Stereotactic arrhythmia radioablation: A multicenter pre-post intervention safety evaluation of the implantable cardioverter-defibrillator function.

BACKGROUND: Stereotactic arrhythmia radioablation (STAR) appears to be beneficial in selected patients with therapy-refractory ventricular tachycardia (VT). However, high-dose radiotherapy used for STAR-treatment may affect functioning of the patients' implantable cardioverter defibrillator (ICD) by direct effects of radiation on ICD components or cardiac tissue. Currently, the effect of STAR on ICD functioning remains unknown. METHODS: A retrospective pre-post multicenter study evaluating ICD functioning in the 12-month before and after STAR was performed. Patients with (non)ischemic cardiomyopathies with therapy-refractory VT and ICD who underwent STAR were included and the occurrence of ICD-related adverse events was collected. Evaluated ICD parameters included sensing, capture threshold and impedance. A linear mixed-effects model was used to investigate the association between STAR, radiotherapy dose and changes in lead parameters over time. RESULTS: In total, 43 patients (88% male) were included in this study. All patients had an ICD with an additional right atrial lead in 34 (79%) and a ventricular lead in 17 (40%) patients. Median ICD-generator dose was 0.1 Gy and lead tip dose ranged from 0-32 Gy. In one patient (2%), a reset occurred during treatment, but otherwise, STAR and radiotherapy dose were not associated with clinically relevant alterations in ICD leads parameters. CONCLUSIONS: STAR treatment did not result in major ICD malfunction. Only one radiotherapy related adverse event occurred during the study follow-up without patient harm. No clinically relevant alterations in ICD functioning were observed after STAR in any of the leads. With the reported doses STAR appears to be safe.

Cardiac stereotactic ablative radiotherapy for control of refractory ventricular tachycardia: initial UK multicentre experience.

BACKGROUND: Options for patients with ventricular tachycardia (VT) refractory to antiarrhythmic drugs and/or catheter ablation remain limited. Stereotactic radiotherapy has been described as a novel treatment option. METHODS: Seven patients with recurrent refractory VT, deemed high risk for either first time or redo invasive catheter ablation, were treated across three UK centres with non-invasive cardiac stereotactic ablative radiotherapy (SABR). Prior catheter ablation data and non-invasive mapping were combined with cross-sectional imaging to generate radiotherapy plans with aim to deliver a single 25 Gy treatment. Shared planning and treatment guidelines and prospective peer review were used. RESULTS: Acute suppression of VT was seen in all seven patients. For five patients with at least 6 months follow-up, overall reduction in VT burden was 85%. No high-grade radiotherapy treatment-related side effects were documented. Three deaths (two early, one late) occurred due to heart failure. CONCLUSIONS: Cardiac SABR showed reasonable VT suppression in a high-risk population where conventional treatment had failed.

Using social media to support small group learning.

BACKGROUND: Medical curricula are increasingly using small group learning and less didactic lecture-based teaching. This creates new challenges and opportunities in how students are best supported with information technology. We explored how university-supported and external social media could support collaborative small group working on our new undergraduate medical curriculum. METHODS: We made available a curation platform (Scoop.it) and a wiki within our virtual learning environment as part of year 1 Case-Based Learning, and did not discourage the use of other tools such as Facebook. We undertook student surveys to capture perceptions of the tools and information on how they were used, and employed software user metrics to explore the extent to which they were used during the year. RESULTS: Student groups developed a preferred way of working early in the course. Most groups used Facebook to facilitate communication within the group, and to host documents and notes. There were more barriers to using the wiki and curation platform, although some groups did make extensive use of them. Staff engagement was variable, with some tutors reviewing the content posted on the wiki and curation platform in face-to-face sessions, but not outside these times. A small number of staff posted resources and reviewed student posts on the curation platform. CONCLUSIONS: Optimum use of these tools depends on sufficient training of both staff and students, and an opportunity to practice using them, with ongoing support. The platforms can all support collaborative learning, and may help develop digital literacy, critical appraisal skills, and awareness of wider health issues in society.

A case-based medical curriculum for the 21st century: The use of innovative approaches in designing and developing a case on mental health.

