Effect of initial treatment strategy on survival of patients with advanced-stage Hodgkin's lymphoma: a systematic review and network meta-analysis

BACKGROUND Several treatment strategies are available for adults with advanced-stage Hodgkin's lymphoma, but studies assessing two alternative standards of care-increased dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPescalated), and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD)-were not powered to test differences in overall survival. To guide treatment decisions in this population of patients, we did a systematic review and network meta-analysis to identify the best initial treatment strategy. METHODS We searched the Cochrane Library, Medline, and conference proceedings for randomised controlled trials published between January, 1980, and June, 2013, that assessed overall survival in patients with advanced-stage Hodgkin's lymphoma given BEACOPPbaseline, BEACOPPescalated, BEACOPP variants, ABVD, cyclophosphamide (mechlorethamine), vincristine, procarbazine, and prednisone (C[M]OPP), hybrid or alternating chemotherapy regimens with ABVD as the backbone (eg, COPP/ABVD, MOPP/ABVD), or doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone combined with radiation therapy (the Stanford V regimen). We assessed studies for eligibility, extracted data, and assessed their quality. We then pooled the data and used a Bayesian random-effects model to combine direct comparisons with indirect evidence. We also reconstructed individual patient survival data from published Kaplan-Meier curves and did standard random-effects Poisson regression. Results are reported relative to ABVD. The primary outcome was overall survival. FINDINGS We screened 2055 records and identified 75 papers covering 14 eligible trials that assessed 11 different regimens in 9993 patients, providing 59 651 patient-years of follow-up. 1189 patients died, and the median follow-up was 5·9 years (IQR 4·9-6·7). Included studies were of high methodological quality, and between-trial heterogeneity was negligible (τ(2)=0·01). Overall survival was highest in patients who received six cycles of BEACOPPescalated (HR 0·38, 95% credibility interval [CrI] 0·20-0·75). Compared with a 5 year survival of 88% for ABVD, the survival benefit for six cycles of BEACOPPescalated is 7% (95% CrI 3-10)-ie, a 5 year survival of 95%. Reconstructed individual survival data showed that, at 5 years, BEACOPPescalated has a 10% (95% CI 3-15) advantage over ABVD in overall survival. INTERPRETATION Six cycles of BEACOPPescalated significantly improves overall survival compared with ABVD and other regimens, and thus we recommend this treatment strategy as standard of care for patients with access to the appropriate supportive care.

Immunotargeting of liposomes to activated vascular endothelial cells: A strategy for site-selective delivery in the cardiovascular system

Endothelial-selective delivery of therapeutic agents, such as drugs or genes, would provide a useful tool for modifying vascular function in various disease states. A potential molecular target for such delivery is E-selectin, an endothelial-specific cell surface molecule expressed at sites of activation in vivo and inducible in cultured human umbilical vein endothelial cells (HUVEC) by treatment with cytokines such as recombinant human interleukin 1β (IL-1β). Liposomes of various types (classical, sterically stabilized, cationic, pH-sensitive), each conjugated with mAb H18/7, a murine monoclonal antibody that recognizes the extracellular domain of E-selectin, bound selectively and specifically to IL-1β-activated HUVEC at levels up to 275-fold higher than to unactivated HUVEC. E-selectin-targeted immunoliposomes appeared in acidic, perinuclear vesicles 2–4 hr after binding to the cell surface, consistent with internalization via the endosome/lysosome pathway. Activated HUVEC incubated with E-selectin-targeted immunoliposomes, loaded with the cytotoxic agent doxorubicin, exhibited significantly decreased cell survival, whereas unactivated HUVEC were unaffected by such treatment. These results demonstrate the feasibility of exploiting cell surface activation markers for the endothelial-selective delivery of biologically active agents via immunoliposomes. Application of this targeting approach in vivo may lead to novel therapeutic strategies in the treatment of cardiovascular disease.

Human resource strategy:introducing a new management typology to make change stick

Human resource management (HRM) is now being seen as a strategic activity. This recognises that change processes must include the management of human resources as part of an integrated approach to strategy. Without also linking management development and business strategy, change will not stick and organisations will not develop. Contributing to the debate about integrating HR and other strategies, including linking management development and business strategy, this paper develops a new Generic Management Typology of co-existing management philosophies in order to help change agents diagnose the culture of an organisation and to modify that culture. The typology is derived from reflecting on research about the global transformation of public service organisations over the last twenty-five years.

