Fasting increases serum bilirubin levels in clinically normal, healthy males but not females : a retrospective study from phase I clinical trial participants

Aim: To examine if fasting affects serum bilirubin levels in clinical healthy males and females. Methods: We utilised retrospective data from phase 1 clinical trials where blood was collected in either a fed or fasting state at screening and pre-dosing time points and analysed for total bilirubin levels as per standard clinical procedures. Participants were clinically healthy males (n = 105) or females (n = 30) aged 18 to 48 inclusive who participated in a phase 1 clinical trial in 2012 or 2013. Results: We found a statistically significant increase in total serum bilirubin levels in fasting males as compared to non-fasting males. The fasting time correlated positively with increased bilirubin levels. The age of the healthy males did not correlate with their fasting bilirubin level. We found no correlation between fasting and bilirubin levels in clinically normal females. Conclusions: The recruitment and screening of volunteers for a clinical trial is a time-consuming and expensive process. This study clearly demonstrates that testing for serum bilirubin should be conducted on non-fasting male subjects. If fasting is required, then participants should not be excluded from a trial based on an elevated serum bilirubin that is deemed non-clinically significant.

Weekly cisplatin concurrently with radiotherapy in head and neck squamous cell cancer : a retrospective analysis of a tertiary institute experience

Radiotherapy combined with three weekly 100 mg/m2 of cisplatin is the accepted standard of care in head and neck squamous cell carcinoma. However, this regimen is associated with severe toxicities with devastating effects on patients. Alternative protocols like weekly 40 mg/m2 have been used in an attempt to reduce toxicities. The main objective of the present study is to identify the dose intensities and toxicities of weekly cisplatin in patients treated in a tertiary centre over a 12 month period. Included patients had squamous cell carcinoma arising in the oral cavity, oropharynx, larynx, or hypopharynx. Patients were excluded if they had nasopharyngeal squamous cell carcinoma, distant metastasis or if they had prior treatment for head and neck cancer excluding neck dissection. During the study period, 52 patients met the inclusion criteria and their data were retrospectively obtained from the patients' database of St James hospital, Dublin. The median age of the study cohort was 54 years (range 33-73). Of the patients, 40 (76.9 %) were male and 12 (20.1 %) were female. The primary tumour sites were as follows: oral cavity and oropharynx in 38 (73 %), larynx in 10 (19 %), and hypopharynx in 4 (8 %). In total, 33 (63.5 %) patients had stage IV disease, while 19 (36.5 %) had stage III disease. Treatment was definitive in 35 (67 %) patients and adjuvant in 17 (35 %). Full-dose radiotherapy was achieved in 50 (96 %) patients. Only 22 (42.3 %) patients completed the intended six cycles of chemotherapy. Cumulative dose of 200 mg/m2 or more was reached in 37 (71 %) patients. The acute adverse effects included grades 3 and 4 mucositis, which occurred in 22 (43.3 %) and 6 patients (12 %), respectively. Grade 3 and 4 neutropenia occurred in six (11.5 %) and three (5.7 %) patients, respectively. The only other haematological toxicity was grade 3 anaemia in 20 (38.4 %) patients. There was no grade 3 or 4 renal toxicity among the study cohort, although grade 2 was observed in six (11.5 %) patients. Death occurred in one patient due to neutropenic septicaemia. In conclusion, weekly cisplatin is associated with moderate to severe toxicities and might lead to suboptimal chemotherapy delivery. More prospective clinical studies are required to determine the optimal chemoradiation regimen in head and neck squamous cell carcinoma.

