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1.
Pain Med ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32022891

RESUMO

OBJECTIVE: The relationship between preexisting osteoarthritic pain and subsequent post-total knee arthroplasty (TKA) pain is not well defined. This knowledge gap makes diagnosis of post-TKA pain and development of management plans difficult and may impair future investigations on personalized care. Therefore, a set of diagnostic criteria for identification of acute post-TKA pain would inform standardized management and facilitate future research. METHODS: The Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership with the US Food and Drug Administration (FDA), the American Pain Society (APS), and the American Academy of Pain Medicine (AAPM) formed the ACTTION-APS-AAPM Pain Taxonomy (AAAPT) initiative to address this goal. A multidisciplinary work group of pain experts was invited to conceive diagnostic criteria and dimensions of acute post-TKA pain. RESULTS: The working group used contemporary literature combined with expert opinion to generate a five-dimensional taxonomical structure based upon the AAAPT framework (i.e., core diagnostic criteria, common features, modulating factors, impact/functional consequences, and putative mechanisms) that characterizes acute post-TKA pain. CONCLUSIONS: The diagnostic criteria created are proposed to define the nature of acute pain observed in patients following TKA.

2.
Anesthesiology ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32022771

RESUMO

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: The Perioperative Ischemic Evaluation-2 study (POISE-2) authors previously reported that neither aspirin nor clonidine reduced a 30-day composite of nonfatal myocardial infarction or death. Aspirin caused perioperative bleeding, and clonidine provoked hypotension and bradycardia.In a subgroup analysis of patients who had previous percutaneous coronary interventions, those given aspirin had fewer infarctions or deaths. WHAT THIS ARTICLE TELLS US THAT IS NEW: This article reports 1-yr outcomes of the POISE-2 study. Consistent with the 30-day analysis, neither aspirin nor clonidine reduced a 1-yr composite of nonfatal myocardial infarction or death.In a subgroup analysis of patients who had prior percutaneous coronary interventions, those given aspirin had significantly fewer nonfatal myocardial infarctions and/or deaths. BACKGROUND: The authors previously reported that perioperative aspirin and/or clonidine does not prevent a composite of death or myocardial infarction 30 days after noncardiac surgery. Moreover, aspirin increased the risk of major bleeding and clonidine caused hypotension and bradycardia. Whether these complications produce harm at 1 yr remains unknown. METHODS: The authors randomized 10,010 patients with or at risk of atherosclerosis and scheduled for noncardiac surgery in a 1:1:1:1 ratio to clonidine/aspirin, clonidine/aspirin placebo, clonidine placebo/aspirin, or clonidine placebo/aspirin placebo. Patients started taking aspirin or placebo just before surgery; those not previously taking aspirin continued daily for 30 days, and those taking aspirin previously continued for 7 days. Patients were also randomly assigned to receive clonidine or placebo just before surgery, with the study drug continued for 72 h. RESULTS: Neither aspirin nor clonidine had a significant effect on the primary 1-yr outcome, a composite of death or nonfatal myocardial infarction, with a 1-yr hazard ratio for aspirin of 1.00 (95% CI, 0.89 to 1.12; P = 0.948; 586 patients [11.8%] vs. 589 patients [11.8%]) and a hazard ratio for clonidine of 1.07 (95% CI, 0.96 to 1.20; P = 0.218; 608 patients [12.1%] vs. 567 patients [11.3%]), with effect on death or nonfatal infarction. Reduction in death and nonfatal myocardial infarction from aspirin in patients who previously had percutaneous coronary intervention at 30 days persisted at 1 yr. Specifically, the hazard ratio was 0.58 (95% CI, 0.35 to 0.95) in those with previous percutaneous coronary intervention and 1.03 (95% CI, 0.91to 1.16) in those without (interaction P = 0.033). There was no significant effect of either drug on death, cardiovascular complications, cancer, or chronic incisional pain at 1 yr (all P > 0.1). CONCLUSIONS: Neither perioperative aspirin nor clonidine have significant long-term effects after noncardiac surgery. Perioperative aspirin in patients with previous percutaneous coronary intervention showed persistent benefit at 1 yr, a plausible sub-group effect.

