Radiation therapist peer review: Raising the bar on quality and safety in radiation oncology

Purpose An emerging developmental tool to help radiation therapists achieve better outcomes is 'peer review'. This review of the current literature summarises the challenges and benefits of peer review in both individual and departmental practice. Discussion There is compelling evidence supporting peer review implementation at both individual and department level in many professions. Implementing peer review requires that radiation therapists and other radiation oncology professionals embrace a culture that supports safety. Peer review can identify trends and barriers associated with quality radiotherapy and share best practice or recommend changes accordingly. Support for peer review must come from pre-registration educational systems as well as clinical managers. Continuing professional development in the workplace is nurtured by peer review of radiotherapy practice and an aptitude for this should be viewed as important to the profession as technical and clinical skills. Conclusion It is clear that peer review has the potential to facilitate reflective practice, improve staff motivation and help foster a culture of quality and safety in radiation oncology. To drive the issues of quality and safety a step further radiation therapists need to accept the challenge of adopting peer review methods in day-to-day practice.

Female genital cutting : An overview of Australian legal principles, ethical controversies, and medical, legal and social challenges

Female genital cutting (also often called female genital mutilation, or female circumcision) is a cultural practice that originated thousands of years ago. Female genital cutting has various forms, some of which are more invasive than others, but all of which produce health, legal and social consequences for those involved. Due to patterns of immigration in Australia, especially since the 1990s, there are women in Australia who have experienced female genital cutting. There may be some families, or some parents, who still hold a cultural commitment to female genital cutting. As a result, female genital cutting presents complex legal, ethical, medical and social challenges in contemporary Australian society. Medical practitioners and other health and welfare workers may encounter women who have experienced genital cutting and who require treatment for its sequelae. Currently, legislative frameworks for female genital cutting vary across states and territories, including the penalties for conducting it, and for removing a child for the purpose of conducting it outside Australia. This presentation provides an overview of the history, nature and consequences of the various forms of female genital cutting, and of the major Australian legal principles, ethical controversies, and medical, legal and social challenges in this field.

The development and evaluation of a medical imaging training immersive environment

Introduction A novel realistic 3D virtual reality (VR) application has been developed to allow medical imaging students at Queensland University of Technology to practice radiographic techniques independently outside the usual radiography laboratory. Methods A flexible agile development methodology was used to create the software rapidly and effectively. A 3D gaming environment and realistic models were used to engender presence in the software while tutor-determined gold standards enabled students to compare their performance and learn in a problem-based learning pedagogy. Results Students reported high levels of satisfaction and perceived value and the software enabled up to 40 concurrent users to prepare for clinical practice. Student feedback also indicated that they found 3D to be of limited value in the desktop version compared to the usual 2D approach. A randomised comparison between groups receiving software-based and traditional practice measured performance in a formative role play with real equipment. The results of this work indicated superior performance with the equipment for the VR trained students (P = 0.0366) and confirmed the value of VR for enhancing 3D equipment-based problem-solving skills. Conclusions Students practising projection techniques virtually performed better at role play assessments than students practising in a traditional radiography laboratory only. The application particularly helped with 3D equipment configuration, suggesting that teaching 3D problem solving is an ideal use of such medical equipment simulators. Ongoing development work aims to establish the role of VR software in preparing students for clinical practice with a range of medical imaging equipment.

Psychological health of medical and dental students in Saudi Arabia : a longitudinal study

Introduction: Many studies have indicated the poor psychological health of medical and dental students. However, few studies have assessed the longitudinal trajectory of that psychological health at different times in an academic year. Aim: To evaluate the positive and negative aspects of psychological health among preclinical medical and dental students in Saudi Arabia prospectively. Methods: A total of 317 preclinical medical and dental students were recruited for a longitudinal study design from second and third-year students at Umm Al-Qura University in the 2012-2013 academic year. The students were assessed at the middle of the first term and followed up after 3-monthes at the beginning of the second term. Questionnaires included assessment of depression, anxiety, stress, self-efficacy, and satisfaction with life. Results: Depression, anxiety, stress, and satisfaction with life were improved significantly at the beginning of the second term, whereas self-efficacy did not change significantly. The medical, female, and third-year student subgroups had the most significant changes. Depression and stress were significantly changed at the beginning of the second term in most demographic subgroups. Conclusion: Preclinical medical and dental students have different psychological health levels at different times of the same academic year. It is recommended to consider time of data collection when analyzing the results of such studies.

