Exceeding the guideline-recommended maximum daily dose of opioids for long-term treatment of non-cancer pain in Germany - a large retrospective observational study.

BACKGROUND: High-dose long-term opioid therapy (LTOT) has been associated with increased mortality and hospitalizations. Therefore, the evidence-based German guideline on LTOT for chronic non-cancer pain (CNCP) recommends to only exceed the maximum daily dose (MDD) of opioids in exceptional cases. This study aimed to determine the portion of LTOT patients who exceeded the guideline-recommended MDD and identify predictors of exceeding in administrative claims data. METHODS: The retrospective observational analysis of opioid prescriptions in patients receiving LTOT for CNCP was based on administrative claims by a large German statutory health insurance company. Patients with at least two quarters of opioid prescriptions between January 2018 and June 2019 were included and followed up for two years. Predictors were identified by logistic regression. In addition, the number of patients still in opioid therapy and the extent of exceeded MDDs were analyzed over time. RESULTS: The sample consisted of 113,475 patients. Overall, 10.5% of the patients exceeded the guideline-recommended MDD averaged over the observation period. Strong predictors for exceeding the MDD were receiving opioid prescriptions from > 7 physicians (OR = 7.66, p < .001), receiving predominantly strong opioids (OR = 6.79, p < .001) and receiving opioids for at least one year prior to inclusion (OR = 5.35, p < .001). Within the non-exceeding group, 28.1% discontinued opioid therapy. In contrast, 9.9% of patients in the exceeding group discontinued opioid therapy, whereas the vast majority remained on treatment until the end of the observation period. Furthermore, a slight increase in prescribed doses was observed over time. CONCLUSIONS: The results indicate that a moderate proportion of patients exceeded the guideline-recommended MDD. However, certain patient groups were more likely to receive high doses. This applied in particular to those who were already on treatment at the time of inclusion and continued to receive opioids until the end of the observation period. Further research should examine whether the continuous opioid therapy among the patients with exceeding the guideline-recommended MDD might be related to specific indications, a lack of therapeutic options or avoidance of withdrawal. TRIAL REGISTRATION: German Clinical Trials Register (drks.de/search/en). Identifier: DRKS00024854. Registered 28 April 2021.

Long versus short-term opioid therapy for fibromyalgia syndrome and risk of depression, sleep disorders and suicidal ideation: a population-based, propensity-weighted cohort study.

OBJECTIVE: Fibromyalgia syndrome (FMS) is characterised by widespread pain and is associated with mood disorders such as depression as well as poor sleep quality. These in turn have been linked to increased risk of suicidal ideation. Clinical guidelines generally do not recommended opioids in FMS, but they are routinely prescribed to a considerable proportion of FMS patients. We assessed the association of long-term opioid prescription for FMS with risk of depression, sleep disorders and suicidal ideation, when compared with short-term opioid use. METHODS: Retrospective cohort study combing several population-wide databases covering a population of five million inhabitants, including all adults who received an initial opioid prescription from 2014 to 2018 specifically prescribed for FMS. We examined the occurrence of depression, sleep disorders or suicidal ideation outcomes in patients with an initial long-term opioid prescription (>90 days) versus those who received a short-term treatment (<29 days). We employed multivariable Cox regression modelling and inverse probability of treatment weighting based on propensity scores and we performed several sensitivity analyses. RESULTS: 10 334 patients initiated short-term (8309, 80.40%) or long-term (2025, 19.60%) opioids for FMS. In main adjusted analyses, long-term opioid use was associated with an increased risk for depression (HR: 1.58, 95% CI 1.29 to 1.95) and sleep disorder (HR: 1.30, 95% CI 1.09 to 1.55) but not with suicidal ideation (HR: 1.59, 95% CI 0.96 to 2.62). In models assessing outcomes since day 90, an increased risk for suicidal ideation was observed (HR: 1.76, 95% CI 1.05 to 2.98). CONCLUSION: These findings suggest that continued opioid use for 90 days or more may aggravate depression and sleep problems in patients with FMS when compared with patterns of short-term treatment.

