As the number and severity of complications related to cocaine use reported to the French Addictovigilance Network have increased, the French health authorities requested a national epidemiologic study of the data collected by this network from 2010 to 2016. For this purpose, the spontaneous reports (SRs) linked to cocaine notified by health professionals were analyzed as well as the data from the pharmacoepidemiological surveys OPPIDUM (observation of illegal drugs and misuse of psychotropic medications) and DRAMES (deaths related to the abuse of licit and illicit psychoactive substances). In total, 1 265 SRs were analyzed (510% increase from 2010 to 2016). Users were mainly men (952/1 261; 75%), with a median age of 35.0 years [IQ25–75: 28–42]. Cocaine was consumed through the intranasal route by 52% of users (416/797), followed by intravenous administration (32%, 253/797) and inhalation (24%, 190/797). The use of cocaine powder and crack cocaine was reported in 70% (475/674) and 23% (154/674) of SRs, respectively. Cocaine was consumed with other psychoactive substances and alcohol in 47% (603/1265) and 60% (387/649) of cases, respectively. The main cocaine‐related complications were psychiatric complications (29%), neurologic complications (24%) and cardiovascular complications (23%). Analysis of the OPPIDUM survey data showed that in 2016, 15.9 and 2.4% of the included subjects consumed cocaine or crack cocaine the week preceding the survey, the highest rate for the 2006–2016 period. The DRAMES survey indicated that cocaine‐related deaths increased by threefold from 2014 to 2016. These data confirm that cocaine use in France is worrying with an increase in the number of severe complications and deaths.

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CD19-directed CAR T-cells have been remarkably successful in treating patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and transformed follicular lymphoma (t-FL). In this cohort study, we treated 60 patients with axicabtagene ciloleucel or tisagenlecleucel. Complete and partial metabolic responses (CMR/PMR) were obtained in 40% and 23% of patients, respectively. After 6.9 months of median follow-up, median progression-free survival (mPFS) and overall survival (mOS) were estimated at 3.1 and 12.3 months, respectively. Statistical analyses revealed that CMR, PFS, and OS were all significantly associated with age-adjusted international prognostic index (aaIPI, p < 0.05). T-cell subset phenotypes in the apheresis product tended to correlate with PFS. Within the final product, increased percentages of both CD4 and CD8 CAR+ effector memory cells (p = 0.02 and 0.01) were significantly associated with CMR. Furthermore, higher CMR/PMR rates were observed in patients with a higher maximal in vivo expansion of CAR T-cells (p = 0.05) and lower expression of the LAG3 and Tim3 markers of exhaustion phenotype (p = 0.01 and p = 0.04). Thus, we find that aaIPI at the time of infusion, phenotype of the CAR T product, in vivo CAR T-cell expansion, and low levels of LAG3/Tim3 are associated with the efficacy of CAR T-cell therapy in DLBCL patients.

Purpose:We analyzed the relationship between use of anticholinergic drugs to treat overactive bladder (OAB) and risk of incident dementia in older patients, overall and for each drug separately.Materials and Methods:We conducted a nested case-control study using the French National Medical-Administrative Database. We identified incident dementia cases and controls from January 1, 2013 to December 31, 2018 in individuals aged ≥60 years. Controls were matched 5:1 to cases by date of case diagnosis (index date), age, sex, and income. We set a 5-year exposure period ending 2 years before the index date (lag-time period to avoid protopathic bias). We quantified cumulative exposure to flavoxate, oxybutynin, solifenacin, trospium, and fesoterodine using defined daily doses (DDDs). We performed conditional logistic regression analyses adjusted for factors known to be associated with OAB and/or dementia including obesity, diabetes, stroke, coronary heart disease, and psychotic disorders.Results:We analyzed 4,810 cases and 24,050 matched controls with a median age of 82 years. OAB anticholinergic use was associated with an increased risk of dementia (adjusted OR [aOR]=1.23, 95% CI 1.10–1.37) with a cumulative dose-response: aOR=1.07 (95% CI 0.91–1.25) for 1-90 DDDs, aOR=1.29 (1.05–1.58) for 91–365 DDDs and aOR=1.48 (1.22–1.80) for >365 DDDs. Considering each OAB anticholinergic separately showed a particularly marked increased risk of dementia for oxybutynin and solifenacin, but no increased risk for trospium.Conclusions:When treating OAB in older patients, OAB anticholinergics should be used with caution, taking into account the patient's cognitive status, the anticholinergic load, and the different therapeutic options.

Background and purpose A clinical risk score for sudden unexpected death in epilepsy (SUDEP) in patients with drug‐resistant focal epilepsy could help improve prevention. Methods A case–control study was conducted including (i) definite or probable SUDEP cases collected by the French National Sentinel Mortality Epilepsy Network and (ii) control patients from the French national research database of epilepsy monitoring units. Patients with drug‐resistant focal epilepsy were eligible. Multiple logistic regressions were performed. After sensitivity analysis and internal validation, a simplified risk score was developed from the selected variables. Results Sixty‐two SUDEP cases and 620 controls were included. Of 21 potential predictors explored, seven were ultimately selected, including generalized seizure frequency (>1/month vs. <1/year: adjusted odds ratio [AOR] 2.6, 95% confidence interval [CI] 1.25–5.41), nocturnal or sleep‐related seizures (AOR 4.49, 95% CI 2.68–7.53), current or past depression (AOR 2.0, 95% CI 1.19–3.34) or the ability to alert someone of an oncoming seizure (AOR 0.57, 95% CI 0.33–0.98). After internal validation, a clinically usable score ranging from −1 to 8 was developed, with high discrimination capabilities (area under the receiver operating curve 0.85, 95% CI 0.80–0.90). The threshold of 3 has good sensitivity (82.3%, 95% CI 72.7–91.8), whilst keeping a good specificity (82.7%, 95% CI 79.8–85.7). Conclusions These results outline the importance of generalized and nocturnal seizures on the occurrence of SUDEP, and show a protective role in the ability to alert someone of an oncoming seizure. The SUDEP‐CARE score is promising and will need external validation. Further work, including paraclinical explorations, could improve this risk score.