Activation of forkhead box O transcription factors by oncogenic BRAF promotes p21cip1-dependent senescence

Oncogene-induced senescence (OIS) is a potent tumor-suppressive mechanism that is thought to come at the cost of aging. The Forkhead box O (FOXO) transcription factors are regulators of life span and tumor suppression. However, whether and how FOXOs function in OIS have been unclear. Here, we show a role for FOXO4 in mediating senescence by the human BRAFV600E oncogene, which arises commonly in melanoma. BRAFV600E signaling through mitogen-activated protein kinase/extracellular signal-regulated kinase kinase resulted in increased reactive oxygen species levels and c-Jun NH 2 terminal kinase-mediated activation of FOXO4 via its phosphorylation on Thr223, Ser226, Thr447, and Thr451. BRAFV600E-induced FOXO4 phosphorylation resulted in p21cip1-mediated cell senescence independent of p16 ink4a or p27kip1. Importantly, melanocyte-specific activation of BRAFV600E in vivo resulted in the formation of skin nevi expressing Thr223/Ser226-phosphorylated FOXO4 and elevated p21cip1. Together, these findings support a model in which FOXOs mediate a trade-off between cancer and aging.

Transcriptional pathway signatures predict MEK addiction and response to selumetinib (AZD6244)

Selumetinib (AZD6244, ARRY-142886) is a selective, non-ATP-competitive inhibitor of mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK)-1/2. The range of antitumor activity seen preclinically and in patients highlights the importance of identifying determinants of response to this drug. In large tumor cell panels of diverse lineage, we show that MEK inhibitor response does not have an absolute correlation with mutational or phospho-protein markers of BRAF/MEK, RAS, or phosphoinositide 3-kinase (PI3K) activity. We aimed to enhance predictivity by measuring pathway output through coregulated gene networks displaying differential mRNA expression exclusive to resistant cell subsets and correlated to mutational or dynamic pathway activity. We discovered an 18-gene signature enabling measurement of MEK functional output independent of tumor genotype. Where the MEK pathway is activated but the cells remain resistant to selumetinib, we identified a 13-gene signature that implicates the existence of compensatory signaling from RAS effectors other than PI3K. The ability of these signatures to stratify samples according to functional activation of MEK and/or selumetinib sensitivity was shown in multiple independent melanoma, colon, breast, and lung tumor cell lines and in xenograft models. Furthermore, we were able to measure these signatures in fixed archival melanoma tumor samples using a single RT-qPCR-based test and found intergene correlations and associations with genetic markers of pathway activity to be preserved. These signatures offer useful tools for the study of MEK biology and clinical application of MEK inhibitors, and the novel approaches taken may benefit other targeted therapies.

Identification of direct transcriptional targets of V600EBRAF/MEK signalling in melanoma

Oncogenic mutations in BRAF are common in melanoma and drive constitutive activation of the MEK/ERK pathway. To elucidate the transcriptional events downstream of V600EBRAF/MEK signalling we performed gene expression profiling of A375 melanoma cells treated with potent and selective inhibitors of V600EBRAF and MEK (PLX4720 and PD184352 respectively). Using a stringent Bayesian approach, we identified 69 transcripts that appear to be direct transcriptional targets of this pathway and whose expression changed after 6 h of pathway inhibition. We also identified several additional genes whose expression changed after 24 h of pathway inhibition and which are likely to be indirect transcriptional targets of the pathway. Several of these were confirmed by demonstrating their expression to be similarly regulated when BRAF was depleted using RNA interference, and by using qRT-PCR in other BRAF mutated melanoma lines. Many of these genes are transcription factors and feedback inhibitors of the ERK pathway and are also regulated by MEK signalling in NRAS mutant cells. This study provides a basis for understanding the molecular processes that are regulated by V600EBRAF/MEK signalling in melanoma cells.

Can bone tissue engineering contribute to therapy concepts after resection of musculoskeletal sarcoma?

