Benchmark measurements and simulations of dose perturbations due to metallic spheres in proton beams

Monte Carlo simulations are increasingly used for dose calculations in proton therapy due to its inherent accuracy. However, dosimetric deviations have been found using Monte Carlo code when high density materials are present in the proton beamline. The purpose of this work was to quantify the magnitude of dose perturbation caused by metal objects. We did this by comparing measurements and Monte Carlo predictions of dose perturbations caused by the presence of small metal spheres in several clinical proton therapy beams as functions of proton beam range and drift space. Monte Carlo codes MCNPX, GEANT4 and Fast Dose Calculator (FDC) were used. Generally good agreement was found between measurements and Monte Carlo predictions, with the average difference within 5% and maximum difference within 17%. The modification of multiple Coulomb scattering model in MCNPX code yielded improvement in accuracy and provided the best overall agreement with measurements. Our results confirmed that Monte Carlo codes are well suited for predicting multiple Coulomb scattering in proton therapy beams when short drift spaces are involved. © 2013 Elsevier Ltd. All rights reserved

Prevalence of extraintestinal manifestations in paediatric patients with Inflammatory Bowel Disease : results from the Swiss IBD Cohort Study

Background: There is a paucity of data from large cohort studies on the prevalence and type of extraintestinal manifestations in pediatric patients with Crohn's disease (CD) and ulcerative colitis (UC). We aimed to assess the prevalence and type of EIM in pediatric patients with inflammatory bowel disease (IBD). Methods: Data from patients enrolled in the Pediatric Swiss IBD Cohort Study (P-SIBDCS) were analyzed. Since 2008 the P-SIBDCS collects data on patients aged 2-17 from hospitals and private practices across Switzerland. Results of continuous data are reported as median and interquartile range

Dacarbazine (DTIC) versus vaccination with autologous peptide-pulsed dendritic cells (DC) in first-line treatment of patients with metastatic melanoma: a randomized phase III trial of the DC study group of the DeCOG

Background: This randomized phase III trial was designed to demonstrate the superiority of autologous peptide-loaded dendritic cell (DC) vaccination over standard dacarbazine (DTIC) chemotherapy in stage IV melanoma patients. Patients and methods: DTIC 850 mg/m2 intravenously was applied in 4-week intervals. DC vaccines loaded with MHC class I and II-restricted peptides were applied subcutaneously at 2-week intervals for the first five vaccinations and every 4 weeks thereafter. The primary study end point was objective response (OR); secondary end points were toxicity, overall (OS) and progression-free survival (PFS). Results: At the time of the first interim analysis 55 patients had been enrolled into the DTIC and 53 into the DC-arm (ITT). OR was low (DTIC: 5.5%, DC: 3.8%), but not significantly different in the two arms. The Data Safety & Monitoring Board recommended closure of the study. Unscheduled subset analyses revealed that patients with normal serum LDH and/or stage M1a/b survived longer in both arms than those with elevated serum LDH and/or stage M1c. Only in the DC-arm did those patients with (i) an initial unimpaired general health status (Karnofsky = 100) or (ii) an HLA-A2+/HLA-B44− haplotype survive significantly longer than patients with a Karnofsky index <100 (P = 0.007 versus P = 0.057 in the DTIC-arm) or other HLA haplotypes (P = 0.04 versus P = 0.57 in DTIC-treated patients). Conclusions: DC vaccination could not be demonstrated to be more effective than DTIC chemotherapy in stage IV melanoma patients. The observed association of overall performance status and HLA haplotype with overall survival for patients treated by DC vaccination should be tested in future trials employing DC vaccine

What is a hospital bed day worth? A contingent valuation study of hospital Chief Executive Officers

BACKGROUND: Decreasing hospital length of stay, and so freeing up hospital beds, represents an important cost saving which is often used in economic evaluations. The savings need to be accurately quantified in order to make optimal health care resource allocation decisions. Traditionally the accounting cost of a bed is used. We argue instead that the economic cost of a bed day is the better value for making resource decisions, and we describe our valuation method and estimations for costing this important resource. METHODS: We performed a contingent valuation using 37 Australian Chief Executive Officers’ (CEOs) willingness to pay (WTP) to release bed days in their hospitals, both generally and using specific cases. We provide a succinct thematic analysis from qualitative interviews post survey completion, which provide insight into the decision making process. RESULTS: On average CEOs are willing to pay a marginal rate of $216 for a ward bed day and$436 for an Intensive Care Unit (ICU) bed day, with estimates of uncertainty being greater for ICU beds. These estimates are significantly lower (four times for ward beds and seven times for ICU beds) than the traditional accounting costs often used. Key themes to emerge from the interviews include the importance of national funding and targets, and their associated incentive structures, as well as the aversion to discuss bed days as an economic resource. CONCLUSIONS: This study highlights the importance for valuing bed days as an economic resource to inform cost effectiveness models and thus improve hospital decision making and resource allocation. Significantly under or over valuing the resource is very likely to result in sub-optimal decision making. We discuss the importance of recognising the opportunity costs of this resource and highlight areas for future research. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12913-017-2079-5) contains supplementary material, which is available to authorized users