3.
Anesth Analg ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32049671

RESUMO

Chronic pain is a highly prevalent and complex health problem that is associated with a heavy symptom burden, substantial economic and social impact, and also, very few highly effective treatments. This review examines evidence for the efficacy and safety of magnesium in chronic pain. The previously published protocol for this review was registered in International Prospective Register of Systematic Reviews (PROSPERO), MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched until September 2018. We included randomized controlled trials (RCTs) comparing magnesium (at any dose, frequency, or route of administration) with placebo using participant-reported pain measures. A total of 9 RCTs containing 418 participants were included. Three studies examined neuropathic pain (62 participants), 3 examined migraines (190 participants), 2 examined complex regional pain syndrome (86 participants), and 1 examined low back pain with a neuropathic component (80 participants). Heterogeneity of included studies precluded any meta-analyses. No judgement could be made about safety because adverse events were inconsistently reported in the included studies. Evidence of analgesic efficacy from included studies was equivocal. However, reported efficacy signals in some of the included trials provide a rationale for more definitive studies. Future, larger-sized trials with good assay sensitivity and better safety assessment and reporting, as well as careful attention to formulations with optimal bioavailability, will serve to better define the role of magnesium in the management of chronic pain.

4.
Clin J Pain ; 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31977375

RESUMO

OBJECTIVE: Current treatments for chronic pain have limited effectiveness and tolerability. With growing interest in the potential of cannabinoids, there is a need to inform risk-benefit considerations. Thus, this focused systematic review assesses the quality of safety assessment and reporting in chronic noncancer pain cannabinoid trials. METHODS: The protocol for this review has been published, and, registered in PROSPERO. We searched MEDLINE, EMBASE, The Cochrane Library, Scopus and PsychINFO for double-blind, placebo-controlled, randomized controlled trials of cannabinoids for chronic pain, with a primary outcome related to pain. The primary review outcome is adherence to the 2004 CONSORT Harms extension. Secondary outcomes included type, reporting method, frequency and severity of AEs, trial participant withdrawals, and reasons for withdrawals. RESULTS: In total, 43 studies (4,436 participants) were included. Type of cannabinoid (number of studies) included nabiximols (12), dronabinol (8), nabilone (7), oral cannabis extract preparations (5), smoked THC (5), vaporised THC (3), novel synthetic cannabinoids (2), sublingual cannabis extract preparations (1). The median CONSORT score was 7. On average, 3-4 recommendations of the CONSORT guidelines were not being met in trials. Seventeen trials did not provide their method of adverse event (AE) assessment, fourteen trials did not report on serious adverse events (SAEs) and, seven trials provided no quantitative data about AEs. DISCUSSION: Better harms assessment and reporting are needed in chronic pain cannabinoid trials. Improvements may be achieved through: expanded education/knowledge translation, increased research regulation by ethics boards, funding agencies and journals, and greater emphasis on safety assessment and reporting throughout research training.

6.
J Pain ; 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31843583

RESUMO

The estimated probability of progressing from phase 3 analgesic clinical trials to regulatory approval is approximately 57%, suggesting that a considerable number of treatments with phase 2 trial results deemed sufficiently successful to progress to phase 3 do not yield positive phase 3 results. Deficiencies in the quality of clinical trial conduct could account for some of this failure. An Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) meeting was convened to identify potential areas for improvement in trial conduct in order to improve assay sensitivity (i.e., ability of trials to detect a true treatment effect). We present recommendations based on presentations and discussions at the meeting, literature reviews, and iterative revisions of this article. The recommendations relate to the following areas: (1) study design (i.e., to promote feasibility), (2) site selection and staff training, (3) participant selection and training, (4) treatment adherence, (5) data collection, and (8) data and study monitoring. Implementation of these recommendations may improve the quality of clinical trial data and thus the validity and assay sensitivity of clinical trials. Future research regarding the effects of these strategies will help identify the most efficient use of resources for conducting high quality clinical trials. Perspective Every effort should be made to optimize the quality of clinical trial data. This manuscript discusses considerations to improve conduct of pain clinical trials based on research in multiple medical fields and the expert consensus of pain researchers and stakeholders from academia, regulatory agencies, and industry.

