Search

Nontargeted screening (NTS) utilizing liquid chromatography electrospray ionization high-resolution mass spectrometry (LC/ESI/HRMS) is increasingly used to identify environmental contaminants. Major differences in the ionization efficiency of compounds in ESI/HRMS result in widely varying responses and complicate quantitative analysis. Despite an increasing number of methods for quantification without authentic standards in NTS, the approaches are evaluated on limited and diverse data sets with varying chemical coverage collected on different instruments, complicating an unbiased comparison. In this interlaboratory comparison, organized by the NORMAN Network, we evaluated the accuracy and performance variability of five quantification approaches across 41 NTS methods from 37 laboratories. Three approaches are based on surrogate standard quantification (parent-transformation product, structurally similar or close eluting) and two on predicted ionization efficiencies (RandFor- IE and MLR- IE ). Shortly, HPLC grade water, tap water, and surface water spiked with 45 compounds at 2 concentration levels were analyzed together with 41 calibrants at 6 known concentrations by the laboratories using in-house NTS workflows. The accuracy of the approaches was evaluated by comparing the estimated and spiked concentrations across quantification approaches, instrumentation, and laboratories. The RandFor- IE approach performed best with a reported mean prediction error of 15× and over 83% of compounds quantified within 10× error. Despite different instrumentation and workflows, the performance was stable across laboratories and did not depend on the complexity of water matrices.

Stroke is one of the most common causes of mortality and disability worldwide. Antithrombotic therapy represents the mainstay in primary and secondary prevention, both in cardioembolic and non-cardioembolic stroke. Particularly, direct oral anticoagulants play a crucial role in atrial fibrillation, the most common cause of cardioembolic stroke, whereas single or dual antiplatelet therapy is preferred in non-cardioembolic stroke. However, the limitations related to the residual risk of cardioembolic or cerebrovascular events, and the risk of major bleeding, still represent unmet medical needs. To overcome them, new drugs inhibiting Factor XI (FXI) and Factor XII have been proposed, with a selective inhibition of contact pathway of coagulation, delineating a new anticoagulant approach. This review provides a summary of the currently available evidence and future perspectives on FXI inhibitors, that can represent an additional therapeutic option in the primary and secondary prevention of cardioembolic and non-cardioembolic ischemic stroke, also in challenging therapeutic contexts., (© 2024. The Author(s).)

Several studies indicate a link between personal distress and vulnerability to depression. The literature also suggests that personal distress is associated with emotion dysregulation and that emotion dysregulation plays a role in depression. However, which of the various emotion regulation difficulties mediates the relationship between personal distress and depression remains unexplored. This study therefore aims to investigate the mediating role of specific emotion regulation difficulties in the relationship between personal distress and depression. Of the 702 initially recruited participants, 635 completed a survey comprising the Interpersonal Reactivity Index, the Difficulties in Emotion Regulation Scale, and the Beck Depression Inventory. A mediation analysis was used to explore which emotion regulation difficulties mediate the relationship between personal distress and depression. Over a quarter (27%) of participants reported moderate-severe depression symptoms. Difficulties in accessing adaptive emotion regulation strategies and in having a clear understanding about one's own emotions partly mediated the relationship between personal distress and depression symptoms. Our results are the first to indicate that personal distress is linked to depression risk through specific emotion regulation difficulties in medical students. They also highlight possible modifiable skills that could be targeted by prevention intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Colonnello, Castellano, Mazzetti and Russo.)

Research on cerebrovascular events in atrial fibrillation (AF) patients taking non-vitamin K antagonist oral anticoagulants (NOACs) with antiseizure medications (ASMs) is limited, highlighting a significant gap in literature. We assessed thrombotic and hemorrhagic risks in patients on NOACs and ASMs versus those on NOACs or ASMs alone. We analyzed a retrospective cohort from five centers, including AF and epilepsy patients on both medications (n = 188), AF patients on NOACs (n = 298), and epilepsy patients on ASMs (n = 50), with a 3-year follow-up. Propensity score matching adjusted for cardiovascular risk differences. The primary outcomes were ischemic stroke, transient ischemic attack, and major bleeding. Results showed the ASM+NOAC group had a higher risk of primary outcomes compared to the NOAC-only group (5.68% vs. 1.18%, hazard ratio = 5.72, 95% confidence interval = 2.22-14.73), with no events in the ASM-only group. This suggests an increased risk for patients on combined NOAC and ASM therapy, underlining the need for careful drug interaction consideration., (© 2024 International League Against Epilepsy.)

