NSAIDs, analgesics, antiplatelet drugs, and decline in renal function: a retrospective case-control study with SIDIAP database.

INTRODUCTION: We aim to explore the association between NSAIDs consumption, Symptomatic Slow Action Drugs for Osteoarthritis (SYSADOA), analgesics, and antiplatelet drugs, and decline in renal function by estimated Glomerular Filtration Rate (eGFR). METHODS: We performed a case-control study using the SIDIAP database in Catalonia. We considered defined cases, patients with an eGFR value ≤ 45 ml/min/1.73 m2 in the period 2010-2015 with a previous eGFR value ≥ 60, and no eGFR ≥ 60 after this period. Controls had an eGFR ≥ 60 with no previous eGFR < 60. Five controls were selected for each case, matched by sex, age, index date, Diabetes Mellitus and Hypertension. We estimated Odds Ratios (OR, 95% Confidence Intervals) of decline in renal function for drugs group adjusting with logistic regression models, by consumption measured in DDD. There were n = 18,905 cases and n = 94,456 controls. The mean age was 77 years, 59% were women. The multivariate adjusted model showed a low risk for eGFR decline for NSAIDs (0.92;0.88-0.97), SYSADOA (0.87;0.83-0.91) and acetaminophen (0.84;0.79-0.89), and an high risk for metamizole (1.07;1.03-1.12), and antiplatelet drugs (1.07;1.03-1.11). The low risk in NSAIDs was limited to propionic acid derivatives (0.92;0.88-0.96), whereas an high risk was observed for high doses in both acetic acid derivatives (1.09;1.03-1.15) and Coxibs (1.19;1.08-1.30). Medium and high use of major opioids shows a high risk (1.15;1.03-1.29). Triflusal showed high risk at medium (1.23;1.02-1.48) and high use (1.68;1.40-2.01). CONCLUSION: We observed a decline in renal function associated with metamizole and antiplatelet agent, especially triflusal, and with high use of acetic acid derivates, Coxibs, and major opioids. Further studies are necessary to confirm these results.

Efficacy and Safety of Naldemedine for Opioid-Induced Constipation in Children.

Background: Naldemedine, a peripherally acting opioid µ receptor antagonist, is effective for prevention of opioid-induced constipation (OIC); however, evidence on its use in children is limited. Objective: To evaluate the efficacy and safety of naldemedine in pediatric patients with OIC. Design, Setting/Subjects: Retrospective analysis of 32 pediatric patients with OIC treated with naldemedine in a single institution in Japan from June 2017 to March 2021. Measurements: Efficacy was evaluated in 13 evaluable patients with bowel movement (BM) response, defined as those with at least three BMs in the first 7 days after naldemedine initiation and an increase of at least one BM from baseline. Safety was evaluated by examining adverse events (AEs) based on the Common Terminology Criteria for AEs (v5.0). Results: BM response was recorded in 11 of the 13 patients (85%), and the number BMs per day significantly increased from 0.43 before naldemedine to 1.00 after naldemedine (p = 0.025). The most common AE was diarrhea, observed in 16 of the 32 patients (50%), and all instances were grade 1 or 2. In three of the 16 patients, naldemedine was discontinued owing to worsening diarrhea. Conclusions: In pediatric patients, naldemedine resulted in a high rate of BM response and increased the BM frequency, indicating its efficacy. In some patients, grade 2 diarrhea required naldemedine discontinuation, suggesting that it should be used with caution in pediatric patients. Further studies are warranted to determine the optimal naldemedine dose in pediatric patients.

Rationale and Design for the BLOCK-SAH Study (Pterygopalatine Fossa Block as an Opioid-Sparing Treatment for Acute Headache in Aneurysmal Subarachnoid Hemorrhage): A Phase II, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial with a Sequential Parallel Comparison Design.

