical Cohort participants, 2000-2014. Three trajectories were identified: (1) 72% never/sporadic opioid use (referent group), (2) 11% episodic use (associated with female sex, depression, drug-related diagnoses, antiretroviral therapy use, and undetectable HIV RNA), and (3) 16% chronic use (associated with older age, female sex, and mental health diagnoses). Overall, opioid prescription decreased substantially with longer time in HIV care among both episodic and chronic users.
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)
Full Text Available Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers are the basis of renoprotection therapy in chronic kidney disease. Parallel to decrease of glomerular filtration rate, there is an increase in the activity of the sympathetic nervous system, and the number of functioning nephrons reduces, which requires a change of treatment regimen. Reducing the risk of cardiovascular events on the background of increased hypertension probably dictates the need for a priority administration of sympatholytics, calcium channel blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers withdrawal. ARAMONEL formula: ARAMONEL — AR(BA(CEIMO(xonidineNE(bivololL(ercandipine is changed to MNELD — M(oxonidineNE(bivololL(ercandipineD(iuretic that is used by us in recent years. Combined use of torsemide and xipamide is allowed. Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers withdrawal requires evidence, which may be obtained in STOP-ACEi trial.
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
identify factors associated with receiving opioid prescriptions. Psychiatric disorders , including generalized anxiety disorder , panic disorder , depression...collected information regarding substance use disorder (defined as substance abuse/dependence diagnoses for alcohol, amphetamine, cannabis , cocaine, opioids...most commonly diagnosed substance use disorders were alcohol (11.8%), cannabis (3.7%), or other substance use disorder (8.8%). Opioids were prescribed to
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
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
Larun, Lillebeth; Brurberg, Kjetil G; Odgaard-Jensen, Jan; Price, Jonathan R
Chronic fatigue syndrome (CFS) is characterised by persistent, medically unexplained fatigue, as well as symptoms such as musculoskeletal pain, sleep disturbance, headaches and impaired concentration and short-term memory. CFS presents as a common, debilitating and serious health problem. Treatment may include physical interventions, such as exercise therapy, which was last reviewed in 2004. The objective of this review was to determine the effects of exercise therapy (ET) for patients with CFS as compared with any other intervention or control.• Exercise therapy versus 'passive control' (e.g. treatment as usual, waiting-list control, relaxation, flexibility).• Exercise therapy versus other active treatment (e.g. cognitive-behavioural therapy (CBT), cognitive treatment, supportive therapy, pacing, pharmacological therapy such as antidepressants).• Exercise therapy in combination with other specified treatment strategies versus other specified treatment strategies (e.g. exercise combined with pharmacological treatment vs pharmacological treatment alone). We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL) and SPORTDiscus up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. We located unpublished or ongoing trials through the World Health Organization (WHO) International Clinical Trials Registry Platform (to May 2014). We screened reference lists of retrieved articles and contacted experts in the field for additional studies SELECTION CRITERIA: Randomised controlled trials involving adults with a primary diagnosis of CFS who were able to participate in exercise therapy. Studies had to compare exercise therapy with passive control, psychological therapies, adaptive pacing therapy or pharmacological therapy. Two review authors independently performed study selection, risk of bias assessments and data extraction. We
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…
Full Text Available Abstract Background There is good evidence for the effectiveness of opioid substitution therapy (OST for injecting drug users (IDUs in middle and high-income countries but little evidence regarding the provision of OST by non-government organisations (NGOs in resource-poor settings. This paper reports on outcomes of an NGO-based OST program providing sub-lingual buprenorphine to opiate dependent IDUs in two north-east Indian states (Manipur and Nagaland, a region where conflict, under-development and injecting of heroin and Spasmoproxyvon (SP are ongoing problems. The objectives of the study were: 1 to calculate OST treatment retention, 2 to assess the impact on HIV risk behaviours and quality of life, and 3 to identify client characteristics associated with cessation of treatment due to relapse. Methods This study involves analysis of data that were routinely and prospectively collected from all clients enrolled in an OST program in Manipur and Nagaland between May 2006 and December 2007 (n = 2569, 1853 in Manipur and 716 in Nagaland using standardised questionnaires, and is best classified as operational research. The data were recorded at intake into the program, after three months, and at cessation. Outcome measures included HIV risk behaviours and quality of life indicators. Predictors of relapse were modelled using binary logistic regression. Results Of all clients enrolled in OST during the month of May 2006 (n = 713, 72.8% remained on treatment after three months, and 63.3% after six months. Statistically significant (p = 0.05 improvements were observed in relation to needle sharing, unsafe sex, incidents of detention, and a range of quality of life measures. Greater spending on drugs at intake (OR 1.20, frequently missing doses (OR 8.82, and having heroin rather than SP as the most problematic drug (OR 1.95 were factors that increased the likelihood of relapse, and longer duration in treatment (OR 0.76 and regular family involvement in
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.
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...
Brenner, Darren M; Stern, Emily; Cash, Brooks D
Opioids are a mainstay in the treatment of chronic non-cancer pain syndromes, but their analgesic benefits come at a cost as opioid-related constipation occurs in 40-80% of individuals taking chronic opioids. Furthermore, as 10-20% of the population suffers from constipation at baseline, it should be expected that while a proportion of individuals will develop constipation as a direct consequence of opioids (OIC), others will experience it as an exacerbation of their baseline constipation (OEC). Herein, we review the evidence-based data for treatments directed at opioid-related constipation focusing on individuals with non-cancer pain syndromes and provide a template for the development of differentiated treatment algorithms for OIC and OEC. Historical and current treatment protocols recommend traditional laxatives, but these are ineffective in up to 50%, due in part to the heterogeneous pathogenesis of constipation. Therapeutic decisions must be tailored to account for this overlapping pathogenesis. OIC and OEC are distinct entities. As such, additional research and guidelines should address these as different patient populations.
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.
Full Text Available Marzia Lazzari,1 Claudio Marcassa,2 Silvia Natoli,1 Roberta Carpenedo,1 Clarissa Caldarulo,1 Maria B Silvi,1 Mario Dauri1 1Department of Emergency and Critical Care Medicine, Pain Medicine and Anaesthesiology, Tor Vergata Polyclinic, University of Rome, Rome, 2Cardiology Division, Fondazione Maugeri IRCCS Veruno, Novara, Italy Purpose: Chronic pain has a high prevalence in the aging population. Strong opioids also should be considered in older people for the treatment of moderate to severe pain or for pain that impairs functioning and the quality of life. This study aimed to assess the efficacy and safety of the direct switch to low-dose strong opioids (World Health Organization-Step III drugs in elderly, opioid-naive patients.Patients and methods: This was a single-center, retrospective, observational study in opioid-naive patients aged ≥75 years, with moderate to severe chronic pain (>6-month duration and constipation, who initiated treatment with prolonged-release oxycodone/naloxone (OXN-PR. Patients were re-evaluated after 15, 30, and 60 days (T60, final observation. Response to treatment was defined as an improvement in pain of ≥30% after 30 days of therapy without worsening of constipation.Results: One-hundred and eighty-six patients (mean ± SD age 80.7±4.7 years; 64.5% women with severe chronic pain (mean average pain intensity 7.1±1.0 on the 11-point numerical rating scale and constipation (mean Bowel Function Index 64.1±24.4; 89.2% of patients on laxatives were initiated treatment with OXN-PR (mean daily dose 11.3±3.5 mg. OXN-PR reduced pain intensity rapidly and was well tolerated; 63.4% of patients responded to treatment with OXN-PR. At T60 (mean daily OXN-PR dose, 21.5±9.7 mg, the pain intensity was reduced by 66.7%. In addition, bowel function improved (mean decrease of Bowel Function Index from baseline to T60, -28.2, P<0.0001 and the use of laxatives decreased. Already after 15 days and throughout treatment, ~70
Zgierska, Aleksandra E; Ircink, James; Burzinski, Cindy A; Mundt, Marlon P
Opioid-treated chronic low back pain (CLBP) is debilitating, costly, and often refractory to existing treatments. This secondary analysis aims to pilot-test the hypothesis that mindfulness meditation (MM) can reduce economic burden related to opioid-treated CLBP. Twenty-six-week unblinded pilot randomized controlled trial, comparing MM, adjunctive to usual-care, to usual care alone. Outpatient. Thirty-five adults with opioid-treated CLBP (≥30 morphine-equivalent mg/day) for 3 + months enrolled; none withdrew. Eight weekly therapist-led MM sessions and at-home practice. Costs related to self-reported healthcare utilization, medication use (direct costs), lost productivity (indirect costs), and total costs (direct + indirect costs) were calculated for 6-month pre-enrollment and postenrollment periods and compared within and between the groups. Participants (21 MM; 14 control) were 20 percent men, age 51.8 ± 9.7 years, with severe disability, opioid dose of 148.3 ± 129.2 morphine-equivalent mg/d, and individual annual income of $18,291 ± $19,345. At baseline, total costs were estimated at $15,497 ± 13,677 (direct: $10,635 ± 9,897; indirect: $4,862 ± 7,298) per participant. Although MM group participants, compared to controls, reduced their pain severity ratings and pain sensitivity to heat stimuli (p < 0.05), no statistically significant within-group changes or between-group differences in direct and indirect costs were noted. Adults with opioid-treated CLBP experience a high burden of disability despite the high costs of treatment. Although this pilot study did not show a statistically significant impact of MM on costs related to opioid-treated CLBP, MM can improve clinical outcomes and should be assessed in a larger trial with long-term follow-up.
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
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.
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.
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.
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.
Polonsky, Maxim; Azbel, Lyuba; Wickersham, Jeffrey A.; Taxman, Faye S.; Grishaev, Evgeny; Dvoryak, Sergey; Altice, Frederick L.
Background 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. Methods 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 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. Conclusion In Ukraine, adoption of OST is more influenced by ideological biases and prejudices than by existing scientific evidence. By elucidating existing attitudes among CJS personnel, this assessment will help direct subsequent interventions to address the barriers to implementing evidence-based HIV prevention treatments. PMID:25620732
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 suggests that bup/nal may provide pain relief in chronic pain patients 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 chronic pain patients may include reversal of opioid-induced hyperalgesia as well as 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. PMID:24509068
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
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 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. PMID:26185466
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.
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.
van Koppen, A.N.|info:eu-repo/dai/nl/314088350
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
Moisset, Xavier; Trouvin, Anne-Priscille; Tran, Viet-Thi; Authier, Nicolas; Vergne-Salle, Pascale; Piano, Virginie; Martinez, Valeria
An urgent need is to improve the efficacy and safety of use of strong opioids in chronic non-cancer pain (CNCP) through responsible prescription rules supported by scientific evidence. Clinical questions addressing the indication, the benefice, the risk and the precautions were formulated. A task force composed of physicians from several medical specialties involved in managing CNCP was charged to elaborate evidence-based recommendations. A systematic literature search was performed using CENTRAL, MEDLINE and EMBASE databases. The approach of the Grading of Recommendations Assessment, Development and Evaluation was applied to evaluate outcomes. We selected 21 meta-analyses and 31 cohort studies for analysis. Fifteen recommendations are provided. Strong opioids are not recommended in fibromyalgia and primary headaches. Strong opioids have been shown to be moderately effective against CNCP due to osteoarthritis of the lower limbs, and for back pain and neuropathic pain. Their introduction is advised only after the failure of first-line treatments, combined with patient care, provided that the patient is made aware of the advantages and risks. It is not advisable to continue strong opioids treatment for longer than three months if no improvement in pain, function or quality of life is observed. It is also recommended not to prescribe doses exceeding 150mg/day morphine equivalent. Misuse risk factors should be investigated before prescription and misuse should be assessed at each renewal. Priority should be given to extended-release forms. It is recommended not to use transmucosal rapid-release forms of fentanyl for the management of CNCP. These recommendations are intended for all doctors needing to prescribe strong opioids in CNCP. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
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: email@example.com
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
Pielech, Melissa; Sieberg, Christine B; Simons, Laura E
To help address the unique needs of parents of children with chronic pain, a four module, parent-only, group art therapy curriculum was designed and implemented within an interdisciplinary pain rehabilitation treatment program. We evaluated perceived satisfaction and helpfulness of the group intervention. Fifty-three parents of children experiencing chronic pain enrolled in a day hospital interdisciplinary pain rehabilitation program participated. The voluntary parent art therapy group was offered one time per week for one hour. Participants completed a measure of satisfaction, helpfulness, and perceived social support at the end of each group session. Parents enjoyed participating in the group, agreed that they would try art therapy again, and found it to be a helpful, supportive, and validating experience. Initial results are promising that group art therapy is an appropriate and helpful means of supporting parents of children with chronic pain during interdisciplinary pain rehabilitation.
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.
Ulbricht, Korinna; Layer, Peter; Andresen, Viola
Chronic, non-infectious diarrhea can be caused by a variety of gastrointestinal diseases. In anamnesis, it is important to take accompanying warning symptoms and specific triggers into account. The fecal inflammatory marker calprotectin may help differentiating between organic and functional gastrointestinal disorders, but it is not specific. Among other options, gelling fibres, Loperamide and Cholestyramine as well as probiotics are available for the symptomatic treatment of chronic diarrhea. For long-term treatment of chronic diarrhea with the enkephalinase inhibitor racecadotril, which is approved for acute diarrhea, only limited data are available. Eluxadolin presents a new therapeutic option. It can alleviate abdominal pain and diarrhea by modulation of opioid receptors in the enteric nervous system. Additional approaches in intractable irritable bowel syndrome with diarrhea (IBS-D) include 5-HT3 receptor antagonists, the antibiotic Rifaximin as well as low-dose tricyclic antidepressants. Specific diets such as the low-FODMAP diet can also relieve symptoms in IBS. © Georg Thieme Verlag KG Stuttgart · New York.
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: firstname.lastname@example.org
Bojko, Martha J.; Mazhnaya, Alyona; Makarenko, Iuliia; Marcus, Ruthanne; Dvoriak, Sergii; Islam, Zahedul; Altice, Frederick L.
Aims 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. Methods 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. Findings 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. Conclusions 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. PMID:27087758
Hassan, Ahmed N; Howe, Aaron S; Samokhvalov, Andriy V; Le Foll, Bernard; George, Tony P
Patients with opioid use disorders and mood and anxiety symptoms have a variable prognosis. Few randomized controlled trials (RCTs) have evaluated treatment of depression or anxiety in patients receiving opioid agonist therapies (OAT). This review evaluates studies of pharmacotherapy/psychotherapy for treating symptoms of depression or anxiety in patients receiving OAT. Public databases were searched for clinical trials of pharmacotherapy or psychotherapy for managing depression or anxiety symptoms in adults receiving OAT. Subsequently, we conducted a random effects meta-analysis model of RCTs by antidepressants subclasses. In our literature search, we identified 22 RCTs, eight of which were eligible for meta-analysis. Seven studies evaluated antidepressants in patients already maintained on OAT; two studies reported significant results for antidepressant effects versus placebo. Similarly, two of the seven studies that initiated antidepressants with OAT had advantages over placebo. Meta-analysis of grouped data revealed that tricyclic antidepressants (TCAs) (n = 235) significantly improved mean depression scores (SMD = -2.35, 95%CI: [-4.35, -0.34], z = -2.29, p = .022) while Selective Serotonin Reuptake Inhibitors (SSRIs) (n = 311) were not significantly different than placebo (SMD = 0.47, 95%CI: [-0.35, 1.30], z = 1.12, p = .263). Four out of five studies that implemented psychotherapeutic approaches reported a greater reduction of depressive symptoms than the comparison group. To date, psychotherapy has the most documented evidence for efficacy. TCAs appears effective but with more adverse effects than SSRIs. Further studies of OAT and adjunct antidepressant treatments for dual diagnosis patients are warranted. (Am J Addict 2017;26:551-563). © 2017 American Academy of Addiction Psychiatry.
There are several therapies designed to increase body awareness. They are commonly known as body awareness therapies (BAT) and include Basic BAT, Mensendieck and Feldenkrais therapy. A focus on emotions is important in all these therapies. In this article the aim and development of Basic BAT is described together with evaluations of treatments including Basic BAT. Multidisciplinary studies have shown that Basic BAT can increase health-related quality of life and cost-effectiveness. However Basic BAT needs to be further studied in relation to patients with fibromyalgia (FM) and chronic pain. Studies so far indicate that Basic BAT has positive effects.
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
Vainer, J.; Habets, J. H. M.; Schalla, S.; Lousberg, A. H. P.; de Pont, C. D. J. M.; V??, S. A.; Brans, B. T.; Hoorntje, J. C. A.; Waltenberger, J.
Background Cardiac shockwave therapy (CSWT) might improve symptoms and decrease ischaemia burden by stimulating collateral growth in chronic ischaemic myocardium. This prospective study was performed to evaluate the feasibility and safety of CSWT. Methods We included 33 patients (mean age 70???7 years, mean left ventricular ejection fraction 55???12?%) with end-stage coronary artery disease, chronic angina pectoris and reversible ischaemia on myocardial scintigraphy. CSWT was applied to the i...
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.