7.
Cochrane Database Syst Rev ; 2019(11)2019 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-31747720

RESUMO

BACKGROUND: Pain following brain surgery can compromise recovery. Several pharmacological interventions have been used to prevent pain after craniotomy; however, there is currently a lack of evidence regarding which interventions are most effective. OBJECTIVES: The objectives are to assess the effectiveness of pharmacological interventions for prevention of acute postoperative pain in adults undergoing brain surgery; compare them in terms of additional analgesic requirements, incidence of chronic headache, sedative effects, length of hospital stay and adverse events; and determine whether these characteristics are different for certain subgroups. SEARCH METHODS: We searched MEDLINE, Embase, CINAHL, CENTRAL, Web of Science and two trial registries together with reference checking and citation searching on 28th of November 2018. SELECTION CRITERIA: We included blinded and non-blinded, randomized controlled trials evaluating pharmacological interventions for the prevention of acute postoperative pain in adults undergoing neurosurgery, which had at least one validated pain score outcome measure. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. We calculated mean differences for the primary outcome of pain intensity; any pain scores reported on a 0 to 100 scale were converted to a 0 to 10 scale. MAIN RESULTS: We included 42 completed studies (3548 participants) and identified one ongoing study. Nonsteroidal anti-inflammatories (NSAIDs) Nonsteroidal anti-inflammatories (NSAIDs) reduce pain up to 24 hours (0 to 6 hours, MD -1.16, 95% CI -1.57 to -0.76; 12 hours, MD -0.62, 95% CI -1.11 to -0.14; 24 hours, MD -0.66, 95% CI -1.18 to -0.13; 6 studies, 742 participants; all high-quality evidence). Results for other outcomes were imprecise (additional analgesic requirements: MD 1.29 mg, 95% CI -5.0 to 2.46, 4 studies, 265 participants; nausea and vomiting RR 1.34, 95% CI 0.30 to 5.94, 2 studies, 345 participants; both low-quality evidence). Dexmedetomidine reduces pain up to 12 hours (0 to 6 hours, MD -0.89, 95% CI -1.27 to -0.51, moderate-quality evidence; 12 hours, MD -0.81, 95% CI -1.21 to -0.42, low-quality evidence). It did not show efficacy at 24 hours (MD -0.08, 95% CI -0.32 to 0.16; 2 studies, 128 participants; low-quality evidence). Dexmedetomidine may decrease additional analgesic requirements (MD -21.36 mg, 95% CI -34.63 to -8.1 mg, 2 studies, 128 participants, low-quality evidence). Results for other outcomes were imprecise (nausea and vomiting RR -0.43, 95% CI 0.06 to 3.08, 3 studies, 261 participants; hypotension RR 0.5, 95% CI 0.05 to 5.28, 3 studies, 184 participants; both low-quality evidence). Scalp blocks may reduce pain up to 48 hours (0 to 6 hours, MD -0.98, 95% CI -1.66 to -0.3, 10 studies, 414 participants; 12 hours, MD -0.95, 95% CI -1.53 to -0.37, 8 studies, 294 participants; 24 hours, MD -0.78, 95% CI -1.52 to -0.05, 9 studies, 433 participants, all low-quality evidence; 48 hours, MD -1.34, 95% CI -2.57 to -0.11, 4 studies, 135 participants, very low-quality evidence. When studies with high risk of bias were excluded, significance remained at 12 hours only. Scalp blocks may decrease additional analgesia requirements (SMD -1.11, 95% CI -1.97 to -0.25, 7 studies, 314 participants). Results for other outcomes were imprecise (nausea and vomiting RR 0.66, 95% CI 0.33 to 1.32, 4 studies, 165 participants, very low-quality evidence). Scalp Infiltration may reduce pain postoperatively but efficacy was inconsistent, with a significant effect at 12 and 48 hours only (12 hours, MD -0.71, 95% CI -1.34 to -0.08, 7 studies, 309 participants, low-quality evidence; 48 hours, MD - 1.09, 95% CI -2.13 to - 0.06, 3 studies, 128 participants, moderate-quality evidence). No benefit was observed at other times (0 to 6 hours, MD -0.64, 95% CI -1.28 to -0.00, 9 studies, 475 participants, moderate-quality evidence; 24 hours, MD -0.39, 95% CI -1.06 to 0.27,6 studies, 260 participants, low-quality evidence. Scalp infiltration may reduce additional analgesia requirements MD -9.56 mg, 95% CI -15.64 to -3.49, 6 studies, 345 participants, very low-quality evidence). When studies with high risk of bias were excluded, scalp infiltration lost the pain benefit at 12 hours and effects on additional analgesia requirements, but retained the pain-reducing benefit at 48 hours (MD -0.56, 95% CI -1.20 to -0.32, 2 studies, 100 participants, very low-quality evidence). Results for other outcomes were imprecise (nausea and vomiting, RR 0.74, 95% CI 0.48 to 1.41, 4 studies, 318 participants, low-quality evidence). Pregabalin or gabapentin may reduce pain up to 6 hours (2 studies, 202 participants), MD -1.15,95% CI -1.66 to -0.6, 2 studies, 202 participants, low-quality evidence). One study examined analgesic efficacy at 12 hours showing significant benefit. No analgesia efficacy was shown at later times (24 hours, MD -0.29, 95% CI -0.78 to -0.19; 48 hours, MD - 0.06, 95% CI -0.86 to 0.77, 2 studies, 202 participants, low-quality evidence). Additional analgesia requirements were not significantly less (MD -0.37 (95% CI -1.10 to 0.35, 3 studies, 234 participants, low-quality evidence). Risk of nausea and vomiting was significantly reduced (RR 0.51, 95% CI 0.29 to 0.89, 3 studies, 273 participants, low-quality evidence). Results for other outcomes were imprecise (additional analgesia requirements: MD -0.37, 95% CI -1.10 to 0.35, 3 studies, 234 participants, low-quality evidence). Acetaminophen did not show analgesic benefit (0 to 6 hours, MD -0.35, 95% CI -1.00 to 0.30; 12 hours, MD -0.51, 95% CI -1.04 to 0.03, 3 studies, 332 participants, moderate-quality evidence; 24 hours, MD -0.34, 95% CI -1.20 to 0.52, 4 studies, 439 participants, high-quality evidence). Results for other outcomes remained imprecise (additional analgesia requirements, MD 0.07, 95% CI -0.86 to 0.99, 4 studies, 459 participants, high-quality evidence; length of hospitalizations, MD -3.71, 95% CI -14.12 to 6.7, 2 studies, 335 participants, moderate-quality evidence). AUTHORS' CONCLUSIONS: There is high-quality evidence that NSAIDs reduce pain up to 24 hours postoperatively. The evidence for reductions in pain with dexmedetomidine, pregabalin or gabapentin, scalp blocks, and scalp infiltration is less certain and of very low to moderate quality. There is low-quality evidence that scalp blocks and dexmedetomidine may reduce additional analgesics requirements. There is low-quality evidence that gabapentin or pregabalin may decrease nausea and vomiting, with the caveat that the total number of events for this comparison was low.

