The use of patient experience feedback in rehabilitation quality improvement and codesign activities: Scoping review of the literature.

OBJECTIVE: To characterize the literature, reported enablers, and gaps on the use of patient experience feedback for person-centered rehabilitation quality improvement and codesign activities. DESIGN: Scoping Review. DATA SOURCES: Scientific databases (PubMed, CINAHL, Rehabdata, Scopus, Web of Science, ProQuest), website searches (e.g. Beryl Institute), snowballing, and key-informant recommendations. METHODS: Two independent reviewers performed title and abstract screenings and full-text reviews. Eligibility focused on English-language, peer-reviewed (all time) and gray literature (last five years) that used patient experience feedback in rehabilitation improvement activities. The aims, settings, methods, findings, implications, and reported limitations were extracted, followed by content analyses identifying reported enablers and gaps. RESULTS: Among the 901 unique references and 52 full texts reviewed, ten were included: four used patient experience surveys for improving patient experiences; six used codesign methodologies to engage patient feedback in service improvement activities. Implementation enablers included securing managerial support, having a structured methodology and facilitator, using efficient processes, engaging staff experiences, and using appreciative inquiry. Reported study gaps included limited follow-up, low sample sizes, analytical limitations, lack of reported limitations, or narrow range of perspectives (e.g. not from people with severe impairments). CONCLUSION: Few examples of the use of patient experience feedback in quality improvement or codesign activities were found in the rehabilitation literature. Patient experience improvement activities relied exclusively on retrospective survey data, which were not combined with often more actionable forms (e.g. qualitative, real time) of patient experience feedback. Further research might consider design of activities that collect and use patient experience feedback for rehabilitation service improvements.

Analysis of microscopic bone properties in an osteoporotic sheep model: a combined biomechanics, FE and ToF-SIMS study.

The present study deals with the characterization of bone quality in a sheep model of postmenopausal osteoporosis. Sheep were sham operated ( n = 7), ovariectomized ( n = 6), ovariectomized and treated with deficient diet ( n = 8) or ovariectomized, treated with deficient diet and glucocorticoid injections ( n = 7). The focus of the study is on the microscopic properties at tissue level. Microscopic mechanical properties of osteoporotic bone were evaluated by a combination of biomechanical testing and mathematical modelling. Sample stiffness and strength were determined by compression tests and finite-element analysis of stress states was conducted. From this, an averaged microscopic Young's modulus at tissue level was determined. Trabecular structure as well as mineral and collagen distribution in samples of sheep vertebrae were analysed by micro-computed tomography and time-of-flight secondary ion mass spectrometry. In the osteoporotic sheep model, a disturbed fibril structure in the triple treated group was observed, but bone loss only occurred in form of reduced trabecular number and thickness and cortical decline, while quality of the residual bone was preserved. The preserved bone tissue properties in the osteoporotic sheep model allowed for an estimation of bone strength which behaves similar to the human case.

Cellular automaton models for time-correlated random walks: derivation and analysis.

Many diffusion processes in nature and society were found to be anomalous, in the sense of being fundamentally different from conventional Brownian motion. An important example is the migration of biological cells, which exhibits non-trivial temporal decay of velocity autocorrelation functions. This means that the corresponding dynamics is characterized by memory effects that slowly decay in time. Motivated by this we construct non-Markovian lattice-gas cellular automata models for moving agents with memory. For this purpose the reorientation probabilities are derived from velocity autocorrelation functions that are given a priori; in that respect our approach is "data-driven". Particular examples we consider are velocity correlations that decay exponentially or as power laws, where the latter functions generate anomalous diffusion. The computational efficiency of cellular automata combined with our analytical results paves the way to explore the relevance of memory and anomalous diffusion for the dynamics of interacting cell populations, like confluent cell monolayers and cell clustering.

The biology and mathematical modelling of glioma invasion: a review.

Adult gliomas are aggressive brain tumours associated with low patient survival rates and limited life expectancy. The most important hallmark of this type of tumour is its invasive behaviour, characterized by a markedly phenotypic plasticity, infiltrative tumour morphologies and the ability of malignant progression from low- to high-grade tumour types. Indeed, the widespread infiltration of healthy brain tissue by glioma cells is largely responsible for poor prognosis and the difficulty of finding curative therapies. Meanwhile, mathematical models have been established to analyse potential mechanisms of glioma invasion. In this review, we start with a brief introduction to current biological knowledge about glioma invasion, and then critically review and highlight future challenges for mathematical models of glioma invasion.