E. I. Chukanova
Full Text Available The paper presents current views on the pathogenetic mechanisms of cerebral ischemia. It discusses the role of neurotrophins in the processes of neuroplasticity. Experimental and clinical studies of the neuropeptide drug Cerebrolysin are reviewed. The authors describe in detail the results of the clinical trial and a health economic analysis of the effects of Cerebrolysin on the time course of clinical changes, progression, and risk of exacerbations in patients with chronic cerebral ischemia.
Full Text Available The paper is devoted to the problem of treatment of chronic dermatopathies. There are demonstrated the data of study of therapeutic efficiency and tolerance of Bedan cream I patients with dermatopathies. Bedan cream used in a complex therapy of chronic dermatopathies was shown to lead to earlier reduction of objective and subjective signs of chronic dermatosis and clinical regression. It was found a good tolerance of Bedan cream: its application was not associated with deterioration of general condition of skin, its irritation and allergization.
Chang-Chien, George C; Odonkor, Charles A; Amorapanth, Prin
Kratom is an unscheduled opioid receptor agonist that comes in the form of dietary supplements currently being abused by chronic pain patients on prescription opioids. Active alkaloids isolated from kratom such as mitragynine and 7-hydroxymitragynine are thought to act on mu- and delta-opioid receptors as well as alpha-2 adrenergic and 5-HT2A receptors. Animal studies suggest that kratom may be more potent than morphine. Consequently, kratom consumption produces analgesic and euphoric feelings among users. In particular, some chronic pain patients on opioids take kratom to counteract the effects of opioid withdrawal. Although the Food and Drug Administration has banned its use as a dietary supplement, kratom continues to be widely available and easily accessible on the Internet at much less expensive rates than some opioid replacement therapies like buprenorphine. There are no federal regulations monitoring the sale and distribution of this drug, yet kratom has been associated with severe signs and symptoms such as hallucinations, delusions, depressions, myalgias, chills, nausea/vomiting, respiratory hepatoxicity, seizures, coma, and death. A search of the pain literature shows past research has not described the use and potential deleterious effects of this drug. Many pain physicians are not familiar with kratom and as providers who take care of high-risk chronic pain patients using prescribed opioids, knowledge of current unregulated opioid receptor agonists with abuse potential is of paramount importance. The goal of this article is to introduce kratom to pain specialists and to spur a conversation on how pain physicians may take the lead to help curb the opioid abuse and overdose epidemic. Further studies may be required to help better understand the clinical and long-term effects of kratom use among chronic pain patients.Key words: Opioid receptor agonist, Kratom, Mitragynine, opioid overdose, chronic pain, substance abuse.
Full Text Available Gregory D Salinas, Caroline O Robinson, Maziar AbdolrasulniaCE Outcomes LLC, Birmingham, AL, USAAbstract: With increasing numbers of patients experiencing chronic pain, opioid therapy is becoming more common, leading to increases in concern about issues of abuse, diversion, and misuse. Further, the US Food and Drug Administration recently released a statement notifying sponsors and manufacturers of extended-release and long-acting opioids of the need to develop Risk Evaluation and Mitigation Strategies (REMS programs in order to ensure that the benefits of this therapy choice outweigh the potential risks. There is little research on physician opinions concerning opioid-prescribing and education policies. To assess attitudes surrounding new opioid policies, a survey was designed and distributed to primary care physicians in October 2011. Data collected from 201 primary care physicians show that most are not familiar with the REMS requirements proposed by the Food and Drug Administration for extended-release and long-acting opioids; there is no consensus among primary care physicians on the impact of prescribing requirements on patient education and care; and increasing requirements for extended-release and long-acting opioid education may decrease opioid prescribing. Physician attitudes toward increased regulatory oversight of opioid therapy prescriptions should be taken into consideration by groups developing these interventions to ensure that they do not cause undue burden on already busy primary care physicians.Keywords: REMS, opioids, attitudes, survey
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.
Santosh Ramdurg; Atul Ambekar; Rakesh Lal
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 Metho...
Turner, Judith A; Shortreed, Susan M; Saunders, Kathleen W; LeResche, Linda; Thielke, Stephen; Von Korff, Michael
Many consider chronic opioid therapy (COT) to be ineffective for fibromyalgia, but empirical evidence is limited. Among patients identified as initiating COT, we examined whether fibromyalgia was associated with different relationships of opioid use to pain and activity interference outcomes 12 months later. We obtained electronic data on diagnoses and opioid prescriptions. We obtained patient self-report data, including pain and activity interference measures, at baseline, 4 months, and 12 months. Among 1218 patients, 429 (35%) met our definition of fibromyalgia. Patients with and without fibromyalgia who had intermittent/lower-dose or regular/higher-dose opioid use at 12 months had similar 12-month pain intensity scores. However, among patients with minimal/no opioid use at 12 months, 12-month pain intensity was greater for those with fibromyalgia (adjusted mean = 5.15 [95% confidence interval, 4.80-5.51]; 0-10 scale) than for those without (4.44 [4.15-4.72]). Similar patterns were observed for 12-month activity interference. Among patients who discontinued opioids by 12 months, those with fibromyalgia were more likely to report bothersome side effects and less likely to report pain improvement as important reasons for discontinuation (P fibromyalgia had worse outcomes and were less likely to have discontinued because of pain improvement. Among patients continuing COT, pain and activity interference outcomes were worse than those of patients with minimal/no opioid use and did not differ for those with fibromyalgia vs those with diverse other chronic pain conditions.
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.
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.
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.
Xu, Luo-Jia; Chen, Jie
To investigate the efficacy of nutrition support therapy in children with chronic diarrhea. A retrospective analysis was performed for the clinical data of 48 children with chronic diarrhea who were hospitalized between July 2012 and July 2014. These children were divided into children) and ≤1 year group (21 children). Twenty-seven of these patients, who had malnutrition, were divided into enteral nutrition (EN) group (10 children), partial parenteral nutrition (PPN)+EN group (16 children), and total parenteral nutrition (TPN) group (1 child). The therapeutic process and outcome were compared between different age groups and children receiving different treatments. Among the 48 children, short bowel syndrome, viral enteritis, a history of intestinal surgery, and malabsorption syndrome were common causes of chronic diarrhea, and 24 children (50%) had unknown causes. In the aspect of nutritional assessment on admission, the children with moderate underweight than the ≤1 year group (Pdiarrhea were relieved after treatment. Among 27 children receiving nutritional therapy, 4 were not improved, and the other children achieved remission of symptoms and improvements in nutritional status. Besides etiological treatment, nutrition support therapy can be applied as part of multimodality therapy in children with chronic diarrhea. This can effectively improve nutritional status and relieve the symptoms of diarrhea.
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
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
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 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
Full Text Available Flaminia Coluzzi,1,2 Joseph Pergolizzi,3,4 Robert B Raffa,5 Consalvo Mattia1,2 1Department of Medical and Surgical Sciences and Biotechnologies, Unit of Anesthesiology, Intensive Care Medicine and Pain Therapy, Faculty of Pharmacy and Medicine – Polo Pontino, Sapienza University of Rome, Latina, Italy; 2SIAARTI Study Group on Acute and Chronic Pain, Rome, Italy; 3Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 4Naples Anesthesia and Pain Associates, Naples, FL, 5Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, USA Abstract: The current literature describes the possible risks for bone fracture in chronic analgesics users. There are three main hypotheses that could explain the increased risk of fracture associated with central analgesics, such as opioids: 1 the increased risk of falls caused by central nervous system effects, including sedation and dizziness; 2 reduced bone mass density caused by the direct opioid effect on osteoblasts; and 3 chronic opioid-induced hypogonadism. The impact of opioids varies by sex and among the type of opioid used (less, for example, for tapentadol and buprenorphine. Opioid-associated androgen deficiency is correlated with an increased risk of osteoporosis; thus, despite that standards have not been established for monitoring and treating opioid-induced hypogonadism or hypoadrenalism, all patients chronically taking opioids (particularly at doses ≥100 mg morphine daily should be monitored for the early detection of hormonal impairment and low bone mass density. Keywords: opioids side effects, bone metabolism, fractures, OPIAD, endocrine system, chronic pain
Lishmanov, Yu. B.; Stakheev, D. L.; Krylatov, A. V.; Naryzhnaya, N. V.; Maslov, L. N.; Ovchinnikov, M. V.; Kolář, František
Roč. 145, č. 6 (2008), s. 696-699 ISSN 0007-4888 R&D Projects: GA ČR(CZ) GA305/07/0875 Institutional research plan: CEZ:AV0Z50110509 Keywords : arrhythmias * infarction * opioids Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 0.258, year: 2008
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.
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....
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
Full Text Available Abstract Background 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. Methods 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 (DDDd and average treatment prevalence per day in percent (adTP. Accordingly, the DDDd 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. Results 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. Conclusions 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
Dissemond, J; Protz, K; Hug, J; Reich-Schupke, S; Kröger, K
Compression therapy, together with modern moist wound treatment, is the basis for a successful conservative treatment of patients with chronic leg ulcers. In clinical practice, it is often the patients themselves who apply compression therapies. Many of the mostly elderly patients, however, are not able to reach their legs and feet due to movement restrictions, such as arthritis, arthrosis and even obesity. An adequate compression therapy also requires extensive experience and regular training. In practice only the minority of patients can perform bandaging well and therefore this should not be recommended. Self-management with do-it-yourself medical devices will become more and more important in the future. In addition to the psychological factors, cost aspects and demographic change, an expected lack of qualified nursing staff due to the number of elderly patients who are potentially in need of care means that self-management is becoming increasingly more important. For the essentially important compression therapy of patients with chronic leg ulcers, there already exist various therapy options. The needs, preferences and abilities of the patients concerned can be considered when selecting the appropriate system. Particularly for the self-management of compression therapy, adaptive compression bandages are suitable for patients with leg ulcers during the initial decompression phase and ulcer stocking systems in the subsequent maintenance phase.
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...
Adam, V Nesek; Matolić, M; Stojčić, E Grizelj; Mršić, V; Rašić, Ž
The result of the increase in drug abuse is a growing number of patients receiving methadone or buprenorphine substitution therapy. Physicians are increasingly confronted with patients on substitution therapy at the time when they are developing acute pain conditions or when they need surgery. Although pain has sensory qualities, it is a very personal and complex experience. The intensity and duration of pain are influenced by numerous factors. Poorly controlled pain leads to unnecessary suffering of the patients with the possibility of permanent changes in behavior and reduced quality of life. Efficacious pain treatment is considered a basic right of every patient. Because of the complex mechanisms of the emergence and transmission of pain and the emotional components that are involved in the experience of pain, appropriate pain relief in patients on substitution therapy is a major challenge for both the physicians and the patients. The article gives an overview of issues related to the treatment of acute pain and perioperative treatment in patients on substitution therapy with methadone and buprenorphine. The article highlights the wrong common misconception about pain treatment in these patients, which also are the most common cause of their inadequate treatment.
Vizir, V A; Berezin, A E
To evaluate effectiveness of nonpeptide angiotensin-2 subtype-1 receptor antagonist losartan in therapy of symptomatic congestive heart failure in patients with ischemic heart disease, 116 patients were examined at the age of 36-62 (mean age 50.6 +/- 4.22). They had angina pectoris of functional class II-III (according to CCS) and congestive heart failure of functional class II-III (according to NYHA). All the patients were randomized into two groups. 60 patients of group 1 received basic medication with nitrates, diuretic (on demand), digoxin and aspirin. 56 patients of group 2 received basic medication and losartan (cozaar, MSD, USA) in the dose 25 mg/day for 48 weeks. Echocardiographic monitoring of the treatment efficacy was made. The outcomes of the treatment evidence that losartan improves the patients' clinical status and heart failure functional class. For twelve weeks losartan reduced left ventricular and atrial dilation positively influencing the isometric inotropic indices. In 48 weeks losartan arrested progression of pathologic remodelling of the left ventricle and prevents depression of total myocardial contractility. Losartan's positive effect in restriction of negative evolution of cardiac failure manifests on the treatment week 3.
Gomes, Tara; Juurlink, David N; Dhalla, Irfan A; Mailis-Gagnon, Angela; Paterson, J Michael; Mamdani, Muhammad M
Background Opioid therapy for patients with chronic nonmalignant pain remains controversial, primarily because of safety concerns and the potential for abuse. The objective of this study was to examine trends in opioid utilization for nonmalignant pain among recipients of social assistance and to explore the relation between dose of analgesic and mortality. Methods Using a cross-sectional study design, we characterized annual trends in prescriptions for and daily dose of opioid analgesics between 2003 and 2008 for beneficiaries (aged 15 to 64 years) of Ontario’s public drug plan. We defined moderate, high and very high dose thresholds as daily doses of up to 200, 201 to 400, and more than 400 mg oral morphine (or equivalent), respectively. In an exploratory cohort study, we followed, over a 2-year period, patients who received at least one prescription for an opioid in 2004 to investigate the relation between opioid dose and opioid-related mortality. Results Over the study period, opioid prescribing rates rose by 16.2%, and 180 974 individuals received nearly 1.5 million opioid prescriptions in 2008. Also by 2008, the daily dose dispensed exceeded 200 mg morphine equivalent for almost a third (32.6%) of recipients of long-acting oxycodone but only 20.3% of those treated with fentanyl or other long-acting opioids. Among patients for whom high or very high doses of opioids were dispensed in 2004, 19.3% of deaths during the subsequent 2 years were opioid-related, occurring at a median age of 46 years. Two-year opioid-related mortality rates were 1.63 per 1000 population (95% confidence interval [CI] 1.42–1.85) among people with moderate-dose prescriptions, 7.92 per 1000 population (95% CI 5.25–11.49) among those with high-dose prescriptions, and 9.94 per 1000 population (95% CI 2.78–25.12) among those with very-high-dose prescriptions. Interpretation Among socio-economically disadvantaged patients in Ontario, the use and dose of opioids for nonmalignant pain
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...
... 2014:chap 162. Lank PM, Kusin S. Ethanol and opioid intoxication and withdrawal. In: Adams JG, ed. Emergency Medicine . 2nd ed. Philadelphia, PA: Elsevier Saunders; 2013:chap 154. National Institute on Drug Abuse. Opioids. National Institute on Drug Abuse Web site. Updated ...
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.
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
Full Text Available Martin Hale,1 Veronica Urdaneta,2 M Todd Kirby,3 Qinfang Xiang,4 Richard Rauck5 1Gold Coast Research, LLC, Plantation, FL, USA; 2Pharmacovigilance and Risk Management, 3Clinical Development, 4Biometrics, Endo Pharmaceuticals Inc., Malvern, PA, USA; 5Carolinas Pain Institute, Wake Forest Baptist Health, Winston Salem, NC, USA Background: This open-label, single-arm study was conducted to evaluate the long-term safety and efficacy of a novel buprenorphine formulation, buprenorphine buccal film, in the treatment of moderate-to-severe chronic pain requiring around-the-clock opioids.Methods: The primary purpose of this study was to evaluate the long-term safety and tolerability of buprenorphine buccal film. Five hundred and six patients who completed previous studies with buprenorphine buccal film (n=445; rollover patients or were recruited de novo for this study (n=61 were enrolled in this study. All patients underwent a dose titration period of ≤6 weeks, during which doses of buprenorphine buccal film were adjusted to a maximum 900 µg every 12 hours, depending on tolerability and the need for rescue medication. An optimal dose was defined as the dose that the patient found satisfactory for both pain relief and tolerability, without the need for rescue medication or with ≤2 tablets of rescue medication per day. Once the optimal dose was reached, treatment was continued for ≤48 weeks. Pain intensity was measured throughout the study using a 0–10 numerical rating scale.Results: Of 435 patients achieving an optimal dose of buprenorphine buccal film who commenced long-term treatment, 158 (36.3% completed 48 weeks of treatment. Treatment-related adverse events occurred in 116 patients (22.9% during the titration phase and 61 patients (14.0% during the long-term treatment phase, and adverse events leading to discontinuation of treatment occurred in 14 (2.8% and 14 (3.2% patients, respectively. The most common adverse events were those typically
Full Text Available BACKGROUND: Cannabinoid 2 receptor (CB2R agonists attenuate inflammatory pain but the precise mechanism implicated in these effects is not completely elucidated. We investigated if the peripheral nitric oxide-cGMP-protein kinase G (PKG-ATP-sensitive K(+ (KATP channels signaling pathway triggered by the neuronal nitric oxide synthase (NOS1 and modulated by opioids, participates in the local antinociceptive effects produced by a CB2R agonist (JWH-015 during chronic inflammatory pain. METHODOLOGY/PRINCIPAL FINDINGS: In wild type (WT and NOS1 knockout (NOS1-KO mice, at 10 days after the subplantar administration of complete Freund's adjuvant (CFA, we evaluated the antiallodynic (von Frey filaments and antihyperalgesic (plantar test effects produced by the subplantar administration of JWH-015 and the reversion of their effects by the local co-administration with CB2R (AM630, peripheral opioid receptor (naloxone methiodide, NX-ME or CB1R (AM251 antagonists. Expression of CB2R and NOS1 as well as the antinociceptive effects produced by a high dose of JWH-015 combined with different doses of selective L-guanylate cyclase (ODQ or PKG (Rp-8-pCPT-cGMPs inhibitors or a KATP channel blocker (glibenclamide, were also assessed. Results show that the local administration of JWH-015 dose-dependently inhibited the mechanical and thermal hypersensitivity induced by CFA which effects were completely reversed by the local co-administration of AM630 or NX-ME, but not AM251. Inflammatory pain increased the paw expression of CB2R and the dorsal root ganglia transcription of NOS1. Moreover, the antinociceptive effects of JWH-015 were absent in NOS1-KO mice and diminished by their co-administration with ODQ, Rp-8-pCPT-cGMPs or glibenclamide. CONCLUSIONS/SIGNIFICANCE: These data indicate that the peripheral antinociceptive effects of JWH-015 during chronic inflammatory pain are mainly produced by the local activation of the nitric oxide-cGMP-PKG-KATP signaling pathway
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.
