Dual acquisition of 18F-FMISO and 18F-FDOPA

Metabolic imaging using positron emission tomography (PET) has found increasing clinical use for the management of infiltrating tumours such as glioma. However, the heterogeneous biological nature of tumours and intrinsic treatment resistance in some regions means that knowledge of multiple biological factors is needed for effective treatment planning. For example, the use of 18F-FDOPA to identify infiltrative tumour and 18F-FMISO for localizing hypoxic regions. Performing multiple PET acquisitions is impractical in many clinical settings, but previous studies suggest multiplexed PET imaging could be viable. The fidelity of the two signals is affected by the injection interval, scan timing and injected dose. The contribution of this work is to propose a framework to explicitly trade-off signal fidelity with logistical constraints when designing the imaging protocol. The particular case of estimating 18F-FMISO from a single frame prior to injection of 18F-FDOPA is considered. Theoretical experiments using simulations for typical biological scenarios in humans demonstrate that results comparable to a pair of single-tracer acquisitions can be obtained provided protocol timings are carefully selected. These results were validated using a pre-clinical data set that was synthetically multiplexed. The results indicate that the dual acquisition of 18F-FMISO and 18F-FDOPA could be feasible in the clinical setting. The proposed framework could also be used to design protocols for other tracers.

Clinical pathways for chronic cough in children

Background Chronic cough (a cough lasting longer than four weeks) is a common problem internationally. Chronic cough has associated economic costs and is distressing to the child and to parents; ignoring cough may lead to delayed diagnosis and progression of serious underlying respiratory disease. Clinical guidelines have been shown to lead to efficient and effective patient care and can facilitate clinical decision making. Cough guidelines have been designed to facilitate the management of chronic cough. However, treatment recommendations vary, and specific clinical pathways for the treatment of chronic cough in children are important, as causes of and treatments for cough vary significantly from those in adults. Therefore, systematic evaluation of the use of evidence-based clinical pathways for the management of chronic cough in children would be beneficial for clinical practice and for patient care. Use of a management algorithm can improve clinical outcomes; such management guidelines can be found in the guidelines for cough provided by the American College of Chest Physicians (ACCP) and the British Thoracic Society (BTS). Objectives To evaluate the effectiveness of using a clinical pathway in the management of children with chronic cough. Search methods The Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register, MEDLINE, EMBASE, review articles and reference lists of re levant articles were searched. The latest search was conducted in January 2014. Selection criteria All randomised controlled trials of parallel-group design comparing use versus non-use of a clinical pathway for treatment of chronic cough in children (< 18 years of age). Data collection and analysis Results of searches were reviewed against predetermined cr iteria for inclusion. Two review authors independently selected studies and performed data extraction in duplicate. Main results One study was included in the review. This multi-centre trial was based in five Australian hospitals and recruited 272 children with chronic cough. Children were randomly assigned to early (two weeks) or delayed (six weeks) referral to respiratory specialists who used a cough management pathway. When an intention-to-treat analysis was performed, clinical failure at six wee ks post randomisation (defined as < 75% improvement in cough score, or total resolution for fewer than three consecutive days) was significantly less in the early pathway arm compared with the control arm (odds ratio (OR) 0.35, 95% confidence interval (CI) 0.21 to 0.58). These results indicate that one additional child will be cured for e very five children treated via th e cough pathway (number needed to treat for an additional beneficial outcome (NNTB) = 5, 95% CI 3 to 9) at six weeks. Cough-specific parent-reported quality of life scores were significantly better in th e early-pathway group; the mean difference (MD) between groups was 0.60 (95% CI 0.19 to 1.01). Duration of cough post randomisation was significantly shorter in the intervention group (early-pathway arm) compared with the control group (delayed-pathway arm) (MD -2.70 weeks, 95% CI -4.26 to -1.14). Authors’ conclusions. Current evidence suggests that using a clinical algorithm for the management of children with ch r onic cough in h ospital outpatient settings is more effective than providing wait-list care. Futher high-quality randomised controlled trials are needed to perform ongoing evaluation of cough management pathways in general practitioner and other primary care settings.

