Self-poisoning by E-cigarette and E-liquids: National Reports to French Poison Control Centers from July 2019 to December 2020: VIGIlance and VAPE: The VIGIVAPE Study.

INTRODUCTION: Exposure to e-cigarette liquids, whether intentional or accidental, might lead to adverse events. This study aimed to describe the prevalence and characteristics of exposures to e-liquids reported to French Poison Control Centers. METHODS: All e-liquids exposure cases reported to French Poison Control Centers from July 1, 2019, to December 31, 2020, were reviewed. Information was collected about the patient's characteristics, exposure circumstances, management and outcome. RESULTS: About 919 cases of exposure to e-liquids were reported. Ages ranged from one month to 89 years, with a mean age of 16.6 ± 18.6 years and a median age of 4 years. The highest number of exposures-50.7%-concerned infants (0-4 years), 3.1% children (5-11 years), 5.9% adolescents (12-17 years), and 40.1% of cases concerned adults. The majority of cases were accidental (95.0%). Intentional exposures (4.9%) were mainly observed in patients older than 12 years of age (P < 0.001). The route of exposure was ingestion in 73.7% of the cases. A total of 455 exposures showed no symptoms or signs related to poisoning. High nicotine concentration in e-liquids was associated with an increase in hospital management (Odds-ratio from 1.77 to 2.60). CONCLUSION: Involuntary exposures to e-liquids occurred more often in children under the age of five, mainly by ingestion. Unlike intentional ingestions, unintentional ingestions rarely resulted in severe adverse events. These findings highlight the importance of ongoing surveillance to prevent such exposures and associated injuries, emphasizing the need for effective regulation of these products.

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.

Poisoning during the COVID-19 outbreak and lockdown: retrospective analysis of exposures reported to French poison control centres.

INTRODUCTION: The aim was to assess the impact of the COVID-19 pandemic on French Poison Control Centre (PCC) call characteristics. METHODS: Reported cases of xenobiotic exposures from 1 March to 30 April in 2018, 2019, and 2020 were extracted from the French National Database of Poisonings. The collected data included call, patient, and exposure characteristics for both general calls and for calls involving sentinel xenobiotic categories related to the COVID-19 pandemic. The 2020 exposures were compared to 2018-2019 exposures by using simple logistic models in order to provide effect size with odds ratios. RESULTS: From March to April 2020, 32,182 exposures were reported to French PCCs with an overall increase of 5.6% compared to exposures in the same time frame in 2018-2019. A similar increase in calls was observed in non-epidemic and epidemic COVID-19 areas with an increase in calls from the public (+13.6%) while calls from health-professionals decreased (-7.5%). Despite the increase in exposures, the incidence of symptomatic exposures remained stable (-0.4%) with a decrease in severity (moderate/severe -17.2%). A significant increase in exposures to home cleaning products containing biocides, essential oils, and alcohol-based hand sanitizers (odds ratio >1.3, p < .0001) was observed. DISCUSSION AND CONCLUSION: The COVID-19 pandemic altered calls to French PCCs with a small increase in calls during the study period and changes in the pattern of exposure. These changes possibly reflected the indirect consequences of the COVID-19 pandemic i.e., limited access to primary care, fear of contracting COVID-19 and anxiety related to home isolation.

Why are people increasingly attending the emergency department? A study of the French healthcare system.

OBJECTIVE: It is often asserted that the crowding phenomenon in emergency departments (ED) can be explained by an increase in visits considered as non-urgent. The aim of our study was to quantify the increase in ED visit rates and to determine whether this increase was explained by non-severe visit types. METHODS: This observational study covers all ED visits between 2002 and 2015 by adult inhabitants of the Midi-Pyrénées region in France. Their characteristics were collected from the emergency visit summaries. We modelled the visit rates per year using linear regression models, and an increase was considered significant when the 95% CIs did not include zero. The severity of the patients' condition during ED visit was determined through the 'Clinical Classification of Emergency' score. Non-severe visits were those where the patient was stable, and the physician deemed no intervention necessary. Intermediate-severity visits concerned patients who were stable but requiring diagnostic or therapeutic procedures. RESULTS: The 37 studied EDs managed >7 million visits between 2002 and 2015. There was an average increase of +4.83 (95% CI 4.33 to 5.32) visits per 1000 inhabitants each year. The increase in non-severe visit types was +0.88 (95% CI 0.42 to 1.34) per 1000 inhabitants, while the increase in intermediate-severity visit types was +3.26 (95% CI 2.62 to 3.91) per 1000 inhabitants. This increase affected all age groups and all sexes. DISCUSSION: It appears that the increase in ED use is not based on an increase in non-severe visit types, with a greater impact of intermediate-severity visit types requiring diagnostic or therapeutic procedures in ED.

