Thymidylate synthase expression and outcome of patients receiving pemetrexed for advanced nonsquamous non-small-cell lung cancer in a prospective blinded assessment phase II clinical trial

INTRODUCTION In retrospective analyses of patients with nonsquamous non-small-cell lung cancer treated with pemetrexed, low thymidylate synthase (TS) expression is associated with better clinical outcomes. This phase II study explored this association prospectively at the protein and mRNA-expression level. METHODS Treatment-naive patients with nonsquamous non-small-cell lung cancer (stage IIIB/IV) had four cycles of first-line chemotherapy with pemetrexed/cisplatin. Nonprogressing patients continued on pemetrexed maintenance until progression or maximum tolerability. TS expression (nucleus/cytoplasm/total) was assessed in diagnostic tissue samples by immunohistochemistry (IHC; H-scores), and quantitative reverse-transcriptase polymerase chain reaction. Cox regression was used to assess the association between H-scores and progression-free/overall survival (PFS/OS) distribution estimated by the Kaplan-Meier method. Maximal χ analysis identified optimal cutpoints between low TS- and high TS-expression groups, yielding maximal associations with PFS/OS. RESULTS The study enrolled 70 patients; of these 43 (61.4%) started maintenance treatment. In 60 patients with valid H-scores, median (m) PFS was 5.5 (95% confidence interval [CI], 3.9-6.9) months, mOS was 9.6 (95% CI, 7.3-15.7) months. Higher nuclear TS expression was significantly associated with shorter PFS and OS (primary analysis IHC, PFS: p < 0.0001; hazard ratio per 1-unit increase: 1.015; 95%CI, 1.008-1.021). At the optimal cutpoint of nuclear H-score (70), mPFS in the low TS- versus high TS-expression groups was 7.1 (5.7-8.3) versus 2.6 (1.3-4.1) months (p = 0.0015; hazard ratio = 0.28; 95%CI, 0.16-0.52; n = 40/20). Trends were similar for cytoplasm H-scores, quantitative reverse-transcriptase polymerase chain reaction and other clinical endpoints (OS, response, and disease control). CONCLUSIONS The primary endpoint was met; low TS expression was associated with longer PFS. Further randomized studies are needed to explore nuclear TS IHC expression as a potential biomarker of clinical outcomes for pemetrexed treatment in larger patient cohorts. © 2013 by the International Association for the Study of Lung Cancer.

Objectifying the Subjective : Assessment and Feedback in Creative Arts Studio Learning and Teaching

This paper examines the Assessment and Feedback aspects of Studio Teaching as Creative Arts pedagogy. Prompted by USQ’s newly offered Bachelor of Creative Arts (BCA), the author has developed an Assessment Matrix specifically designed to satisfy a number of imperatives, including: • ‘objectifying’ the subjective aspects of creative practice as assessable coursework/research • providing the means by which accurate, detailed, personalised and confidential feedback may be provided to students individually • providing consistent, accurate, meaningful assessment records for student, lecturer, and institution • ensuring consistency, continuity, and transparency of assessment processes and records to satisfy quality audits • minimising marking and assessment time, whilst maximising assessment integrity and depth • requiring only basic level skills and knowledge of a computer application already in common use (Microsoft Excel) • adaptability to a range of creative courses ‐ across disciplines This Assessment Matrix has been in development (and trialled) since January 2009.

Honesty about adverse events - more honoured in the breach than in the observance

The medical board of Australia Code of conduct reminds doctors that" "When adverse events occur, you have a responsibility to be open and honest in your communication with your patient, to review what has occurred and to report appropriately." More honoured in the breach rather than the observence may or may not be correct. Faced with the English concerns and the Netherlands research, an evidence based assessment of compliance with the ethical duty to disclose adverse events is warranted.

Hospital liability for sexual assault of a patient

Hospital liability for alleged sexual assault upon a medicated patient by an orderly - non-delegable duty owed by a hospital to its patients - vicarious liability - liability for criminal conduct by employer - recruitment processes - assessment of damages.

