Does a communication skills program enable symptom and distress screening?: The impact of training on radiation therapists' confidence, knowledge, and use of distress screening.

INTRODUCTION: Due to the prevalence of distress following a cancer diagnosis, routine symptom and distress screening is recommended as best practice. RTs perceive psychosocial support and screening to be part of their role, however feel they lack the education and skills to perform this confidently. The study aimed to evaluate the impact of providing communication skills training (RT Prepare CST) on the perceived barriers, knowledge, attitude, role, and confidence of radiation therapists (RTs) in using routine symptom and distress screening. METHODS: A single-arm, pre-post intervention design was implemented. All RTs at one regional and one rural centre participated in RT Prepare CST. RTs completed a questionnaire: pre-intervention (T1); immediately post-intervention (T2); and, three months post-intervention (T3). Cochran's Q and McNemar's tests for non-parametric data were conducted to compare outcomes over time. RESULTS: Of 39 RTs approached, 37 (95%) consented to participate with 36 (92%) completing questionnaires at all three time points. Significant and sustained improvements post-intervention were noted from T1-T3 including: confidence in describing the PROMPT-Care tool to patients (p=0.002), discussing psychosocial issues (p=0.014); recognising signs of anxiety/depression (p<0.001); dealing with signs of anxiety (p=0.002), depression (p=0.015) and distress (p=0.008) as well as agreeing 'the tool is useful in identifying psychosocial problems' (p=0.029). CONCLUSIONS: RT Prepare CST was effective in increasing confidence, knowledge and attitudes of RTs in the psychosocial care of patients with a change in RT behaviour noted by a significant increase in the number of patients screened following the intervention. Providing routine CST and emotional cues training to RTs enhances their ability to care for patients holistically, equipping them with skills to be included within a psychosocial model of care. Engaged leadership and role models are essential to sustain the learnings from education programs and provide an environment to discuss and define roles within radiation therapy departments.

Traumatic pseudoaneurysm of the superficial temporal artery.

Pseudoaneurysm of the superficial temporal artery is rare. It is typically caused by blunt force to the temporal region, and presents as a painless, preauricular, pulsatile mass during the following weeks. We think that its infrequent incidence and unusual presentation warrants an increase in awareness to aid accurate and timely diagnosis. We present a case that developed a few weeks after a head injury, and its subsequent management.

Co-culture of chondrons and mesenchymal stromal cells reduces the loss of collagen VI and improves extracellular matrix production.

Adult articular chondrocytes are surrounded by a pericellular matrix (PCM) to form a chondron. The PCM is rich in hyaluronan, proteoglycans, and collagen II, and it is the exclusive location of collagen VI in articular cartilage. Collagen VI anchors the chondrocyte to the PCM. It has been suggested that co-culture of chondrons with mesenchymal stromal cells (MSCs) might enhance extracellular matrix (ECM) production. This co-culture study investigates whether MSCs help to preserve the PCM and increase ECM production. Primary bovine chondrons or chondrocytes or rat MSCs were cultured alone to establish a baseline level for ECM production. A xenogeneic co-culture monolayer model using rat MSCs (20, 50, and 80%) was established. PCM maintenance and ECM production were assessed by biochemical assays, immunofluorescence, and histological staining. Co-culture of MSCs with chondrons enhanced ECM matrix production, as compared to chondrocyte or chondron only cultures. The ratio 50:50 co-culture of MSCs and chondrons resulted in the highest increase in GAG production (18.5 ± 0.54 pg/cell at day 1 and 11 ± 0.38 pg/cell at day 7 in 50:50 co-culture versus 16.8 ± 0.61 pg/cell at day 1 and 10 ± 0.45 pg/cell at day 7 in chondron monoculture). The co-culture of MSCs with chondrons appeared to decelerate the loss of the PCM as determined by collagen VI expression, whilst the expression of high-temperature requirement serine protease A1 (HtrA1) demonstrated an inverse relationship to that of the collagen VI. Together, this implies that MSCs directly or indirectly inhibited HtrA1 activity and the co-culture of MSCs with chondrons enhanced ECM synthesis and the preservation of the PCM.

