Towards fully-facilitated DES modelling:a successful project

The literature suggests that increasing stakeholder engagement in modelling has a positive impact on healthcare improvement projects using discrete-event simulation (DES). This suggests analysts should strive for the ‘fully-facilitated’ mode of simulation, meaning conducting the whole simulation project together with stakeholders. This paper investigates whether this might be possible in practice. This work arose from a research project with an Italian hospital. The paper describes a simulation project that succeeds in being fully-facilitated through all stages as far as the implementation stage, through combining Business Process Model and Notation (BPMN) and DES. We believe it is the first time that a fully-facilitated DES project in healthcare has been described

3D extracellular matrix derived model of alveolar rhabdomyosarcoma

INTRODUCTION: Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood, among the subtypes the Alveolar (ARMS) is the more aggressive with a higher tendency to metastasize [1]. Integrins are a class of transmembrane adhesion molecules that mediate survival, differentiation, migration and differentiation [2]. Here we investigate the role of integrins in ARMS metastatic migration in an engineered 3D scaffold. METHODS: ARMS xenografts are obtained from subcutaneous injection of RH30 cells in immunodeficient mice. Composition of the ECM is determined by proteomic analysis. The main components of the ECM are used to enrich a 3D collagen scaffold cultured in a perfusion bioreactor. Cells are analyzed by qPCR for the expression of a panel of integrins. Presence of the protein is confirmed by flow cytometry immunofluorescence. MMPs expression is evaluated by zymography. RESULTS: Verified the expression of human and ARMS marker and typical tumor morphology in xenografts, they are processed for proteomic analysis. Proteomic data analysis is currently under investigation. Preliminary data culturing RH30 cells in 3D bioreactor show upregulation of ITG5 and CXCR4 receptor compared to 2D condition. Localization and quantification at protein level will be assessed respectively by immunofluorescence and cytofluorimetry. Expression of MMP-9 and MMP-2 has been assessed by zymography comparing the expression of these MMPs in 2D vs 3D bioreactor and RH30 isolated from the xenograft. DISCUSSION & CONCLUSIONS: Preliminary data on ITG expression show that in 3D scaffold the expression of ITG5 and CXCR4 is upregulated. In parallel the active form of MMP-2 is more present in 3D models compared to 2D. Other groups reported a mechanical interaction between ITG5 and MMP-2 [3]. This interaction will be studied in a more representative engineered 3D scaffold to shed light on the complex interaction between ECM and metastatic progression

A BPMN extension to support discrete-event simulation for healthcare applications:an explicit representation of queues, attributes and data-driven decision points

Stakeholder engagement in simulation projects is important, especially in healthcare where there is a plurality of stakeholder opinions, objectives and power. One promising approach for increasing engagement is facilitated modelling. Currently, the complexity of producing a simulation model means that the ‘model coding’ stage is performed without the involvement of stakeholders, interrupting the possibility of a fully-facilitated project. Early work demonstrated that with currently-available software tools we can represent a simple healthcare process using Business Process Model and Notation (BPMN) and generate a simulation model automatically. However, for more complex processes, BPMN currently has a number of limitations, namely the ability to represent queues and data-driven decision points. To address these limitations, we propose a conceptual design for an extension to BPMN (BPMN4SIM) using Model Driven Architecture. Application to an elderly emergency care pathway in a UK hospital shows that BPMN4SIM is able to represent a more-complex business process

Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia

<p>Abstract</p> <p>Background</p> <p>One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study.</p> <p>Methods/Design</p> <p>The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome.</p> <p>Discussion</p> <p>The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia.</p> <p>Trial Registration</p> <p><b>Clincaltrials.gov Identifier</b>: NCT00395915</p

Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: results and lessons of an underpowered randomised clinical trial