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).
Chronic hepatitis B virus (HBV) infection is a well-recognized risk factor for the development of hepatocellular carcinoma (HCC), which is becoming a more prevalent clinical problem, especially in HBV-endemic areas. It is estimated that 1.25 million people in the United States and more than 300 million people worldwide are chronically infected with HBV. Despite the introduction of universal vaccination against hepatitis B in over 100 countries, persistent HBV infection is still a serious problem worldwide, causing an estimated annual death rate of one million. It may take several decades until the effect of vaccination will be translated into reduced transmission and morbidity. Meanwhile, patients with persistent HBV infection require better antiviral therapeutic modalities than are currently available. It is well accepted that antiviral therapy for chronic hepatitis B is effective to improve prognosis of patients with HBV by preventing development of hepatitis state and HCC. The therapeutic endpoints for hepatitis B treatment are: 1) sustained suppression of HBV replication, as indicated by HBsAg and HBeAg loss, 2) decrease of serum HBV DNA of an undetectable level by a non-PCR method, 3) remission of disease, as shown by normalization of ALT, 4) improvement in liver histology, and 5) reduction of the acute exacerbation, cirrhosis, and HCC. In the present, the antiviral treatment of hepatitis B consists of either interferon alpha or oral lamivudine alone or in combination with existing therapy. Each major antiviral drug of interferon alpha and lamivudine has pros and cons, and effect of combination therapy of both drugs is also still limited. More powerful and safe new antiviral therapies are required to achieve final goal of these therapeutic endpoints. Management of chronic hepatitis B requires significant knowledge of approved pharmacotherapeutic agents and their limitations. Therapeutic options for managing hepatitis infection after liver transplantation (LT
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
Streltzer, Jon; Davidson, Raymond; Goebert, Deborah
In some countries, particularly the United States and Canada, there has been a growing problem of opioid dependence associated with the treatment of chronic pain. Controversy exists regarding the efficacy and safety of opioid therapy, particularly in high doses for extended periods of time. This study reports on the outcome of chronic pain patients treated with buprenorphine in an outpatient psychiatric consultation clinic. Forty three consecutive outpatient clinic chronic pain patients with a DSM-IV diagnosis of opioid dependence and treated with buprenorphine during a 3-year period were monitored for follow-up periods of up to 5 years. All subjects were dependent on drugs prescribed for pain and were divided into two groups: those who had a history of abuse of alcohol or drugs and those who did not Historical, physical, demographic, and outcome data were collected. The majority of patients were male, not working, and between the ages of 45-60. Follow-up revealed that treatment with buprenorphine was effective. Most patients had improved pain with treatment of the opioid dependence. There were no differences between those with or without a history of substance abuse. Patients often improved with much less preoccupation with pain, expressing great satisfaction with buprenorphine treatment. Buprenorphine is an effective tool when treating the opioid-dependent chronic pain patient. © American Academy of Addiction Psychiatry.
Greiwe, Justin; Bernstein, Jonathan A
Chronic urticaria affects up to 1-3% of the general population and contributes to significant direct and indirect medical costs as well as decreased quality of life, which has a significant economic impact on our health care system. Areas covered: Given the prevalence of this condition on a large sector of the population, finding lasting relief for refractory cases is essential and is the focus of this review. Expert commentary: The choice of appropriate therapy in chronic refractory urticaria is not a 'one-size fits all' approach. Treatment should take multiple factors into consideration including the chronicity of hives, presence of physical urticaria, type of cellular infiltrate on skin histopathology, patient age, concomitant comorbid conditions, as well as patient preference and cost.
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
Seip-Cammack, Katharine M.; Reed, Brian; Zhang, Yong; Ho, Ann; Kreek, Mary Jeanne
Rationale/objectives Heroin addiction is characterized by recurrent cycles of drug use, abstinence and relapse. It is likely that neurobiological changes during chronic heroin exposure persist across withdrawal and impact behavioral responses to re-exposure. We hypothesized that, after extended withdrawal, heroin-withdrawn rats would express behavioral tolerance and/or sensitization in response to heroin re-exposure and that these responses might be associated with altered mu-opioid receptor (MOPr) activity. Methods Male Fischer rats were exposed chronically to escalating doses of heroin (7.5–75mg/kg/day), experienced acute spontaneous withdrawal and extended (10-day) abstinence, and were re-exposed chronically to heroin. Homecage behaviors and locomotor activity in response to heroin, as well as somatic withdrawal signs, were recorded. Separate groups of rats were sacrificed after extended abstinence and MOPr expression and G-protein coupling were analyzed using [3H]DAMGO and [35S]GTPγS assays. Results The depth of behavioral stupor was lower during the initial days of heroin re-exposure compared to the initial days of the first exposure period. Behavioral responses (e.g., stereotypy) and locomotion were elevated in response to heroin re-exposure at low doses. Rats conditioned for heroin place preference during the chronic re-exposure period expressed heroin preference during acute withdrawal; this preference was stronger than rats conditioned during chronic heroin exposure that followed chronic saline and injection-free periods. Extended withdrawal was associated with increased MOPr expression in the caudate-putamen and frontal and cingulate cortices. No changes in G-protein coupling were identified. Conclusions Aspects of tolerance/sensitization to heroin are present even after extended abstinence and may be associated with altered MOPr density. PMID:22829433
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.
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...... cognition resulting in complex interactions between pain, opioids and cognition. The literature on this complexity is sparse and information regarding the cognitive effects of opioids in chronic pain patients is substantially lacking. Two previous systematic reviews on cancer pain and non-cancer pain...... patients only using controlled studies were updated. Fourteen controlled studies on the cognitive effects of opioids in chronic non-cancer pain patients and eleven controlled studies in cancer pain patients were included and analyzed. Opioid treatment involved slightly opposite outcomes in the two patient...
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 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
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.
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: email@example.com
Fredheim, Olav Magnus S; Borchgrevink, Petter C; Mahic, Milada; Skurtveit, Svetlana
Clinical studies of short duration have demonstrated that strong opioids improve pain control in selected patients with chronic nonmalignant pain. However, high discontinuation rates and dose escalation during long-term treatment have been indicated. The aim of the present study was to determine discontinuation rates, dose escalation, and patterns of co-medication with benzodiazepines. The Norwegian Prescription Database provides complete national data at an individual level on dispensed drugs. A complete national cohort of new users of strong opioids was followed up for 5 years after initiation of therapy with strong opioids. Of the 17,248 persons who were new users of strong opioids in 2005, 7229 were dispensed a second prescription within 70 days and were assumed to be intended long-term users. A total of 1233 persons in the study cohort were still on opioid therapy 5 years later. This equals 24% of the study cohort who were still alive. Of the participants, 21% decreased their annual opioid dose by 25% or more, whereas 21% kept a stable dose (± 24%) and 34% more than doubled their opioid dose from the first to the fifth year. High annual doses of opioids were associated with high annual doses of benzodiazepines at the end of follow-up. It is an issue of major concern that large dose escalation is common during long-term treatment, and that that high doses of opioids are associated with high doses of benzodiazepines. These findings make it necessary to question whether the appropriate patient population receives long-term opioid treatment. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
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.
Stanghellini, V; Bellacosa, L; Cogliandro, R
Chronic constipation is a common condition in the general population. Although the majority of affected individuals do not seek medical consultation and search for remedies for their condition in the pharmacy or herbal shops, the actual health burden caused by this condition is extremely high. Many laxatives are available, but patients are often dissatisfied with the therapies adopted, whether prescribed by a doctor or self prescribed, and this leads to further social and health burdens. All of the available guidelines promote initiating the therapy of any type of constipation by ensuring an adequate intake of dietary fiber and water. However, high amounts of insoluble vegetable fiber such as those normally contained in fruits and vegetables, can lead to a further worsening of the digestive symptoms typical of chronic constipation, such as bloating and distension and pain. Better results can be obtained with soluble fibers, such as psyllium. Among the various available laxatives, polyethylene glycol (PEG), or macrogol, is the product which has been most studied and has produced the best results with the least number of side effects. This is an inert not absorbable molecule that, diluted in water, forms an isotonic solution that prevents part of the water from being absorbed, thus increasing the volume of the intestinal contents, reducing the consistency and facilitating transport and evacuation. The combination of psyllium and PEG could combine the advantages of fiber and isotonic solutions and represent an important therapeutic option for patients suffering from chronic constipation.
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
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.
Full Text Available Temporomandibular disorders such as bruxism may cause painful clinical conditions and over time lead to chronic facial pain. A combination of therapeutic strategies that are usually undertaken by dentists and gnathologists to reduce bruxism episodes and consequently pain, are myofunctional therapy, pharmacological treatment, intraoral interventions and behavioural treatments. The aim of this work was to understand if myofuntional therapy alone can be a useful therapy for the reduction of chronic facial pain. 24 patients, 9 male and 15 female, age ranging between 25 and 45, were treated with a myofunctional therapy for 9 month. Each patient was evaluated through a numeric pain intensity scale ranging from 0 to 10 and the number of bruxism episodes/hour per patient were also recorded; electromyographic examinations of the temporal, masseter, sternocleidomastoid and digastric muscles were performed to evaluate muscle activation. Each patient was tested before (T0 and after (T1 the treatment period. Pain intensity decreased from T0 to T1 (8.13±0.39 vs. 1.75±2.43, respectively, p<0.01. The number of bruxism episodes also significatively decreased between T0 and T1 (24 vs. 9, p<0.01. Electromyographic assessment showed a decrease in the tonic activity of the masseter muscle (T0: 1.88±0.31 vs. T1: 1.4±0.25 μV; p<0.05 and a reduction of the electric activity of the temporal and digastric muscles during serration of the mandible (T0: 167.9±19.6 μV Vs T1: 144.6+16.43 μV; p<0.05 and T0: 58.97+8.38 μV Vs T1: 52.79+7.44 μV; p<0.05, respectively. Myofunctional therapy could be used to reduce facial pain as a consequence of bruxism episodes.
Messina, Giuseppe; Martines, Francesco; Thomas, Ewan; Salvago, Pietro; Fabris, Giovanni Battista Menchini; Poli, Luciano; Iovane, Angelo
Temporomandibular disorders such as bruxism may cause painful clinical conditions and over time lead to chronic facial pain. A combination of therapeutic strategies that are usually undertaken by dentists and gnathologists to reduce bruxism episodes and consequently pain, are myofunctional therapy, pharmacological treatment, intraoral interventions and behavioural treatments. The aim of this work was to understand if myofuntional therapy alone can be a useful therapy for the reduction of chronic facial pain. 24 patients, 9 male and 15 female, age ranging between 25 and 45, were treated with a myofunctional therapy for 9 month. Each patient was evaluated through a numeric pain intensity scale ranging from 0 to 10 and the number of bruxism episodes/hour per patient were also recorded; electromyographic examinations of the temporal, masseter, sternocleidomastoid and digastric muscles were performed to evaluate muscle activation. Each patient was tested before (T0) and after (T1) the treatment period. Pain intensity decreased from T0 to T1 (8.13±0.39 vs. 1.75±2.43, respectively, p<0.01). The number of bruxism episodes also significatively decreased between T0 and T1 (24 vs. 9, p<0.01). Electromyographic assessment showed a decrease in the tonic activity of the masseter muscle (T0: 1.88±0.31 vs. T1: 1.4±0.25 μV; p<0.05) and a reduction of the electric activity of the temporal and digastric muscles during serration of the mandible (T0: 167.9±19.6 μV Vs T1: 144.6+16.43 μV; p<0.05 and T0: 58.97+8.38 μV Vs T1: 52.79+7.44 μV; p<0.05, respectively). Myofunctional therapy could be used to reduce facial pain as a consequence of bruxism episodes. PMID:29118958
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.
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.
Full Text Available Abstract Background Chronic immune thrombocytopenia (ITP is a debilitating autoimmune disorder that causes a reduction in blood platelets and increased risk of bleeding. ITP is currently managed with various pharmacologic therapies and splenectomy. This study was conducted to assess patient perceived and reported treatment side effects, as well as the perceived burden or bother, and need to reduce or stop treatment, associated with these side effects among adult patients with chronic ITP. Methods A Web-enabled survey was administered to members of a US-based ITP patient support group. Patients reported demographic and clinical characteristics, ITP treatments' side effects for treatments received since diagnosed, level of bother (or distress, and need to reduce or stop treatment, associated with side effects. Current and past exposure was assessed for five specific treatment types: corticosteroids (CS, intravenous immunoglobulin (IVIg, anti-D immunoglobulin (anti-D, rituximab (RT, and splenectomy (SPL, as well as for other patient-referenced therapies (captured as "other". Results The survey was completed by 589 patients; 78% female, 89% white, mean age 48 years (SD = 14.71, and 68% reported a typical low platelet count of P P P P Conclusions Current ITP treatments, particularly corticosteroids, are associated with multiple bothersome side effects that may lead to patients stopping or reducing therapy. Open, informed and complete communication between clinician and patient regarding both the benefits and the side effects of ITP treatment may better prepare patients for their prescribed regimens.
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.
Yue, Jin-Huan; Zhang, Shi-Jun; Sun, Qi; Sun, Zhong-Ren; Wang, Xin-Xin; Golianu, Brenda; Lu, Ying; Zhang, Qinhong
Several studies suggest that local warming therapy (LWT) may help to treat chronic wounds, such as pressure ulcers, venous ulcers, arterial ulcers, and diabetic foot ulcers. However, evidence supporting the efficacy of this treatment is still incomplete. This study aimed to assess the effects of LWT in treating chronic wounds. For this review, we searched the Cochrane Wounds Specialized Register (March 6, 2017); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2017 issue 3); Ovid MEDLINE (1946 to March 6, 2017); Ovid Embase (1974 to March 6, 2017); EBSCO CINAHL (1982 to March 6, 2017); Chinese Biomedical Literature Database (1980 to March 20, 2017); China National Knowledge Infrastructure (1980 to March 20, 2017); VIP Information (1980 to March 20, 2017) (Chinese Database); and Wanfang Data (1980 to March 20, 2017). We did not apply date or language restrictions. Published or unpublished randomized controlled trials (RCTs) analyzing the effects of LWT in the treatment of chronic wounds (pressure ulcers, venous ulcers, arterial ulcers, and diabetic foot ulcers) were screened and selected. Two review authors independently conducted study selection, we planned that 2 review authors would also assess risk of bias and extract study data. No studies (RCTs) met the inclusion criteria for this review. Thus, it was impossible to undertake a meta-analysis or a narrative description of studies. The effects of LWT for treating chronic wounds are unclear because we did not identify any studies that met the inclusion criteria for this review. Quality improvement for LWT trials is urgently needed.
Vestergaard, Christian; Deleuran, Mette
Chronic urticaria is a debilitating disease characterized by itching and hives with or without angioedema lasting for more than 6 weeks. The disease carries a significant emotional and economic burden for the patient and often results in an odyssey between doctors of different specialities. Patients suffering from chronic urticaria are considered more difficult to satisfy, treat and to have a bigger emotional burden than the average patient in dermatology, paediatric and general practice settings. A joint initiative under the Dermatology section of the European Academy of Allergy and Clinical immunology (EAACI), the Global Allergy and Asthma European Network (GA2LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO) has resulted in recently published guidelines for the diagnosis, classification and treatment of chronic urticarial: these guidelines are clinically useful and have a high success rate when followed in daily clinical practice. The treatment of choice for chronic urticaria is still nonsedating antihistamines although other treatments are available, with omalizumab (humanized IgG anti IgE antibodies) as the newest therapy. The pathogenesis of urticaria is poorly understood but autoimmunity is considered as one of the major underlying causes for this disease, although other theories exist. PMID:26568807
Chronic low back pain is a common condition affecting a significant proportion of the population and has large economic implications on the society. Acupuncture has grown in popularity as an alternative therapy for chronic low back pain. Recent National Institute for Health and Clinical Excellence (NICE) guidelines on low back pain offer a course of acupuncture as a baseline treatment option according to patient preference. The aim of this systematic review was to evaluate if this treatment option is justified in view of recent evidence available on the efficacy of acupuncture. Studies included were identified by a PubMed search for relevant, randomised, controlled trials on the 23 July 2009. A systematic review was performed. Fifteen randomised controlled trials were identified. Of these, four met the eligibility criteria and were critically appraised. These trials suggest acupuncture can be superior to usual care in treating chronic low back pain, especially, when patients have positive expectations about acupuncture. NICE guidelines of a course of acupuncture, offered according to patient preference as a treatment option for chronic low back pain, are justified.
