Marked increase in severe neurological disorders after nitrous oxide abuse: a retrospective study in the Greater Paris area.

BACKGROUND: Recreational nitrous oxide (N2O) use has become more widespread worldwide, leading to an increase in myelopathies and peripheral neuropathies. The aim of this study was to describe clinical and socioeconomical characteristics of severe N2O-induced (NI) neurological disorders (NI-NDs), to determine its incidence in the Greater Paris area and to compare it with that of similar inflammatory neurological disorders. METHODS: We performed a retrospective multicentric cohort study of all adult patients with severe NI-NDs in the neurology and general internal medicine departments of the Greater Paris area from 2018 to 2021. The incidence was compared with that of non-NI-myelitis and Guillain-Barré syndrome (GBS) using a sample of 91,000 hospitalized patients sourced from health insurance data. RESULTS: Among 181 patients, 25% had myelopathy, 37% had peripheral neuropathy and 38% had mixed disease. Most were aged between 20 and 25 years, lived in socially disadvantaged urban areas, and exhibited high rates of unemployment (37%). The incidence of NI-NDs increased during 2020 and reached a peak mid-2021. The 2021 incidence in 20-25-year-olds was 6.15 [4.72; 8.24] per 100,000 persons for NI-myelopathy and 7.48 [5.59; 9.37] for NI-peripheral neuropathy. This was significantly higher than for non-NI-myelitis (0.35 [0.02; 2.00]) and GBS (2.47 [0.64; 4.30]). The incidence of NI-NDs was two to three times higher in the most socially disadvantaged areas. CONCLUSION: The recent increase in recreational N2O use has led to a rise in the incidence of severe NI-NDs, particularly in young adults with low socioeconomic status for whom NI-NDs strongly outweigh similar neurological disorders.

Short message service as a tool for mass follow-up of patients requesting a poison centre: a retrospective comparative study in France.

INTRODUCTION: The short message service is an alternative to telephone follow-up of exposure cases reported to poison centres. The aim of this study was to compare the proportion of exposure cases successfully followed up and the respective cost of telephone and short message service follow-up between two poison centres, one using both methods of follow-up (Paris centre) and the other using telephone follow-up only (Nancy centre). METHODS: In 2021, we included cases eligible for short message service follow-up at both centres. Eligibility criteria were calls from the public reporting non-toxic or minor toxic exposure not requiring medical consultation. We collected the follow-up type (telephone/short message service) and outcome (success/failure). The cost of each type of follow-up was estimated. RESULTS: In 2021, 16,867 and 11,107 exposure cases were eligible for short message service follow-up at the Paris and Nancy centres, respectively. The Paris centre followed up 86.2 per cent of cases by short message service, and the remainder by telephone, while the Nancy centre followed up all cases by telephone. The Paris centre had a greater follow-up rate compared to the Nancy centre (93.0 per cent versus 43.6 per cent; P < 0.0001). Overall, the success rates were similar between the two centres (P = 0.06), with short message service and telephone follow-up showing comparable success rates (88.1 per cent versus 88.7 per cent; P = 0.25). On average, telephone follow-up took almost twice as long (1.51 min versus 0.85 min) and cost 1.3 times more (0.59 euros versus 0.45 euros) than short message service follow-up. DISCUSSION: Short message service follow-up allows more patients to be successfully followed up at a lower cost compared to telephone-only follow-up, albeit with potential differences in information quality. CONCLUSIONS: Short message service follow-up is a promising tool for poison centres to follow up with patients. Further studies are needed to assess the quality of the data collected and caller satisfaction.

Trends in adverse drug reactions related to oral weak opioid analgesics in therapeutic use in adults: A 10-year French vigilances retrospective study.

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.

Rituximab-Induced Serum Sickness Overlapping With Anaphylaxis: A Case Report.