The introduction of case-based learning (CBL) by the School of Medicine at Cardiff University has encouraged innovation in medical teaching and learning. During years one and two of the modernized MBBCh program, students complete 17 cases as part of the newly developed C21 curriculum that emphasizes a patient-oriented and student-centered approach to learning. The mental health case, which is presented in year 2, incorporates a number of novel teaching resources that aim to enhance the students' learning experience and to further reinforce the patient-oriented and community-based philosophy of C21. These include the use of fictionalized video diaries, virtual patient cases, e-learning workbooks, an interactive practical session, and community placements. Novel teaching methods and resources were evaluated by students in terms of effectiveness and value as learning resources through the administration of a structured mixed questionnaire. The results revealed that students valued the inclusion of these resources, which they evaluated as having contributed to their understanding of the subject area. Furthermore, the case was found to have had an impact on student interest in psychiatry as a specialty as well as a career choice. The positive student evaluation of this case supports the innovations in teaching delivery inspired by C21.

A medical curriculum in transition: audit and student perspective of undergraduate teaching of ethics and professionalism.

INTRODUCTION: The General Medical Council (GMC) stipulates that doctors must be competent professionals, not merely scholars and practitioners. Medical school curricula should enable students to develop professional values and competencies. Additionally, medical schools are moving towards integrated undergraduate curricula, Cardiff's C21 being one such example. METHODS: We carried out an audit to determine the extent to which C21 delivers GMC professionalism competencies, and a student questionnaire to explore student perspective on ethics and professionalism. RESULTS AND DISCUSSION: C21 delivers explicit or implicit teaching for all major GMC competencies, though some missed opportunities remain. The questionnaire responses showed that most students value ethics and professionalism teaching, and that it is most well received when delivered in a variety of ways and contexts throughout the curriculum. We also note that some respondents confuse ethics and professionalism with the policing of student behaviour. CONCLUSIONS: C21 and curricula like it offer many opportunities for nurturing ethically and professionally competent physicians. Students appear to value this, though there remains confusion between medical school discipline and ethics and professionalism which needs further explication.

End-of-life care decisions for haemodialysis patients - 'We only tend to have that discussion with them when they start deteriorating'.

BACKGROUND: Haemodialysis patients receive very little involvement in their end-of-life care decisions. Issues relating to death and dying are commonly avoided until late in their illness. This study aimed to explore the experiences and perceptions of doctors and nurses in nephrology for involving haemodialysis patients in end-of-life care decisions. METHODS: A semi-structured qualitative interview study with 15 doctors and five nurses and thematic analysis of their accounts was conducted. The setting was a large teaching hospital in Wales, UK. RESULTS: Prognosis is not routinely discussed with patients, in part due to a difficulty in estimation and the belief that patients do not want or need this information. Advance care planning is rarely carried out, and end-of-life care discussions are seldom initiated prior to patient deterioration. There is variability in end-of-life practices amongst nephrologists; some patients are felt to be withdrawn from dialysis too late. Furthermore, the possibility and implications of withdrawal are not commonly discussed with well patients. Critical barriers hindering better end-of-life care involvement for these patients are outlined. CONCLUSIONS: The study provides insights into the complexity of end-of-life conversations and the barriers to achieving better end-of-life communication practices. The results identify opportunities for improving the lives and deaths of haemodialysis patients.

Interpretation of Renal Quality of Life Profile scores in routine clinical practice: an aid to treatment decision-making.