Safety of Co-Crystal of Tramadol-Celecoxib (CTC) in Patients with Acute Moderate-to-Severe Pain: Pooled Analysis of Three Phase 3 Randomized Trials.

INTRODUCTION: Multi-modal analgesia is desirable for the management of acute pain since it can provide effective pain relief at lower doses, thereby aiding tolerability. Co-crystal of tramadol-celecoxib (CTC) provides effective analgesia in models of acute pain. Co-crystallization can alter the pharmacokinetics of individual components, potentially improving tolerability. We sought to better understand the safety and tolerability of CTC in patients with acute postoperative pain. METHODS: We conducted a pooled analysis of safety data from three phase 3 randomized controlled trials in adults with acute moderate-to-severe pain following oral surgery, bunionectomy, and elective abdominal hysterectomy. We present data for CTC 200 mg twice daily (BID) and its comparators: tramadol 50 mg four times daily (QID) (one trial), tramadol 100 mg QID (two trials), celecoxib 100 mg BID (two trials), and placebo (three trials). RESULTS: In total, n = 551 patients received CTC 200 mg BID, n = 183 received tramadol 50 mg QID, n = 368 received tramadol 100 mg QID, n = 388 received celecoxib 100 mg BID, and n = 274 received placebo. The prevalence of adverse events (AEs) related to study drug up to 48 h was numerically lower with CTC 200 mg BID (35.9%) than with tramadol 50 mg QID (47.5%) and 100 mg QID (44.8%) but greater than with celecoxib 100 mg BID (12.4%) and placebo (20.4%). The most frequent AEs related to study drug up to 48 h were somnolence, nausea, dizziness, and vomiting, which occurred more frequently in patients receiving tramadol 100 mg QID than in those receiving CTC 200 mg BID. CONCLUSION: CTC 200 mg BID appears to be better tolerated than tramadol 100 mg QID, possibly because of reduced total exposure to tramadol. This may contribute to a more favorable benefit-risk profile for CTC versus individual components, making it a promising treatment for acute pain. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT03108482, NCT02982161 (EudraCT: 2016-000592-24), NCT03062644 (EudraCT: 2016-000593-38).

Comparison of the recovery profile of sufentanil and remifentanil in total intravenous anesthesia: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Remifentanil is a short-acting opioid and can be administered during surgery without the risk of delayed postoperative recovery but concerns about hyperalgesia and the shortages of remifentanil lead anesthetists to consider long-acting opioids for Total Intravenous Anesthesia (TIVA). Sufentanil is a more potent opioid with a longer context-sensitive half-life but can promote good postoperative analgesia due to its residual effect. This meta-analysis aimed to compare the recovery profile of remifentanil and sufentanil for TIVA. METHODS: The search strategy was performed in PubMed, CENTRAL, and Web of Science for RCTs comparing sufentanil and remifentanil as part of TIVA in adults undergoing noncardiac surgery. Risk of bias and the quality of evidence were performed using RoB2 and GRADEpro, respectively. The primary outcome was time to tracheal extubation. Secondary analyses included postoperative analgesia, respiratory depression, and Postoperative Nausea and Vomiting (PONV). RESULTS: Sufentanil increases the time to extubate, MD = 4.29 min; 95% CI: 2.33 to 6.26; p = 0.001. It also reduces the need for postoperative rescue analgesia, logOR = -1.07; 95% CI: -1.62 to -0.52; p = 0.005. There were no significant differences between both opioids for PONV, logOR = 0.50; 95% CI: -0.10 to 1.10; p = 0.10 and respiratory depression, logOR = 1.21; 95% CI: -0.42 to 2.84; p = 0.15. CONCLUSION: Sufentanil delays the time to tracheal extubation compared with remifentanil but is associated with a reduced need for postoperative rescue analgesia. No significant differences were observed between the two opioids in terms of postoperative respiratory depression or PONV.

A Patent-Pending Ointment Containing Extracts of Five Different Plants Showed Antinociceptive and Anti-Inflammatory Mechanisms in Preclinical Studies.