8.
Pain ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31738228

RESUMO

Many genetic markers have been associated with variations in treatment response to analgesics, but none have been assessed in the context of combination therapies. In this study, the treatment effects of nortriptyline and morphine were tested for an association with genetic markers relevant to pain pathways. Treatment effects were determined for single and combination therapies. A total of 24 functional single nucleotide polymorphisms were tested within the gene loci of mu-opioid receptor (OPRM1) gene locus, ATP-Binding Cassette B1 Transporter (ABCB1), Cytochrome P450 gene family (CYP2C19 and CYP2D6), catecholamine inactivator Catechol-O-Methyl Transferase (COMT), and serotonin receptor 2A (HTR2A). Genotyping was performed in a population of neuropathic pain patients who previously participated in a clinical trial. For monotherapy, neither nortriptyline nor morphine responses were associated with single nucleotide polymorphisms. However, for nortriptyline + morphine combination therapy, the single nucleotide polymorphism rs1045642 within the drug efflux pump ABCB1 transporter significantly predicted analgesic response. The presence of the C allele accounted for 51% of pain variance in this subgroup in response to combination treatment. The T-allele homozygotes demonstrated only 20% improvement in pain scores, whereas the C-allele homozygotes 88%. There was no significant contribution of rs1045642 to the medication side effects under all treatment conditions. The UK Biobank data set was then used to validate this genetic association. Here, patients receiving similar combination therapy (opioid + tricyclic antidepressant) carrying the C allele of rs1045642 displayed 33% fewer body pain sites than patients without that allele, suggesting better pain control. In all, our results show a robust effect of the rs1045642 polymorphism in response to chronic pain treatment with a nortriptyline + morphine combination.

