Structured Telephone Support or Telemonitoring Programs for Patients with Chronic Heart Failure

Background: Specialised disease management programmes for chronic heart failure (CHF) improve survival, quality of life and reduce healthcare utilisation. The overall efficacy of structured telephone support or telemonitoring as an individual component of a CHF disease management strategy remains inconclusive. Objectives: To review randomised controlled trials (RCTs) of structured telephone support or telemonitoring compared to standard practice for patients with CHF in order to quantify the effects of these interventions over and above usual care for these patients. Search strategy: Databases (the Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment Database (HTA) on The Cochrane Library, MEDLINE, EMBASE, CINAHL, AMED and Science Citation Index Expanded and Conference Citation Index on ISI Web of Knowledge) and various search engines were searched from 2006 to November 2008 to update a previously published non-Cochrane review. Bibliographies of relevant studies and systematic reviews and abstract conference proceedings were handsearched. No language limits were applied. Selection criteria: Only peer reviewed, published RCTs comparing structured telephone support or telemonitoring to usual care of CHF patients were included. Unpublished abstract data was included in sensitivity analyses. The intervention or usual care could not include a home visit or more than the usual (four to six weeks) clinic follow-up. Data collection and analysis: Data were presented as risk ratio (RR) with 95% confidence intervals (CI). Primary outcomes included all-cause mortality, all-cause and CHF-related hospitalisations which were meta-analysed using fixed effects models. Other outcomes included length of stay, quality of life, acceptability and cost and these were described and tabulated. Main results: Twenty-five studies and five published abstracts were included. Of the 25 full peer-reviewed studies meta-analysed, 16 evaluated structured telephone support (5613 participants), 11 evaluated telemonitoring (2710 participants), and two tested both interventions (included in counts). Telemonitoring reduced all-cause mortality (RR 0.66, 95% CI 0.54 to 0.81, P < 0.0001) with structured telephone support demonstrating a non-significant positive effect (RR 0.88, 95% CI 0.76 to 1.01, P = 0.08). Both structured telephone support (RR 0.77, 95% CI 0.68 to 0.87, P < 0.0001) and telemonitoring (RR 0.79, 95% CI 0.67 to 0.94, P = 0.008) reduced CHF-related hospitalisations. For both interventions, several studies improved quality of life, reduced healthcare costs and were acceptable to patients. Improvements in prescribing, patient knowledge and self-care, and New York Heart Association (NYHA) functional class were observed. Authors' conclusions: Structured telephone support and telemonitoring are effective in reducing the risk of all-cause mortality and CHF-related hospitalisations in patients with CHF; they improve quality of life, reduce costs, and evidence-based prescribing.

The impact of software-as-a-service on business models of leading software vendors : experiences from three exploratory case studies

The number of software vendors offering ‘Software-as-a-Service’ has been increasing in recent years. In the Software-as-a-Service model software is operated by the software vendor and delivered to the customer as a service. Existing business models and industry structures are challenged by the changes to the deployment and pricing model compared to traditional software. However, the full implications on the way companies create, deliver and capture value are not yet sufficiently analyzed. Current research is scattered on specific aspects, only a few studies provide a more holistic view of the impact from a business model perspective. For vendors it is, however, crucial to be aware of the potentially far reaching consequences of Software-as-a-Service. Therefore, a literature review and three exploratory case studies of leading software vendors are used to evaluate possible implications of Software-as-a-Service on business models. The results show an impact on all business model building blocks and highlight in particular the often less articulated impact on key activities, customer relationship and key partnerships for leading software vendors and show related challenges, for example, with regard to the integration of development and operations processes. The observed implications demonstrate the disruptive character of the concept and identify future research requirements.

Relative entropy rate based design for linear hybrid system models

Hybrid system representations have been applied to many challenging modeling situations. In these hybrid system representations, a mixture of continuous and discrete states is used to capture the dominating behavioural features of a nonlinear, possible uncertain, model under approximation. Unfortunately, the problem of how to best design a suitable hybrid system model has not yet been fully addressed. This paper proposes a new joint state measurement relative entropy rate based approach for this design purpose. Design examples and simulation studies are presented which highlight the benefits of our proposed design approaches.

Robust designs for Poisson regression models

We consider the problem of how to construct robust designs for Poisson regression models. An analytical expression is derived for robust designs for first-order Poisson regression models where uncertainty exists in the prior parameter estimates. Given certain constraints in the methodology, it may be necessary to extend the robust designs for implementation in practical experiments. With these extensions, our methodology constructs designs which perform similarly, in terms of estimation, to current techniques, and offers the solution in a more timely manner. We further apply this analytic result to cases where uncertainty exists in the linear predictor. The application of this methodology to practical design problems such as screening experiments is explored. Given the minimal prior knowledge that is usually available when conducting such experiments, it is recommended to derive designs robust across a variety of systems. However, incorporating such uncertainty into the design process can be a computationally intense exercise. Hence, our analytic approach is explored as an alternative.