BACKGROUND: Acute post-subarachnoid hemorrhage (SAH) headaches are common and severe. Management strategies for post-SAH headaches are limited, with heavy reliance on opioids, and pain control is overall poor. Pterygopalatine fossa (PPF) nerve blocks have shown promising results in treatment of acute headache, including our preliminary and published experience with PPF-blocks for refractory post-SAH headache during hospitalization. The BLOCK-SAH trial was designed to assess the efficacy and safety of bilateral PPF-blocks in awake patients with severe headaches from aneurysmal SAH who require opioids for pain control and are able to verbalize pain scores. METHODS: BLOCK-SAH is a phase II, multicenter, randomized, double-blinded, placebo-controlled clinical trial using the sequential parallel comparison design (SPCD), followed by an open-label phase. RESULTS: Across 12 sites in the United States, 195 eligible study participants will be randomized into three groups to receive bilateral active or placebo PPF-injections for 2 consecutive days with periprocedural monitoring of intracranial arterial mean flow velocities with transcranial Doppler, according to SPCD (group 1: active block followed by placebo; group 2: placebo followed by active block; group 3: placebo followed by placebo). PPF-injections will be delivered under ultrasound guidance and will comprise 5-mL injectates of 20 mg of ropivacaine plus 4 mg of dexamethasone (active PPF-block) or saline solution (placebo PPF-injection). CONCLUSIONS: The trial has a primary efficacy end point (oral morphine equivalent/day use within 24 h after each PPF-injection), a primary safety end point (incidence of radiographic vasospasm at 48 h from first PPF-injection), and a primary tolerability end point (rate of acceptance of second PPF-injection following the first PPF-injection). BLOCK-SAH will inform the design of a phase III trial to establish the efficacy of PPF-block, accounting for different headache phenotypes.

Analgesic efficacy and safety of erector spinae plane block in pediatric patients undergoing elective surgery: A systematic review and Meta-analysis of randomized controlled trials.

STUDY OBJECTIVE: Ultrasound-guided erector spinae plane block (ESPB) is commonly used for perioperative analgesia in adults; however, its analgesic efficacy and safety in pediatric patients remain uncertain. This review aimed to determine whether ultrasound-guided ESPB can improve analgesic efficacy and safety in pediatric surgery. DESIGN: Meta-analysis of randomized controlled trials. SETTING: Perioperative setting. PATIENTS: Pediatric patients undergoing elective surgery under general anesthesia. INTERVENTIONS: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, KoreaMed, Web of Science, Scopus, and ClinicalTrials.gov databases for eligible published randomized controlled studies (RCTs) comparing ESPB with controls (no block or other block) in pediatric patients undergoing elective surgery under general anesthesia. MEASUREMENTS: The primary outcome was cumulative opioid consumption after surgery. Other outcomes included intraoperative opioid consumption, time to first request for rescue analgesia, number of patients requiring rescue analgesics, and pain scores after surgery. The safety outcomes were the incidences of bradycardia, hypotension, and postoperative vomiting. MAIN RESULTS: The analysis included 17 RCTs comprising 919 participants: 461 in the ESPB group, 269 in the no-block group (no block/sham block), and 189 in the other block group. Compared with the control group (no block and other blocks), ESPB significantly reduced the cumulative opioid consumption (intravenous morphine milligram equivalents) after surgery (standardized mean difference = -1.51; 95% confidence interval, -2.39 to -0.64; P = 0.0002; I2 = 92.9%) and intraoperative opioid consumption, and lowered average pain scores up to 24 h after surgery. ESPB extended the time to the first request for rescue analgesia and decreased the number of patients requiring rescue analgesics. Furthermore, ESPB lowered the pain score at most time points for 24 h after surgery, improved parental satisfaction, and reduced the incidence of postoperative vomiting compared with that in no block/sham block. CONCLUSIONS: ESPB provides effective and safe perioperative analgesia in pediatric patients undergoing elective surgery under general anesthesia.

Changes in analgesic prescriptions in Dutch general practice.