A method for matching patients to advanced prostate cancer clinical trials

Objective: To illustrate a new method for simplifying patient recruitment for advanced prostate cancer clinical trials using natural language processing techniques. Background: The identification of eligible participants for clinical trials is a critical factor to increase patient recruitment rates and an important issue for discovery of new treatment interventions. The current practice of identifying eligible participants is highly constrained due to manual processing of disparate sources of unstructured patient data. Informatics-based approaches can simplify the complex task of evaluating patient’s eligibility for clinical trials. We show that an ontology-based approach can address the challenge of matching patients to suitable clinical trials. Methods: The free-text descriptions of clinical trial criteria as well as patient data were analysed. A set of common inclusion and exclusion criteria was identified through consultations with expert clinical trial coordinators. A research prototype was developed using Unstructured Information Management Architecture (UIMA) that identified SNOMED CT concepts in the patient data and clinical trial description. The SNOMED CT concepts model the standard clinical terminology that can be used to represent and evaluate patient’s inclusion/exclusion criteria for the clinical trial. Results: Our experimental research prototype describes a semi-automated method for filtering patient records using common clinical trial criteria. Our method simplified the patient recruitment process. The discussion with clinical trial coordinators showed that the efficiency in patient recruitment process measured in terms of information processing time could be improved by 25%. Conclusion: An UIMA-based approach can resolve complexities in patient recruitment for advanced prostate cancer clinical trials.

A strong lightweight authentication protocol for low-cost RFID systems

RFID is an important technology that can be used to create the ubiquitous society. But an RFID system uses open radio frequency signal to transfer information and this leads to pose many serious threats to its privacy and security. In general, the computing and storage resources in an RFID tag are very limited and this makes it difficult to solve its secure and private problems, especially for low-cost RFID tags. In order to ensure the security and privacy of low-cost RFID systems we propose a lightweight authentication protocol based on Hash function. This protocol can ensure forward security and prevent information leakage, location tracing, eavesdropping, replay attack and spoofing. This protocol completes the strong authentication of the reader to the tag by twice authenticating and it only transfers part information of the encrypted tag’s identifier for each session so it is difficult for an adversary to intercept the whole identifier of a tag. This protocol is simple and it takes less computing and storage resources, it is very suitable to some low-cost RFID systems.

An improved protocol for the isolation of total genomic DNA from Labyrinthulomycetes

Many protocols have been used for extraction of DNA from Thraustochytrids. These generally involve the use of CTAB, phenol/chloroform and ethanol. They also feature mechanical grinding, sonication, N2 freezing or bead beating. However, the resulting chemical and physical damage to extracted DNA reduces its quality. The methods are also unsuitable for large numbers of samples. Commercially-available DNA extraction kits give better quality and yields but are expensive. Therefore, an optimized DNA extraction protocol was developed which is suitable for Thraustochytrids to both minimise expensive and time-consuming steps prior to DNA extraction and also to improve the yield. The most effective method is a combination of single bead in TissueLyser (Qiagen) and Proteinase K. Results were conclusive: both the quality and the yield of extracted DNA were higher than with any other method giving an average yield of 8.5 µg/100 mg biomass.

Document timespan normalisation and understanding temporality for clinical records search

Previous qualitative research has highlighted that temporality plays an important role in relevance for clinical records search. In this study, an investigation is undertaken to determine the effect that the timespan of events within a patient record has on relevance in a retrieval scenario. In addition, based on the standard practise of document length normalisation, a document timespan normalisation model that specifically accounts for timespans is proposed. Initial analysis revealed that in general relevant patient records tended to cover a longer timespan of events than non-relevant patient records. However, an empirical evaluation using the TREC Medical Records track supports the opposite view that shorter documents (in terms of timespan) are better for retrieval. These findings highlight that the role of temporality in relevance is complex and how to effectively deal with temporality within a retrieval scenario remains an open question.

Plantar pressure in diabetic peripheral neuropathy patients with active foot ulceration, previous ulceration and no history of ulceration: A meta-analysis of observational studies

Aims Elevated dynamic plantar pressures are a consistent finding in diabetes patients with peripheral neuropathy with implications for plantar foot ulceration. This meta-analysis aimed to compare the plantar pressures of diabetes patients that had peripheral neuropathy and those with neuropathy with active or previous foot ulcers. Methods Published articles were identified from Medline via OVID, CINAHL, SCOPUS, INFORMIT, Cochrane Central EMBASE via OVID and Web of Science via ISI Web of Knowledge bibliographic databases. Observational studies reporting barefoot dynamic plantar pressure in adults with diabetic peripheral neuropathy, where at least one group had a history of plantar foot ulcers were included. Interventional studies, shod plantar pressure studies and studies not published in English were excluded. Overall mean peak plantar pressure (MPP) and pressure time integral (PTI) were primary outcomes. The six secondary outcomes were MPP and PTI at the rear foot, mid foot and fore foot. The protocol of the meta-analysis was published with PROPSERO, (registration number CRD42013004310). Results Eight observational studies were included. Overall MPP and PTI were greater in diabetic peripheral neuropathy patients with foot ulceration compared to those without ulceration (standardised mean difference 0.551, 95% CI 0.290–0.811, p<0.001; and 0.762, 95% CI 0.303–1.221, p = 0.001, respectively). Sub-group analyses demonstrated no significant difference in MPP for those with neuropathy with active ulceration compared to those without ulcers. A significant difference in MPP was found for those with neuropathy with a past history of ulceration compared to those without ulcers; (0.467, 95% CI 0.181– 0.753, p = 0.001). Statistical heterogeneity between studies was moderate. Conclusions Plantar pressures appear to be significantly higher in patients with diabetic peripheral neuropathy with a history of foot ulceration compared to those with diabetic neuropathy without a history of ulceration. More homogenous data is needed to confirm these findings.

