Alcohol use disorder (AUD) is a leading cause of morbidity and mortality. 1-2 Alcohol consumption is related to approximately 4% of the global burden of disease. 1 It has been estimated that, in clinical settings and compared to the general population, the relative risk of mortality is 3.38 for male patients and 4.57 for female patients with AUD. 2 Patients who reduce their alcohol consumption may halve this increased risk of mortality compared to patients with AUD who do not. 3 However, currently the approved pharmacotherapies that may help patients with AUD to achieve abstinence and/or reduce alcohol consumption to lower drinking levels are limited in number and efficacy. 4-5 Therefore, there is an urgent need to develop more effective treatments in this area. Preclinical and human studies suggest that baclofen, a GABA B receptor agonist, might be a novel treatment for patients with moderate to severe AUD. 6 Notably, a few years after initial randomized clinical trials (RCTs) were conducted, the potential use of this medication for AUD dramatically increased in its popularity due to a French case report describing the use of very high doses of baclofen to treat alcohol craving and drinking. 7 This intriguing yet purely anecdotical case report led to significant scientific and mass media attention and to the use of baclofen (off-label) in the treatment of AUD, such that the French drugs regulatory agency became involved in evaluating the use of baclofen in AUD. However, clinical studies conducted in Europe, USA, Australia, Israel and that evaluated baclofen efficacy in AUD have yielded conflicting results with some but not all RCTs showing an effect of baclofen. 6 The three recent meta-analyses do not draw definitive conclusions on the efficacy of baclofen in the treatment of AUD. 8-10 In fact, one meta-analysis 8 found no significant superiority of baclofen over placebo on the outcomes of each study whereas the other two found that baclofen treatment significantly increased the rate of abstinent patients 9-10 and time to first lapse 9 compared to placebo. Furthermore, one meta-analysis found larger effect sizes of baclofen among heavy drinkers and studies using lower doses. 9 The other study found no significant efficacy of baclofen in reducing the severity of craving for alcohol, anxiety, and depression. 10 In addition, these two meta-analyses reported no significant efficacy of baclofen on other important outcomes such as rate of abstinence days 9-10 or rate of heavy drinking days. 10 Chiefly, all three meta-analyses found overall a small effect size and substantial heterogeneity among studies. 8-10 Following the publication of these metaanalyses, 8-10 a further RCT has been completed and data analysis is currently under way (JC Garbutt, unpublished; ClinicalTrials.gov: NCT01980706). Despite the lack of consistent evidence of efficacy, baclofen is frequently used off-label to treat AUD, especially in some European countries and Australia. However, there is significant variability in the use of baclofen for cl...

We report for the first time that increased peripheral chemoreflex sensitivity directly decreases sympathetic baroreflex function in CHF patients. This interaction contributes to sympathetic overactivity and blunted sympathetic baroreflex function of CHF patients and may explain how chemoreceptors contribute to the bad prognosis of CHF patients.

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.

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Synthetic opioids (SO) are a major risk for public health across the world. These drugs can be divided into 2 categories, pharmaceutical and non-pharmaceutical fentanyls. A new generation of SO has emerged on the drug market since 2010. North America is currently facing an opioid epidemic of morbi-mortality, caused by over-prescription of opioids, illegally diverted prescribed medicines, the increasing use of heroin and the emergence of SO. Furthermore, this opioid crisis is also seen in Europe. SO are new psychoactive substances characterized by different feature such as easy availability on the Internet, low price, purity, legality, and lack of detection in laboratory tests. They have not been approved or are not recommended for human use. Opioid misuse is associated with somatic and psychiatric complications. For many substances, limited pharmacological information is available, increasing the risk of harmful adverse events. Health actors and the general population need to be clearly informed of the potential risks and consequences of the diffusion and use of SO.

