Conceptual modelling of the flow of frail elderly through acute-care hospitals: An evidence-based management approach

This is the author accepted manuscript. The final version is available from Emerald via the DOI in this record.The ageing of the world’s population is causing an increase in the number of frail patients admitted to hospitals. In the absence of appropriate management and organisation, these patients risk an excessive length of stay and poor outcomes. To deal with this problem, we propose a conceptual model to facilitate the pathway of frail elderly patients across acute-care hospitals, focused on avoiding improper wait times and treatment during the process. The conceptual model is developed to enrich the standard flowchart of a clinical pathway in the hospital. The modified flowchart encompasses new organisational units and activities carried out by new dedicated professional roles. The proposed variant aims to provide a correct assessment of frailty at the entrance, a better management of the patient’s stay during different clinical stages and an early discharge, sending the patient home or to other facilities, avoiding a delayed discharge. The model is completed by a set of indicators aimed at measuring performance improvements and creating a strong database of evidence on the managing of frail elderly’s pathways, providing proper information that can validate the model when applied in current practice. The paper proposes a design of the clinical path of frail patients in acute-care hospitals, combining elements that, according to an evidence-based management approach, have proved to be effective in terms of outcomes, costs and organisational issues. We can therefore expect an improvement in the treatment of frail patients in hospital, avoiding their functional decline and worsening frailty conditions, as often happens in current practice following the standard path of other patients The framework proposed is a conceptual model to manage frail elderly patients in acute-care wards. Our research approach lacks application to real data and proof of effectiveness. Further work will be devoted to implementing a simulation model for a specific case study and verifying the impact of the conceptual model in real care settings. The framework proposed is a conceptual model to manage frail elderly patients in acute-care wards. Our research approach lacks application to real data and proof of effectiveness. Further work will be devoted to implementing a simulation model for a specific case study and verifying the impact of the conceptual model in real care settings. This paper fulfills an identified need to study and provide solutions for the management of frail elderly patients in acute-care hospitals, and generally to produce value in a patient-centred model

Thermal stability and aggregation of sulfolobus solfataricus b-glycosidase are dependent upon the N-e-methylation of specific lysyl residues: critical role of in vivo post-translational modifications.

Methylation in vivo is a post-translational modification observed in several organisms belonging to eucarya, bacteria, and archaea. Although important implications of this modification have been demonstrated in several eucaryotes, its biological role in hyperthermophilic archaea is far from being understood. The aim of this work is to clarify some effects of methylation on the properties of β-glycosidase from Sulfolobus solfataricus, by a structural comparison between the native, methylated protein and its unmethylated counterpart, recombinantly expressed in Escherichia coli. Analysis by Fourier transform infrared spectroscopy indicated similar secondary structure contents for the two forms of the protein. However, the study of temperature perturbation by Fourier transform infrared spectroscopy and turbidimetry evidenced denaturation and aggregation events more pronounced in recombinant than in native β-glycosidase. Red Nile fluorescence analysis revealed significant differences of surface hydrophobicity between the two forms of the protein. Unlike the native enzyme, which dissociated into SDS-resistant dimers upon exposure to the detergent, the recombinant enzyme partially dissociated into monomers. By electrospray mapping, the methylation sites of the native protein were identified. A computational analysis of β-glycosidase three-dimensional structure and comparisons with other proteins from S. solfataricus revealed analogies in the localization of methylation sites in terms of secondary structural elements and overall topology. These observations suggest a role for the methylation of lysyl residues, located in selected domains, in the thermal stabilization of β-glycosidase from S. solfataricu

the allergen mus m 1 0102 cysteine residues and molecular allergology

Abstract Mus m 1.0102 is a member of the mouse Major Urinary Protein family, belonging to the Lipocalins superfamily. Major Urinary Proteins (MUPs) are characterized by highly conserved structural motifs. These include a disulphide bond, involved in protein oxidative folding and protein structure stabilization, and a free cysteine residue, substituted by serine only in the pheromonal protein Darcin (MUP20). The free cysteine is recognized as responsible for the onset of inter- or intramolecular thiol/disulphide exchange, an event that favours protein aggregation. Here we show that the substitution of selected cysteine residues modulates Mus m 1.0102 protein folding, fold stability and unfolding reversibility, while maintaining its allergenic potency. Recombinant allergens used for immunotherapy or employed in allergy diagnostic kits require, as essential features, conformational stability, sample homogeneity and proper immunogenicity. In this perspective, recombinant Mus m 1.0102 might appear reasonably adequate as lead molecule because of its allergenic potential and thermal stability. However, its modest resistance to aggregation renders the protein unsuitable for pharmacological preparations. Point mutation is considered a winning strategy. We report that, among the tested mutants, C138A mutant acquires a structure more resistant to thermal stress and less prone to aggregation, two events that act positively on the protein shelf life. Those features make that MUP variant an attractive lead molecule for the development of a diagnostic kit and/or a vaccine