Identifying key factors leading to the optimal care pathway for patients with ST-segment elevation myocardial infarction: Results from the RESCAMIP registry.

BACKGROUND: In France, when someone presents with chest pain, it is recommended to call a health emergency number. The patient talks with an emergency doctor at a medical dispatch centre, who decides whether (or not) to send a Mobile Intensive Care Unit (MICU). Patients with an ST-segment elevation myocardial infarction (STEMI) should have an MICU as their first medical contact, to speed up confirmation of diagnosis and enable them to benefit from reperfusion therapy as quickly as possible. AIM: To evaluate the proportion of patients with STEMI benefiting from an optimal care pathway, and to identify the key factors leading to this pathway. METHODS: RESCAMIP was a multicentre registry conducted between May 2015 and May 2017 in Midi-Pyrénées. All patients treated for STEMI within 12hours of symptoms onset, without initially going into cardiac arrest, were included. RESULTS: Data from 1371 patients with STEMI were analysed; 60% had an MICU as their first medical contact. In-hospital mortality was 4%. Factors associated with calling the medical dispatch centre when presenting chest pain were: age>65 years (odds ratio [OR] 1.37, 95% confidence interval [CI] 1.02-1.83), personal history of cardiovascular disease (OR 1.9, 95% CI 1.22-2.96) and having cardiovascular risk factors (OR 1.84, 95% CI 1.35-2.5). Factors associated with sending an MICU as first medical contact were: male sex (OR 2.11, 955 CI 1.49-2.99) and personal history of cardiovascular disease (OR 1.69, 95% CI 1.07-2.65). CONCLUSIONS: The proportion of patients with STEMI going through non-optimal pathways was 40% in our area. We note that there are sex-based inequalities in accessing MICUs.

How to Manage Self-Poisoning With Baclofen in Alcohol Use Disorder? Current Updates.

Specialists in addiction medicine continue to debate whether baclofen is still indicated to treat alcohol use disorders in view of conflicting results as to its efficacy. This review summarizes current knowledge on self-poisoning with baclofen focusing of alcohol-use disorder in order to provide an overview of the reliable scientific knowledge on management of such an intoxication. Moreover, as alcohol-dependent patients experience many psychiatric co-morbidities, the risk in suicide attempt using baclofen seems real. Numerous studies have suggested that patients given daily-doses of baclofen higher than 80 mg/day are more likely to attempt suicides than others. Following an ingestion of a large amount of baclofen, central nervous system depression is usually observed. Seizures require the patient to be admitted in intensive care unit and should be treated like other toxicological seizures. Cardiac complications include prolonged QTc interval, degree heart block, premature atrial contractions, and supraventricular tachycardia, hypotension and bradycardia. In cases of intoxication, the elimination half-life of baclofen may last between 12 and 36 h post-overdose and renal failure is known to delay its clearance. Rarely measured in clinical practice, the toxic level of baclofen blood level ranges from 1.1 to 3.5 mg/l, and coma or fatal intoxication are observed from 6 to 9.6 mg/l. Baclofen withdrawal has been observed but making the diagnosis of withdrawal in case of suspected self-poisoning is difficult as baclofen intoxication and baclofen withdrawal share many clinical signs. Admission to hospital to manage of suicide attempt with baclofen is mandatory and should not be limited to baclofen alone. It needs to include other aspects of the overall care of patients with alcohol disorders (psychological and psychosocial interventions, management of comorbid mental conditions and physical complications).

The Use of Baclofen as a Treatment for Alcohol Use Disorder: A Clinical Practice Perspective.

Alcohol use disorder (AUD) is a brain disorder associated with high rates of mortality and morbidity worldwide. Baclofen, a selective gamma-aminobutyric acid-B (GABA-B) receptor agonist, has emerged as a promising drug for AUD. The use of this drug remains controversial, in part due to uncertainty regarding dosing and efficacy, alongside concerns about safety. To date there have been 15 randomized controlled trials (RCTs) investigating the use of baclofen in AUD; three using doses over 100 mg/day. Two additional RCTs have been completed but have not yet been published. Most trials used fixed dosing of 30-80 mg/day. The other approach involved titration until the desired clinical effect was achieved, or unwanted effects emerged. The maintenance dose varies widely from 30 to more than 300 mg/day. Baclofen may be particularly advantageous in those with liver disease, due to its limited hepatic metabolism and safe profile in this population. Patients should be informed that the use of baclofen for AUD is as an "off-label" prescription, that no optimal fixed dose has been established, and that existing clinical evidence on efficacy is inconsistent. Baclofen therapy requires careful medical monitoring due to safety considerations, particularly at higher doses and in those with comorbid physical and/or psychiatric conditions. Baclofen is mostly used in some European countries and Australia, and in particular, for patients who have not benefitted from the currently used and approved medications for AUD.

