Analysis of opioid analgesics consumption in Africa: a longitudinal study from a 20-year continental perspective.

BACKGROUND: Opioid analgesics are essential for managing acute and chronic pain in diseases such as cancer. Inadequate opioid access remains a major public health concern in low-income regions including Africa. This study aimed to provide updated and comprehensive data on changes in opioid consumption, specifically in Africa. METHODS: This longitudinal study has updated and expanded upon the International Narcotics Control Board data obtained from 1999 to 2021, assessing opioid consumption trends across all African countries. The defined daily doses for statistical purposes (SDDD) was used to determine the changes in opioid consumption in Africa. In addition, we used sub-analyses of the data to delve into individual substances, income levels, cancer incidence, cancer mortality, and sub-regional cluster analysis (based on the language spoken) to identify possible disparities and inform further research and tailored solutions. FINDINGS: Our results indicate a persistently low and stagnant trend in opioid consumption between 2001-03 and 2019-21, from 73 SDDD (95% CI 69-77) to 55 SDDD (32-79). In-depth analysis revealed a morphine consumption increase from 735 SDDD in 1999 to 1115 SDDD in 2021. Moreover, opioid consumption was closely related to country-level income levels, with most of the low-income and lower-middle-income African countries reporting low opioid consumption. Notably, the escalating incidence and mortality rates associated with cancer in Africa indicated a misalignment with the trajectory of opioid use. Additionally, French-speaking African countries exhibited lower opioid usage than the rest of the continent, suggesting avenues for research into cultural, political, and social aspects. INTERPRETATION: In the context of global doubling in opioid consumption, Africa has shown insufficient and stagnant opioid consumption during the last 20 years. These findings underscore the need for policy reform to facilitate safe and responsible opioid access in Africa, particularly for legitimate indications such as cancer pain and palliative care. FUNDING: None. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Mobile Health App and Web Platform (eDOL) for Medical Follow-Up of Patients With Chronic Pain: Cohort Study Involving the French eDOL National Cohort After 1 Year.

BACKGROUND: Chronic pain affects approximately 30% of the general population, severely degrades quality of life and professional life, and leads to additional health care costs. Moreover, the medical follow-up of patients with chronic pain remains complex and provides only fragmentary data on painful daily experiences. This situation makes the management of patients with chronic pain less than optimal and may partly explain the lack of effectiveness of current therapies. Real-life monitoring of subjective and objective markers of chronic pain using mobile health (mHealth) programs could better characterize patients, chronic pain, pain medications, and daily impact to help medical management. OBJECTIVE: This cohort study aimed to assess the ability of our mHealth tool (eDOL) to collect extensive real-life medical data from chronic pain patients after 1 year of use. The data collected in this way would provide new epidemiological and pathophysiological data on chronic pain. METHODS: A French national cohort of patients with chronic pain treated at 18 pain clinics has been established and followed up using mHealth tools. This cohort makes it possible to collect the determinants and repercussions of chronic pain and their evolutions in a real-life context, taking into account all environmental events likely to influence chronic pain. The patients were asked to complete several questionnaires, body schemes, and weekly meters, and were able to interact with a chatbot and use educational modules on chronic pain. Physicians could monitor their patients' progress in real time via an online platform. RESULTS: The cohort study included 1427 patients and analyzed 1178 patients. The eDOL tool was able to collect various sociodemographic data; specific data for characterizing pain disorders, including body scheme; data on comorbidities related to chronic pain and its psychological and overall impact on patients' quality of life; data on drug and nondrug therapeutics and their benefit-to-risk ratio; and medical or treatment history. Among the patients completing weekly meters, 49.4% (497/1007) continued to complete them after 3 months of follow-up, and the proportion stabilized at 39.3% (108/275) after 12 months of follow-up. Overall, despite a fairly high attrition rate over the follow-up period, the eDOL tool collected extensive data. This amount of data will increase over time and provide a significant volume of health data of interest for future research involving the epidemiology, care pathways, trajectories, medical management, sociodemographic characteristics, and other aspects of patients with chronic pain. CONCLUSIONS: This work demonstrates that the mHealth tool eDOL is able to generate a considerable volume of data concerning the determinants and repercussions of chronic pain and their evolutions in a real-life context. The eDOL tool can incorporate numerous parameters to ensure the detailed characterization of patients with chronic pain for future research and pain management. TRIAL REGISTRATION: ClinicalTrials.gov NCT04880096; https://clinicaltrials.gov/ct2/show/NCT04880096.

