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.

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.

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.

Analgesic opioid use disorders in patients with chronic non-cancer pain: A holistic approach for tailored management.

Chronic pain is a major public health issue that frequently leads to analgesic opioid prescriptions. These prescriptions could cause addiction issues in high-risk patients with associated comorbidities, especially those of a psychiatric, addictive, and social nature. Pain management in dependent patients is complex and is yet to be established. By combining the views of professionals from various specialties, we conducted an integrative review on this scope. This methodology synthesizes knowledge and results of significant practical studies to provide a narrative overview of the literature. The main results consisted in first proposing definitions that could allow shared vocabulary among health professionals regardless of their specialties. Next, a discussion was conducted around the main strategies for managing prescription opioid dependence, as well as pain in the context of opioid dependence and associated comorbidities. As a conclusion, we proposed to define the contours of holistic management by outlining the main guidelines for creating a multidisciplinary care framework for multi-comorbid patients with chronic pathologies.

Opioid epidemic: Does rheumatological practice favors risk for patients? National survey on rheumatologists' opioid prescriptions and compliance to guidelines for strong opioid prescription.

OBJECTIVES: Given the scope of rheumatology and its prevalence of pain, it seems needed that a study should focus on prescription habits, in the midst of the international opioid epidemic and given the moderate efficacy of strong opioids in chronic musculoskeletal conditions. We compared rheumatologists' opioid prescribing patterns in non-cancer pain with recommended practice. METHODS: We performed a cross-sectional study of the French health insurance database, including all patients aged 16 years or over reimbursed for at least one strong opioid prescription from a rheumatologist in 2015. A nationwide survey of all registered rheumatologists in France was performed with a 47-item questionnaire in June 2015. RESULTS: Only 2.4% of the patients receiving a strong opioid in 2015 (n=700,946) had at least one prescription from a rheumatologist. Rheumatologists prescribed mostly morphine, and significantly less oxycodone and fentanyl (P<0.00001) than other specialists. Rheumatologists prescribed a mean of 35.8mg morphine equivalent/day. A response rate of 33.7% was obtained to the questionnaire. Acute musculoskeletal pain was the principal condition for strong opioids prescription, with 94.5% re-evaluating opioid treatment within two weeks of initiation. For efficacy, 80% said that they stopped treatment if no benefit was observed after a test period (mean=1.2 months). Rheumatologists with pain management training were significantly more likely to evaluate pain before prescribing strong opioids (P=0.001), evaluate efficacy within three months (P=0.01) and screen for risk factors for misuse at initiation (P<0.0001). CONCLUSIONS: For non-cancer pain, rheumatologists generally prescribe opioids for short periods, at low doses, mostly according to national recommendations. Pain education strongly affected opioid prescription by rheumatologists.

Moderate-to-severe eosinophilia induced by treatment with immune checkpoint inhibitors: 37 cases from a national reference center for hypereosinophilic syndromes and the French pharmacovigilance database.

A better understanding of immune-related adverse events is essential for the early detection and appropriate management of these phenomena. We conducted an observational study of cases recorded at the French reference center for hypereosinophilic syndromes and in the French national pharmacovigilance database. Thirty-seven reports of eosinophilia induced by treatment with immune checkpoint inhibitors (ICIs) were included. The median [range] time to the absolute eosinophil count (AEC) peak was 15 [4─139] weeks. The median AEC was 2.7 [0.8─90.9] G/L. Eosinophil-related manifestations were reported in 21 of the 37 cases (57%). If administered, corticosteroids were always effective (n = 10 out of 10). Partial or complete remission of eosinophilia was obtained in some patients not treated with corticosteroids, after discontinuation (n = 12) or with continuation (n = 4) of the ICI. The AEC should be monitored in ICI-treated patients. If required by oncologic indications, continuation of ICI may be an option in asymptomatic hypereosinophilic patients, and in corticosteroid responders.

Chronic Pain Opioid-Maintained Patients Receive Less Analgesic Opioid Prescriptions.

