Chronic Non-cancer Pain Patients Research Articles

Primary care-based interventions for secondary prevention of opioid dependence in chronic non-cancer pain patients on pharmaceutical opioids: systematic review.

Globally almost one third of adults with chronic non-cancer pain (CNCP) are prescribed opioids. Prevention of opioid dependence among these patients is a public health priority. Synthesise the evidence on the effectiveness of primary care-based interventions for secondary prevention of opioid dependence in CNCP patients on pharmaceutical opioids. Systematic review of randomised controlled trials (RCTs) and comparative non-randomised studies of interventions from high-income countries. We searched five databases for studies on non-tapering secondary prevention interventions such as tools for predicting dependence, screening tools for early recognition of dependence, prescribing/medication monitoring, and specialist support. We examined multiple outcomes, including reduction in opioid dosage. Primary analyses were restricted to RCTs with data synthesised using an effect direction plot. Risk of bias was assessed using the Cochrane risk of bias (RoB2) tool. Of 7,102 identified reports, 18 studies were eligible (8 RCTs). Most used multiple interventions/components. Of the seven RCTs at low risk of bias or 'some concerns', five showed a positive intervention effect on at least one relevant outcome, four of which included a nurse care manager and/or other specialist support. The remaining two RCTs showed no positive effect of automated symptom monitoring and optimised analgesic management by a nurse care manager/physician pain specialist team, or of a mobile opioid management app. We identify a clear need for further adequately powered high quality studies. The conclusions that can be drawn on intervention effectiveness are limited by the sparsity and inconsistency of available data.

Prescribing pattern insights from a longitudinal study of older adult inpatients with polypharmacy and chronic non-cancer pain.

The present study sought to determine the prevalence of chronic non-cancer pain (CNCP) among older adult inpatients with polypharmacy. It also aimed to analyse prescription patterns and assess the therapy adequacy and patient complexity for those with and without CNCP. This 4-year longitudinal study examined data from an exhaustive acute care hospital register on home-dwelling older adult patients (≥65) with polypharmacy. Commonly known combinations of potentially inappropriate medications were used to estimate therapy adequacy. Patient complexity was evaluated by comparing number of comorbidities and investigating physical and cognitive deficits. We determined a prevalence of CNCP of 9.7% among all older adult inpatients with polypharmacy, rising to 11.3% for those aged ≥85. Overall, CNCP patients were prescribed more drugs and had more comorbidities and physical and cognitive deficits than patients without CNCP. Older adult patients with CNCP received more analgesics, greater quantities of opioids, paracetamol and co-analgesics and elevated opioid dosages. Older adult patients with CNCP aged ≥85 received fewer analgesics, opioids, non-steroidal anti-inflammatory drugs and co-analgesics but more paracetamol. Older adult patients with CNCP were prescribed more potentially inappropriate medications involving opioids. In particular, 24.5% received an opioid and a hypnotic (benzodiazepine or Z-drug), and 8.6% received an opioid and a gabapentinoid. Observed differences in medication use between older adult inpatients with or without CNCP may be relevant for clinical practice. Potentially inadequate co-prescribing (such as hypnotics and opioids) affects a higher proportion of patients with CNCP and may have serious unintended consequences. This study describes differences in prescription patterns between people with and without chronic non-cancer pain in a large dataset of 20,422 discharges. The differences found may be relevant to clinical practice. In particular, high co-prescribing of opioids and hypnotics may have serious unintended consequences. Greater physical and cognitive deficits may indicate greater patient complexity, and appropriate interventions need to be developed to improve the management of this vulnerable patient group.

Clinical prediction of opioid use disorder in chronic pain patients: a cohort-retrospective study with a pharmacogenetic approach.