Substance use disorder of equimolar oxygen-nitrous oxide mixture in French sickle-cell patients: results of the PHEDRE study.

BACKGROUND: In many countries, nitrous oxide is used in a gas mixture (EMONO) for short-term analgesia. Cases of addiction, with significant misuse, have been reported in hospitalized patients. Patients suffering from sickle cell disease (SCD) could represent a high-risk population for substance use disorder (SUD) due to their significant pain crisis and repeated use of EMONO. The objective of the PHEDRE study was to assess the prevalence of SUD for EMONO in French SCD patients. RESULTS: A total of 993 patients were included. Among 339 EMONO consumers, only 38 (11%) had a SUD, with very few criteria, corresponding mainly to a mild SUD due to a use higher than expected (in quantity or duration) and relational tensions with the care teams. Almost all patients (99.7%) were looking for an analgesic effect, but 68% of patients were also looking for other effects. The independent risks factors associated with at least one SUD criterion were: the feeling of effects different from the expected therapeutic effects of EMONO, at least one hospitalization for vaso occlusive crisis in the past 12 months and the presence of a SUD for at least one other analgesic drug. CONCLUSIONS: The use of EMONO was not problematic for the majority of patients. Manifestations of SUD that led to tensions with healthcare teams should alert and lead to an evaluation, to distinguish a true addiction from a pseudoaddiction which may be linked to an insufficient analgesic treatment related to an underestimation of pain in SCD patients. TRIAL REGISTRATION: Clinical Trials, NCT02580565. Registered 16 October 2015, https://clinicaltrials.gov/.

A phase-II study based on dose adjustment according to UGT1A1 polymorphism: is irinotecan underdosed in first-line FOLFIRI regimen for mCRC?

PURPOSE: Irinotecan has considerable importance in the treatment of metastatic colorectal cancer (mCRC). UDP-glucoronyltransferase (UGT) 1A1 is responsible for the inactivation of SN-38, a metabolite of irinotecan. Depending on UGT1A1 polymorphism, the activity of the UGT enzyme can be reduced leading to more frequent occurrence of adverse events related to irinotecan. The present study aimed to assess the safety and efficacy of different doses of irinotecan adjusted according to UGT1A1 polymorphism. METHODS: Thirty-four patients treated with FOLFIRI as first-line treatment for mCRC were included in this study. The irinotecan dosage was adapted on the basis of UGT1A1 polymorphisms: *1/*1 (370 mg/m2); *1/*28 (310 mg/m2), and *28/*28 (180 mg/m2). The incidence of grades 3 and 4 toxicities (neutropenia, febrile neutropenia, and diarrhoea) was recorded. Response was assessed according to the RECIST 1.1 criteria. RESULTS: On the basis of UGT1A1 genotyping, 20 patients were *1/*1 (58.8%), 12 were *1/*28 (35.3%) and 2 were *28/*28 (5.9%). Seven patients experienced at least one severe toxicity, i.e., 21% of the population, amounting to eleven adverse events. Concerning the response rate, 15 patients (44%) had partial or complete response. CONCLUSION: This study demonstrates that mCRC patients treated with FOLFIRI can tolerate a higher dose of irinotecan than the standard dose, i.e., > 180 mg/m2, on the basis of their UGT1A1 genotype, without increased toxicities. TRIAL REGISTRATION: NCT01963182 (registered on 16/10/2013, Clermont-Ferrand, France).

The French ecology of medical care. A nationwide population-based cross sectional study.

PURPOSE: Studies in the United States, Canada, Belgium, and Switzerland showed that the majority of health problems are managed within primary health care; however, the ecology of French medical care has not yet been described. METHODS: Nationwide, population-based, cross sectional study. In 2018, we included data from 576,125 beneficiaries from the General Sample of Beneficiaries database. We analysed the reimbursement of consultations with (i) a general practitioner (GP), (ii) an outpatient doctor other than a GP, (iii) a doctor from a university or non-university hospital; and the reimbursement of (iv) hospitalization in a private establishment, (v) general hospital, and (vi) university hospital. For each criterion, we calculated the average monthly number of reimbursements reported on 1,000 beneficiaries. For categorical variables, we used the χ2 test, and to compare means we used the z test. All tests were 2-tailed with a P-value < 5% considered significant. RESULTS: Each month, on average, 454 (out of 1,000) beneficiaries received at least 1 reimbursement, 235 consulted a GP, 74 consulted other outpatient doctors in ambulatory care and 24 in a hospital, 13 were hospitalized in a public non-university hospital and 10 in the private sector, and 5 were admitted to a university hospital. Independently of age, people consulted GPs twice as much as other specialists. The 13-25-year-old group consulted the least. Women consulted more than men. Individuals covered by complementary universal health insurance had more care. CONCLUSIONS: Our study on reimbursement data confirmed that, like in other countries, in France the majority of health problems are managed within primary health care.

