Serum lidocaine (lignocaine) concentrations during prolonged perioperative infusion in patients undergoing breast cancer surgery: A secondary analysis of a randomised controlled trial.

Perioperative lidocaine (lignocaine) infusions are being employed with increasing frequency. The determinants of systemic lidocaine concentrations during prolonged administration are unclear. In the Long-term Outcomes after Lidocaine Infusions for PostOperative Pain (LOLIPOP) pilot trial, the impact of infusion duration and body size metrics on serum lidocaine concentrations was examined with regression models in 48 women undergoing breast cancer surgery. Lidocaine was delivered as an intravenous bolus (1.5 mg/kg) and infusion (2 mg/kg per h) intraoperatively, followed by a 12-h subcutaneous infusion (1.33 mg/kg per h) postoperatively. Dosing was based on total body weight. Wound infiltration with other long-acting local anaesthetics was permitted. Protein binding and pharmacogenomic data were also collected. Lidocaine concentrations (median (interquartile range) (range)) during prolonged administration were in the safe and potentially therapeutic range: post-anaesthesia care unit 2.16 (1.73-2.82) (1.12-6.06) µg/ml; ward 1.41 (1.22-1.75) (0.64-2.81) µg/ml. Concentrations increased non-linearly during the early intravenous phase of administration (mean rise 1.21 µg/ml per hour of infusion, P = 0.007) but reached a pseudo steady-state during the later subcutaneous phase. Higher dose rates received per kilogram of lean (P = 0.004), adjusted (P = 0.006) and ideal body weight (P = 0.009) were associated with higher steady-state concentrations. The lidocaine free fraction was unaffected by the presence of ropivacaine, and phenotypes linked to slow metabolism were infrequent. Serum lidocaine concentrations reached a pseudo steady-state during a 12-h postoperative infusion. Greater precision in steady-state concentrations can be achieved by dosing on lean body weight versus adjusted or ideal body weight (equivalent lean body weight doses: intravenous bolus 2.5 mg/kg; intravenous infusion 3.33 mg/kg per h; subcutaneous infusion 2.22 mg/kg per h.

Health-related quality of life in patients accessing medicinal cannabis in Australia: The QUEST initiative results of a 3-month follow-up observational study.

AIMS: Patients with chronic health conditions not responding to conventional treatment can access medicinal cannabis (MC) prescriptions from clinicians in Australia. We aimed to assess overall health-related quality of life (HRQL), pain, fatigue, sleep, anxiety, and depression in a large real-world sample of patients accessing prescribed medicinal cannabis. We hypothesized that all patient-reported outcomes (PROs) would improve from baseline to 3-months. METHODS: The QUEST Initiative is a large prospective multicenter study of patients with any chronic health condition newly prescribed medicinal cannabis between November 2020 and December 2021. Eligible patients were identified by 120 clinicians at medical centers across six Australian states. Consenting participants completed the EuroQol Group EQ-5D-5L health status questionnaire; European Organization for Research & Treatment of Cancer Quality of Life questionnaire (QLQ-C30); Patient-Reported Outcomes Measurement Information System (PROMIS) Short Forms in Fatigue and Sleep Disturbance, and the Depression Anxiety Stress Scale (DASS-21) before starting therapy, at 2-weeks titration, then monthly for 3-months. RESULTS: Of the 2762 consenting participants, 2327 completed baseline and at least one follow-up questionnaire. Ages ranged between 18-97 years (mean 51y; SD = 15.4), 62.8% were female. The most commonly treated conditions were chronic pain (n = 1598/2327; 68.7%), insomnia (n = 534/2327; 22.9%), generalized anxiety (n = 508/2327; 21.5%), and mixed anxiety and depression (n = 259/2327; 11%). Across the whole cohort both EQ-5D-5L utility scores and QLQ-C30 summary scores showed clinically meaningful improvement in HRQL from baseline to mean follow-up with d = 0.54 (95%CI:0.47 to 0.59) and d = 0.64 (95%CI:0.58 to 0.70) respectively; and clinically meaningful improvement in fatigue (d = 0.54; 95%CI:0.48 to 0.59). There was clinically meaningful reduction of pain for those with chronic pain (d = 0.65; 95%CI:0.57 to 0.72); significant improvements for those with moderate to extremely severe anxiety (X2 = 383; df = 4; p<0.001) and depression (X2 = 395; df = 4; p<0.001); and no changes in sleep disturbance. CONCLUSIONS: We observed statistically significant, clinically meaningful improvements in overall HRQL and fatigue over the first 3-months in patients with chronic health conditions accessing prescribed medical cannabis. Anxiety, depression, and pain also improved over time, particularly for those with corresponding health conditions. The study continues to follow-up patients until 12-months to determine whether improvements in PROs are maintained long-term. TRAIL REGISTRATION: Study registration - Australian New Zealand Clinical Trials Registry: ACTRN12621000063819. https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12621000063819.

