Showing papers by "Ian Gilron published in 2012"

Combination pharmacotherapy for the treatment of neuropathic pain in adults

Abstract: Background Pharmacotherapy remains an important modality for the treatment of neuropathic pain. However, as monotherapy current drugs are associated with limited efficacy and dose-related side effects. Combining two or more different drugs may improve analgesic efficacy and, in some situations, reduce overall side effects (e.g. if synergistic interactions allow for dose reductions of combined drugs). Objectives This review evaluated the efficacy, tolerability and safety of various drug combinations for the treatment of neuropathic pain. Search methods We identified randomised controlled trials (RCTs) of various drug combinations for neuropathic pain from CENTRAL, MEDLINE, EMBASE and handsearches of other reviews and trial registries. The most recent search was performed on 9 April 2012. Selection criteria Double-blind, randomised studies comparing combinations of two or more drugs (systemic or topical) to placebo and/or at least one other comparator for the treatment of neuropathic pain. Data collection and analysis Data extracted from each study included: proportion of participants a) reporting ≥ 30% pain reduction from baseline OR ≥ moderate pain relief OR ≥ moderate global improvement; b) dropping out of the trial due to treatment-emergent adverse effects; c) reporting each specific adverse effect (e.g. sedation, dizziness) of ≥ moderate severity. The primary comparison of interest was between study drug(s) and one or both single-agent comparators. We combined studies if they evaluated the same drug class combination at roughly similar doses and durations of treatment. We used RevMan 5 to analyse data for binary outcomes. Main results We identified 21 eligible studies: four (578 participants) evaluated the combination of an opioid with gabapentin or pregabalin; two (77 participants) evaluated an opioid with a tricyclic antidepressant; one (56 participants) of gabapentin and nortriptyline; one (120 participants) of gabapentin and alpha-lipoic acid, three (90 participants) of fluphenazine with a tricyclic antidepressant; three (90 participants) of an N-methyl-D-aspartate (NMDA) blocker with an agent from a different drug class; five (604 participants) of various topical medications; one (313 participants) of tramadol with acetaminophen; and another one (44 participants) of a cholecystokinin blocker (L-365,260) with morphine. The majority of combinations evaluated to date involve drugs, each of which share some element of central nervous system (CNS) depression (e.g. sedation, cognitive dysfunction). This aspect of side effect overlap between the combined agents was often reflected in similar or higher dropout rates for the combination and may thus substantially limit the utility of such drug combinations. Meta-analysis was possible for only one comparison of only one combination, i.e. gabapentin + opioid versus gabapentin alone. This meta-analysis involving 386 participants from two studies demonstrated modest, yet statistically significant, superiority of a gabapentin + opioid combination over gabapentin alone. However, this combination also produced significantly more frequent side effect-related trial dropouts compared to gabapentin alone. Authors' conclusions Multiple, good-quality studies demonstrate superior efficacy of two-drug combinations. However, the number of available studies for any one specific combination, as well as other study factors (e.g. limited trial size and duration), preclude the recommendation of any one specific drug combination for neuropathic pain. Demonstration of combination benefits by several studies together with reports of widespread clinical polypharmacy for neuropathic pain surely provide a rationale for additional future rigorous evaluations. In order to properly identify specific drug combinations which provide superior efficacy and/or safety, we recommend that future neuropathic pain studies of two-drug combinations include comparisons with placebo and both single-agent components. Given the apparent adverse impact of combining agents with similar adverse effect profiles (e.g. CNS depression), the anticipated development and availability of non-sedating neuropathic pain agents could lead to the identification of more favourable analgesic drug combinations in which side effects are not compounded.

Considerations for improving assay sensitivity in chronic pain clinical trials: IMMPACT recommendations.

Abstract: A number of pharmacologic treatments examined in recent randomized clinical trials (RCTs) have failed to show statistically significant superiority to placebo in conditions in which their efficacy had previously been demonstrated. Assuming the validity of previous evidence of efficacy and the comparability of the patients and outcome measures in these studies, such results may be a consequence of limitations in the ability of these RCTs to demonstrate the benefits of efficacious analgesic treatments vs placebo ("assay sensitivity"). Efforts to improve the assay sensitivity of analgesic trials could reduce the rate of falsely negative trials of efficacious medications and improve the efficiency of analgesic drug development. Therefore, an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials consensus meeting was convened in which the assay sensitivity of chronic pain trials was reviewed and discussed. On the basis of this meeting and subsequent discussions, the authors recommend consideration of a number of patient, study design, study site, and outcome measurement factors that have the potential to affect the assay sensitivity of RCTs of chronic pain treatments. Increased attention to and research on methodological aspects of clinical trials and their relationships with assay sensitivity have the potential to provide the foundation for an evidence-based approach to the design of analgesic clinical trials and expedite the identification of analgesic treatments with improved efficacy and safety.