Background/Objectives: The antinociceptive and anti-inflammatory effects of a patent-pending ointment containing plant extracts from Eucalyptus globulus, Curcuma longa, Hamamelis virginiana, Echinacea purpurea, and Zingiber officinale were evaluated. Methods: Plant extracts were chemically characterized by gas chromatography-mass spectroscopy. The antinociceptive activity of the ointment was assessed using the hot plate, tail flick, and formalin tests, whereas the anti-inflammatory activity was measured using the acute and chronic TPA-induced ear edema tests. Mechanisms of action were evaluated using inhibitors from signaling pathways related to pain response and by using histological analysis and assessing the expression and activity of pro-inflammatory mediators. Results: The ointment showed antinociceptive and anti-inflammatory effects like those observed with diclofenac gel (1.16% v/v) and ketoprofen gel (2.5% v/v). The antinociceptive actions of the ointment are mediated by the possible participation of the opiodergic system and the nitric oxide pathway. The anti-inflammatory response was characterized by a decrease in myeloperoxidase (MPO) activity and by a reduction in ear swelling and monocyte infiltration in the acute inflammation model. In the chronic model, the mechanism of action relied on a decrease in pro-inflammatory mediators such as COX-2, IL-1ß, TNF-α, and MPO. An in-silico study with myristic acid, one of the compounds identified in the ointment's plant mixture, corroborated the in vivo results. Conclusions: The ointment showed antinociceptive activities mediated by the decrease in COX-2 and NO levels, and anti-inflammatory activity due to the reduction in IL-1ß and TNFα levels, a reduction in MPO activity, and a decrease in NF-κB and COX-2 expression.

Cyclooxygenase 2 Inhibitors for Headache After Elective Cranial Neurosurgery: Results from a Systematic Review of Efficacy of Cyclooxygenase 2 Inhibitors for Headache After Acute Brain Injury.

Headache management after acute brain injury (ABI) is challenging. Although opioids are commonly used, selective cyclooxygenase 2 inhibitors (COXIBs) may be promising alternatives. However, concerns about cardiovascular effects and bleeding risk have limited their use. We aimed at summarizing available data on efficacy of COXIBs for headache management following ABI. A systematic review was conducted through MEDLINE and Embase for articles published through September 2023 (PROSPERO identifier: CRD42022320453). No language filters were applied to the initial searches. Interventional or observational studies and systematic reviews assessing efficacy of COXIBs for headache in adults with ABI were eligible. Article selection was performed by two independent reviewers using DistillerSR. Descriptive statistics were used for data analysis, and meta-analysis was unfeasible because of study heterogeneity. Of 3190 articles identified, 6 studies met inclusion criteria: 4 randomized controlled trials and 2 retrospective cohort studies, all conducted in elective cranial neurosurgical patients (total N = 738) between 2006 and 2022. Five studies used COXIBs in the intervention group only. Of the six studies, four found a reduction in overall pain scores in the intervention group, whereas one showed improvement only at 6 h postoperatively, and one did not find significant differences. Pain scores decreased between 4 and 15%, the largest shift being from moderate to mild severity. Three studies found an overall opioid use reduction throughout hospitalization in the intervention group, whereas one reported a reduction at 12 h postoperatively only. Opioid consumption decreased between 9 and 90%. Two studies found a decrease in hospital length of stay by ~ 1 day in the intervention group. The one study reporting postoperative hemorrhage found a statistically nonsignificant 3% reduction in the intervention group. COXIBs may serve as opioid-sparing adjunctive analgesics for headache control after elective cranial surgery. Limited or no literature exists for other forms of ABI, and additional safety data remain to be elucidated.

Comparing modalities of opioid education in patients undergoing total knee arthroplasty: a randomized pilot trial.