Chronic pain is a risk factor for incident Alzheimer's disease: a nationwide propensity-matched cohort using administrative data.

Introduction: Chronic pain (CP) is one of the most disabling conditions in the elderly and seems to be a risk factor for the development of Alzheimer's disease and related dementias (ADRD). Only one study, using national administrative health databases, assessed and demonstrated that chronic pain (all types of pain) was a risk factor for dementia, but without assessing the impact of pain medications. Method: To assess the impact of all types of chronic pain and the long-term use of pain medications on the person-years incidence of ADRD, a retrospective nationwide healthcare administrative data study was performed using the national inter-regime health insurance information system (SNIIRAM) to the French national health data system (SNDS). Incident people >50 years old with chronic pain, defined by at least 6-months duration analgesics treatment or by a diagnosis/long-term illness of chronic pain between 2006 and 2010, were included. Chronic pain individuals were matched with non-CP individuals by a propensity score. Individuals were followed up from 9 to 13 years to identify occurrences of ADRD from 2006. Results: Among 64,496 French individuals, the incidence of ADRD was higher in the chronic pain population than control (1.13% vs. 0.95%, p <0.001). Chronic pain increases the risk of ADRD (HR = 1.23) and the incidence of ADRD was higher for women and increased significantly with age. Discussion: Our study highlights the importance of prevention, diagnosis, and management of chronic pain in elderly to reduce the risk of development and/or worsening of dementia.

People who inject oral morphine favor experimentation with injectable opioid substitution.

BACKGROUND: The French Addictovigilance network has observed the existence of the intravenous use of oral morphine capsules among people suffering from opioid use disorders. According to persons who inject morphine, these capsules are easy to dissolve and then inject, giving them the image of an "injectable" opioid substitution treatment (OST). In France, validated OSTs are only available orally, so dissolving morphine capsules represents the only alternative for patients who are not sufficiently relieved by oral forms. This practice presents risks related to the potential persistence of particles of the oral galenic in the injectable solution, despite its filtration, but also risks-notably of overdose-related to the pharmacological effects of opioids and to variations of the quantities of morphine extracted during the dissolution of the capsules. We conducted an online survey among the people concerned to collect data on their needs and expectations regarding a possible injectable substitution. METHOD: An anonymous online survey including all voluntary respondents residing in France and using oral morphine intravenously was conducted in partnership with the Psychoactif harm reduction organization, from 23/03/2020 to 01/04/2021. RESULTS: The analysis of the 157 exploitable questionnaires showed that 41% of the respondents obtained their drugs only from illegal markets. The others received, regularly or occasionally, medical prescriptions, reimbursed in 84% of cases. For 78% of the respondents, injection was the most frequent route of morphine administration, with 3.8 ± 2 injections per day. 56% of the respondents were receiving an OST, on prescription (79%), monthly (86%), in addition to morphine. Skenan® capsules were the most frequently used (81%) and 47.2% of the respondents had already experienced injection-related complications. 95% of the respondents were in favor of experimenting with an injectable morphine substitution. Those who never received medical prescriptions were the youngest (< 25 years) respondents, they reported only occasional use of morphine, and always intravenously. CONCLUSION: Oral morphine capsules dissolved and injected intravenously are not a safe and sustainable injectable substitution. Respondents wish to be able to benefit from an injectable substitution with a formulation adapted to the intravenous route. The availability of an injectable substitution would facilitate harm reduction and entry into care for the people concerned, particularly the youngest who have never received morphine prescriptions.

Prevalence of Chronic Pain Among People with Dementia: A Nationwide Study Using French Administrative Data.