9.
Pain Rep ; 4(3): e647, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31583333

RESUMO

Introduction: The clinical setting of acute pain has provided some of the first approaches for the development of analgesic clinical trial methods. Objectives: This article reviews current methods and challenges and provides recommendations for future design and conduct of clinical trials of interventions to treat acute pain. Conclusion: Growing knowledge about important diverse patient factors as well as varying pain responses to different acute pain conditions and surgical procedures has highlighted several emerging needs for acute pain trials. These include development of early-phase trial designs that minimize variability and thereby enhance assay sensitivity, minimization of bias through blinding and randomization to treatment allocation, and measurement of clinically relevant outcomes such as movement-evoked pain. However, further improvements are needed, in particular for the development of trial methods that focus on treating complex patients at high risk of severe acute pain.

10.
Pain Rep ; 4(3): e697, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31583338

RESUMO

Introduction: The evolution of pain treatment is dependent on successful development and testing of interventions. Proof-of-concept (POC) studies bridge the gap between identification of a novel target and evaluation of the candidate intervention's efficacy within a pain model or the intended clinical pain population. Methods: This narrative review describes and evaluates clinical trial phases, specific POC pain trials, and approaches to patient profiling. Results: We describe common POC trial designs and their value and challenges, a mechanism-based approach, and statistical issues for consideration. Conclusion: Proof-of-concept trials provide initial evidence for target use in a specific population, the most appropriate dosing strategy, and duration of treatment. A significant goal in designing an informative and efficient POC study is to ensure that the study is safe and sufficiently sensitive to detect a preliminary efficacy signal (ie, a potentially valuable therapy). Proof-of-concept studies help avoid resources wasted on targets/molecules that are not likely to succeed. As such, the design of a successful POC trial requires careful consideration of the research objective, patient population, the particular intervention, and outcome(s) of interest. These trials provide the basis for future, larger-scale studies confirming efficacy, tolerability, side effects, and other associated risks.

11.
Pain Rep ; 4(3): e741, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31583356

RESUMO

Pain is an experience that affects many people worldwide and is associated with higher mortality and lower quality of life. Cannabinoid, cannabis, and cannabis-based medicines (CBMs) are thought to reduce pain, but a proliferation of different products has led to variability in trials, creating a challenge when determining the assessment of efficacy in systematic reviews. We will conduct 2 systematic reviews commissioned by the International Association for the Study of Pain Task Force on the use of cannabinoids, cannabis, and CBMs for pain management: first, an overview review of systematic reviews to summarise the evidence base and second, a systematic review of randomised controlled trials of cannabinoids, cannabis, and CBMs. In these reviews we will determine the harm and benefit of CBM from the current literature and will interpret the findings in light of the quality of evidence and reviews included. We will search online databases and registries in any language for systematic reviews and randomised controlled trials. We will include studies that evaluate any cannabinoid or CBM vs any control for people with acute and chronic pain. Our primary outcomes for both reviews are the number of participants achieving (1) a 30% and (2) 50% reduction in pain intensity, (3) moderate improvement, and (4) substantial improvement. A number of secondary outcome measures will also be included. We will assess risk of bias and quality of evidence. We will analyse data using fixed and random effect models, with separate comparators for cannabis and CBMs. Prospero ID (CRD42019124710; CRD42019124714).

12.
Pain Rep ; 4(3): e742, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31583357

RESUMO

Introduction: With the increasing availability of cannabis and cannabinoids and their potential utility for pain treatment, there is a growing need to evaluate the risk-benefit considerations of cannabinoids for the management of pain. As part of the IASP Cannabis and Cannabinoids Task Force, this protocol describes a planned overview of systematic reviews summarizing the risks of harm with cannabinoids that are relevant to patients receiving pain treatment. Methods: This overview will involve literature searches of several databases and a defined search strategy that will target systematic reviews or meta-analyses of cannabinoids where harms are the primary focus. Data extraction will include various features of the cannabinoid(s) and the harm(s) being studied as well as other methodological features of each included systematic review. Methodological quality of each included review will be assessed using AMSTAR-2 as well as compliance with the PRISMA harms checklist. Prospero registration pending. Discussion: The broad overview of reviews defined by this protocol is expected to synthesize available good quality evidence of harms that will help inform risk-benefit considerations about the use of cannabinoids for pain management.

