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.

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.

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.

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.

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.

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.

Trajectories of antidepressant drugs during pregnancy: A cohort study from a community-based sample.

AIMS: The aim of this study was to monitor the trajectories of antidepressant use during pregnancy and the postpartum period among women chronically treated with antidepressants before their pregnancy, and to assess characteristics associated with each trajectory. METHODS: This cohort study included all pregnant women whose data were included in the General Sample of Beneficiaries (EGB) database affiliated with the French Health Insurance System, from 2009 to 2014. Women were followed up until 6 months after childbirth. Chronic treatment was defined as exposure over the 6-month period preceding pregnancy. A group-based trajectory model (GBMT) was estimated to identify distinctive longitudinal profiles of antidepressant use. RESULTS: Among 760 women chronically treated with antidepressants before their pregnancy, 55.8% stopped their treatment permanently in the first trimester, 20.4% discontinued it for a minimum of 3 months and resumed it postpartum, and 23.8% maintained it throughout pregnancy and postpartum. No sociodemographic or medical characteristics were associated with any trajectory group. Women who maintained treatment presented more frequent obstetric complications and postpartum psychiatric disorders. Among women who interrupted treatment, prescription of benzodiazepines and anxiolytics decreased initially but rose postpartum to a higher level than before pregnancy. CONCLUSIONS: Pregnant women treated with antidepressant require a re-evaluation of psychiatric treatment. It is necessary to pay attention to obstetric complications for severely depressed women. Additionally, as relapse was associated with increased benzodiazepine use, it is important to carefully monitor all women who stop antidepressant treatment during pregnancy.

Perception of pharmacy students toward opioid-related disorders and roles of community pharmacists: A French nationwide cross-sectional study.

Background: Community pharmacists are among the frontline health professionals who manage patients with an opioid-related disorder (ORD). Pharmacists frequently have a negative attitude toward these patients, which could have a negative impact on their management. However, education on ORD may improve the attitude of future healthcare professionals. This cross-sectional study aimed to assess French pharmacy students' perceptions of ORD. Methods: This online survey was performed by emails sent to French pharmacy schools (between January 14, 2019 and May 31, 2019). The primary outcome was the perception (visual analogic scale) of ORD as a disease, the roles of community pharmacies (delivery of opioid agonist therapy-OAT and harm reduction kits), and the efficacy of OAT. The secondary outcomes assessed professional experience, university experience of and education on ORD, and the individual characteristics of students. Results: Among the 1,994 students included, 76.3% perceived ORD as a disease and felt that it was normal for pharmacists to deliver OAT (78.9%) and harm reduction kits (74.6%). However, only 46.9% perceived OAT as being effective. Multivariable analyses showed that females had a more positive perception in recognizing ORD as a disease. The progression through university years increased the positive perception of ORD as a disease and the delivery of OAT and harm reduction kits by pharmacists. Education on substance-related disorders had no impact on any scores. Students who had already delivered OAT had a negative perception of their efficacy. The students who had already performed pharmacy jobs or traineeships had a negative perception of harm reduction kit delivery. Conclusion: Education on substance-related disorders had no impact on students' perceptions. It seemed that the maturity acquired through university years had a stronger impact on the students' perceptions of ORD. Efforts must be made to improve our teaching methods and reinforce the confidence of students in the roles of community pharmacists.

Risk assessment of using off-label morphine sulfate in a population-based retrospective cohort of opioid-dependent patients.

AIMS: Several addictovigilance studies have described the off-label use of morphine sulfate (MS) for nonchronic pain in opioid use disorder (OUD) patients as an alternative to conventional opioid substitution treatments (OSTs). This study primarily sought to compare the incidence of unintentional opioid-related overdose in the year following the prescription initiation in off-label MS users, compared to OST-maintained patients. METHODS: Sequential cohorts of OUD patients who were regularly dispensed MS, buprenorphine, or methadone, between 1 April 2012 and 31 December 2014, were retrospectively identified using the French nationwide healthcare data system. The incidence of overdoses, deaths, doctor shopping, and complications of a viral, bacterial or thrombotic nature, was compared using the Cox regression method. RESULTS: Overall, 1075, 20 834 and 9778 OUD patients without chronic-pain were included in the MS, buprenorphine, and methadone cohorts, respectively. Overdose incidence was 3.8 (P < .01 [95% confidence interval (CI): 2.1-6.8]) and 2.0 (P = .02 [95%CI: 1.1-3.6]) higher in the MS cohort vs buprenorphine and methadone, respectively. Death incidence was 9.1 (P < .01 [95%CI: 3.2-25.9]) and 3.9 (P < .01 [95%CI: 1.4-10.7]) higher in the MS cohort vs buprenorphine and methadone, respectively. The incidences of other associated risks were significantly higher in the MS group vs OSTs, except for hepatitis C viral infection and thrombotic complications. CONCLUSION: This first French comprehensive nationwide study reveals increasing overdose, death, bacterial infection, abuse and diversion risks when off-label MS is initiated as alternative to OST. These results question the relevance of prescribing MS as a safe opioid maintenance treatment, considering its health risk profile.