BACKGROUND: Patients undergoing total knee arthroplasty (TKA) experience significant postoperative pain and routinely require opioids, yet they often lack knowledge regarding appropriate use and handling of these medications. Evidence suggests that educational interventions in various formats may help reinforce proper usage and improve postoperative pain control. The aim of this study is to compare the institution standard of care (webinar) with two novel educational interventions-one in-person and the other a video recording-that focus specifically on the use of opioids and pain control. METHODS: This prospective, randomized pilot study included 42 patients undergoing TKA. Patients were randomized into one of three groups: (1) webinar: 50 min virtual session standard of care at Hospital for Special Surgery (HSS), (2) in-person education, or (3) video education. The primary outcomes of this study were the number of opioid refill requests through postoperative day (POD) 30 and POD 60. The secondary outcomes evaluated Numerical Rating Scale (NRS) pain scores, opioid consumption in oral morphine equivalents (OME), surveys on medication usage and opioid knowledge, reported medication storage and disposal. We hypothesize that the novel educational interventions, presented either in-person or by video, will lead to a decrease in opioid refills within 60 days compared with current education delivered through virtual webinar. RESULTS: No significant differences were found among groups in the number of opioid refill requests, average NRS pain score, or OME consumption at any time point. Opioid refill requests ranged from 0% to 16.7% at POD 30 (Fisher's exact test, p=0.625) and from 0% to 8.3% at POD 60 (p=1.000). The median opioid refill request was zero requests per group from POD 21 to 60 (webinar 0 (0.0, 0.0), in-person 0 (0.0, 0.0), video 0 (0.0, 0.0), Kruskal-Wallis test, p=0.381). Average NRS pain scores were 5 or below for all groups on POD 1, 7 and 14. By POD 7, all groups had an average daily intake OME of 14 or below. CONCLUSIONS: Overall, patients in each group did well with postoperative pain management after TKA and had minimal opioid refill requests. There were no statistically significant differences in outcomes of NRS pain scores or opioid usage among groups suggesting that educational interventions were similarly effective. As a pilot trial, study demonstrated successful recruitment and retention of participants, and important feedback was elicited from patients regarding education, as well. Of note, this was a pilot study and was likely underpowered to detect a difference. TRIAL REGISTRATION NUMBER: NCT05593341.

Conotoxins: emerging analgesics for neck and spinal surgery pain management.

Conotoxins, peptides derived from the venom of marine cone snails, have emerged as promising analgesics for managing pain associated with neck and spinal surgery. These toxins target specific neurotransmitter receptors and ion channels in the nervous system, offering an alternative to traditional opioids with potentially fewer side effects. By interacting with receptors such as nicotinic acetylcholine and voltage-gated sodium and calcium channels, conotoxins disrupt pain signal transmission and induce muscle relaxation, providing effective pain relief. Research into conotoxins is ongoing, with the goal of developing novel, safer analgesics that mitigate the risks of opioid addiction. This exploration not only holds promise for surgical pain management but also advances our understanding of venom pharmacology and its therapeutic applications.

Understanding the role of intraoperative hypothermia in perioperative opioid requirements in immediate implant-based breast reconstruction.

BACKGROUND: The relationship between perioperative temperatures and postoperative pain is unknown. The present study investigated the relationship of intraoperative hypothermia and perioperative opioid requirements after immediate implant-based breast reconstruction. METHODS: A retrospective chart review was conducted on patients undergoing immediate implant-based breast reconstruction from 2019-2023. Patients were classified into the hypothermic group (majority of procedure <36.0 °C) or normothermic group (majority of procedure ≥36.0 °C). Cumulative inpatient opioid requirements (morphine milli-equivalents [MMEs]) and frequency of patients requiring "high-dose opioids" (≥100 MMEs) were collected and compared between the groups. RESULTS: In total, 536 patients (835 breasts) were included, among whom 135 (25.1%) were hypothermic. The hypothermic group had lower mean intraoperative (88.4 vs. 99.1 MMEs, P = 0.007) and postoperative (45.6 vs. 56.8 MMEs, P = 0.006) than the normothermic group. Mean (B = 14.6, P = 0.004) and nadir (B = 10.4, P = 0.038) intraoperative temperatures directly predicted higher opioid requirements while higher percentages of the procedure time spent under 36 °C (B = -27.6, P = 0.004) predicted lower opioid requirements. The hypothermic group was associated with 66% decreased odds of requiring high-dose opioids after adjusting for differences in patient and operative characteristics (P = 0.007). CONCLUSION: Hypothermia is associated with decreased perioperative opioid requirements. Future studies should further investigate ideal temperature thresholds for warming protocols to minimize postoperative pain.