The impact of a perceptual and adaptive learning module on transoesophageal echocardiography interpretation by anaesthesiology residents.

BACKGROUND: The role of transoesophageal echocardiography (TOE) in anaesthetic practice is expanding. We evaluated the effect of a TOE perceptual and adaptive learning module (PALM) on first-yr anaesthesiology residents' performance, in diagnosing cardiac pathology by TOE. METHODS: First-yr residents were assigned to a group (n = 12) that used a TOE PALM or a control group that did not (n = 12). Both groups received a TOE pretest that measured their accuracy and response times. The PALM group completed the PALM and a posttest within 30 min and a delayed test six months later. The control group received a delayed test six months after their pretest. Accuracy and fluency (accurate responses within 10 s) were measured. RESULTS: The PALM group had statistically significant improvements for both accuracy and fluency (P < 0.0001) in diagnosing cardiac pathology by TOE. After six months, the PALM group's performance remained significantly higher than their pretest values for accuracy (P = 0.0002, d = 2.7) and fluency (P < 0.0001, d = 2.3). CONCLUSIONS: In this pilot study, exposure to a PALM significantly improved accuracy and fluency in diagnosing TOE cardiac pathology, in a group of first-year anaesthesiology residents. PALMs can significantly improve learning and pattern recognition in medical education.

Study investigating the role of skeletal muscle mass estimation in metastatic spinal cord compression.

BACKGROUND: Age-related loss of functional muscle mass is associated with reduced functional ability and life expectancy. In disseminated cancer, age-related muscle loss may be exacerbated by cachexia and poor nutritional intake, increasing functional decline, morbidity and accelerate death. Patients with spinal metastases frequently present for decompressive surgery with decision to operate based upon functional assessment. A subjective assessment of physical performance has, however, been shown to be a poor indicator of life expectancy in these patients. We aimed to develop an objective measure based upon lean muscle mass to aid decision making, in these individuals, by investigating the association between muscle mass and 1-year survival. METHODS: Muscle mass was calculated as total psoas area (TPA)/ vertebral body area (VBA), by two independent blinded doctors from CT images, acquired within 7 days of spinal metastases surgery, at the mid L3 vertebral level. Outcome at 1 year following surgery was recorded from a prospectively updated metastatic spinal cord compression database. RESULTS: 86 patients were followed for 1 year, with an overall mortality of 39.5%. Mortality rates at 1 year were significantly high among patients in the lowest quartile of muscle mass, compared with those in the highest quartile (57.1 vs 23.8%, p=0.02). CONCLUSION: Death within 1 year in individuals with spinal metastases is related to lean muscle mass at presentation. Assessment of lean muscle mass may inform decision to operate in patients with spinal metastases.

Postoperative atrial fibrillation in liver transplantation.

Postoperative atrial fibrillation (POAF) is common after major surgeries and is associated with increased morbidity and mortality. POAF after liver transplantation (LT) has not been reported. This study was undertaken to investigate the incidence, impact, and risk factors of POAF in LT patients. After IRB approval, LT between January 2006 and August 2013 at our center were retrospectively reviewed. POAF that occurred within 30 days after LT was included. Patients with and without POAF were compared and independent risk factors were identified by logistic regression. Of 1387 adults LT patients, 102 (7.4%) developed POAF during the study period. POAF was associated with significantly increased mortality, graft failure, acute kidney injury and prolonged hospital stay. Independent risk factors included age, body weight, MELD score, presence of previous history of AF, the vasopressors use prior to LT and pulmonary artery diastolic pressure at the end of LT surgery (odds ratios 2.0-7.2, all p < 0.05). A risk index of POAF was developed and patients with the high-risk index had more than 60% chance of developing POAF. These findings may be used to stratify patients and to guide prophylaxis for POAF in the posttransplant period.

PR55α-containing protein phosphatase 2A complexes promote cancer cell migration and invasion through regulation of AP-1 transcriptional activity.