BACKGROUND: Increases in opioid prescriptions have been described; however, recent trends and prescribing patterns of analgesics in Dutch general practice are largely unknown. OBJECTIVE: To investigate recent changes in the number of analgesic prescriptions, and the indications for prescribing strong opioids. Furthermore, we aim to identify risk factors for chronic opioid use in Dutch general practice. DESIGN AND SETTING: A retrospective cohort study from 1 July 2013 to 31 June 2022, using a primary care practice based research network. SUBJECTS: Patients with ≥1 prescription for analgesics during the study period were included. MAIN OUTCOME MEASURE: Changes in the number of prescriptions for paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs) and opioids in Dutch general practice during the 9-year study period. Moreover, we analyzed indications for prescribing strong opioids by the general practitioner (GP). RESULTS: A total of 18,433 analgesic users were identified. Over time, prescriptions for paracetamol, NSAIDs and weak opioids decreased, while the number of strong opioid prescriptions increased. General practitioners prescribed more strong opioids for non-malignant pain, whereas prescriptions for malignant pain remained stable over time. Risk factors for chronic opioid use (≥90 days) included older age, lower educational level, smoking status and having a history of a musculoskeletal or psychological disorder, a malignancy or sexual, physical or psychological abuse. CONCLUSIONS: Considering the increase in strong opioid prescriptions for benign conditions, GPs need to be vigilant for patients who are at risk for chronic use. Regular monitoring and awareness for psychosocial factors in treatment of chronic pain may be key in preventing harms associated with persistent opioid use.

Risk Factors Related to Postoperative Dizziness Among Patients Who Underwent General Anesthesia and Intraoperative Analgesics: A Prospective Cohort Study.

PURPOSE: To describe postoperative dizziness for patients who received analgesics during general anesthesia and to investigate the factors related to the trend of dizziness within 3 days after surgery. DESIGN: A prospective cohort study. METHODS: This is a longitudinal study. The severity of dizziness was assessed from the day of the surgery until the third day post surgery. Generalized estimation equation models were created to determine the predictive effect of each independent variable separately. FINDINGS: After surgery, the incidence of dizziness was 42.1%. Approximately 10% of participants experienced severe dizziness. Participants with postoperative nausea and vomiting were more likely to experience postoperative dizziness. In addition, age, education level, history of motion sickness, surgical specialties, laparoscopic surgery, and long-acting analgesic use had an impact on the trend of postoperative dizziness. More than 25% of participants who used long-acting analgesics experienced dizziness on the third postoperative day. CONCLUSIONS: Postoperative dizziness was common among participants who received analgesics during general anesthesia. Monitoring for postoperative dizziness may need to be prolonged, especially in patients taking long-acting analgesics. For patients at high risk for postoperative dizziness, preventive measures such as adjusting analgesic and anesthetic medications may be necessary.

Exploring Analgesic Use Patterns Among Cancer Survivors With Chronic Chemotherapy-Induced Peripheral Neuropathy.

OBJECTIVES: To explore cancer survivors' historical and current use of analgesics for chronic chemotherapy-induced peripheral neuropathy (CIPN). SAMPLE & SETTING: 142 post-treatment cancer survivors who received neurotoxic chemotherapy and were experiencing moderate to severe CIPN. METHODS & VARIABLES: Participants completed the Treatment-Induced Neuropathy Assessment Scale at baseline and reported all analgesics used to manage CIPN. Frequency of historical or current prescription analgesic use for chronic CIPN was described and stratified by CIPN pain severity. RESULTS: At baseline, 31% of participants reported historical use of analgesics for CIPN and 46% of participants were currently using analgesics for CIPN. Gabapentin was the most frequently used analgesic, historically (20%) and currently (34%), and duloxetine was used less frequently (6% historical use, 10% current use). Many participants with severe pain (59%) reported using analgesics for CIPN. IMPLICATIONS FOR NURSING: Duloxetine, the first-line treatment for chronic CIPN pain, was used less frequently than gabapentin, a common prescription analgesic for neuropathic pain. Further research is needed to determine strategies to promote the implementation of evidence-based CIPN treatments in clinical practice.

Evaluating potential unexpected adverse events and mortality after oral analgesics administration in fracture care-a cohort study.