Opioids are widely used in chronic non-cancer pain (CNCP) management. However, they remain controversial due to serious risk of causing opioid use disorder (OUD). Our main aim was to develop a predictive model for future clinical translation that include pharmacogenetic markers. An observational study was conducted in 806 pre-screened Spanish CNCP patients, under long-term use of opioids, to compare cases (with OUD, N.=137) with controls (without OUD, N.=669). Mu-opioid receptor 1 (OPRM1, A118G, rs1799971) and catechol-O-methyltransferase (COMT, G472A, rs4680) genetic variants plus cytochrome P450 2D6 (CYP2D6) liver enzyme phenotypes were analyzed. Socio-demographic, clinical and pharmacological outcomes were also registered. A logistic regression model was performed. The model performance and diagnostic accuracy were calculated. OPRM1-AA genotype and CYP2D6 poor and ultrarapid metabolizers together with three other potential predictors: 1) age; 2) work disability; 3) oral morphine equivalent daily dose (MEDD), were selected with a satisfactory diagnostic accuracy (sensitivity: 0.82 and specificity: 0.85), goodness of fit (P=0.87) and discrimination (0.89). Cases were ten-year younger with lower incomes, more sleep disturbances, benzodiazepines use, and history of substance use disorder in front of controls. Functional polymorphisms related to OPRM1 variant and CYP2D6 phenotypes may predict a higher OUD risk. Established risk factors such as young age, elevated MEDD and lower incomes were identified. A predictive model is expected to be implemented in clinical setting among CNCP patients under long-term opioids use.

Chronic Non-cancer Pain and Associated Risks of Incident Mild Cognitive Impairment and Alzheimer's Disease and Related Dementias in Middle-Aged and Older Adults.

The goal of this study is to investigate the association between chronic non-cancer pain (CNCP) and mild cognitive impairment (MCI)/Alzheimer's disease and related dementias (ADRDs) development among adults aged ≥50 using administrative claims data from a national commercial health insurance company during 2007-2017. To reduce selection bias, propensity-score matching was applied to select comparable CNCP and non-CNCP patients. Time-dependent Cox proportional-hazards regressions were conducted to estimate the hazard ratios (HRs) of incident MCI/ADRDs. Of 170,900 patients with/without CNCP, 0.61% developed MCI and 2.33% had been diagnosed with ADRDs during the follow-up period. Controlling for potential confounders, CNCP patients had a 123% increase in MCI risk (HR = 2.23; 95% CI = 1.92-2.58) and a 44% increase in ADRDs risk (HR = 1.44; 95% CI = 1.34-1.54) relative to non-CNCP patients. CNCP is a risk factor for MCI/ADRDs. Promoting awareness and improving early CNCP diagnosis in middle-aged and older adults should be incorporated into cognitive impairment and dementia prevention.

Prevalence and Characteristics of Medicinal Cannabis Use among Chronic Pain Patients; A Post- Legalization Study in a Tertiary Care Setting in Thailand

Objective: Cannabinoid products have been applied for numerous medical conditions, including chronic pain. Thailand was the first country in South East Asia to legalize medical cannabinoids. This study aims to explore prevalence, characters, attitude, side effects of medical cannabinoid use, and pain-related outcome among the chronic cancer and non-cancer pain population at Siriraj Hospital. Materials and Methods: 200 chronic cancer pain and 670 chronic noncancer pain patients were collected by questionnaires and interviews. Data included demographic data, clinical diagnosis, pain treatment, knowledge, attitude, pattern of use, side effects and quality of life of cannabinoid extracts. Results: Prevalence of active cannabis user was 15% in chronic cancer pain and 3.1% in noncancer pain. Oil extract sublingual was the most common form. Pain control was the most common initial reason for usage. No serious side effects were reported. Common side effects were dry oral mucosa, drowsiness, and headache. The most common source was obtained from friends. 36% of the patients believed they had enough understanding of medical cannabis, while 68.5% agreed that it is appropriate to use in Thailand. In cancer patients, the Edmonton Symptom Assessment System (ESAS) subscale for lack of appetite, anxiety, and subscale for a brief pain inventory (BPI) for enjoyment of life were higher among active users. In patients with noncancer pain, only the mood subscale BPI was lower among active users. Conclusion: Medical cannabis usage is common compared with general population in Thai patients with chronic pain and may be associated with increased pain interference and cancer-related symptoms. Nonmedical license prescription and nonmedical license cannabis products were common in Thailand.

Opioid-Related Respiratory Depression in Non-Cancer Patients, as Reported in the Japanese Adverse Drug Event Report Database.