Interventions to Improve the Oral Health of People with Dementia or Cognitive Impairment: A Review of the Literature.

OBJECTIVE: Oral diseases and conditions are prevalent among older people with dementia and cognitive impairment. While many interventions have been advocated for use in this population, evidence for their effectiveness is unclear. Our objective was to review systematically the content and effectiveness of interventions and implementation strategies used to improve or maintain the oral health of people with dementia or cognitive impairment. METHODS: Original studies published in English at any time until January 2015 were identified through electronic searches of the Medline, Embase, CINAHL, Scopus and Cochrane databases and hand searches of eligible studies and relevant reviews. Two investigators independently abstracted study characteristics and assessed the methodological quality of eligible studies. Results were presented as a narrative review because significant heterogeneity among included studies precluded a meta-analysis. RESULTS: The 18 included studies varied considerably in terms of size, scope and focus. Only two studies were identified that had been designed specifically for and examined exclusively in people with dementia or cognitive impairment. All studies were in residential care; none was population-based. While several studies reported positive effects, a number of methodological weaknesses were identified and the overall quality of included studies was poor. The specific outcomes targeted varied across studies but most studies focused almost exclusively on proximal clinical oral health outcomes such as levels of dental or denture plaque. Attempts to measure intervention integrity were limited and there was usually little or no effort to evaluate intervention effects over a sustained period. CONCLUSION: There is a lack of high quality evidence to support the effectiveness of oral health interventions and implementation strategies for older people with dementia or cognitive impairment. More rigorous, large scale research is needed in this area. Recommendations are provided to improve the overall quality of evaluation in this area. Emphasis must be placed on developing evidence-based, achievable and sustainable oral health strategies if the needs of people with dementia and cognitive impairment are to be met into the future.

Extracting cellular automaton rules from physical Langevin equation models for single and collective cell migration.

Cellular automata (CA) are discrete time, space, and state models which are extensively used for modeling biological phenomena. CA are "on-lattice" models with low computational demands. In particular, lattice-gas cellular automata (LGCA) have been introduced as models of single and collective cell migration. The interaction rule dictates the behavior of a cellular automaton model and is critical to the model's biological relevance. The LGCA model's interaction rule has been typically chosen phenomenologically. In this paper, we introduce a method to obtain lattice-gas cellular automaton interaction rules from physically-motivated "off-lattice" Langevin equation models for migrating cells. In particular, we consider Langevin equations related to single cell movement (movement of cells independent of each other) and collective cell migration (movement influenced by cell-cell interactions). As examples of collective cell migration, two different alignment mechanisms are studied: polar and nematic alignment. Both kinds of alignment have been observed in biological systems such as swarms of amoebae and myxobacteria. Polar alignment causes cells to align their velocities parallel to each other, whereas nematic alignment drives cells to align either parallel or antiparallel to each other. Under appropriate assumptions, we have derived the LGCA transition probability rule from the steady-state distribution of the off-lattice Fokker-Planck equation. Comparing alignment order parameters between the original Langevin model and the derived LGCA for both mechanisms, we found different areas of agreement in the parameter space. Finally, we discuss potential reasons for model disagreement and propose extensions to the CA rule derivation methodology.

Why one-size-fits-all vaso-modulatory interventions fail to control glioma invasion: in silico insights.

Gliomas are highly invasive brain tumours characterised by poor prognosis and limited response to therapy. There is an ongoing debate on the therapeutic potential of vaso-modulatory interventions against glioma invasion. Prominent vasculature-targeting therapies involve tumour blood vessel deterioration and normalisation. The former aims at tumour infarction and nutrient deprivation induced by blood vessel occlusion/collapse. In contrast, the therapeutic intention of normalising the abnormal tumour vasculature is to improve the efficacy of conventional treatment modalities. Although these strategies have shown therapeutic potential, it remains unclear why they both often fail to control glioma growth. To shed some light on this issue, we propose a mathematical model based on the migration/proliferation dichotomy of glioma cells in order to investigate why vaso-modulatory interventions have shown limited success in terms of tumour clearance. We found the existence of a critical cell proliferation/diffusion ratio that separates glioma responses to vaso-modulatory interventions into two distinct regimes. While for tumours, belonging to one regime, vascular modulations reduce the front speed and increase the infiltration width, for those in the other regime, the invasion speed increases and infiltration width decreases. We discuss how these in silico findings can be used to guide individualised vaso-modulatory approaches to improve treatment success rates.