Management of precipitated opiate withdrawal syndrome induced by nalmefene mistakenly prescribed in opiate-dependent patients: a review for clinicians.

INTRODUCTION: Nalmefene, a long-acting µ-opioid antagonist approved to treat alcohol use disorder, is occasionally mistakenly prescribed to opiate-dependent or opioid-treated patients. We review recent literature on drug-drug interactions between nalmefene and opioids that lead to precipitated opioid withdrawal, and focus on its management and planning for care at discharge. Areas covered: This article provides a brief and comprehensive review of management of precipitated opioid withdrawal syndrome when nalmefene is associated with an opioid, whether misused or legally prescribed. Expert opinion: When treating an opiate-dependent patient with co-occurring alcohol use disorder, both conditions need to be a focus of clinical attention. New drugs for alcohol use disorder have been approved, but must be given cautiously and with a full understanding of their potential drug-drug interactions with opioid medications. Opiate-dependent patients should be intensively monitored for risk factors of alcohol use disorder and should be continuously motivated for treatment maintenance. When nalmefene is administered to opiate-dependent patients, acute opioid withdrawal syndrome may occur. Management of precipitated acute opioid withdrawal may include short or long-acting µ-opioid agonists during hospitalization, in addition to supportive treatment. The best management of polydrug abusers is based on a multidisciplinary approach, which should be pursued and improved through continuing medical education.

Self-poisoning with baclofen in alcohol-dependent patients: national reports to French Poison Control Centers, 2008-2013.

BACKGROUND: Alcohol use disorders are frequently associated with self-intoxication in attempted suicide. In France since 2008, the off-label use of baclofen for treatment of alcohol dependence has greatly increased, leading to temporary regulation of use of the drug. At the request of the national authorities, the French Poison Control Centers carried out a retrospective survey to give an overview of baclofen exposure in this population. METHODS: A retrospective study was carried out from January 2008 to December 2013, focusing on baclofen exposures in alcohol-dependent patients managed by the nine national French Poison Control Centers. RESULTS: 294 observations of baclofen exposures in alcohol-dependent patients were identified in our database. Of these, 220 were suicide attempts by self-poisoning and 74 were unintentional. The mean age of patients was 41.7 years, with a sex-ratio of 1.6. Patients attempting suicide with baclofen were younger than those with unintentional exposures, and 43.6% of them were women (vs 22.9%, p < 0.01). The mean supposed ingested dose was higher (480.7 mg) in patients who attempted suicide (vs 192.5 mg, p < 0.0001). 21.8% of intentional exposures involved baclofen alone. Psychiatric comorbidity (50.4%) was more frequent in the group of self-poisoning (p < 0.001). 132 patients were coded as severely exposed (60.0%). Nine victims died, but the causal link between self-poisoning with baclofen and fatal outcome should be interpreted with particular caution. CONCLUSIONS: Baclofen self-poisoning by alcohol-dependent patients is a serious concern for the French health authorities. Our results are similar to those previously published, suggesting that most patients with baclofen overdose should be admitted to an intermediate or intensive care unit as the clinical course requires close monitoring. Because suicidal ideation and suicide attempts are more prevalent in people with substance use disorders than in the general population, and because of the lack of recommendations governing baclofen prescription in such a situation, its use needs to be better controlled.

Cannabis Hyperemesis Syndrome in the Emergency Department: How Can a Specialized Addiction Team Be Useful? A Pilot Study.