Developing the atlas of cancer in Queensland : methodological issues

Background: Achieving health equity has been identified as a major challenge, both internationally and within Australia. Inequalities in cancer outcomes are well documented, and must be quantified before they can be addressed. One method of portraying geographical variation in data uses maps. Recently we have produced thematic maps showing the geographical variation in cancer incidence and survival across Queensland, Australia. This article documents the decisions and rationale used in producing these maps, with the aim to assist others in producing chronic disease atlases. Methods: Bayesian hierarchical models were used to produce the estimates. Justification for the cancers chosen, geographical areas used, modelling method, outcome measures mapped, production of the adjacency matrix, assessment of convergence, sensitivity analyses performed and determination of significant geographical variation is provided. Conclusions: Although careful consideration of many issues is required, chronic disease atlases are a useful tool for assessing and quantifying geographical inequalities. In addition they help focus research efforts to investigate why the observed inequalities exist, which in turn inform advocacy, policy, support and education programs designed to reduce these inequalities.

Stochastic models for regulatory networks of the genetic toggle switch

Bistability arises within a wide range of biological systems from the λ phage switch in bacteria to cellular signal transduction pathways in mammalian cells. Changes in regulatory mechanisms may result in genetic switching in a bistable system. Recently, more and more experimental evidence in the form of bimodal population distributions indicates that noise plays a very important role in the switching of bistable systems. Although deterministic models have been used for studying the existence of bistability properties under various system conditions, these models cannot realize cell-to-cell fluctuations in genetic switching. However, there is a lag in the development of stochastic models for studying the impact of noise in bistable systems because of the lack of detailed knowledge of biochemical reactions, kinetic rates, and molecular numbers. In this work, we develop a previously undescribed general technique for developing quantitative stochastic models for large-scale genetic regulatory networks by introducing Poisson random variables into deterministic models described by ordinary differential equations. Two stochastic models have been proposed for the genetic toggle switch interfaced with either the SOS signaling pathway or a quorum-sensing signaling pathway, and we have successfully realized experimental results showing bimodal population distributions. Because the introduced stochastic models are based on widely used ordinary differential equation models, the success of this work suggests that this approach is a very promising one for studying noise in large-scale genetic regulatory networks.

Brivanib alaninate, a dual inhibitor of vascular endothelial growth factor receptor and fibroblast growth factor receptor tyrosine kinases, induces growth inhibition in mouse models of human hepatocellular carcinoma

PURPOSE: Hreceptor (VEGFR) and FGF receptor (FGFR) signaling pathways. EXPERIMENTAL DESIGN: Six different s.c. patient-derived HCC xenografts were implanted into mice. Tumor growth was evaluated in mice treated with brivanib compared with control. The effects of brivanib on apoptosis and cell proliferation were evaluated by immunohistochemistry. The SK-HEP1 and HepG2 cells were used to investigate the effects of brivanib on the VEGFR-2 and FGFR-1 signaling pathways in vitro. Western blotting was used to determine changes in proteins in these xenografts and cell lines. RESULTS: Brivanib significantly suppressed tumor growth in five of six xenograft lines. Furthermore, brivanib-induced growth inhibition was associated with a decrease in phosphorylated VEGFR-2 at Tyr(1054/1059), increased apoptosis, reduced microvessel density, inhibition of cell proliferation, and down-regulation of cell cycle regulators. The levels of FGFR-1 and FGFR-2 expression in these xenograft lines were positively correlated with its sensitivity to brivanib-induced growth inhibition. In VEGF-stimulated and basic FGF stimulated SK-HEP1 cells, brivanib significantly inhibited VEGFR-2, FGFR-1, extracellular signal-regulated kinase 1/2, and Akt phosphorylation. CONCLUSION: This study provides a strong rationale for clinical investigation of brivanib in patients with HCC.

Refining animal models in fracture research: Seeking consensus in optimising both animal welfare and scientific validity for appropriate biomedical use

Background In an attempt to establish some consensus on the proper use and design of experimental animal models in musculoskeletal research, AOVET (the veterinary specialty group of the AO Foundation) in concert with the AO Research Institute (ARI), and the European Academy for the Study of Scientific and Technological Advance, convened a group of musculoskeletal researchers, veterinarians, legal experts, and ethicists to discuss, in a frank and open forum, the use of animals in musculoskeletal research. Methods The group narrowed the field to fracture research. The consensus opinion resulting from this workshop can be summarized as follows: Results & Conclusion Anaesthesia and pain management protocols for research animals should follow standard protocols applied in clinical work for the species involved. This will improve morbidity and mortality outcomes. A database should be established to facilitate selection of anaesthesia and pain management protocols for specific experimental surgical procedures and adopted as an International Standard (IS) according to animal species selected. A list of 10 golden rules and requirements for conduction of animal experiments in musculoskeletal research was drawn up comprising 1) Intelligent study designs to receive appropriate answers; 2) Minimal complication rates (5 to max. 10%); 3) Defined end-points for both welfare and scientific outputs analogous to quality assessment (QA) audit of protocols in GLP studies; 4) Sufficient details for materials and methods applied; 5) Potentially confounding variables (genetic background, seasonal, hormonal, size, histological, and biomechanical differences); 6) Post-operative management with emphasis on analgesia and follow-up examinations; 7) Study protocols to satisfy criteria established for a "justified animal study"; 8) Surgical expertise to conduct surgery on animals; 9) Pilot studies as a critical part of model validation and powering of the definitive study design; 10) Criteria for funding agencies to include requirements related to animal experiments as part of the overall scientific proposal review protocols. Such agencies are also encouraged to seriously consider and adopt the recommendations described here when awarding funds for specific projects. Specific new requirements and mandates related both to improving the welfare and scientific rigour of animal-based research models are urgently needed as part of international harmonization of standards.