gp100/pmel17 and tyrosinase encode multiple epitopes recognized by Th1-type CD4+T cells

CD4+ T cells modulate the magnitude and durability of CTL responses in vivo, and may serve as effector cells in the tumour microenvironment. In order to identify the tumour epitopes recognized by tumour-reactive human CD4+ T cells, we combined the use of an HLA-DR4/peptide binding algorithm with an IFN-γ ELISPOT assay. Two known and three novel CD4+ T cell epitopes derived from the gp 100/pmel17 and tyrosinase melanocyte-associated antigens were confirmed or identified. Of major interest, we determined that freshly-isolated PBMC frequencies of Th1-type CD4+ T recognizing these peptides are frequently elevated in HLA-DR4+ melanoma patients (but not normal donors) that are currently disease-free as a result of therapeutic intervention. Epitope-specific CD4+ T cells from normal DR4+ donors could be induced, however, after in vitro stimulation with autologous dendritic cell pulsed with antigens (peptides or antigen-positive melanoma lysates) or infected with recombinant vaccinia virus encoding the relevant antigen. Peptide-reactive CD4+ T cells also recognized HLA-DR4+ melanoma cell lines that constitutively express the relevant antigen. Based on these data, these epitopes may serve as potent vaccine components to promote clinically-relevant Th1-type CD4+ T cell effector function in situ. http://www.bjcancer.com © 2001 Cancer Research Campaig

Comparison of user groups' perspectives of barriers and facilitators to implementing electronic health records: a systematic review

<p>Abstract</p> <p>Background</p> <p>Electronic health record (EHR) implementation is currently underway in Canada, as in many other countries. These ambitious projects involve many stakeholders with unique perceptions of the implementation process. EHR users have an important role to play as they must integrate the EHR system into their work environments and use it in their everyday activities. Users hold valuable, first-hand knowledge of what can limit or contribute to the success of EHR implementation projects. A comprehensive synthesis of EHR users' perceptions is key to successful future implementation. This systematic literature review was aimed to synthesize current knowledge of the barriers and facilitators influencing shared EHR implementation among its various users.</p> <p>Methods</p> <p>Covering a period from 1999 to 2009, a literature search was conducted on nine electronic databases. Studies were included if they reported on users' perceived barriers and facilitators to shared EHR implementation, in healthcare settings comparable to Canada. Studies in all languages with an empirical study design were included. Quality and relevance of the studies were assessed. Four EHR user groups were targeted: physicians, other health care professionals, managers, and patients/public. Content analysis was performed independently by two authors using a validated extraction grid with pre-established categorization of barriers and facilitators for each group of EHR users.</p> <p>Results</p> <p>Of a total of 5,695 potentially relevant publications identified, 117 full text publications were obtained after screening titles and abstracts. After review of the full articles, 60 publications, corresponding to 52 studies, met the inclusion criteria. The most frequent adoption factors common to all user groups were design and technical concerns, ease of use, interoperability, privacy and security, costs, productivity, familiarity and ability with EHR, motivation to use EHR, patient and health professional interaction, and lack of time and workload. Each user group also identified factors specific to their professional and individual priorities.</p> <p>Conclusions</p> <p>This systematic review presents innovative research on the barriers and facilitators to EHR implementation. While important similarities between user groups are highlighted, differences between them demonstrate that each user group also has a unique perspective of the implementation process that should be taken into account.</p