Resection of musculoskeletal sarcoma can result in large bone defects where regeneration is needed in a quantity far beyond the normal potential of self-healing. In many cases, these defects exhibit a limited intrinsic regenerative potential due to an adjuvant therapeutic regimen, seroma, or infection. Therefore, reconstruction of these defects is still one of the most demanding procedures in orthopaedic surgery. The constraints of common treatment strategies have triggered a need for new therapeutic concepts to design and engineer unparalleled structural and functioning bone grafts. To satisfy the need for long-term repair and good clinical outcome, a paradigm shift is needed from methods to replace tissues with inert medical devices to more biological approaches that focus on the repair and reconstruction of tissue structure and function. It is within this context that the field of bone tissue engineering can offer solutions to be implemented into surgical therapy concepts after resection of bone and soft tissue sarcoma. In this paper we will discuss the implementation of tissue engineering concepts into the clinical field of orthopaedic oncology.

Engineered microenvironments provide new insights into ovarian and prostate cancer progression and drug responses

Tissue engineering technologies, which have originally been designed to reconstitute damaged tissue structure and function, can mimic not only tissue regeneration processes but also cancer development and progression. Bioengineered approaches allow cell biologists to develop sophisticated experimentally and physiologically relevant cancer models to recapitulate the complexity of the disease seen in patients. Tissue engineering tools enable three-dimensionality based on the design of biomaterials and scaffolds that re-create the geometry, chemistry, function and signalling milieu of the native tumour microenvironment. Three-dimensional (3D) microenvironments, including cell-derived matrices, biomaterial-based cell culture models and integrated co-cultures with engineered stromal components, are powerful tools to study dynamic processes like proteolytic functions associated with cancer progression, metastasis and resistance to therapeutics. In this review, we discuss how biomimetic strategies can reproduce a humanised niche for human cancer cells, such as peritoneal or bone-like microenvironments, addressing specific aspects of ovarian and prostate cancer progression and therapy response.

Social support, self-efficacy, trauma and well-being in emergency medical dispatchers

Emergency Medical Dispatchers (EMDs) respond to crisis calls for ambulance; they dispatch paramedics and provide emotional and medical assistance to callers. Despite the stressful nature and exposure to potentially traumatising events in this role, there has been no published research specifically investigating well-being or posttraumatic growth among EMDs. Extrapolating from research conducted among other emergency services workers (e. g., paramedics, police), literature attests to the importance of self efficacy and social support in promoting mental health in emergency service workers. Therefore, this study assessed the impact of self efficacy, and giving and receiving social support on psychological well-being, posttraumatic growth (PTG), and symptoms of posttraumatic stress disorder (PTSD). Sixty EMDs (50% response rate) completed an online questionnaire. Three hierarchical multiple regression analyses were conducted to ascertain predictors of well-being, PTG and PTSD. Receiving social support emerged as a significant positive predictor of well-being and PTG, and a significant negative predictor of PTSD. Self efficacy was found to significantly and positively predict well-being, and shift-work was found to significantly and negatively predict PTSD. These results highlight that self efficacy and receiving social support are likely to be important for enhancing well-being within this population, and that receiving social support is also likely to facilitate positive post-trauma responses. Such findings have implications for the way emergency service personnel are educated with reference to aspects of mental health and how best to support personnel in order to achieve optimal mental health outcomes for all.

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.