A comparative analysis of risk stratification tools for emergency department patients with chest pain

Background: Appropriate disposition of emergency department (ED) patients with chest pain is dependent on clinical evaluation of risk. A number of chest pain risk stratification tools have been proposed. The aim of this study was to compare the predictive performance for major adverse cardiac events (MACE) using risk assessment tools from the National Heart Foundation of Australia (HFA), the Goldman risk score and the Thrombolysis in Myocardial Infarction risk score (TIMI RS). Methods: This prospective observational study evaluated ED patients aged ≥30 years with non-traumatic chest pain for which no definitive non-ischemic cause was found. Data collected included demographic and clinical information, investigation findings and occurrence of MACE by 30 days. The outcome of interest was the comparative predictive performance of the risk tools for MACE at 30 days, as analyzed by receiver operator curves (ROC). Results: Two hundred eighty-one patients were studied; the rate of MACE was 14.1%. Area under the curve (AUC) of the HFA, TIMI RS and Goldman tools for the endpoint of MACE was 0.54, 0.71 and 0.67, respectively, with the difference between the tools in predictive ability for MACE being highly significant [chi2 (3) = 67.21, N = 276, p < 0.0001]. Conclusion: The TIMI RS and Goldman tools performed better than the HFA in this undifferentiated ED chest pain population, but selection of cutoffs balancing sensitivity and specificity was problematic. There is an urgent need for validated risk stratification tools specific for the ED chest pain population.

The radiation therapy patient as a student assessor

Background Radiation Therapy students at Queensland University of Technology undertake clinical placement across a wide range of sites Interpersonal skills with clinical staff and patients are an essential component: – Lectures – Role playing – Expert patient input

The competent prescriber: 12 core competencies for safe prescribing

Prescribing errors remain a significant cause of patient harm. Safe prescribing is not just about writing a prescription, but involves many cognitive and decision-making steps. A set of national prescribing competencies for all prescribers (including non-medical) is needed to guide education and training curricula, assessment and credentialing of individual practitioners. We have identified 12 core competencies for safe prescribing which embody the four stages of the prescribing process – information gathering, clinical decision making, communication, and monitoring and review. These core competencies, along with their learning objectives and assessment methods, provide a useful starting point for teaching safe and effective prescribing.

Assessment of diabetic neuropathy using novel corneal markers.

Diabetic peripheral neuropathy is a debilitating condition that affects approximately 50 per cent of diabetic patients. The symptoms of neuropathy include numbness and tingling or pain in the arms and legs. If left untreated, patients with numbness might develop foot ulcers, which might ultimately require foot amputation. Currently the only method of directly examining peripheral nerves is to conduct skin punch biopsies, which are uncomfortable and invasive.

Nutrition screening and assessment in Parkinson's disease : a comparison of methods

Background & Aims Nutrition screening and assessment enable early identification of malnourished people and those at risk of malnutrition. Appropriate assessment tools assist with informing and monitoring nutrition interventions. Tool choice needs to be appropriate to the population and setting. Methods Community-dwelling people with Parkinson’s disease (>18 years) were recruited. Body mass index (BMI) was calculated from weight and height. Participants were classified as underweight according to World Health Organisation (WHO) (≤18.5kg/m2) and age specific (<65 years,≤18.5kg/m2; ≥65 years,≤23.5kg/m2) cut-offs. The Mini-Nutritional Assessment (MNA) screening (MNA-SF) and total assessment scores were calculated. The Patient-Generated Subjective Global Assessment (PG-SGA), including the Subjective Global Assessment (SGA), was performed. Sensitivity, specificity, positive predictive value, negative predictive value and weighted kappa statistic of each of the above compared to SGA were determined. Results Median age of the 125 participants was 70.0(35-92) years. Age-specific BMI (Sn 68.4%, Sp 84.0%) performed better than WHO (Sn 15.8%, Sp 99.1%) categories. MNA-SF performed better (Sn 94.7%, Sp 78.3%) than both BMI categorisations for screening purposes. MNA had higher specificity but lower sensitivity than PG-SGA (MNA Sn 84.2%, Sp 87.7%; PG-SGA Sn 100.0%, Sp 69.8%). Conclusions BMI lacks sensitivity to identify malnourished people with Parkinson’s disease and should be used with caution. The MNA-SF may be a better screening tool in people with Parkinson’s disease. The PG-SGA performed well and may assist with informing and monitoring nutrition interventions. Further research should be conducted to validate screening and assessment tools in Parkinson’s disease.  