The proto-oncogene c-Jun is a component of activator protein-1 (AP-1) transcription factor complexes that regulates processes essential for embryonic development, tissue homeostasis and malignant transformation. Induction of gene expression by c-Jun involves stimulation of its transactivation ability and upregulation of DNA binding capacity. While it is well established that the former requires JNK-mediated phosphorylation of S63/S73, the mechanism(s) through which binding of c-Jun to its endogenous target genes is regulated remains poorly characterized. Here we show that interaction of c-Jun with chromatin is positively regulated by protein phosphatase 2A (PP2A) complexes targeted to c-Jun by the PR55α regulatory subunit. PR55α-PP2A specifically dephosphorylates T239 of c-Jun, promoting its binding to genes regulating tumour cell migration and invasion. PR55α-PP2A also enhanced transcription of these genes, without affecting phosphorylation of c-Jun on S63. These findings suggest a critical role for interplay between JNK and PP2A pathways determining the functional activity of c-Jun/AP-1 in tumour cells.

FRA-1 as a driver of tumour heterogeneity: a nexus between oncogenes and embryonic signalling pathways in cancer.

Tumour heterogeneity is a major factor undermining the success of therapies targeting metastatic cancer. Two major theories are thought to explain the phenomenon of heterogeneity in cancer--clonal evolution and cell plasticity. In this review, we examine a growing body of work implicating the transcription factor FOS-related antigen 1 (FRA-1) as a central node in tumour cell plasticity networks, and discuss mechanisms regulating its activity in cancer cells. We also discuss evidence from the FRA-1 perspective supporting the notion that clonal selection and cell plasticity represent two sides of the same coin. We propose that FRA-1-overexpressing clones featuring high plasticity undergo positive selection during consecutive stages of multistep tumour progression. This model underscores a potential mechanism through which tumour cells retaining elevated levels of plasticity acquire a selective advantage over other clonal populations within a tumour.

Liver transplantation in recipients receiving renal replacement therapy: outcomes analysis and the role of intraoperative hemodialysis.

The Model for End-Stage Liver Disease (MELD) system has dramatically increased the number of recipients requiring pretransplant renal replacement therapy (RRT) prior to liver transplantation (LT). Factors affecting post-LT outcomes and the need for intraoperative RRT (IORRT) were analyzed in 500 consecutive recipients receiving pretransplant RRT, including comparisons among recipients not receiving IORRT (No-IORRT, n = 401), receiving planned IORRT (Pl-IORRT, n = 70), and receiving emergent, unplanned RRT after LT initiation (Em-IORRT, n = 29). Despite a median MELD of 39, overall 30-day, 1-, 3- and 5-year survivals were 93%, 75%, 68% and 65%, respectively. Em-IORRT recipients had significantly more intraoperative complications (arrhythmias, postreperfusion syndrome, coagulopathy) compared with both No-IORRT and Pl-IORRT and greater 30-day graft loss (28% vs. 10%, p = 0.004) and need for retransplantation (24% vs. 10%, p = 0.099) compared with No-IORRT. A risk score based on multivariate predictors of IORRT accurately identified recipients with chronic (sensitivity 84%, specificity 72%, concordance-statistic [c-statistic] 0.829) and acute (sensitivity 93%, specificity 61%, c-statistic 0.776) liver failure requiring IORRT. In this largest experience of LT in recipients receiving RRT, we report excellent survival and propose a practical model that accurately identifies recipients who may benefit from IORRT. For this select group, timely initiation of IORRT reduces intraoperative complications and improves posttransplant outcomes.

Methotrexate and liver fibrosis in people with psoriasis: a systematic review of observational studies.

Methotrexate (MTX) is an effective treatment for psoriasis but concerns regarding the development of liver fibrosis prevent optimal use. The primary objective of this systematic review was to assess whether MTX use increases the risk of developing fibrosis in people with psoriasis. Searches were performed on Medline, Embase, the Cochrane Database and Clinical Trials Register from inception until September 2013 for studies including at least two liver biopsies in people with psoriasis. Double extraction using predefined data fields was performed. Randomized controlled trials and observational studies were considered. Statistical analysis was performed using Review Manager 5. Quality of observational studies was assessed using a study quality bias checklist. Eight observational studies met the inclusion criteria (n = 429 patients). The pooled risk difference (RD) of developing significant liver fibrosis was 0·09 [95% confidence interval (CI) -0·03 to 0·20]. The RD for developing 'any fibrosis' was 0·22 (95% CI 0·04-0·41). The RD for cirrhosis was 0·04 (95% CI 0·02-0·07). There was no clear association between cumulative dose of MTX and fibrosis. Obesity, diabetes and alcohol use were under-reported. The quality of the included studies was weak and the degree of selection bias means the results are not generalizable to all patients with psoriasis taking MTX. High-quality, population-based studies that consider potential confounders common in psoriasis population are justified for better prediction of the subset of patients at risk of liver fibrosis. In this highly selected review population, MTX use appears to contribute to the development of 'any' fibrosis without clear evidence of risk stratifiers.