Ethical values in emergency medical services: A pilot study

Background Ambulance professionals often address conflicts between ethical values. As individuals’ values represent basic convictions of what is right or good and motivate behaviour, research is needed to understand their value profiles. Objectives To translate and adapt the Managerial Values Profile to Spanish and Swedish, and measure the presence of utilitarianism, moral rights and/or social justice in ambulance professionals’ value profiles in Spain and Sweden. Methods The instrument was translated and culturally adapted. A content validity index was calculated. Pilot tests were carried out with 46 participants. Ethical considerations This study conforms to the ethical principles for research involving human subjects and adheres to national laws and regulations concerning informed consent and confidentiality. Findings Spanish professionals favoured justice and Swedish professionals’ rights in their ambulance organizations. Both countries favoured utilitarianism least. Gender differences across countries showed that males favoured rights. Spanish female professionals favoured justice most strongly of all. Discussion Swedes favour rights while Spaniards favour justice. Both contexts scored low on utilitarianism focusing on total population effect, preferring the opposite, individualized approach of the rights and justice perspectives. Organizational investment in a utilitarian perspective might jeopardize ambulance professionals’ moral right to make individual assessments based on the needs of the patient at hand. Utilitarianism and a caring ethos appear as stark opposites. However, a caring ethos in its turn might well involve unreasonable demands on the individual carer’s professional role. Since both the justice and rights perspectives portrayed in the survey mainly concern relationship to the organization and peers within the organization, this relationship might at worst be given priority over the equal treatment and moral rights of the patient. Conclusion A balanced view on ethical perspectives is needed to make professionals observant and ready to act optimally – especially if these perspectives are used in patient care. Research is needed to clarify how justice and rights are prioritized by ambulance services and whether or not these organization-related values are also implemented in patient care.

Outcomes in gastric and junctional cancer using neoadjuvant and adjuvant chemotherapy (epirubicin, oxaliplatin, and capecitabine) and radical surgery

Background The MAGIC/UK Medical Research Council (MRC) trial set the standard of care for treatment of resectable gastric and junctional adenocarcinoma, demonstrating that perioperative chemotherapy with epirubicin, cisplatin and 5-fluorouracil (ECF) confers a survival benefit over surgery alone. The randomized ECF for advanced and locally advanced esophagogastric cancer (REAL-2) trial showed that, in the metastatic setting, the EOX regimen (epirubicin, oxaliplatin and capecitabine) is as effective as ECF, with a favourable toxicity profile. Methods Consecutive patients with resectable gastric or junctional adenocarcinoma treated with perioperative EOX, between 2007 and 2012, were retrospectively analysed. Results Fifty-nine patients (12 female, 47 male), commenced EOX therapy; 47 underwent surgery. A good pathological response was seen in 34 %, (16/47). Disease recurrence occurred in 19 patients (19/47, 40 %). Median overall survival was 22 months, with 4-year survival of 47 %. Chemotoxicities were consistent with those previously reported for this regimen. Conclusion This study in a high-volume centre demonstrates that EOX in resectable gastric and junctional adenocarcinoma is associated with a reasonable safety profile, and efficacy consistent with that reported for ECF.

Prevalence and clinical outcomes for patients with ALK-positive resected stage I to III adenocarcinoma : results from the European Thoracic Oncology Platform Lungscape Project

PURPOSE: The prevalence of anaplastic lymphoma kinase (ALK) gene fusion (ALK positivity) in early-stage non-small-cell lung cancer (NSCLC) varies by population examined and detection method used. The Lungscape ALK project was designed to address the prevalence and prognostic impact of ALK positivity in resected lung adenocarcinoma in a primarily European population. METHODS: Analysis of ALK status was performed by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) in tissue sections of 1,281 patients with adenocarcinoma in the European Thoracic Oncology Platform Lungscape iBiobank. Positive patients were matched with negative patients in a 1:2 ratio, both for IHC and for FISH testing. Testing was performed in 16 participating centers, using the same protocol after passing external quality assessment. RESULTS: Positive ALK IHC staining was present in 80 patients (prevalence of 6.2%; 95% CI, 4.9% to 7.6%). Of these, 28 patients were ALK FISH positive, corresponding to a lower bound for the prevalence of FISH positivity of 2.2%. FISH specificity was 100%, and FISH sensitivity was 35.0% (95% CI, 24.7% to 46.5%), with a sensitivity value of 81.3% (95% CI, 63.6% to 92.8%) for IHC 2+/3+ patients. The hazard of death for FISH-positive patients was lower than for IHC-negative patients (P = .022). Multivariable models, adjusted for patient, tumor, and treatment characteristics, and matched cohort analysis confirmed that ALK FISH positivity is a predictor for better overall survival (OS). CONCLUSION: In this large cohort of surgically resected lung adenocarcinomas, the prevalence of ALK positivity was 6.2% using IHC and at least 2.2% using FISH. A screening strategy based on IHC or H-score could be envisaged. ALK positivity (by either IHC or FISH) was related to better OS.