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.
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.
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)
V. B. Grinevich
Full Text Available Background: Chronic pancreatitis is characterized by an imbalance of pro-inflammatory and anti-inflammatory cytokines, reflecting the presence of chronic systemic inflammation. The functional state of microbial-tissue complex of the intestine determines the severity of chronic systemic inflammation. Restoration of normal microbial-tissue complex functioning of the intestine reduces the severity of inflammatory changes in the pancreas.Aim: To study clinical efficacy of combination of chronic pancreatitis through correction of the functional state of intestinal microbial-tissue complex.Materials and methods: The analyzed patient sample included 117 patients with uncomplicated chronic pancreatitis and moderate pain syndrome, moderate exocrine and endocrine, with their mean age of 43.9 ± 11.6 years (men, 40.9 ± 13.5 years and women, 48.6 ± 11.7 years. Patients with chronic pancreatitis were divided into 2 groups, with the Results: After combination therapy of chronic pancreatitis with the agent for correction of the functional state of intestinal microbial-tissue complex, there was a significant (p < 0.05 reduction in the representation of pathogenic and conditionally pathogenic microflora, with a significant increase in the primary intestinal flora, as well as a decrease in cytokines TNF-α (74.32 ± 11.22 ng/ml before treatment, 31.34 ± 8.92 ng/ml after treatment and IL-1β (25.32 ± 4.36 ng/ml before treatment, 10.52 ± 3.52 ng/ml after treatment, a significant decrease in cortisol (456.53 ± 68.99 nmol/ml before treatment, 382.61 ± 60.24 nmol/ml after treatment. The significant improvement of metabolic abnormalities was associated with positive clinical dynamics and improvement of quality of life.Conclusion: Treatment strategies in chronic pancreatitis should include agents restoring the functioning of intestinal microbial-tissue complex and positively affecting metabolic and hormonal milieu.
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 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.
Agustí, A G; Carrera, M; Barbé, F; Muñoz, A; Togores, B
Venturi masks (VMs) and nasal prongs (NPs) are widely used to treat acute respiratory failure (ARF) in chronic obstructive pulmonary disease (COPD). In this study, these devices were compared in terms of their potentiality to worsen respiratory acidosis and their capacity to maintain adequate (> 90%) arterial oxygenation (Sa,O2) through time (approximately 24 h). In a randomized cross-over study, 18 consecutive COPD patients who required hospitalization because of ARF were studied. After determining baseline arterial blood gas levels (on room air), patients were randomized to receive oxygen therapy through a VM or NPs at the lowest possible inspiratory oxygen fraction that resulted in an initial Sa,O2 of > or = 90%. Arterial blood gas levels were measured again 30 min later (on O2), and Sa,O2 recorded using a computer during the subsequent approximately 24 h. Patients were then crossed-over to receive O2 therapy by means of the alternative device (NPs or VM), and the same measurements obtained again in the same order. It was observed that both the VM and NPs improved arterial oxygen tension (pO2 was O2 therapy and, particularly, the initial Sa,O2 achieved after initiation of O2 therapy (pO2 90%) level of arterial oxygenation in patients with chronic obstructive pulmonary disease and moderate acute respiratory failure: 1) the initial arterial oxygen saturation on oxygen should be maximized whenever possible by increasing the inspiratory oxygen fraction; 2) this strategy seems feasible because neither the VM nor NPs worsen respiratory acidosis significantly; and 3) the Venturi mask (better than nasal prongs) should be recommended.
Sánchez Del Águila, Manuel J; Schenk, Michael; Kern, Kai-Uwe; Drost, Tanja; Steigerwald, Ilona
Chronic pain is often challenging to address appropriately. Although patients with severe chronic pain may respond to treatment with an opioid analgesic, opioids are often associated with adverse effects that may lead patients to disrupt or discontinue therapy. In addition, opioid analgesics alone may not be effective for all types of chronic pain, including neuropathic pain. Tapentadol prolonged release (PR), a centrally acting analgesic with 2 mechanisms of action (μ-opioid receptor agonism and noradrenaline reuptake inhibition), provides strong and reliable analgesia across a range of indications, including nociceptive, neuropathic, and mixed types of chronic pain, and is associated with an improved tolerability profile relative to classic opioid analgesics. The purpose of this article was to review the recent literature on different aspects related to the clinical use of tapentadol PR. A review was conducted of the current literature and relevant unpublished data on initiation and titration of tapentadol PR, switching from classic strong opioids, risk of withdrawal after discontinuation, long-term treatment, coadministration with other medications, and risk of abuse and diversion. Tapentadol PR may provide clinically meaningful benefits over classic opioid analgesics, including ease of initiating and titrating tapentadol PR treatment in opioid-naive and opioid-experienced patients, low risk of withdrawal after cessation of tapentadol PR therapy, a favorable pharmacokinetic profile (allowing for coadministration with other medications) of tapentadol PR, and low potential for tapentadol PR abuse. The broad analgesic efficacy of tapentadol PR may simplify chronic pain management by allowing for the treatment of different types of pain with a single analgesic. In addition, tapentadol is associated with a low risk of pharmacokinetic interactions, which permits its use in patients taking multiple medications. Furthermore, the favorable tolerability profile of
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
Thomas F. Kresina
Full Text Available Many new and existing cases of viral hepatitis infections are related to injection drug use. Transmission of these infections can result directly from the use of injection equipment that is contaminated with blood containing the hepatitis B or C virus or through sexual contact with an infected individual. In the latter case, drug use can indirectly contribute to hepatitis transmission through the dis-inhibited at-risk behavior, that is, unprotected sex with an infected partner. Individuals who inject drugs are at-risk for infection from different hepatitis viruses, hepatitis A, B, or C. Those with chronic hepatitis B virus infection also face additional risk should they become co-infected with hepatitis D virus. Protection from the transmission of hepatitis viruses A and B is best achieved by vaccination. For those with a history of or who currently inject drugs, the medical management of viral hepatitis infection comprising screening, testing, counseling and providing care and treatment is evolving. Components of the medical management of hepatitis infection, for persons considering, initiating, or receiving pharmacologic therapy for opioid addiction include: testing for hepatitis B and C infections; education and counseling regarding at-risk behavior and hepatitis transmission, acute and chronic hepatitis infection, liver disease and its care and treatment; vaccination against hepatitis A and B infection; and integrative primary care as part of the comprehensive treatment approach for recovery from opioid abuse and dependence. In addition, participation in a peer support group as part of integrated medical care enhances treatment outcomes. Liver disease is highly prevalent in patient populations seeking recovery from opioid addiction or who are currently receiving pharmacotherapy for opioid addiction. Pharmacotherapy for opioid addiction is not a contraindication to evaluation, care, or treatment of liver disease due to hepatitis virus
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.
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.
Kiran Vasant Godse
Full Text Available Background: There is a felt need for trying newer therapeutic modalities in patients with chronic spontaneous urticaria, especially in the subset of patients classified as non-responders to antihistamines. Autologous serum therapy is an upcoming modality of treatment, and we decided to study its efficacy by subcutaneous route. Aims: To evaluate the effectiveness of subcutaneous autologous serum therapy (AST in CSU. Methods: This was a single blind, placebo-controlled parallel group, randomized, controlled study. Twenty-four patients with CSU (11M: 13 F were given subcutaneous AST and seventeen patients (7 M: 10F patients were given subcutaneous injection normal saline (placebo, along with levocetirizine in an on-demand basis in both groups. Results: Urticaria activity score (UAS came down from 35.74 to 7 at the end of 9 weeks and the patients' requirement of antihistamines also reduced remarkably from 5.8 to 1.7 per week in the serum group. Sub-cutaneous saline group did not show statistically significant fall in UAS. Saline group showed UAS 32.8 at zero week to 22.1 at the end of 9 weeks. DLQI showed significant fall in serum group, from 14.26 to 4 at the end of 9 weeks. Conclusion: Subcutaneous autoserum therapy is effective in treatment of CSU.
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.
Hale, Martin; Urdaneta, Veronica; Kirby, M Todd; Xiang, Qinfang; Rauck, Richard
This open-label, single-arm study was conducted to evaluate the long-term safety and efficacy of a novel buprenorphine formulation, buprenorphine buccal film, in the treatment of moderate-to-severe chronic pain requiring around-the-clock opioids. The primary purpose of this study was to evaluate the long-term safety and tolerability of buprenorphine buccal film. Five hundred and six patients who completed previous studies with buprenorphine buccal film (n=445; rollover patients) or were recruited de novo for this study (n=61) were enrolled in this study. All patients underwent a dose titration period of ≤6 weeks, during which doses of buprenorphine buccal film were adjusted to a maximum 900 µg every 12 hours, depending on tolerability and the need for rescue medication. An optimal dose was defined as the dose that the patient found satisfactory for both pain relief and tolerability, without the need for rescue medication or with ≤2 tablets of rescue medication per day. Once the optimal dose was reached, treatment was continued for ≤48 weeks. Pain intensity was measured throughout the study using a 0-10 numerical rating scale. Of 435 patients achieving an optimal dose of buprenorphine buccal film who commenced long-term treatment, 158 (36.3%) completed 48 weeks of treatment. Treatment-related adverse events occurred in 116 patients (22.9%) during the titration phase and 61 patients (14.0%) during the long-term treatment phase, and adverse events leading to discontinuation of treatment occurred in 14 (2.8%) and 14 (3.2%) patients, respectively. The most common adverse events were those typically associated with opioids, such as nausea, constipation, and headache. In both rollover and de novo patients, pain intensity scores remained constant at approximately 3-4 during long-term treatment, and the dose of buprenorphine buccal film remained unchanged in 86.2% of patients. In appropriate patients, buprenorphine buccal film demonstrated tolerability and efficacy
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
Biel, Merrill A.; Sievert, Chet; Usacheva, Marina; Teichert, Matthew; Balcom, Jim
Background Chronic recurrent sinusitis (CRS) is an inflammatory disease of the facial sinuses and nasal passages that is defined as lasting longer than 12 weeks or occurring more than 4 times per year with symptoms usually lasting more than 20 days. The National Institute for Health Statistics estimates that CRS is one of the most common chronic conditions in the United States affecting an estimated 37 million Americans. The potential etiologies of CRS include bacteria, viruses, allergies, fungi, superantigens and microbial biofilms. In clinical practice there is a significant subpopulation of patients with CRS who remain resistant to cure despite rigorous treatment regimens including surgery, allergy therapy and prolonged antibiotic therapy. The reason for treatment failure is thought to be related to the destruction of the sinus mucociliary defense by the chronic sinus infection resulting in the development of secondary antibiotic resistant microbial colonization of the sinuses and biofilm formation. Antimicrobial photodynamic therapy (aPDT) is a non-antibiotic broad spectrum antimicrobial treatment that has been demonstrated to eradicate antibiotic resistant bacteria and biofilms. Objective The objective of this study was to demonstrate the effectiveness of a non-invasive aPDT treatment method of eradicating antibiotic resistant biofilms/microorganisms known to cause CRS in an in vitro model. Methods Antibiotic resistant planktonic bacteria and fungi and polymicrobial biofilms of Pseudomonas aerugenosa and MRSA were grown on silastic sheets and treated with a methylene blue photosensitizer and 670nm non-thermal activating light. Cultures of the planktonic micoroorganisms and biofilms were obtained before and after light treatment to determine efficacy of planktonic baciteria and biofilm reduction. Results The in vitro CRS planktonic microorganism and biofilm study demonstrated that aPDT reduced the CRS polymicrobial biofilm by >99.9% after a single treatment
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
Boothby, Lisa A; Doering, Paul L
The clinical issues surrounding the use of buprenorphine for the treatment of opioid dependence are reviewed. Opioids continue to be some of the most frequently reported prescription medications in substance abuse- related cases. A semisynthetic derivative of thebaine, buprenorphine hydrochloride is a partial mu-opioid receptor agonist and kappa-receptor antagonist with a long duration of action. The pharmacokinetic and pharmacodynamic profiles of buprenorphine are not well characterized. The ethical and legal issues associated with the maintenance treatment of opioid dependence are complex. Clinical trials have compared the efficacy of methadone, buprenorphine, and buprenorphine-naloxone for the detoxification and maintenance treatment of opioid dependence. Based on the available literature, it appears that buprenorphine, buprenorphine-naloxone, and methadone are similarly efficacious for the treatment of opioid-dependent patients. Buprenorphine-naloxone has less potential for abuse and diversion. The adverse-effect profiles for buprenorphine, buprenorphine-naloxone, and methadone are similar. Once-weekly office visits for patient evaluation and dispensing of buprenorphine seem feasible and convenient for both practitioners and patients. The three phases of opioid maintenance treatment are induction, stabilization, and maintenance. It is good practice for the admitting physician to consult with the patient's addiction treatment provider, when possible, to obtain the patient's treatment history. Buprenorphine is an attractive option for the pharmacologic treatment of opioid dependence. Compliance and adherence to buprenorphine therapy for opioid-dependent patients remain clinical issues. Future research efforts should focus on improving compliance and adherence to buprenorphine therapy.
So-called weak opioid analgesics are often used to treat severe pain, or when paracetamol or a nonsteroidal anti-inflammatory drug (NSAID) proves inadequate. But are weak opioids any more effective than paracetamol or NSAIDs on nociceptive pain, and are they better tolerated than morphine? To answer these questions, we conducted a review of literature using the standard Prescrire methodology. The potency of codeine and tramadol is strongly influenced by the cytochrome P450 isoenzyme CYP2D6 genotype, which varies widely from one person to another. This explains reports of overdosing or underdosing after administration of standard doses of the two drugs. The potency of morphine and that of buprenorphine, an opioid receptor agonist-antagonist, appears to be independent of CYP2D6 activity. All "weak" opioids can have the same dose-dependent adverse effects as morphine. There is no evidence that, at equivalent analgesic efficacy, weak opioids carry a lower risk of addiction than low-dose morphine. Respiratory depression can occur in ultrarapid metabolisers after brief exposure to standard doses of codeine or tramadol. Similar cases have been reported with dihydrocodeine in patients with renal failure. In addition, tramadol can cause a serotonin syndrome, hypoglycaemia, hyponatraemia and seizures. Several trials have compared different weak opioids in patients with post-operative pain. A single dose of a weak opioid, possibly combined with paracetamol, has greater analgesic efficacy than paracetamol alone but is not more effective than an NSAID alone. There is a dearth of evidence on weak opioids in patients with chronic pain. Available trials fail to show that a weak opioid has markedly superior analgesic efficacy to paracetamol or an NSAID. Sublingual buprenorphine at analgesic doses appears less likely to cause respiratory depression, but it seems to have weak analgesic efficacy. In practice, when opioid therapy is needed, there is no evidence that codeine
Full Text Available Pain is a complex experience that is influenced by neurological processes and psychosocial factors and important health problem that affects the individual, society, and work force, leading to reduced quality of life and physical activity and impaired social relations. Many studies have demonstrated the efficacy of cognitive behavioral therapy (CBT in reducing the severity and frequency of pain, improving pain-induced negative mood, and improving quality of life. The patient's cognitive coping, cognitive restructuring, problem solving and relaxation skills are improved with CBT. Considering the biopsychosocial pain model and other literature information, chronic pain management should be organized in a multidisciplinary approach. [JCBPR 2017; 6(3.000: 133-140
Gimbel, Joseph; Spierings, Egilius L.H.; Katz, Nathaniel; Xiang, Qinfang; Tzanis, Evan; Finn, Andrew
Abstract 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 pain reductions ≥30% and ≥50% (P low back pain. PMID:27434505
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
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.
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.
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.
