Increase of high-risk tramadol use and harmful consequences in France from 2013 to 2018: Evidence from the triangulation of addictovigilance data.

AIMS: The aim of this paper is to assess recent developments in non-medical tramadol use, tramadol use disorder, illegal procurement and deaths. METHODS: This study used repeated cross-sectional analysis of data collected nationwide from 2013 to 2018. Analysis was conducted through multisource monitoring of the French Addictovigilance Network of: (1) validated reports of high-risk tramadol use, (2) record systems collecting information from toxicology experts investigating analgesic-related deaths (DTA) and deaths related to substance abuse (DRAMES), and pharmacists for forged prescriptions (OSIAP), and (3) survey of drug users, with investigation of patterns of use while visiting addiction-specialised institutions (OPPIDUM). RESULTS: Despite a plateauing level of tramadol exposure in the French population, the proportion of tramadol reports increased 1.7-fold (187 cases in 2018, 3.2% (95% confidence interval [CI]: 2.74-3.63%), versus 1.9% (95% CI: 1.49-2.42% in 2013). Trends were similar in OSIAP: 11.9% of forged prescriptions in 2018 (95% CI: 10.56-13.45%); 1.7-fold increase; in OPPIDUM: 0.76% (95% CI: 0.55-1.02); 2.2-fold increase; and DRAMES: 3.2% of drug abuse-related deaths in 2018 (95% CI: 1.89-5.16) versus 1.7% in 2013 (95% CI: 0.65-3.84). Tramadol was the primary opioid in analgesic-related deaths in DTA (45% in 2018). Two profiles of high-risk tramadol users were identified: (1) patients treated for pain or with tramadol persistence when pain disappeared (mainly women; mean age 44 years), and (2) individuals with non-medical use for psychoactive effects (mainly men; mean age 36 years). CONCLUSION: The triangulation of the data obtained through addictovigilance monitoring evidenced a recent increase in high-risk tramadol use. These findings have a practical impact on the limitation of the maximal duration of tramadol prescriptions.

Usefulness of early morphological ultrasound in association with cell-free DNA testing in case of atypical serum markers in first trimester of pregnancy: A retrospective study over 5 years.

BACKGROUND: Early morphologic ultrasound, generally carried out in case of atypical first trimester serum markers (PAPP-A and/or free hCGß <0.30 MoM), has not been re-evaluated since the possibility of performing a cell-free fetal DNA analysis in this indication. Our objective was to evaluate the usefulness of early morphological ultrasound in case of atypical profile of serum markers performed in association with Non-Invasive Prenatal Testing (NIPT). METHODS: This was a single-center retrospective study in a tertiary maternity. Between January 2017 and December 2021, women with an atypical first trimester serum markers and low/intermediate risk for trisomy 21 (<1/50) were included. The clinical data, results of first trimester serum markers, NIPT, early morphological ultrasound and subsequent ultrasounds and other investigations (amniocentesis, pregnancy outcomes) were analyzed. RESULTS: After exclusion of women with high-risk of trisomy 21 and lost to follow-up, 163 women were included. In 72 % of cases (117/163), women had a low risk of trisomy 21, and 39 % (59/163) had an early morphological ultrasound. Early morphological ultrasound was useful to detect severe IUGR leading to the suspicion of triploidy (3/163, 1.8 %). In all other situations, it did not allow earlier management. After analysis of the 3 triploidy cases, a collapsed profile for both serum markers was demonstrated (<0.25 MoM). CONCLUSIONS: Systematic early morphological ultrasound in case of an atypical serum marker profile seems useless considering the performance of NIPT. An ultrasound restricted to women with both markers below 0.25 MoM would allow the early detection of triploidy.