Residents' Knowledge regarding Recreational Drug Screening Immunoassays at a Swiss Hospital Group.

Introduction: In case of suspected acute recreational drug toxicity, immunoassays are commonly used as diagnostic tools. Although easy to handle, understanding of their limitations is necessary for a correct interpretation of the results. The aim of this project was to investigate residents' knowledge regarding drug screening immunoassays at a Swiss hospital group. Methods: All residents of a large hospital group in Switzerland were invited by e-mail to participate in an anonymous survey. Following ten multiple choice questions on drug screening tests, the participants were also asked about their demographics, whether they used drug screening tests on a regular basis, and how confident they felt in their ability to interpret test results. Results: The ten knowledge questions were answered by 110 of the 1026 residents (11%). Among the 108 participants with available demographics, 90% were 25-35 years old, 63% were female, and 70% were at least in their 4th year of residency. The median score of correct answers was 4 out of 10 (range 0-7) and in 50% of the questions, the correct answer was the most frequently selected response. No significant differences in the knowledge scores were found based on the training, confidence level, or the frequency of drug tests used in daily work. Conclusion: This survey revealed widespread knowledge gaps among residents regarding the interpretation of immunoassay-based drug test results. These findings can be used to implement educational measures on this topic and might provide a basis for targeted information on common pitfalls to be included in laboratory reports.

Anticoagulation reversal (vitamin K, prothrombin complex concentrates, idarucizumab, andexanet-α, protamine).

Bleeding events are common in patients prescribed anticoagulants and can have devastating consequences. Several specific and nonspecific agents have been developed to reverse the effects of anticoagulant drugs or toxins. Vitamin K, as the oldest of these antidotes, specifically counteracts the effects of pharmaceuticals and rodenticides designed to deplete stores of vitamin K-dependent factors. In cases of life-threatening bleeding, the addition of prothrombin complex concentrates (PCCs) allows for the immediate replacement of coagulation factors. While the use of PCCs has been extended to the non-specific reversal of the effects of newer direct oral anticoagulants, the specific agents idarucizumab, targeting dabigatran and andexanet-α, binding factor Xa inhibitors, have recently been developed and are being preferentially recommended by most guidelines. However, despite having rapid effects on correcting coagulopathy, there is to date a lack of robust evidence establishing the clear superiority of direct oral anticoagulant-specific reversal agents over PCCs in terms of haemostatic efficacy, safety or mortality. For andexanet-α, a potential signal of increased thromboembolic risks, comparatively high costs and low availability might also limit its use, even though emerging evidence appears to bolster its role in intracranial haemorrhage. Protamine is the specific agent for the reversal of unfractionated heparin anticoagulation used mainly in cardiovascular surgery. It is much less effective for low molecular weight heparin fragments and is usually reserved for cases with life-threatening bleeding.

Pharmacokinetics and pharmacodynamics of inhaled nicotine salt and free-base using an e-cigarette: A randomized crossover study.

BACKGROUND: Popular "pod-style" e-cigarettes commonly use nicotine salt-based e-liquids that cause less irritation when inhaled and can deliver higher nicotine concentrations than free-base nicotine. We aimed to investigate the pharmacokinetic and pharmacodynamic effects of different nicotine formulations (salt vs. free-base) and concentrations that might influence systemic nicotine absorption and appeal of e-cigarettes. METHODS: In this randomized, double-blind, within-subject crossover study, 20 non nicotine-naïve participants were switched among three e-liquids (free-base nicotine 20mg/mL, nicotine salt 20mg/mL, nicotine salt 40mg/mL) using a refillable pod system and a standardized vaping protocol (one puff every 30 seconds, 10 puffs total). Serum nicotine concentrations and vital signs were assessed over 180 minutes; direct effects, craving, satisfaction, withdrawal, and respiratory symptoms were measured using questionnaires. CYP2A6 genotypes and the nicotine metabolite ratio were also assessed. RESULTS: Eleven (55%) participants were male and the median age was 23.5 years (range 18-67). All three formulations differed significantly in peak serum nicotine concentration (baseline adjusted Cmax, median (range): 12.0ng/mL (1.6-27.3), 5.4ng/mL (1.9-18.7) and 3.0ng/mL (1.3-8.8) for nicotine salt 40mg/mL, nicotine salt 20mg/mL and free-base 20mg/mL, respectively). All groups reached Cmax 2.0-2.5min (median) after their last puff. Differences in subjective effects were not statistically significant. No serious adverse events were observed. CONCLUSION: Free-base 20mg/mL formulations achieved lower blood nicotine concentrations than nicotine salt 20mg/mL, while 40mg/mL nicotine salt yielded concentrations similar to cigarette smoking. The findings can inform regulatory policy regarding e-liquids and their potential use in smoking cessation. IMPLICATIONS: Nicotine salt formulations inhaled by an e-cigarette led to higher nicotine delivery compared to nicotine free-base formulations with the same nicotine concentration. These findings should be considered in future regulatory discussions. The 40mg/mL nicotine salt formulation showed similar nicotine delivery as combustible cigarettes, albeit at concentrations over the maximum limit for e-liquids allowed in the European Union. Nicotine delivery resembling combustible cigarettes might be beneficial for smokers willing to quit to adequately alleviate withdrawal symptoms. However, increased nicotine delivery can also pose a public health risk, raising concerns about abuse liability, especially among youth and non-smokers.

Dose-related hypoglycemia in venlafaxine poisoning: a retrospective cohort study.