OBJECTIVE: Alzheimer's disease or Related Dementia (ADRD) is known to disturb pain perception and reduce the ability to report it, resulting in underestimation by practitioners and sub-optimal medical management. The aim of this study was to estimate the prevalence of all types of CP among people with ADRD. DESIGN: Nationwide cross-sectional study. SETTINGS: French community-dwelling and nursing home residents. PARTICIPANTS: People with ADRD, >40 years old, treated with cholinesterase inhibitors or memantine, or with a diagnosis/long-term illness of ADRD and matched with a comparison sample. SETTINGS: French community-dwelling and nursing home residents. PARTICIPANTS: People with ADRD, >40 years old, treated with cognitive stimulants (cholinesterase inhibitors and memantine) or with a diagnosis/long-term illness of ADRD and matched with a comparison sample (non-ADRD). MEASUREMENTS: The capture-recapture method was performed to provide estimates of the prevalence of CP. People treated with analgesic drugs for ≥6 months consecutively or with a medical diagnosis of CP (ICD-10 codes) or referred to a pain center were considered as having CP. RESULTS: A total of 48,288 individuals were included, of which 16,096 had ADRD and 32,192 without ADRD. The estimated prevalence of CP in people with ADRD was from 57.7% [52.9;63.3] to 57.9%[53.0;63.9], and slightly higher than the non-ADRD sample (from 49.9%[47.0;53.2] to 50.4%[47.3;53.9], p <0.001). CONCLUSIONS: The prevalence of CP among people living with ADRD was at least the same as or better than individuals without ADRD. This result should alert practitioners' attention to the need for effective pain assessment and management in this population who has difficulties to express and feel pain.

Intravenous misuse of slow-release oral morphine capsules: how much morphine is injected?

BACKGROUND: The injection of morphine from morphine sulfate capsules containing sustained-release microbeads (Skenan®) is a practice frequently described by French intravenous opioid users. They seek an injectable form of substitution for heroin. Depending on how the syringe is prepared, the morphine rates may vary. The dosage of the capsule, the temperature of the dissolving water and the type of filter used have been identified as the parameters most likely to influence the final quantity of morphine in solution before intravenous injection. The aim of our study was to determine the amounts of morphine actually injected, according to the different preparation modalities described by people who inject morphine and the harm reduction equipment made available to them. METHODS: Different morphine syringes were prepared by varying the dosage of the capsule (100 or 200 mg), the temperature of the dissolving water before adding morphine, ambient (≈ 22 °C) or heat (≈ 80 °C) and four filtration devices: risk reduction Steribox® cotton, risk reduction filter "Sterifilt®", "Wheel" filter and cigarette filter. The quantification of the morphine in the syringe body was carried out by liquid phase chromatography coupled with a mass spectrometry detector. RESULTS: The best extraction yields were obtained with heated water, independently of dosages (p < 0.01). Yields of 100 mg capsules varied according to the filter (p < 0.01) and the water temperature (p < 0.01), with maximum yields obtained for solutions dissolved in heated water, then filtered with the "Wheel" filter (83 mg). The yields of the 200 mg capsules varied according to the temperature of the water (p < 0.01), without difference according to the filter used (p > 0.01), and maximum yields obtained for solutions dissolved in heated water (95 mg). CONCLUSIONS: No procedure for dissolving Skenan® led to the complete dissolution of the morphine it contains. Whatever the variations in preparation conditions, the extraction rates of the 200 mg morphine capsules were lower than those of 100 mg, without the risk reduction filters adversely impacting morphine extraction. Offering an injectable substitution to persons who inject morphine would make it possible to reduce the risks and damage, particularly overdoses, associated with variations in dosage due to preparation methods.

Systematic Review and Meta-Analysis of the Prevalence of Chronic Pain Among Patients With Opioid Use Disorder and Receiving Opioid Substitution Therapy.

To assess studies examining the prevalence of chronic pain (CP) in patients treated with Opioid Substitution Treatment (OST - buprenorphine or methadone) for Opioid Used Disorder (OUD), we conducted a systematic review and meta-analysis of the literature between the years 2000 and 2020. We searched EMBASE, PsycINFO, Cochrane, and MEDLINE databases and included studies assessing the prevalence of CP in OUD adults treated with OST. The studies were assessed for risk of bias and overall quality and the results were pooled using a random-effects model. Subgroup analyses and meta-regressions were used to identify possible factors associated with CP. Twenty-three studies reported data on the prevalence of CP in patients treated with OST were evaluated. The prevalence obtained was 45.3% (CI95% [38.7; 52.1]). Overall, 78.3% of the studies had a low risk of bias. Subgroup analysis estimates did not vary according to gender, OST, and CP duration. However, it appeared that the clinical settings was associated with a lower CP prevalence when assessed in primary care sites. Our study provided an estimate regarding the prevalence of CP among OST patients. These patients deserve specific attention from health professionals and health authorities. Thus, the real challenge in OST patients is the implementation of a multidisciplinary approach to manage CP. PERSPECTIVE: Our meta-analysis provided an estimate of CP prevalence, reaching almost 50% of OUD patients with OST. Thus, the urgent challenge in OST patients is to pay systematic attention to chronic pain diagnosis, along with the implementation of a multidisciplinary patient-focused approach for an appropriate management of CP. REGISTRATION: PROSPERO (CRD42021284790).