Present and Future of Pharmacological Management for Acute Moderate-to-Severe Postoperative, Traumatic, or Musculoskeletal Pain in Europe: A Narrative Review.

Acute moderate-to-severe pain is common after surgery, trauma, or musculoskeletal injury, but its management remains suboptimal. Current single-agent treatments are limited by safety concerns, narrow therapeutic windows, and abuse potential, leaving substantial unmet needs. Here, we aimed to review guidelines for the management of acute moderate-to-severe post-surgical, trauma-related, or musculoskeletal pain in adults and discuss existing and potential future analgesics in this setting. We searched PubMed to identify relevant guidelines and existing analgesics for acute pain. To identify compounds in development, we searched ClinicalTrials.gov and the European Union Clinical Trials Register. Guidelines universally recognize the limitations of single-agent analgesics (particularly those with a single mechanism of action [MoA]) and recommend a multimodal approach as an established standard for acute pain. The benefit-risk profiles of traditional treatments, including paracetamol (acetaminophen), nonsteroidal anti-inflammatory drugs, selective cyclooxygenase-2 inhibitors, and opioids, can be improved by combining agents targeting different pain pathways. In multimodal approaches, lower doses of constituent agents can be used to achieve the same or superior analgesic effects relative to the individual agents. In some cases, novel formulations and co-crystal technology offer enhanced physicochemical and pharmacokinetic properties over individual agents. Lastly, initiatives to increase patient awareness and education around pain management may improve treatment satisfaction and quality of life, and hasten recovery. In conclusion, management of acute moderate-to-severe pain remains inadequate. Multimodal analgesics may offer advantages over traditional single-agent treatments (that often have a single MoA) for acute moderate-to-severe post-surgical, trauma-related, or musculoskeletal pain in adults. Multimodal analgesics, combined with patient education initiatives and non-pharmacological measures, when necessary, offer promise in addressing unmet needs in this setting.

Postoperative pain management in children: guidance from the Pain Committee of the European Society for Paediatric Anaesthesiology (ESPA Pain Management Ladder Initiative) Part II.

The ESPA Pain Management Ladder Initiative is a clinical practice advisory based upon expert consensus supported by the current literature to help ensure a basic standard of perioperative pain management for all children. In 2018 the perioperative pain management of six common pediatric surgical procedures was summarised. The current Pain Management Ladder recommendations focus on five more complex pediatric surgical procedures and suggest basic, intermediate, and advanced pain management methods. The aim of this paper is to encourage best possible pain management practice and to support institutions to create their own pain management concepts according to their financial and human resources due to the diversity of clinical settings in Europe. Furthermore, the authors underline that these recommendations are intended for inpatients only.

Trends in fatal poisoning among medical users of analgesics in France from 2013 to 2022: an analysis of the DTA register.

OBJECTIVE: To describe analgesic-related deaths in France and report trends over a 10-year period. STUDY DESIGN: The DTA ("Décès Toxiques par Antalgiques") register is a French database of analgesic-related deaths among people without a history of drug abuse, reported by forensic toxicology experts. METHODS: We included analgesic-related deaths occurring from January 2013 to December 2022 in France. Subject demographic characteristics and medical history, forensic autopsy findings, and toxicology reports were evaluated. RESULTS: Among the 1036 deceased individuals (mean [SD] age, 48.3 [15.6] years), there were slightly more women than men (M:F sex ratio, 0.89:1). Over the entire study period, tramadol was the leading cause of death, ahead of morphine. A relative increase in oxycodone-related mortality was observed (from 6.8% in 2013 to 21.1% in 2022) compared to a progressive decrease in tramadol, morphine, and codeine-related deaths (from 43.2%, 31.1% and 24.3% in 2013 to 37.5%, 26.6% and 20.3% in 2022, respectively). However, no statistically significant variations were found (Chi-squared tests of homogeneity). Other analgesics (buprenorphine, dihydrocodeine, fentanyl, gabapentin, ketamine, methadone, nefopam, and pregabalin) were also implicated in deaths, but with low and stable rates over the period studied. CONCLUSIONS: In France, no increase in fentanyl-related deaths and only a non-significant increase in oxycodone-related deaths were observed over the period 2013-2022. Tramadol was the leading cause of analgesic-related deaths throughout this period. Although close monitoring is still required, particularly for oxycodone, our data do not support the hypothesis of an opioid crisis in France.

