Combining realist evaluation and transformative evaluation to advance research in palliative care: The case of end of life companionship.

BACKGROUND: Palliative care requires innovative methods to understand what works, for whom, in what circumstances and why. Realist evaluation has become one prominent approach due to its preoccupation with building, and testing, causal theories to explain the influence of contextual factors on outcomes. Undertaking realist evaluation is not without challenges and may amplify issues of underrepresentation, disempower those working in palliative care, and produce results with poor ecological validity. Complementary approaches are needed which mitigate these challenges, whilst producing credible findings that advances knowledge. PURPOSE: In this article it is outlined how realist evaluation provides a toolkit to advance research to explain, and empirically test, the complex contours of palliative care. Moreover, it is proposed that transformative evaluation can provide a catalyst to engage and empower those within palliative care, create the opportunity for care transformation, and produce more informed and authentic theories. DISCUSSION: Contemporary issues in palliative care pertain to the complexity of palliative care, the insufficiency of experimental designs alone, and the challenges of achieving inclusive research participation. In this article it is argued that theory led, participatory, opportunistic and naturalistic approaches can provide an antidote to the issues in the literature. The combination also mitigates many methodological critiques of the individual approaches, by increasing the transformative potential of realist evaluation, and explanatory potential of transformative evaluation.

Plasma N-glycans in colorectal cancer risk.

Aberrant glycosylation has been associated with a number of diseases including cancer. Our aim was to elucidate changes in whole plasma N-glycosylation between colorectal cancer (CRC) cases and controls in one of the largest cohorts of its kind. A set of 633 CRC patients and 478 age and gender matched controls was analysed. Additionally, patients were stratified into four CRC stages. Moreover, N-glycan analysis was carried out in plasma of 40 patients collected prior to the initial diagnosis of CRC. Statistically significant differences were observed in the plasma N-glycome at all stages of CRC, this included a highly significant decrease in relation to the core fucosylated bi-antennary glycans F(6)A2G2 and F(6)A2G2S(6)1 (P < 0.0009). Stage 1 showed a unique biomarker signature compared to stages 2, 3 and 4. There were indications that at risk groups could be identified from the glycome (retrospective AUC = 0.77 and prospective AUC = 0.65). N-glycome biomarkers related to the pathogenic progress of the disease would be a considerable asset in a clinical setting and it could enable novel therapeutics to be developed to target the disease in patients at risk of progression.

Twoplex 12/13 C6 aniline stable isotope and linkage-specific sialic acid labeling 2D-LC-MS workflow for quantitative N-glycomics.

Quantitative glycomics represents an actively expanding research field ranging from the discovery of disease-associated glycan alterations to the quantitative characterization of N-glycans on therapeutic proteins. Commonly used analytical platforms for comparative relative quantitation of complex glycan samples include MALDI-TOF-MS or chromatographic glycan profiling with subsequent data alignment and statistical evaluation. Limitations of such approaches include run-to-run technical variation and the potential introduction of subjectivity during data processing. Here, we introduce an offline 2D LC-MSE workflow for the fractionation and relative quantitation of twoplex isotopically labeled N-linked oligosaccharides using neutral 12 C6 and 13 C6 aniline (Δmass = 6 Da). Additional linkage-specific derivatization of sialic acids using 4-(4,6-dimethoxy-1,3,5-trizain-2-yl)-4-methylmorpholinium chloride offered simultaneous and advanced in-depth structural characterization. The potential of the method was demonstrated for the differential analysis of structurally defined N-glycans released from serum proteins of patients diagnosed with various stages of colorectal cancer. The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform is ideally suited for differential glycomic analysis of structurally complex N-glycan pools due to combination and analysis of samples in a single LC-MS injection and the associated minimization in technical variation.

Discovering new clinical markers in the field of glycomics.

Glycosylation modifications have been reported in a number of disease states and, as a result, there is significant focus on the discovery and development of glycan-based biomarkers. Glyco-biomarkers have the potential to enhance the efficacy and efficiency of the diagnostic procedures for these diseases.

Drug metabolism by tumours: its nature, relevance and therapeutic implications.

Drug-metabolising enzymes (DMEs) are present in tumours and are capable of biotransforming a variety of antineoplastics. Tumoural drug metabolism is both a potential mechanism of resistance and a means of achieving optimal therapy. This review addresses the classes of DMEs, their cytotoxic substrates and distribution in specific malignancies. The limitations of preclinical and clinical studies are highlighted. Their role in predicting therapeutic response, the activation of prodrugs and the potential for their modulation for gain is also addressed. The contribution of tumoural DMEs to cancer therapy can only be ascertained through large prospective studies and supported by new technologies. Only then can efforts be concentrated in the design of better prodrugs or combination therapy to optimise individual therapy.