Real-Life Testing of the Prescription Opioid Misuse Index in French Primary Care.

Analgesic opioid (AO) misuse by patients ranges from 0% to 50%. General practitioners are the first prescribers of AO. Our objective was to validate the Prescription Opioid Misuse Index (POMI) in primary care. We conducted a psychometric study in patients with chronic pain who had been taking AOs for at least 3 months and were followed in general practice. Patients responded to the POMI at inclusion and after 2 weeks. The reference used was the DSM-V. Sixty-nine GPs included 160 patients (87 women, 54.4%), mean age 56.4 ± 15.2 years. The total POMI score was 1.50 ± 1.27, and 73/160 (45.6.0%) had a score ≥ 2 (misuse threshold). Internal validity was measured with the Kuder-Richardson coefficient, which was 0.44. Correlations between each item and the total score ranged from 0.06 to 0.35. Test-retest reliability was determined from 145 patients: Lin's concordance coefficient was 0.57 [0.46, 0.68]. Correlation with the DSM-V (Spearman's coefficient) was 0.52. The POMI does not have sufficient psychometric properties to be recommended as a tool to identify the misuse of AOs in primary care. This study clearly showed that there is a need to create a monitoring tool specific to primary care.

Adherence to opioid agonist therapy predicts uptake of direct-acting antivirals in people who use drugs: results from the French national healthcare database (the ANRS FANTASIO study).

BACKGROUND: Opioid agonist therapy (OAT) is associated with reduced injection, reduced HCV transmission, and more opportunities to initiate hepatitis C virus (HCV) treatment in people who use drugs (PWUD). We aimed to study the extent to which adherence to OAT was predictive of increased uptake of direct-acting antivirals (DAA) in PWUD with chronic HCV infection. METHODS: Using the French national healthcare system database, we targeted PWUD (i.e. with a history of OAT) who had chronic HCV infection and were eligible for DAA during 2014-2016. Adherence to OAT was computed as a time-varying variable expressing the proportion of days covered by OAT receipt, over any six-month interval before DAA receipt. We used a Cox proportional hazards model to estimate the association between adherence to OAT and the rate of DAA uptake after adjustment for age, sex, alcohol use disorder, socioeconomic status, and liver disease severity. RESULTS: Among the 22,615 persons included in the ANRS FANTASIO study, 3438 (15.2%) initiated DAA during the study period. After multivariable adjustment, adherence to OAT was associated with a higher rate of DAA initiation. However, this association was not linear, and only individuals on OAT for 20% or more of the time in the previous six-month period had a higher rate of DAA initiation (adjusted hazard ratio [95% confidence interval]: 1.28 [1.18-1.38]). Other variables associated with DAA initiation were male sex, older age, cirrhosis or liver cancer, and higher socioeconomic status. CONCLUSIONS: Adherence to OAT is a major predictor of DAA initiation in PWUD living with chronic HCV infection in France. Our results also suggest that even moderate adherence to OAT can facilitate DAA uptake. Adequate HCV training for OAT prescribers together with interventions to ensure adherence to OAT will help improve DAA initiation rates and reach HCV elimination goals.

Cross-sectional study of the prevalence of prescription opioids misuse in French patients with chronic non-cancer pain: An update with the French version of the POMI scale.

Public health issues related to chronic pain management and the risks of opioid misuse and abuse remain a challenge for practitioners. Data on the prevalence of disorders related to the use of prescribed opioids in patients suffering from chronic pain remains rather patchy, in particular because of the absence of a gold standard for their clinical assessment. We estimated the prevalence of prescription opioid misuse (POM), using a specific and validated opioid misuse scale (POMI-5F scale), in adults with chronic non-cancer pain. Nine-hundred-fifty-one (951) patients with opioids prescription and followed-up in pain clinics and addictology centers for chronic non-cancer pain (CNCP) completed the survey interview. The results suggest that 44.4% of participants have POM, accompanied by overuse (42.5%), use of opioids for effects other than analgesia (30.9%), withdrawal syndrome (65.7%), and craving (6.9%). The motivations cited for POM, apart from pain relief, were to calm down, relax and improve mood. POM was shown to be related to male sex (OR 1.52), young age (OR 2.21) and the presence of nociplastic pain (OR 1.62) of severe intensity (OR 2.31), codeine use (OR 1.72) and co-prescription of benzodiazepines (OR 1.59). Finally, despite the presence of three subgroups of misusers, no factor was associated with the intensity of misuse, reinforcing the view that distinguishing between strong and weak opioids is not appropriate in the context of use disorder. Almost half of patients with CNCP misuse their prescribed opioid. Practitioners should be attentive of profiles of patients at risk of POM, such as young, male patients suffering from severe nociplastic pain, receiving prescription for codeine and a co-prescription for benzodiazepine. We encourage French-speaking practitioners to use the POMI-5F scale to assess the presence of POM in their patients receiving opioid-based therapy. Clinical Trial Registration clinicaltrials.gov, identifier NCT03195374.

