The diagnostic accuracy and cost-effectiveness of magnetic resonance spectroscopy and enhanced magnetic resonance imaging techniques in aiding the localisation of prostate abnormalities for biopsy : a systematic review and economic evaluation

Peer reviewedPublisher PD

Comparison of the performance of photonic band-edge liquid crystal lasers using different dyes as the gain medium

The primary concern of this work is to study the emission characteristics of a series of chiral nematic liquid crystal lasers doped with different laser dyes (DCM, pyrromethene 580, and pyrromethene 597) at varying concentrations by weight (0.5-2 wt %) when optically pumped at 532 nm. Long-wavelength photonic band-edge laser emission is characterized in terms of threshold energy and slope efficiency. At every dye concentration investigated, the pyrromethene 597-doped lasers exhibit the highest slope efficiency (ranging from 15% to 32%) and the DCM-doped lasers the lowest (ranging from 5% to 13%). Similarly, the threshold was found to be, in general, higher for the DCM-doped laser samples in comparison to the pyrromethene-doped laser samples. These results are then compared with the spectral properties, quantum efficiencies and, where possible, fluorescence lifetimes of the dyes dispersed in a common nematic host. In accordance with the low thresholds and high slope efficiencies, the results show that the molar extinction coefficients and quantum efficiencies are considerably larger for the pyrromethene dyes in comparison to DCM, when dispersed in the liquid crystal host.open191

From theory to 'measurement' in complex interventions: methodological lessons from the development of an e-health normalisation instrument

<b>Background</b> Although empirical and theoretical understanding of processes of implementation in health care is advancing, translation of theory into structured measures that capture the complex interplay between interventions, individuals and context remain limited. This paper aimed to (1) describe the process and outcome of a project to develop a theory-based instrument for measuring implementation processes relating to e-health interventions; and (2) identify key issues and methodological challenges for advancing work in this field.<p></p> <b>Methods</b> A 30-item instrument (Technology Adoption Readiness Scale (TARS)) for measuring normalisation processes in the context of e-health service interventions was developed on the basis on Normalization Process Theory (NPT). NPT focuses on how new practices become routinely embedded within social contexts. The instrument was pre-tested in two health care settings in which e-health (electronic facilitation of healthcare decision-making and practice) was used by health care professionals.<p></p> <b>Results</b> The developed instrument was pre-tested in two professional samples (N = 46; N = 231). Ratings of items representing normalisation 'processes' were significantly related to staff members' perceptions of whether or not e-health had become 'routine'. Key methodological challenges are discussed in relation to: translating multi-component theoretical constructs into simple questions; developing and choosing appropriate outcome measures; conducting multiple-stakeholder assessments; instrument and question framing; and more general issues for instrument development in practice contexts.<p></p> <b>Conclusions</b> To develop theory-derived measures of implementation process for progressing research in this field, four key recommendations are made relating to (1) greater attention to underlying theoretical assumptions and extent of translation work required; (2) the need for appropriate but flexible approaches to outcomes measurement; (3) representation of multiple perspectives and collaborative nature of work; and (4) emphasis on generic measurement approaches that can be flexibly tailored to particular contexts of study

A systematic review of the clinical effectiveness of 64-slice or higher computed tomography angiography as an alternative to invasive coronary angiography in the investigation of suspected coronary artery disease

<p>Abstract</p> <p>Background</p> <p>This systematic review summarized recent evidence pertaining to the clinical effectiveness of 64-slice or higher computed tomography angiography (CTA) in patients with suspected coronary artery disease (CAD). If CTA proves to be a successful diagnostic performance measure, it could prevent the use of invasive diagnostic procedures in some patients. This would provide multiple health and cost benefits, particularly for under resourced areas where invasive coronary angiography is not always available.</p> <p>Methods</p> <p>A systematic method of literature searching and selection was employed with searches limited to December 2006 to March 2009. Included studies were quality assessed using National Health and Medical Research Council (NHMRC) diagnostic levels of evidence and a modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Individual and pooled diagnostic performance measures were calculated using standard meta-analytic techniques at the patient, vessel and segment level. A positive result was defined as greater than or equal to 50% stenosis.</p> <p>Results</p> <p>Twenty-eight studies were included in the systematic review examining 3,674 patients. The primary meta-analysis at the patient-level indicated a sensitivity of 98.2% and specificity of 81.6%. The median (range) positive predictive value (PPV) was 90.5% (76%-100%) and negative predictive value (NPV) 99.0% (83%-100%). In all vessels, the pooled sensitivity was 94.9%, specificity 89.5%, and median (range) PPV 75.0% (53%-95%) and NPV 99.0% (93%-100%). At the individual artery level, overall diagnostic accuracy appeared to be slightly higher in the left main coronary artery and slightly lower in the left anterior descending and circumflex artery. In all segments, the sensitivity was 91.3%, specificity 94.0% and median (range) PPV 69.0% (44%-86%) and NPV 99.0% (98%-100%).</p> <p>Conclusions</p> <p>The high sensitivity indicates that CTA can effectively identify the majority of patients with significant coronary artery stenosis. The high NPV at the patient, vessel and segment level establishes CTA as an effective non-invasive alternative to invasive coronary angiography (ICA) for the exclusion of stenosis.</p

Systematic review and economic modelling of the relative clinical benefit and cost-effectiveness of laparoscopic surgery and robotic surgery for removal of the prostate in men with localised prostate cancer