PURPOSE: High Renal Quality of Life Profile (RQLP) scores are associated with impaired health-related quality of life; however, the clinical meaning of the scores is difficult for clinicians and healthcare planners to interpret. The aim of this study was to determine clinical significance of RQLP scores which could be used to aid clinical decision-making. METHODS: The anchor-based technique (a method for categorizing numeric scores to ease interpretation) was used to develop a categorization system for the RQLP scores using a global question (GQ). The GQ scores (i.e. no effect to extremely large effect) were mapped against the RQLP scores, and intraclass correlation coefficient (ICC) was used to test their agreement. The RQLP and the GQ were administered to 260 adult patients (males = 165 and females = 95) with chronic renal failure (CRF). RESULTS: The mean RQLP score was 67.2, median = 61, SD = 41.5, and range 0-172. The mean GQ score was 1.74, median = 2, SD = 1.27, and range 0-4. The mean, mode, and median of the GQ scores for each RQLP score were used to devise several sets of categories of RQLP score, and the ICC test of agreement was calculated. The proposed set of RQLP score banding for adoption includes: 0-20 = no effect on patient's life (GQ = 0, n = 35); 21-51 = small effect on patient's life (GQ = 1, n = 66); 52-93 = moderate effect on patient's life (GQ = 2, n = 87); 94-134 = very large effect on patient's life (GQ = 3, n = 54); and 135-172 = extremely large effect on patient's life (GQ = 4, n = 18). The ICC coefficient for the proposed banding system was 0.80. CONCLUSION: The proposed categorization of the RQLP will aid the clinical interpretation of change in RQLP score informing treatment decision-making in routine practice.

Spatial, Temporal, and Matrix Variability of Clostridium botulinum Type E Toxin Gene Distribution at Great Lakes Beaches.

Clostridium botulinum type E toxin is responsible for extensive mortality of birds and fish in the Great Lakes. The C. botulinum bontE gene that produces the type E toxin was amplified with quantitative PCR from 150 sloughed algal samples (primarily Cladophora species) collected during summer 2012 from 10 Great Lakes beaches in five states; concurrently, 74 sediment and 37 water samples from four sites were also analyzed. The bontE gene concentration in algae was significantly higher than in water and sediment (P < 0.05), suggesting that algal mats provide a better microenvironment for C. botulinum. The bontE gene was detected most frequently in algae at Jeorse Park and Portage Lake Front beaches (Lake Michigan) and Bay City State Recreation Area beach on Saginaw Bay (Lake Huron), where 77, 100, and 83% of these algal samples contained the bontE gene, respectively. The highest concentration of bontE was detected at Bay City (1.98 × 10(5) gene copies/ml of algae or 5.21 × 10(6) g [dry weight]). This study revealed that the bontE gene is abundant in the Great Lakes but that it has spatial, temporal, and matrix variability. Further, embayed beaches, low wave height, low wind velocity, and greater average water temperature enhance the bontE occurrence.

Bacterial pathogen gene abundance and relation to recreational water quality at seven Great Lakes beaches.

Quantitative assessment of bacterial pathogens, their geographic variability, and distribution in various matrices at Great Lakes beaches are limited. Quantitative PCR (qPCR) was used to test for genes from E. coli O157:H7 (eaeO157), shiga-toxin producing E. coli (stx2), Campylobacter jejuni (mapA), Shigella spp. (ipaH), and a Salmonella enterica-specific (SE) DNA sequence at seven Great Lakes beaches, in algae, water, and sediment. Overall, detection frequencies were mapA>stx2>ipaH>SE>eaeO157. Results were highly variable among beaches and matrices; some correlations with environmental conditions were observed for mapA, stx2, and ipaH detections. Beach seasonal mean mapA abundance in water was correlated with beach seasonal mean log10 E. coli concentration. At one beach, stx2 gene abundance was positively correlated with concurrent daily E. coli concentrations. Concentration distributions for stx2, ipaH, and mapA within algae, sediment, and water were statistically different (Non-Detect and Data Analysis in R). Assuming 10, 50, or 100% of gene copies represented viable and presumably infective cells, a quantitative microbial risk assessment tool developed by Michigan State University indicated a moderate probability of illness for Campylobacter jejuni at the study beaches, especially where recreational water quality criteria were exceeded. Pathogen gene quantification may be useful for beach water quality management.

Epidemiology and outcome of community-acquired acute kidney injury.