Use of ketamine wafer for pain management by volunteer emergency medical technicians in rural Western Australia.

OBJECTIVE: To describe the use of sublingual ketamine wafers administered by volunteer emergency medical technicians (EMTs) for pain management to patients in rural Western Australia (WA). METHODS: This retrospective cohort study included patients older than 12 years who were attended by volunteer EMTs in Esperance, Lancelin and Kalbarri, WA and received analgesic medications from 2018 to 2021. Patients who received ketamine wafers with/without other analgesics were compared to (i) patients who received only oral paracetamol and (ii) patients who received inhalational methoxyflurane without ketamine wafers with/without paracetamol. RESULTS: The present study included 826 patients, among whom 149 patients received ketamine wafer with/without other analgesics, 82 paracetamol only and 595 methoxyflurane with/without paracetamol. Patients who received ketamine wafers were younger (median age 49 years vs 54 years for the paracetamol group vs 58 years for the methoxyflurane group), required a longer median transport interval (56 min vs 20 min vs 8 min), trauma-related (73% vs 35% vs 54%), and presented higher median initial pain score (9 vs 3 vs 8 out of 10) than those who received paracetamol and those who received methoxyflurane, respectively. Eight in the ketamine wafers group (5.4%) had a record of nausea/vomiting after the administration of ketamine wafers. CONCLUSIONS: Sublingual ketamine wafer was administered by volunteer EMTs without any evidence of major adverse events in rural WA and deemed useful as an additional pain management option when long transport to hospital was needed. No other symptoms that may be associated with the use of ketamine were recorded.

Evaluating Adherence of Evidence-Based Post-Operative Discharge Opioid Prescribing Guidelines and Patient Outcomes Two Weeks Post-Discharge.

Introduction: There is a growing public health concern regarding inappropriate prescribing practices of discharge analgesia. A tertiary Australian hospital first developed its Postoperative Inpatients Discharge Analgesia Guidelines after an initial audit in 2015. Adherence to the guidelines were evaluated in 2016 and 2017 which show reduced compliance from 93.5% in 2016 to 83.4% in 2017. Aim: To assess ongoing compliance with the guidelines five years following its implementation and to evaluate patient outcome in terms of its clinical impact and minimization of harmful events. Methods: Prescribing data were obtained for discharge analgesic medication for 200 surgical patients from August 2019 to April 2020. Records were assessed against the hospital's Postoperative Inpatients Discharge Analgesia Guidelines and compared with equivalent data from the previous 2015, 2016, and 2017 audits. Patients were interviewed by telephone two weeks after hospital discharge. Results: Prescribing of analgesia was most compliant with overall guidelines for paracetamol (100% unchanged from 2017), followed by celecoxib (98%, up from 96% in 2017), tramadol IR (89% up from 74% in 2017), and pregabalin (89% up from 50% in 2017). Two weeks after discharge, 112 (56%) patients were surveyed and reported a mean pain-score of 2 (95% CI 1.5-2.5) out of 10 at that time. Thirty-two (29%) patients interviewed were still taking pain medication, with 17 (53%) taking medication supplied from the hospital. Seventy-eight (88%) patients stored their pain medication in an unlocked location. Among those no longer taking analgesia, 28 (43%) had unused pain medications, and only two (6%) had returned these to a community pharmacist. Conclusion: This study found that compliance with hospital discharge analgesia prescribing guidelines has increased, although there is room for improvement. Follow-up of the participants reveals high rates of unused opioids, improper storage and disposal of their pain medication.

Pregabalin vs placebo to prevent chronic pain after whiplash injury in at-risk individuals: results of a feasibility study for a large randomised controlled trial.