The role of HR in cross-border mergers and acquisitions:the case of Indian pharmaceutical firms

Mergers and acquisitions (M&) are increasingly becoming a strategy of choice for companies attempting to achieve and sustain competitive advantage. However, not all M&As are a success. In this paper, we examine the three main reasons highlighted in the literature as major causes of M&A failure (clashing corporate cultures, absence of clear communication, and employee involvement) in three Indian pharmaceutical companies, and we analyze the role played by the HR function in addressing them. Also, we discuss the importance of gaining the commitment and focus of the workforce during the acquisition process through employee involvement.

HR outsourcing:the impact on HR role, competency development and relationships

The business benefits of an outsourcing strategy are well documented, and HR is encouraged to outsource in order to add value. Yet little is known about how HR outsourcing affects the HR role, competencies and relationships with senior management. These issues are examined through 27 semi-structured interviews with senior HR professionals, comparing HR departments engaged in HR outsourcing with those maintaining full in-house HR provision. The findings indicate that HR outsourcing stymies HR role transformation. HR outsourcers experienced limited skill development and an increased focus on cost reduction at the expense of their strategic position. In contrast, non-HR outsourcers actively engaged in other parts of the business, developing competencies that garnered trust and support of senior managers. The benefits of an external HR community appear limited. The study suggests that an 'internal' HR community is better placed to enhance HR departmental roles. © 2013 John Wiley & Sons Ltd.

Russia and the Global Security Strategy of the European Union

The present article reviews the relations between the EU and Russia in the past decade and shows the deterioration of the bilateral relations. The Putin´s Russia has become a very active geostrategic player, with a worrying behaviour, breaking balances in the international scene established since the end of the Cold War. Russia is a priority in the Foreign and Security Policy of the European Global Security Strategy, but has become also a clear competitor. This last aspect is not sufficiently underlined in the Strategy and thus the strategic framework is not clear. In parallel, it is not clear in the Strategy which are the tools the EU has to defend its neighbourhood when their independence, sovereignty or territorial defence may be put in question. This question goes beyond the support to the resilience of those neighbours.

European life project: a global strategy for the responsible use of a coastal lagoon: a case study from Portugal

Rin de Aveiro is a coastal lagoon located at the Central Region of Portugal subjected to the influence of the tides, resulting in a set of characteristic biotopes favouring anthropic and natural processes. Once managed and controlled correctly, each of these biotopes will allow simultaneously the biodiversity and integration in the making of the wetland landscape. In 1998, one of the final conclusions of the "MARIA" Demonstration Programme for the Integrated Management of Ria de Aveiro was that the poor current state of the environment area resulted from a set of interrelated factors. The Programme selected four (4) pilot-projects towards the integrated management of the lagoon biotopes as possible scenarios for an intervention. This selection was based in criteria related to environmental priorities and the maintenance of traditional economic activities in the region. The idea of choosing projects that would involve the whole geographic space of the Ria, without forgetting the other important themes interrelated with the Management Structure, emerged as a relevant aspect for their definition. Thus, and as a first test of this Management Structure functionality, the following task forces were put forward: Recovery and valorisation of the piers; Recovery of the former salt pans; Management of the agricultural fields of Baixo-Vouga; Implementation of measures for the classification of the Protected Landscape Area of the River Caster Mouth. This payer will report the main results of these pilot-projects attained during their first year period, especially the intervention strategies defined by the Partnership created for this aim.

An hr-adaptive discontinuous Galerkin method for advection-diffusion problems

We propose an adaptive mesh refinement strategy based on exploiting a combination of a pre-processing mesh re-distribution algorithm employing a harmonic mapping technique, and standard (isotropic) mesh subdivision for discontinuous Galerkin approximations of advection-diffusion problems. Numerical experiments indicate that the resulting adaptive strategy can efficiently reduce the computed discretization error by clustering the nodes in the computational mesh where the analytical solution undergoes rapid variation.

A second order control-volume finite-element least-squares strategy for simulating diffusion in strongly anisotropic media

An unstructured mesh �nite volume discretisation method for simulating di�usion in anisotropic media in two-dimensional space is discussed. This technique is considered as an extension of the fully implicit hybrid control-volume �nite-element method and it retains the local continuity of the ux at the control volume faces. A least squares function recon- struction technique together with a new ux decomposition strategy is used to obtain an accurate ux approximation at the control volume face, ensuring that the overall accuracy of the spatial discretisation maintains second order. This paper highlights that the new technique coincides with the traditional shape function technique when the correction term is neglected and that it signi�cantly increases the accuracy of the previous linear scheme on coarse meshes when applied to media that exhibit very strong to extreme anisotropy ratios. It is concluded that the method can be used on both regular and irregular meshes, and appears independent of the mesh quality.