Opioid-induced respiratory depression (RD) is a potentially life-threatening adverse drug event. This study used the Japanese Adverse Drug Event Report (JADER) database to investigate the profile of opioid-related RD in non-cancer patients. We analyzed data recorded in the JADER database between April 2004 and February 2020, which were downloaded from the Pharmaceutical and Medical Devices Agency website. Reporting odds ratios for RD were calculated for the 20 opioids approved in Japan, and daily dose and onset time were further analyzed for opioids used in chronic non-cancer pain (CNCP). Among the opioids, RD adverse event signals were detected for 22 combinations of opioids and administration routes in non-cancer patients. Of these combinations, transdermal buprenorphine and oral tramadol/acetaminophen were approved for CNCP and tended to be reported more frequently in elderly patients. The median daily doses of transdermal buprenorphine and oral tramadol/acetaminophen were 10.0 and 22.5 mg of daily oral morphine equivalent doses, respectively, which are within the standard range for starting dosage. The median time-to-onset of transdermal buprenorphine and oral tramadol/acetaminophen was 6.5 and 4.0 days, respectively, and 75% of cases were reported within 20 to 40 days after the start of treatment. The hazard type for both opioids was classified as early failure. Our findings suggest that elderly CNCP patients should be closely monitored after the start of opioid treatment, especially during the first week and, if possible, for 1 month, even if starting doses are within ranges recommended by the manufacturer and guidelines.

Digital Behavioural Interventions to Reduce Opioid Use in Chronic Non-Cancer Pain Patients: A Systematic Review

Abstract Introduction Opioid medications have become increasingly prevalent in the treatment of chronic non-cancer pain1. This increase in opioid usage has given rise to the ‘Opioid Crisis’ which refers to the significant increase in overdose, addiction, and deaths in the USA and Canada particularly2. Furthermore, the World Health Organisation has declared there to have been approximately 0.5 million deaths in relation to drug use worldwide, with more than 70% of those deaths related to opioids3. Advances in technology have paved the way for the use of digital behavioural interventions, such as mobile applications, virtual reality, and online therapies, to potentially mitigate opioid use in patients suffering from chronic non-cancer pain. These interventions aim to assist individuals in modifying health behaviours to promote overall well-being and may serve as a preventive measure against the detrimental effects of long-term opioid use. Aim This systematic review aimed to evaluate the current evidence regarding the effectiveness of digital behavioural interventions in reducing opioid use among chronic non-cancer pain patients. Methods A comprehensive search was conducted in three electronic databases (MEDLINE, EMBASE, and Web of Science) using specific search terms. Primary outcomes focused on opioid usage measurements, while secondary outcomes pertained to pain measurements. Eligible studies included adult patients with chronic non-cancer pain (excluding cancer/palliative patients) who received opioid prescriptions and engaged in digital behavioural interventions in any setting. Two researchers double-screened eligible studies based on titles and abstracts, excluding duplicates and those not meeting the eligibility criteria. Data extraction was performed, and study quality was assessed using the Cochrane Risk of Bias Tool (double-screened). Ethical approval was not required as this study was a systematic review. Results Out of 30,388 articles identified, six studies conducted in the USA met the inclusion criteria. Risk of bias assessment revealed one study with a low risk, two with some concerns, and the majority with a high risk of bias. The publication dates of the identified papers ranged from 2016 to 2021. There was an overall participant population of 605. The interventions included virtual reality, mobile health applications, web-based cognitive-behavioural therapy, guided audio-visual relaxation, and an electronic health toolkit. Two studies reported a specific reduction in opioid use, while three studies did not provide direct measurements for opioid use. However, these studies indicated a reduction in opioid analgesic usage by reporting either over-the-counter analgesic measures or a Current Opioid Misuse Measure score. Discussion/Conclusion This systematic review was conducted in response to the need for updated pain management strategies. The literature suggests that digital behavioural interventions hold promise for reducing opioid use among chronic non-cancer pain patients. However, due to limitations in the included studies, such as sample size, heterogeneity, and potential bias, further research is needed to fully understand their effectiveness. Future studies should focus on optimising the design and delivery of the interventions tailored to this patient population. Continued research in this area has the potential to address the societal burden of opioid misuse and improve patients' quality of life.

Long-term deprescription in chronic pain and opioid use disorder patients: Pharmacogenetic and sex differences.