AIMS: Very little data exist regarding community-acquired acute renal injury (CA-AKI). We have identified and characterized a patient cohort with CA-AKI, and documented its impact on renal function and patient mortality. METHODS: Using the database of the Medical Biochemistry Department of the Cardiff and Vale University Health Board we identified all patients with CA-AKI over a 1 month period in 2009. Follow-up biochemical and clinical data were used to determine short-term (3 months) and long-term (3 years) outcomes. Comparisons were made to a random and an age/sex matched group. RESULTS: Patients with CA-AKI were older than a non-AKI cohort (70.3 vs 57.1 years; P < 0.0001), with a 61% male predominance. 38% had pre-existing chronic kidney disease (CKD) compared with 25% in the age- and sex-matched non-CA-AKI cohort (P = 0.007). 54% of CA-AKI were admitted for inpatient care. Admission was associated with a higher incidence of complete recovery of renal function. Mortality at 3 months was 16.5%, and was related to the severity of AKI. Over the 3 years of follow-up 71% of patients with CA-AKI developed progressive CKD which was more likely following incomplete/no recovery of renal function and in the context of pre-existing CKD. Three year mortality was 45%, which was higher than that of the age/sex matched control cohort (15.7%; P < 0.0001), but was not related to the development of progressive CKD. CONCLUSIONS: CA-AKI carries significant implications in terms of both development of progressive renal disease and high long-term patient mortality.

Acute kidney injury risk factor recognition in three teaching hospitals in Ethiopia.

BACKGROUND: A key objective of the Nephrology Sister Centre Programme between the renal units in Cardiff and Addis Ababa, sponsored by the International Society of Nephrology, is to facilitate development of the local clinical service in Ethiopia specifically focused on the management of acute kidney injury (AKI). OBJECTIVES: To examine the relationship between AKI risk factor recognition and monitoring of renal function in three hospitals in Ethiopia. METHODS: Cross-sectional data were gathered regarding renal function monitoring, recording the presence of AKI risk-associated comorbidities and prescription of nephrotoxic medications across the disciplines of medicine, surgery, obstetrics and gynaecology. Results. Patients were more likely to have their renal function checked at the hospital with specialist services. Across all centres, the highest proportion of patients who had renal function measurements were those admitted to a medical ward. There was a positive relationship between documented comorbidities and the measurement of renal function but not between the prescription of nephrotoxic drugs and measurement of renal function. CONCLUSION: There was great variability in the extent to which doctors recognised the presence of risk factors for the development of AKI. Failure to identify these risk factors represents a lost opportunity to identify patients at high risk of developing renal injury who would benefit from renal function monitoring.

Prevalence of risk factors for foot ulceration in a general haemodialysis population.

It is well documented that diabetic foot ulceration contributes to increased morbidity and mortality associated with renal replacement therapy. Much less is known about the risk of foot ulceration and lower limb amputation in the non-diabetic dialysis population. The aim of this study was to determine if the prevalence of risks factors for lower limb amputation in a stable haemodialysis population was greater in the diabetic cohort compared with the non-diabetic cohort. The study design is a prospective observational cohort study. Sixty patients attending a satellite haemodialysis unit in Cardiff were invited to have a comprehensive foot assessment as part of a Podiatry service review. The medical notes and hospital information system were used to identify the diabetic cohort. Patients were classified according to diabetic status (diabetic versus non-diabetic). The Renal Foot Screening Tool was developed to prospectively identify risk factors associated with foot ulceration. The assessment included peripheral neuropathy (PN), peripheral arterial disease (PAD) and foot pathology (FP). Fifty-seven patients gave informed verbal consent prior to inclusion. Risk factors for foot ulceration were recorded at baseline in the diabetic (n = 24) and non-diabetic (n = 33) groups and mortality data was revisited after a 3-year period. FP was identified in 79% of patients. Eighteen per cent of the non-diabetic patients had PN. PAD was identified in 45% of diabetic and 30% of non-diabetic patients. Forty-nine per cent of the total cohort had ≥2 of the 3 independent risk factors for foot ulceration (16/24 diabetic versus 12/33 non-diabetic). The presence of PAD and PN was predictive of mortality independent of age. The limitations of this study are its small sample size and patients were from a single satellite dialysis unit. There was a high prevalence of risk factors for foot ulceration in this population, which were not confined to the diabetic cohort. These findings suggest that non-diabetic patients on haemodialysis therapy are also at risk of developing foot ulceration. Further work on strategies to monitor and prevent FP in this high-risk cohort is needed to minimize morbidity and mortality associated with foot ulceration.