Experiences of countertransference: Reports of clinical psychology students

While historically linked with psychoanalysis, countertransference is recognised as an important component of the experience of therapists, regardless of the therapeutic modality. This study considers the implications of this for the training of psychologists. Fifty-five clinical psychology trainees from four university training programmes completed an anonymous questionnaire that collected written reports of countertransference experiences, ratings of confidence in managing these responses, and supervision in this regard. The reports were analysed using a process of thematic analysis. Several themes emerged including a desire to protect or rescue clients, feeling criticised or controlled by clients, feeling helpless, and feeling disengaged. Trainees varied in their reports of awareness of countertransference and the regularity of supervision in this regard. The majority reported a lack of confidence in managing their responses, and all reported interest in learning about countertransference. The implications for reflective practice in postgraduate psychology training are discussed.

The Queensland high risk foot form (QHRFF): Is it a reliable and valid clinical research tool for foot disease?

Background Foot disease complications, such as foot ulcers and infection, contribute to considerable morbidity and mortality. These complications are typically precipitated by “high-risk factors”, such as peripheral neuropathy and peripheral arterial disease. High-risk factors are more prevalent in specific “at risk” populations such as diabetes, kidney disease and cardiovascular disease. To the best of the authors’ knowledge a tool capturing multiple high-risk factors and foot disease complications in multiple at risk populations has yet to be tested. This study aimed to develop and test the validity and reliability of a Queensland High Risk Foot Form (QHRFF) tool. Methods The study was conducted in two phases. Phase one developed a QHRFF using an existing diabetes foot disease tool, literature searches, stakeholder groups and expert panel. Phase two tested the QHRFF for validity and reliability. Four clinicians, representing different levels of expertise, were recruited to test validity and reliability. Three cohorts of patients were recruited; one tested criterion measure reliability (n = 32), another tested criterion validity and inter-rater reliability (n = 43), and another tested intra-rater reliability (n = 19). Validity was determined using sensitivity, specificity and positive predictive values (PPV). Reliability was determined using Kappa, weighted Kappa and intra-class correlation (ICC) statistics. Results A QHRFF tool containing 46 items across seven domains was developed. Criterion measure reliability of at least moderate categories of agreement (Kappa > 0.4; ICC > 0.75) was seen in 91% (29 of 32) tested items. Criterion validity of at least moderate categories (PPV > 0.7) was seen in 83% (60 of 72) tested items. Inter- and intra-rater reliability of at least moderate categories (Kappa > 0.4; ICC > 0.75) was seen in 88% (84 of 96) and 87% (20 of 23) tested items respectively. Conclusions The QHRFF had acceptable validity and reliability across the majority of items; particularly items identifying relevant co-morbidities, high-risk factors and foot disease complications. Recommendations have been made to improve or remove identified weaker items for future QHRFF versions. Overall, the QHRFF possesses suitable practicality, validity and reliability to assess and capture relevant foot disease items across multiple at risk populations.

Angular dependence of the response of the nanoDot OSLD system for measurements at depth in clinical megavoltage beams

Purpose The purpose of this investigation was to assess the angular dependence of a commercial optically stimulated luminescence dosimeter (OSLD) dosimetry system in MV x-ray beams at depths beyondd max and to find ways to mitigate this dependence for measurements in phantoms. Methods Two special holders were designed which allow a dosimeter to be rotated around the center of its sensitive volume. The dosimeter's sensitive volume is a disk, 5 mm in diameter and 0.2 mm thick. The first holder rotates the disk in the traditional way. It positions the disk perpendicular to the beam (gantry pointing to the floor) in the initial position (0°). When the holder is rotated the angle of the disk towards the beam increases until the disk is parallel with the beam (“edge on,” 90°). This is referred to as Setup 1. The second holder offers a new, alternative measurement position. It positions the disk parallel to the beam for all angles while rotating around its center (Setup 2). Measurements with five to ten dosimeters per point were carried out for 6 MV at 3 and 10 cm depth. Monte Carlo simulations using GEANT4 were performed to simulate the response of the active detector material for several angles. Detector and housing were simulated in detail based on microCT data and communications with the manufacturer. Various material compositions and an all-water geometry were considered. Results For the traditional Setup 1 the response of the OSLD dropped on average by 1.4% ± 0.7% (measurement) and 2.1% ± 0.3% (Monte Carlo simulation) for the 90° orientation compared to 0°. Monte Carlo simulations also showed a strong dependence of the effect on the composition of the sensitive layer. Assuming the layer to completely consist of the active material (Al2O3) results in a 7% drop in response for 90° compared to 0°. Assuming the layer to be completely water, results in a flat response within the simulation uncertainty of about 1%. For the new Setup 2, measurements and Monte Carlo simulations found the angular dependence of the dosimeter to be below 1% and within the measurement uncertainty. Conclusions The dosimeter system exhibits a small angular dependence of approximately 2% which needs to be considered for measurements involving other than normal incident beams angles. This applies in particular to clinicalin vivo measurements where the orientation of the dosimeter is dictated by clinical circumstances and cannot be optimized as otherwise suggested here. When measuring in a phantom, the proposed new setup should be considered. It changes the orientation of the dosimeter so that a coplanar beam arrangement always hits the disk shaped detector material from the thin side and thereby reduces the angular dependence of the response to within the measurement uncertainty of about 1%. This improvement makes the dosimeter more attractive for clinical measurements with multiple coplanar beams in phantoms, as the overall measurement uncertainty is reduced. Similarly, phantom based postal audits can transition from the traditional TLD to the more accurate and convenient OSLD.