13.
Front Immunol ; 10: 473, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30936874

RESUMO

Circulating immune cells, which are recruited to the site of injury/disease, secrete various inflammatory mediators that are critical to nociception and pain. The role of tissue-resident immune cells, however, remains poorly characterized. One of the first cells to be activated in peripheral tissues following injury are γδT cells, which serve important roles in infection, disease, and wound healing. Using a mouse line lacking these cells, we sought to identify their contribution to inflammatory pain. Three distinct models of peripheral inflammatory pain were used: intraplantar injection of formalin (spontaneous inflammatory pain), incisional wound (acute inflammatory pain), and intraplantar injection of complete Freund's adjuvant (chronic inflammatory pain). Our results show that absence of γδT cells does not alter baseline sensitivity, nor does it result in changes to mechanical or thermal hypersensitivity after tissue injury. Myeloid cell recruitment did show differential changes between models of acute and chronic inflammatory pain. These results were consistent in both male and female mice, suggesting that there are no sex differences in these outcomes. This comprehensive characterization suggests that γδT cells do not contribute to basal sensitivity or the development and maintenance of inflammatory pain.

14.
J Pain ; 20(8): 980-993, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30844507

RESUMO

Persistent postsurgical pain is defined as pain localized to the area of surgery of a duration of ≥2 months and is, unfortunately, a common complication after breast cancer surgery. Although there is insufficient evidence to support any preventative strategy, prior literature suggests the possible efficacy of intravenous lidocaine and perioperative pregabalin in preventing persistent pain after surgery. To determine feasibility of conducting a larger definitive trial, we conducted a multicenter 2 × 2 factorial, randomized, placebo-controlled pilot trial of 100 female patients undergoing breast cancer surgery. Patients were randomized to receive an intraoperative lidocaine infusion (1.5 mg/kg bolus followed by 2 mg/kg/h) or placebo and perioperative pregabalin (300 mg preoperatively, 75 mg twice daily for 9 days) or placebo. All feasibility criteria were surpassed; recruitment of 100 patients was accomplished within 42 weeks, with a follow-up rate of 100% and study drug compliance of ≥80%. At 3 months, 53% of patients reported persistent neuropathic pain. Although there was no interaction between lidocaine and pregabalin, lidocaine decreased the development of persistent neuropathic pain (43.1% vs 63.3%; relative risk = .68; 95% confidence interval = .47-1.0). Pregabalin did not reduce persistent pain (60% vs 46%; relative risk = 1.3; 95% confidence interval = .90-1.90) and neither pregabalin nor lidocaine impacted acute postoperative pain, opioid consumption, pain interference, or quality of life. Our pilot trial successfully demonstrated feasibility and provided promising data for conducting further trials of intraoperative lidocaine infusions during breast cancer surgeries. Clinical trial number: NCT02240199 PERSPECTIVE: This article reports the findings of a pilot randomized, controlled trial evaluating the effects of perioperative pregabalin and intraoperative lidocaine infusions in patients undergoing breast cancer surgery. This trial demonstrated the feasibility of conducting a larger trial and provided promising data that these interventions may decrease the development of persistent pain.

15.
BMJ Open ; 9(2): e022995, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30826789

RESUMO

INTRODUCTION: Approximately 400 000 Americans and 36 000 Canadians undergo cardiac surgery annually, and up to 56% will develop chronic postsurgical pain (CPSP). The primary aim of this study is to explore the association of pain-related beliefs and gender-based pain expectations on the development of CPSP. Secondary goals are to: (A) explore risk factors for poor functional status and patient-level cost of illness from a societal perspective up to 12 months following cardiac surgery; and (B) determine the impact of CPSP on quality-adjusted life years (QALYs) borne by cardiac surgery, in addition to the incremental cost for one additional QALY gained, among those who develop CPSP compared with those who do not. METHODS AND ANALYSES: In this prospective cohort study, 1250 adults undergoing cardiac surgery, including coronary artery bypass grafting and open-heart procedures, will be recruited over a 3-year period. Putative risk factors for CPSP will be captured prior to surgery, at postoperative day 3 (in hospital) and day 30 (at home). Outcome data will be collected via telephone interview at 6-month and 12-month follow-up. We will employ generalised estimating equations to model the primary (CPSP) and secondary outcomes (function and cost) while adjusting for prespecified model covariates. QALYs will be estimated by converting data from the Short Form-12 (version 2) to a utility score. ETHICS AND DISSEMINATION: This protocol has been approved by the responsible bodies at each of the hospital sites, and study enrolment began May 2015. We will disseminate our results through CardiacPain.Net, a web-based knowledge dissemination platform, presentation at international conferences and publications in scientific journals. TRIAL REGISTRATION NUMBER: NCT01842568.