Adherence to CONSORT harms-reporting recommendations in publications of recent analgesic clinical trials: an ACTTION systematic review.

Abstract: Recommendations for harms (ie, adverse events) reporting in randomized clinical trial publications were presented in a 2004 extension of the Consolidated Standards of Reporting Trials (CONSORT) statement. Our objectives were to assess harms reporting in 3 major pain journals (European Journal of Pain, Journal of Pain, and PAIN®) to determine whether harms reporting improved following publication of the 2004 CONSORT recommendations, and to examine study factors associated with adequacy of harms reporting. A total of 101 randomized, double-blind, noninvasive pharmacologic trials were identified in the 2000-2003 (epoch 1) and 2008-2011 (epoch 2) issues of these journals. Out of 10 reporting recommendations, the mean number fulfilled was 6.08 (SD2.65). Although more harms recommendations were fulfilled in epoch 2 (m(2)=6.49, SD2.66) than in epoch 1 (m(1)=5.39, SD2.52; P=0.04), only the recommendation to report harms per arm was satisfied by >90% of trials in epoch 2, whereas <60% reported withdrawals due to harms. Several trial characteristics (study design, participant type, pain type, frequency of treatment administration, treatment administration method, sponsor, and number of randomized participants) were significantly associated with harms reporting. However, when trial characteristics and epoch were entered into a multiple regression analysis, only trials studying pain patients, those using oral treatments, and industry-sponsored trials were associated with better harms reporting. Despite some improvement in harms reporting, greater improvement is needed to provide informative, consistent reporting of adverse events and safety in analgesic clinical trials.

Chronic pain, healthcare utilization, and quality of life following gastrointestinal surgery

Abstract: Objectives Our aim in this pilot study was to identify potential predictors of chronic post-surgical pain (CPSP) and other outcomes to consider for inclusion in future prospective studies of CPSP following abdominal gastrointestinal surgery.

Chronic pain, healthcare utilization, and quality of life following gastrointestinal surgery Douleur chronique, utilisation des soins de santé et qualité de vie après chirurgie digestive

Abstract: Objectives Our aim in this pilot study was to identify potential predictors of chronic post-surgical pain (CPSP) and other outcomes to consider for inclusion in future prospective studies of CPSP following abdominal gastrointestinal surgery. Methods We followed 76 surgical patients during this prospective single-centre cohort study. Pain characteristics, health-related quality of life (HRQOL), and healthcare utilization were assessed preoperatively, at six weeks postoperatively, and at six months postoperatively. Statistical analyses included descriptive statistics and repeated measures analysis of variance. Results Prior to surgery, 42% of patients reported no pain, 18% reported remote pain, and 33% reported pain at the surgical site. Six months after surgery, 29% of patients with preoperative remote pain and 35% of patients with preoperative pain at the surgical site reported CPSP. Painrelated interference declined from the preoperative to postoperative period; however, six months after surgery almost one-third of participants continued to report painrelated interference with mood (28%), sleep (30%), and enjoyment of life (30%). Consistent with studies of other surgical procedures, measures of anxiety and depression were associated with an increased risk of CPSP. During the six months following surgery, 12% of patients visited the Emergency Department, 15% visited non-traditional providers, and 9.2% visited a walk-in clinic for pain. Compared with Canadian norms, HRQOL was poorer in all domains preoperatively, in all domains but mental health six weeks postoperatively, and in most domains six months postoperatively. Conclusion This feasibility study provides a template for future studies of CPSP following gastrointestinal surgery. Author contributions Elizabeth VanDenKerkhof and Wilma Hopman contributed substantially to all aspects of this manuscript, including conception and design; acquisition, analysis, and interpretation of data; drafting the article, and revising the article critically for important intellectual content. Rosemary Wilson contributed substantially to the conception and design of the manuscript. Paul Belliveau and Rosemary Wilson contributed substantially to the acquisition of data. Michelle Reitsma and David Goldstein also contributed to the acquisition of data. Michelle Reitsma contributed to the analysis of data. Paul Belliveau, Rosemary Wilson, and Ian Gilron contributed substantially to the interpretation of data. David Goldstein also contributed to the interpretation of data. Michelle Reitsma contributed to drafting the article. Paul Belliveau, Rosemary Wilson, and Ian Gilron contributed substantially to revising the article critically for important intellectual content. David Goldstein also contributed to revising the article critically for important intellectual content. E. G. VanDenKerkhof, DrPH (&) R. A. Wilson, PhD Department of Anesthesiology & Perioperative Medicine, School of Nursing, Queen’s University, Kingston, ON K7L 4V1, Canada e-mail: ev5@queensu.ca W. M. Hopman, MA Department of Community Health & Epidemiology, Clinical Research Centre, Kingston General Hospital, Queen’s University, Kingston, ON, Canada M. L. Reitsma, MSc D. H. Goldstein, MB BCH I. Gilron, MD Department of Anesthesiology & Perioperative Medicine, Queen’s University, Kingston, ON K7L 4V1, Canada P. Belliveau, MD Department of Surgery, Queen’s University, Kingston, ON, Canada I. Gilron, MD Department of Biomedical & Molecular Sciences, Queen’s University, Kingston, ON, Canada 123 Can J Anesth/J Can Anesth (2012) 59:670–680 DOI 10.1007/s12630-012-9712-x