Reduced fibrosis in recurrent HCV with tacrolimus, azathioprine and steroids versus tacrolimus: randomised trial long term outcomes.

OBJECTIVE: Early results of a randomised trial showed reduced fibrosis due to recurrent HCV hepatitis with tacrolimus triple therapy (TT) versus monotherapy (MT) following transplantation for HCV cirrhosis. We evaluated the clinical outcomes after a median 8 years of follow-up, including differences in fibrosis assessed by collagen proportionate area (CPA). DESIGN: 103 consecutive liver transplant recipients with HCV cirrhosis receiving cadaveric grafts were randomised to tacrolimus MT (n=54) or TT (n=49) with daily tacrolimus (0.1 mg/kg divided dose), azathioprine (1 mg/kg) and prednisolone (20 mg), the last tailing off to zero by 6 months. Both groups had serial transjugular biopsies with hepatic venous pressure gradient (HVPG) measurement. Time to reach Ishak stage 4 was the predetermined endpoint. CPA was measured in all biopsies. Factors associated with HCV recurrence were evaluated. Clinical decompensation was the first occurrence of ascites/hydrothorax, variceal bleeding or encephalopathy. RESULTS: No significant preoperative, peri-operative or postoperative differences between groups were found. During 96 months median follow-up, stage 4 fibrosis was reached in 19 MT/11 TT with slower fibrosis progression in TT (p=0.009). CPA at last biopsy was 12% in MT and 8% in TT patients (p=0.004). 14 MT/ three TT patients reached HVPG≥10 mm Hg (p=0.002); 10 MT/three TT patients, decompensated. Multivariately, allocated MT (p=0.047, OR 3.23, 95% CI 1.01 to 10.3) was independently associated with decompensation: 14 MT/ seven TT died, and five MT/ four TT were retransplanted. CONCLUSIONS: Long term immunosuppression with tacrolimus, azathioprine and short term prednisolone in HCV cirrhosis recipients resulted in slower progression to severe fibrosis assessed by Ishak stage and CPA, less portal hypertension and decompensation, compared with tacrolimus alone. ISRCTN94834276--Randomised study for immunosuppression regimen in liver transplantation.

Right salpingo-ovarian and distal ileal entrapment within a paracaecal hernia presenting as acute appendicits.

INTRODUCTION: Pericaecal hernias are a rare subgroup of internal abdominal hernias that present with abdominal pain and occasionally with features of bowel obstruction. PRESENTATION OF CASE: A 72 year old female presented with a 24-h history of sharp, localised right iliac fossa pain, and no other symptoms. Clinical examination confirmed localised peritonism in the right iliac fossa. A tentative diagnosis of acute appendicitis was considered but in view of age a CT scan was performed. An area of abnormality in the right iliac fossa region was noted. At laparoscopy a macroscopically normal appendix and caecum was found. A smooth non-indentable mass in the lateral right iliac fossa contained loops of distal ileum, passing through a retro-caecal mesenteric defect consistent with a paraceacal hernia, with entrapment of the right ovary and fallopian tube. A right salpingectomy as performed and subsequent histopathological examination confirmed infarction of the fallopian tube. DISCUSSION: Internal abdominal hernias are reported to have a post mortem incidence ranging between 0.2 and 0.9% of which only 10-15% are accounted for by pericaecal hernias. Types of pericaecal hernias include: ileocolic, retrocaecal, ileocaecal and paracaecal. These hernias are predisposed by the embryological development of the caecum retracting to the posterior abdominal wall and forming potential fossae. CONCLUSION: This case highlights the need to consider a pericaecal hernia as a differential cause of right iliac fossa peritonism, and an indication for radiological imaging such as CT scan when the history is atypical for acute appendicitis.