INTRODUCTION: Analgesic selection per individual's tolerance is essential to avoid risks. The study evaluated current oral analgesic prescription practice, analgesic adverse effects-related factors, unexpected events, and mortality post-fracture surgery. RESEARCH DESIGN AND METHODS: The present prospective cohort study from June 2022 to July 2023 enrolled a total of 198 proximal femoral, ankle, and hindfoot trauma fracture patients. Stratification was done for oral analgesics prescribed at hospital discharge and 1 week with their accompanying toxicity assessed for 2 weeks. Analyzed Kaplan-Meier curve and the absolute risk for possible analgesics-related deaths. RESULTS: Following oral analgesic administration, 122 (62%) patients experienced adverse events. In seven expiries, five were possibly due to acetaminophen added tramadol combined with any of pregabalin, diclofenac, etoricoxib, or gabapentin (absolute risk 2.5%, 97.5% proportion 2 weeks survival). Three (2% of 122) patients taking acetaminophen added tramadol or diclofenac experienced unexpected serious adverse events. Elderly diabetic and hypertensive hip fracture patients expired or experienced unexpected events. CONCLUSION: Data suggest that oral acetaminophen added tramadol combined with any of pregabalin, diclofenac, etoricoxib, or gabapentin might increase the death risk or unexpected serious adverse events in elderly diabetic and hypertensives suffering from intertrochanteric/femoral neck fracture. Safe analgesic selection is necessitated for at-risk patients.

A Rare Outcome for Transient Parotitis After Upper Gastrointestinal Endoscopy: A Case Report and Brief Review of the Literature.

Upper gastrointestinal (GI) endoscopy, though generally safe, can rarely cause complications such as transient parotitis, which typically resolves within 24 hours. Parotitis may occur due to salivary duct blockage, venous congestion from straining, or reflex parasympathetic stimulation. We discuss a 33-year-old chronic alcoholic man who developed right parotid gland swelling immediately following an upper GI endoscopy, conducted without sedation to evaluate his epigastric pain, vomiting, anorexia, and weight loss. His blood tests and abdominal ultrasound were normal. Patient developed sharp pain and swelling in the right parotid gland post-procedure. An ultrasound revealed diffuse gland swelling without abscess or lymph node enlargement. He was treated with analgesics, warm compresses, and a semisolid diet, leading to symptom resolution within 12 hours. Post-endoscopy transient parotitis is rare and typically benign, with limited evidence from case reports and small series. Diagnosis through ultrasound is crucial to exclude other causes, and treatment is mainly symptomatic, involving analgesics and warm compresses, with antibiotics if infection is suspected. This case report and brief review of literature underscore the self-limiting nature of transient parotitis following endoscopy.

ICU patients receiving remifentanil do not experience reduced duration of mechanical ventilation: a systematic review of randomized controlled trials and network meta-analyses based on Bayesian theories.

Background: The purpose of this network meta-analysis (NMA) was to evaluate the efficacy of intravenous opioid µ-receptor analgesics in shortening the duration of mechanical ventilation (MV) in ICU patients. Methods: Randomized controlled trials comparing the efficacy of remifentanil, sufentanil, morphine, and fentanyl on the duration of MV in ICU patients were searched in Embase, Cochrane, Pubmed, and Web of Science electronic databases. The primary outcome was MV duration. The Bayesian random-effects framework was used to evaluate relative efficacy. Results: In total 20 studies were included in this NMA involving 3,442 patients. Remifentanil was not associated with a reduction in the duration of MV compared with fentanyl (mean difference (MD) -0.16; 95% credible interval (CrI): -4.75 ~ 5.63) and morphine (MD 3.84; 95% CrI: -0.29 ~ 10.68). The secondary outcomes showed that, compared with remifentanil, sufentanil can prolong the duration of extubation. No regimen significantly shortened the ICU length of stay and improved the ICU mortality, efficacy, safety, and drug-related adverse events. Conclusion: Among these analgesics, remifentanil did not appear to be associated with a reduction in MV duration. Clinicians should carefully titrate the analgesia of MV patients to prevent a potentially prolonged duration of MV due to excessive or inadequate analgesic therapy. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, CRD42021232604.