ABSTRACT: There are few effective treatments for acute whiplash-associated disorders (WADs). Early features of central sensitisation predict poor recovery. The effect of pregabalin on central sensitisation might prevent chronic pain after acute whiplash injury. This double blind, placebo-controlled randomised controlled trial examined feasibility and potential effectiveness of pregabalin compared with placebo for people with acute WAD. Twenty-four participants with acute WAD (<48 hours) and at risk of poor recovery (pain ≥5/10) were recruited from hospital emergency departments in Queensland, Australia, and randomly assigned by concealed allocation to either pregabalin (n = 10) or placebo (n = 14). Pregabalin was commenced at 75 mg bd, titrated to 300 mg bd for 4 weeks, and then weaned over 1 week. Participants were assessed at 5 weeks and 3, 6, and 12 months. Feasibility issues included recruitment difficulties and greater attrition in the placebo group. For the primary clinical outcome of neck pain intensity, attrition at 5 weeks was pregabalin: 10% and placebo: 36% and at 12 months was pregabalin: 10% and placebo: 43%. Pregabalin may be more effective than placebo for the primary clinical outcome of neck pain intensity at 3 months (mean difference: -4.0 [95% confidence interval -6.2 to -1.7]) on an 11-point Numerical Rating Scale. Effects were maintained at 6 months but not 12 months. There were no serious adverse events. Minor adverse events were more common in the pregabalin group. A definitive large randomised controlled trial of pregabalin for acute whiplash injury is warranted. Feasibility issues would need to be addressed with modifications to the protocol.

A Quality-of-Life Evaluation Study Assessing Health-Related Quality of Life in Patients Receiving Medicinal Cannabis (the QUEST Initiative): Protocol for a Longitudinal Observational Study.

BACKGROUND: Evidence supports several countries introducing legislation to allow cannabis-based medicine as an adjunctive treatment for the symptomatic relief of chronic pain, chemotherapy-induced nausea, spasticity in multiple sclerosis (MS), epileptic seizures, depression, and anxiety. However, clinical trial participants do not represent the entire spectrum of disease and health status seen in patients currently accessing medicinal cannabis in practice. OBJECTIVE: This study aims to collect real-world data to evaluate health-related quality of life in patients prescribed medicinal cannabis oil and describe any differences over time, from before starting therapy to after 3 and 12 months of therapy. METHODS: Adult patients newly prescribed medicinal cannabis oil by authorized prescribers and under the Special Access Schemes across Australia will be screened for eligibility and invited to participate. A sample size of 2142 is required, with a 3-month follow-up. All participants will complete the EuroQol 5-Dimension; European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-30; Depression, Anxiety, and Stress Scale-21; Patients' Global Impression of Change; Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form (SF) version 1.0: Sleep Disturbance 8b; and PROMIS SF Fatigue 13a questionnaires. Patients with chronic pain conditions will also complete the PROMIS SF version 1.0: Pain Intensity 3a and PROMIS SF version 1.0: Pain Interference 8a. Patients with movement disorders will also complete Quality of Life in Neurological Disorders (Neuro-QoL) SF version 1.0: Upper Extremity Function (Fine Motor and Activities of Daily Living) and if chorea is indicated, the Neuro-QoL SF version 2.0: Huntington's Disease health-related Quality of LIFE-Chorea 6a. All questionnaires will be administered at baseline, 2 weeks (titration), monthly up to 3 months, and then every 2 months up to 1 year. RESULTS: Recruitment commenced in November 2020. By June 2021, 1095 patients were screened for the study by 69 physicians in centers across 6 Australian states: Australian Capital Territory, New South Wales, Queensland, South Australia, Victoria, and Western Australia. Of the patients screened, 833 (39% of the target sample size) provided consent and completed baseline questionnaires. Results are expected to be published in 2022. Results of this study will show whether patient-reported outcomes improve in patients accessing prescribed medicinal cannabis from baseline to 3 months and whether any changes are maintained over a 12-month period. This study will also identify differences in improvements in patient-reported outcomes among patients with different chronic conditions (eg, chronic pain, MS, epilepsy, Parkinson disease, or cancer). CONCLUSIONS: This protocol contains detailed methods that will be used across multiple sites in Australia. The findings from this study have the potential to be integral to treatment assessment and recommendations for patients with chronic pain and other health indicators for accessing medicinal cannabis. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ANZCTRN12621000063819; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380807&isReview=true. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/32327.

Successful rotation from long-acting full agonist opioids to sublingual buprenorphine/naloxone using a microdosing approach.