The inappropriate use of antibiotics gives rise to detrimental consequences, both physical and emotional, with a decreased quality of life and higher levels of anxiety and depression. The current observational study aimed to investigate the association between awareness, beliefs, and behaviors toward antibiotics, highlighting the modulating role of individual and psychological factors in response to illness and medication. Through an online questionnaire, several psychological indexes, as well as knowledge of, attitude toward, and experiences with antibiotics, both individual and family-related, were assessed in a sample of 100 responders (74 females, mean age 33.37 ± 11.36). A positive association between intake behavior, awareness, and individual attitude emerged. Familial approach to antibiotics appears as a predictor of individual attitude and behavior toward these drugs, and awareness about antibiotic risks mediate the relationship between the tendency to be more compliant with prescriptions (R 2 = 0.300; MSE = 1.541; F(2, 98) = 20.737; p < 0.0001). Moreover, individuals with a personality characterized by higher conscientiousness are more aware of antibiotic risks ( p < 0.01), whereas individuals with a lower awareness are those with higher indexes of psychophysical discomfort (i.e., anxiety, perceived stress, somatization) and levels of emotional rebound ( p < 0.05). Anxiety (F(3, 96) = 3.874; p = 0.012; R 2 = 0.108) and somatization (F(2, 97) = 3.114; p = 0.030; R 2 = 0.089) also significatively moderated the intake behavior, despite the family approach. Overall, the current study provides preliminary findings regarding the way in which family experiences and individual psychological aspects may be influencing factors in the behavior and attitude towards antibiotics and can be used to plan patient-centered therapeutic communication and education.

Introduction: Patients with Haemophilia (PWH) need orthopaedic treatments and often they undergo surgery. Classically, PWH with inhibitors have to face such procedures earlier than other patients. Major orthopaedic surgery is not easy and complications are frequent. Emicizumab is the first monoclonal antibody introduced for haematological prophylaxis for PWH with inhibitors, achieving an efficacious haemostasis also in patients with severe haemophilia A with inhibitors, later demonstrated for PWH without inhibitors. A few years ago, emicizumab was also proposed for PWH undergoing surgery, as it supports excellent bleeding control. The literature on orthopaedic surgery using an emicizumab protocol is scarce: only isolated case reports with short-term follow-ups are available. Aim: The purpose of this study is the assessment of the mid-term outcomes of major orthopaedic surgery performed in a population of patients with and without inhibitors and an emicizumab regimen. Methods: We reviewed the records of 13 PWH (eight with high-titre inhibitors, five without) with a mean age of 54.6 years, undergoing 15 orthopaedic surgical procedures between 2017 and 2022: primary knee and hip arthroplasty, revision, pseudotumor excision, or amputation. Their prophylaxis consisted of the combination of emicizumab and boluses of rFVIIa (PWH with inhibitors) or rFVIII (PWH without inhibitors). The clinical parameters of evaluation were: VAS, Haemophilic Joint Health Score (HJHS), and standard radiologic studies. Follow-up was conducted at 1, 3, 6 months, and then yearly. The survival rate of all implants was also assessed. Results: The mean follow-up was 38.8 months (range: 12-65). All patients were successfully treated without complications during surgery. During the postoperative period, a patient affected by a septic complication two months after his pseudotumor excision underwent an above-the-knee amputation. All patients were regularly discharged to the rehabilitative ward, reporting satisfaction for pain reduction and improved joint and global function at the VAS and HJHS scores. No revisions or implant failures were recorded. Conclusions: A prophylaxis regimen with emicizumab and factor replacement in PWH with or without inhibitors undergoing major orthopaedic surgery ensures effective bleeding control and good postoperative clinical outcomes at mid-term follow-up, and may be routinely adopted in dedicated high-volume hospitals. This series is the most consistent to date reported at a single Haemophilia centre.