Molecular network analysis using reverse phase protein microarrays for patient tailored therapy.

The practice of medicine has always aimed at individualized treatment of disease. The relationship between patient and physician has always been a personal one, and the physician's choice of treatment has been intended to be the best fit for the patient's needs. The necessary pooling/grouping of disease families and their assignment to a number of drugs or treatment methods has, consequently, led to an increase in the number of effective therapies. However, given the heterogeneity of most human diseases, and cancer specifically, it is currently impossible for the treating clinician to effectively predict a patient's response and outcome based on current technologies, much less the idiosyncratic resistances and adverse effects associated with the limited therapeutic options.

Development of reverse phase protein microarrays for clinical applications and patient-tailored therapy

While genomics provide important information about the somatic genetic changes, and RNA transcript profiling can reveal important expression changes that correlate with outcome and response to therapy, it is the proteins that do the work in the cell. At a functional level, derangements within the proteome, driven by post-translational and epigenetic modifications, such as phosphorylation, is the cause of a vast majority of human diseases. Cancer, for instance, is a manifestation of deranged cellular protein molecular networks and cell signaling pathways that are based on genetic changes at the DNA level. Importantly, the protein pathways contain the drug targets in signaling networks that govern overall cellular survival, proliferation, invasion and cell death. Consequently, the promise of proteomics resides in the ability to extend analysis beyond correlation to causality. A critical gap in the information knowledge base of molecular profiling is an understanding of the ongoing activity of protein signaling in human tissue: what is activated and “in use” within the human body at any given point in time. To address this gap, we have invented a new technology, called reverse phase protein microarrays, that can generate a functional read-out of cell signaling networks or pathways for an individual patient obtained directly from a biopsy specimen. This “wiring diagram” can serve as the basis for both, selection of a therapy and patient stratification.

Using patient specific finite element models to understand the biomechanics of paediatric spinal deformity surgery

Adolescent idiopathic scoliosis (AIS) is a spinal deformity, which may require surgical correction by attaching rods to the patient’s spine using screws inserted into the vertebrae. Complication rates for deformity correction surgery are unacceptably high. Determining an achievable correction without overloading the adjacent spinal tissues or implants requires an understanding of the mechanical interaction between these components. We have developed novel patient specific modelling software to create individualized finite element models (FEM) representing the thoracolumbar spine and ribcage of scoliosis patients. We are using these models to better understand the biomechanics of spinal deformity correction.

Gene amplified in oesophageal cancer 1 (GAEC1) amplification in colorectal cancers and its impact on patient's survival

GAEC1 (gene amplified in oesophageal cancer 1) is located at 7q22.1, first identified in oesophageal cancer.1 Initial work indicated that GAEC1 can act as an oncogene.2 Our pilot study found ∼80% of colorectal cancers showing amplification of GAEC1.3 In this research, we will study GAEC1 copy number in colon cancer cell lines and colorectal tissues, and its prognostic significance. Two human colon cancer cell lines (SW480 and SW48) and one normal colonic epithelial cell line (FHC) were obtained from American Type Culture Collection. Culturing conditions for these cell lines were as published previously.4 Tissues were collected from 283 patients (213 Australian; 70 Japanese) diagnosed with colorectal cancers. Ninety surgically removed non-cancer colorectal tissues (diverticular diseases, hyperplastic polyps and volvulus) were used as controls. H&E stained sections from each cancer were checked to select a block with sufficient cancer tissue and representative morphological features for each patient for DNA extraction...

Measuring patient flow variations : a cross-organisational process mining approach

Variations that exist in the treatment of patients (with similar symptoms) across different hospitals do substantially impact the quality and costs of healthcare. Consequently, it is important to understand the similarities and differences between the practices across different hospitals. This paper presents a case study on the application of process mining techniques to measure and quantify the differences in the treatment of patients presenting with chest pain symptoms across four South Australian hospitals. Our case study focuses on cross-organisational benchmarking of processes and their performance. Techniques such as clustering, process discovery, performance analysis, and scientific workflows were applied to facilitate such comparative analyses. Lessons learned in overcoming unique challenges in cross-organisational process mining, such as ensuring population comparability, data granularity comparability, and experimental repeatability are also presented.