More than half of patients with opioid use disorder for chronic non-cancer pain (CNCP) reduced their dose through a progressive opioid withdrawal supported by a rotation to buprenorphine and/or tramadol. The aim of this research is to analyse the long-term effectiveness of opioid deprescription taking into account the impact of sex and pharmacogenetics on the inter-individual variability. A cross-sectional study was carried out from October 2019 to June 2020 on CNCP patients who had previously undergone an opioid deprescription (n = 119 patients). Demographic, clinical (pain, relief and adverse events) and therapeutic (analgesic use) outcomes were collected. Effectiveness (< 50 mg per day of morphine equivalent daily dose without any aberrant opioid use behaviour) and safety (number of side-effects) were analysed in relation to sex differences and pharmacogenetic markers impact [OPRM1 genotype (rs1799971) and CYP2D6 phenotypes]. Long-term opioid deprescription was achieved in 49 % of the patients with an increase in pain relief and a reduction of adverse events. CYP2D6 poor metabolizers showed the lowest long-term opioid doses. Here, women showed a higher degree of opioid deprescription, but increased use of tramadol and neuromodulators, as well as an increased number of adverse events. Long-term deprescription was successful in half of the cases. Understanding sex and gender interaction plus a genetic impact could help to design more individualized strategies for opioid deprescription.

Impact of CYP2D6 genotype on opioid use disorder deprescription: an observational prospective study in chronic pain with sex-differences.

Introduction: Opioid deprescription is the process of supervised tapering and safe withdrawal when a potentially inappropriate use is detected. This represents a challenge in chronic non-cancer pain (CNCP) patients who may respond differently to the procedure. Our aim was to analyze the potential impact of CYP2D6 phenotypes and sex on the clinical and safety outcomes during an opioid use disorder (OUD) tapering process. Methods: A prospective observational study was conducted on CNCP ambulatory OUD patients (cases, n = 138) who underwent a 6-month opioid dose reduction and discontinuation. Pain intensity, relief and quality of life (Visual analogue scale, VAS 0-100mm), global activity (GAF, 0-100 scores), morphine equivalent daily dose (MEDD), analgesic drugs adverse events (AEs) and opioid withdrawal syndrome (OWS, 0-96 scores) were recorded at basal and final visits. Sex differences and CYP2D6 phenotypes (poor (PM), extensive (EM) and ultrarapid (UM) metabolizers based on CYP2D6*1, *2, *3, *4, *5, *6, *10, *17, *41, 2D6*5, 2D6 × N, 2D6*4 × 2 gene variants) were analyzed. Results: Although CYP2D6-UM consumed three-times less basal MEDD [40 (20-123) mg/day, p = 0.04], they showed the highest number of AEs [7 (6-11), p = 0.02] and opioid withdrawal symptoms (46 ± 10 scores, p = 0.01) after deprescription. This was inversely correlated with their quality of life (r = -0.604, p < 0.001). Sex-differences were evidenced with a tendency to a lower analgesic tolerability in females and lower quality of life in men. Discussion: These data support the potential benefits of CYP2D6-guided opioid deprescription, in patients with CNCP when OUD is detected. Further studies are required to understand a sex/gender interaction.

Long-term opioid treatment and endocrine measures in chronic non-cancer pain patients.