CONTEXT: Several case reports describe hypoglycemia in the context of venlafaxine overdose, while investigations at therapeutic dose suggested a neutral effect on glucose homeostasis. Studies on hypoglycemia in venlafaxine intoxication are lacking. METHODS: Single-center retrospective cohort study of non-diabetic patients presenting with a laboratory-confirmed antidepressant overdose to the department of clinical toxicology of a tertiary care hospital over a 12-year period. Our main goal was to investigate the association of hypoglycemia as the primary outcome with venlafaxine exposure using multiple logistic regression. Multi-drug exposures were included. We further aimed to describe the association of blood glucose (BG)/hypoglycemia with antidepressant dose, seizures and length of hospital stay. RESULTS: 525 antidepressant intoxications were included, 85 of which involved venlafaxine. Hypoglycemia occurred in 34.1% (29/85) of venlafaxine intoxications and in 10.7% (47/440) of non-venlafaxine antidepressant overdoses. Venlafaxine exposure was significantly associated with hypoglycemia (adjusted odds ratio (OR): 6.6, 95% confidence interval (CI): 3.5-12.6). Venlafaxine-associated hypoglycemia was mainly mild (BG: 51-70 mg/dL), in 75.8% of cases, to moderate (BG: 31-50 mg/dL), in 20.7%, with one case of severe hypoglycemia (BG: 30 mg/dL). BG was significantly inversely correlated with dose in the venlafaxine group (Spearman's correlation coefficient: -0.47, p = 0.002) but not in other commonly prescribed antidepressants. Regardless of venlafaxine exposure, hypoglycemia was associated with seizures (adjusted OR: 5.3, 95% CI: 2.6-10.6) and with a 2.7 day increase in hospital length of stay (95% CI: 1.3-4.2). CONCLUSION: A dose-related, mild to moderate hypoglycemia occurred in over one-third of venlafaxine poisonings. In overdose of other antidepressants, hypoglycemia was seen less frequently and without significant dose-dependency. Regardless of venlafaxine exposure, hypoglycemia was associated with seizures and prolonged length of stay, although these factors are likely primarily determined by other toxicities. BG monitoring in venlafaxine overdose should be considered.

Extracorporeal multiorgan support including CO2-removal with the ADVanced Organ Support (ADVOS) system for COVID-19: A case report.

A substantial part of COVID-19-patients suffers from multi-organ failure (MOF). We report on an 80-year old patient with pulmonary, renal, circulatory, and hepatic failure. We decided against the use of extracorporeal membrane oxygenation (ECMO) due to old age and a SOFA-score of 13. However, the patient was continuously treated with the extracorporeal multi-organ- "ADVanced Organ Support" (ADVOS) device (ADVITOS GmbH, Munich, Germany). During eight 24h-treatment-sessions blood flow (100-300 mL/min), dialysate flow (160-320 mL/min) and dialysate pH (7.6-9.0) were adapted to optimize arterial PaCO2 and pH. Effective CO2 removal and correction of acidosis could be demonstrated by mean arterial- versus post-dialyzer values of pCO2 (68.7 ± 13.8 vs. 26.9 ± 11.6 mmHg; p < 0.001). The CO2-elimination rate was 48 ± 23mL/min. The initial vasopressor requirement could be reduced in parallel to pH-normalization. Interruptions of ADVOS-treatment repeatedly resulted in reversible deteriorations of paCO2 and pH. After 95 h of continuous extracorporeal decarboxylating therapy the patient had markedly improved circulatory parameters compared to baseline. In the context of secondary pulmonary infection and progressive liver failure, the patient had a sudden cardiac arrest. In accordance with the presumed patient will, we decided against mechanical resuscitation. Irrespective of the outcome we conclude that extracorporeal CO2 removal and multiorgan-support were feasible in this COVID-19-patient. Combined and less invasive approaches such as ADVOS might be considered in old-age-COVID-19 patients with MOF.

An internet-based survey of 96 German-speaking users of "bath salts": frequent complications, risky sexual behavior, violence, and delinquency.

OBJECTIVE: To define the demographics of German-speaking "bath salt" users. DESIGN: Prospective web-based survey of volunteer users of "bath salts". Subject recruitment/exclusion: Participation was solicited by posts in web forums frequented by users of synthetic cathinones. An invitation to participate was also disseminated via regional drug information centers. Responses were discarded if participants refused data analysis, provided incomplete surveys, were under 18 years of age (five cases), and in case of clearly improbable answers (i.e., two cases with profanity typed in free-form input fields). Overall 96 out of 180 participants provided complete questionnaires. These were further analyzed. RESULTS AND CONCLUSIONS: 74% of respondents were male. 41% were under the age of 30 and a further 38% between 30 and 39 years old. Cathinones were used on more than 10 days in the preceding year by 62% of study subjects. The nasal and intravenous routes of administration were most often used. About 80% of respondents reported binge use. There were frequent co-administrations of opioids and opiates. The most common complication was prolonged confusion (47%). 16% had been involuntarily confined. One third had thoughts of violence and 16% acted on these thoughts either against themselves or others. About 44% reported high-risk sexual activity under the influence of cathinones. About 31% had driven or ridden a bike while intoxicated. About 6% had problems with law-enforcement for selling cathinones and 16% for crimes committed under the influence of cathinones. In conclusion, cathinone users are typically young males in their twenties and thirties. Most are experienced drug users, particularly of alcohol and opiates/opioids. The impact on society is tremendous as evidenced by high rates of self-reported violence, high-risk sexual activity, crimes, and traffic violations.