Turner, Judith A.; Shortreed, Susan M.; Saunders, Kathleen W.; LeResche, Linda; Thielke, Stephen; Von Korff, Michael
Many consider chronic opioid therapy (COT) to be ineffective for fibromyalgia, but empirical evidence is limited. Among patients identified as initiating COT, we examined whether fibromyalgia was associated with different relationships of opioid use to pain and activity interference outcomes 12 months later. We obtained electronic data on diagnoses and opioid prescriptions. We obtained patient self-report data, including pain and activity interference measures, at baseline, 4 months, and 12 months. Among 1,218 patients, 429 (35%) met our definition of fibromyalgia. Patients with and without fibromyalgia who had intermittent/lower-dose or regular/higher-dose opioid use at 12 months had similar 12-month pain intensity scores. However, among patients with minimal/no opioid use at 12 months, 12-month pain intensity was greater for those with fibromyalgia (adjusted mean = 5.15 [95% CI = 4.80, 5.51]; 0-10 scale) than for those without (4.44 [4.15, 4.72]). Similar patterns were observed for 12-month activity interference. Among patients who discontinued opioids by 12 months, those with fibromyalgia were more likely to report bothersome side effects and less likely to report pain improvement as important reasons for discontinuation (P-values fibromyalgia had worse outcomes and were less likely to have discontinued due to pain improvement. Among patients continuing COT, pain and activity interference outcomes were worse than those of patients with minimal/no opioid use and did not differ for those with fibromyalgia versus those with diverse other chronic pain conditions. PMID:27643834
Trang, Tuan; Al-Hasani, Ream; Salvemini, Daniela; Salter, Michael W; Gutstein, Howard; Cahill, Catherine M
Treating pain is one of the most difficult challenges in medicine and a key facet of disease management. The isolation of morphine by Friedrich Sertürner in 1804 added an essential pharmacological tool in the treatment of pain and spawned the discovery of a new class of drugs known collectively as opioid analgesics. Revered for their potent pain-relieving effects, even Morpheus the god of dreams could not have dreamt that his opium tincture would be both a gift and a burden to humankind. To date, morphine and other opioids remain essential analgesics for alleviating pain. However, their use is plagued by major side effects, such as analgesic tolerance (diminished pain-relieving effects), hyperalgesia (increased pain sensitivity), and drug dependence. This review highlights recent advances in understanding the key causes of these adverse effects and explores the effect of chronic pain on opioid reward. Chronic pain is pervasive and afflicts >100 million Americans. Treating pain in these individuals is notoriously difficult and often requires opioids, one of the most powerful and effective classes of drugs used for controlling pain. However, their use is plagued by major side effects, such as a loss of pain-relieving effects (analgesic tolerance), paradoxical pain (hyperalgesia), and addiction. Despite the potential side effects, opioids remain the pharmacological cornerstone of modern pain therapy. This review highlights recent breakthroughs in understanding the key causes of these adverse effects and explores the cellular control of opioid systems in reward and aversion. The findings will challenge traditional views of the good, the bad, and the ugly of opioids. Copyright © 2015 the authors 0270-6474/15/3513879-10$15.00/0.
Al-Hasani, Ream; Salvemini, Daniela; Salter, Michael W.; Gutstein, Howard
Treating pain is one of the most difficult challenges in medicine and a key facet of disease management. The isolation of morphine by Friedrich Sertürner in 1804 added an essential pharmacological tool in the treatment of pain and spawned the discovery of a new class of drugs known collectively as opioid analgesics. Revered for their potent pain-relieving effects, even Morpheus the god of dreams could not have dreamt that his opium tincture would be both a gift and a burden to humankind. To date, morphine and other opioids remain essential analgesics for alleviating pain. However, their use is plagued by major side effects, such as analgesic tolerance (diminished pain-relieving effects), hyperalgesia (increased pain sensitivity), and drug dependence. This review highlights recent advances in understanding the key causes of these adverse effects and explores the effect of chronic pain on opioid reward. SIGNIFICANCE STATEMENT Chronic pain is pervasive and afflicts >100 million Americans. Treating pain in these individuals is notoriously difficult and often requires opioids, one of the most powerful and effective classes of drugs used for controlling pain. However, their use is plagued by major side effects, such as a loss of pain-relieving effects (analgesic tolerance), paradoxical pain (hyperalgesia), and addiction. Despite the potential side effects, opioids remain the pharmacological cornerstone of modern pain therapy. This review highlights recent breakthroughs in understanding the key causes of these adverse effects and explores the cellular control of opioid systems in reward and aversion. The findings will challenge traditional views of the good, the bad, and the ugly of opioids. PMID:26468188
Herbst, M.; Fritz, H.; Sauer, R.; Nuesslein, H.G.; Manger, B.J.; Kalden, J.R.
Eleven patients with refractory rheumatoid arthritis were submitted to a total lymphoid irradiation up to a dose of 20 Gy. A constant improvement of clinical symptoms was observed in four out of the eleven patients already during the treatment and in the other patients not later than two months after. The frequency of attacks decreased and the number of joints involved in the attack was reduced. Morning rigidity and joint swellings decreased. One patient developed joint empyemas 4 and 26 months after the treatment. Four patients died in the meantime. In two patients the cause of death were renal insufficiency and a postoperative cardiogenic shock associated with generalized amyloidosis. The third patient died because of a toxically induced left cardiac decompensation with sepsis that could not be controlled by antibiotic drugs and multiple joint empyemas. The fourth patient developed an abscess after surgical treatment of a Kaposi syndrome. She died three months later from acute left cardiac decompensation. The therapy induced a lymphocytopenia with decrease of T helper lympocytes and unchanged number of T suppressor lymphocytes. The constant therapy results of total lymphoid irradiation in primary chronic polyarthritis is probably due to this modification in the immune regulation. (orig.) [de
Miller, Anya; Hall, Francis; Ahsan, Syed
The incidence of chronic otitis media with effusion (COME) after radiotherapy for nasopharyngeal or sinonasal tumors is relatively high. It is often a difficult-to-treat problem in these patients. In this retrospective study, we sought to describe the clinical course of COME in 51 patients-33 men and 18 women, aged 39 to 90 years (mean: 58.9 ± 15)-who had been referred to the Henry Ford Health System in Detroit between 2001 and 2011 for management of a tumor that had involved either the nasopharyngeal area or the sinonasal area. The median length of follow-up from the time of cancer diagnosis was 32 months. Of the 51 patients, 23 (45.1%) developed COME before, during, or after radiation therapy. Of these 23 patients, 13 (56.5%) did not experience any improvement after treatment with various combinations of therapies, including myringotomy, tympanostomy tube placement, otic drops, oral antibiotics, and corticosteroid nasal sprays. No patient- or tumor-specific factors were found to be significantly associated with the incidence of COME after irradiation to the sinonasal area. Older age and squamous cell tumor pathology were found to be significant factors for the resolution of COME after it had developed, whereas treatments with tympanostomy tubes and ear drops were not. Because of the high incidence of COME after radiotherapy and the high rate of COME's failure to resolve after tympanostomy tube insertion, we suggest that these patients require an alternative treatment.
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.
ZHANG, TING; ZHOU, XIANGDONG
Airway mucus hypersecretion is a significant clinical and pathological feature of chronic inflammatory airway diseases. Its clinical presentations include recurrent coughing and phlegm. Airway mucus is closely associated with the occurrence, development and prognosis of chronic inflammatory airway diseases and critically affects the lung function, quality of life, hospitalization rate and mortality of patients with chronic inflammatory airway diseases. Therefore, expectorant therapies targeti...
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
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.
Mehendale, Anand W; Goldman, Mark P; Mehendale, Rachel P
Throughout history, opioids have effectively alleviated pain but not without the risk of addiction and death. Seductive and dangerous, full of promise and destruction, opioids are both revered and feared by Western culture. Their exponential use in "developed countries" is now an enormous public health problem and requires us to harness their properties with scientific rigor and adequate safeguards. The use of opioids for the treatment of chronic nonterminal pain (CNTP) has been a relatively new phenomenon which has coincided with the proclamation by the Joint Commission on Accreditation of Health Care Organization in 2000 that pain assessment be the "fifth vital sign," notwithstanding the fact that pain is a symptom and not a sign.(1) Nonetheless, this resulted in a culture of a marked increase in use of opioids for acute and chronic pain management. Consequently, there are many unintended outcomes which include opioid-induced hyperalgesia increased diversion, addiction, and death. Understandably, this has resulted in many regulatory responses from such agencies such as the Drug Enforcement Administration (DEA) and state medical boards. This article proposes a clinically relevant paradigm of opioid overuse pain syndrome. The goal of this article is to inform the clinicians of the complicated neurobiology of opioids. It is our hope that scientists rather than government regulators dictate the appropriate response to the epidemic of over prescription of opioids. A similar designation of "medication overuse headache" has resulted in near extinction of excessive use of opioids in the field of headache medicine.
Glenn, Matthew C.; Sohler, Nancy L.; Starrels, Joanna L.; Maradiaga, Jeronimo; Jost, John J.; Arnsten, Julia H.; Cunningham, Chinazo O.
Background Opioid analgesic use and disorders have dramatically increased among the general American population and those receiving methadone maintenance treatment (MMT). Most research among MMT patients focuses on opioid analgesics misuse or disorders; few studies focus on MMT patients prescribed opioid analgesics. We describe demographic, clinical, and substance use characteristics of MMT patients prescribed opioid analgesics and compare them to MMT patients not prescribed opioid analgesics. Methods We conducted a cross-sectional secondary data analysis using screening interviews from a parent study. From 2012–2015, we recruited adults from 3 MMT Bronx clinics. Questionnaire data included: patterns of opioid analgesic use, substance use, comorbid illnesses, and demographic characteristics. Our main dependent variable was patients’ report of currently taking prescribed opioid analgesics. To compare characteristics between MMT patients prescribed and not prescribed opioid analgesics, we conducted chi-squared tests, t-tests, and Mann-Whitney U tests. Results Of 611 MMT patients, most reported chronic pain (62.0%), HCV infection (52.1%), and currently using illicit substances (64.2%). Of the 29.8% who reported currently taking prescribed opioid analgesics, most misused their opioid analgesics (57.5%). Patients prescribed (versus not prescribed) opioid analgesics were more likely to report HIV infection (aOR=1.6, 95% CI: 1.1–2.3) and chronic pain (aOR=7.6, 95% CI: 4.6–12.6). Conclusion Among MMT patients primarily in three Bronx clinics, nearly one-third reported taking prescribed opioid analgesics. Compared to patients not prescribed opioid analgesics, those prescribed opioid analgesics were more likely to report chronic pain and HIV infection. However, between these patients, there was no difference in illicit substance use. These findings highlight the complexity of addressing chronic pain in MMT patients. PMID:26731299
Glenn, Matthew C; Sohler, Nancy L; Starrels, Joanna L; Maradiaga, Jeronimo; Jost, John J; Arnsten, Julia H; Cunningham, Chinazo O
Opioid analgesic use and disorders have dramatically increased among the general American population and those receiving methadone maintenance treatment (MMT). Most research among MMT patients focuses on opioid analgesics misuse or disorders; few studies focus on MMT patients prescribed opioid analgesics. We describe demographic, clinical, and substance use characteristics of MMT patients prescribed opioid analgesics and compare them with MMT patients not prescribed opioid analgesics. We conducted a cross-sectional secondary data analysis using screening interviews from a parent study. From 2012 to 2015, we recruited adults from 3 MMT Bronx clinics. Questionnaire data included patterns of opioid analgesic use, substance use, comorbid illnesses, and demographic characteristics. Our main dependent variable was patients' report of currently taking prescribed opioid analgesics. To compare characteristics between MMT patients prescribed and not prescribed opioid analgesics, we conducted chi-square tests, t tests, and Mann-Whitney U tests. Of 611 MMT patients, most reported chronic pain (62.0%), hepatitis C virus (HCV) infection (52.1%), and current use of illicit substances (64.2%). Of the 29.8% who reported currently taking prescribed opioid analgesics, most misused their opioid analgesics (57.5%). Patients prescribed (versus not prescribed) opioid analgesics were more likely to report human immunodeficiency virus (HIV) infection (adjusted odds ratio [aOR] = 1.6, 95% confidence interval [CI]: 1.1-2.3) and chronic pain (aOR = 7.6, 95% CI: 4.6-12.6). Among MMT patients primarily in 3 Bronx clinics, nearly one third reported taking prescribed opioid analgesics. Compared with patients not prescribed opioid analgesics, those prescribed opioid analgesics were more likely to report chronic pain and HIV infection. However, between these patients, there was no difference in illicit substance use. These findings highlight the complexity of addressing chronic pain in MMT patients.
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
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.
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
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.
Price, Jonathan R; Mitchell, Edward; Tidy, Elizabeth; Hunot, Vivien
Chronic fatigue syndrome (CFS) is a common, debilitating and serious health problem. Cognitive behaviour therapy (CBT) may help to alleviate the symptoms of CFS. To examine the effectiveness and acceptability of CBT for CFS, alone and in combination with other interventions, compared with usual care and other interventions. CCDANCTR-Studies and CCDANCTR-References were searched on 28/3/2008. We conducted supplementary searches of other bibliographic databases. We searched reference lists of retrieved articles and contacted trial authors and experts in the field for information on ongoing/completed trials. Randomised controlled trials involving adults with a primary diagnosis of CFS, assigned to a CBT condition compared with usual care or another intervention, alone or in combination. Data on patients, interventions and outcomes were extracted by two review authors independently, and risk of bias was assessed for each study. The primary outcome was reduction in fatigue severity, based on a continuous measure of symptom reduction, using the standardised mean difference (SMD), or a dichotomous measure of clinical response, using odds ratios (OR), with 95% confidence intervals (CI). Fifteen studies (1043 CFS participants) were included in the review. When comparing CBT with usual care (six studies, 373 participants), the difference in fatigue mean scores at post-treatment was highly significant in favour of CBT (SMD -0.39, 95% CI -0.60 to -0.19), with 40% of CBT participants (four studies, 371 participants) showing clinical response in contrast with 26% in usual care (OR 0.47, 95% CI 0.29 to 0.76). Findings at follow-up were inconsistent. For CBT versus other psychological therapies, comprising relaxation, counselling and education/support (four studies, 313 participants), the difference in fatigue mean scores at post-treatment favoured CBT (SMD -0.43, 95% CI -0.65 to -0.20). Findings at follow-up were heterogeneous and inconsistent. Only two studies compared CBT
Renner, Fritz; DeRubeis, Robert; Arntz, Arnoud; Peeters, Frenk; Lobbestael, Jill; Huibers, Marcus J H
The underlying mechanisms of symptom change in schema therapy (ST) for chronic major depressive disorder (cMDD) have not been studied. The aim of this study was to explore the impact of two potentially important mechanisms of symptom change, maladaptive schemas (proxied by negative idiosyncratic core-beliefs) and the therapeutic alliance. We drew data from a single-case series of ST for cMDD. Patients with cMDD (N = 20) received on average 78 repeated weekly assessments over a course of up to 65 individual sessions of ST. Focusing on repeated assessments within-individuals, we used mixed regression to test whether change in core-beliefs and therapeutic alliance preceded, followed, or occurred concurrently with change in depressive symptoms. Changes in core-beliefs did not precede but were concurrently related to changes in symptoms. Repeated goal and task agreement ratings (specific aspects of alliance) of the same session, completed on separate days, were at least in part associated with concurrent changes in symptoms. By design this study had a small sample-size and no control group. Contrary to what would be expected based on theory, our findings suggest that change in core-beliefs does not precede change in symptoms. Instead, change in these variables occurs concurrently. Moreover, alliance ratings seem to be at least in part colored by changes in current mood state. Copyright © 2017 Elsevier Ltd. All rights reserved.
Dewilde, W; Verheugt, F W A; Breet, N; Koolen, J J; Ten Berg, J M
Chronic oral anticoagulant treatment is obligatory in patients (class I) with mechanical heart valves and in patients with atrial fibrillation with CHADS2 score >1. When these patients undergo percutaneous coronary intervention with placement of a stent, there is also an indication for treatment with aspirin and clopidogrel. Unfortunately, triple therapy is known to increase the bleeding risk. For this group of patients, the bottom line is to find the ideal therapy in patients with indications for both chronic anticoagulation therapy and percutaneous intervention to prevent thromboembolic complications such as stent thrombosis without increasing the risk of bleeding. (Neth Heart J 2010;18:444-50.).
Angheluta, Anne-Marie; Lee, Bonnie K.
Chronic pain is acknowledged as a phenomenological experience resulting from biological, psychological, and social interactions. Consequently, treatment for this complex and debilitating health phenomenon is often approached from multidisciplinary and biopsychosocial perspectives. One approach to treating chronic pain involves implementing…
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.
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.
Shavit, Yehuda; Grace, Peter M.; Rice, Kenner C.; Maier, Steven F.; Watkins, Linda R.