The prevalence of chronic non-cancer pain (CNCP) has increased dramatically the past decades, which combined with indiscriminate use of prescribed opioids has become a public health problem. Endocrine dysfunction may be a complication of long-term opioid treatment (L-TOT), but the evidence is limited. This study aimed at investigating the associations between L-TOT and endocrine measures in CNCP patients. Cortisol (spot and after stimulation), thyrotropin (TSH), thyroxin (T4), insulin-like growth factor 1 (IGF-1), prolactin (PRL), 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone (DHEAS), sex hormone-binding globulin (SHBG), total testosterone (TT) and free testosterone (fT) were measured. Group comparisons were done between CNCP patients in L-TOT and controls as well as between patients on high- or low-dose morphine equivalents. Eighty-two CNCP patients (38 in L-TOT and 44 controls not receiving opioids) were included. Low TT (p = 0.004) and fT concentrations (p < 0.001), high SHBG (p = 0.042), low DEAS (p = 0.017) and low IGF-1 (p = 0.003) in men were found when comparing those in L-TOT to controls and high PRL (p = 0.018), low IGF-1 standard deviation score (SDS) (p = 0.006) along with a lesser, but normal cortisol response to stimulation (p = 0.016; p = 0.012) were found when comparing L-TOT to controls. Finally, a correlation between low IGF-1 levels and high opioid dose was observed (p < 0.001). Our study not only supports previous findings but even more interestingly disclosed new associations. We recommend future studies to investigate endocrine effects of opioids in larger, longitudinal studies. In the meanwhile, we recommend monitoring endocrine function in CNCP patients when prescribing L-TOT. This clinical study found associations between L-TOT, androgens, growth hormone and prolactin in patients with CNCP compared to controls. The results support previous studies as well as add new knowledge to the field, including an association between high opioid dose and low growth hormone levels. Compared to existing research this study has strict inclusion/exclusion criteria, a fixed time period for blood sample collection, and adjustments for potential confounders, which has not been done before.

Feasibility and Acceptability of an Overdose Prevention Intervention Delivered by Community Pharmacists for Patients Prescribed Opioids for Chronic Non-Cancer Pain.

There have been increases in prescriptions of high strength opioids for chronic non-cancer pain (CNCP), but CNCP patients perceive themselves as being at low risk of opioid overdose and generally have limited overdose awareness. This study examined how an overdose prevention intervention (opioid safety education, naloxone training, and take-home naloxone (THN)) delivered by community pharmacists for patients prescribed high-strength opioids for CNCP would work in practice in Scotland. Twelve patients received the intervention. CNCP patients and Community Pharmacists were interviewed about their experiences of the intervention and perceptions of its acceptability and feasibility. CNCP patients did not initially perceive themselves as being at risk of overdose but, through the intervention, developed insight into opioid-related risk and the value of naloxone. Pharmacists also identified patients' low risk perceptions and low overdose awareness. While pharmacists had positive attitudes towards the intervention, they outlined challenges in delivering it under time and resource pressures and during the COVID-19 pandemic. Overdose prevention interventions are required in the CNCP population as this group has elevated risk factors for overdose but are commonly overlooked. Customised overdose prevention interventions for CNCP patients attend to gaps in overdose awareness and risk perceptions in this population.

Comparative Study of Opioid Initiation With Tramadol, Short-acting Hydrocodone, or Short-acting Oxycodone on Opioid-related Adverse Outcomes Among Chronic Noncancer Pain Patients.

To compare the safety profiles of low and high-dose tramadol, short-acting hydrocodone, and short-acting oxycodone therapies among chronic noncancer pain individuals. A retrospective cohort study of individuals with back/neck pain/osteoarthritis with an initial opioid prescription for tramadol, hydrocodone, or oxycodone was conducted using IQVIA PharMetrics Plus claims for Academics database (2006 to 2020). Two cohorts were created for separately studying opioid-related adverse events (overdoses, accidents, self-inflicted injuries, and violence-related injuries) and substance use disorders (opioid and nonopioid). Patients were followed from the index date until an outcome event, end of enrollment, or data end. Time-varying exposure groups were constructed and Cox regression models were estimated. A total of 1,062,167 (tramadol [16.5%], hydrocodone [61.1%], and oxycodone [22.4%]) and 986,809 (tramadol [16.5%], hydrocodone [61.3%], and oxycodone [22.2%]) individuals were in the adverse event and substance use disorder cohorts. All high-dose groups had elevated risk of nearly all outcomes, compared with low-dose hydrocodone. Compared with low-dose hydrocodone, low-dose oxycodone was associated with a higher risk of opioid overdose (hazard ratio: 1.79 [1.37 to 2.33]). No difference in risk was observed between low-dose tramadol and low-dose hydrocodone (hazard ratio: 0.85 [0.64 to 1.13]). Low-dose oxycodone had higher risks of an opioid use disorder, and low-dose tramadol had a lower risk of accidents, self-inflicted injuries, and opioid use disorder compared with low-dose hydrocodone. Low-dose oxycodone had a higher risk of opioid-related adverse outcomes compared with low-dose tramadol and hydrocodone. This should be interpreted in conjunction with the benefits of pain control and functioning associated with oxycodone use in future research.