16.
J Immunol Res ; 2019: 9020234, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30723751

RESUMO

Skin-resident γδ T cells play an important role in maintaining the immune barrier at the epithelial surface. Their roles in wound healing, regulation of immune response to injury, and reepithelialization have been characterized extensively in the mouse, though their function in human skin remains largely unknown. Human skin-resident γδ T cells sparsely populate the skin and are often small and rounded in appearance. Those in the mouse ear and back, which line the dermal barrier, are highly arborized cells with many processes extending from the cell body. To date, these cells have been studied primarily in the mouse ear and back; however, it is important to further identify and characterize γδ T cells in other body sites to better understand their function and study their contribution to injury and disease. We developed a novel method to visualize these cells in the skin (whole-mount and cryosections) that when combined with flow cytometry allowed us to assess differences in skin-resident γδ T cell numbers, morphology, and activation state in the ear, back, and footpad (chosen for their importance in immunological and pain research). In comparing cell length, number of dendritic processes, and expression of the activation marker CD69, we found that γδ T cell morphology and activation states vary significantly among the three tissue environments. Specifically, γδ T cells in the footpad are smaller, have fewer processes, and show the highest levels of activation compared to back- and ear-resident cells. Our observations suggest that our understanding of skin-resident γδ T cell functionality, drawn from the experiments performed in the ear and back tissue, may not be applicable to all skin environments. The footpad-resident cells also more closely resemble γδ T cells in human skin, suggesting that cells in this tissue environment may serve as a better translational model when studying γδ T cell function/activity.


Assuntos
Ativação Linfocitária , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Pele/citologia , Pele/imunologia , Linfócitos T/imunologia , Animais , Antígenos CD/imunologia , Antígenos de Diferenciação de Linfócitos T/imunologia , Citometria de Fluxo , , Humanos , Imuno-Histoquímica , Lectinas Tipo C/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Cicatrização
17.
JMIR Res Protoc ; 8(1): e11637, 2019 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-30688655

RESUMO

BACKGROUND: Chronic pain affects a significant proportion of the population and presents a major challenge to clinicians and pain specialists. Despite the availability of pharmacologic treatment options such as opioids, many patients continue to experience persistent pain. Cannabinoids present an alternative option with some data on efficacy; however, to date, a systematic review of adverse events (AEs) assessment and reporting in randomized clinical trials (RCTs) involving cannabinoids has not been performed. As a result, it is unclear whether a clear profile of cannabinoid-associated AEs has been accurately detailed in the literature. As cannabinoids are likely to become readily available for patients in the near future, it is important to study how well AEs have been reported in trials so that the safety profile of cannabinoids can be better understood. OBJECTIVE: With a potentially enormous shift toward cannabinoid use for managing chronic pain and spasticity, this study aims to reveal the adequacy of AE reporting and cannabinoid-specific AEs in this setting. Spasticity is a major contributor to chronic pain in patients with multiple sclerosis (MS), with a comorbidity of 75%. Many cannabinoid studies have been performed in MS-related painful spasticity with relevant pain outcomes, and these studies will be included in this review for comprehensiveness. The primary outcome will be the quality of AE assessment and reporting by adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines. Secondary outcomes will include the type of AE, method of AE reporting, severity of AE, frequency of AEs, patient withdrawals, and reasons for withdrawals. METHODS: We will perform a systematic review by searching for primary reports of double-blind, randomized controlled trials of cannabinoids compared with placebo and any active comparator treatments for chronic pain, with a primary outcome directly related to pain (eg, pain intensity, pain relief, and pain-related interference). We will search the following databases: MEDLINE, Embase, Cochrane Library, and PsycINFO. RevMan software will be used for meta-analysis. RESULTS: The protocol has been registered on the International Prospective Register of Systematic Reviews (CRD42018100401). The project was funded in 2018 and screening has been completed. Data extraction is under way and the first results are expected to be submitted for publication in January or February 2019. CONCLUSIONS: This review will better elucidate the safety of cannabinoids for the treatment of chronic pain and spasticity through identifying gaps in the literature for AE reporting. Like in any new therapy, it is essential that accurate information surrounding the safety and efficacy of cannabinoids be clearly outlined and identified to balance the benefit and harm described for patients. TRIAL REGISTRATION: PROSPERO CRD42018100401; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=100401. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/11637.

