Modelling the influence of RKIP on the ERK signalling pathway using the stochastic process algebra PEPA

This paper examines the influence of the Raf Kinase Inhibitor Protein (RKIP) on the Extracellular signal Regulated Kinase (ERK) signalling pathway [5] through modelling in a Markovian process algebra, PEPA [11]. Two models of the system are presented, a reagent-centric view and a pathway-centric view. The models capture functionality at the level of subpathway, rather than at a molecular level. Each model affords a different perspective of the pathway and analysis. We demonstrate the two models to be formally equivalent using the timing-aware bisimulation defined over PEPA models and discuss the biological significance

Impairment-based assessments for patients with lateral ankle sprain: A systematic review of measurement properties

Study design Systematic review. Background and objective The International Ankle Consortium developed a core outcome set for the assessment of impairments in patients with lateral ankle sprain (LAS) without consideration of measurement properties (MP). Therefore, the aim of this study is to investigate MPs of assessments for the evaluation of individuals with a history of LAS. Methods This systematic review of measurement properties follows PRISMA and COSMIN guidelines. Databases Pubmed, CINAHL, Embase, Web of Science, Cochrane Library and SPORTDiscus were searched for eligible studies (last search: July 2022). Studies on MP of specific tests and patient-reported outcome measurements (PROMs) in patients with acute and history of LAS (>4 weeks post injury) were deemed eligible. Results Ten studies of acute LAS and 39 studies of history of LAS patients with a total of 3313 participants met the inclusion criteria. Anterior Drawer Test (ADT) in supine position five days post injury and Reverse Anterolateral Drawer Test are recommended in acute settings in single studies. In the history of LAS patients, Cumberland Ankle Instability Tool (CAIT) (4 studies) as a PROM, Multiple Hop (3 studies) and Star Excursion Balance Tests (SEBT) (3 studies) for dynamic postural balance testing showed good MPs. No studies investigated pain, physical activity level and gait. Only single studies reported on swelling, range of motion, strength, arthrokinematics, and static postural balance. Limited data existed on responsiveness of the tests in both subgroups. Conclusion There was good evidence to support the use of CAIT as PROM, Multiple Hop, and SEBT for dynamic postural balance testing. Insufficient evidence exists in relation to test responsiveness, especially in the acute situation. Future research should assess MPs of assessments of other impairments associated with LAS

Determining key clinical predictors for chronic ankle instability and return to sports with cost of illness analysis: protocol of a prospective cohort study

Introduction: Ankle sprains are common in sports and the general population. Although considered innocuous, a large proportion has residual complaints such as recurrent ankle sprains and develop chronic ankle instability. Although some predicting factors are identified, there is no unequivocality regarding the development of chronic ankle instability, nor about the optimal rehabilitation for an acute ankle sprain. Alongside the biomechanical impairments, ankle sprains are a burden on society due to substantial economic costs. Therefore, we aim to identify key clinical predictors of chronic ankle instability or recovery after acute lateral ankle sprain. Additionally, we aim to determine cost-of-illness of patients who developed chronic ankle instability. Methods and analysis: This prospective cohort study (Clinicaltrials.gov: NCT05637008 - pre-results) aims to recruit adult (18-55 years) patients with an acute lateral ankle sprain who are active in sports. Clinical assessments and patient-reported outcome measures will be used to collect data at 7-14 days, 6 weeks, 12 weeks and 12 months after enrolment in the study. The primary outcome will be chronic ankle instability at 12-month follow-up. Salient outcomes will be analysed by logistic regression to determine association with the development of chronic ankle instability. Participants will fill in a cost diary containing direct and indirect costs related to their injury. Ethics and disseminations: The ethical committee of the Antwerp University Hospital (B3002022000138) has given approval of the protocol and consent forms on 10 October 2022. We perform this study according to the Helsinki Declaration. We will present results at conferences or webinars and publish in peer-reviewed articles.NCT05637008

Timely identification of palliative patients and anticipatory care planning by GPs: Practical application of tools and a training programme

Background: Palliative care is mainly restricted to terminal care. General practitioners (GPs) are not trained to early identify palliative patients with cancer, COPD or heart failure. With the help of the RADboud indicators for PAlliative Care needs (RADPAC), we trained GPs to identify patients’ needs and to make a proactive care plan. They were also able to join two role-plays where they discussed the patient’s future, and consulted a palliative care consultant to fine-tune the care plan. We evaluated the programme with the GPs and consultants and noted its impact on their daily practice. Methods: Two years after they had participated in the programme, we held semi-structured interviews with the GPs and a focus group interview with the consultants and performed a thematic content analysis. Results: Six consultants and nine GPs participated in the programme. Most GPs and consultants mentioned positive changes in the thinking or acting of GPs regarding early palliative care. A number continued to use the tool to identify patients; most of the others noted they had internalised the indicators. Although half of them still considered discussing end-of-life aspects difficult, part icularly in patients with organ failure, the others were more easily able to discuss the future with their palliative patients. Conclusion: Although most GPs and consultants were positive about the training programme and applying it in daily practice, we conclude that in future programmes, more attention needs to paid to timely identification of palliative patients with COPD or CHF and how to discuss the future with them