[Surveillance system on drug abuse: Interest of the French national OPPIDUM program of French addictovigilance network]. / Dispositif pharmacoépidémiologique de surveillance des substances psychoactives : intérêts du programme national OPPIDUM du Réseau français d'addictovigilance.

It is important to assess drug abuse liability in 'real life' using different surveillance systems. OPPIDUM ('Observation of illegal drugs and misuse of psychotropic medications') surveillance system anonymously collects information on drug abuse and dependence observed in patients recruited in specialized care centers dedicated to drug dependence. The aim of this article is to demonstrate the utility of OPPIDUM system using 2015 data. OPPIDUM is a cross-sectional survey repeated each year since 1995. In 2015, 5003 patients described the modality of use of 10,159 psychoactive drugs. Among them, 77% received an opiate maintenance treatment: 68% methadone (half of them consumed capsule form) and 27% buprenorphine (39% consumed generic form). Brand-name buprenorphine is more often injected than generic buprenorphine (10% vs. 2%) and among methadone consumers 7% of methadone capsule consumers have illegally obtained methadone (vs. 9% for syrup form). The proportion of medications among psychoactive drugs injected is important (42%), with morphine representing 21% of the total psychoactive drugs injected and buprenorphine, 16%. OPPIDUM highlighted emergent behaviors of abuse with some analgesic opioids (like tramadol, oxycodone or fentanyl), pregabalin, or quetiapine. OPPIDUM highlighted variations of drugs use regarding geographic approaches or by drug dependence care centers (like in harm reduction centers). OPPIDUM clearly demonstrated that collection of valid and useful data on drug abuse is possible, these data have an interest at regional, national and international levels.

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.

Impact of clinical characteristics and management on the prognosis of unselected heart failure patients.

PURPOSE: Heart failure (HF) is a major public health issue. This study conducted a real-life analysis of the impact of clinical characteristics and medical management of HF on its prognosis. METHODS: Analysis was based on the EGB ("Echantillon Généraliste des Bénéficiaires") database. A cohort comprising 1825 adult patients with a first admission for HF between 2009 and 2011 was created and followed until June 2013 (median 22.3 [7.7-34.5] months) for survival analysis. RESULTS: Mean age was 77.3 ± 13.2 years (53 % ≥80 years). The overall incidence of HF admission was 117 [112-122] per 100,000 population with a marked increase in patients >80 years (1297 [1217-1348]). At discharge, only 8 % of patients received recommended combination of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB), beta-blockers (BB) and mineralocorticoid receptor antagonists (MRA). Only prescription levels of BB and vitamin K antagonists, at discharge, increased during the study period. In-hospital mortality was 9 % and survival was 71.6 %[69.5-73.6] and 52.0 %[49.4-54.6] at 12 and 36 months, respectively. In multivariate analysis, female gender [HR:0.78 (0.67-0.91), p = 0.001], ACEi/ARB + BB + MRA [0.41 (0.28-0.60), p < 0.001] and ACEi/ARB + BB [0.47 (0.39-0.57) p < 0.001] treatments were associated with improved survival, conversely to age 70-79 [1.90 (1.20-3.00), p = 0.003] and ≥80 [3.50 (2.30-5.40), p < 0.001], cardiogenic shock [3.00 (2.10-4.40), p < 0.001], acute pulmonary edema [1.70 (1.10-2.50), p = 0.01], denutrition [1.80 (1.45-2.24), p < 0.001], dilated cardiomyopathy [1.20 (1.00-1.40), p = 0.02] and in-hospital acute renal failure [1.36 (1.05-1.78), p = 0.002]. CONCLUSIONS: These real-life HF data provide insight into prognostic factors and "real-world" pharmacological management in this unselected HF population, confirming the benefit of ACEi/ARB + BB ± MRAs on patient survival.

Heart failure prognosis and management in over-80-year-old patients: data from a French national observational retrospective cohort.