The consultative process used in outreach : a narrative account

Aim The aim of this paper was to provide a narrative account of the communication skills used in an effective outreach consultation utilizing Neighbour’s consultative model. Other consultation models were considered; however, because of their overly comprehensive approach or emphasis on behaviour modification, these were deemed inappropriate. Background The nursing profession has endured significant changes of late and as a result is developing more autonomous roles in both the community and the acute health care settings. In the past, the term consultancy was used within the medical context; nowadays, there are advance nurse practitioners for whom consultancy is an integral part of their role. Although every nursing interaction is in essence a consultation, the fact that nurses are taking up on new advanced roles highlights the necessity for nurses to develop their consultation skills even further. Therefore, it makes sense to explore what aspects of that consultancy role needs special consideration in order to ensure that positive outcomes are achieved. Conclusions This paper has used a narrative account to uncover those salient skills needed to enhance the therapeutic relationship with a patient requiring the services of outreach. Furthermore, the application of a recognized consultation model was used to elucidate the underpinning knowledge of systematic history taking and assessment as well as demonstrating the communication skills and strategies needed to increase the patient’s participation and empowerment throughout the consultation. Relevance to clinical practice Effective communication skills encompassed in a consultative model are integral to the success in safeguarding the well-being of patients requiring advanced levels of care. Prejudging or pre-empting information being conveyed can be detrimental to patient safety and may prolong or complicate treatment plans.

Sedation breaks : are they good for the critically ill patient? A review.

Background:  Tradition has led us to believe that a heavily sedated patient is a comfortable, settled, compliant patient for whom sedation will improve outcome. The current move witnessed in clinical practice today of limiting sedation has led health care in recent years to question the benefit and necessity of routine, continuous sedation for all patients requiring mechanical ventilation. However, as a result there has been a rise in the amount of agitation being reported as being experienced by patients with the daily withdrawal of sedation. Aims:  The purpose of this paper is to review current arguments for and against perserving with agitation versus re-sedating, when it presents during the daily sedation breaks. Findings:  Of the literature reviewed, the question to re-sedate the mechanically ventilated agitated patient during sedation breaks remains an issue of contention. Although there is evidence focusing on the psychological effects of long-term sedation and sedation breaks specifically, the complex nature of critical illness in some cases means that individualized care is of paramount importance and in-depth assessment is crucial when deciding to re-sedate in the face of undetermined agitation. Agitation has been closely linked with several incidents that can be detrimental to patient safety, such as removal of lines and unplanned self-extubation. Conclusion:  The recommendations of this review are that nurses should re-commence sedation if the patient becomes agitated following a sedation break. Aims:  The purpose of this paper is to review current arguments for and against perserving with agitation versus re-sedating, when it presents during the daily sedation breaks. Findings:  Of the literature reviewed, the question to re-sedate the mechanically ventilated agitated patient during sedation breaks remains an issue of contention. Although there is evidence focusing on the psychological effects of long-term sedation and sedation breaks specifically, the complex nature of critical illness in some cases means that individualized care is of paramount importance and in-depth assessment is crucial when deciding to re-sedate in the face of undetermined agitation. Agitation has been closely linked with several incidents that can be detrimental to patient safety, such as removal of lines and unplanned self-extubation. Conclusion:  The recommendations of this review are that nurses should re-commence sedation if the patient becomes agitated following a sedation break.