Avian mycobacteriosis in psittacines: a retrospective study of 123 cases.

One hundred and twenty-three cases of mycobacterioses were diagnosed in psittacine birds from a total of 9,241 submissions for necropsy examination or histopathology made to the California Animal Health and Food Safety Laboratory System between 1990 and 2007. The species affected most commonly were Amazon parrots (Amazona spp.)(n = 32; 26%) and grey-cheeked parakeets Brotogeris pyrrophterus (n = 23; 18.7%). The main gross findings on necropsy examination were enlarged and mottled pale livers and spleens and thickening of the small intestinal wall with numerous pale miliary nodules on the mucosa. Microscopical examination revealed infiltration of foamy macrophages and giant cells containing acid-fast bacteria in various organs. The gene encoding mycobacterial 65 kDa heat shock protein (hsp65) was amplified by nested polymerase chain reaction (PCR) from DNA extracted from 22 cases. The species of Mycobacterium involved was determined by analysis of restriction endonuclease patterns of the PCR products. Mycobacterium genavense was detected in 19 cases and Mycobacterium avium in two cases. One parrotlet (Touit spp.) had a mixed infection of both species of mycobacteria. It is concluded that M. genavense is the primary cause of mycobacteriosis in psittacine birds and the potential for zoonotic disease should be considered, especially for immunocompromised owners.

Quantification of the relative roles of niche and neutral processes in structuring gastrointestinal microbiomes.

The theoretical description of the forces that shape ecological communities focuses around two classes of models. In niche theory, deterministic interactions between species, individuals, and the environment are considered the dominant factor, whereas in neutral theory, stochastic forces, such as demographic noise, speciation, and immigration, are dominant. Species abundance distributions predicted by the two classes of theory are difficult to distinguish empirically, making it problematic to deduce ecological dynamics from typical measures of diversity and community structure. Here, we show that the fusion of species abundance data with genome-derived measures of evolutionary distance can provide a clear indication of ecological dynamics, capable of quantifying the relative roles played by niche and neutral forces. We apply this technique to six gastrointestinal microbiomes drawn from three different domesticated vertebrates, using high-resolution surveys of microbial species abundance obtained from carefully curated deep 16S rRNA hypervariable tag sequencing data. Although the species abundance patterns are seemingly well fit by the neutral theory of metacommunity assembly, we show that this theory cannot account for the evolutionary patterns in the genomic data; moreover, our analyses strongly suggest that these microbiomes have, in fact, been assembled through processes that involve a significant nonneutral (niche) contribution. Our results demonstrate that high-resolution genomics can remove the ambiguities of process inference inherent in classic ecological measures and permits quantification of the forces shaping complex microbial communities.

A 19S proteasomal subunit cooperates with an ERK MAPK-regulated degron to regulate accumulation of Fra-1 in tumour cells.

Fos-related antigen-1 (Fra-1) is a member of the Activator Protein-1 (AP-1) transcription factor superfamily that is overexpressed in a variety of cancers, including colon, breast, lung, bladder and brain. High Fra-1 levels are associated with enhanced cell proliferation, survival, migration and invasion. Despite its frequent overexpression, the molecular mechanisms that regulate the accumulation of Fra-1 proteins in tumour cells are not well understood. Here, we show that turnover of Fra-1, which does not require ubiquitylation, is cooperatively regulated by two distinct mechanisms-association with the 19S proteasomal subunit, TBP-1, and by a C-terminal degron, which acts independently of TBP-1, but is regulated by RAS-ERK (extracellular signal-regulated kinase) signalling. TBP-1 depletion stabilized Fra-1 and further increased its levels in tumour cells expressing RAS-ERK pathway oncogenes. These effects correlated with increased AP-1 transcriptional activity. We suggest that during Fra-1 degradation, association with TBP-1 provides a mechanism for ubiquitin-independent proteasomal recognition, while the C terminus of the protein regulates its subsequent proteolytic processing.