BACKGROUND: As lithium treatment might be effective in reducing the risk of deliberate self-harm (DSH) in adult patients with unipolar affective disorders, we designed a pragmatic randomised trial to assess its efficacy in more than 200 patients with treatment-resistant depression. However, we randomised 56 patients only. The aim of this report is therefore twofold: first, to disseminate the results of this underpowered study which may be incorporated into future meta-analytical reviews; second, to analyse some critical aspects of the study which might explain failure to reach the target sample size.METHODS: We carried out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode were allocated to add lithium to usual care (intervention arm) versus usual care alone (control arm). Suicide completion and acts of DSH during the 12 months of follow-up constituted the composite primary outcome.RESULTS: Of 58 patients screened for inclusion, 29 were allocated to lithium plus usual care and 27 were assigned to usual care without lithium. Six patients in the lithium plus usual care group and seven in the usual care group committed acts of DSH during the follow-up phase. The survival probability did not differ between the two treatment arms (Chi2 = 0.17, p =0.676). With regard to changes in the severity of depressive symptomatology from baseline to endpoint, no significant differences were detected.CONCLUSIONS: The present study failed to achieve the minimum sample size needed to detect a clinically meaningful difference between the two treatment arms. Consequently, the finding that lithium, in addition to usual care, did not exert a positive effect in terms of reduction of DSH after 12 months of follow-up is likely due to the lack of sufficient statistical power to detect a difference, if a difference existed. The dissemination of the results of this underpowered study will inform future meta-analytical reviews on lithium and suicide-related outcomes.TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00927550

The contribution of cyber-physical production systems to activity-based costing in manufacturing. An interventionist research approach

This study aims to investigate how the implementation of Cyber-Physical Production Systems (CPPS) in small manufacturing firms can facilitate the implementation of the Activity-based Costing method in calculating production costs, in order to increase the reliability of the costing information for decision-making purposes. The collaboration of the research team with managers allowed an in-depth knowledge of the manufacturing problems of the investigated firm, allowing the analysis of the manufacturing process under both a costing and a managerial perspective. Findings which emerge from the analysis show that the integration between CPPS investments and ABC, through the real-time measurement of resources by sensors, apps and part program, lead to useful information about operations, allowing to improve their performances and reduce resource consumption. As a result, a model of integration between the factory control system, the communication network and the production system is proposed

Theory of constraints applied to scheduled and unscheduled patient flows: does it improve process performance?

Theory of constraints (TOC) is particularly effective for improving processes and maximising efficiency in systems that are resource-constrained. One of the most common applications of TOC in the service sector is healthcare, particularly patient flows which can be considered analogous to 'production lines'. However, one of the main TOC techniques, 'drum-bufferrope' (DBR), is still poorly implemented in healthcare services. The study provides a new approach where traditional DBR or 'DBR for goods' (DBRG) is customised to improve admissions scheduling in a scheduled patient flow. However, when arrivals of patients are necessarily unscheduled the DBRG is not applicable. For these circumstances, a new procedure is also provided. This procedure uses a variant of DBR ('DBR for services'. DBRS) that is adapted here for an unscheduled patient flow. The purpose of both the adapted DBRG and DBRS is to provide rules to control the throughput of patients. As ever in flow systems, there is a trade-off between minimising patient flow times and maximising the patient throughput volumes. The decision on where to be on this trade-off is the decision of service managers, perhaps subject to service-level agreements. To demonstrate this trade-off under the TOC DBR rules, several simulation experiments are conducted

Modelling of in vivo LIPUS stimulation of murine intestinal wall

Low Intensity Pulsed Ultrasound could enable a 'wireless biopsy' of gut diseases such as ulcerative colitis, by triggering the release of pathology-characterizing molecules from the intestinal wall cells. Prior to the in vivo validation, the prediction of the acoustic propagation through living tissues results fundamental to guide the design of the experimental setting and to be able to reach the target with the desired ultrasound regime. In this work we propose a simulation framework able to precisely predict the ultrasound dose at the target (i.e., mouse colon) for the above-mentioned application