BACKGROUND: Chronic cannabis users may experience cyclical episodes of nausea and vomiting and learned behavior of hot bathing. This clinical condition, known as cannabis hyperemesis syndrome, was first reported in 2004. OBJECTIVE: Our aim was to promote early recognition of this syndrome in emergency departments (EDs) and to increase referral to addiction specialists. METHODS: Cannabis abusers were admitted to the ED for vomiting or abdominal pain from June 1, 2014 to January 1, 2015 and diagnosed with cannabis hyperemesis syndrome by a specialized addiction team. Then, medical records were examined retrospectively. RESULTS: Seven young adults were included. Their mean age was 24.7 years (range 17-39 years) and the majority were men (male-to-female ratio 1.2). Biological and toxicological blood samples were taken in all patients. Tetrahydrocannabinol blood level was measured in 4 patients, with a mean blood concentration of 11.6 ng/mL. Radiographic examination including abdominal computed tomography and brain imaging were negative, as was upper endoscopy. Five patients compulsively took hot baths in an attempt to decrease the symptoms. Treatment was symptomatic. Five patients have started follow-up with the specialized addiction team. CONCLUSIONS: Cannabis hyperemesis syndrome is still under-diagnosed 10 years after it was first described. Physicians should be aware of this syndrome to avoid repeated hospitalizations or esophageal complications. Greater awareness should lead to prompt treatment and prevention of future recurrence through cannabis cessation. Addiction specialists, as well as medical toxicologists, are experts in the management of cannabis abusers and can help re-establish the role of medical care in this population in collaboration with emergency physicians.

Microenvironment rigidity modulates responses to the HER2 receptor tyrosine kinase inhibitor lapatinib via YAP and TAZ transcription factors.

Stiffness is a biophysical property of the extracellular matrix that modulates cellular functions, including proliferation, invasion, and differentiation, and it also may affect therapeutic responses. Therapeutic durability in cancer treatments remains a problem for both chemotherapies and pathway-targeted drugs, but the reasons for this are not well understood. Tumor progression is accompanied by changes in the biophysical properties of the tissue, and we asked whether matrix rigidity modulated the sensitive versus resistant states in HER2-amplified breast cancer cell responses to the HER2-targeted kinase inhibitor lapatinib. The antiproliferative effect of lapatinib was inversely proportional to the elastic modulus of the adhesive substrata. Down-regulation of the mechanosensitive transcription coactivators YAP and TAZ, either by siRNA or with the small-molecule YAP/TEAD inhibitor verteporfin, eliminated modulus-dependent lapatinib resistance. Reduction of YAP in vivo in mice also slowed the growth of implanted HER2-amplified tumors, showing a trend of increasing sensitivity to lapatinib as YAP decreased. Thus we address the role of stiffness in resistance to and efficacy of a HER2 pathway-targeted therapeutic via the mechanotransduction arm of the Hippo pathway.

Parental cannabis abuse and accidental intoxications in children: prevention by detecting neglectful situations and at-risk families.

OBJECTIVES: Cannabis intoxication in toddlers is rare and mostly accidental. Our objectives were to focus on the characteristics and management of children under the age of 6 years who were admitted to our emergency department with cannabis poisoning reported as accidental by parents, and to point out the need to consider accidental cannabis ingestions as an indicator of neglect. METHODS: The medical records of children hospitalized for cannabis poisoning in a pediatric emergency department from January 2007 to November 2012 were retrospectively evaluated. Data collected included age, sex, drug ingested, source of drug, intentional versus accidental ingestion, pediatric intensive care unit or hospital admission, treatment and length of hospital stay, toxicology results, and rate of child protectives services referral. RESULTS: Twelve toddlers (4 boys and 8 girls; mean age, 16.6 months) were included. All had ingested cannabis. Their parents reported the ingestion. Seven children experienced drowsiness or hypotonia. Three children were given activated charcoal. Blood screening for cannabinoids, performed in 2 cases, was negative in both, and urine samples were positive in 7 children (70%). All children had favorable outcomes after being hospitalized from 2 to 48 hours. Nine children were referred to social services for further assessment before discharge. CONCLUSIONS: Cannabis intoxication in children should be reported to child protection services with the aim of prevention, to detect situations of neglect and at-risk families. Legal action against the parents may be considered. Accidental intoxication and caring parents should be no exception to this rule.

Blood alcohol concentration in intoxicated patients seen in the emergency department: does it influence discharge decisions?

OBJECTIVE: The purpose of this study was to investigate whether blood alcohol concentration (BAC) measurement was routinely requested in emergency departments and whether the observation period in the emergency department allowed sufficient time for alcohol elimination before the patient was discharged. METHOD: A retrospective review of medical records of all emergency alcohol-related admissions over a 12-month period from January 2012, in patients older than 18 years, was conducted. We estimated BAC at discharge for each patient by using the following formula: [BAC at admission--(length of stay × 15)]. Then, we focused on patients discharged from the emergency department with an estimated BAC greater than 50 mg/100 ml because of the risk of subsequent legal proceedings, because this is the legal limit for driving in France. RESULTS: A total of 907 patients admitted for acute alcohol intoxication (F10.0) were included, of whom 592 were male. Women were more likely to be admitted at night. The mean length of stay was 18.7 hours. BAC was measured in 893 patients. Patients ages 35-49 years had the highest measured BAC. No repeat BAC was taken before the discharge decision. Three hundred thirteen patients were discharged with an estimated BAC above 50 mg/100 ml. CONCLUSIONS: Emergency physicians routinely requested BAC at admission but did not request alcohol kinetics while the patient was under observation. The discharge decision was based on clinical judgment. Doctors who do not advise patients appropriately before discharge may be guilty of negligence in their duty of care.