End-of-life care in the intensive care unit : a systematic review of qualitative studies investigating the experiences and perceptions of the patient's family

Review question/objective The review objective is to synthesise the best available evidence on experiences and perceptions of family members of intensive care unit patients on the adequacy of end-of-life care, where life-support modalities have been withheld or withdrawn. Inclusion criteria Types of participants This review will consider studies that report on the experiences and perceptions of patients’ families on EOLC in the ICU, where life-support modalities have been withheld or withdrawn. The family is defined as “those who are closest to the patient... the family may include the biological family, family by acquisition, and the family of choice and friends”. Phenomena of interest The phenomena of interest for this review are the patients’ families experiences, perceptions or views on the adequacy of EOLC delivered in the ICU, where life-support modalities were withheld or withdrawn. These experiences may refer to the following views on domains of care considered important at the end-of-life in the ICU, which have been described already in the existing literature: timely, consistent, and compassionate communication, clinician availability, clinical decision making based on patients’ preferences, goals and values, physical care implemented to maintain patient comfort, holistic interdisciplinary care and bereavement care for families of patients who died.

Analysis of distance learner value assessment of distance education in engineering

Numerous research studies have evaluated whether distance learning is a viable alternative to traditional learning methods. These studies have generally made use of cross-sectional surveys for collecting data, comparing distance to traditional learners with intent to validate the former as a viable educational tool. Inherent fundamental differences between traditional and distance learning pedagogies, however, reduce the reliability of these comparative studies and constrain the validity of analyses resulting from this analytical approach. This article presents the results of a research project undertaken to analyze expectations and experiences of distance learners with their degree programs. Students were given surveys designed to examine factors expected to affect their overall value assessment of their distance learning program. Multivariate statistical analyses were used to analyze the correlations among variables of interest to support hypothesized relationships among them. Focusing on distance learners overcomes some of the limitations with assessments that compare off- and on-campus student experiences. Evaluation and modeling of distance learner responses on perceived value for money of the distance education they received indicate that the two most important influences are course communication requirements, which had a negative effect, and course logistical simplicity, which revealed a positive effect. Combined, these two factors accounted for approximately 47% of the variability in perceived value for money of the educational program of sampled students. A detailed focus on comparing expectations with outcomes of distance learners complements the existing literature dominated by comparative studies of distance and nondistance learners.

Geometric sensitivity of patient-specific finite element models of the spine to variability in user-selected anatomical landmarks

Software to create individualised finite element (FE) models of the osseoligamentous spine using pre-operative computed tomography (CT) data-sets for spinal surgery patients has recently been developed. This study presents a geometric sensitivity analysis of this software to assess the effect of intra-observer variability in user-selected anatomical landmarks. User-selected landmarks on the osseous anatomy were defined from CT data-sets for three scoliosis patients and these landmarks were used to reconstruct patient-specific anatomy of the spine and ribcage using parametric descriptions. The intra-observer errors in landmark co-ordinates for these anatomical landmarks were calculated. FE models of the spine and ribcage were created using the reconstructed anatomy for each patient and these models were analysed for a loadcase simulating clinical flexibility assessment. The intra-observer error in the anatomical measurements was low in comparison to the initial dimensions, with the exception of the angular measurements for disc wedge and zygapophyseal joint (z-joint) orientation and disc height. This variability suggested that CT resolution may influence such angular measurements, particularly for small anatomical features, such as the z-joints, and may also affect disc height. The results of the FE analysis showed low variation in the model predictions for spinal curvature with the mean intra-observer variability substantially less than the accepted error in clinical measurement. These findings demonstrate that intra-observer variability in landmark point selection has minimal effect on the subsequent FE predictions for a clinical loadcase.