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Up to 1/2 of outpatients prescribed clozapine may be partially/fully non-adherent, based on therapeutic drug monitoring (TDM). Three indices for measuring partial/full non-adherence are proposed a: 1) clozapine concentration/dose (C/D) ratio which drops to half or more of what is expected in the patient; 2) clozapine/norclozapine ratio that becomes inverted; and 3) clozapine concentration that becomes non-detectable. These 3 proposed indices are based on a literature review and 17 cases of possible non-adherence from 3 samples: 1) an inpatient study in a Chinese hospital, 2) an inpatient randomized clinical trial in a United States hospital, and 3) and a Uruguayan outpatient study. The first index of non-adherence is a clozapine C/D ratio which is less than half the ratio corresponding to the patient's specific ancestry group and sex-smoking subgroup. Knowing the minimum therapeutic dose of the patient based on repeated TDM makes it much easier to establish non-adherence. The second index is inverted clozapine/norclozapine ratios in the absence of alternative explanations. The third index is undetectable concentrations. By using half-lives, the chronology of the 3 indices of non-adherence was modeled in two patients: 1) the clozapine C/D ratio dropped to ≥1/2 of what is expected from the patient (around day 2); 2) the clozapine/norclozapine ratio became inverted (around day 3); and 3) the clozapine concentration became undetectable by the laboratory (around days 9–11). Prospective studies should further explore these proposed clozapine indices in average patients, poor metabolizers (3 presented) and ultrarapid metabolizers (2 presented). [Display omitted] [ABSTRACT FROM AUTHOR]

Objectives: The decision to prescribe a medication and the choice of which one are often complex, particularly in the field of child and adolescent psychiatry where evidence is scarce. The aim of this review is to provide a synthesis of psychotropic drugs approved in children and adolescents for psychiatric indications in several countries. Methods: All psychopharmacological treatments used in child and adolescent psychiatry, approved by at least one regulatory agency from Switzerland, the United Kingdom, France, the European Union, or the United States, were considered. A comprehensive review of the summaries of product characteristics was performed. Results: A total of 143 psychotropic drugs were included: 47 anxiolytics/hypnotics, 45 antidepressants, 37 antipsychotics, 10 medications for attention-deficit/hyperactivity disorder (ADHD), and 4 mood stabilizers. Only a few of these drugs were approved for use in children or adolescents (38%) at least for a single psychiatric diagnosis in at least one country. The therapeutic class with the lowest rate of approved status was antidepressants (20%), followed by mood stabilizers (25%), anxiolytics/hypnotics (28%), antipsychotics (57%), and medications for ADHD (100%). Important differences in approved diagnoses, ages, and doses were observed between regulatory agencies. Tables presenting drugs for approved diagnoses based on age and regulatory agencies are presented in this article. Drugs classified by regulatory agencies, with complete data on diagnoses, ages, doses, pharmaceutical forms, and particular restrictions, are presented as Supplementary Material. Conclusion: This article provides an overview to prescribers with respect to the approved medications in children and adolescents in selected European countries and the United States. [ABSTRACT FROM AUTHOR]

Abstract: Matrix effects, which represent an important issue in liquid chromatography coupled to mass spectrometry or tandem mass spectrometry detection, should be closely assessed during method development. In the case of quantitative analysis, the use of stable isotope-labelled internal standard with physico-chemical properties and ionization behaviour similar to the analyte is recommended. In this paper, an example of the choice of a co-eluting deuterated internal standard to compensate for short-term and long-term matrix effect in the case of chiral (R,S)-methadone plasma quantification is reported. The method was fully validated over a concentration range of 5–800ng/mL for each methadone enantiomer with satisfactory relative bias (−1.0 to 1.0%), repeatability (0.9–4.9%) and intermediate precision (1.4–12.0%). From the results obtained during validation, a control chart process during 52 series of routine analysis was established using both intermediate precision standard deviation and FDA acceptance criteria. The results of routine quality control samples were generally included in the ±15% variability around the target value and mainly in the two standard deviation interval illustrating the long-term stability of the method. The intermediate precision variability estimated in method validation was found to be coherent with the routine use of the method. During this period, 257 trough concentration and 54 peak concentration plasma samples of patients undergoing (R,S)-methadone treatment were successfully analysed for routine therapeutic drug monitoring. [Copyright &y& Elsevier]

