Comparison of the performance of HPV tests in women with abnormal cytology: results of a study within the NHS cervical screening programme.

OBJECTIVE: The use of testing for human papillomavirus (HPV) is now recognized as an efficient means of triaging women with low-grade cytological abnormalities to either immediate referral to colposcopy or return to routine recall. We aimed to determine the sensitivity and specificity of each of four newer tests for HPV relative to the Qiagen Hybrid Capture 2 (HC2) assay in order to determine whether they could be approved for use in triage in the NHS cervical screening programme. METHODS: We compared the performance of each of four different HPV assays (Abbott M2000, Roche Cobas, Hologic Cervista and Gen-Probe APTIMA) with that of HC2 in order to determine the sensitivity and specificity of each test relative to HC2 for the detection of cervical intraepithelial neoplasia (CIN) grade 2 or worse, using routine cytology samples reported as borderline (atypical squamous cells) or mild dyskaryosis (low-grade squamous intraepithelial lesion) from six laboratories in England. All women who were found to be HPV positive on any test were referred to colposcopy. RESULTS: Between 2072 and 4217 tests were performed with each assay. All four assays were shown to have a relative sensitivity of no worse than 95% compared with HC2 when a cut-off of 2 relative light units (RLU) was used. All assays had higher relative specificity than HC2 for both borderline and mild cytology referrals (1.06-1.61). CONCLUSIONS: All assays tested met the criteria required. Consequently, all have now been approved for use in HPV triage in the NHS cervical screening programme.

The establishment of a 3D breast photography service in medical illustration.

This paper aims to describe the development of a 3D breast photography service managed by the Medical Illustration Department, in the Belfast Health and Social Care Trust, Northern Ireland. Dedicated 3D breast photography equipment was installed in Medical Illustration for 18 months. Women were referred for a variety of indications including pre- and post-surgical assessment. A dedicated 3D breast photography protocol was developed locally and this requires further refinement to allow reproducibility in other centres. There are image/data artefacts associated with this technology and special techniques are required to reduce these. Specialist software is necessary for clinicians and scientists to use 3D breast photography data in surgical planning and measurement of surgical outcome.

Variation in radiographic protocols in paediatric interventional cardiology.

The aim of this work is to determine current radiographic protocols in paediatric interventional cardiology (IC) in the UK and Ireland. To do this we investigated which imaging parameters/protocols are commonly used in IC in different hospitals, to identify if a standard technique is used and illustrate any variation in practice. A questionnaire was sent to all hospitals in the UK and Ireland which perform paediatric IC to obtain information on techniques used in each clinical department and on the range of clinical examinations performed. Ethical and research governance approval was sought from the Office for Research Ethics Committees Northern Ireland and the individual trusts. A response rate of 79% was achieved, and a wide variation in technique was found between hospitals. The main differences in technique involved variations in the use of an anti-scatter grid and the use of additional filtration to the radiation beam, frame rates for digital acquisition and pre-programmed projections/paediatric specific programming in the equipment. We conclude that there is no standard protocol for carrying out paediatric IC in the UK or Ireland. Each hospital carries out the IC procedure according to its own local protocols resulting in a wide variation in radiation dose.

The NHS breast screening programme (pathology) EQA: experience in recent years relating to issues involved in individual performance appraisal.

BACKGROUND: The original role of the National Health Service breast screening programme (pathology) external quality assessment (EQA) scheme was educational; it aimed to raise standards, reinforce use of common terminology, and assess the consistency of pathology reporting of breast disease in the UK. AIMS/METHODS: To examine the performance (scores) of pathologists participating in the scheme in recent years. The scheme has evolved to help identify poor performers, reliant upon setting an acceptable cutpoint. Therefore, the effects of different cutpoint strategies were evaluated and implications discussed. RESULTS/CONCLUSIONS: Pathologists who joined the scheme improved over time, particularly those who did less well initially. There was no obvious association between performance and the number of breast cancer cases reported each year. This is not unexpected because the EQA does not measure expertise, but was established to demonstrate a common level of performance (conformity to consensus) for routine cases, rather than the ability to diagnose unusual/difficult cases. A new method of establishing cutpoints using interquartile ranges is proposed. The findings also suggest that EQA can alter a pathologist's practice: those who leave the scheme (for whatever reason) have, on average, marginally lower scores. Consequently, with the cutpoint methodology currently used (which is common to several EQA schemes) there is the potential for the cutpoint to drift upwards. In future, individuals previously deemed competent could subsequently be erroneously labelled as poor performers. Due consideration should be given to this issue with future development of schemes.

Impact of a national external quality assessment scheme for breast pathology in the UK.

BACKGROUND: This article presents the results and observed effects of the UK National Health Service Breast Screening Programme (NHSBSP) external quality assurance scheme in breast histopathology. AIMS/METHODS: The major objectives were to monitor and improve the consistency of diagnoses made by pathologists and the quality of prognostic information in pathology reports. The scheme is based on a twice yearly circulation of 12 cases to over 600 registered participants. The level of agreement was generally measured using kappa statistics. RESULTS: Four main situations were encountered with respect to diagnostic consistency, namely: (1) where consistency is naturally very high-this included diagnosing in situ and invasive carcinomas (and certain distinctive subtypes) and uncomplicated benign lesions; (2) where the level of consistency was low but could be improved by making guidelines more detailed and explicit-this included histological grading; (3) where consistency could be improved but only by changing the system of classification-this included classification of ductal carcinoma in situ; and (4) where no improvement in consistency could be achieved-this included diagnosing atypical hyperplasia and reporting vascular invasion. Size measurements were more consistent for invasive than in situ carcinomas. Even in cases where there is a high level of agreement on tumour size, a few widely outlying measurements were encountered, for which no explanation is readily forthcoming. CONCLUSIONS: These results broadly confirm the robustness of the systems of breast disease diagnosis and classification adopted by the NHSBSP, and also identify areas where improvement or new approaches are required.