Buprenorphine/naloxone (BPN/NX) is a first-line treatment for opioid use disorder. Conventional treatment guidelines recommend a period of opioid abstinence and the presence of moderate withdrawal before initiation to avoid precipitated withdrawal. A newer approach of "microdosing" removes this requirement and has potential benefits. We present two cases of successful induction of BPN/NX using a microdosing regimen in an inpatient withdrawal unit. Both cases did not result in precipitated withdrawal and did not necessitate prior cessation of other opioids. This case report highlights how the use of microdosing to induct BPN/NX treatment can reduce potential barriers and complications with treatment initiation.

Efficacy and Tolerability of Oral Compared with Sublingual Ketamine Lozenges as Rescue Analgesics in Adults for Acute Pain: The OSKet Trial.

BACKGROUND AND OBJECTIVE: Ketamine is an N-methyl-D-aspartate receptor (NMDA) antagonist used widely as an intravenous analgesic for treatment of acute pain. Its use as oral and sublingual analgesics is not well studied. This study aims to compare the clinical efficacy and tolerability of oral (PO) versus sublingual (SL) ketamine lozenges in adult patients with moderate-to-severe breakthrough pain. METHODS: The study had a randomized, double-blind crossover design in 23 inpatients requiring ketamine as rescue analgesics when pain scores exceeded 4/10 on the Numerical Rating Scales. Each participant received either SL 50 mg ketamine lozenge and PO placebo lozenge or SL placebo lozenge and PO 50 mg ketamine lozenge in two treatment periods with a minimum 24-h washout. Pain scores and adverse effects were documented half hourly for the first 2 h, then one hourly for the next 2 h after treatment. The time to first effect and time to meaningful pain relief were recorded. Patients reported their satisfaction and a global impression of change (GIC) at the end of each treatment period. Data were analysed using random effects regression models. RESULTS: Sixteen subjects completed both days, 7 completed 1 day. Time to first effect was 13.1 min PO versus 6.6 min SL (p = 0.069), time to meaningful pain relief was 29.4 min PO versus 10.8 min SL (p = 0.02). Pain scores were not significantly different at all time points post-treatment. Satisfaction and GIC scores were similar for both groups. Overall, adverse events occurred more often with SL administration (p = 0.02). CONCLUSIONS: Sublingual administration of ketamine led to a faster onset of pain relief (but also a higher adverse event rate), but in all other aspects treatment with ketamine given sublingually and orally produced similar analgesic effects. ACTRN: ACTRN12621000240842, 08/03/2021, retrospectively registered.

Do NSAIDs Really Interfere with Healing after Surgery?

Perioperative analgesia should be multimodal to improve pain relief, reduce opioid use and thereby adverse effects impairing recovery. Non-steroidal anti-inflammatory drugs (NSAIDs) are an important non-opioid component of this approach. However, besides potential other adverse effects, there has been a longstanding discussion on the potentially harmful effects of NSAIDs on healing after surgery and trauma. This review describes current knowledge of the effects of NSAIDs on healing of bones, cartilage, soft tissue, wounds, flaps and enteral anastomoses. Overall, animal data suggest some potentially harmful effects, but are contradictory in most areas studied. Human data are limited and of poor quality; in particular, there are only very few good randomized controlled trials (RCTs), but many cohort studies with potential for significant confounding factors influencing the results. The limited human data available are not precluding the use of NSAIDs postoperatively, in particular, short-term for less than 2 weeks. However, well-designed and large RCTs are required to permit definitive answers.

Persistent Spinal Pain Syndrome: A Proposal for Failed Back Surgery Syndrome and ICD-11.

OBJECTIVE: For many medical professionals dealing with patients with persistent pain following spine surgery, the term Failed back surgery syndrome (FBSS) as a diagnostic label is inadequate, misleading, and potentially troublesome. It misrepresents causation. Alternative terms have been suggested, but none has replaced FBSS. The International Association for the Study of Pain (IASP) published a revised classification of chronic pain, as part of the new International Classification of Diseases (ICD-11), which has been accepted by the World Health Organization (WHO). This includes the term Chronic pain after spinal surgery (CPSS), which is suggested as a replacement for FBSS. METHODS: This article provides arguments and rationale for a replacement definition. In order to propose a broadly applicable yet more precise and clinically informative term, an international group of experts was established. RESULTS: 14 candidate replacement terms were considered and ranked. The application of agreed criteria reduced this to a shortlist of four. A preferred option-Persistent spinal pain syndrome-was selected by a structured workshop and Delphi process. We provide rationale for using Persistent spinal pain syndrome and a schema for its incorporation into ICD-11. We propose the adoption of this term would strengthen the new ICD-11 classification. CONCLUSIONS: This project is important to those in the fields of pain management, spine surgery, and neuromodulation, as well as patients labeled with FBSS. Through a shift in perspective, it could facilitate the application of the new ICD-11 classification and allow clearer discussion among medical professionals, industry, funding organizations, academia, and the legal profession.

