Determinants of knowledge-sharing networks in primary care

Background. Around the world, health reforms are increasingly fostering collaboration and integration among primary care physicians with the aim of facilitating knowledge sharing and evidence-informed decision making. Although extant research on this topic is abundant, the evidence and results regarding social and organizational factors affecting the formation of knowledge-sharing networks in this setting are inconclusive. Purposes. The aim of this article is to explore multiple theoretical mechanisms explaining the formation of knowledge-sharing networks among primary care physicians across relevant clinical areas. Methodology/Approach. The data are collected from two local health authorities (LHAs) in the Italian National Health Service that are responsible for delivering primary care in two Italian regions. Exponential random graph models are used to test the hypotheses. Findings. Our findings indicate that knowledge-sharing networks are highly correlated across clinical areas. In addition, knowledge-sharing networks are highly reciprocal and clustered. We also observe that formal models adopted to foster collaboration have remarkably different effects on the formation of knowledge networks, depending upon the diverse knowledge management approaches adopted in the surveyed LHAs. Practice Implications. Primary care organizations need to develop and implement knowledge management practices in order to help physicians in identifying knowledge domain experts as well as to support connections through formal groupings and incentives

From network ties to network structures: Exponential Random Graph Models of interorganizational relations

Theoretical accounts of network ties between organizations emphasize the interdependence of individual intentions, opportunities, and actions embedded in local configurations of network ties. These accounts are at odds with empirical models based on assumptions of independence between network ties. As a result, the relation between models for network ties and the observed network structure of interorganizational fields is problematic. Using original fieldwork and data that we have collected on collaborative network ties within a regional community of hospital organizations we estimate newly developed specifications of Exponential Random Graph Models (ERGM) that help to narrow the gap between theories and empirical models of interorganizational networks. After controlling for the main factors known to affect partner selection decisions, full models in which local dependencies between network ties are appropriately specified outperform restricted models in which such dependencies are left unspecified and only controlled for statistically. We use computational methods to show that networks based on empirical estimates produced by models accounting for local network dependencies reproduce with accuracy salient features of the global network structure that was actually observed. We show that models based on assumptions of independence between network ties do not. The results of the study suggest that mechanisms behind the formation of network ties between organizations are local, but their specification and identification depends on an accurate characterization of network structure. We discuss the implications of this view for current research on interorganizational networks, communities, and field

Assimilation and differentiation: A multilevel perspective on organizational and network change

This paper builds on recently derived stochastic actor-oriented models (SAOMs) for the coevolution of one-mode and two-mode networks, and extends them to the analysis of how concurrent multilevel processes of (internal) organizational and (external) network change affect one another over time. New effects are presented that afford specification and identification of two apparently conflicting micro-relational mechanisms that jointly affect decisions to modify the portfolio of internal organizational activities. The first mechanism, assimilation, makes network partners more similar by facilitating the replication and diffusion of experience. The second mechanism, functional differentiation, operates to maintain and amplify differences between network partners by preventing or limiting internal organizational change. We illustrate the empirical value of the model in the context of data that we have collected on a regional community of hospital organizations connected by collaborative patient transfer relations observed over a period of seven years. We find that processes of social influence conveyed by network ties may lead both to similarity and differences among connected organizations. We discuss the implications of the results in the context of current research on interorganizational networks

Investigating the temporal dynamics of inter-organizational exchange: patient transfers among Italian hospitals

Previous research on interaction behavior among organizations (resource exchange, collaboration, communication) has typically aggregated records of those behaviors over time to constitute a ‘network’ of organizational relationships. We instead directly study structural-temporal patterns in organizational exchange, focusing on the dynamics of reciprocation. Applying this lens to a community of Italian hospitals during the period 2003-2007, we observe two mechanisms of interorganizational reciprocation: organizational embedding and resource dependence. We flesh out these two mechanisms by showing how they operate in distinct time frames: Dependence operates on contemporaneous exchange structures, whereas embedding develops through longer-term historical patterns. We also show how these processes operate differently in competitive and noncompetitive contexts, operationalized in terms of market differentiation and geographic space. In noncompetitive contexts, we observe both logics of reciprocation, dependence in the short term and embedding over the long term, developing into patterns of generalized exchange in this population. In competitive contexts, we observe neither form of reciprocation and instead observe the microfoundations of status hierarchies in exchange

Assessing social and economic impact of subcutaneous mAbs in oncology

Background: Rituximab and trastuzumab were the first monoclonal antibodies (mAbs) approved for the treatment of cancer patients. Both antibodies are administered intravenously (EV), but subcutaneous (SC) formulations have recently been developed. SC formulations proved to be as safe and effective as EV and to offer substantial benefits to the patient. Objective: The aim of this study was to provide a multidimensional assessment of the impact of rituximab and trastuzumab SC compared to the EV formulation, providing a particular focus on expected social and economic benefits for the patient. Methods: The best established HTA methods were applied to gather and organize evidence concerning the clinical, economic, organizational, social and ethical impact of SC formulations of rituximab and trastuzumab. Social aspects were investigated applying regression methods to data collected with a previous research, while the potential savings associated with the use of SC formulations were estimated by a simple economic model applying the societal perspective. Results Patients undergoing subcutaneous formulation are significantly more satisfied with their treatment experience than those treated with intravenous formulation. Subcutaneous formulation reduces patient dosing times, with a positive effect on the care provider's autonomy and productivity. Potential savings associated with the use of rituximab SC were estimated in € 4,050 per patient per year on average. For trastuzumab SC the estimated potential savings amounted to € 3,400 per patient per year, on average. Conclusion Rituximab and trastuzumab are promising treatment options significantly improving patients qol and reducing the treatment burden in terms of societal costs

FAIRifying Clinical Studies Metadata: A Registry for the Biomedical Research.