Renal impairment among acute hospital admissions in a rural Ethiopian hospital.

AIM: Acute renal injury (AKI) is a relatively common clinical condition, reported to be associated with high rates of in-hospital mortality. Although here is an extensive literature on the nature and consequence of AKI in the developed World, much less is known in the developing World and more specifically in sub-Saharan Africa, which is addressed directly in this study. METHODS: We describe the prevalence, clinical characteristics and impact of AKI in patients admitted to a single centre in Ethiopia with no dedicated renal services. RESULTS: Renal function tests are not preformed routinely in many Ethiopian hospitals. This occurred in 32% of all patients in this study, falling to 23% on surgical wards. As a consequence no cases of AKI were identified in the context of surgical admissions. AKI was only identified in a cohort of patients on medical wards, with a prevalence of roughly 20% of medical patients in which renal function was measured. The patients with AKI were younger than those at risk of AKI in studies from the developed World but were older than those who did not develop AKI in this study. In the majority of cases AKI could be considered to be pre-renal in its origin. In contrast to studies in the developed World, AKI did not adversely impact on either duration of hospital stay or on patient mortality. Residual renal impairment was, however, common at the point of discharge. CONCLUSION: The data suggest subtle differences in the nature and impact of AKI between those published and mainly derived from the developed world and patients in sub-Saharan Africa.

An analytical approach to acceptance criteria for quality assurance of Intensity Modulated Radiotherapy.

Detectability and impact of potential treatment machine errors on IMRT treatments were evaluated. The ability of the gamma index to detect deliberately introduced errors was assessed and their clinical impact was assessed using Tumour Control Probability (TCP) and Normal Tissue Complication Probability. TCP was only marginally affected by 2mm errors in MLC position. Dose delivery errors had greater impact but were not detected as effectively using the gamma index. Acceptance criteria should include mean dose as well as gamma to help identify errors in the delivered dose.

Adult day-case renal biopsy: a single-centre experience.

BACKGROUND: Despite improvements in safety seen over the last 20 years, percutaneous renal biopsy is still associated with haemorrhagic complications. Due to concerns over delayed bleeding, most nephrologists would advocate overnight observation. Recent evidence in both adult and paediatric populations suggest that in some groups, this is unnecessary. Since 1991, we have provided a day-case renal biopsy service performing 70 such procedures per year. In this study, we present a retrospective analysis of this practice. METHODS: A total of 192 patients over a consecutive 3-year period were analysed retrospectively. Patients were selected according to standardized criteria, and biopsy was performed using a modern technique (automated biopsy needles under ultrasound guidance). Complications were identified by examination of case notes and local hospital admission databases, and by telephone interview. Our pathology database was examined for sample adequacy and diagnosis. RESULTS: There were no delayed complications in the study group with 187 patients (97.4%) being discharged home on the same day. Major complications occurred in five patients (2.6%), all related to bleeding. Of these, two needed radiological intervention to achieve haemostasis. Sufficient tissue for diagnosis was achieved in 97% of cases, with a mean of 47 ± 23 glomeruli obtained per patient. Most biopsies were obtained with ≤ 2 passes (84%). CONCLUSIONS: Our findings show that in selected adult patients, renal biopsy can be performed as a day-case procedure. Given the benefits of day-case strategies in terms of patient and healthcare costs, we advocate increased utilization of this technique.

Population synchrony of a native fish across three Laurentian Great Lakes: evaluating the effects of dispersal and climate.

