CDX2 as a Prognostic Biomarker in Stage II and Stage III Colon Cancer.

Background The identification of high-risk stage II colon cancers is key to the selection of patients who require adjuvant treatment after surgery. Microarray-based multigene-expression signatures derived from stem cells and progenitor cells hold promise, but they are difficult to use in clinical practice. Methods We used a new bioinformatics approach to search for biomarkers of colon epithelial differentiation across gene-expression arrays and then ranked candidate genes according to the availability of clinical-grade diagnostic assays. With the use of subgroup analysis involving independent and retrospective cohorts of patients with stage II or stage III colon cancer, the top candidate gene was tested for its association with disease-free survival and a benefit from adjuvant chemotherapy. Results The transcription factor CDX2 ranked first in our screening test. A group of 87 of 2115 tumor samples (4.1%) lacked CDX2 expression. In the discovery data set, which included 466 patients, the rate of 5-year disease-free survival was lower among the 32 patients (6.9%) with CDX2-negative colon cancers than among the 434 (93.1%) with CDX2-positive colon cancers (hazard ratio for disease recurrence, 3.44; 95% confidence interval [CI], 1.60 to 7.38; P=0.002). In the validation data set, which included 314 patients, the rate of 5-year disease-free survival was lower among the 38 patients (12.1%) with CDX2 protein-negative colon cancers than among the 276 (87.9%) with CDX2 protein-positive colon cancers (hazard ratio, 2.42; 95% CI, 1.36 to 4.29; P=0.003). In both these groups, these findings were independent of the patient's age, sex, and tumor stage and grade. Among patients with stage II cancer, the difference in 5-year disease-free survival was significant both in the discovery data set (49% among 15 patients with CDX2-negative tumors vs. 87% among 191 patients with CDX2-positive tumors, P=0.003) and in the validation data set (51% among 15 patients with CDX2-negative tumors vs. 80% among 106 patients with CDX2-positive tumors, P=0.004). In a pooled database of all patient cohorts, the rate of 5-year disease-free survival was higher among 23 patients with stage II CDX2-negative tumors who were treated with adjuvant chemotherapy than among 25 who were not treated with adjuvant chemotherapy (91% vs. 56%, P=0.006). Conclusions Lack of CDX2 expression identified a subgroup of patients with high-risk stage II colon cancer who appeared to benefit from adjuvant chemotherapy. (Funded by the National Comprehensive Cancer Network, the National Institutes of Health, and others.).

Scandals in health-care: their impact on health policy and nursing.

Through an analysis of several high-profile scandals in health-care in the UK, this article discusses the nature of scandal and its impact on policy reform. The nursing profession is compared to social work and medicine, which have also undergone considerable examination and change as a result of scandals. The author draws on reports from public inquiries from 1945 to 2013 to form the basis of the discussion about policy responses following scandals in health-care. In each case, the nature of the scandal, the public and government discourses generated by events and the policy response to those failings are explored. These scandals are compared to the recent scandal at Mid Staffordshire Hospital. Conclusions are drawn about the impact of these events on the future of the profession and on health policy directions. Recent events have raised public anxieties about caring practices in nursing. Health policy reform driven by scandal may obscure the effect of under resourcing in health services and poses a very real threat to the continued support for state-run services. Understanding the socially constructed nature of scandal enables the nurse to develop a greater critical awareness of policy contexts in order that they can influence health service reform.

What choice? Risk and responsibilisation in cardiovascular health policy.

Employing a policy-as-discourse approach, we explore how the language of choice, risk and responsibilisation influences cardiovascular disease policy. We analyse four key pieces of public health literature produced in the UK between 1999 and 2013 that consider the prevention and treatment of coronary heart disease: Saving Lives: Our Healthier Nation; National Service Framework for Coronary Heart Disease; Mending Hearts and Brains and Cardiovascular Disease Outcomes Strategy. This critical discourse analysis problematises how neoliberal discourses of responsibilisation, risk and choice operate to govern health practices. Textual analysis reveals there are multiple dimensions evident in the way that responsibility for health is framed. Organisations are considered responsible 'for' illness prevention strategies and service provision, while individuals are conceptualised as responsible 'to' maintain healthy lifestyles. Conceptualising individuals as responsible health-conscious consumers enables a backward-looking narrative that holds individuals to account. Furthermore analysis reveals assumptions and messages that demonstrate the operation of moral discourses around patient behaviour. We suggest moral dimensions to public health strategies obscure the structural disparities that influence healthy life chances, imposing a system of limitations and exclusions that lead to allocation of liability and attributing blame for illness.

Anti-Oppressive Practice and Reflexive Lifeworld-Led Approaches to Care: A Framework for Teaching Nurses about Social Justice.

This paper was initially written for a European Academy of Caring Science workshop and aimed to provide clarity and direction about Caring Science by offering some ideas emerging from the philosophy, themes, and projects of EACS. An underpinning concept for the work of the Academy is the lifeworld. The focus of the workshop was to explore the lifeworld of the patient, student, and carer. The intention was to promote discussion around the need to provide alternative ways to conceptualise caring relevant knowledge, naming phenomena and practices central to caring sciences, and the educational curriculum and its adequacy for caring science. This paper seeks to identify concepts and approaches to understanding oppression, power, and justice which enable nurses to challenge the structures in health care environments which discriminate or disempower clients. Anti-oppressive practice theory and reflexive lifeworld-led approaches to care enable nurses to be critical of their practice. A framework for teaching social justice in health care is offered to augment teaching students to challenge oppressive practice and to assist nurses to reflect and develop conceptual models to guide practices which are central to promoting caring interactions.