Oral Morphine as an Alternative Substitution Treatment for Opioid Use Disorder, a Rare but Non-risk-free Use.

Background: National health monitoring agencies have reported the alternative use of morphine sulfate painkiller for maintenance treatment of opioid use disorder (OUD), associated with a potential increase in overdose risk. Objectives: This study sought to assess the prevalence of regular and occasional legally prescribed morphine use in patients treated for OUD and compare their characteristics to those of patients receiving conventional opioid maintenance treatment (OMT), buprenorphine or methadone. Then, we assessed the factors associated with opioid overdose risk. Methods: Data were extracted from the French national healthcare system database, covering the entire population in 2015. Diagnosis associated with hospital discharge and long-term disease codes were extracted to select the population and identify outcomes and covariates. OUD non-chronic pain patients were divided into regular (≤35 days between dispensing and ≥3 months of continuous treatment duration) morphine users, and occasional users. Their sociodemographic and health characteristics were compared to OMT controls. A multivariate logistic regression model was performed to determine factors associated with opioid overdose. Results: In patients treated for OUD, 2,237 (2.2%) morphine users (1,288 regular and 949 occasional), 64,578 (63.7%) buprenorphine and 34,638 (34.1%) methadone controls were included. The prevalence of regular morphine use among patients treated for OUD regularly receiving an opioid was 1.3%. Compared to users who receive morphine regularly, occasional users had an increased risk of overdose [OR = 2.2 (1.5-3.3)], while the risk was reduced in the buprenorphine group [OR = 0.5 (0.4-0.7)] and not significantly different for methadone [OR = 1.0 (0.7-1.4)]. Other overdose risk factors were low-income, comorbidity, i.e., psychiatric conditions, alcohol use disorder or complications related to intravenous drug use, and coprescription with benzodiazepines or pregabalin. These factors were more frequent in morphine groups. Conclusions: Patients that were prescribed oral morphine represented a small minority of the treated for OUD. The poorer health condition affected by numerous comorbidities and higher risk of opioid overdose in patients treated with oral morphine compared with OMT controls points toward the need to better supervise the practices of these patients, to strengthen multidisciplinary care and risk reduction measures.

Transcultural validation of a French-European version of the Prescription Opioid Misuse Index Scale (POMI-5F).

PURPOSE: The Prescription Opioid Misuse Index scale (POMI) is a brief questionnaire used to assess opioid prescription misuse. In view of the increase in the prescription of opioid analgesics for chronic noncancer pain (CNCP), this tool is particularly useful during medical consultations to screen opioid misuse in patients using opioids. We sought to generate and validate a French-European translation of the POMI. METHODS: We conducted an observational, longitudinal, and multicenter psychometric study with crosscultural validation. All adult CNCP patients who were treated with opioids for at least three months, were followed in pain clinics, and spoke French were eligible. From September 2015 to November 2017, we included 163 patients and analyzed 154. We performed a pretest on a sample of representative patients to evaluate acceptability and understanding of translation. Study patients completed the POMI scale at a pain clinic (test phase), and we assessed test-retest reliability after two to four weeks by a second completion of the POMI scale at home by patients (retest phase). We subsequently explored psychometric properties of the POMI (acceptability, internal consistency, reproducibility, and external validity). RESULTS: Due to poor internal consistency and reproducibility, items 4, 7, and 8 of the original POMI scale were removed, and we proposed a five-question French-European version (POMI-5F). The internal consistency of POMI-5F was good (Cronbach's α = 0.71), as was test-retest reliability (r = 0.65 [0.55-0.67]). The external validity of POMI-5F, compared with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, was moderate but significant (r = 0.45; P < 0.001). The optimal POMI-5F cut-off score to indicate misuse was 2/5 (sensitivity = 0.95 and specificity = 0.54). CONCLUSION: We generated and validated a French-European translation of the POMI scale, POMI-5F, for use by French researchers and physicians to identify opioid misuse in CNCP patients.