Vastly stimulated by the discovery of opioid receptors in the early 1970s, preclinical and clinical research was directed at the study of stereoselective neuronal actions of opioids, especially those played in their crucial analgesic role. However, during the past decade, a new appreciation of the non-neuronal actions of opioids has emerged from preclinical research, with specific appreciation for the nonclassic and nonstereoselective sites of action. Opioid activity at Toll-like receptors, newly recognized innate immune pattern recognition receptors, adds substantially to this unfolding story. It is now apparent from molecular and rodent data that these newly identified signaling events significantly modify the pharmacodynamics of opioids by eliciting proinflammatory reactivity from glia, the immunocompetent cells of the central nervous system. These central immune signaling events, including the release of cytokines and chemokines and the associated disruption of glutamate homeostasis, cause elevated neuronal excitability, which subsequently decreases opioid analgesic efficacy and leads to heightened pain states. This review will examine the current preclinical literature of opioid-induced central immune signaling mediated by classic and nonclassic opioid receptors. A unification of the preclinical pharmacology, neuroscience, and immunology of opioids now provides new insights into common mechanisms of chronic pain, naive tolerance, analgesic tolerance, opioid-induced hyperalgesia, and allodynia. Novel pharmacological targets for future drug development are discussed in the hope that disease-modifying chronic pain treatments arising from the appreciation of opioid-induced central immune signaling may become practical. PMID:21752874
El-Kheir, Wael Abo; Gabr, Hala; Awad, Mohamed Reda; Ghannam, Osama; Barakat, Yousef; Farghali, Haithem A M A; El Maadawi, Zeinab M; Ewes, Ibrahim; Sabaawy, Hatem E
Spinal cord injuries (SCI) cause sensory loss and motor paralysis. They are normally treated with physical therapy, but most patients fail to recover due to limited neural regeneration. Here we describe a strategy in which treatment with autologous adherent bone marrow cells is combined with physical therapy to improve motor and sensory functions in early stage chronic SCI patients. In a phase I/II controlled single-blind clinical trial (clinicaltrials.gov identifier: NCT00816803), 70 chronic cervical and thoracic SCI patients with injury durations of at least 12 months were treated with either intrathecal injection(s) of autologous adherent bone marrow cells combined with physical therapy or with physical therapy alone. Patients were evaluated with clinical and neurological examinations using the American Spinal Injury Association (ASIA) Impairment Scale (AIS), electrophysiological somatosensory-evoked potential, magnetic resonance imaging (MRI), and functional independence measurements. Chronic cervical and thoracic SCI patients (15 AIS A and 35 AIS B) treated with autologous adherent bone marrow cells combined with physical therapy showed functional improvements over patients in the control group (10 AIS A and 10 AIS B) treated with physical therapy alone, and there were no long-term cell therapy-related side effects. At 18 months posttreatment, 23 of the 50 cell therapy-treated cases (46%) showed sustained functional improvement. Compared to those patients with cervical injuries, a higher rate of functional improvement was achieved in thoracic SCI patients with shorter durations of injury and smaller cord lesions. Therefore, when combined with physical therapy, autologous adherent bone marrow cell therapy appears to be a safe and promising therapy for patients with chronic SCI of traumatic origin. Randomized controlled multicenter trials are warranted.
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.
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
To estimate the effects of needle and syringe programmes (NSP) and opioid substitution therapy (OST), alone or in combination, for preventing acquisition of hepatitis C virus (HCV) in people who inject drugs (PWID). Systematic review and meta-analysis. Bibliographic databases were searched for studies measuring concurrent exposure to current OST (within the last 6 months) and/or NSP and HCV incidence among PWID. High NSP coverage was defined as regular NSP attendance or ≥ 100% coverage (receiving sufficient or greater number of needles and syringes per reported injecting frequency). Studies were assessed using the Cochrane risk of bias in non-randomized studies tool. Random-effects models were used in meta-analysis. We identified 28 studies (n = 6279) in North America (13), United Kingdom (five), Europe (four), Australia (five) and China (one). Studies were at moderate (two), serious (17) critical (seven) and non-assessable risk of bias (two). Current OST is associated with 50% [risk ratio (RR) =0.50, 95% confidence interval (CI) = 0.40-0.63] reduction in HCV acquisition risk, consistent across region and with low heterogeneity (I 2 = 0, P = 0.889). Weaker evidence was found for high NSP coverage (RR = 0.79, 95% CI = 0.39-1.61) with high heterogeneity (I 2 = 77%, P = 0.002). After stratifying by region, high NSP coverage in Europe was associated with a 56% reduction in HCV acquisition risk (RR = 0.44, 95% CI = 0.24-0.80) with low heterogeneity (I 2 = 12.3%, P = 0.337), but not in North America (RR = 1.58, I 2 = 89.5%, P = Grades of Recommendation Assessment, Development and Evaluation (GRADE) criteria, the evidence on OST and combined OST/NSP is low quality, while NSP is very low. Opioid substitution therapy reduces risk of hepatitis C acquisition and is strengthened in combination with needle and syringe programmes (NSP). There is weaker evidence for the impact of needle syringe programmes alone, although stronger evidence
Full Text Available Aim: The present study proposes an assessment of the clinical effects on periodontal level generated by the adjunctive periodontal therapy with sub-antimicrobial doses of doxycycline in patients with chronic periodontitis and osteoporosis.
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 information from four subject groups was collected: non-dependent opioid users (NOD) [n=163]; opioid-dependent (OD) patients in methadone maintenance treatment (MMT) [n=143]; opioid-dependent MMT-resistant patients in heroin-assisted treatment (HAT) [n=138]; and healthy controls with no history of opioid use (HC) [n=153]. Eighty-two variants in eight opioid system genes were studied. To establish the role of these genes in (a) non-dependent opioid use, and (b) heroin dependence, the following groups were compared: HC vs. NOD; HC vs. OD (MMT+HAT); and NOD vs. OD (MMT+HAT). Five unique SNPs in four genes showed nominally significant associations with non-dependent opioid use and heroin dependence. The association of the delta opioid receptor (OPRD1) intronic SNP rs2236861 with non-dependent opioid use (HC vs. NOD) remained significant after correction for multiple testing (OR=0.032; p corrected =0.015). This SNP exhibited a significant gene-gene interaction with prepronociceptin (PNOC) SNP rs2722897 (OR=5.24; p corrected =0.041) (HC vs. NOD). This study identifies several new and some previously reported associations of variants with heroin dependence and with non-dependent opioid use, an important and difficult to obtain group not extensively studied previously. Further studies are warranted to confirm and elucidate the potential roles of these variants in the vulnerability to illicit drug use and drug addiction. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
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
Gendron, Louis; Cahill, Catherine M.; von Zastrow, Mark; Schiller, Peter W.
Opioids are among the most effective analgesics available and are the first choice in the treatment of acute severe pain. However, partial efficacy, a tendency to produce tolerance, and a host of ill-tolerated side effects make clinically available opioids less effective in the management of chronic pain syndromes. Given that most therapeutic opioids produce their actions via µ-opioid receptors (MOPrs), other targets are constantly being explored, among which δ-opioid receptors (DOPrs) are being increasingly considered as promising alternatives. This review addresses DOPrs from the perspective of cellular and molecular determinants of their pharmacological diversity. Thus, DOPr ligands are examined in terms of structural and functional variety, DOPrs’ capacity to engage a multiplicity of canonical and noncanonical G protein–dependent responses is surveyed, and evidence supporting ligand-specific signaling and regulation is analyzed. Pharmacological DOPr subtypes are examined in light of the ability of DOPr to organize into multimeric arrays and to adopt multiple active conformations as well as differences in ligand kinetics. Current knowledge on DOPr targeting to the membrane is examined as a means of understanding how these receptors are especially active in chronic pain management. Insight into cellular and molecular mechanisms of pharmacological diversity should guide the rational design of more effective, longer-lasting, and better-tolerated opioid analgesics for chronic pain management. PMID:27343248
松倉, 康夫; 上村, 史朗; 川本, 篤彦; 坂口, 泰弘; 山野, 繁; 藤本, 眞一; 橋本, 俊雄; 土肥, 和紘
Recently, many patients with ischemic heart disease (IHD), including myocardial infarction, angina pectoris, and patients with coronary stent implantation, are receiving chronic aspirin therapy in expectation of its anti-platelet effects. It is well known that, in patients with rheumatic disease on chronic aspirin therapy, aspirin-induced peptic ulcer is frequent and limits its clinical usefulness. In this study, we studied 482 IHD patients after coronary intervention to evaluate the incidenc...
Batista, Alexandre Apolinário de Souza; Diniz, Leandro Silva Rezende; Oliveira, Vinícius Cunha; Venturini, Claudia
AbstractIntroduction The health locus of control is defined as the perception of individuals in relation to whom they believe to be responsible for their health condition, including low back pain.Objective To identify whether individuals suffering from chronic low back pain in active physical therapy treatment believe they are responsible for their own condition.Material and methods Cross-sectional study involving 28 patients under active physical therapy treatment for non-specific chronic lo...
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....
extensively on our training materials as these will be necessary to move towards implementation. We plan to work on developing a training manual based ...AWARD NUMBER: W81XWH-12-2-0109 TITLE: Telephone-Delivered Cognitive Behavioral Therapy for Chronic Pain Following Traumatic Brain Injury...2015 - 29 Sep 2016 4. TITLE AND SUBTITLE Telephone-Delivered Cognitive Behavioral Therapy for Chronic Pain 5a. CONTRACT NUMBER Following Traumatic
Stepanova, Maria; Thompson, Alexander; Doyle, Joseph; Younossi, Issah; de Avila, Leyla; Younossi, Zobair M
There is a paucity of patient-reported outcomes (PROs) data for people undergoing hepatitis C virus (HCV) treatment who are treated with opioid substitution therapy (OST) for addiction. Patients enrolled in phase 3 clinical trials of sofosbuvir completed 4 PRO instruments-SF-36v2, FACIT-F, CLDQ-HCV, and WPAI-HCV-before, during, and after treatment. A total of 8450 HCV-infected subjects were included; 4.8% (407) were receiving OST. At baseline, OST recipients had significantly (P < .0001) lower PRO scores (by -3.5 to -15.6 on a 0-100 scale). By the end of treatment, subjects receiving pegylated interferon, ribavirin, and sofosbuvir (IFN+RBV+SOF) experienced significant decreases in PROs regardless of OST use. Subjects receiving IFN-free RBV-containing regimens had significant but smaller PRO decreases, again similar in the OST and non-OST groups. Finally, subjects treated with regimens free of both IFN and RBV (IFN/RBV-free) showed improvements in nearly all PROs during treatment, with improvements more pronounced in OST recipients. Achieving a sustained virological response for 12 consecutive weeks after treatment cessation (SVR-12) was associated with improvement of PROs in OST recipients treated with IFN/RBV-free regimens. In contrast, OST recipients who achieved SVR-12 with IFN+RBV+SOF did not have consistent PRO gains after the SVR-12. Receiving IFN-free regimens leads to PRO improvement during treatment and after the SVR-12, regardless of OST status. HCV-infected subjects receiving OST did not experience similar PRO improvements with IFN-containing therapy, suggesting that IFN-based therapy may be less suitable for this vulnerable population.
Malogiannis, I.A.; Arntz, A.; Spyropoulou, A.; Tsartsara, E.; Aggeli, A.; Karveli, S.; Vlavianou, M.; Pehlivanidis, A.; Papadimitriou, G.N.; Zervas, I.
Background and objectives: This study tested the effectiveness of schema therapy (ST) for patients with chronic depression. Methods: Twelve patients with a diagnosis of chronic depression participated. The treatment protocol consisted of 60 sessions, with the first 55 sessions offered weekly and the
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....
Plumbe, Lee; Peters, Susan; Bennett, Sally; Vicenzino, Bill; Coppieters, Michel W.
This is the protocol for a review and there is no abstract. The objectives are as follows: To examine the efficacy of mirror therapy, graded motor imagery, and virtual illusion for improving pain and function levels in chronic pain states, including, but not limited to, chronic regional pain
Evans, Christopher J.; Cahill, Catherine M.
Opioid drugs are potent modulators of many physiological and psychological processes. When given acutely, they can elicit the signature responses of euphoria and analgesia that societies have coveted for centuries. Repeated, or chronic, use of opioids induces adaptive or allostatic changes that modify neuronal circuitry and create an altered normality — the “drug-dependent” state. This state, at least that exhibited by those maintained continuously on long-acting opioid drugs such as methadon...
Martin, Caren McHenry; Forrester, Charles Samuel
Pain is a common complaint in the elderly, and opioids are useful agents for management of both acute and chronic pain. Opioids are known to cause a variety of adverse effects, and these adverse effects can be particularly problematic for the frail elderly patient and may limit their use. As a result, this can lead to undertreatment of pain and poor patient outcome. Understanding, anticipating, and managing opioid side effects is an important component of care for the elderly patient.
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.
Kim, Young; Cortez, Alexander R; Wima, Koffi; Dhar, Vikrom K; Athota, Krishna P; Schrager, Jason J; Pritts, Timothy A; Edwards, Michael J; Shah, Shimul A
Preoperative exposure to narcotics has recently been associated with poor outcomes after elective major surgery, but little is known as to how preoperative opioid use impacts outcomes after common, emergency general surgical procedures (EGS). A high-volume, single-center analysis was performed on patients who underwent EGS from 2012 to 2013. EGS was defined as the seven emergent operations that account for 80% of the national burden. Preoperative opioid use was defined as having an active opioid prescription within 7 days prior to surgery. Chronic opioid use was defined as having an opioid prescription concurrent with 90 days after discharge. A total of 377 patients underwent EGS during the study period. Preoperative opioid use was present in 84 patients (22.3%). Preoperative opioid users had longer hospital LOS (10.5 vs 6 days), higher costs of care ($25,331 vs $11,454), and higher 30-day readmission rates (22.6 vs 8.2%) compared with opioid-naïve patients (p preoperative opioid use was predictive of LOS (RR 1.19 [1.01-1.41]) and 30-day hospital readmission (OR 2.69 [1.25-5.75]) (p Preoperative opioid users required more narcotic refills compared with opioid-naïve patients (5 vs 0 refills, p preoperative opioid users (p Preoperative opioid use is associated with greater resource utilization after emergency general surgery, as well as vastly different postoperative opioid prescription patterns. These findings may help to inform the impact of preoperative opioid use on patient care, and its implications on hospital and societal cost.
J.F. Bergmann (Jilling)
textabstractChronic hepatitis C infection is a major health problem and a leading cause of chronic liver disease. The hepatitis C virus was discovered in 1989 (1, 2). The virus is a small, enveloped, single-stranded, positive sense RNA virus and is a member of the hepacivirus genus in the family
Madden, Lynn; Bojko, Martha J; Farnum, Scott; Mazhnaya, Alyona; Fomenko, Tatiana; Marcus, Ruthanne; Barry, Declan; Ivanchuk, Irina; Kolomiets, Viktor; Filippovych, Sergey; Dvoryak, Sergey; Altice, Frederick L
Opioid agonist therapies (OAT) like methadone and buprenorphine maintenance treatment remain markedly under-scaled in Ukraine despite adequate funding. Clinicians and administrators were assembled as part of an implementation science strategy to scale-up OAT using the Network for Improvement of Addiction Treatment (NIATx) approach. Nominal Group Technique (NGT), a key ingredient of the NIATx toolkit, was directed by three trained coaches within a learning collaborative of 18 OAT clinicians and administrators to identify barriers to increase OAT capacity at the regional "oblast" level, develop solutions, and prioritize local change projects. NGT findings were supplemented from detailed notes collected during the NGT discussion. The top three identified barriers included: (1) Strict regulations and inflexible policies dictating distribution and dispensing of OAT; (2) No systematic approach to assessing OAT needs on regional or local level; and (3) Limited funding and financing mechanisms combined with a lack of local/regional control over funding for OAT treatment services. NGT provides a rapid strategy for individuals at multiple levels to work collaboratively to identify and address structural barriers to OAT scale-up. This technique creates a transparent process to address and prioritize complex issues. Targeting these priorities allowed leaders at the regional and national level to advocate collectively for approaches to minimize obstacles and create policies to improve OAT services. Copyright © 2017 Elsevier B.V. All rights reserved.
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
Mozurkewich, Ellen L; Rayburn, William F
Buprenorphine and methadone are opioid-receptor agonists used as opioid substitution therapy during pregnancy to limit exposure of the fetus to cycles of opioid withdrawal and reduce the risk of infectious comorbidities of illicit opioid use. As part of a comprehensive care plan, such therapy may result in improved access to prenatal care, reduced illicit drug use, reduced exposure to infections associated with intravenous drug use, and improved maternal nutrition and infant birth weight. This article describes differences in patient selection between the two drugs, their relative safety during pregnancy, and changes in daily doses as a guide for prescribing clinicians. Copyright © 2014 Elsevier Inc. All rights reserved.
Lenehan, Patrick John; Schramm, Craig M; Collins, Melanie Sue
Chronic azithromycin therapy is recommended for CF patients with persistent Pseudomonas aeruginosa colonization. Other macrolide antibiotics have been reported to cause QT prolongation, but cardiac effects of azithromycin have not been studied in pediatric populations. We analyzed changes in QTc interval after starting chronic azithromycin in a pediatric CF population. Adolescent males showed increased QTc intervals after initiation of therapy. Given the possible effects of azithromycin on the QTc interval, particularly in patients predisposed to cardiac events, we suggest that the QTc interval of CF patients should be monitored throughout the course of chronic azithromycin. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
Lazarev, V N; Govorun, V M; Aleksandrova, N M; Lopukhin, Iu M
Gene therapy of chronic infectious diseases of urogenital tract represents a new perspective field in the modern biological and medical sciences. In the review discuss one of the new directions in gene therapy of urogenital infections caused by Mycoplasma: inhibition of mycoplasmal infection after administration of recombinant plasmid vectors, expressed the genes of cytotoxic peptides.
Geraets, J.J.; Goossens, M.E.J.B.; Groot, I.J.M. de; Bruijn, C.P. de; Bie, R.A. de; Dinant, G.J.; Heijden, G.W. van der; Heuvel, W.J.A. van den
An operant behavioural and time-contingent graded exercise therapy program was developed to improve functional ability irrespective of pain experience in patients with chronic shoulder complaints. The clinical effectiveness of graded exercise therapy compared to usual care was evaluated in a
Full Text Available BACKGROUND: Current evidence does not clearly support the provision of nocturnal oxygen therapy in patients with chronic obstructive pulmonary disease (COPD who desaturate during sleep but who would not otherwise qualify for long-term oxygen therapy (LTOT.
