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With recent evolution of cannabis legalization around the world, cannabis edibles are booming, and determining their concentration in Δ9-tetrahydrocannabinol (Δ9-THC), the regulated psychoactive substance, remains a challenge for toxicology laboratories, which must prove whether the product has legal status or not. Cannabinoids are a large family of structurally similar and lipophilic molecules, requiring dedicated pre-analytical methods, as well as efficient chromatographic separation to differentiate cannabinoid isomers which are distinguished by their psychoactive properties and their legal status. Here, we present two independent cases of cannabis edibles, for which we performed analysis of homemade cannabis chocolate cakes and of the resins and herbs used for cooking. Quantitation was carried out with a new developed standard addition method, to avoid matrix effects and matrix-dependent calibration. Extraction by QuEChERs method, followed by targeted and non-targeted analysis by ultra-high performance liquid chromatography hyphenated to high resolution mass spectrometry (UHPLC–HRMS) allowed the identification of several phytocannabinoids, mainly Δ9-tetrahydrocannabinol (Δ9-THC), cannabidiol (CBD) and their acid precursors Δ9-THC acid (THCA) and CBD acid (CBDA). Δ9-THC was identified in significant concentrations (mg/g) in both edibles, even though one was prepared with CBD herb. This work highlights the need to analyze cannabis edibles, as well as the resins and herbs used in their preparation if it is homemade, and it proposes a reliable analytical method for toxicology laboratories. [ABSTRACT FROM AUTHOR]

Aim: To describe the symptoms, patient demographics, and trends over time of adverse drug reactions (ADRs) related to weak opioid analgesics reported to the French vigilance networks. Methods: Retrospective study of data from French Poison Control Centers and Pharmacovigilance Centers databases of weak opioid analgesics‐related ADRs cases, with high causality score, in adults, in therapeutic analgesic use, without co‐exposure, between 2011 and 2020. Results: The number of cases was 388 in the Poisonings database and 155 in the Pharmacovigilance database; ratio of the number of these cases to all reported cases during the study period was 0.02% and 0.03%, respectively. Tramadol was most often involved (74% and 56.1%, respectively), followed by codeine (26% and 38.7%, respectively). There was no significant variation in the number of cases reported. Cases most often involved young adults (median age: 40 years) and mostly women (76%). Gastrointestinal symptoms were mostly reported (80% and 65%, respectively) as described in the Summary of Products Characteristics. Patterns of ADRs were comparable in both databases, except for codeine‐associated acute pancreatitis and anaphylaxis that were reported in the Pharmacovigilance database. No fatality was observed. Severity was more often observed in the Pharmacovigilance database (30%) than in the Poisonings database (moderate toxicity: 7%). Conclusion: ADRs mostly occurred among young women using tramadol, without significant variation in the number of reported cases over time. Serious ADRs were more frequently reported to the Pharmacovigilance database, particularly for codeine. Women seemed to be at greater risk of ADRs. [ABSTRACT FROM AUTHOR]

Data regarding immediate-release (IR)-tramadol exposures in children remain sparse. We aimed to investigate the incidence of IR-tramadol exposures in ≤6-year-old children, to describe the characteristics and resulting outcome of ingestions involving IR-tramadol alone, and to estimate a clinically relevant toxic dose in this population. Retrospective analysis of IR-tramadol exposures in ≤6-year-old children, collected by the French Poison Control Centers (PCCs) in 2003–2019. The incidence was estimated using IR-tramadol prescription data from the Health Improvement Network database (the French version of THIN). The Poison severity score (PSS) was used to grade severity. We found 1260 IR-tramadol exposures in ≤6-year-old children. The number of cases per 100,000 IR-tramadol-treated patients increased over time (p <.0001). One hundred forty-five cases involving IR-tramadol alone were analyzed. The median age was 3.0 years (IQR: 1.9, 4.0), the M/F ratio was 1.5 and the median dose was 5.0 mg/kg (IQR 3.3–11.1). Half of the children (49.7%) remained asymptomatic (PSS0) while 29.6% and 14.5% developed minor (PSS1) or moderate-to-severe (PSS2–PSS3) neurological symptoms, respectively. Twelve children developed respiratory depression. No seizures and no fatality were reported. All symptomatic children recovered within 24 h. The ingested IR-tramadol dose was positively correlated with the PSS (p <.0001). Using a receiver operating characteristic (ROC) curve approach (area under the curve, 0.92; p <.001), ingestion of ≥7.4 mg/kg IR-tramadol was appropriate to recommend hospital referral (sensitivity, 100% [95% confidence interval (CI), 85–100]; specificity, 73% [95% CI, 64–80]; predictive positive value, 39% [95% CI, 35–57]; negative predictive value, 100% [95% CI, 96–100]). Children who ingested <7.4 mg/kg IR-tramadol developed no (n = 68) or minor (n = 22) neurological symptoms. Despite increasing tramadol prescriptions in adults during the study period in France, oral exposure to IR-tramadol in ≤6-year-old children was rare but possibly responsible for severe toxicity. Children with no underlying disease and concomitant medication ingesting <7.4 mg/kg IR-tramadol alone could be observed at home. However, given the observed variability in the onset of seizures after tramadol ingestion, which can occur at ingested tramadol doses below 7.4 mg and even at therapeutic doses, parents or guardians should be specifically warned about the risk of seizures. [ABSTRACT FROM AUTHOR]