RéSUMé: OBJECTIF: L'échelle Prescription Opioid Misuse Index (POMI) est un questionnaire court utilisé pour évaluer le mésusage de la prescription d'opioïdes. Face à l'augmentation de la prescription d'antalgiques opioïdes pour les douleurs chroniques non cancéreuses (DCNC), cet outil est particulièrement utile lors des consultations médicales pour dépister le mésusage chez les patients utilisateurs d'opioïdes. Nous avons cherché à générer et à valider une traduction franco-européenne de la POMI. MéTHODES: Nous avons mené une étude psychométrique observationnelle, longitudinale et multicentrique avec une validation transculturelle. Tous les patients souffrant de DCNC, traités par opioïdes depuis au moins trois mois, suivis en structures douleur chronique et parlant le Français étaient éligibles. De septembre 2015 à novembre 2017, 163 patients ont été inclus et 154 analysés. Un pré-test a été réalisé sur un échantillon de patients représentatifs pour évaluer l'acceptabilité et la compréhension de la traduction. Les patients de l'étude ont rempli l'échelle POMI (phase TEST) au sein du centre investigateur et la fiabilité du test­retest a été évaluée après deux à quatre semaines par un second remplissage de l'échelle POMI à domicile par les patients (phase RETEST). Ensuite, les propriétés psychométriques de l'échelle POMI ont été explorées (acceptabilité, cohérence interne, reproductibilité et validité externe). RéSULTATS: En raison d'une faible cohérence interne et reproductibilité, les items 4, 7 et 8 de l'échelle POMI originale ont été supprimés, et nous avons proposé une version française (Europe) à cinq questions (POMI-5F). La cohérence interne de l'échelle POMI-5F était bonne (α de Cronbach = 0,71), tout comme la fiabilité test­retest (r = 0,65 [0,55­0,67]). La validité externe du POMI-5F, comparée à la cinquième édition du Manuel diagnostique et statistique des troubles mentaux (DSM-5), était modérée mais significative (r = 0,45; P < 0,001). Le score seuil optimal du POMI-5F pour indiquer un mésusage était de 2/5 (sensibilité = 0,95 et spécificité = 0,54). CONCLUSION: Nous avons généré et validé une traduction franco-européenne de l'échelle POMI, POMI-5F, pour une utilisation par les chercheurs et les médecins français afin d'identifier le mésusage des opioïdes chez les patients souffrant de DCNC.

eDOL mHealth App and Web Platform for Self-monitoring and Medical Follow-up of Patients With Chronic Pain: Observational Feasibility Study.

BACKGROUND: Chronic pain affects approximately 30% of the general population, severely degrades quality of life (especially in older adults) and professional life (inability or reduction in the ability to work and loss of employment), and leads to billions in additional health care costs. Moreover, available painkillers are old, with limited efficacy and can cause significant adverse effects. Thus, there is a need for innovation in the management of chronic pain. Better characterization of patients could help to identify the predictors of successful treatments, and thus, guide physicians in the initial choice of treatment and in the follow-up of their patients. Nevertheless, current assessments of patients with chronic pain provide only fragmentary data on painful daily experiences. Real-life monitoring of subjective and objective markers of chronic pain using mobile health (mHealth) programs can address this issue. OBJECTIVE: We hypothesized that regular patient self-monitoring using an mHealth app would lead physicians to obtain deeper understanding and new insight into patients with chronic pain and that, for patients, regular self-monitoring using an mHealth app would play a positive therapeutic role and improve adherence to treatment. We aimed to evaluate the feasibility and acceptability of a new mHealth app called eDOL. METHODS: We conducted an observational study to assess the feasibility and acceptability of the eDOL tool. Patients completed several questionnaires using the tool over a period of 2 weeks and repeated assessments weekly over a period of 3 months. Physicians saw their patients at a follow-up visit that took place at least 3 months after the inclusion visit. A composite criterion of the acceptability and feasibility of the eDOL tool was calculated after the completion of study using satisfaction surveys from both patients and physicians. RESULTS: Data from 105 patients (of 133 who were included) were analyzed. The rate of adherence was 61.9% (65/105) after 3 months. The median acceptability score was 7 (out of 10) for both patients and physicians. There was a high rate of completion of the baseline questionnaires and assessments (mean 89.3%), and a low rate of completion of the follow-up questionnaires and assessments (63.8% (67/105) and 61.9% (65/105) respectively). We were also able to characterize subgroups of patients and determine a profile of those who adhered to eDOL. We obtained 4 clusters that differ from each other in their biopsychosocial characteristics. Cluster 4 corresponds to patients with more disabling chronic pain (daily impact and comorbidities) and vice versa for cluster 1. CONCLUSIONS: This work demonstrates that eDOL is highly feasible and acceptable for both patients with chronic pain and their physicians. It also shows that such a tool can integrate many parameters to ensure the detailed characterization of patients for future research works and pain management. TRIAL REGISTRATION: ClinicalTrial.gov NCT03931694; http://clinicaltrials.gov/ct2/show/NCT03931694.