Treatment of Pain in Cirrhosis: Advice to Caregivers of Those with Rock Livers.

PURPOSE: When one considers the significant role of the liver in medication absorption and metabolism, clinicians must appreciate the important ramifications for medication dosing and monitoring in patients with cirrhosis. For many medications, dose adjustments may be necessary to minimize toxicities or avoid adverse effects from drug accumulation. Clinicians could be well served if they can understand in some detail how pharmacokinetic properties are altered in cirrhosis. METHODS: A PubMed search of the English medical literature starting with 1980 using keywords cirrhosis, pain management, and analgesics was performed, and additional papers were found using references from the first round of papers. FINDINGS: Patients with cirrhosis often have significant reductions in first-pass metabolism, altered volumes of distribution, and marked reductions in both renal and hepatic elimination of drugs. These factors may contribute to much higher levels of drug exposure compared to the general population. In terms of drug dosing, FDA labeling is often ambiguous and even incongruous with observed pharmacokinetic changes. IMPLICATIONS: This article may provide guidance for clinicians to optimize pain management in people living with cirrhosis. KEY MESSAGE: Current FDA labeling for dosing analgesic drugs in patients with cirrhosis is either vague or not consistent with findings from newer pharmacokinetic research. With this review, we hope to provide insight and guidance to clinicians on how to dose-adjust medications commonly utilized in pain management in these patients.

Differences in opioid prescriptions by race among U.S. older adults with a hip fracture transitioning to community care.

BACKGROUND: Appropriate pain management can facilitate rehabilitation after a hip fracture as patients transition back to the community setting. Differences in opioid prescribing by race may exist during this critical transition period. METHODS: We conducted a retrospective cohort study of older adult U.S. Medicare beneficiaries with a hip fracture to examine whether the receipt and dose of opioids differs between Black and White patients as they transitioned back to the community setting. We stratified beneficiaries by whether they received institutional post-acute care (PAC). Outcomes were (1) receipt of an opioid and (2) opioid doses in the first 90 days in the community in milligram morphine equivalents (MMEs; also presented in mg oxycodone). We estimated relative rates and risk differences of opioid receipt and dose differences using Poisson and linear regression models, respectively, using the parametric g-formula to standardize for age and sex. RESULTS: We identified 164,170 older adults with hip fracture (mean age = 82.7 years; 75% female; 72% with PAC; 46% with opioid use after fracture). Overall use of opioids in the community was similar between Black and white beneficiaries. Black beneficiaries had lower average doses in their first 90 days in both total cumulative doses (PAC group: 165 [95% CI -264 to -69] fewer MMEs [-248 mg oxycodone]; no PAC: 167 [95% CI -274 to -62] fewer MMEs [-251 mg oxycodone]) and average MME per days' supply of medication (PAC: -3.0 [-4.6 to -1.4] fewer MMEs per day [-4.5 mg oxycodone]; no PAC: -4.7 [-4.6 to -1.4] fewer MMEs per day [-7.1 mg oxycodone]). In secondary analyses, Asian beneficiaries experienced the greatest differences (e.g., 617-653 fewer cumulative mg oxycodone). CONCLUSION: Racial differences exist in pain management for Medicare beneficiaries after a hip fracture. Future work should examine whether these differences result in disparities in short- and long-term health outcomes.

Caffeine, but not paracetamol (acetaminophen), enhances muscular endurance, strength, and power.