Improving the oral health of frail and functionally dependent elderly.

The Australian Government endorsed a national evidence based oral health model when it introduced the first Nursing Home Oral and Dental Health Plan in 2010. Called Better Oral Health in Residential Care, it promotes a multidisciplinary approach with doctors, nurses, care workers and dental professionals sharing responsibility for the four key processes of oral health screening, oral health care planning, daily oral hygiene and access to dental treatment. Frail and dependent residents are most conveniently treated on-site, hence an aged care/dental partnership is encouraged to facilitate the use of portable dental equipment in the delivery of dental care. Currently, few dentists provide services to residential aged care facilities (RACFs), with loss of clinical time in practice, difficulty in providing clinical care in a non-dental environment and lack of referral pathways from the RACFs to the dentists contributing to the problem. The need to establish a model of care involving dental hygienists/oral health therapists in RACFs has merit. Minimal intervention treatment using glass ionomer cement (GIC) and silver fluoride is ideal in aged care. However, GIC has limitation in dry mouths with low pH caused by polypharmacy or disease. Palliative and definitive treatment techniques need to be individualized with consideration of a patient's ability to maintain their own mouths as well as their mental and physical competence. The range of products available to address the oral diseases common to the frail elderly is growing. The oral health care provider is required to establish a preventive regime that is tailored to the patient's needs, is realistic and under revision as the patient's needs change.

C-reactive protein level is a prognostic indicator for survival and improves the predictive ability of the R-IPI score in diffuse large B-cell lymphoma patients.

BACKGROUND: High levels of C-reactive protein (CRP), an acute phase protein, proofed being associated with decreased clinical outcome in small-scale studies in diffuse large B-cell lymphoma (DLBCL). The aim of this study was to evaluate the prognostic impact of pretreatment CRP levels on overall survival (OS) and disease-free survival (DFS) in a large bicentre study of DLBCL patients. METHODS: Data from 477 DLBCL patients, diagnosed and treated between 2004 and 2013 at two Austrian centres, were evaluated retrospectively. The prognostic influence of CRP and other factors, including age, tumour stage, and revised International Prognostic Index (R-IPI) on 5-year OS and 5-year DFS, were studied by Kaplan-Meier curves as well as univariate and multivariate Cox regression models. Influence of CRP on the predictive accuracy of the R-IPI score was determined by the Harrell concordance index. RESULTS: Kaplan-Meier curves revealed elevated CRP as a factor for decreased 5-year OS and DFS in DLBCL patients (P<0.001, log-rank test). An independent significant association between high CRP levels and poor clinical outcome in multivariate analysis for 5-year OS (HR=1.51, CI 95%=1.04-2.20, P=0.031) and for DFS (HR=1.91, CI 95%=1.28-2.85, P=0.002) was found. The estimated concordance index was 0.75 using the original R-IPI score and 0.79 when CRP was added. CONCLUSIONS: In the present study, we demonstrated high CRP levels at diagnosis of DLBCL as an independent poor prognostic factor for clinical outcome. Adding CRP to the well-established prognostic models such as the R-IPI score might improve their predictive ability.

The derived neutrophil to lymphocyte ratio is an independent prognostic factor in patients with diffuse large B-cell lymphoma.

BACKGROUND: With growing evidence on the role of inflammation in cancer biology, the systemic inflammatory response has been postulated as having prognostic significance in a wide range of different cancer types. Recently, the derived neutrophil to lymphocyte ratio (dNLR) has been proposed as an easily determinable prognostic factor in cancer patients. Nevertheless, its prognostic significance in diffuse large B-cell lymphoma (DLBCL) patients has never been explored. METHODS: Data from 290 consecutive DLBCL patients, diagnosed between 2004 and 2013 at a single Austrian centre, were evaluated retrospectively. The prognostic influence of the dNLR and other clinico-pathological factors including age, lactate dehydrogenase, cell of origin category and Ann Arbor stage on 5-year overall- (OS) and disease-free (DFS) survival was studied by Kaplan-Meier curves. To evaluate the independent prognostic relevance of dNLR, univariate and multivariate Cox regression models were applied. RESULTS: An independent significant association between high dNLR and poor clinical outcome in multivariate analysis for OS (HR=2.02, confidence interval (CI) 95%=1.17-3.50, P=0.011), as well as DFS (HR=2.15, CI 95%=1.04-4.47, P=0.038), was identified. CONCLUSION: In the present study, we showed that a high dNLR at diagnosis of DLBCL represents an independent poor prognostic factor for clinical outcome. Our data encourage the further validation of this easily available parameter in prospective studies and as a potential stratification tool in clinical trials.