18.
JMIR Res Protoc ; 8(1): e11654, 2019 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-30635260

RESUMO

BACKGROUND: Chronic pain is a highly prevalent and complex health problem that is associated with a severe symptom burden, as well as substantial economic and social impact. Many patients with chronic pain still suffer from unrelieved or undertreated pain due to the incomplete efficacy and dose-limiting adverse effects of current therapies. Long-term and high-dose opioid use has considerably increased in the past 20 years despite limited evidence supporting its effectiveness in several chronic pain conditions, and serious concerns have emerged regarding adverse effects and potential misuse. Until recently, the steady increase in opioid prescribing rates has been associated with rising opioid-related mortality and other serious problems, emphasizing the need for better nonopioid therapies. Emerging evidence supports the safe use of magnesium in controlling chronic pain, but its overall efficacy and safety is still unclear. OBJECTIVE: This paper aims to assess the efficacy and safety of magnesium compared with a placebo for the treatment of chronic noncancer pain. METHODS: We will conduct a detailed search on Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE from their inception until the date the searches are run to identify relevant randomized controlled trials. The reference lists of retrieved studies as well as Web-based trial registries will also be searched. We will include randomized double-blind trials comparing magnesium (at any dose, frequency, or route of administration) with placebo using participant-reported pain assessment. Two reviewers will independently evaluate studies for eligibility, extract data, and assess trial quality and potential bias. Risk of bias will be assessed using criteria outlined in the Cochrane Handbook for Systematic Review of Interventions. Primary outcomes for this review will include any validated measure of pain intensity or pain relief. Dichotomous data will be used to calculate the risk ratio and number needed to treat or harm. The quality of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: This protocol is grant-funded and has undergone a peer-review process through the Queen's University Department of Anesthesiology and Perioperative Medicine Vandewater Endowed Studentship. This project is also supported, in part, by the Chronic Pain Network of the Canadian Institutes of Health Research Strategy for Patient-Oriented Research. The electronic database search strategies are currently being developed and modified. The entire review is expected to be completed by January 1, 2019. CONCLUSIONS: The completion of this review is expected to identify available high-quality evidence describing the efficacy and safety of magnesium for the treatment of chronic noncancer pain. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/11654.

20.
Pain ; 159(11): 2339-2346, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30015707

RESUMO

Multiple recent pharmacological clinical trials in neuropathic pain have failed to show beneficial effect of drugs with previously demonstrated efficacy, and estimates of drug efficacy seems to have decreased with accumulation of newer trials. However, this has not been systematically assessed. Here, we analyze time-dependent changes in estimated treatment effect size in pharmacological trials together with factors that may contribute to decreases in estimated effect size. This study is a secondary analysis of data from a previous published NeuPSIG systematic review and meta-analysis, updated to include studies published up till March 2017. We included double-blind, randomized, placebo-controlled trials examining the effect of drugs for which we had made strong or weak recommendations for use in neuropathic pain in the previously published review. As the primary outcome, we used an aggregated number needed to treat for 50% pain reduction (alternatively 30% pain reduction or moderate pain relief). Analyses involved 128 trials. Number needed to treat values increased from around 2 to 4 in trials published between 1982 and 1999 to much higher (less effective) values in studies published from 2010 onwards. Several factors that changed over time, such as larger study size, longer study duration, and more studies reporting 50% or 30% pain reduction, correlated with the decrease in estimated drug effect sizes. This suggests that issues related to the design, outcomes, and reporting have contributed to changes in the estimation of treatment effects. These factors are important to consider in design and interpretation of individual study data and in systematic reviews and meta-analyses.


Assuntos
Analgésicos/uso terapêutico , Neuralgia/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Feminino , Humanos , Masculino , PubMed/estatística & dados numéricos , Estudos Retrospectivos
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