Specialist role coaching and skill training periodisation: A football goalkeeping case study

© The Author(s) 2020. In sports like association football, professional teams are increasingly devoting resources to the role-based development of individual athletes and sub-groups. By employing ‘specialist coaches’ into athlete-support structures, clubs aim to facilitate individualised athlete training programs to enhance performance preparation as well as skill learning and talent development. Here, we discuss how contemporary pedagogical training approaches, like Nonlinear Pedagogy and the Constraints-Led approach, can enhance effectiveness of specialist role-based athlete development programs to facilitate performance functionality. We argue the need for a model of specialist role-based coaching practice in high performance sports organisations, based on a unified theoretical rationale, such as ecological dynamics. To exemplify the nature of specialist role-based coaching, a case study addresses how Nonlinear Pedagogy and Constraints-Led approach are being used for training professional football goalkeepers in an U23 years age group. Integrating key concepts from ecological dynamics, allied to principles of Nonlinear Pedagogy and the Constraints-Led approach, common skill training principles for specialist role coaches are highlighted. These illustrate the use of the recently introduced ‘Periodization of Skill Training’ framework for specialist role coaching, practically exemplifying a way to harness opportunities for performance enhancement and individualised talent development in the football goalkeeping context

Effectiveness of Carboplatin and Paclitaxel as First- and Second-Line Treatment in 61 Patients with Metastatic Melanoma

BACKGROUND: Patients with metastatic melanoma have a very unfavorable prognosis with few therapeutic options. Based on previous promising experiences within a clinical trial involving carboplatin and paclitaxel a series of advanced metastatic melanoma patients were treated with this combination. METHODS: Data of all patients with cutaneous metastatic melanoma treated with carboplatin and paclitaxel (CP) at our institution between October 2005 and December 2007 were retrospectively evaluated. For all patients a once-every-3-weeks dose-intensified regimen was used. Overall and progression free survival were calculated using the method of Kaplan and Meier. Tumour response was evaluated according to RECIST criteria. RESULTS: 61 patients with cutaneous metastatic melanoma were treated with CP. 20 patients (85% M1c) received CP as first-line treatment, 41 patients (90.2% M1c) had received at least one prior systemic therapy for metastatic disease. Main toxicities were myelosuppression, fatigue and peripheral neuropathy. Partial responses were noted in 4.9% of patients, stable disease in 23% of patients. No complete response was observed. Median progression free survival was 10 weeks. Median overall survival was 31 weeks. Response, progression-free and overall survival were equivalent in first- and second-line patients. 60 patients of 61 died after a median follow up of 7 months. Median overall survival differed for patients with controlled disease (PR+SD) (49 weeks) compared to patients with progressive disease (18 weeks). CONCLUSIONS: Among patients with metastatic melanoma a subgroup achieved disease control under CP therapy which may be associated with a survival benefit. This potential advantage has to be weighed against considerable toxicity. Since response rates and survival were not improved in previously untreated patients compared to pretreated patients, CP should thus not be applied as first-line treatment

Genomic epidemiology and population structure of Neisseria gonorrhoeae from remote highly endemic Western Australian populations

Background: Neisseria gonorrhoeae causes gonorrhoea, the second most commonly notified sexually transmitted infection in Australia. One of the highest notification rates of gonorrhoea is found in the remote regions of Western Australia (WA). Unlike isolates from the major Australian population centres, the remote community isolates have low rates of antimicrobial resistance (AMR). Population structure and whole-genome comparison of 59 isolates from the Western Australian N. gonorrhoeae collection were used to investigate relatedness of isolates cultured in the metropolitan and remote areas. Core genome phylogeny, multilocus sequencing typing (MLST), N. gonorrhoeae multi-antigen sequence typing (NG-MAST) and N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) in addition to hierarchical clustering of sequences were used to characterize the isolates. Results: Population structure analysis of the 59 isolates together with 72 isolates from an international collection, revealed six population groups suggesting that N. gonorrhoeae is a weakly clonal species. Two distinct population groups, Aus1 and Aus2, represented 63% of WA isolates and were mostly composed of the remote community isolates that carried no chromosomal AMR genotypes. In contrast, the Western Australian metropolitan isolates were frequently multi-drug resistant and belonged to population groups found in the international database, suggesting international transmission of the isolates. Conclusions: Our study suggests that the population structure of N. gonorrhoeae is distinct between the communities in remote and metropolitan WA. Given the high rate of AMR in metropolitan regions, ongoing surveillance is essential to ensure the enduring efficacy of the empiric gonorrhoea treatment in remote WA