Treating pain and opioid use disorder represents a clinical challenge. While most studies that have assessed opioid analgesic use in opioid substitution treatment (OST) patients primarily address opioid analgesic misuse (1, 2), only few studies focused on OST patients assessed the prescription of analgesic opioids for chronic pain. We sought to compare the prevalence of analgesic opioid prescription (AOP) in two groups of chronic non-cancer pain (CNCP) patients: OST patients vs. the general population. This was a population-based cross-sectional study based on the French national healthcare claims database SNIIRAM (Système National d'Informations Inter-Régimes de l'Assurance Maladie) covering over 66 million people (98.8% of the French population). Overall, 67,173 participants ≥15 years old undergoing continuous OST in 2015 ("OST patients" group) were included and age- and gender-matched by means of a 1:1 ratio with 67,173 patients without OST ("control" group). In each group, patients with cancer conditions were excluded and those having received opioid and non-opioid analgesics for at least 3 months were identified (CNCP patients). Compared to control patients, CNCP OST patients received less AOP (47.8 vs. 68.0%, p < 0.0001) and more often non-opioid prescription (52.2 vs. 32.0%, p < 0.0001). In multivariate analysis, CNCP OST patients were 2.7 times less likely to be prescribed analgesic opioids (adjusted odds ratio [OR] = 2.7 [2.42-3.01], p < 0.0001) than control patients. AOP correlated in CNCP OST patients with: age ≤ 40 years old, female gender, low-income status, methadone-maintained treatment, mental health disorder, hepatitis C virus (HCV) infection, and alcohol abuse disorder. Opioid analgesics were less often prescribed in CNCP OST patients. AOP prevalence was 2.7-fold lower than in the general population. Chronic pain management in OST patients needs to be reinforced through additional physician training and a multidisciplinary approach.

Agomelatine: a new opportunity to reduce neuropathic pain-preclinical evidence.

Antidepressants are first-line treatments of neuropathic pain but not all these drugs are really effective. Agomelatine is an antidepressant with a novel mode of action, acting as an MT1/MT2 melatonergic receptor agonist and a 5-HT2C receptor antagonist that involves indirect norepinephrine release. Melatonin, serotonin, and norepinephrine have been involved in the pathophysiology of neuropathic pain. Yet, no study has been conducted to determine agomelatine effects on neuropathic pain in animal models. Using 3 rat models of neuropathic pain of toxic (oxaliplatin/OXA), metabolic (streptozocin/STZ), and traumatic (sciatic nerve ligation/CCI [chronic constriction nerve injury]) etiologies, we investigated the antihypersensitivity effect of acute and repeated agomelatine administration. We then determined the influence of melatonergic, 5-HT2C, α-2 and ß-1/2 adrenergic receptor antagonists in the antihypersensitivity effect of agomelatine. The effect of the combination of agomelatine + gabapentin was evaluated using an isobolographic approach. In STZ and CCI models, single doses of agomelatine significantly and dose dependently reduced mechanical hypersensitivity. After daily administrations for 2 weeks, this effect was confirmed in the CCI model and agomelatine also displayed a marked antihypersensitivity effect in the OXA model. The antihypersensitivity effect of agomelatine involved melatonergic, 5-HT2C, and α-2 adrenergic receptors but not beta adrenoceptors. The isobolographic analysis demonstrated that the combination of agomelatine + gabapentin had additive effects. Agomelatine exerts a clear-cut antihypersensitivity effect in 3 different neuropathic pain models. Its effect is mediated by melatonergic and 5-HT2C receptors and, although agomelatine has no affinity, also by α-2 adrenergic receptors. Finally, agomelatine combined with gabapentin produces an additive antihypersensitivity effect.

Incidence of tramadol shopping behavior in a retrospective cohort of chronic non-cancer pain patients in France.