This study supports the impression that accidental child poisonings with cannabis have been more serious than previously thought for 2 years. This observation may be explained by (1) the increased THC concentration in cannabis and (2) the widespread use in young adults, even after they become parents. Introducing an addiction team inside the PED could help to improve the care links with these parents. What is Known: • Cases of unintentional cannabis intoxication in children have been increasing for many years due to an increase of potency. What is New: • We highlight an increase in more severe presentations in children under the age of 3 occurring over the past 2 years, which will indicate the importance of assessing cannabis abuse in parents by a specialized addiction team.

Abstract-Sympathetic activation contributes to both the initiation and progression of heart failure. The role of anemia in determining sympathetic overactivity in chronic heart failure (CHF) patients is unknown. We tested the hypothesis that, in CHF patients, anemia could lead to increased sympathetic activity through tonic activation of excitatory chemoreceptor afferents. We conducted a double-blind, randomized, vehicle-controlled study to examine the effect of chemoreflex deactivation on muscle sympathetic nerve activity in CHF patients with and without anemia. We compared the effect of breathing 100% oxygen for 15 minutes in 18 stable CHF patients with anemia and 18 control CHF patients matched for age, sex, blood pressure, and body mass index. Baseline muscle sympathetic nerve activity was significantly elevated in CHF patients with anemia compared with patients with CHF alone (56.0Ϯ3.2 versus 45.5Ϯ3.1 bursts per minute; PϽ0.0237). Administration of 100% oxygen led to a significant decrease in muscle sympathetic nerve activity in CHF patients with anemia (from 56.0Ϯ3.4 to 50.9Ϯ3.2 bursts per minute; PϽ0.0019). In contrast, neither room air nor 100% oxygen changed muscle sympathetic nerve activity or hemodynamics in patients with CHF alone. We report for the first time direct evidence of increased sympathetic nerve traffic in patients with CHF-related anemia. Sympathetic hyperactivity in patients with CHF and anemia is partially chemoreflex mediated and could explain how anemia contributes to the progression of CHF and increases morbidity and mortality in these patients. (Hypertension. 2010;55:1012-1017.)

The coronavirus disease 2019 (COVID-19) pandemic has made alcohol-based hand sanitizers (ABHS) widely available in public places. This may warrant determining whether cases of unintentional ocular exposure are increasing, especially in children.OBJECTIVE To describe the epidemiologic trend of pediatric eye exposures to ABHS and to report the severity of the ocular lesions. DESIGN, SETTING, AND PARTICIPANTSRetrospective case series conducted from April 1, 2020, to August 24, 2020. Cases were retrieved from the national database of the French Poison Control Centers (PCC) and from a pediatric ophthalmology referral hospital in Paris, France. Cases of ocular exposure to chemical agents in children younger than 18 years during the study period were reviewed. Cases of ABHS exposure were included.EXPOSURES The following data were collected: age, sex, circumstances of exposure, symptoms, size of the epithelial defect at first examination, time between the incident and re-epithelialization, and medical and/or surgical management. MAIN OUTCOMES AND MEASURESComparison of the number of eye exposures to ABHS in children between April to August 2020 and April to August 2019. RESULTSBetween April 1 and August 24, 2020, there were 7 times more pediatric cases of ABHS eye exposures reported in the PCC database compared with the same period in 2019 (9.9% of pediatric eye exposures in 2020 vs 1.3% in 2019; difference, 8.6%; 95% CI, 7.4-9.9; P < .001). The number of cases occurring in public places increased in 2020 (from 16.4% in May to 52.4% in August). Similarly, admissions to the eye hospital for ABHS exposure increased at the same period (16 children in 2020 including 10 boys; mean [SD] age, 3.5 [1.4] years vs 1 boy aged 16 months in 2019). Eight of them presented with a corneal and/or conjunctival ulcer, involving more than 50% of the corneal surface for 6 of them. Two cases required amniotic membrane transplant.CONCLUSIONS AND RELEVANCE These data support the likelihood of an increasing number of unintentional ocular exposures to ABHS in the pediatric population. To maintain good public compliance with hand disinfection, these findings support that health authorities should ensure the safe use of these devices and warn the parents and caregivers about their potential danger for children.