Phyto-pharmacological and computational profiling of Bombax ceiba Linn. Leaves revealed pharmacological properties against oxidation, hyperglycemia, pain, and diarrhea.

The present study aimed to conduct phytochemical and pharmacological profiling of methanolic crude extract of leaves of Bombax ceiba Linn. via experimental and computational approaches. Six secondary metabolites were isolated chromatographically, and the structures were elucidated by extensive analyses of high-resolution 1H and 13C NMR data. The separated compounds were characterized as ß-sitosterol (1), ß-amyrin (2), ß-amyrin acetate (3), ß-amyrin palmitate (4), ß-amyrone (5), and isoscopoletin (6). DPPH free radical scavenging assay, tail-tipping method, writhing assay, and castor oil-induced diarrheal mice methods, respectively, were used to assess the antioxidant, hypoglycemic, analgesic, and anti-diarrheal activities of the leaf extract of B. ceiba plant species. The study observed significant reductions (p < 0.05) in the level of blood glucose at 30, 60, 120, and 180 min following the administration of the crude extracts (200 mg/kg body weight (bw) and 400 mg/kg bw). These reductions occurred in a time-dependent manner. Additionally, both doses of the investigated extracts exhibited significant (p < 0.05) central and peripheral analgesic effects compared to morphine (2 mg/kg bw) and diclofenac sodium (50 mg/kg bw), respectively. Furthermore, the 400 mg/kg bw extract demonstrated anti-diarrheal activity, reducing 54.17 % of diarrheal episodes in mice compared to loperamide with 70.83 % inhibition. The computational investigations yielded results consistent with existing in vivo findings. The results obtained from molecular docking showed that the isolated compounds had a better or comparable binding affinity to the active binding sites of the glutathione reductase enzyme, mu-opioid receptor, cyclooxygenase 2 (COX-2), glucose transporter 3 (GLUT 3), and kappa opioid receptor. These findings may indicate that the compounds isolated from the B. ceiba plant species have antioxidant, analgesic, hypoglycemic, and anti-diarrheal, properties. Consequently, it was inferred that the plant B. ceiba might be beneficial in dealing with oxidation, diarrhea, hyperglycemia, and pain. Nonetheless, further investigations are necessary to perform thorough phytochemical profiling and elucidate the exact mechanistic ways of the crude extract and the isolated phytoconstituents.

Deprescribing NSAIDs: The Potential Role of Community Pharmacists.

Non-steroidal anti-inflammatory drugs (NSAIDs) are largely used for controlling various pain conditions and are widely available in community pharmacies, with and without prescription. Despite their effectiveness, NSAIDs can pose significant risks due to potential side effects and drug interactions, particularly in polypharmacy and comorbidity contexts and for vulnerable users. This study investigated whether and how NSAIDs deprescribing can be conducted at the community pharmacy level by assessing pharmacists' confidence, attitudes, and potential barriers and facilitators. Additionally, we aimed to identify any deprescribing guidelines that pharmacists could use. A literature search and a cross-sectional digital questionnaire targeting community pharmacists in Norway were conducted. Results showed that study participants (N = 73) feel confident in identifying needs for deprescribing NSAIDs but barriers such as time constraints, lack of financial compensation, and communication challenges were noted. Participants reported positive attitudes toward deprescribing but highlighted a need for better guidelines and training. This study highlights a gap in specific guidelines for deprescribing NSAIDs and a potential for enhancing pharmacists' roles in the deprescribing process, for example, through training and improved financial incentives. Further research is encouraged to develop concrete strategies for an effective implementation where community pharmacists can be involved in the deprescribing of NSAIDs.

Efficacy and safety of hydromorphone for cancer pain: a systematic review and meta-analysis.