BACKGROUND: Caffeine is one of the most popular ergogenic aids consumed by athletes. Caffeine's ergogenic effect has been generally explained by its ability to bind to adenosine receptors, thus modulating pain and reducing perceived exertion. Another pharmacological agent that may improve performance due to its analgesic proprieties is paracetamol. This study aimed to explore the effects of caffeine, paracetamol, and caffeine + paracetamol consumption on muscular endurance, strength, power, anaerobic endurance, and jumping performance. METHODS: In this randomized, crossover, double-blind study, 29 resistance-trained participants (11 men and 18 women) ingested either a placebo, caffeine (3 mg/kg), paracetamol (1500 mg) or caffeine + paracetamol 45 min before the testing sessions. The testing sessions included performing the bench press exercise with 75% of one-repetition maximum to momentary muscular failure, isokinetic knee extension and flexion at angular velocities of 60°/sec and 180°/sec, Wingate, and countermovement jump (CMJ) tests. RESULTS: Compared to placebo, isolated caffeine ingestion increased the number of repetitions performed in the bench press (p = 0.005; d = 0.42). Compared to placebo, isolated caffeine ingestion and/or caffeine + paracetamol consumption was ergogenic for strength (torque), muscular endurance (total work), or power in the isokinetic assessment, particularly at slower angular velocities (p = 0.027 to 0.002; d = 0.16 to 0.26). No significant differences between the conditions were observed for outcomes related to the Wingate and CMJ tests. CONCLUSION: This study provided novel evidence into the effectiveness of caffeine, paracetamol, and their combination on exercise performance. We found improvements in muscular endurance, strength, or power only when caffeine was consumed in isolation, or in combination with paracetamol. Isolated paracetamol consumption did not improve performance for any of the analyzed outcomes, thus calling into question its ergogenic potential.

Efficacy of local pain management strategies for patients undergoing anterior iliac crest bone harvesting: a systematic review.

Anterior Iliac crest bone harvesting (AICBH) is a common surgical procedure with applications in various medical specialties, but it is often accompanied by significant postoperative pain. Effective pain management is therefore essential for optimising patient outcomes. This systematic literature review aimed to evaluate the effectiveness of local donor site pain management interventions in AICBH procedures. It followed the Cochrane Handbook for Systematic Reviews of Interventions version 6.4 guidelines and adhered to the PRISMA 2020 statement for comprehensive and high-quality reporting. A comprehensive search was conducted across PubMed, Cochrane, and Embase to identify relevant studies. Inclusion criteria encompassed randomised controlled trials assessing pain management strategies in AICBH patients. The methodological quality of the included studies was assessed using the Jadad scale. Data extraction focused on medication types, administration modes, pain scores, and use of narcotics. Fourteen eligible studies were included. Methodological quality varied, with most studies demonstrating a low risk of bias. Medication types included amide and opioid groups, administered via single-shot injections or infusion systems. Results indicated that indwelling iliac crest catheters with bupivacaine showed significant postoperative reductions in pain scores and narcotics use compared with other techniques. The findings suggest that use of an indwelling catheter with bupivacaine is an effective pain management strategy for AICBH patients. However, heterogeneity among the studies and a lack of standardised methodologies pose limitations. Further homogeneous and standardised studies are therefore needed to strengthen the evidence base and inform clinical practice.

Opioid Use and Outcomes in Patients Hospitalized With Acute Severe Ulcerative Colitis.

BACKGROUND: Opioid use has not been shown to improve hospitalized inflammatory bowel disease patient pain scores and may prolong the length of stay (LOS). Additional clinical implications of opioid use, particularly high amounts, in the hospital setting have not yet been explored. We sought to determine how high opioid use impacts clinical outcomes in acute severe ulcerative colitis (ASUC). METHODS: In this single-center study, we identified all patients hospitalized with ASUC who received intravenous corticosteroids from July 1, 2014 to December 31, 2021. Clinical outcomes including opioid exposure, cumulative intravenous corticosteroid dose, biologic rescue therapy initiation date, colectomy rate, opioid prescription at discharge, LOS, and hospitalization cost were collected. High opioid use was defined as ≥40 oral morphine equivalents (OMEs) per day. A univariable logistic regression was performed to evaluate the association of high opioid use with ASUC outcomes. RESULTS: 185 eligible hospitalizations for ASUC were evaluated. 75 patients (41%) received opioids during hospitalization, and 20 patients (11%) received ≥40 OMEs/day. High opioid use was associated with a median 3-day delay in biologic rescue therapy initiation when compared with low/no opioid use (P = .02). 70% of patients with high opioid use received an opioid prescription at discharge compared with 10% of those with low/no use (P < .001). Opioid use was not associated with LOS, duration of corticosteroid therapy, colectomy rate, or hospitalization cost. CONCLUSIONS: Among ASUC hospitalizations, high opioid use was associated with delayed biologic rescue therapy initiation and higher rates of opioid prescriptions at discharge.