A clinical audit to compare peritonitis rates between peritoneal dialysis delivery systems

Peritonitis is a major problem for patients with end-stage kidney disease undergoing peritoneal dialysis (PD). It is the main cause of failure of PD. Two different PD delivery systems are used across Australia although there is inconsistent evidence comparing the systems. The aim of this retrospective audit is to compare the rates and risk of peritonitis in a cohort of incident patients using two PD delivery systems. All consecutive patients starting PD between 1 August 2010 and 31 March 2012 were included and followed until 30 June 2013. Data relating to accepted risk factors for peritonitis were collected and analysed. There were 50 patients (26 men; 24 women) aged between 30 and 87 years. There were 29 episodes of peritonitis in 17 patients. Rates of peritonitis were 1 episode per 69.19 patient-months compared with 1 episode per 18.67 patient-months. Mean times to first episode of peritonitis were 13.11 months compared to 7.13 months. The relative risk of PD-related peritonitis was twice as high (RR = 2.04, 95% CI = 0.85 to 4.94) for patients using the one system (44.4%) compared to a second system (21.7%). Since this is not a randomised trial no firm conclusions can be drawn. Centres should also monitor peritonitis rates for each system.

Randomised clinical trial of a family-based lifestyle intervention for childhood obesity involving parents as the exclusive agents of change

Parent-centred interventions for childhood obesity aim to improve parents' skills and confidence in managing children's dietary and activity patterns, and in promoting a healthy lifestyle in their family. However, few studies assess changes in parenting over the course of treatment. This study describes the evaluation of a lifestyle-specific parenting program (Group Lifestyle Triple P) on multiple child and parent outcomes. One-hundred-and-one families with overweight and obese 4- to 11-year-old children participated in an intervention or waitlist control condition. The 12-week intervention was associated with significant reductions in child BMI z score and weight-related problem behaviour. At the end of the intervention, parents reported increased confidence in managing children's weight-related behaviour, and less frequent use of inconsistent or coercive parenting practices. All short-term intervention effects were maintained at one-year follow-up assessment, with additional improvements in child body size. The results support the efficacy of Group Lifestyle Triple P and suggest that parenting influences treatment outcomes. Further research is needed to evaluate the long-term effectiveness of the intervention and to elucidate the mechanisms of change. © 2010 Elsevier Ltd.

The lean paradox : How can healthcare facilities shrink while clinical spaces expand?

Lean principles create highly efficient healthcare facilities by maximising the clinical value of every part of a facility and by removing everything else. In order that clinical accommodation can be used for a diverse set of functions including unexpected tasks and processes that haven’t even been invented, they have to be big. But somewhat surprisingly, whole facilities tend to shrink in terms of gross floor areas by disposing of non-clinical spaces when designed using Lean principles. And with the whole unit – the building costs shrink too. Using examples from the UK and the USA, this talk explores the unexpected solutions and improved outcomes when designers use a Lean approach to design.

Convergence of regenerative medicine and synthetic biology to develop standardized and validated models of human diseases with clinical relevance

In order to progress beyond currently available medical devices and implants, the concept of tissue engineering has moved into the centre of biomedical research worldwide. The aim of this approach is not to replace damaged tissue with an implant or device but rather to prompt the patient's own tissue to enact a regenerative response by using a tissue-engineered construct to assemble new functional and healthy tissue. More recently, it has been suggested that the combination of Synthetic Biology and translational tissue-engineering techniques could enhance the field of personalized medicine, not only from a regenerative medicine perspective, but also to provide frontier technologies for building and transforming the research landscape in the field of in vitro and in vivo disease models.