Fra-1 controls motility of bladder cancer cells via transcriptional upregulation of the receptor tyrosine kinase AXL.

Fos-related antigen 1 (Fra-1) is a Fos family member overexpressed in several types of human cancers. Here, we report that Fra-1 is highly expressed in the muscle-invasive form of the carcinoma of the bladder (80%) and to a lesser extent in superficial bladder cancer (42%). We demonstrate that in this type of cancer Fra-1 is regulated via a C-terminal instability signal and C-terminal phosphorylation. We show that manipulation of Fra-1 expression levels in bladder cancer cell lines affects cell morphology, motility and proliferation. The gene coding for AXL tyrosine kinase is directly upregulated by Fra-1 in bladder cancer and in other cell lines. Importantly, our data demonstrate that AXL mediates the effect of Fra-1 on tumour cell motility but not on cell proliferation. We suggest that AXL may represent an attractive therapeutic target in cancers expressing high Fra-1 levels.

Cognitive errors detected in anaesthesiology: a literature review and pilot study.

BACKGROUND: Cognitive errors are thought-process errors, or thinking mistakes, which lead to incorrect diagnoses, treatments, or both. This psychology of decision-making has received little formal attention in anaesthesiology literature, although it is widely appreciated in other safety cultures, such as aviation, and other medical specialities. We sought to identify which types of cognitive errors are most important in anaesthesiology. METHODS: This study consisted of two parts. First, we created a cognitive error catalogue specific to anaesthesiology practice using a literature review, modified Delphi method with experts, and a survey of academic faculty. In the second part, we observed for those cognitive errors during resident physician management of simulated anaesthesiology emergencies. RESULTS: Of >30 described cognitive errors, the modified Delphi method yielded 14 key items experts felt were most important and prevalent in anaesthesiology practice (Table 1). Faculty survey responses narrowed this to a 'top 10' catalogue consisting of anchoring, availability bias, premature closure, feedback bias, framing effect, confirmation bias, omission bias, commission bias, overconfidence, and sunk costs (Table 2). Nine types of cognitive errors were selected for observation during simulated emergency management. Seven of those nine types of cognitive errors occurred in >50% of observed emergencies (Table 3). CONCLUSIONS: Cognitive errors are thought to contribute significantly to medical mishaps. We identified cognitive errors specific to anaesthesiology practice. Understanding the key types of cognitive errors specific to anaesthesiology is the first step towards training in metacognition and de-biasing strategies, which may improve patient safety.

Analysis of sintered polymer scaffolds using concomitant synchrotron computed tomography and in situ mechanical testing.

The mechanical behaviour of polymer scaffolds plays a vital role in their successful use in bone tissue engineering. The present study utilised novel sintered polymer scaffolds prepared using temperature-sensitive poly(DL-lactic acid-co-glycolic acid)/poly(ethylene glycol) particles. The microstructure of these scaffolds was monitored under compressive strain by image-guided failure assessment (IGFA), which combined synchrotron radiation computed tomography (SR CT) and in situ micro-compression. Three-dimensional CT data sets of scaffolds subjected to a strain rate of 0.01%/s illustrated particle movement within the scaffolds with no deformation or cracking. When compressed using a higher strain rate of 0.02%/s particle movement was more pronounced and cracks between sintered particles were observed. The results from this study demonstrate that IGFA based on simultaneous SR CT imaging and micro-compression testing is a useful tool for assessing structural and mechanical scaffold properties, leading to further insight into structure-function relationships in scaffolds for bone tissue engineering applications.

Are FoxP3(+) cells involved in hyporesponsiveness to interferon/ribavirin therapy in chronic hepatitis C?

We aimed to clarify the role of liver-infiltrating FoxP3(+) T cells for the response to therapy in chronic hepatitis C. Liver biopsies from 52 patients were collected prior to the start of interferon/ribavirin treatment, and the kinetics of viral decay during treatment were compared in patients with high and low infiltration of FoxP3(+) cells. These groups did not differ with respect to the effectiveness of early viral clearance or the frequency of sustained viral response. Our data imply that FoxP3(+) cell-mediated immunosuppression is not a major mechanism of hyporesponsiveness to interferon-based therapy in chronic hepatitis C.