Evidence‐based medicine meets person‐centred care: a collaborative perspective on the relationship

In a recent list‐serve, the way forward for evidence‐based medicine was discussed. The purpose of this paper was to share the reflections and multiple perspectives discussed in this peer‐to‐peer encounter and to invite the reader to think with a mind for positive change in the practice of health care. Let us begin with a simple question. What if we dared to look at evidence‐based medicine (EBM) and informed shared decision making like two wheels on a bike? They both need to be full of substance, well connected, lubricated and working in balance, propelled and guided by a competent driver, with good vision to get the bike where we want it to go. We need all the tools in the toolkit for the bike to stay operational and to meet the needs of the driver. By the same rationale, evidence alone is necessary but not sufficient for decision making; values are necessary and if neglected, may default to feelings based on social pressures and peer influence. Medical decisions, even shared ones, lack focus without evidence and application. Just as a bike may need a tune up from time to time to maintain optimal performance, EBM may benefit from a tune up where we challenge ourselves to move away from general assumptions and traditions and instead think clearly about the issues we face and how to ask well‐formed, specific questions to get the answers to meet the needs we face in health care.     

Epistemic injustice in assessment of delusions

Delusions are one of the most elusive concepts in psychiatry. There have been several theories on the nature and definition of delusions. Jaspers described them as entailing a total transformation of reality and considered primary delusions as un‐understandable. When it comes to clinical practice, psychiatrists resort to criteria of falsity, incorrigibility, conviction and being out of keeping with the person's culture. All these criteria have been subject to various criticisms, some of which will be discussed in the paper. We will use the concept of epistemic injustice to explore the role of stereotypes and prejudice in the identification of delusions. We will discuss cases where patients are suffering from testimonial injustice by virtue of having a mental disorder that is so often associated with attributions of irrationality, bizarreness and incomprehensibility. Two vignettes will be presented to show that this is often the case in clinical practice. We will discuss relevant issues around the epistemology of the delusions. We think that in order to challenge the testimonial injustice, there needs to be an awareness of its possibility and thus recognition of the role of certain stereotypes in assessing these mental states. Challenging the stigma against mentally ill and adopting a holistic view of delusions can help tackle the prejudice that pre‐empt the testimonial injustice.     

Gemcitabine resistant pancreatic cancer cell lines acquire an invasive phenotype with collateral hypersensitivity to histone deacetylase inhibitors

Gemcitabine based treatment is currently a standard first line treatment for patients with advanced pancreatic cancer, however overall survival remains poor, and few options are available for patients that fail gemcitabine based therapy. To identify potential molecular targets in gemcitabine refractory pancreatic cancer, we developed a series of gemcitabine resistant (GR) cell lines. Initial drug exposure selected for an early resistant phenotype that was independent of drug metabolic pathways. Prolonged drug selection pressure after 16 weeks, led to an induction of cytidine deaminase (CDA) and enhanced drug detoxification. Cross resistance profiles demonstrate approximately 100-fold cross resistance to the pyrimidine nucleoside cytarabine, but no resistance to the same in class agents, azacytidine and decitabine. GR cell lines demonstrated a dose dependent collateral hypersensitivity to class I and II histone deacetylase (HDAC) inhibitors and decreased expression of 3 different global heterochromatin marks, as detected by H4K20me3, H3K9me3 and H3K27me3. Cell morphology of the drug resistant cell lines demonstrated a fibroblastic type appearance with loss of cell-cell junctions and an altered microarray expression pattern, using Gene Ontology (GO) annotation, consistent with progression to an invasive phenotype. Of particular note, the gemcitabine resistant cell lines displayed up to a 15 fold increase in invasive potential that directly correlates with the level of gemcitabine resistance. These findings suggest a mechanistic relationship between chemoresistance and metastatic potential in pancreatic carcinoma and provide evidence for molecular pathways that may be exploited to develop therapeutic strategies for refractory pancreatic cancer.