BACKGROUND: Cancer pain significantly impacts individuals' quality of life, with opioids being employed as the primary means for pain relief. Nevertheless, concerns persist regarding the adverse reactions and effectiveness of opioids such as morphine. Hydromorphone, recognized as a potent opioid, is a viable alternative for managing cancer-related pain. The goal of this systematic review and meta-analysis was to determine the effectiveness and safety characteristics of hydromorphone in comparison to other opioids, as well as different methods of administering this medication within the scope of cancer pain treatment. METHODS: The PubMed, Embase, Cochrane Library, Scopus, and Web of Science databases were searched on December 25th, 2023. Following the PRISMA guidelines, a systematic investigation of databases was carried out, and suitable studies were chosen according to predetermined criteria (PICO framework). The meta-analyses were performed using a random-effects model. RESULTS: This review included 18 RCTs with 2271 patients who compared hydromorphone with morphine, oxycodone, or fentanyl, as well as other types of hydromorphone. Hydromorphone demonstrated efficacy similar to that of morphine and oxycodone in reducing cancer pain intensity, decreasing additional analgesic consumption, and improving quality of life. However, morphine showed slight superiority over hydromorphone in reducing breakthrough pain. Adverse events were comparable between hydromorphone and morphine or oxycodone. Patient-controlled and clinician-controlled hydromorphone administration routes yielded similar outcomes. CONCLUSIONS: The outcomes of this study substantiate the efficacy of hydromorphone in the management of cancer-related pain, demonstrating similar levels of effectiveness and safety as morphine and oxycodone. These findings are consistent with prior comprehensive analyses, suggesting that hydromorphone is a feasible choice for alleviating cancer-associated pain. Additional investigations are warranted to determine its efficacy in distinct patient cohorts and for different modes of administration. TRIAL REGISTRATION: Prospero registration ID: CRD42024517513. Link: https://www.crd.york.ac.uk/PROSPERO/#recordDetails .

Topical amitriptyline in burning mouth syndrome: A retrospective real-world evidence study.

OBJECTIVE: To evaluate the effectiveness, tolerability, and safety of topical amitriptyline as a potential route of administration for the management of burning mouth syndrome. BACKGROUND: Burning mouth syndrome is a complex, idiopathic, and debilitating orofacial pain disorder that impairs quality of life, with a prevalence of up to 18% in menopausal women. Available drugs to alleviate its burning sensation have inconsistent and limited efficacy. Given its physicochemical properties, excellent tolerability, and ability to target peripheral pathways, topical amitriptyline seems a promising mechanistically specific analgesic drug for burning mouth syndrome. METHODS: In this retrospective cross-sectional real-world evidence study, patients with burning mouth syndrome who were prescribed topical amitriptyline for 8 weeks were identified. Eligibility criteria stemmed from ICHD-3, ICOP, and consensus definitions. The primary outcome measure was mean daily pain intensity (on a 0-10 scale); secondary outcomes included adverse events and patient global impression of improvement. Data are given as the mean ± SD. RESULTS: A total of 15 patients fulfilling the eligibility criteria were included and analyzed. Mean daily pain was 6.7 ± 2.1 at baseline and 3.7 ± 2.3 after treatment, with a mean reduction of 3.1 ± 2.8 (p = 0.002). Half of the patients experienced a decrease in pain by at least 50% (p = 0.008). Several mild adverse events were reported, such as somnolence or dry mouth. CONCLUSIONS: Topical amitriptyline may be a safe and potent route of administration in the treatment of burning mouth syndrome, a hypothesis to be tested in further controlled trials.