Retrospective evaluation of dosimetric quality for prostate carcinomas treated with 3D conformal, intensity-modulated and volumetric-modulated arc radiotherapy

Introduction This study examines and compares the dosimetric quality of radiotherapy treatment plans for prostate carcinoma across a cohort of 163 patients treated across 5 centres: 83 treated with three-dimensional conformal radiotherapy (3DCRT), 33 treated with intensity-modulated radiotherapy (IMRT) and 47 treated with volumetric-modulated arc therapy (VMAT). Methods Treatment plan quality was evaluated in terms of target dose homogeneity and organ-at-risk sparing, through the use of a set of dose metrics. These included the mean, maximum and minimum doses; the homogeneity and conformity indices for the target volumes; and a selection of dose coverage values that were relevant to each organ-at-risk. Statistical significance was evaluated using two-tailed Welch’s T-tests. The Monte Carlo DICOM ToolKit software was adapted to permit the evaluation of dose metrics from DICOM data exported from a commercial radiotherapy treatment planning system. Results The 3DCRT treatment plans offered greater planning target volume dose homogeneity than the other two treatment modalities. The IMRT and VMAT plans offered greater dose reduction in the organs-at-risk: with increased compliance with recommended organ-at-risk dose constraints, compared to conventional 3DCRT treatments. When compared to each other, IMRT and VMAT did not provide significantly different treatment plan quality for like-sized tumour volumes. Conclusions This study indicates that IMRT and VMAT have provided similar dosimetric quality, which is superior to the dosimetric quality achieved with 3DCRT.

The impact of OCR accuracy on automated cancer classification of pathology reports

Objective To evaluate the effects of Optical Character Recognition (OCR) on the automatic cancer classification of pathology reports. Method Scanned images of pathology reports were converted to electronic free-text using a commercial OCR system. A state-of-the-art cancer classification system, the Medical Text Extraction (MEDTEX) system, was used to automatically classify the OCR reports. Classifications produced by MEDTEX on the OCR versions of the reports were compared with the classification from a human amended version of the OCR reports. Results The employed OCR system was found to recognise scanned pathology reports with up to 99.12% character accuracy and up to 98.95% word accuracy. Errors in the OCR processing were found to minimally impact on the automatic classification of scanned pathology reports into notifiable groups. However, the impact of OCR errors is not negligible when considering the extraction of cancer notification items, such as primary site, histological type, etc. Conclusions The automatic cancer classification system used in this work, MEDTEX, has proven to be robust to errors produced by the acquisition of freetext pathology reports from scanned images through OCR software. However, issues emerge when considering the extraction of cancer notification items.

Classification of pathology reports for cancer registry notifications

Objective: To develop a system for the automatic classification of pathology reports for Cancer Registry notifications. Method: A two pass approach is proposed to classify whether pathology reports are cancer notifiable or not. The first pass queries pathology HL7 messages for known report types that are received by the Queensland Cancer Registry (QCR), while the second pass aims to analyse the free text reports and identify those that are cancer notifiable. Cancer Registry business rules, natural language processing and symbolic reasoning using the SNOMED CT ontology were adopted in the system. Results: The system was developed on a corpus of 500 histology and cytology reports (with 47% notifiable reports) and evaluated on an independent set of 479 reports (with 52% notifiable reports). Results show that the system can reliably classify cancer notifiable reports with a sensitivity, specificity, and positive predicted value (PPV) of 0.99, 0.95, and 0.95, respectively for the development set, and 0.98, 0.96, and 0.96 for the evaluation set. High sensitivity can be achieved at a slight expense in specificity and PPV. Conclusion: The system demonstrates how medical free-text processing enables the classification of cancer notifiable pathology reports with high reliability for potential use by Cancer Registries and pathology laboratories.

Clinician-driven automated classification of limb fractures from free-text radiology reports

The aim of this research is to report initial experimental results and evaluation of a clinician-driven automated method that can address the issue of misdiagnosis from unstructured radiology reports. Timely diagnosis and reporting of patient symptoms in hospital emergency departments (ED) is a critical component of health services delivery. However, due to disperse information resources and vast amounts of manual processing of unstructured information, a point-of-care accurate diagnosis is often difficult. A rule-based method that considers the occurrence of clinician specified keywords related to radiological findings was developed to identify limb abnormalities, such as fractures. A dataset containing 99 narrative reports of radiological findings was sourced from a tertiary hospital. The rule-based method achieved an F-measure of 0.80 and an accuracy of 0.80. While our method achieves promising performance, a number of avenues for improvement were identified using advanced natural language processing (NLP) techniques.