Superabsorbent polymers are marketed as toys, and cases of ingestion in children are increasingly reported. Even if these cases are usually considered benign, bowel obstruction has been reported. To investigate the exposure characteristics, clinical presentation, management, and outcome of patients who developed bowel obstruction following ingestion of superabsorbent polymer-made products. Databases were searched (no start date − 2020/01/31) using the following keywords: ("superabsorbent" OR "polymer" OR "hydrogel" OR "crystal" OR "jelly" OR "Orbeez" OR "beads") AND ("ingestion" OR "obstruction" OR "perforation") AND ("intestinal" OR "bowel"). All cases of bowel obstruction following superabsorbent polymer-made product ingestion were included. Report selection: We found 25 reports reporting 43 cases of bowel obstruction following superabsorbent polymer-made product ingestion. All the reports were retrospective, including 20 case reports and 4 case series. Patient characteristics and clinical presentation: Age ranged from 6 to 36 months, and the female/male sex ratio was 1.3. The median delay between the ingestion of the product and the onset of the first symptoms (available in only four reports) was 1.0 [0.7;1.8] day (from 15 h to 2 days). The median delay between the onset of gastrointestinal symptoms and hospital admission, available for all but 15 patients, was 3 [2;4] days (from 15 h to 30 days). The reported symptoms were persistent vomiting in all cases, associated with constipation (11/43), diarrhea (1/43), abdominal pain (1/43), and clinically assessed dehydration (14/43). Abdominal palpation found abdominal tenderness or distension in 11/43 and 28/43 patients, respectively. An abdominal mass was palpated in 3/43 patients. Two patients presented with fever, and three patients developed seizures. Characteristics of exposure: Ingestion of superabsorbent polymer-made products was reported by relatives on hospital admission in only 10/43 cases. Based on imaging and/or surgically/endoscopically removed products, all were bead-shaped objects. The median number of beads removed (available in 27/43) was 1 [1–2] (range from 1 to 6). Their median diameter (available in 21/43 patients) at the time of the diagnosis of bowel obstruction – i.e., at hydrated state – was 30 [30;36] mm (range from 25 to 65 mm). Imaging findings: Abdominal radiography, performed in 31/43 patients, never showed evidence of foreign body ingestion Abdominal computed tomography scanning, performed in 10/43 patients, visualized an intraluminal mass in 5/10 cases. Abdominal ultrasound performed in 34/43 patients allowed visualization of a rounded intraluminal image that corresponded to a bead in 28/34 patients but led to a correct diagnosis of foreign body-induced bowel obstruction in only 15/34 cases. One case reported the contributory use of abdominal MRI. Beads were always located in the small bowel (from the duodenum to the terminal ileum). Removal of beads: Bead removal required endoscopy in 2/43 cases and surgery in 41/43 cases (enterotomy or resection in 36/43 and 5/43 cases, respectively). In 3/36 cases, additional enterotomy was performed to remove beads that had not been found during the first surgery. The delay between the onset of gastrointestinal symptoms and removal procedures ranged from 1 to 7 days. Outcome: Except for two fatal cases, the outcome was favorable. Ingestion of superabsorbent polymer-made beads can be responsible for fatal bowel obstruction in children related to the increase in bead size within the intestinal tract. Diagnosis is made difficult by the radiolucent properties of the beads. The management of bowel obstruction probably most often requires endoscopic or surgical procedures. Children under 4 years of age are probably the most at risk of developing bowel obstruction. [ABSTRACT FROM AUTHOR]

In France, pregabalin is widely prescribed in adults but still not approved for children. We aimed to investigate the incidence of pregabalin exposure in ≤6-year-old children, to describe the characteristics and outcome of ingestions involving pregabalin alone, and to estimate a clinically relevant toxic dose in this population. Retrospective analysis of pregabalin exposures in ≤6-year-old children, collected by the French Poison Control Centers in 2004–2019. The incidence was estimated using pregabalin prescription data from the Health Improvement Network database (the French version of THIN). The poison severity score (PSS) was used to grade severity. We found 313 unintentional immediate-release pregabalin ingestions in ≤6-year-old children. The number of cases per 100,000 pregabalin-treated adults increased over time (p < 0.001). One hundred twenty-six cases involving pregabalin alone (age, 2 years [1.6–3.0] (median [25th–75th percentiles]); median ingested dose 6.4 mg/kg [3.6–10.9]) were analyzed. No child presented an underlying neurological/cardiac disease and/or took concomitant medications. Most of the children (77%) remained asymptomatic (PSS0) while 21% and 2% developed minor (PSS1) or moderate (PSS2) neurological symptoms, respectively. No severe complications/fatalities were reported. All symptomatic children recovered within 24 h. The ingested pregabalin dose was positively correlated with PSS (p < 0.0001). Using a ROC curve approach (area under the curve, 0.85; p < 0.001), ingestion of ≥19.4 mg/kg pregabalin was appropriate to recommend hospital referral (sensitivity, 39% [95% confidence interval (95% CI), 24–56], specificity, 100% [95% CI, 96–100], predictive positive value, 100% [95% CI, 64–100], and negative predictive value, 85% [95% CI, 82–89]). Symptomatic children who ingested <19.4 mg/kg pregabalin developed minor symptoms. Despite increasing prescriptions in adults in France, unintentional pregabalin ingestions in ≤6-year-old children remain rare and cause minimal toxicity. Children with no underlying neurological/cardiac disease and concomitant medication ingesting <19.4 mg/kg immediate-release pregabalin alone can be safely observed at home. [ABSTRACT FROM AUTHOR]