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Abstract Background Every year, over 65,000 Australians experience an acute coronary syndrome (ACS) and around one-third occur in people with prior coronary heart disease. Cardiac rehabilitation (CR) aims to prevent a repeat ACS by supporting patients’ return to an active and fulfilling lifestyle. CR programs are efficacious, but audits of clinical practice show variability of program delivery, which may compromise patient outcomes. Core components, quality indicators and accreditation of programs have been introduced internationally to increase program standardisation. With Australian quality indicators (QIs) for cardiac rehabilitation recently introduced, we aimed to conduct a survey in one state of Australia to assess the extent to which programs adhere to the measurement of QIs comparing country, metropolitan, telephone and face to face programs. Methods A cross- sectional survey design with face validity testing was used to formulate questions to evaluate cardiac rehabilitation program and personnel characteristics and QI adherence. Between October 2020- December 2021, 23 cardiac rehabilitation programs across country and metropolitan areas were invited to participate. Quality improvement was defined as adherence to the Australian Quality Indicators, and we developed an objective score to calculate program performance categorised by quartiles. Significance of CR completion and time to enrolment between program type (telephone versus face to face) and location (country versus metropolitan were compared using Pearson’s Chi-square and Mann–Whitney U tests. Results Among the 23 CR programs, 15 were country and 8 metropolitan-based and 22 were face to face and 1 telephone-based. Median wait time from discharge was 27.0 days, (interquartile range 19.3–46.0) across all programs and country completions of enrolled were 76.9% versus metropolitan 56.5%, p

In vitro chemical safety assessment often relies on simple and general cytotoxicity endpoint measurements and fails to adequately predict human toxicity. To improve the in vitro chemical safety assessment, it is important to understand the underlying mechanisms of toxicity. Here we introduce ToxProfiler, a novel human-based reporter assay that quantifies the chemical-induced stress responses at a single-cell level and reveals the toxicological mode-of-action (MoA) of novel drugs and chemicals. The assay accurately measures the activation of seven major cellular stress response pathways (oxidative stress, cell cycle stress, endoplasmic reticulum stress, ion stress, protein stress, autophagy and inflammation) that play a role in the adaptive responses prior to cellular toxicity. To assess the applicability of the assay in predicting the toxicity MoA of chemicals, we tested a set of 100 chemicals with well-known in vitro and in vivo toxicological profiles. Concentration response modeling and point-of-departure estimation for each reporter protein allowed for chemical potency ranking and revealed the primary toxicological MoA of chemicals. Furthermore, the assay could effectively group chemicals based on their shared toxicity signatures and link them to specific toxicological targets, e.g. mitochondrial toxicity and genotoxicity, and different human pathologies, including liver toxicity and cardiotoxicity. Overall, ToxProfiler is a quantitative in vitro reporter assay that can accurately provide insight into the toxicological MoA of compounds, thereby assisting in the future mechanism-based safety assessment of chemicals., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Amer Jamalpoor reports a relationship with Toxys b.v. that includes: employment. Bas ter Braak reports a relationship with Toxys b.v. that includes: employment. Giel Hendriks reports a relationship with Toxys b.v. that includes: employment. Liesanne Loonstra-Wolters reports a relationship with Toxys b.v. that includes: employment. Toxys b.v. holds the exclusive commercial license for ToxProfiler reporter technology and offers the ToxProfiler assay as a service. BtB, GH and AJ are currently employed at Toxys. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Adolescents presenting with medically unexplained symptoms (MUS) in non-mental healthcare settings, particularly Emergency Departments (EDs), pose diagnostic challenges necessitating a comprehensive bio-psycho-social approach. Amid the youth mental health crisis, recognising psychological distress is imperative. This study delved into physicians' perceptions and diagnostic tendencies regarding such cases, exploring the potential overshadowing of psychosomatic presentations by medicalized diagnoses in EDs., Methods: Our study involved 74 physicians, representing 82% of eligible respondents in the Paediatric Emergency Medicine Department, and was conducted using an online questionnaire examining perceptions of case scenarios with psychosomatic presentations., Results: Results disclosed a prevalent inclination toward medical diagnoses, with less than 10% of physicians considering psychosomatic conditions in specific scenarios. Interestingly, psychosomatic diagnoses were more probable for symptoms like headaches, shortness of breath, and chest pain. The study uncovered a possible bias among physicians towards medical diagnoses in EDs for adolescents with MUS, possibly stemming from physicians' focus on physical care, diagnostic uncertainties, cognitive biases, and concerns about stigmatisation., Conclusion: Adolescents with MUS seeking assistance in non-mental health settings may encounter delayed mental health diagnoses and interventions. Psychosomatic symptoms could signify stressors or underlying mental health disorders. Recognising psychosocial distress early on is crucial for optimal mental health outcomes. Consequently, the study advocates for a paradigm shift towards a holistic bio-psychosocial approach in both medical education and practice., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Non-invasive brain stimulation, such as repetitive transcranial magnetic stimulation (rTMS), is increasingly used in the treatment of neurological diseases and psychiatric disorders. Where rTMS is already an accepted treatment option for depression, in the Netherlands/Belgium, no consensus exist on the application of rTMS for (obsessive-compulsive disorder (OCD). People with OCD who do not respond enough to exposure therapy and serotonergic antidepressants are in great need for treatment alternatives., Aim: Consensus statement on the application of rTMS as treatment for OCD METHOD: Evaluation of the current literature on the efficacy of rTMS for OCD, mainly based on recent meta-analysis, by a broad group of experts in the field of rTMS, OCD and treatment guidelines., Results: rTMS is a potentially effective treatment for OCD with a medium effect size (g ≈ 0,5). Based on the current literature it is not yet clear which rTMS protocol is the most effective., Conclusion: based on the evidence for rTMS in OCD, and the non-invasive nature of the treatment modality, rTMS can considered in cases with OCD who do not respond enough to exposure therapy and serotonergic antidepressants, prior to the start of more invasive treatment alternatives, such as deep brain stimulation or lesion surgery.