Serum sickness (SS) and anaphylaxis are well-documented complications of rituximab (RTX) infusions. While the first presents usually as a triad of fever, rash, and arthralgias occurring seven to 14 days after infusion, the second presents as a sudden onset of hemodynamic instability, bronchospasm, and a pruritic erythematous rash, occurring within the first few hours after infusion. We present here a case of serum sickness associated with anaphylaxis five days after the first infusion of a second course of RTX. Only eight cases of rituximab-induced serum sickness (RISS) associated with hemodynamic instability have been reported. We describe the first case of proven anaphylaxis with an elevated tryptase serum level occurring in conjunction with RISS, six days after a third RTX infusion.

French Scorpionism (Mainland and Oversea Territories): Narrative Review of Scorpion Species, Scorpion Venom, and Envenoming Management.

Sixty-seven scorpion species have been described in France and its territories, where they have been found to be heterogeneously distributed. Indeed, only one species can be found on Réunion Island, while 38 species exist in French Guiana. The number of stings is also heterogenous, with up to 90 stings per 100,000 inhabitants occurring annually. Scorpion species can frequently be determined through simple visual factors, including species of medical importance (i.e., Buthus, Centruroides and Tityus). Scorpion venom is composed of local enzymes and peptides with a cysteine-stabilized α/ß motif (NaTxs, Ktxs, Calcines), which allow for venom diffusion and the prey's incapacitation, respectively. Harmful scorpion species are limited to Centruroides pococki in the French West Indies, which can induce severe envenoming, and the Tityus obscurus and Tityus silvestris in French Guiana, which can cause fatalities in children and can induce severe envenoming, respectively. Envenomation by one of these scorpions requires hospital monitoring as long as systemic symptoms persist. Typical management includes the use of a lidocaine patch, pain killers, and local antiseptic. In the case of heart failure, the use of dobutamine can improve survival, and pregnant women must consult an obstetrician because of the elevated risk of preterm birth or stillbirth. France does not have scorpion antivenom, as scorpion stings are generally not fatal.

Fitness to Serve in the Armed Forces and Internal Medicine: A Retrospective Study.

INTRODUCTION: Assessment of the medical fitness to serve in the armed forces has two objectives: to prevent the military operations from being jeopardized by a medical issue, and to protect soldiers from the sequelae of diseases that could become complicated in the operational field, especially in overseas operations where soldiers are exposed to a remote setting and a long evacuation time. Little is known about fitness decisions for soldiers with systemic or autoimmune diseases. Therefore, we conducted a single-center retrospective study of internal medicine fitness decisions. MATERIALS AND METHODS: All the fitness decisions discussed from September 2019 to December 2020 in our department of internal medicine were reviewed. Gender, age, army or service, rank, garrison and health topic were collected from the medical files. Our Military Hospital local ethics committee, in accordance with the French law, approved this study. RESULTS: There were 41 cases, involving 31 men and 10 women (mean age: 31 years), presenting with autoimmune or systemic diseases, metabolic disorders, thrombophilia, congenital or acquired malformations or organ failure, miscellaneous nephropathies, or hemogram abnormalities. Four patients were taking immunosuppressive agents, 3 biologics, and 4 anticoagulants. Among the 15 civilians requiring medical fitness assessment to enlistment, 6 were declared fit. They presented with a history of juvenile idiopathic arthritis with intermediate uveitis without relapse for 7 years, Mayer-Rokitansky-Küster-Hauser syndrome type II with ectopic kidney, solitary kidney with normal renal function and with hypertension, isolated proteinuria, proteinuria with microscopic hematuria, and muscular fibrolipoma with a history of surgical treatment of a vascular malformation. Among the 26 patients already enlisted in the armed forces, 9 were referred for assessment of medical fitness to serve overseas. Two soldiers were assessed as fit without restrictions; one presented with a history of a single episode of deep vein thrombosis after surgery, and the other had a history of monoclonal gammopathy of renal significance without relapse and without treatment for 8 years. Four soldiers were assessed as fit only for overseas territories with sanitary structures similar to mainland France. They presented with immunoglobulin A (IgA) nephropathy and treatment with angiotensin-converting enzyme inhibitor, mevalonate kinase deficiency and treatment with anakinra, chronic idiopathic thrombocytopenic purpura, and history of unilateral partial renal infarction. The 17 other soldiers were referred for dispensation, long-sickness leave granting, or for specification toward administrative coding of their disease. CONCLUSIONS: We have described the first exhaustive study of specialized fitness decisions referred to an internal medicine department. One-third of the referred patients were declared fit to serve in the armed forces. Further studies are needed to confirm these results, as our study was monocentric. Fitness decisions must take into account the disease, the treatment, and the operational field characteristics. Soldiers with systemic diseases controlled by immunosuppressive agents can serve in tropical areas if they can reach adequate sanitary structures in a short time. The knowledge of systemic diseases as well as the skillfulness of the internists, which are regularly projected to the operational fields, allows them to provide pragmatic fitness expertise to myriad complex situations.