Introduction: We aim to evaluate the association of early versus late venous thromboembolism (VTE) prophylaxis on in-hospital mortality among patients with severe blunt isolated traumatic brain injuries., Methods: Data from the American College of Surgeons Trauma Quality Program Participant Use File for 2017-2021 were analyzed. The target population included adult trauma patients with severe isolated traumatic brain injury (TBI). VTE prophylaxis types (low molecular weight heparin and unfractionated heparin) and their administration timing were analyzed in relation to in-hospital complications and mortality., Results: The study comprised 3609 patients, predominantly Caucasian males, with an average age of 48.5 y. Early VTE prophylaxis recipients were younger (P < 0.01) and more likely to receive unfractionated heparin (P < 0.01). VTE prophylaxis later than 24 h was associated with a higher average injury severity score and longer intensive care unit stays (P < 0.01). Logistic regression revealed that VTE prophylaxis later than 24 h was associated with significant reduction of in-hospital mortality by 38% (odds ratio 0.62, 95% confidence interval 0.40-0.94, P = 0.02). Additionally, low molecular weight heparin use was associated with decreased mortality odds by 30% (odds ratio 0.70, 95% confidence interval 0.55-0.89, P < 0.01)., Conclusions: VTE prophylaxis later than 24 h is associated with a reduced risk of in-hospital mortality in patients with severe isolated blunt TBI, as opposed to VTE prophylaxis within 24 h. These findings suggest the need for timely and appropriate VTE prophylaxis in TBI care, highlighting the critical need for a comprehensive assessment and further research concerning the safety and effectiveness of VTE prophylaxis in these patient populations., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Patients with liver cirrhosis (LC) demonstrate significantly elevated mortality rates following a traumatic event. This study aims to examine and compare the clinical outcomes in adult trauma patients with pre-existing LC undergoing laparotomy or non-operative management (NOM). Additionally, the study aims to investigate various patient outcomes, including mortality rate based on transfusion needs and timing., Methods: This retrospective cohort study utilized the American College of Surgeons Trauma Quality Program Participant Use File (ACS-TQIP-PUF) 2017-21 to compare laparotomy vs NOM in adults (≥18 years) with pre-existing LC who presented to trauma facilities with isolated blunt solid organ abdominal injuries (Injury Severity Score ≥16, Abbreviated Injury Scale solid organ abdomen ≥3)., Results: Among 929 patients, 38.2% underwent laparotomy, while 61.7% received NOM. The in-hospital mortality rate was lower for patients who received NOM (52.3% vs 20.0%, P < .01). The risk of in-hospital mortality was significantly associated with laparotomy (OR 5.22, 95% CI: 2.06-13.18, P < .01) and sepsis (OR 99.50, 95% CI: 6.99-1415.28, P < .01). On average an increase in blood units in 4 hours was observed among those who experienced an in-hospital mortality (OR 5.65, 95% CI: 3.05-8.24, P < .01) and those who underwent laparotomy (OR 3.85, 95% CI: 1.36-6.34, P < .01)., Conclusion: Trauma patients with moderate to severe isolated organ injury and Liver cirrhosis had significantly higher mortality rates, acute renal failure, whole blood units received, as well as longer ICU-LOS when undergoing laparotomy compared to non-operative management., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: National parks in the United States experience a significant number of annual visits, and with increasing popularity, injuries are expected to rise. This study aims to assess fatal injuries in the top ten most visited U.S. national parks from 2013 to 2022 to improve current policies and develop effective prevention strategies., Methods: A cross-sectional study was conducted using public National Park Service data. Data including visitor demographics, injury cause, and location, were collected. Fatal injuries were categorized by season, age group, and gender., Results: Summer had the highest total number of fatal injuries. The winter season had the highest rate of fatal injuries per 10 million visitors. The number of fatal injuries per 10 million visitors decreased from 2013 to 2022 for most parks. The South Region reported the highest total number of fatalities. The West Region demonstrated higher rates when adjusted for visitor volume. Fatal injuries were most prevalent in the 35-44 age group, followed by the 15-24 and 25-34 age groups, with the least incidents in the 0-14 age group, and were more common among males (71.5 % of total injuries)., Conclusion: This study found the highest number of total injuries occurring in summer; however, winter presented a higher risk per visitor. Slips and falls were the most common cause of injuries, requiring targeted safety measures. Males in the 35-44 age group reported the highest fatality rates. These findings highlight the necessity for improved monitoring and reporting to better understand injury causes and formulate specific, evidence-based policies for prevention., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Workers' compensation claims among Medicare beneficiaries have not been described previously. To examine the healthcare burden of work-related injury and illness among Medicare beneficiaries, we assessed the characteristics, healthcare utilization, and financial costs among Medicare beneficiaries with claims for which workers' compensation was the primary payer., Methods: We extracted final action fee-for-service Medicare claims from 1999 to 2016 where workers' compensation had primary responsibility for claim payment and beneficiary, claim type, diagnoses, and cost information from these claims., Results: During 1999-2016, workers' compensation was the primary payer for 2,010,200 claims among 330,491 Medicare beneficiaries, and 58.7% of these beneficiaries had more than one claim. Carrier claims submitted by noninstitutional providers constituted the majority (94.5%) of claims. Diagnosis codes indicated 19.4% of claims were related to diseases of the musculoskeletal system and connective tissue and 12.9% were related to disease of the circulatory system. Workers' compensation insurance paid $880.4 million for these claims while Medicare paid $269.7 million and beneficiaries paid $37.4 million., Conclusions: Workers' compensation paid 74% of the total amount to providers for these work-related medical claims among Medicare beneficiaries. Claim diagnoses were similar to those of all workers' compensation claims in the United States. Describing these work-related claims helps identify the healthcare burden due to occupational injury and illness among Medicare beneficiaries resulting from employment and identifies a need for more comprehensive collection and surveillance of work-related medical claims., (© 2021 Wiley Periodicals LLC.)