Assessing Opioid Abuse in Chronic Pain Patients: Further Validation of the Prescription Opioid Misuse Index (POMI) Using Item Response Theory

AbstractDue the limitations of the previous validations, the purpose of this study was to further validate the Prescription Opioid Misuse Index (POMI) in a larger sample of chronic non-cancer pain (CNCP) patients and to examine differential item functioning (DIF) across sex. Participants (n=225 CNCP patients under long-term opioid therapy) completed patient characteristics, self-reported POMI and DSM-5 prescription opioid use disorder measurements. Reliability and factor structure were assessed using both item response theory and classical test theory. ROC curve analysis was used to establish the optimum cut-off score for detecting the presence of DSM-5 prescription opioid-use disorder. Concurrent validity was also tested. The POMI showed a unidimensional factor structure and acceptable internal consistency (ωcat =0.62). DIF analysis showed that males and females respond similarly to each item of the POMI, supporting unbiased measurement of the latent trait across both groups. A cut-off point of 2 is suggested in order to maximize the accuracy of the instrument as a first-screening tool for opioid misuse (AUC=0.78; p&lt;0.001; CI 95%: 0.72–0.85). Concurrent validity of the POMI was high with DSM-5 moderate to severe opioid-use disorder criteria (OR=7.824, p&lt;0.001). These results indicate that the POMI is a valid and clinically feasible screening instrument for detecting CNCP patients who misuse opioid medications. The short length of the scale could meet the needs of clinical practice as it allows clinicians to precisely identify and monitor prescription opioid misuse in both male and female patients.

Comparison of Older and Younger Patients Referred to a Non-interventional Community Pain Clinic in the Greater Toronto Area (GTA).

To compare demographic and pain characteristics of older (≥ 65) vs younger (< 65) chronic non-cancer pain patients referred to a community pain clinic in the Greater Toronto Area (GTA), Ontario, Canada. This is a retrospective study of 644 consecutive new patients with pain seen during 2016-2017 (older group n = 126; younger group n = 518). Demographic characteristics, Brief Pain Inventory pain ratings, and diagnosis were obtained using retrospective chart review. Patients were classified into groupI (pure biomedical pathology), groupII (mixed biomedical causes and psychological factors) and groupIII (no detectable physical pathology but psychological factors were considered important). Older patients comprised 19.6% of the overall population (higher than the average GTA older population). Regarding older vs younger group, male/female ratio was 1:1.3 vs 1:1.7 respectively, while 71% of the older patients were foreign born vs 37% of the younger group (p < 0.001). Low back was the most prevalent pain site for both groups; 70% of the older patients were classified as groupI vs 35% of the younger patients (p < 0.0001), and only 6% as groupIII (vs 18% of the younger population, p < 0.05). The study points to considerable differences between younger and older patients with pain with the latter presenting with significant biomedical pathology but lesser psychopathology. The results are comparable to those obtained from a university pain clinic as well as a rural Northern Ontario clinic. Implications of the study for planning of pain care are discussed.

Sex Differences in Oxycodone/Naloxone vs. Tapentadol in Chronic Non-Cancer Pain: An Observational Real-World Study.

Despite the large body of research on sex differences in pain, there is a lack of translation to real-world pain management. Our aim was to analyse the sex differences in the analgesic response to oxycodone/naloxone (OXN) and tapentadol (TAP), in comparison with other opioids (OPO) commonly prescribed for chronic non-cancer pain (CNCP). An observational and cross-sectional study was conducted on ambulatory CNCP patients (n = 571). Sociodemographic, clinical (pain intensity, relief, and quality of life), safety (adverse events (AEs), adverse drug reactions), hospital frequentations and pharmacological (morphine equivalent daily dose (MEDD)) variables were collected. Multiple linear regressions were carried out to assess the association between sex and outcomes. Sex differences were observed, with lower female tolerability and higher hospital frequentation, especially in the OXN group (OR AEs report = 2.8 [1.8–4.4], p < 0.001). Here, females showed higher hospital use (23% hospital admission, 30% prescription change, p < 0.05), requiring a higher MEDD (127 ± 103 mg/day, p < 0.05), compared to OXN men. Regardless of the opioid group, CNCP women were significantly older than men (three years), with significantly higher benzodiazepine use (OR = 1.6 [1.1–2.3]), more constipation (OR = 1.34 [0.93–1.90]) and headache (OR = 1.45 [0.99–2.13]) AEs, than men who were more likely to refer sexual dysfunction (OR = 2.77 [1.53–5.01]), and loss of libido (OR = 1.93 [1.22–3.04]). Sex-differences were found related to poorer female drug tolerability and higher hospital resources, even worst in OXN female users. Other differences related to older female ages and benzodiazepine prescription, need to be further analysed from a gender perspective.