Poison control centres and alternative forms of communication: comparison of response rates between text message and telephone follow-up.

INTRODUCTION: In recent years, the number of patients managed by poison control centres (PCCs) has increased without a proportional increase in the number of physicians. To improve efficiency without neglecting patient follow-up, some PCCs have begun using text messages. We evaluated the difference in response rates between text messaging and traditional telephone follow-up. MATERIALS AND METHODS: This retrospective, monocentric, non-randomised cohort study was conducted using data from calls made by the New Aquitaine PCC between February 27, 2019, and March 31, 2019. Patients were contacted up to three times by a phone call or short message service (SMS). RESULTS: For the analysis, 823 patients were included. At the end of follow-up, the response rates were similar in the phone call and SMS group (94 vs. 94%; p = 0.76) with median [interquartile range] response times of 0 min [0; 27 min] and 29 min [6; 120 min], respectively. The response rates did not differ in subgroups stratified according to sex, self-poisoning vs. relative response, age class, and solicitation during working hours vs. outside of working hours (all p > 0.5). Moreover, health practitioners required 2.4-fold more time to call than to send text messages (p < 0.001), and all practitioners were satisfied or very satisfied with text messaging implementation. CONCLUSION: Patients had good adherence to text messages. Text messages are easy to use, rapid, and allow the physician to easily prioritise follow-up without occupying the emergency line. Additionally, the costs of installation and maintenance are low for text message systems; these low costs facilitate the implementation of such services in various medical situations.

Exposure to immediate-release tramadol in children 6 years and under - a nationwide French poison control center study.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Bowel obstruction following ingestion of superabsorbent polymers beads: literature review.

RATIONALE: 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. OBJECTIVE: To investigate the exposure characteristics, clinical presentation, management, and outcome of patients who developed bowel obstruction following ingestion of superabsorbent polymer-made products. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Increase in pregabalin recreational use in adolescents in France.

INTRODUCTION: Misuse/abuse of pregabalin is increasing worldwide. French Poison Control Centers (PCCs) recently received several unusual calls regarding the recreational use of pregabalin in adolescents. This study aims to describe this new and specific population of pregabalin misusers. METHODS: We extracted all cases of pregabalin intentional exposures reported to the French National Database of Poisonings (FNDP) from 2004 to 2020. We compared the proportion of recreational exposure to pregabalin between adolescents (10-17 years) and adults (>18 years). We reviewed all cases of pregabalin recreational exposures in adolescent in order to describe the characteristics of this population. RESULTS: During the study period, 382 cases of acute intentional exposure to pregabalin were reported in adolescents and 1188 in adults, 94/382 (24.6%) and 43/1188 (3.6%) were pregabalin recreational use, respectively (p < .0001). Almost all cases of pregabalin recreational use in adolescent were reported from 2018 (86/94; 91%). Most of those adolescent patients were males (male/female ratio - 5.3:1) and the median age was 15 years (range: 11-17.8). They were homeless or living in migrant shelters in most of the cases (73/90, 81%). Two-third of these exposures (62/94; 66%) involved other toxicant(s) than pregabalin. Most of the patients remains asymptomatic (10/94; 11%), or developed minor to moderate neurological symptoms (76/94; 81%). Eight developed severe symptoms (8/94; 8%) including coma (5/8) or generalized seizures (2/8). Five patients (5/8) required oro-tracheal intubation. No fatality was reported. CONCLUSIONS: We observed a sharp increase in pregabalin recreational use in adolescents in France. It should lead to prevention campaigns, targeted at the population at risk described in this study.