The data produced during a research project are too often collected for the sole purpose of the study, therefore hindering profitable reuse in similar contexts. The growing need to counteract this trend has recently led to the formalization of the FAIR principles that aim to make (meta)data Findable, Accessible, Interoperable and Reusable, for humans and machines. Since their introduction, efforts are ongoing to encourage FAIR principles adoption and to implement solutions based on them. This paper reports on the FAIR-compliant registry we developed to collect and serve metadata describing clinical trials. The design of the registry is based on the FAIR Data Point (FDP) specifications, the state-of-the-art reference for FAIRified metadata sharing. To map the metadata relevant to our use case, we have extended the DCAT-based semantic model of the FDP adopting well-established ontologies in the biomedical and clinical domain, like the Semanticscience Integrated Ontology (SIO). Current implementation is based on the Molgenis software and provides both a user interface and a REST API for metadata discovering. At present the registry is being loaded with the metadata of the 18 clinical studies included in the 'I FAIR Program', a project finalised to the dissemination of FAIR best practices among the clinical researchers in Sardinia (Italy). After a testing phase, the registry will be publicly available, while the new model and the source code will be released open source

Ubiquitination as a key regulatory mechanism for O3-induced cutaneous redox inflammasome activation

NLRP1 is one of the major inflammasomes modulating the cutaneous inflammatory responses and therefore linked to a variety of cutaneous conditions. Although NLRP1 has been the first inflammasome to be discovered, only in the past years a significant progress was achieved in understanding the molecular mechanism and the stimuli behind its activation. In the past decades a crescent number of studies have highlighted the role of air pollutants as Particulate Matter (PM), Cigarette Smoke (CS) and Ozone (O3) as trigger stimuli for inflammasomes activation, especially via Reactive Oxygen Species (ROS) mediators. However, whether NLRP1 can be modulated by air pollutants via oxidative stress and the mechanism behind its activation is still poorly understood. Here we report for the first time that O3, one of the most toxic pollutants, activates the NLRP1 inflammasome in human keratinocytes via oxidative stress mediators as hydrogen peroxide (H2O2) and 4-hydroxy-nonenal (4HNE). Our data suggest that NLRP1 represents a target protein for 4HNE adduction that possibly leads to its proteasomal degradation and activation via the possible involvement of E3 ubiquitin ligase UBR2. Of note, Catalase (Cat) treatment prevented inflammasome assemble and inflammatory cytokines release as well as NLRP1 ubiquitination in human keratinocytes upon O3 exposure. The present work is a mechanistic study that follows our previous work where we have showed the ability of O3 to induce cutaneous inflammasome activation in humans exposed to this pollutant. In conclusion, our results suggest that O3 triggers the cutaneous NLRP1 inflammasome activation by ubiquitination and redox mechanism

Linking provenance and its metadata in multi-organizational environments

Reproducibility issues are widely reported in life sciences. As a response, scientific communities have called for enhanced provenance information documenting the complete research life cycle, starting from biological or environmental material acquisition and ending with translating research results into practice. The integrity and trustworthiness of such provenance can be achieved by applying versioning mechanisms and cryptographic techniques, such as hashes or digital signatures, which are provenance metadata. However, the available provenance literature lacks an analysis of mechanisms for the exchange of provenance and its metadata between organizations as well as a grounded proposal of linking provenance and its metadata. In this work, we provide an in-depth analysis of the approaches for coupling provenance information and its metadata with documented research objects in the context of multi-organizational processes, leading to the categorization of possible approaches, description of their key properties, and derivation of requirements for underlying provenance models. We address the requirements by proposing a mechanism for linking provenance and its metadata by extending the Common Provenance Model, the open conceptual foundation for the ISO 23494 provenance standard series, currently under development. The concepts are demonstrated and validated on two complex use cases. This work is intended as a harmonized source of information on provenance coupling in the context of exchange of provenance between organizations, which can be used when designing or choosing a provenance solution. This type of usage is exemplified in the extension of the Common Provenance Model as another step toward a provenance standard for life sciences

Alteration of serotonin transporter density and activity in fibromyalgia

The aim of the study was to evaluate the kinetic parameters of a specific serotonin transporter (SERT) and serotonin uptake in a mentally healthy subset of patients with fibromyalgia. Platelets were obtained from 40 patients and 38 healthy controls. SERT expression and functionality were evaluated through the measurement of [(3)H]paroxetine binding and the [(3)H]serotonin uptake itself. The values of maximal membrane binding capacity (B(max)) were statistically lower in the patients than in the healthy volunteers, whereas the dissociation constant (K(d)) did not show any statistically significant variations. Moreover, a decrease in the maximal uptake rate of SERT (V(max)) was demonstrated in the platelets of patients, whereas the Michaelis constant (K(m)) did not show any statistically significant variations. Symptom severity score (tiredness, tender points index and Fibromyalgia Impact Questionnaire) were negatively correlated with B(max )and with V(max), and positively correlated with K(m). A change in SERT seems to occur in fibromyalgic patients, and it seems to be related to the severity of fibromyalgic symptoms