In this single-center study of patients hospitalized with acute severe ulcerative colitis, opioid use was associated with delayed initiation of biologic rescue therapy and higher rates of discharge prescriptions for opioids.

Development of pharmacy-based best practices to support safer use and management of prescription opioids based on an e-Delphi methodology.

BACKGROUND: Opioid utilization and related harm have increased in recent decades, notably in Australia, the United States, Canada, and some European countries. For people who are prescribed opioids, pharmacies offer an accessible, regular point-of-contact, providing a unique opportunity to address opioid prescription drugs risks. OBJECTIVE: This project aimed to develop consensus-based, best practice statements for improving the safer use of prescription opioids through community pharmacy settings. METHODS: The e-Delphi technique is used to obtain consensus from experts about issues where conclusive evidence is lacking, using multiple rounds of online participation. The investigator group identified an international group of potential participants with relevant expertise who were invited to the study, and asked to identify other experts for invitation. The e-Delphi process comprised three online rounds, involving (1) statement idea generation, (2) developing statement consensus, and (3) confirming and ranking statements. RESULTS: A diverse group of 42 experts (76 % female, 6 countries) participated, comprising pharmacists (n = 24, 57 %), medical doctors of differing specialties (n = 12, 29 %), and/or researchers (n = 28, 67 %), with a mean of 15 years' professional experience (SD = 8.08). Eighty-five statements were initially developed in Round 1, and 78 were supported with amendments, with suggestions to merge and remove items in Round 2, resulting in 72 final statements which were all endorsed in Round 3. Items spanned seven themes: education, monitoring outcomes and risk, deprescribing and pain management, overdose education and naloxone, opioid agonist treatment, staff education, and overarching practices. Preferred terminology was determined in Round 2 and confirmed in Round 3. CONCLUSIONS: Community pharmacies offer a unique opportunity to support the safer use of prescription opioids. These 72 best practice statements provide practical guidance on specific practices that pharmacists can undertake to support patients' safer use of prescription opioids and prevent or reduce harms from prescribed opioid use.

Comparing cognitive behavioral therapy and social prescribing in patients with loneliness on long-term opioid therapy to reduce opioid misuse: protocol for a randomized controlled trial.

BACKGROUND: Patients with chronic pain on opioids frequently experience loneliness, which is associated with poorer health outcomes and higher risk for opioid misuse and opioid use disorder. Given that almost half of opioids are prescribed in primary care, a critical need exists for the development and testing of interventions to reduce loneliness in primary care patients at risk for opioid misuse. Cognitive behavioral therapy and social prescribing have been shown to be efficacious in reducing loneliness and improving outcomes in other populations but have not been tested in patients at risk for substance use disorder. The overall objective of our study is to reduce opioid misuse and opioid use disorder by addressing loneliness in patients on long-term opioid therapy in real-world primary care settings. METHODS: We will conduct a 3-arm pragmatic, randomized controlled trial to compare the effectiveness of two group-based, telehealth-delivered interventions with treatment as usual: (1) cognitive behavioral therapy to address maladaptive thought patterns and behaviors around social connection and (2) a social prescribing intervention to connect participants with social opportunities and develop supportive social networks. Our primary outcome is loneliness as measured by the UCLA Loneliness Scale and our dependent secondary outcome is opioid misuse as measured by the Common Opioid Misuse Measure. We will recruit 102 patients on long-term opioid therapy who screen positive for loneliness from 2 health care systems in Washington State. Implementation outcomes will be assessed using the RE-AIM framework. DISCUSSION: Our study is innovative because we are targeting loneliness, an under-addressed but critical social risk factor that may prevent opioid misuse and use disorder in the setting where most patients are receiving their opioid prescriptions for chronic pain. If successful, the project will have a positive impact in reducing loneliness, reducing opioid misuse, improving function and preventing substance use disorder. TRIAL REGISTRATION: NCT06285032, issue date: February 28, 2024, original.