Pregabalin for neuropathic pain in primary care settings: recommendations for dosing and titration.

Pregabalin is one of the first-line treatments approved for the management of neuropathic pain (NeP). While many patients benefit from treatment with pregabalin, they are often treated with suboptimal doses, possibly due to unfamiliarity around prescribing the drug and/or side effects that can occur with up-titration. This narrative review discusses key aspects of initiating, titrating, and managing patients prescribed pregabalin therapy, and addresses concerns around driving and the potential for abuse, as well as when to seek specialist opinion. To ensure that patients derive maximum therapeutic benefit from the drug, we suggest a 'low and slow' dosing approach to limit common side effects and optimize tolerability alongside patients' expectations. When requiring titration to higher doses, we recommend initiating 'asymmetric dosing,' with the larger dose in the evening. Fully engaging patients in order for them to understand the expected timeline for efficacy and side effects (including their resolution), can also help determine the optimal titration tempo for each individual patient. The 'low and slow' approach also recognizes that patients with NeP are heterogeneous in terms of their optimal therapeutic dose of pregabalin. Hence, it is recommended that general practitioners closely monitor patients and up-titrate according to pain relief and side effects to limit suboptimal dosing or premature discontinuation.

Classification algorithm for the International Classification of Diseases-11 chronic pain classification: development and results from a preliminary pilot evaluation.

ABSTRACT: The International Classification of Diseases-11 (ICD-11) chronic pain classification includes about 100 chronic pain diagnoses on different diagnostic levels. Each of these diagnoses requires specific operationalized diagnostic criteria to be present. The classification comprises more than 200 diagnostic criteria. The aim of the Classification Algorithm for Chronic Pain in ICD-11 (CAL-CP) is to facilitate the use of the classification by guiding users through these diagnostic criteria. The diagnostic criteria were ordered hierarchically and visualized in accordance with the standards defined by the Society for Medical Decision Making Committee on Standardization of Clinical Algorithms. The resulting linear decision tree underwent several rounds of iterative checks and feedback by its developers, as well as other pain experts. A preliminary pilot evaluation was conducted in the context of an ecological implementation field study of the classification itself. The resulting algorithm consists of a linear decision tree, an introduction form, and an appendix. The initial decision trunk can be used as a standalone algorithm in primary care. Each diagnostic criterion is represented in a decision box. The user needs to decide for each criterion whether it is present or not, and then follow the respective yes or no arrows to arrive at the corresponding ICD-11 diagnosis. The results of the pilot evaluation showed good clinical utility of the algorithm. The CAL-CP can contribute to reliable diagnoses by structuring a way through the classification and by increasing adherence to the criteria. Future studies need to evaluate its utility further and analyze its impact on the accuracy of the assigned diagnoses.

Multi-Criteria Decision Analysis to Develop an Efficacy-Safety Profile of Parenteral Analgesics Used in the Treatment of Postoperative Pain.

BACKGROUND: Identifying the optimal treatment in an acute postoperative setting remains a challenge. Multiple analgesic options are available, but comparing outcomes is limited by a lack of head-to-head trials. In addition, decisions based on efficacy only do not take drug safety into account. In such cases, multi-criteria decision analysis (MCDA) can be utilized to quantify and compare the efficacy and safety data of various drugs. METHODOLOGY: The efficacy-safety profiles of eight parenteral, postoperative analgesics (acetaminophen, diclofenac, ketorolac, metamizole, morphine, nefopam, parecoxib, tramadol) widely used in Europe were evaluated using an MCDA model that included 17 criteria: three for efficacy and 14 for safety. Each drug was scored on each criterion on a scale from 0 (worst) to 100 (best), according to published data and the judgment of an expert panel. A weighting process was then applied to standardize the impact of each criterion and adjust drugs' preference scores accordingly, normalizing them on the 0-100 scale. Sensitivity analyses were also performed, including a model in which analgesic profiles were compared when opioid sparing effect was set at a zero value for all drugs. RESULTS: In the primary model, efficacy and safety had relative weightings of 64% and 36%, respectively. Efficacy and safety criteria with the highest values were pain relief (relative weight, 29%) and gastrointestinal effects (12%). Parecoxib received the highest overall score (93), followed by diclofenac (80), and ketorolac (75). Morphine scored the lowest (57), due to the lack of an opioid sparing effect. When opioid sparing was given a zero rating, parecoxib remained the highest scoring analgesic (93), followed by diclofenac (80), metamizole (76), and morphine (76). Parecoxib remained the most preferred analgesic in several other sensitivity analyses. CONCLUSION: This MCDA-based assessment suggests that parecoxib has the most favorable efficacy-safety profile among the assessed postoperative analgesics.