Climate and dispersal are the two most commonly cited mechanisms to explain spatial synchrony among time series of animal populations, and climate is typically most important for fishes. Using data from 1978-2006, we quantified the spatial synchrony in recruitment and population catch-per-unit-effort (CPUE) for bloater (Coregonus hoyi) populations across lakes Superior, Michigan, and Huron. In this natural field experiment, climate was highly synchronous across lakes but the likelihood of dispersal between lakes differed. When data from all lakes were pooled, modified correlograms revealed spatial synchrony to occur up to 800 km for long-term (data not detrended) trends and up to 600 km for short-term (data detrended by the annual rate of change) trends. This large spatial synchrony more than doubles the scale previously observed in freshwater fish populations, and exceeds the scale found in most marine or estuarine populations. When analyzing the data separately for within- and between-lake pairs, spatial synchrony was always observed within lakes, up to 400 or 600 km. Conversely, between-lake synchrony did not occur among short-term trends, and for long-term trends, the scale of synchrony was highly variable. For recruit CPUE, synchrony occurred up to 600 km between both lakes Michigan and Huron (where dispersal was most likely) and lakes Michigan and Superior (where dispersal was least likely), but failed to occur between lakes Huron and Superior (where dispersal likelihood was intermediate). When considering the scale of putative bloater dispersal and genetic information from previous studies, we concluded that dispersal was likely underlying within-lake synchrony but climate was more likely underlying between-lake synchrony. The broad scale of synchrony in Great Lakes bloater populations increases their probability of extirpation, a timely message for fishery managers given current low levels of bloater abundance.

Advances in intensity-modulated radiotherapy delivery.

Fixed-field intensity-modulated treatments, delivered by conventional linac-plus-multileaf systems, have rapidly become the most common form of IMRT. Several innovative alternative IMRT options are also now available, including tomotherapy, CyberKnife and jaws-only linacs. These innovative approaches have divergent rationales. Jaws-only IMRT is being developed because it allows treatments to be delivered using conventional linacs without expensive multileaf collimators and not because it improves dose distributions. On the other hand, tomotherapy and CyberKnife systems have different geometric degrees of freedom, beam sizes and modulation techniques than those of conventional linacs, which may enable these innovative systems to deliver superior dose distributions to some treatment sites. Because conventional linacs are themselves finely honed machines, enhancement of one aspect of machine performance is sometimes accompanied by diminution of another. For example, tomotherapy systems possess an enhanced rotational IMRT capability but currently can only deliver coplanar radiation beams. Thus the various delivery systems may prove optimal for different types of treatments, specific machine designs excelling for specific disease sites. In practice, of course, IMRT delivery systems will be distinguished not just by the quality of the dose distributions they deliver but also by factors not discussed in this chapter, such as the efficiency of their treatment process, the integration of on-board imaging into that process, and their ability to measure, minimise and compensate for the effects of respiratory motion, a major detriment to accurate IMRT delivery.

Glucose modulates handling of apoptotic cells by mesangial cells: involvement of TGF-beta1.

Glucose stimulates proapoptotic signalling pathways in mesangial cells. Studies focused on inflammatory glomerular injury have demonstrated that removal of apoptotic mesangial cells occurs by neighbouring non-apoptotic mesangial cells. The aim of this study was to define the effect of ambient glucose concentration on mesangial handling of apoptotic cells, and in addition to examine the response made by the mesangial cell. We used a co-culture model in which neutrophils aged overnight to induce apoptosis, or apoptotic mesangial cells, labelled with a fluorescent dye, were added to mesangial cells to study phagocytosis. Exposure of mesangial cells to an ambient glucose concentration of 25 mM D-glucose before addition of apoptotic cells led in an increase in mesangial cell phagocytosis. Ingestion of apoptotic cells was inhibited by blocking alpha v beta 3 integrin-vitronectin receptor or thrombospondin-1. Furthermore, glucose-dependent stimulation of phagocytosis was inhibited by a blocking antibody to TGF-beta1. Co-culture of apoptotic cells with mesangial cells stimulated synthesis of TGF-beta1 as compared to freshly isolated neutrophils. Increased TGF-beta1 synthesis was dependent on direct contact between the two cell types but was not dependent on phagocytosis of apoptotic cells, as TGF-beta1 generation was not affected by inhibition of the thrombospondin-1 pathway. We propose a model in which apoptotic cell binding but not phagocytosis stimulates enhanced mesangial cell TGF-beta1 synthesis. Furthermore phagocytosis, which involves the thrombospondin-1 pathway, is uncoupled from binding of apoptotic cells, which stimulated TGF-beta1 synthesis.