Yarborough, Bobbi Jo H; Stumbo, Scott P; Janoff, Shannon L; Yarborough, Micah T; McCarty, Dennis; Chilcoat, Howard D; Coplan, Paul M; Green, Carla A
Opioid abuse and misuse are significant public health issues. The CDC estimated 72% of pharmaceutical-related overdose deaths in the US in 2012 involved opioids. While studies of opioid overdoses have identified sociodemographic characteristics, agents used, administration routes, and medication sources associated with overdoses, we know less about the context and life circumstances of the people who experience these events. We analyzed interviews (n=87) with survivors of opioid overdoses or family members of decedents. Individuals experiencing overdoses were members of a large integrated health system. Using ICD codes for opioid overdoses and poisonings, we identified participants from five purposefully derived pools of health-plan members who had: 1) prescriptions for OxyContin(®) or single-ingredient sustained-release oxycodone, 2) oxycodone single-ingredient immediate release, 3) other long-acting opioids, 4) other short-acting opioids, or 5) no active opioid prescriptions. Individuals who experienced opioid overdoses abused and misused multiple medications/drugs; experienced dose-related miscommunications or medication-taking errors; had mental health and/or substance use conditions; reported chronic pain; or had unstable resources or family/social support. Many had combinations of these risks. Most events involved polysubstance use, often including benzodiazepines. Accidental overdoses were commonly the result of abuse or misuse, some in response to inadequately treated chronic pain or, less commonly, medication-related mistakes. Suicide attempts were frequently triggered by consecutive negative life events. To identify people at greater risk of opioid overdose, efforts should focus on screening for prescribed and illicit polysubstance use, impaired cognition, and changes in life circumstances, psychosocial risks/supports, and pain control. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Wojcikowski, Ken; Vigar, Vanessa J; Oliver, Christopher J
Context • The mechanisms of chronic pain involve complex neuroplastic changes at all 3 orders of neurons involved in the transmission of pain as well as changes in the descending inhibitory pathway. Although traditional pharmaceutical therapies have some efficacy, substantial scope exists for a new model of individualized therapy, tailored to the specific response of each patient. Because changes occur at all levels of the pain pathway, successful treatment may require a combination of therapies with different mechanisms of action. Objective • The research team intended to examine the potential changes within the peripheral nervous system (PNS) and central nervous system (CNS) of patients with chronic pain and to propose a model of chronic pain treatment involving multimodal, complementary therapies for individualized treatment targeting multiple sites along the pain pathway. Design • The research team performed a review of the literature in the field. The study took place in the School of Health and Human Sciences at Southern Cross University (Lismore, New South Wales, Australia). Interventions • A growing body of evidence supports the use of a variety of complementary therapies to treat chronic pain, including curcumin, capsaicin, vitamin D, omega-3 fatty acids, lipoic acid, acupuncture, yoga, meditation, and mindfulness meditation. These therapies vary with respect to the mechanisms by which they act and the potential areas of effect along the pain pathway. Results • The literature review showed a number of complementary therapies may be efficacious in reducing chronic pain and/or the need for analgesics, which may offer a reduced adverse effect profile. These therapies include curcumin, capsaicin, vitamin D, omega-3 fatty acids, lipoic acid, acupuncture, yoga, meditation, and mindfulness meditation. Response rates to treatment are likely to vary between people and within therapies. Conclusions • The available evidence suggests that efficacious
Freburger, Janet K; Carey, Timothy S; Holmes, George M
There are limited population-based studies of determinants of physical therapy use for chronic low back pain (LBP) and of the types of treatments received by individuals who see a physical therapist. The purposes of this study were: (1) to identify determinants of physical therapy use for chronic LBP, (2) to describe physical therapy treatments for chronic LBP, and (3) to compare use of treatments with current best evidence on care for this condition. This study was a cross-sectional, population-based telephone survey of North Carolinians. Five hundred eighty-eight individuals with chronic LBP who had sought care in the previous year were surveyed on their health and health care use. Bivariate and multivariable analyses were conducted to identify predisposing, enabling, and need characteristics associated with physical therapy use. Descriptive analyses were conducted to determine the use of physical treatments for individuals who saw a physical therapist. Use of treatments was compared with evidence from systematic reviews. Of our sample, 29.7% had seen a physical therapist in the previous year, with a mean of 15.6 visits. In multivariable analyses, receiving workers' compensation, seeing physician specialists, and higher Medical Outcomes Study 12-Item Short-Form Health Survey questionnaire (SF-12) physical component scores were positively associated with physical therapy use. Having no health insurance was negatively associated with physical therapy use. Exercise was the most frequent treatment received (75% of sample), and traction was the least frequent treatment received (7%). Some effective treatments were underutilized, whereas some ineffective treatments were overutilized. Only one state was examined, and findings were based on patient report. Fewer than one third of individuals with chronic LBP saw a physical therapist. Health-related and non-health-related factors were associated with physical therapy use. Individuals who saw a physical therapist did not
... include codeine, morphine and oxycodone. If you take opioids during pregnancy, they can cause serious problems for your baby, like premature birth and drug withdrawal called NAS. Even if you use an opioid ...
... who take them as prescribed by a doctor. Opioid withdrawal can cause: restlessness muscle and bone pain sleep ... View Online Download PDF Dramatic Increases in Maternal Opioid Use ... in a drug withdrawal syndrome in newborns called neonatal abstinence syndrome (NAS). ...
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...
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...
Fanelli, Guido; Fanelli, Andrea
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.
Fanelli, Guido; Fanelli, Andrea
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. PMID:26229442
Koo, Charles C.; Lin, Ray S.; Wang, Tyng-Guey; Tsauo, Jau-Yih; Yang, Pan-Chyr; Yen, Chen-Tung; Biswal, Sandip
As chronic pain affects 115 million people and costs $600B annually in the US alone, effective noninvasive nonpharmacological remedies are desirable. The purpose of this study was to determine the efficacy and the generalisability of Noxipoint therapy (NT), a novel electrotherapy characterised by site-specific stimulation, intensity-and-submodality-specific settings and a immobilization period, for chronic neck and shoulder pain. Ninety-seven heavily pretreated severe chronic neck/shoulder pain patients were recruited; 34 and 44 patients were randomly allocated to different treatment arms in two patient-and-assessor-blinded, randomised controlled studies. The participants received NT or conventional physical therapy including transcutaneous electrical nerve stimulation (PT-TENS) for three to six 90-minute sessions. In Study One, NT improved chronic pain (−89.6%, Brief Pain Inventory, p < 0.0001, 95% confidence interval), function (+77.4%, range of motion) and quality of life (+88.1%) at follow-up (from 4 weeks to 5 months), whereas PT-TENS resulted in no significant changes in these parameters. Study Two demonstrated similar advantages of NT over PT-TENS and the generalisability of NT. NT-like treatments in a randomised rat study showed a similar reduction in chronic hypersensitivity (−81%, p < 0.01) compared with sham treatments. NT substantially reduces chronic neck and shoulder pain, restores function, and improves quality of life in a sustained manner. PMID:26552835
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
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.
Yu, Li; Xu, Xianghuai; Hang, Jingqing; Cheng, Kewen; Jin, Xiaoyan; Chen, Qiang; Lv, Hanjing; Qiu, Zhongmin
Empirical three-step therapy has been proved in just one hospital. This study aimed to demonstrate applicability of the sequential empirical three-step therapy for chronic cough in different clinical settings. Sequential empirical three-step therapy was given to patients with chronic cough in one tertiary and three secondary care respiratory clinics. Recruiters were initially treated with methoxyphenamine compound as the first-step therapy, followed by corticosteroids as the second-step therapy and the combination of a proton-pump inhibitor and a prokinetic agent as the third-step therapy. The efficacy of the therapy was verified according to the changes in cough symptom score between pre- and post-treatment, and compared among the different clinics. In total 155 patients in one tertiary clinic and 193 patients in secondary care clinics were recruited. The total dropout ratio is significantly higher in the secondary care clinics than that in the tertiary clinic (9.3% versus 3.2%, p = 0.023). The therapeutic success rate for cough was 38.7% at first-step therapy, 32.3% at second-step therapy and 20.0% at third-step therapy in the tertiary clinic, and comparable to corresponding 49.7%, 31.1% and 4.1% in secondary care clinics. Furthermore, the overall cough resolution rate was not significantly different (91.0% versus 85.0%, p = 0.091). However, the efficacy of the third-step therapy is much higher (20.0% versus 4.1%, p = 0.001) in the tertiary clinic than in the secondary care clinics. Sequential empirical three-step therapy is universally efficacious and useful for management of chronic cough in different clinical settings.
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.
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 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
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.
R. Roomer (Robert)
textabstractThe hepatitis C virus was first discovered in 1989 as the major cause of chronic non-A non-B hepatitis. The hepatitis C virus is a single stranded RNA virus that belongs to the family of flaviviruses. The primary target of the hepatitis C virus are hepatocytes where viral
Ozsoy, Riza C.; van Leuven, Sander I.; Kastelein, John J. P.; Arisz, Lambertus; Koopman, Marion G.
PURPOSE OF REVIEW: Dyslipidemia is a prevalent condition in patients with chronic renal disease, but is often left untreated. Statin treatment constitutes an effective way to improve lipid abnormalities. This review summarizes present studies on dyslipidemia and its treatment in patients with
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.
Sprengers, D.; Janssen, H. L. A.
Hepatitis B virus (HBV) is one of the most prevalent viral pathogens of man with around 350 million chronically infected patients. It has been postulated that in persistently infected individuals the HBV-specific immune response is too weak to eliminate HBV from all infected hepatocytes, but
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.
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.)
Deroanne, Adrien; Deroanne, Didier; Florkin, Marc; Kaux, Jean-François
Background and aim: radial shock wave therapy (RSWT) is a relatively new way to treat chronic tendinopathies, such as lateral epicondylitis. However, very few studies have been realized on this subject, and the results are very divergent. We aimed to observe the impact of this technique on chronic lateral elbow pain. Method: fifteen subjects who had a lateral epicondylitis for at least 3 months were included in the study. Two groups were formed: experimental (10 subjects) who received 6 s...
Israel, C W; Ekosso-Ejangue, L; Sheta, M-K
Cardiac pacemakers, implantable cardioverter defibrillators (ICD) and systems for cardiac resynchronization therapy (CRT) represent an important component of heart failure therapy. Pacemakers only play a role in bradycardia-associated heart failure and require optimal programming to prevent ventricular desynchronization. Primary prophylactic ICD implantation is indicated in patients with a left ventricular ejection fraction of ≤ 35 %, clinical stages NYHA II-III and a life expectancy > 1 year. The CRT is indicated in patients with a left bundle branch block but only in individual cases for other QRS morphologies of heart failure should always include remote monitoring to detect events early and to implement treatment accordingly. New developments include quadripolar left ventricular leads and pacing from multiple sites simultaneously thus enabling better resynchronization. Stimulation for modulation of cardiac contractility and the autonomous nervous system are currently being clinically tested. The optimal utilization of device therapy improves the course of heart failure and prevents cardiac decompensation and fatalities.
Jensen, Donald M; Ascione, Antonio
The development of new antiviral therapies in the treatment of hepatitis C virus (HCV) is reviewed, including a discussion of the potential advances that this treatment will bring. Data from new molecules in Phase I and II clinical trials, specifically polymerase and protease inhibitors, will be discussed. The potential for resistance has been reported when these have been used as monotherapy. However, their use in combination with pegylated interferon, particularly in the presence of ribavirin, has resulted in significant improvements in antiviral activity. Preliminary studies have confirmed that the new molecules are well tolerated and further clinical studies are underway to evaluate their efficacy. Nevertheless, because of its critical role at all stages of therapy, pegylated interferon is likely to remain the cornerstone of HCV therapy.
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.
Kirkman, Danielle L.; Edwards, David G.; Lennon-Edwards, Shannon
Physical activity levels are low in patients with chronic kidney disease (CKD). Evidence indicates that a sedentary lifestyle contributes to increased morbidity and mortality risk; thus, increasing physical activity is an undeniable aspect of a healthy lifestyle. Despite the myriad of health benefits associated with exercise, as well as clinical guidelines in its favor, exercise is still not prescribed as part of routine care in the CKD patient population. This article briefly discusses the b...
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...
Gerdesmeyer, Ludger; Mittermayr, Rainer; Fuerst, Martin; Al Muderis, Munjed; Thiele, Richard; Saxena, Amol; Gollwitzer, Hans
Chronic Achilles tendinopathy has been described as the most common overuse injury in sports medicine. Several treatment modalities such as activity modification, heel lifts, arch supports, stretching exercises, nonsteroidal anti-inflammatories, and eccentric loading are known as standard treatment mostly without proven evidence. After failed conservative therapy, invasive treatment may be considered. Extracorporeal shock wave therapy (ESWT) has been successfully used in soft-tissue pathologies like lateral epicondylitis, plantar fasciitis, tendinopathy of the shoulder and also in bone and skin disorders. Conclusive evidence recommending ESWT as a treatment for Achilles tendinopathy is still lacking. In plantar fasciitis as well as in calcific shoulder tendinopathy shock wave therapy is recently the best evaluated treatment option. This article analysis the evidence based literature of ESWT in chronic Achilles tendinopathy. Recently published data have shown the efficacy of focused and radial extracorporeal shock wave therapy. Copyright © 2015 IJS Publishing Group Limited. All rights reserved.
Shen, K F; Crain, S M
In a previous study we demonstrated that injection (i.p.) of low doses of GM1 ganglioside in mice rapidly attenuates morphine's analgesic effects. This result is consonant with our electrophysiologic studies in nociceptive types of dorsal root ganglion (DRG) neurons in culture, which showed that exogenous GM1 rapidly increased the efficacy of excitatory (Gs-coupled) opioid receptor functions. By contrast, treatment of DRG neurons with the non-toxic B-subunit of cholera toxin (CTX-B) which binds selectively to GM1, blocked the excitatory, but not inhibitory, effects of morphine and other bimodally-acting opioid agonists, thereby resulting in a net increase in inhibitory opioid potency. The present study provides more direct evidence that endogenous GM1 plays a physiologic role in regulating excitatory opioid receptor functions in vivo by demonstrating that cotreatment with remarkably low doses of CTX-B (10 ng/kg, s.c.) selectively blocks hyperalgesic effects elicited by morphine or by a kappa opioid agonist, thereby unmasking potent opioid analgesia. These results are comparable to the effects of cotreatment of mice with morphine plus an ultra-low dose of the opioid antagonist, naltrexone (NTX) which blocks opioid-induced hyperalgesic effects, unmasking potent opioid analgesia. Low-dose NTX selectively blocks excitatory opioid receptors at their recognition site, whereas CTX-B binds to, and interferes with, a putative allosteric GM1 regulatory site on excitatory opioid receptors. Furthermore, chronic cotreatment of mice with morphine plus CTX-B attenuates development of opioid tolerance and physical dependence, as previously shown to occur during cotreatment with low-dose NTX.
Full Text Available Ultra-low-dose opioid antagonists enhance opioid analgesia and reduce analgesic tolerance and dependence by preventing a G protein coupling switch (Gi/o to Gs by the mu opioid receptor (MOR, although the binding site of such ultra-low-dose opioid antagonists was previously unknown. Here we show that with approximately 200-fold higher affinity than for the mu opioid receptor, naloxone binds a pentapeptide segment of the scaffolding protein filamin A, known to interact with the mu opioid receptor, to disrupt its chronic opioid-induced Gs coupling. Naloxone binding to filamin A is demonstrated by the absence of [(3H]-and FITC-naloxone binding in the melanoma M2 cell line that does not contain filamin or MOR, contrasting with strong [(3H]naloxone binding to its filamin A-transfected subclone A7 or to immunopurified filamin A. Naloxone binding to A7 cells was displaced by naltrexone but not by morphine, indicating a target distinct from opioid receptors and perhaps unique to naloxone and its analogs. The intracellular location of this binding site was confirmed by FITC-NLX binding in intact A7 cells. Overlapping peptide fragments from c-terminal filamin A revealed filamin A(2561-2565 as the binding site, and an alanine scan of this pentapeptide revealed an essential mid-point lysine. Finally, in organotypic striatal slice cultures, peptide fragments containing filamin A(2561-2565 abolished the prevention by 10 pM naloxone of both the chronic morphine-induced mu opioid receptor-Gs coupling and the downstream cAMP excitatory signal. These results establish filamin A as the target for ultra-low-dose opioid antagonists previously shown to enhance opioid analgesia and to prevent opioid tolerance and dependence.
Wang, Hoau-Yan; Frankfurt, Maya; Burns, Lindsay H.