Understanding chronic inflammatory and neuropathic pain

Abstract: This meeting report highlights the main topics presented at the conference "Chronic Inflammatory and Neuropathic Pain," convened jointly by the New York Academy of Sciences, MedImmune, and Grunenthal GmbH, on June 2-3, 2011, with the goal of providing a conducive environment for lively, informed, and synergistic conversation among participants from academia, industry, clinical practice, and government to explore new frontiers in our understanding and treatment of chronic and neuropathic pain. The program included leading and emerging investigators studying the pathophysiological mechanisms underlying neuropathic and chronic pain, and experts in the clinical development of pain therapies. Discussion included novel issues, current challenges, and future directions of basic research in pain and preclinical and clinical development of new therapies for chronic pain.

The Canadian Survey of Standards of Electroconvulsive Therapy Practice: a call for accreditation.

Abstract: Objective:To report the results of the policies and procedures subsection of a nationwide electroconvulsive therapy (ECT) survey: Canadian Electroconvulsive Therapy Survey/Enquete canadienne sur le...

Canadian survey of perianesthetic care for patients receiving electroconvulsive therapy.

Abstract: OBJECTIVES We report on the anesthesia subsection of a comprehensive nationwide survey (Canadian Electroconvulsive Therapy Survey/Enquete canadienne sur les electrochocs) on the practice of electroconvulsive therapy (ECT) in Canada. METHODS This comprehensive survey was sent to the 175 Canadian institutions identified as providers of ECT in 2007. Among other topics, 9 anesthesia-related questions were administered regarding anesthesiology consultation; high-risk patients; credentials of the anesthesia provider; monitoring, airway, and resuscitation equipment; anesthetic induction, muscle relaxant, vasoactive, and other perianesthetic drugs and practices; and postanesthetic discharge. RESULTS Sixty-one percent (107/175) of the institutions returned completed survey questionnaires. More than 70% of the sites reported pre-ECT anesthesiology consultation for all (61%) or most (11%) patients. In more than 90%, a Canadian Royal College-certified anesthesiologist, or equivalent, provided anesthetic care. Routine use of oximetry, electrocardiography, and blood pressure monitoring were reported by all but 2 sites; use of bite block was reported by all but 4 sites; and preoxygenation was reported by all but 7 sites. Dantrolene and capnography were not reported as readily available by 35% and 40%, respectively, with comparatively less frequent availability at non-operating room and lower-volume sites. CONCLUSIONS These results suggest safe practices of anesthesia for ECT in Canada. Further attention needs to be paid to ready availability of dantrolene and capnography, particularly at non-operating room ECT sites. Improvements in anesthetic care of patients undergoing ECT may be realized through continued knowledge translation efforts and by expanding access to currently unavailable anesthetic induction agents and, in some settings, limited clinical anesthesiology resources.