Central mechanisms of pain in orofacial pain patients: Implications for management.

BACKGROUND: Central sensitization (CS) is a form of neuroplasticity characterized by changes in the neural sensitivity, responsiveness, and/or output that are not contingent on peripheral input nor activity-dependent. CS is characterized by activation of unmyelinated C-fibers resulting in a cascade of events at molecular and cellular levels which eventuate into generation of synaptic currents at rest. CS, therefore, contributes to heightened generalized pain sensitivity, further complicates the process of reaching a diagnosis, and increases the possibility of treatment failure. BODY: Trigeminal nerve is the main sensory supplier of the anterior part of the head, including the intraoral structures. Primary afferent nociceptors of the trigeminal nerve and low threshold mechanoreceptors synapse with wide dynamic range (WDR) neurons in the pons. This multifaceted network of nerve interactions which is further complicated by the modulatory circuits that can suppress or heighten the activity of WDR neurons is one of the main contributors to CS. The importance of CS in orofacial pain disorders is emphasized in the context of chronic pain development. As for all chronic pain conditions, it is crucial to consider the biopsychosocial aspects of chronic orofacial pain in managing this diverse group of conditions. This review highlights current understanding of the biopsychosocial model and central mechanisms contributing to the pathogenesis of chronic orofacial pain.

Potential for Harm Associated with Discharge Opioids After Hospital Stay: A Systematic Review.

INTRODUCTION: Mounting evidence highlights the adverse effects of opioids. In spite of this, clinicians often prescribe excessive number of discharge opioids. The aim of this systematic review is to analyse the potential of harm from discharge opioids after inpatient care including excessive prescribing of discharge opioids, improper handling of unused opioids, and unintentional chronic opioid use. METHODS: A systematic search of MEDLINE, EMBASE, and Cochrane databases at the cut-off date of 1 December 2018 was conducted for studies reporting on various harmful effects of discharge opioids after inpatient care. RESULTS: Twenty-eight studies analysed the potential for harm of discharge opioids after various inpatient surgical or medical procedures. On average, patients consumed only 38% of the prescribed discharge opioid pills. Seventy-two percent of patients stored their leftover opioids in an unlocked location, and failure to dispose of unused opioids was reported in 94.5% of patients. These factors may contribute to the increasing rate of opioid misuse and diversion in the community. In addition, discharge opioids contribute to prolonged opioid use; the proportion of opioid-naïve patients still consuming opioids 3 months after hospital discharge is 10.4%. At 6 months, the proportion is 4.4%. Unintentional chronic opioid use is associated with pre-operative opioid use, history of substance use, specific comorbidities, and invasive surgical procedures. CONCLUSION: This systematic review suggests that the current discharge opioid prescribing practices can be improved. Lack of patient education regarding storage and disposal of opioids also contributes to the increasing rate of opioid misuse, diversion, and unintended long-term use. More high-quality research with comparable outcomes is needed. Evidence-based hospital guidelines and public health policies are needed to improve opioid stewardship.

The Influence of a Positive Empathetic Interaction on Conditioned Pain Modulation and Manipulation-induced Analgesia in People With Lateral Epicondylalgia.