Automatic classification of free-text radiology reports to identify limb fractures using machine learning and the SNOMED CT ontology

Objective To develop and evaluate machine learning techniques that identify limb fractures and other abnormalities (e.g. dislocations) from radiology reports. Materials and Methods 99 free-text reports of limb radiology examinations were acquired from an Australian public hospital. Two clinicians were employed to identify fractures and abnormalities from the reports; a third senior clinician resolved disagreements. These assessors found that, of the 99 reports, 48 referred to fractures or abnormalities of limb structures. Automated methods were then used to extract features from these reports that could be useful for their automatic classification. The Naive Bayes classification algorithm and two implementations of the support vector machine algorithm were formally evaluated using cross-fold validation over the 99 reports. Result Results show that the Naive Bayes classifier accurately identifies fractures and other abnormalities from the radiology reports. These results were achieved when extracting stemmed token bigram and negation features, as well as using these features in combination with SNOMED CT concepts related to abnormalities and disorders. The latter feature has not been used in previous works that attempted classifying free-text radiology reports. Discussion Automated classification methods have proven effective at identifying fractures and other abnormalities from radiology reports (F-Measure up to 92.31%). Key to the success of these techniques are features such as stemmed token bigrams, negations, and SNOMED CT concepts associated with morphologic abnormalities and disorders. Conclusion This investigation shows early promising results and future work will further validate and strengthen the proposed approaches.

ShARe/CLEF eHealth Evaluation Lab 2013, Task 3: Information retrieval to address patients' questions when reading clinical reports

This paper presents the results of task 3 of the ShARe/CLEF eHealth Evaluation Lab 2013. This evaluation lab focuses on improving access to medical information on the web. The task objective was to investigate the effect of using additional information such as the discharge summaries and external resources such as medical ontologies on the IR effectiveness. The participants were allowed to submit up to seven runs, one mandatory run using no additional information or external resources, and three each using or not using discharge summaries.

BDNF and TNF-α polymorphisms in memory

Here, we investigate the genetic basis of human memory in healthy individuals and the potential role of two polymorphisms, previously implicated in memory function. We have explored aspects of retrospective and prospective memory including semantic, short term, working and long-term memory in conjunction with brain derived neurotrophic factor (BDNF) and tumor necrosis factor-alpha (TNF-alpha). The memory scores for healthy individuals in the population were obtained for each memory type and the population was genotyped via restriction fragment length polymorphism for the BDNF rs6265 (Val66Met) SNP and via pyrosequencing for the TNF-alpha rs113325588 SNP. Using univariate ANOVA, a significant association of the BDNF polymorphism with visual and spatial memory retention and a significant association of the TNF-alpha polymorphism was observed with spatial memory retention. In addition, a significant interactive effect between BDNF and TNF-alpha polymorphisms was observed in spatial memory retention. In practice visual memory involves spatial information and the two memory systems work together, however our data demonstrate that individuals with the Val/Val BDNF genotype have poorer visual memory but higher spatial memory retention, indicating a level of interaction between TNF-alpha and BDNF in spatial memory retention. This is the first study to use genetic analysis to determine the interaction between BDNF and TNF-alpha in relation to memory in normal adults and provides important information regarding the effect of genetic determinants and gene interactions on human memory.

Automated classification of limb fractures from free-text radiology reports using a clinician-informed gazetteer methodology

Background Timely diagnosis and reporting of patient symptoms in hospital emergency departments (ED) is a critical component of health services delivery. However, due to dispersed information resources and a vast amount of manual processing of unstructured information, accurate point-of-care diagnosis is often difficult. Aims The aim of this research is to report initial experimental evaluation of a clinician-informed automated method for the issue of initial misdiagnoses associated with delayed receipt of unstructured radiology reports. Method A method was developed that resembles clinical reasoning for identifying limb abnormalities. The method consists of a gazetteer of keywords related to radiological findings; the method classifies an X-ray report as abnormal if it contains evidence contained in the gazetteer. A set of 99 narrative reports of radiological findings was sourced from a tertiary hospital. Reports were manually assessed by two clinicians and discrepancies were validated by a third expert ED clinician; the final manual classification generated by the expert ED clinician was used as ground truth to empirically evaluate the approach. Results The automated method that attempts to individuate limb abnormalities by searching for keywords expressed by clinicians achieved an F-measure of 0.80 and an accuracy of 0.80. Conclusion While the automated clinician-driven method achieved promising performances, a number of avenues for improvement were identified using advanced natural language processing (NLP) and machine learning techniques.