Prevalence of problematic pharmaceutical opioid use in patients with chronic non-cancer pain: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Chronic non-cancer pain (CNCP) is one of the most common causes of disability globally. Opioid prescribing to treat CNCP remains widespread, despite limited evidence of long-term clinical benefit and evidence of harm such as problematic pharmaceutical opioid use (POU) and overdose. The study aimed to measure the prevalence of POU in CNCP patients treated with opioid analgesics. METHOD: A comprehensive systematic literature review and meta-analysis was undertaken using MEDLINE, Embase and PsycINFO databases from inception to 27 January 2021. We included studies from all settings with participants aged ≥ 12 with non-cancer pain of ≥ 3 months duration, treated with opioid analgesics. We excluded case-control studies, as they cannot be used to generate prevalence estimates. POU was defined using four categories: dependence and opioid use disorder (D&OUD), signs and symptoms of D&OUD (S&S), aberrant behaviour (AB) and at risk of D&OUD. We used a random-effects multi-level meta-analytical model. We evaluated inconsistency using the I2 statistic and explored heterogeneity using subgroup analyses and meta-regressions. RESULTS: A total of 148 studies were included with > 4.3 million participants; 1% of studies were classified as high risk of bias. The pooled prevalence was 9.3% [95% confidence interval (CI) = 5.7-14.8%; I2 = 99.9%] for D&OUD, 29.6% (95% CI = 22.1-38.3%, I2 = 99.3%) for S&S and 22% (95% CI = 17.4-27.3%, I2 = 99.8%) for AB. The prevalence of those at risk of D&OUD was 12.4% (95% CI = 4.3-30.7%, I2 = 99.6%). Prevalence was affected by study setting, study design and diagnostic tool. Due to the high heterogeneity, the findings should be interpreted with caution. CONCLUSIONS: Problematic pharmaceutical opioid use appears to be common in chronic pain patients treated with opioid analgesics, with nearly one in 10 experiencing dependence and opioid use disorder, one in three showing signs and symptoms of dependence and opioid use disorder and one in five showing aberrant behaviour.

Predictors of persistent opioid use in Australian primary care: A retrospective cohort study, 2018-2022.

OBJECTIVE: To examine the predictors of persistent opioid use ('persistence') in people initiating opioids for non-cancer pain in Australian primary care. DESIGN: A retrospective cohort study. SETTING: Australian primary care. SUBJECTS: People prescribed opioid analgesics between 2018-2022, identified through the Population Level Analysis and Reporting (POLAR) database. METHODS: Persistence was defined as receiving opioid prescriptions for at least 90 days with a gap of less than 60 days between subsequent prescriptions. Multivariable logistic regression was used to examine the predictors of persistent opioid use. RESULTS: The sample consisted of 343,023 people initiating opioids for non-cancer pain; of these, 16,527 (4.8%) developed persistent opioid use. Predictors of persistence included older age (≥75 vs 15-44 years: Adjusted odds ratio: 1.67, 95% CI: 1.58-1.78), concessional beneficiary status (1.78, 1.71-1.86), diagnosis of substance use disorder (1.44, 1.22-1.71) and chronic pain (2.05, 1.85-2.27), initiation of opioid therapy with buprenorphine (1.95, 1.73-2.20) and long-acting opioids (2.07, 1.90-2.25), provision of higher quantity of opioids prescribed at initiation (total OME of ≥ 750mg vs < 100mg: 7.75, 6.89-8.72), provision of repeat/refill opioid prescriptions at initiation (2.94, 2.77-3.12), and prescription of gabapentinoids (1.59, 1.50-1.68), benzodiazepines (1.43, 1.38-1.50) and z-drugs (e.g., zopiclone, zolpidem; 1.61, 1.46-1.78). CONCLUSIONS: These findings add to the limited evidence of individual-level factors associated with persistent opioid use. Further research is needed to understand the clinical outcomes of persistent opioid use in people with these risk factors to support the safe and effective prescribing of opioids.

Study of PT1 Peptide Analgesic and Anti-Inflammatory Activity on a Local Inflammation Model in Mice CD-1.

PT1 peptide isolated from the venom of spider Geolycosa sp. is a modulator of P2X3 receptors that play a role in the development of inflammation and the transmission of pain impulses. The anti-inflammatory and analgesic efficacy of the PT1 peptide was studied in a model of complete Freund's adjuvant-induced paw inflammation in CD-1 mice. The analgesic activity of PT1 peptide was maximum after intramuscular injection at a dose of 0.01 mg/kg, which surpassed the analgesic effect of diclofenac at a dose of 1 mg/kg. The anti-inflammatory activity was maximum after intramuscular injection at a dose of 0.0001 mg/kg; a decrease in paw thickness was observed as soon as 2 h after the administration of the PT1 peptide against the background of inflammation development. All tested doses of PT1 peptide showed high anti-inflammatory activity 4 and 24 h after administration. PT1 peptide at a dose of 0.01 mg/kg when injected intramuscularly simultaneously produced high anti-inflammatory and analgesic effects compared to other doses of the peptide. Increasing the dose of PT1 peptide led to a gradual decrease in its analgesic and anti-inflammatory activity; increasing the dose of intramuscular injection to 0.1 and 1 mg/kg is inappropriate.