OBJECTIVE: Conditioned pain modulation (CPM) and manipulation-induced analgesia (MIA) are 2 forms of endogenous analgesia. Many forms of analgesia can be influenced by the nature of the patient-clinician interaction. The aim of this study was to evaluate the influence of an empathetic and supportive interaction on CPM and MIA in people with lateral epicondylalgia (LE). MATERIAL AND METHODS: In a double-blind, randomized, controlled trial, 68 participants with LE were assigned to 2 groups: the empathetic and neutral interaction groups. The interactions were carried out by a trained, professional role-play actor, playing the part of a research assistant. The research assistant actor spent 15 minutes before CPM and MIA assessment interacting with the participants in an empathetic or neutral manner. Immediately after the interaction, a blinded assessor measured pressure pain threshold at the symptomatic elbow and ipsilateral wrist during CPM and MIA testing. Linear mixed models were used to evaluate differences in CPM and MIA responses between the interaction groups. RESULTS: There was a significant difference in Consultation and Relational Empathy scores between the groups (P<0.001), indicating that the intervention group experienced a more empathic interaction. Both groups showed a significant increase in pressure pain threshold measures, indicative of a CPM and MIA analgesic response (P<0.001), however, the analgesic responses were greater in the group that had experienced a supportive, empathetic interaction (post CPM, wrist: P<0.001; elbow: P=0.001) (post MIA wrist: P<0.001; elbow: P=0.001). DISCUSSION: A single session of empathetic interaction positively influenced both CPM and MIA responses in people with LE.

The relationship between the reporting of euphoria events and early treatment responses to pregabalin: an exploratory post-hoc analysis.

BACKGROUND: Euphoria is a complex, multifactorial problem that is reported as an adverse event in clinical trials of analgesics including pregabalin. The relationship between the reporting of euphoria events and pregabalin early treatment responses was examined in this exploratory post-hoc analysis. METHODS: Data were from patients with neuropathic or non-neuropathic chronic pain enrolled in 40 randomized clinical trials, who received pregabalin (75-600 mg/day) or placebo. Reports of treatment-emergent euphoria events were based on the Medical Dictionary of Regulatory Activities preferred term "euphoric mood". Prevalence rates of euphoria events overall and by indication were assessed. Post-treatment endpoints included ≥30% improvements in pain and sleep scores up to 3 weeks as well as a ≥1-point improvement in daily pain score up to 11 days after treatment. RESULTS: 13,252 patients were analyzed; 8,501 (64.1%) and 4,751 (35.9%) received pregabalin and placebo, respectively. Overall, 1.7% (n=222) of patients reported euphoria events. Among pregabalin-treated patients, a larger proportion who reported euphoria events achieved an early pain response compared with those who did not report euphoria (30% pain responders in week 1 with euphoria events [43.0%], without euphoria events [24.2%]). Results were similar for weeks 2 and 3. For Days 2-11, a larger proportion of pregabalin-treated patients with (relative to without) euphoria events were 1-point pain responders. Findings were similar in pregabalin-treated patients for sleep endpoints (30% sleep responders in week 1 with euphoria events [50.7%], without euphoria events [36.1%]). Similar results were found for weeks 2 and 3. Patients who received placebo showed similar patterns, although the overall number of them who reported euphoria events was small (n=13). CONCLUSION: In patients who received pregabalin for neuropathic or non-neuropathic chronic pain, those who experienced euphoria events may have better early treatment responses than those who did not report euphoria events.

The effect of guideline implementation on discharge analgesia prescribing (two years on).

The provision of appropriate discharge analgesia can be challenging and is often prescribed by some of the most junior members of the medical team. Opioid abuse has been considered a growing public health crisis and physician overprescribing is a major contributor. In 2015 an initial audit of discharge analgesia at the Royal Perth Hospital led to the development of discharge analgesia guidelines. Compliance with these guidelines was assessed by a follow-up audit in 2016, which showed improved practice. This audit assesses discharge analgesia prescribing practices two years following guideline implementation. Dispensing data were obtained for analgesic medication over a three-month period from April to July 2017 and 100 unique patients were chosen using computer generated randomisation. Patients' medical records were assessed against the hospital's Postoperative Inpatients Discharge Analgesia Guidelines. The data collected were then compared with equivalent data from the previous 2015 and 2016 audits. Overall 83.4% of the 170 discharge analgesia prescriptions written were compliant with guidelines. The highest overall compliance rates were achieved for paracetamol (100%, up from 95.9% in 2016), celecoxib (96%, down from 100% in 2016), and oxycodone immediate release (IR) (74%, down from 88.9% in 2016). The quantity of oxycodone IR given on discharge complied with quantity guidelines in only 56% of cases. Overall there has been a significant and sustained improvement in appropriateness of discharge analgesia prescribing since 2015, though the results from 2017 show less compliance than 2016 and that achieving compliance with quantity guidelines is an ongoing challenge. This demonstrates the challenge of obtaining high adherence to guidelines over a longer time period.