Ultra-low-dose opioid antagonists enhance opioid analgesia and reduce analgesic tolerance and dependence by preventing a G protein coupling switch (Gi/o to Gs) by the mu opioid receptor (MOR), although the binding site of such ultra-low-dose opioid antagonists was previously unknown. Here we show that with approximately 200-fold higher affinity than for the mu opioid receptor, naloxone binds a pentapeptide segment of the scaffolding protein filamin A, known to interact with the mu opioid receptor, to disrupt its chronic opioid-induced Gs coupling. Naloxone binding to filamin A is demonstrated by the absence of [3H]-and FITC-naloxone binding in the melanoma M2 cell line that does not contain filamin or MOR, contrasting with strong [3H]naloxone binding to its filamin A-transfected subclone A7 or to immunopurified filamin A. Naloxone binding to A7 cells was displaced by naltrexone but not by morphine, indicating a target distinct from opioid receptors and perhaps unique to naloxone and its analogs. The intracellular location of this binding site was confirmed by FITC-NLX binding in intact A7 cells. Overlapping peptide fragments from c-terminal filamin A revealed filamin A2561-2565 as the binding site, and an alanine scan of this pentapeptide revealed an essential mid-point lysine. Finally, in organotypic striatal slice cultures, peptide fragments containing filamin A2561-2565 abolished the prevention by 10 pM naloxone of both the chronic morphine-induced mu opioid receptor–Gs coupling and the downstream cAMP excitatory signal. These results establish filamin A as the target for ultra-low-dose opioid antagonists previously shown to enhance opioid analgesia and to prevent opioid tolerance and dependence. PMID:18253501
Wang, Hoau-Yan; Frankfurt, Maya; Burns, Lindsay H
Ultra-low-dose opioid antagonists enhance opioid analgesia and reduce analgesic tolerance and dependence by preventing a G protein coupling switch (Gi/o to Gs) by the mu opioid receptor (MOR), although the binding site of such ultra-low-dose opioid antagonists was previously unknown. Here we show that with approximately 200-fold higher affinity than for the mu opioid receptor, naloxone binds a pentapeptide segment of the scaffolding protein filamin A, known to interact with the mu opioid receptor, to disrupt its chronic opioid-induced Gs coupling. Naloxone binding to filamin A is demonstrated by the absence of [(3)H]-and FITC-naloxone binding in the melanoma M2 cell line that does not contain filamin or MOR, contrasting with strong [(3)H]naloxone binding to its filamin A-transfected subclone A7 or to immunopurified filamin A. Naloxone binding to A7 cells was displaced by naltrexone but not by morphine, indicating a target distinct from opioid receptors and perhaps unique to naloxone and its analogs. The intracellular location of this binding site was confirmed by FITC-NLX binding in intact A7 cells. Overlapping peptide fragments from c-terminal filamin A revealed filamin A(2561-2565) as the binding site, and an alanine scan of this pentapeptide revealed an essential mid-point lysine. Finally, in organotypic striatal slice cultures, peptide fragments containing filamin A(2561-2565) abolished the prevention by 10 pM naloxone of both the chronic morphine-induced mu opioid receptor-Gs coupling and the downstream cAMP excitatory signal. These results establish filamin A as the target for ultra-low-dose opioid antagonists previously shown to enhance opioid analgesia and to prevent opioid tolerance and dependence.
Hommel, Kristine; Rasmussen, Soren; Kamper, Anne-Lise
Background. The incidence of chronic renal replacement therapy (RRT) varies markedly between Danish nephrology centres. The aim of the present study was to establish if there is regional and social variation in the incidence of chronic RRT in Denmark when analysed according to patient residence...... origin was obtained from Statistics Denmark. Rates of incident RRT patients were standardized for regional differences of sex and age as well as income, educational status and ethnic origin. Poisson regression was used when comparing rates. Results. Age- and sex-standardized incident chronic RRT rates...
Even with the remarkable results of cardiac resynchronization therapy (CRT) in the large randomized trials, approximately 30-40% of the patients failed to improve after CRT when the established selection criteria are used, highlighting the need for improvement of the current criteria. In addition,
obtained before the study commenced, while individual patient's informed consent was duly obtained before their participation. Infrared therapy was applied to subjects' low back region in prone lying, after being tested for thermal sensation using test tubes containing cold and warm water respectively. The patients' low back.
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 ac...
Kelly, Catherine G; Cudney, Shirley; Weinert, Clarann
To investigate the spontaneous use of creative arts as a complementary therapy by rural women in the Western United States who are coping with chronic illness. Women to Women Project was an 11-week research-based computer intervention that provided health education and support to rural women with chronic illnesses in an effort to help them better adapt to living with chronic conditions. Through the use of text queries, messages posted to an unprompted, online support and health education forum were examined for references to the spontaneous use of creative arts and their influence as a complementary therapy for dealing with chronic illness. In three identified themes-coping with pain, relaxation/quality of life, and giving back to others-participants strongly suggested that creative activity was an important strategy for coping with chronic illness and that it contributed to reduced pain and increased overall well-being, regardless of whether it was the expression of a previously learned skill or a practice established after the onset of chronic illness. The use of creative arts and developing art-making interventions could significantly benefit rural individuals coping with chronic illness. Discovering methods of implementing creative arts interventions in rural populations warrants further study.
DeAngelo, D J
The outcomes for patients with chronic myeloid leukemia have improved dramatically with the development and availability of BCR–ABL1 tyrosine kinase inhibitors (TKIs) over the past decade. TKI therapy has a superior safety profile compared with the previous standard of care, interferon-α, and most adverse events (AEs) observed with front-line and second-line TKI treatment are managed with supportive care. However, some patients are intolerant to TKI therapy and experience AEs that cannot be m...
The degree of opioid responsiveness in patients with different pain syndromes associated with advanced head and neck cancer was studied with the aid of various indices that have proved to be easy to compare and capable of eliciting individual profiles of opioid responsiveness in cancer patients with pain. Thirty-seven patients requiring opioid therapy for more than 6 weeks were reviewed. The opioid escalation index (OEI) was lower in aged patients, albeit not significantly. Significant differences in OEI were found among patients belonging to the different categories of responses proposed. Although higher doses were needed than reported in the general population, pain was considered acceptable and most patients were classified as partially responsive. Neuropathic pain was associated with higher OEIs. The indices applied will be useful in clinical research to demonstrate individual profiles of opioid responsiveness, from cases of easy and immediate pain control to unresponsiveness to opioid treatment, which can be difficult to evaluate in the clinical setting.
Morisawa, Norihiko; Koshima, Yohei; Satoh, Jun-Ichi; Maruyama, Yukio; Kuriyama, Satoru; Yokoo, Takashi; Amemiya, Morimasa
Combination therapy with Daclatasvir (DCV) plus Asunaprevir (ASV) has been proven effective in patients with chronic hepatitis C virus (HCV) infection. However, little is known as to the effect of this therapy in patients with reduced renal function. Focusing on CKD patients whose renal function has declined, the present trial addresses the efficacy and safety of this combination therapy in CKD patients with reduced estimated glomerular filtration rate (eGFR). The study design is a single-center, retrospective longitudinal observational study enrolling 106 patients with (n = 29) or without (n = 77) CKD. After the treatment with combined DCV with ASV for chronic HCV genotype 1b, patients were followed for a total of 48 weeks and the comparison was made in clinical parameters between the two groups. (1) The majority of patients in both groups achieved sustained virological response at 24 weeks (90.8 % in the non-CKD group, and 93.1 % in the CKD). (2)The reduction rate in HCV-RNA levels 2 weeks after commencing the treatment was faster in the CKD group than that in the non-CKD group (81.8 vs. 79.2 %, p < 0.01). (3) Three patients in the CKD group and 6 patients in the non-CKD group withdrew from the treatment because of the adverse events. Combination therapy with DCV plus ASV for chronic HCV genotype 1b infection is useful and tolerable, not only in patients with normal eGFR, but also in those with CKD with declined eGFR. Viral eradication at an early phase of the treatment appears to be faster in CKD patients.
Ueda, Yoshihide; Kaido, Toshimi; Ito, Takashi; Ogawa, Kohei; Yoshizawa, Atsushi; Fujimoto, Yasuhiro; Mori, Akira; Miyagawa-Hayashino, Aya; Haga, Hironori; Marusawa, Hiroyuki; Chiba, Tsutomu; Uemoto, Shinji
Chronic rejection (CR) has been reported to be associated with antiviral therapy for recurrent hepatitis C in liver transplant (LT) recipients. The aims of this study were to clarify the details of antiviral therapy-associated CR after living-donor liver transplantation (LDLT) and to identify the factors associated with CR. A retrospective chart review was performed on 125 recipients who had received antiviral therapy for recurrent hepatitis C after LDLT between January 2001 and September 2012. The characteristics of patients who developed CR during or within 6 months after antiviral therapy were compared with those of 76 patients who did not develop CR despite receiving antiviral therapy for more than 1 year. Seven of 125 (6%) patients developed CR during or within 6 months after the end of antiviral therapy. CR was diagnosed after a median (range) of 9 (1-16) months of antiviral therapy. In five patients, rejection progressed rapidly and resulted in death within 3 months after diagnosis. Analysis revealed two significant factors associated with CR: reduction of the immunosuppressant dose during antiviral therapy and a low fibrosis score as the indication for antiviral therapy. CR developed in association with antiviral therapy for recurrent hepatitis C after LDLT. This complication may be prevented by ensuring that the immunosuppressant dose is not reduced during antiviral therapy.
Crain, S M; Shen, K F
Electrophysiologic studies of opioid effects on nociceptive types of dorsal root ganglion (DRG) neurons in organotypic cultures have shown that morphine and most mu, delta, and kappa opioid agonists can elicit bimodal excitatory as well as inhibitory modulation of the action potential duration (APD) of these cells. Excitatory opioid effects have been shown to be mediated by opioid receptors that are coupled via Gs to cyclic AMP-dependent ionic conductances that prolong the APD, whereas inhibitory opioid effects are mediated by opioid receptors coupled via Gi/Go to ionic conductances that shorten the APD. Selective blockade of excitatory opioid receptor functions by low (ca. pM) concentrations of naloxone, naltrexone, etorphine and other specific agents markedly increases the inhibitory potency of morphine or other bimodally acting agonists and attenuates development of tolerance/dependence. These in vitro studies have been confirmed by tail-flick assays showing that acute co-treatment of mice with morphine plus ultra-low-dose naltrexone or etorphine remarkably enhances the antinociceptive potency of morphine whereas chronic co-treatment attenuates development of tolerance and naloxone-precipitated withdrawal-jumping symptoms.
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
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.
Maschio, G; Oldrizzi, L
Controversies still exist about the use and the effects of low protein diets in chronic renal failure. The contrasting - sometimes opposite - results published over the last 30 years in several studies can be read and explained by a series of errors included in those studies. The new Comedy of Errors starts from the misinterpretation of experimental studies, the lack of appropriacy of clinical trials' design; it continues with neglecting the role of patients' compliance as well as of other clinical findings, here included the role of blood pressure. Finally pitfalls in the intrepretation of the results of clinical trials and meta-analyses were identified.
M. T. Baedilova; S. E. Lebed'kova; O. Yu. Trusova; V. V. Sumenko; T. N. Ignatova
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...
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.
Zhdanov, K V; Gusev, D A; Kozlov, K V; Shishkin, M K; Sukachev, V S; Shakhmanov, D M; Zhabrov, S S
In order to evaluate effectiveness and safety of antiviral therapy schemes examined and treated 191 patients with chronic bepatitis C were assigned standard interferon and ribavirin, pegslated interferon and ribavirin, the total duration of the course coput 24-48 weeks. Based on clinical and laboratory parameters evaluated the safety of antiviral therapy. Formation of sustainable viral response, depending on the genotype observed, was given at 58,9-70%.of patients. In case of insufficient. antiviral therapy was prescribed a second course that will improve the effectiveness of treatment to 90-95%. Correction of adverse events was held lower dosages of interferon and/or ribavirin.
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.
Moroz L.V. Moroz L.V.
Molecular and genetic analysis of IL28V (rs12979860 gene polymorphism, located at a distance of 3 thousand nucleotide pairs from IL28V gene, using the polymerase chain reaction allows to predict the success of combination antiviral therapy, and the presence of C/C genotype can be a predictor of sustained virological response in patients chronic hepatitis C.
Nijhof, S.L.; Priesterbach, L.P.; Uiterwaal, C.S.; Bleijenberg, G.; Kimpen, J.L.L.; Putte, E.M. van de
OBJECTIVE: Cognitive behavioral therapy (CBT) is known to be an effective treatment of adolescents with chronic fatigue syndrome (CFS), but its availability is limited. Fatigue in Teenagers on the Internet (FITNET), an Internet-based CBT program for adolescents with CFS, has been developed as an
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.
de Man, R. A.; Schalm, S. W.; Heijtink, R. A.; Berk, L.; den Ouden, J.; ten Kate, F. J.; Chamuleau, R. A.; Reesink, H. W.
For patients with chronic hepatitis B e (HBe)-positive hepatitis, long-term results of pilot studies with lymphoblastoid interferon-alpha, acyclovir, or a combination, and of a randomized controlled trial of interferon/desciclovir combination therapy are presented. HBe seroconversion was observed in
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
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
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.
Clark, Edward; Kumar, Anand; Langote, Amit; Lapinsky, Stephen; Dodek, Peter; Kramer, Andreas; Wood, Gordon; Bagshaw, Sean M; Wood, Ken; Gurka, Dave; Sood, Manish M
To describe the clinical characteristics and in-hospital mortality of chronic dialysis-dependent end-stage kidney disease patients with septic shock in comparison to septic shock patients not receiving chronic dialysis. Using an international, multicenter database, we conducted a retrospective analysis of data collected from 10,414 patients admitted to the intensive care unit (ICU) with septic shock from 1989 to 2013, of which 800 (7.7 %) were chronic dialysis patients. Data on demographic characteristics, sites of infection, microbial pathogens, antimicrobial usage patterns, and in-hospital mortality were aggregated and compared for chronic dialysis and non-dialysis patients. Multivariate time-varying Cox models with and without propensity score matching were constructed to determine the association between dialysis and in-hospital death. Septic shock secondary to central venous catheter infection, peritonitis, ischemic bowel, and cellulitis was more frequent in chronic dialysis patients. The isolation of resistant organisms (10.7 vs. 7.1 %; p = 0.005) and delays in receiving antimicrobials (6.0 vs. 5.0 h) were more common in chronic dialysis patients than in non-dialysis patients. Delayed appropriate antimicrobial therapy was associated with an increased risk of death in chronic dialysis patients (p septic shock differ from those of similar non-dialysis patients. However, there was no significant difference in mortality between the chronic dialysis and non-dialysis patients with septic shock enrolled in this analysis.
Kirkman, Danielle L; Edwards, David G; Lennon-Edwards, Shannon
Physical activity levels are low in patients with chronic kidney disease (CKD). Evidence indicates that a sedentary lifestyle contributes to increased morbidity and mortality risk; thus, increasing physical activity is an undeniable aspect of a healthy lifestyle. Despite the myriad of health benefits associated with exercise, as well as clinical guidelines in its favor, exercise is still not prescribed as part of routine care in the CKD patient population. This article briefly discusses the benefits of regular exercise implemented across all stages of CKD on independent predictors of survival such as cardiorespiratory fitness, cardiovascular health and protein-energy wasting. Health care providers of the multidisciplinary nephrology team play a pivotal role in the encouragement and implementation of increasing physical activity levels. In order to increase physical activity counseling and enhance healthcare providers' confidence in prescribing exercise for CKD patients, general recommendations for physical activity in these patients are provided.
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
Mattson, Shawn K; Polk, Julia P; Nyirjesy, Paul
Chronic nongonococcal nonchlamydial cervicitis is a condition of unknown etiology. Data about treatment options are limited. Our goal was to review a single center's experience in managing women with chronic NGNCC. We evaluated all encounters at a tertiary care center with ICD-9 code for cervicitis between April 2008 and March 2014. Cases were defined by having two of the following 3 diagnostic criteria: mucopurulent discharge noted by (1) patient or (2) practitioner, and (3) cervical bleeding upon gentle probing. All women had negative nucleic acid amplification testing for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis. Information regarding patient demographics, symptoms, findings, treatment, and outcomes were analyzed. Cure was defined as resolution of patient-specific diagnostic criteria. Sixty-one women were identified. The mean age was 31 years; 73.7% were white, and 59% were nulliparous. The mean duration of symptoms was 25.2 months. Initially, all 61 patients received one of 3 antibiotic treatments. The cure rate after initial antibiotic treatment was 65.6%. Nineteen patients required at least one further treatment. Additional treatments included secondary antibiotics, hormonal treatments, vaginal hydrocortisone, silver nitrate, cryotherapy, and loop excision electrosurgical procedure. Cure rates were as follows: 57.9% with antibiotics, 50% with hormone treatment, 0% with hydrocortisone, 100% with silver nitrate, 0% with cryotherapy, and 100% with loop electrosurgical excisional procedure. Of the initial 61 women, 93.4% were eventually cured. Nongonococcal nonchlamydial cervicitis is a condition that can cause unremitting symptoms. Most patients will respond to antibiotics, although other treatments including surgery may be necessary.