Direct oral anticoagulant plasma level measurement in clinical practice: A French single-institution retrospective study.

INTRODUCTION: To describe patient characteristics and clinical situations where DOAC assays were ordered and determine whether the assays indications and subsequent patient management were consistent with current guidelines. METHODS: Retrospective study of data from patients with prescriptions for three DOACs: dabigatran, rivaroxaban and apixaban treated at Percy Military Hospital (France) between 2016 and 2019. RESULTS: During the study period, 196 DOAC measurements were performed on 148 patients (median age: 82.5 years). The most frequently prescribed DOAC was rivaroxaban (57.5%) and the commonest indication was nonvalvular atrial fibrillation (77%). Measurements were performed on 3.5% of patients with an active prescription for DOAC, and DOAC prescriptions complied with the product's characteristic summary in 62.8% of cases. The number of assays performed increased 2.5-fold between 2017 and 2019. Most DOAC assays were ordered due to emergency surgery or procedures (46.9%), bleeding (19.9%) or a risk of drug accumulation (13.8%). Time from the last DOAC dose to sample collection was specified in the medical file in only 25.5% of cases. Reasons for ordering DOAC measurements were consistent with the guidelines in 87.2% of cases. Subsequent clinical decisions were consistent with the guidelines in 86.2% of cases. CONCLUSIONS: DOAC assays ordering frequency was rare but increased during study. Acute clinical situations were the most common source of test orders. A correct interpretation of the results and subsequent management occurred in most but not all cases, indicating the need for additional education for physicians to raise awareness about tests indications and results interpretation.

Unintentional exposure to pregabalin in ≤6-year-old children: a nationwide French Poison Control Center study.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Envenomation by Centruroides pococki scorpion with neuromuscular toxicity.

Cases of human envenomation by Centruroides pococki are exceptionally reported in human. We report a Class III human envenomation by C. pococki in Guadeloupe, French West Indies, with neuromuscular toxicity that has never been described before. Symptoms resolved within a few hours, without the need for intravenous scorpion-specific antivenom.

Acute occupational exposure to holothurians (Cucumaria frondosa) resulting in irritating symptoms: About three cases.

Holothurians are marine invertebrates also known as sea cucumbers. They are used in fresh or dried forms in various cuisines around the world and have alleged medicinal properties. Consequently, sea cucumbers, notably the orange-footed sea cucumber (Cucumaria frondosa)are increasingly harvested from the environment or farmed via aquaculture. We report three cases of unusual occupational exposure to C. frondosa resulting in cutaneous, respiratory and ocular irritating symptoms. These symptoms occurred as sea cucumbers were cut on half and eviscerated manually, following a machine breakdown in a sea cucumber processing factory. Given the composition of holothurians, these symptoms probably resulted from the aerosolization of various holothurins, saponins secreted by sea cucumbers as mean of defense. Treatment was solely symptomatic and included decontamination of the skin and the eyes, inhaled glucocorticoids, anticholinergic agents and oral glucocorticoids. As the exposure resulted from a machine breakdown, no specific protective equipment was put in place. Employees were advised not to handle manuallythe sea cucumbers in case such a breakdown was to happen again.