[Knowledge about radon and its associated risk perception in France]. / Connaissance et perception du risque dû au radon en France.

PURPOSE: Radon exposure is a major environmental risk in health. It remains badly known by the general population. It is the second cause of lung cancer, after tobacco smoking. The aim of this cross-sectional general population survey was to describe radon exposure risk knowledge and the socioeconomic factors related to this knowledge. MATERIALS AND METHODS: The Cancer Barometer survey 2010 questioned the French population about its knowledge of radon as such and as health risk factor. This survey was a two-stage random sampling with computer-assisted telephone interview that was performed from April 3, 2010 to August 7, 2010 on a sample of 3,359 people aged 15 to 75 years old. RESULTS: Among people aged 15 to 75 years old, only one in five knows that radon is a natural gas coming from the ground. This knowledge is more frequent among people living in an area that is directly concerned by radon, among men and increases with age, with the level of education and the level of income. Radon risk remains still widely underestimated by the general public, including in areas concerned by this risk. When people were confronted with radon exposure, few intended to remedy by improving their home. CONCLUSION: The success of prevention initiatives implies the support and the collaboration of various national and local actors. To improve their impact for the prevention of lung cancers, it could be more effective to couple these actions with prevention messages on tobacco.

Unrelated SCT induces long-term remission in patients with blastic plasmacytoid dendritic cell neoplasm.

Blastic plasmacytoid DC neoplasm (BPDCN) is a rare haematopoietic malignancy with an aggressive behaviour. We evaluated five patients allografted as consolidative treatment with an unrelated donor in first or subsequent remission. Four patients received a reduced intensity-conditioning regimen because of age or co-morbidities. As the stem cell sources, two umbilical cord blood-(UCB), two PBSC- and one BM graft were used. No GVHD was observed in the patients who received a UCB graft. However, both developed a post-transplant-associated lymphoproliferative disease. So far, only one patient has experienced relapse and was consecutively treated by escalated donor lymphocyte infusions (DLI). A potent graft-versus-leukaemia (GVL) effect was induced leading to a 17-month-long CR. Four patients are still in ongoing CR with median disease-free and overall survivals of 17 and 21 months. Thus, allogeneic SCT in BPDCN offers a potential curative option for patients with a compatible donor. UCB is an attractive alternative as a stem cell source. For relapsing patients, DLI can exert a powerful GVL effect.

'Go or grow': the key to the emergence of invasion in tumour progression?

Uncontrolled proliferation and abnormal cell migration are two of the main characteristics of tumour growth. Of ultimate importance is the question what are the mechanisms that trigger the progression from benign neoplasms (uncontrolled/autonomous proliferation) to malignant invasive tumours (high migration). In the following, we challenge the currently prevailing view that the emergence of invasiveness is mainly the consequence of acquired cancer cell mutations. To study this, we mainly focus on the 'glioblastoma multiforme' (GBM) tumour which is a particularly aggressive and invasive tumour. In particular, with the help of a simple growth model, we demonstrate that the short time required for the recurrence of a GBM tumour after a gross total resection cannot be deduced solely from a mutation-based theory. We propose that the transition to invasive tumour phenotypes can be explained on the basis of the microscopic 'Go or Grow' mechanism (migration/proliferation dichotomy) and the oxygen shortage, i.e. hypoxia, in the environment of a growing tumour. We test this hypothesis with the help of a lattice-gas cellular automaton. Finally, we suggest possible therapies that could help prevent the progression towards malignancy and invasiveness of benign tumours.

The cellular basis of cell sorting kinetics.