Validity of family child care providers' proxy reports on children's physical activity

Background Interventions to promote physical activity (PA) in children attending family child care homes (FCCHs) require valid, yet practical, measurement tools. The aim of this study was to assess the validity of two proxy report instruments designed to measure PA in children attending FCCHs. Methods A sample of 37 FCCH providers completed the Burdette parent proxy report, modified for the family child care setting for 107 children 3.4±1.2 years of age. A second sample of 42 FCCH providers completed the Harro parent and teacher proxy report, modified for the family child care setting, for 131 children 3.8±1.3 years of age. Both proxy reports were assessed for validity using accelerometry as a criterion measure. Results Significant positive correlations were observed between provider-reported PA scores from the modified Burdette proxy report and objectively measured total PA (r=0.30; p<0.01) and moderate-to-vigorous PA (MVPA; r=0.34; p<0.01). Across levels of provider-reported PA, both total PA and MVPA increased significantly in a linear dose-response fashion. The modified Harro proxy report was not associated with objectively measured PA. Conclusion Proxy PA reports completed by family child care providers may be a valid assessment option in studies where more burdensome objective measures are not feasible.

A design approach to the study of people's experiences with technologies in the context of public transport

Relevant to the study of people’s attitudes towards public transport use is the consideration to the role of technology as part of the travel experience. Technologies aim to enhance daily tasks but tend to change the way people interact with products and can be perceived as difficult to use. This is critical in the context of “public use” where products and services are to be used by the population at large: adults, children, elderly, people with disabilities, and tourists. From different perspectives, the topic of users and the use of technologies have been studied in the social sciences and human computer interaction fields; however, earlier approaches fail to address the ways in which experiential knowledge informs people’s interactions with products and technologies, and how such information could guide the design of future technologies. This paper describes a pilot study, part of a larger ongoing exploratory research that investigates people’s experiences with infrastructure, systems, and technologies in the context of public transport. The methodological approach included focus groups, field observations, and retrospective verbal reports. At this stage, the study found that four context led factors were the primary source of reference informing participants’ actions and interactions; they are: (i) context >> experience, (ii) context >> interface, (iii) context >> knowledge, (iv) context >> emotion.

Practice and Procedure - Uniform Civil Procedure Rules 1999 r 212(2) - whether draft expert reports must be disclosed

In Mitchell Contractors Pty Ltd v Townsville-Thuringowa Water Supply Joint Board [2004] QSC 329, Douglas J considered the issue of broad significance for litigation practitioners of whether draft expert reports fall within the description in r212(2) of the Uniform Civil Procedure Rules 1999 (Qld) of documents "consisting of a statement or report of an expert" and are therefore not privileged from disclosure.

Auditor communication in an evolving environment : going beyond SAS 600 auditors' reports on financial statements

In 1993 the Auditing Practices Board issued an expanded audit report, SAS 600 Auditors’ Reports on Financial Statements, in an attempt to educate users and to clarify certain matters pertaining to the audit function. This paper investigates the extent to which the new audit report, SAS 600, has been successful in aligning the views of auditors, preparers and users about issues dealt with in the expanded audit report, and the extent to which the three groups considered that it would be useful for additional matters, including corporate governance, to be reported upon by the auditor. Our findings suggest that SAS 600 has been successful in clarifying the purpose of the audit and the respective responsibilities of auditors and directors. However, to meet the expectations of users and to add more value, the audit report needs to provide more information about the findings of the audit.