PURPOSE: The aim of the study was to assess the impact of clinical characteristics and management on the mid- to long-term follow-up prognosis of unselected over-80-year-old patients hospitalized for a first heart failure (HF) episode in a real-life setting. Despite the increasing proportion of HF patients over 80 years of age, the latter remain a poorly studied population. METHODS: Analysis was based on the EGB ("Echantillon Généraliste des Bénéficiaires") database. A cohort comprising 1825 adult patients with a first admission for HF between 2009 and 2011 was created and followed until June 2013 for survival analysis. RESULTS: Over-80-year-old patients represented 53 % of this cohort, with a median follow-up of 18.6 (3.3-29.5) months. Only 5 % of patients over 80 years received an optimal treatment at discharge [combination of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB), beta-blockers (BB), and mineralocorticoid receptor antagonists (MRA)]. During the follow-up period, only BB prescription levels (p = 0.02) increased. In over-80-year-olds, in-hospital mortality was 12 % (range, 10-14) and survival was 62.8 % (59.6-65.7) and 48.7 % (45.4-51.9) at 12 and 24 months, respectively. On multivariate analysis, dyslipidemia [0.74 (0.58-0.94), p = 0.02], vitamin K antagonists [0.55 (0.44-0.69), p < 0.001], ACEi/ARB + BB + MRA [0.56 (0.32-0.96), p = 0.04], and ACEi/ARB + BB [0.57 (0.45-0.72), p < 0.001] were associated with improved survival, conversely to cardiogenic shock [3.37 (1.90-5.98), p < 0.001], denutrition [1.61 (1.24-2.09), p < 0.001], and age over 90 [1.35 (1.09-1.67), p = 0.01]. CONCLUSIONS: These real-life HF data provide insight into prognostic factors and demonstrate that over-80-year-old HF patients displaying several comorbidities are poorly managed, despite the confirmed clinical benefit of HF drugs.

Assessment of thermal sensitivity in rats using the thermal place preference test: description and application in the study of oxaliplatin-induced acute thermal hypersensitivity and inflammatory pain models.

Thermal sensitivity is an essential characteristic of some painful states, including oxaliplatin-induced neuropathy. The thermal place preference test (TPPT) was designed to finely assess thermal sensitivity in rodents. The TPPT monitors the time spent by unrestrained rodents on a test plate at fixed temperatures (5-50°C) compared with an adjacent reference plate at a neutral temperature (25°C). Here, we report the results of a study designed (i) to validate the optimal methodological parameters for measuring thermal sensitivity in rats, (ii) to assess the thermal sensitivity of healthy rats and animal models of pain and (iii) to explore the pharmacological effects of analgesic drugs. The most reproducible conditions occurred when the TPPT was performed in the morning and in the dark for 3 min with the reference plate set to 25°C. The temperature preferences of healthy rats were more than 17°C and less than 40°C. When compared with control animals, oxaliplatin-treated rats showed thermal hypersensitivity at 12, 20 and 35°C, and carrageenan-treated rats showed thermal hypersensitivity at 15 and 45°C. Duloxetine (2.5 mg/kg, intraperitoneal) reversed oxaliplatin-induced cold hypersensitivity (20°C) and morphine (1 mg/kg, intravenous) reversed carrageenan-induced heat hypersensitivity (45°C). We conclude that the TPPT enables a fine-grained assessment of thermal sensitivity that is relevant to the pathophysiological exploration of animal pain models and to the pharmacological assessment of analgesic drugs.

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.

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).

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/.

Emerging trends in understanding chemotherapy-induced peripheral neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major concern in oncology practice given the increasing number of cancer survivors and the lack of effective treatment. The incidence of peripheral neuropathy depends upon the anticancer drug used, but is commonly under-reported in clinical trials. Several animal models have been developed in an attempt to better characterize the pathophysiological mechanisms underlying these CIPN and to find more specific treatments. Over the past two decades, three main trends have emerged from preclinical research on CIPN. There is a compelling body of evidence that neurotoxic anticancer drugs affect the peripheral sensory nerve by directly targeting the mitochondria and producing oxidative stress, by functionally impairing the ion channels and/or by triggering immunological mechanisms through the activation of satellite glial cells. These various neurotoxic events may account for the lack of effective treatment, as neuroprotection may probably only be achieved using a polytherapy that targets all of these mechanisms. The aim of this review is to describe the clinical features of CIPN and to summarize the recent trends in understanding its pathophysiology.