PURPOSE: Opioid analgesic use in chronic non-cancer pain (CNCP) is increasingly prevalent, but the benefits and risks are inadequately understood. In France, tramadol is one of the most used prescription opioids, but studies on its misuse liability in CNCP are still lacking. The aim was to assess the incidence of tramadol shopping behavior in CNCP patients and to identify the associated risk factors. METHODS: A retrospective cohort of CNCP patients aged 18 years and older treated by tramadol for at least six consecutive months between 2005 and 2013 from a sample of the French Health Insurance database was established. Doctor shopping was defined as at least 1 day of overlapping prescriptions written by two or more different prescribers and filled in at least three different pharmacies. RESULTS: A total of 3505 CNCP patients were included with a majority of women (66.4%) and a mean age of 66.4 ± 14.7 years. The median tramadol treatment duration was 260 [interquartile range: 211-356] days. The 1-year incidence rate of tramadol shopping behavior was 1.0% [95%CI: 0.7-1.5]. On multivariate analysis, risk factors associated with tramadol shopping behavior were age (hazard ratio [HR] = 7.4 [95%CI: 2.8-19.7] for age <40, HR = 2.8 [95%CI: 1.0-7.7] for 40 ≤ age < 50, versus age ≥50), low-income status (HR = 8.5 [95%CI: 3.6-20.5]), and prior use of strong opioids (HR = 5.7 [95%CI: 1.9-17.0]). CONCLUSION: Tramadol shopping behavior incidence appears low in CNCP patients but may represent a public health concern given the widespread use of tramadol. Education and best monitoring of high-risk patients are needed to reduce doctor shopping. Copyright © 2016 John Wiley & Sons, Ltd.

Are all heparins safe for on-pump heart surgery?

BACKGROUND: Intravenous Panpharma heparin(®) was used in all on-pump cardiac surgery in our heart-surgery department for a short period. This brand of heparin replaced the previous Choay heparin(®) heparin supplied by the Sanofi-Aventis Laboratory. Unusual postoperative bleedings over this period prompted us to evaluate postoperative hemostasis by comparing these two heparins. METHODS: We compared data from patients who had undergone on-pump cardiac surgery during Panpharma heparin(®) period (group P, 257 patients) to those how received Choay heparin(®) (group C, 194 patients). RESULTS: Despite group P receiving a significantly lower dose of heparin (mean dose 21,000 IU/CEC) compared to group C (mean dose 22,000 IU/CEC) (p = 0.05), the number of surgical re-explorations needed to perfect postoperative hemostasis was significantly higher for group P (3.5% vs. 0) (p = 0.01). Heparin anti-Xa activity after surgery was higher in group P at postoperative h1 and h12 compared to group C, which explained reoperations for hemostasis. CONCLUSION: Despite standardization, variations remain regarding anticoagulant activity between different manufacturing processes and heparin preparations. Surgical teams need to be aware that the biological effects of different brands of heparin may not be as expected and could endanger a usually safe procedure, such as cardiac surgery.

Illicit drugs or medicines taken by parachuting.

Parachuting (also called bombing) is a method of drug delivery where illicit drugs or medicines are ingested after wrapping the substance. There are little data describing parachuting in the literature. To provide a description of this practice, all cases of parachuting reported to the national addictovigilance network up to 31 December 2014 were identified from spontaneous reports and specific surveillance programs. Cases were described according to the type of substance used, patient age and gender, type of complications, context of use and year of the event. Forty-five cases of parachute use were identified and most (n = 43) occurred after 2011. Patients were mostly men (60%), and mean age was 28.9 years. The context of use, known in 19 cases, was mostly recreational. Complications were present in 24 cases, of which eight were serious. The substance was supposed to be 3,4-methylenedioxymethamphetamine (MDMA) in the majority of cases (64.4%); research chemicals were more involved in the most recent years. The physical form was mainly granular (51.6%). The wrappers were a cigarette paper (nine cases) and in one case plastic package; in the other cases, the term of parachute was used without further details. The reason for use was not explained in the majority of cases; two patients indicated using a parachute for faster effect than with a methadone capsule. Clinicians should be aware of this delivery form as the results suggest that it is common and can involve a great variability of drugs.