Comparison of the efficacy and safety of transdermal buprenorphine patch to conventional analgesics after operative fixation of extra capsular fracture of proximal femur.

INTRODUCTION: Proximal femur fractures are common among older individuals and pose challenges in achieving effective post-operative analgesia. Age-related co-morbidities limit the selection of analgesics in this population. This study aimed to compare the safety and effectiveness of transdermal buprenorphine (TDB) patch with traditional analgesics after fixation of an extracapsular fracture of the proximal femur. METHODOLOGY: A prospective randomized controlled study was conducted over a 2-year period, involving 60 patients who underwent surgery for extra capsular intertrochanteric fracture fixation. The patients were randomly assigned to two groups by random envelope method. Group A received an intravenous formulation of paracetamol and tramadol for the initial 48 h, followed by an oral formulation. Group B received a transdermal buprenorphine (TDB) patch delivering 5 mcg/hour immediately after surgery, which continued for 2 weeks postoperatively. During the 14-day monitoring period, patients' pain scores were assessed using the Visual Analog Scale (VAS) at rest and during movement. The primary objective was to maintain a VAS score of 4 or lower. Rescue analgesics were administered if the VAS score reached 6. The secondary objectives included evaluating the quantity of rescue analgesics required and monitoring for any adverse effects or complications. RESULTS: Pain scores at rest and during movement were significantly lower in Group B at all-time points (p-value 0.0006 - ≤ 0.0001), and the requirement for rescue analgesia was also significantly lower in this group. The administration of the TDB patch did not result in any significant adverse effects. CONCLUSION: TDB patch is secure and offers better compliance and analgesia than other analgesics in the postoperative period whilst treating proximal femur extra capsular fracture.

Opioid prescription following radical orchiectomy associated with new persistent opioid use.

INTRODUCTION: Opioid dependence represents a public health crisis and can be observed after outpatient urologic procedures. The purpose of this study was to evaluate the risk of persistent opioid usage after radical orchiectomy for testicular cancer. MATERIALS AND METHODS: The TriNetX Research network database was queried for men between 15 and 45 years undergoing radical orchiectomy for a diagnosis of testicular cancer. All patients with N+ or M+ disease, prior opioid use, and patients who underwent chemotherapy, radiotherapy, or retroperitoneal lymph node dissection were excluded. Patients were stratified whether they were prescribed opioids or not at time of orchiectomy. The incidence of new, persistent opioid use, defined as a prescription for opioids between 3 and 15 months after orchiectomy, was evaluated. RESULTS: A total of 2,911 men underwent radical orchiectomy for testicular cancer, of which 89.8% were prescribed opioids at time of orchiectomy. After propensity score matching for age, race, and history of psychiatric diagnosis, 592 patients were included (296 received opioids, 296 did not). Overall, 0% of patients who did not receive postoperative opioids developed new persistent opioid use, whereas 10.5% of patients who received postoperative opioids developed new persistent opioid use. Patients prescribed postoperative opioids for orchiectomy had statistically higher risk difference of developing new persistent opioid use (Risk Difference: 10.5%; 95% CI: 7.0-14.0; Z: 5.7; P < 0.01). CONCLUSIONS: Postoperative opioid prescription following radical orchiectomy is significantly associated with developing new persistent opioid use, with 1 in 10 young men who received postoperative opioids obtaining a new prescription for opioids well beyond the postoperative period. Future efforts should emphasize nonopioid pathways for pain control following this generally minor procedure.