Patient, family members and community pharmacists' views of a proposed overdose prevention intervention delivered in community pharmacies for patients prescribed high-strength opioids for chronic non-cancer pain: An explorative intervention development study.

Despite opioid prescribing for chronic non-cancer pain (CNCP) having limited therapeutic benefits, recent evidence indicates significant increases in the prescribing of high-strength opioids for individuals with CNCP. Patients prescribed opioids for CNCP have overdose risk factors but generally have low opioid overdose awareness and low perceptions of risk related to prescribed opioids. Currently, there are few bespoke overdose prevention resources for this group. This qualitative study investigated views on a naloxone intervention for people prescribed high-strength opioids for CNCP delivered via community pharmacies. The intervention included overdose risk awareness and naloxone training and provision. Interviews were conducted with eight patients, four family members and two community pharmacists. Participants were convenience sampled and recruited through networks within the Scottish pain community. The Framework approach was used to analyse findings. All participants had positive attitudes towards the intervention, but patients and family members considered risk of overdose to be very low. Three themes were identified: potential advantages of the intervention; potential barriers to the intervention; and additional suggestions and feedback about the intervention. Advantages included the intervention providing essential overdose information for CNCP patients. Barriers included resource and time pressures within community pharmacies. While patients had low overdose knowledge and did not see themselves as being at risk of opioid overdose, they were receptive to naloxone use and positive about the proposed intervention. A feasibility trial is merited to further investigate how the intervention would be experienced within community pharmacy settings.

Myth and Truth in Opioid Consumption with Intrathecal Morphine Pump Implantation in Chronic Pain: A Retrospective Cohort Study with Claims Database in South Korea.

To investigate the opioid consumption and the healthcare resource utilization in patients with the intrathecal drug delivery system (IDDS) therapy and the comprehensive medical management (CMM) alone. A retrospective cohort study with a customized claims database. In a university-based hospital. Patients with complex regional pain syndrome, post-laminectomy syndrome, and fibromyalgia. Using propensity score matching (1:3), we selected patients with morphine infusion through IDDS (IDDS group) and CMM alone (CMM group). The primary endpoints were comparisons of average morphine equivalents daily dosages (MEDD, mg/day) for 6 and 12 months from an index date. The number of emergency room (ER) visits and hospitalizations and the total medical expenditures were compared as secondary outcomes. In total, 82 patients (N = 23 in the IDDS group and N = 59 in the CMM group) were analyzed. Although a 6-month average MEDD did not reach statistical significance, a 12-month average MEDD was significantly decreased in the IDDS group compared to the CMM group (53.2 ± 46.3 vs 123.9 ± 176.4, respectively; P = 0.008). ER visits were more frequent in the IDDS group than the CMM group at baseline (5.4 vs 0.5, respectively; P = .002), which was maintained for 12 months (P < 0.001). Otherwise, the number of hospitalization and the medical expenditures for pain management were not different between the groups for 12 months. The combined IDDS therapy had some benefits in reducing opioid consumption for 1-year follow-up compared to the CMM alone in chronic noncancer pain patients.