Discharge practices for the intensive care patient : a qualitative exploration in the general ward setting

OBJECTIVE: To explore how registered nurses (RNs) in the general ward perceive discharge processes and practices for patients recently discharged from the intensive care unit (ICU). BACKGROUND: Patients discharged from the ICU environment often require complicated and multifaceted care. The ward-based RN is at the forefront of the care of this fragile patient population, yet their views and perceptions have seldom been explored. DESIGN: A qualitative grounded theory design was used to guide focus group interviews with the RN participants. METHODS: Five semi-structured focus group interviews, including 27 RN participants, were conducted in an Australian metropolitan tertiary referral hospital in 2011. Data analyses of transcripts, field notes and memos used concurrent data generation, constant comparative analysis and theoretical sampling. RESULTS: Results yielded a core category of 'two worlds' stressing the disconnectedness between ICU and the ward setting. This category was divided into sub categories of 'communication disconnect' and 'remember the family'. Properties of 'what we say', 'what we write', 'transfer' and 'information needs' respectively were developed within those sub-categories. CONCLUSION: The discharge process for patients within the ICU setting is complicated and largely underappreciated. There are fundamental, misunderstood differences in prioritisation and care of patients between the areas, with a deep understanding of practice requirements of ward based RNs not being understood. The findings of this research may be used to facilitate inter departmental communications and progress practice development.

Withholding and withdrawing life-sustaining treatment in a patient's best interests : Australian judicial deliberations

•Intractable disputes about withholding and withdrawing life-sustaining treatment from adults who lack capacity are rare but challenging. Judicial resolution may be needed in some of these cases. •A central concept for judicial (and clinical) decision making in this area is a patient's “best interests”. Yet what this term means is contested. •There is an emerging Supreme Court jurisprudence that sheds light on when life-sustaining treatment will, or will not, be judged to be in a patient's best interests. •Treatment that is either futile or overly burdensome is not in a patient's best interests. Although courts will consider patient and family wishes, they have generally deferred to the views of medical practitioners about treatment decisions.

Informatics to support patient choice between diverse medical systems

Culturally, philosophically and religiously diverse medical systems including Western medicine, Traditional Chinese Medicine, Ayurvedic Medicine and Homeopathic Medicine, once situated in places and times relatively unconnected from each other, currently co-exist to a point where patients must choose which system to consult. These decisions require comparative analyses, yet the divergence in key underpinning assumptions is so great that comparisons cannot easily be made. However, diverse medical systems can be meaningfully juxtaposed for the purpose of making practical decisions if relevant information is presented appropriately. Information regarding privacy provisions inherent in the typical practice of each medical system is an important element in this juxtaposition. In this paper the information needs of patients making decisions regarding the selection of a medical system are examined.

A young immunocompetent patient with bilateral immune stromal keratitis due to varicella zoster and herpes simplex

This report describes the diagnostic features, clinical management and the issues associated with management of a young immunocompetent male who presented with a presumed left Herpes simplex immune stromal keratitis, and ten months later, a right immune stromal keratitis associated with Herpes zoster ophthalmicus.

A pilot trial of mobile, patient-performed teledermoscopy

BACKGROUND Early detection by skin self-examination (SSE) could improve outcomes from melanoma. Mobile teledermoscopy may aid this process. OBJECTIVES To establish clinical accuracy of SSE plus mobile teledermoscopy compared to clinical skin examination (CSE) and test whether providing people with detailed SSE instructions improves accuracy. METHODS Men and women 50-64 years (n=58) performed SSE plus mobile teledermoscopy in their homes between May and November 2013 and were given technical instructions plus detailed SSE instructions (intervention) or technical instructions only (control). Within three months, they underwent a CSE. Outcome measures included: a) body sites examined, lesions photographed, and missed; b) sensitivityof SSE plus mobile teledermoscopy compared to in-person CSE using either patients or lesions as denominator, and; c) concordance of telediagnosis with CSE. RESULTS: 49 of 58 randomised participants completed the study, and submitted 309 lesions to the teledermatologist (156 intervention; 153 control group). Intervention group participants were more likely to submit lesions from their legs compared to control (p=0.03), no other differences between groups in number or site of missed lesions.11 participants (22%) did not photograph 14 pigmented lesions the dermatologist considered worthwhile photographing or requiring clinical monitoring. Sensitivity of SSE plus mobile teledermoscopy was 81.8% (95% confidence interval 64.5-93.0) using the patient as the denominator and 41.9 (27.6-56.2) using the lesion as denominator.-There was substantial agreement between telediagnosis and CSE (Kappa =0.90) accounting for differential diagnoses. CONCLUSIONS SSE plus mobile teledermoscopy is promising for surveillance of particular lesions even without provision of detailed SSE instructions, but in the format tested in this study, consumers may overlook lesions and send many non-pigmented lesions. This investigation demonstrates that high quality dermoscopic images can be taken by patients at home and for those sent, telediagnosis is highly accurate.