Age-related dysfunction in mechanotransduction impairs differentiation of human mammary epithelial progenitors.

Dysfunctional progenitor and luminal cells with acquired basal cell properties accumulate during human mammary epithelial aging for reasons not understood. Multipotent progenitors from women aged <30 years were exposed to a physiologically relevant range of matrix elastic modulus (stiffness). Increased stiffness causes a differentiation bias towards myoepithelial cells while reducing production of luminal cells and progenitor maintenance. Lineage representation in progenitors from women >55 years is unaffected by physiological stiffness changes. Efficient activation of Hippo pathway transducers YAP and TAZ is required for the modulus-dependent myoepithelial/basal bias in younger progenitors. In older progenitors, YAP and TAZ are activated only when stressed with extraphysiologically stiff matrices, which bias differentiation towards luminal-like phenotypes. In vivo YAP is primarily active in myoepithelia of younger breasts, but localization and activity increases in luminal cells with age. Thus, aging phenotypes of mammary epithelia may arise partly because alterations in Hippo pathway activation impair microenvironment-directed differentiation and lineage specificity.

Self-intoxication with baclofen in alcohol-dependent patients with co-existing psychiatric illness: an emergency department case series.

AIMS: The aim of the study was to describe the characteristics and management of alcohol-dependent patients with co-existing psychiatric illness seen after self-intoxication with oral baclofen in an emergency department (ED). METHODS: A retrospective review of medical records of such patients over a 12-month period from January 2012. RESULTS: Twelve such patients were identified, median age 39.5 years. The median supposed ingested dose of baclofen was 340 mg (range 140-800 mg). Three patients who had co-ingested benzodiazepines had a decreased level of consciousness (Glasgow Coma Scale <8) and flumazenil had been given to reverse coma. Blood alcohol concentration, requested for all patients, was positive in three (ranging from 153 to 495 mg/100 ml). Gastric lavage was performed in two cases. All patients made a full recovery. They were discharged from the ED or intensive care unit after psychiatric assessment. CONCLUSION: Baclofen overdose affects the autonomic and central nervous system. Supportive care is symptom based. Care should be taken when prescribing baclofen with other central nervous system depressants and to patients with past attempted suicide.

Aging phenotypes in cultured normal human mammary epithelial cells are correlated with decreased telomerase activity independent of telomere length.

BACKGROUND: Shortening of telomeres, which are essential for maintenance of genomic integrity, is a mechanism commonly associated with the aging process. Here we ascertained whether changes in telomere lengths or telomerase activity correlated with age in normal human mammary epithelial cells (HMEC), or with phenotypes of aging in breast. Accordingly, flow cytometry fluorescence in situ hybridization (flowFISH) was used to determine relative telomere lengths (RTL), and telomerase activity was measured by the telomeric repeat amplification protocol (TRAP), in a collection of 41 primary HMEC strains established from women aged 16 to 91 years. RESULTS: RTL measurements of HMEC strains that were heterogeneous with respect to lineage composition revealed no significant associations between telomere length with age, maximum observed population doublings, or with lineage composition of the strains. However, within strains, luminal epithelial and cKit-expressing epithelial progenitor cells that were flow cytometry-enriched from individual HMEC strains exhibited significantly shorter telomeres relative to isogenic myoepithelial cells (P < 0.01). In unsorted strains, detectable telomerase activity did not correlate with RTL. Telomerase activity declined with age; the average age of strains that exhibited TRAP activity was 29.7 ± 3.9y, whereas the average age of strains with no detectable TRAP activity was 49.0 ± 4.9y (P < 0.01). Non-detectable TRAP activity also was correlated with phenotypes of aging previously described in HMEC strains; increased proportions of CD227-expressing luminal epithelial cells (P < 0.05) and cKit-expressing progenitor cells (P < 0.05). CONCLUSIONS: Telomere shortening did not correlate with the chronological ages of HMEC strains, whereas decreased telomerase activity correlated with age and with lineage distribution phenotypes characteristic of aging.