Modelling Hospital Medical Wards to Address Patient Complexity: A Case-Based Simulation-Optimization Approach

In this paper we focus on patient flows inside Internal Medicine Departments, with the aim of supporting new organizational models taking into account the patient relevant characteristics such as complexity and frailty. The main contribution of this paper is to develop a Discrete Event Simulation model to describe in detail the pathways of complex patients through medical hospital wards. The model has been applied to reproduce a case study of an Italian middle size hospital. The objective is quantifying the impact on resource use and outcome of introducing a new organizational model for medical departments. The re-organization is mainly focused on changing the available beds assignment among the wards to better address the complexity of care of patients with comorbidities. Following a patient-centered approach, patients are segmented considering the clinical characteristics (i.e. the pathology, proxy of Diagnoses Related Groups classification) and sub-grouped considering other characteristics, such as comorbidities and ward of admission. Then, an optimization component embedded into the model chooses the best pooling strategy to reorganize medical wards, determining the corresponding number of beds able to improve process indicators, such as length of stay. The simulation model is presented, and preliminary results are analyzed and discussed

Vaccinating Italian infants with a new multicomponent vaccine (Bexsero®) against meningococcal B disease: A cost-effectiveness analysis

This is the final version of the article. Available from the publisher via the DOI in this record.The European Medicines Agency has approved a multicomponent serogroup B meningococcal vaccine (Bexsero®) for use in individuals of 2 months of age and older. A cost-effectiveness analysis (CEA) from the societal and Italian National Health Service perspectives was performed in order to evaluate the impact of vaccinating Italian infants less than 1 y of age with Bexsero®, as opposed to non-vaccination. The analysis was carried out by means of Excel Version 2011 and the TreeAge Pro® software Version 2012. Two basal scenarios that differed in terms of disease incidence (official and estimated data to correct for underreporting) were considered. In the basal scenarios, we considered a primary vaccination cycle with 4 doses (at 2, 4, 6 and 12 months of age) and 1 booster dose at the age of 11 y, the societal perspective and no cost for death. Sensitivity analyses were carried out in which crucial variables were changed over probable ranges. In Italy, on the basis of official data on disease incidence, vaccination with Bexsero® could prevent 82.97 cases and 5.61 deaths in each birth cohort, while these figures proved to be three times higher on considering the estimated incidence. The results of the CEA showed that the Incremental Cost Effectiveness Ratio (ICER) per QALY was €109,762 in the basal scenario if official data on disease incidence are considered and €26,599 if estimated data are considered. The tornado diagram indicated that the most influential factor on ICER was the incidence of disease. The probability of sequelae, the cost of the vaccine and vaccine effectiveness also had an impact. Our results suggest that vaccinating infants in Italy with Bexsero® has the ability to significantly reduce meningococcal disease and, if the probable underestimation of disease incidence is considered, routine vaccination is advisable.The study was financed by the Italian Ministry of University and Research (MIUR, project PRIN 2009; Grant number: 2009ZPM4×4)

A 3D-BPP approach for optimising stowage plans and terminal productivity.

This paper addresses the problem of determining stowage plans for containers in a ship, that is the so-called master bay plan problem (MBPP). MBPP is NP-complete [Botter, R.C., Brinati, M.A., 1992. Stowage container planning: A model for getting an optimal solution. IFIP Transactions B (Applications in Technology) B-5, 217\u2013229; Avriel, M., Penn, M., Shpirer, N., 2000. Container ship stowage problem: Complexity and connection to the colouring of circle graphs. Discrete Applied Mathematics 103, 271\u2013279]. We present a heuristic method for solving MBPP based on its relation with the three-dimensional bin packing problem (3D-BPP), where items are containers and the only bin is the ship. We look for stowage plans that take into a proper account structural and operational constraints, related to both the containers and the ship, and maximise some important terminal performance indexes, such as the effective and mean net crane productivity. Our aim is to evaluate how stowage plans can influence the performance of the quay. A validation of the proposed pproach with some test cases related to containership docks at the port of Genoa (Italy) is given. The results of real instances of the problem and the comparison with a validated heuristic for MBPP, show the effectiveness of the proposed approach in producing stowage plans that minimise the total loading time and allow an efficient use of the quay equipment