Cell sorting is a dynamical cooperative phenomenon that is fundamental for tissue morphogenesis and tissue homeostasis. According to Steinberg's differential adhesion hypothesis, the structure of sorted cell aggregates is determined by physical characteristics of the respective tissues, the tissue surface tensions. Steinberg postulated that tissue surface tensions result from quantitative differences in intercellular adhesion. Several experiments in cell cultures as well as in developing organisms support this hypothesis. The question of how tissue surface tension might result from differential adhesion was addressed in some theoretical models. These models describe the cellular interdependence structure once the temporal evolution has stabilized. In general, these models are capable of reproducing sorted patterns. However, the model dynamics at the cellular scale are defined implicitly and are not well-justified. The precise mechanism describing how differential adhesion generates the observed sorting kinetics at the tissue level is still unclear. It is necessary to formulate the concepts of cell level kinetics explicitly. Only then it is possible to understand the temporal development at the cellular and tissue scales. Here we argue that individual cell mobility is reduced the more the cells stick to their neighbors. We translate this assumption into a precise mathematical model which belongs to the class of stochastic interacting particle systems. Analyzing this model, we are able to predict the emergent sorting behavior at the population level. We describe qualitatively the geometry of cell segregation depending on the intercellular adhesion parameters. Furthermore, we derive a functional relationship between intercellular adhesion and surface tension and highlight the role of cell mobility in the process of sorting. We show that the interaction between the cells and the boundary of a confining vessel has a major impact on the sorting geometry.

Evolutionary game theory elucidates the role of glycolysis in glioma progression and invasion.

OBJECTIVES: Tumour progression has been described as a sequence of traits or phenotypes that cells have to acquire if the neoplasm is to become an invasive and malignant cancer. Although genetic mutations that lead to these phenotypes are random, the process by which some of these mutations become successful and cells spread is influenced by tumour microenvironment and the presence of other cell phenotypes. It is thus likely that some phenotypes that are essential in tumour progression will emerge in the tumour population only with prior presence of other different phenotypes. MATERIALS AND METHODS: In this study, we use evolutionary game theory to analyse the interactions between three different tumour cell phenotypes defined by autonomous growth, anaerobic glycolysis, and cancer cell invasion. The model allows us to understand certain specific aspects of glioma progression such as the emergence of diffuse tumour cell invasion in low-grade tumours. RESULTS: We have found that the invasive phenotype is more likely to evolve after appearance of the glycolytic phenotype which would explain the ubiquitous presence of invasive growth in malignant tumours. CONCLUSIONS: The result suggests that therapies, which increase the fitness cost of switching to anaerobic glycolysis, might decrease probability of the emergence of more invasive phenotypes.

Distinct signatures of B-cell homeostatic and activation-dependent chemokine receptors in the development and progression of extragastric MALT lymphomas.

Chemokine receptors mediate migration and activation of lymphocytes through binding of their ligands. Recent studies have revealed important contributions of chemokine receptors to the development, progression, and dissemination of haematopoietic neoplasms. Because the chemokine receptor expression profile in extragastric MALT lymphoma is unknown, we performed a comprehensive study on tissue samples of parotid glands, parotid glands affected by Sjögren syndrome, extragastric MALT lymphoma, and extranodal diffuse large B-cell lymphoma (eDLBCL) originating from MALT lymphoma (transformed MALT lymphoma). By investigating the expression of 19 chemokine receptors by real-time PCR using a semi-quantitative approach and of four chemokine receptors (CCR1, CCR5, CXCR6, and XCR1) by immunohistochemistry, we show that the chemokine receptor expression profiles of extragastric MALT lymphomas differ substantially from those of extranodal DBLCL, with lower expression of CCR1, CCR8, and CXCR3, and the absence of expression of CX3CR1 and XCR1 in eDLBCL. Expression of CCR6, CCR7, CXCR3, CXCR4, and CXCR5, responsible for B-cell homing to secondary lymphoid tissue, was detected in both B-cell malignancies. Expression of CCR4 was just detected in trisomy 3-positive MALT lymphoma cases. Comparing gastric with extragastric MALT lymphomas, up-regulation of CXCR1 and CXCR2 accompanied by down-regulation of CCR8 and CX3CR1 and loss of XCR1 expression in extragastric MALT lymphomas appear to be key determinants for the site of origin of MALT lymphomagenesis. Our results support a model of stepwise progression of extragastric MALT lymphoma from a non-neoplastic event to Sjögren syndrome, to MALT lymphoma, and finally to overt eDLBCL, guided by differentially expressed B-cell homeostatic and activation-dependent chemokine receptors and their ligands.