PMID: 23127367 [PubMed - indexed for MEDLINE] Free full text Funding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Research.Peer reviewedPublisher PD

Urinary EpCAM in urothelial bladder cancer patients: characterisation and evaluation of biomarker potential

Background: Epithelial cell adhesion molecule is overexpressed in bladder tumours and released from bladder cancer cells in vitro. We test the hypotheses that urinary EpCAM could act as a biomarker for primary bladder cancer detection and risk stratification. Methods: Epithelial cell adhesion molecule was measured by ELISA in urine from 607 patients with primary bladder tumours and in urine from 53 non-cancer controls. Mann–Whitney tests and ROC analyses were used to determine statistical significance and discrimination between non-cancer controls and different stages and grades of disease. Multivariable modelling and Kaplan–Meier analyses were used to determine prognostic significance. The structure of urinary EpCAM was investigated by western blotting and mass spectrometry. Results: Urinary EpCAM levels increase with stage and grade of bladder cancer. Alongside grade and stage, elevated urinary EpCAM is an independent indicator of poor prognosis with a hazard ratio of 1.76 for bladder cancer-specific mortality. The soluble form of EpCAM in urine is the extracellular domain generated by cleavage between ala243 and gly244. Further studies are required to define the influence of other urinary tract malignancies and benign urological conditions on urinary EpCAM. Conclusion: The extracellular domain of EpCAM is shed into urine by bladder tumours. Urinary EpCAM is a strong indicator of bladder cancer-specific survival, and may be useful within a multi-marker panel for disease detection or as a stand-alone marker to prioritise the investigation and treatment of patients. The mechanisms and effects of EpCAM cleavage in bladder cancer are worthy of further investigation, and may identify novel therapeutic targets

No role for quality scores in systematic reviews of diagnostic accuracy studies

BACKGROUND: There is a lack of consensus regarding the use of quality scores in diagnostic systematic reviews. The objective of this study was to use different methods of weighting items included in a quality assessment tool for diagnostic accuracy studies (QUADAS) to produce an overall quality score, and to examine the effects of incorporating these into a systematic review. METHODS: We developed five schemes for weighting QUADAS to produce quality scores. We used three methods to investigate the effects of quality scores on test performance. We used a set of 28 studies that assessed the accuracy of ultrasound for the diagnosis of vesico-ureteral reflux in children. RESULTS: The different methods of weighting individual items from the same quality assessment tool produced different quality scores. The different scoring schemes ranked different studies in different orders; this was especially evident for the intermediate quality studies. Comparing the results of studies stratified as "high" and "low" quality based on quality scores resulted in different conclusions regarding the effects of quality on estimates of diagnostic accuracy depending on the method used to produce the quality score. A similar effect was observed when quality scores were included in meta-regression analysis as continuous variables, although the differences were less apparent. CONCLUSION: Quality scores should not be incorporated into diagnostic systematic reviews. Incorporation of the results of the quality assessment into the systematic review should involve investigation of the association of individual quality items with estimates of diagnostic accuracy, rather than using a combined quality score

Indomethacin induces apoptosis via a MRP1-dependent mechanism in doxorubicin-resistant small-cell lung cancer cells overexpressing MRP1

Small-cell lung cancers (SCLCs) initially respond to chemotherapy, but are often resistant at recurrence. The non-steroidal anti-inflammatory drug indomethacin is an inhibitor of multidrug resistance protein 1 (MRP1) function. The doxorubicin-resistant MRP1-overexpressing human SCLC cell line GLC4-Adr was highly sensitive for indomethacin compared with the parental doxorubicin-sensitive line GLC4. The purpose of this study was to analyse the relationship between hypersensitivity to indomethacin and MRP1 overexpression. The experimental design involved analysis of the effect of MRP1 downregulation on indomethacin-induced cell survival and apoptosis in GLC4-Adr and GLC4, using siRNA. In addition the effect of indomethacin on glutathione levels and mitochondrial membrane potential was investigated. Small interfering RNAs directed against MRP1 reduced MRP1 mRNA levels twofold and reduced efflux pump function of MRP1, which was reflected by a 1.8-fold higher accumulation of MRP1 substrate carboxyfluorescein, in si-MRP1 versus si-Luciferase-transfected GLC4-Adr cells. Multidrug resistance protein 1 downregulation decreased initial high apoptosis levels 2-fold in GLC4-Adr after indomethacin treatment for 24 h, and increased cell survival (IC50) from 22.8±2.6 to 30.4±5.1 μM following continuous indomethacin exposure. Multidrug resistance protein 1 downregulation had no effect on apoptosis in GLC4 or on glutathione levels in both lines. Although indomethacin (20 μM) for 2 h decreased glutathione levels by 31.5% in GLC4-Adr, complete depletion of cellular glutathione by L-buthionine (S,R)-sulphoximine only resulted in a small increase in indomethacin-induced apoptosis in GLC4-Adr, demonstrating that a reduced cellular glutathione level is not the primary cause of indomethacin-induced apoptosis. Indomethacin exposure decreased mitochondrial membrane potential in GLC4-Adr cells, suggesting activation of the mitochondrial apoptosis pathway. Indomethacin induces apoptosis in a doxorubicin-resistant SCLC cell line through an MRP1-dependent mechanism. This may have implications for the treatment of patients with MRP1-overexpressing tumours