Oxycodone/naloxone versus tapentadol in real-world chronic non-cancer pain management: an observational and pharmacogenetic study

Tapentadol (TAP) and oxycodone/naloxone (OXN) potentially offer an improved opioid tolerability. However, real-world studies in chronic non-cancer pain (CNCP) remain scarce. Our aim was to compare effectiveness and security in daily pain practice, together with the influence of pharmacogenetic markers. An observational study was developed with ambulatory test cases under TAP (n = 194) or OXN (n = 175) prescription with controls (prescribed with other opioids (control), n = 216) CNCP patients. Pain intensity and relief, quality of life, morphine equivalent daily doses (MEDD), concomitant analgesic drugs, adverse events (AEs), hospital frequentation and genetic variants of OPRM1 (rs1799971, A118G) and COMT (rs4680, G472A) genes, were analysed. Test CNCP cases evidenced a significantly higher pain relief predictable due to pain intensity and quality of life (R2 = 0.3), in front of controls. Here, OXN achieved the greatest pain relief under a 28% higher MEDD, 8–13% higher use of pregabalin and duloxetine, and 23% more prescription change due to pain, compared to TAP. Whilst, TAP yielded a better tolerability due the lower number of 4 [0–6] AEs/patient, in front of OXN. Furthermore, OXN COMT-AA homozygotes evidenced higher rates of erythema and vomiting, especially in females. CNCP real-world patients achieved higher pain relief than other traditional opioids with a better tolerability for TAP. Further research is necessary to clarify the potential influence of COMT and sex on OXN side-effects.

Pharmaceuticalization to Opioid Pharmacovigilance: A Qualitative Investigation of the Impact of Opioid-related Policy Changes and the Perspectives of Residents and Chronic Non-cancer Pain Patients

As a result of the pharmaceuticalization of chronic pain over the past three decades, opioid therapy became a common form of treatment for chronic pain patients. However, the overprescribing of opioids led to the opioid overdose epidemic in the United States. In response, the Centers for Disease Control and Prevention implemented guidelines reducing the number of opioid prescriptions—better known as opioid pharmacovigilance. Little is known about the sociocultural challenges during the transition to opioid pharmacovigilance for the resident/patient relationship. Using a thematic analysis, we analyzed 20 semi-structured interviews of residents and chronic non-cancer pain (CNCP) patients in a family medicine residency practice. Findings suggest that due to the pharmaceuticalization of CNCP and the transition to opioid pharmacovigilance, residents develop a wariness to prescribe opioids, which leads to prejudice against patients. Patients report constrained care and a lack of alternative treatments for chronic pain, which inevitably leads to duplicitous behavior.

Long‐term observational studies with cannabis‐based medicines for chronic non‐cancer pain: A systematic review and meta‐analysis of effectiveness and safety

This systematic review evaluated the effectiveness, tolerability and safety of cannabis-based medicines (CbMs) for chronic non-cancer pain (CNCP) in long-term observational studies. CENTRAL, EMBASE and MEDLINE were searched until December 2021. We included prospective observational studies with a study duration ≥26 weeks. Pooled estimates of event rates of categorical data and standardized mean differences (SMD) of continuous variables were calculated using a random effects model. Six studies were included with 2686 participants, with study duration ranging between 26 and 52 weeks. Pain conditions included nociceptive, nociplastic, neuropathic and mixed pain mechanisms. The certainty of evidence for every outcome was very low. The weighted mean difference of mean pain reduction was 1.75 (95% confidence interval [CI] 0.72 to 2.78) on a 0-10 scale. 20.8% (95% CI 10.2% to 34.0%) of patients reported pain relief of 50% or greater. The effect size for sleep problems was moderate and for depression and anxiety was low. Study completions was reported for 53.3% (95% CI 26.8% to 79.9%) of patients, with dropouts of 6.8% (95% CI 4.3% to 9.7%) due to adverse events. Serious adverse events occurred in 3.0% (95 CI 0.02% to 12.8%) and 0.3% (95% CI 0.1% to 0.6%) of patients died. Information included in observational studies should be regarded with caution. Within the context of observational studies. CbMs had positive effects on multiple symptoms for some CNCP patients and were generally well tolerated and safe. There is very low quality evidence for the long-term effectiveness (pain, sleep, mood, health-related quality of life), tolerability and safety of medical cannabis for chronic non-cancer pain (CNCP) according to reports of prospective observational studies. Predefined criteria of a large magnitude of effect size in these types of studies were not met. Nevertheless, long-term medical cannabis therapy can be considered in some carefully selected and monitored patients with CNCP.