Prevalence of Opioid Use Disorder among Patients with Cancer-Related Pain: A Systematic Review.

BACKGROUND: The opioid use disorder is an international public health problem. Over the past 20 years it has been the subject of numerous publications concerning patients treated for chronic pain other than cancer-related. Patients with cancer-related pain are also at risk of opioid use disorder. The primary objective of this literature review was to determine the prevalence of opioid use disorder in patients with cancer-related chronic pain. Its secondary objective was to identify the characteristics of these opioid users. METHODS: This is a literature review of studies published over the last twenty years, from 1 January 2000 to 31 December 2020 identified by searching the three main medical databases: Pubmed, Cochrane, and Embase. A meta-analysis took account of between and within-study variability with the use of random-effects models estimated by the DerSimonian and Laird method. RESULTS: The prevalence of opioid use disorder was 8% (1-20%) and of the risk of use disorder was 23.5% (19.5-27.8%) with I2 values of 97.8% and 88.7%, respectively. CONCLUSIONS: Further studies are now needed on the prevalence of opioid use disorder in patients treated for cancer-related chronic pain. A screening scale adapted to this patient population is urgently needed.

The Prevalence of Off-label Prescribing of Transmucosal Immediate-Release Fentanyl in France.

CONTEXT: The abuse of opioids and opioid-related harms, including deaths, in the United States are well documented. In the European Union, opioid use has also been increasing, particularly of fentanyl. OBJECTIVE: We assessed the prevalence of off-label prescribing of transmucosal immediate-release fentanyl (TIRF), in France, in 2019. We looked at the patients' and prescribers' characteristics and compared the population of patients who received TIRF in off-label prescriptions with those taking it on-label. We also examined the differences between the patients with and without cancer in the off-label use population. METHODS: This was a population-based cross-sectional study conducted in 2019, using the French national insurance claims database Système National d'Informations Inter-Régimes de l'Assurance Maladie, covering 98.8% of the French population, or 66 million people. RESULTS: We selected 224,000 patients with fentanyl prescriptions. Among them, 23,209 had at least one TIRF delivered. The median age was 71 years (59-85) and most patients were female (55.8%). The prevalence of off-label prescribing of TIRF was 51.8% (n = 12,031), corresponding to 9827 patients not diagnosed with cancer. The three main pharmaceutical TIRF specialties prescribed in two groups were Abstral, Pecfent, and Instanyl. Overall, TIRF was mainly prescribed by private general practitioners (64.8%). CONCLUSION: The prevalence of off-label prescribing of TIRF in France is extremely high. A field survey is now needed 1) to better understand why TIRF is used in conditions not indicated in its marketing authorization, and in what clinical situations, and 2) to determine whether the benefit/risk ratio of such use is favorable.

Opioid Analgesic Prescription in French Children: A National Population-Based Study.

Codeine use was restricted in 2013 and is currently contraindicated for children below the age of 12 years. We examined how the prescription of opioid analgesics in children in France evolved between 2012 and 2018. Our population-based study from the SNIIRAM database (National System of Health Insurance Inter-Regime Information) was designed to determine trends in opioid prescription from 2012 to 2018 in all French children. The number of children who received at least one opioid prescription gradually declined from 452,665 in 2012 (347.5 children per 10,000) to 169,338 in 2018 (130.3 children per 10,000). This decrease was especially marked for codeine (36 children per 10,000 in 2018 vs. 308.5 children per 10,000 in 2012), whereas the number of tramadol prescriptions increased by 171% in 2018 (94.6 children per 10,000). Despite the increase, strong opioids still formed only a small proportion of prescriptions (2.6 children per 10,000 given opioids in 2018). Overall opioid prescriptions in French children dramatically decreased between 2012 and 2018, probably owing to restrictions on the use of codeine. Codeine has been partly replaced by tramadol. Morphine is still probably underused. This suggests that opioids are being used less often for pain management in children.