The absence of treatment studies for obsessive compulsive disorder (OCD) in older adults and the fact that OCD typically starts at a young age and often follows a chronic, fluctuating course quickly leads to therapeutic nihilism for older adults with OCD. In this case report, we present a 72-year-old man with OCD symptoms from the age of 35, who has only been treated with medication and psychotherapy for a recurrent depressive disorder. After a short, intensive exposure and response prevention treatment (four days in two weeks), the OCD symptoms and the depressive symptoms were fully in remission and all medications (venlafaxine, olanzapine, depakine) were discontinued. Treatment gains were maintained with persistent remission until 18 months follow up. This case report shows that a comorbid depressive disorder may lead to undertreatment of OCD. It also shows that long standing OCD can be successfully treated in older adults.

ToxTracker is a mammalian cell reporter assay that predicts the genotoxic properties of compounds with high accuracy. By evaluating induction of various reporter genes that play a key role in relevant cellular pathways, it provides insight into chemical mode-of-action (MoA), thereby supporting discrimination of direct-acting genotoxicants and cytotoxic chemicals. A comprehensive interlaboratory validation trial was conducted, in which the principles outlined in OECD Guidance Document 34 were followed, with the primary objectives of establishing transferability and reproducibility of the assay and confirming the ability of ToxTracker to correctly classify genotoxic and non-genotoxic compounds. Reproducibility of the assay to predict genotoxic MoA was confirmed across participating laboratories and data were evaluated in terms of concordance with in vivo genotoxicity outcomes. Seven laboratories tested a total of 64 genotoxic and non-genotoxic chemicals that together cover a broad chemical space. The within-laboratory reproducibility (WLR) was up to 98% (73%-98% across participants) and the overall between-laboratory reproducibility (BLR) was 83%. This trial confirmed the accuracy of ToxTracker to predict in vivo genotoxicants with a sensitivity of 84.4% and a specificity of 91.2%. We concluded that ToxTracker is a robust in vitro assay for the accurate prediction of in vivo genotoxicity. Considering ToxTracker's robust standalone accuracy and that it can provide important information on the MoA of chemicals, it is seen as a valuable addition to the regulatory in vitro genotoxicity battery that may even have the potential to replace certain currently used in vitro battery assays., (© 2024 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals LLC on behalf of Environmental Mutagenesis and Genomics Society.)