Image registration and subtraction for the visualization of change in diabetic retinopathy screening.

Diabetic retinopathy (DR) is a leading cause of blindness in people of working age in developed countries. DR is characterized by lesions of the retinal microvasculature. This paper describes a technique for visualizing the changes which occur in retinal pathology over a 1 year interval. Pairs of retinal images of the same eye were acuired 12 months apart within a DR screening programme. The images were normalized, registered and subtracted to generate a contrast-enhanced difference image displaying changes in retinal appearance. The normalization factor and registration error were quantified for 104 pairs of retinal images.

3D surface accuracy of CAD generated skull defect contour.

The creation of a satisfactory cosmetic outcome in the repair of cranial defects relies on manual skill. However, computer aided design is gaining acceptance in the creation of custom cranial implants. The purpose of this work is to demonstrate the accuracy of a CAD generated skull defect contours using 3D difference maps. 3D multi-slice CT scanning was carried out on a life size plastic skull. Surface models were generated of the original skull and of temporofrontal and parietal defects. Surface contours were interpolated towards the centre of the defect from the edges where it was blended. The CAD contour deviation ranged from 0.0 mm to 2.0 mm with 80% of the total defect area less than 0.66 mm as measured by difference maps. CAD techniques can be used to produce contours for the repair of cranial defects with minimum deviation from the original skull contour. This enables accurate design and production of cranial implants.

"Virtual unwrapping" of a mummified hand.

The purpose of this work is to demonstrate the feasibility of medical virtual reality technologies in the investigation of a mummified hand. The Ulster Museum obtained the mummy hand, which originated from Thebes, without any identifying information. The mummified hand was investigated using conventional X-ray and 3D multi-slice Computed Tomography (CT). Imaging revealed a range of fractures of the wrist, metacarpals and phalanges whilst 3D CT demonstrated internal structures using volume rendering. The absence of any features of bone healing at the fracture sites would imply that they occurred just prior to death or in the mummified state possibly during excavation. Conventional X-ray imaging indicated that the hand, although small, was likely to have originated from an adult. Medical imaging and virtual reality display will enable us to produce a rapid prototyped model using fused deposition technology. Therefore, further paleopathological research can be performed on the replica without the need to handle the original specimen.

Fuels for memory: the role of oxygen and glucose in memory enhancement.

Recent studies indicate that some aspects of memory can be enhanced by the administration of oxygen or glucose. Considering the dependency of glucose metabolism upon oxygen supply, the present study predicted that administering a combination of 100% oxygen with glucose would have greater memory-enhancing effects than when either substance was administered alone. In a placebo-controlled study, 104 healthy adults were given a glucose or placebo drink, and inhaled 100% oxygen or air for 1 min, before carrying out a number of everyday memory tasks designed to measure short-term and long-term memory. Results showed support for the enhancing effects of oxygen (but not for glucose) on delayed recall. These findings are discussed in relation to the possible cholinergic properties of oxygen and glucose and the implications for their clinical use.

Assessment of distortion in a three-dimensional rotational angiography system.

The purpose of this project was to determine the degree of geometrical distortion in a three-dimensional (3D) image volume generated by a digital fluorography system with rotational image acquisition capabilities. 3D imaging is a valuable adjunct in neuroangiography for visualization and measurement of cerebral aneurysms and for determination of the optimum projection for intervention. To enable spatially accurate 3D reconstruction the system must correct for geometrical distortion in the image intensifier television system as well as for deviations in gantry motion. 3D volumes were reconstructed from 100 X-ray projections acquired over a 180 degrees arc over a period of 8 s. A phantom was constructed to assess geometrical distortion in the three dimensions. The phantom consisted of 1 mm diameter ball bearings embedded in Perspex in a cubic lattice configuration. The ball bearings were placed at 20 mm intervals over a 140 mm cubic volume. Distortion was assessed by taking measurements between points of known separation and using a differential distortion measurement. The maximum error in the 3D location of objects was found to be 1.4 mm, while the differential distortion was found to range from -1.0% to +2.3%. The 3D images were found to have negligible visual distortion, enabling subjective assessments to be made with confidence to aid intervention.

Abdominal aortic aneurysm and stent graft phantom manufactured by medical rapid prototyping.

A novel human aorta phantom built by medical rapid prototypingfor use in computed tomography (CT) scanning is described. The phantom contained a stent graft that was deployed internally to mimic a repaired aortic aneurysm. The phantom was produced to allow assessment of the CT appearance of a stent graft inside an aorta using the new virtual intravascular endoscopy image presentation technique. The stent graft utilized contained suprarenal components (metalfixation struts), and these were placed with these struts covering the renal artery ostia. The phantom was filled with iodinated contrast medium at a concentration that produced a density similar to that found in normal CT angiographic scanning. The model was scanned at a variety of slice thicknesses, pitch and image reconstruction intervals. Visualization of the stent suprarenal components in relation to the renal artery ostia is shown and the overestimation of stent wire strut diameter demonstrated.

Management of the child dental patient.

The ultimate goals of behavior management for children receiving dental treatment are to achieve optimum oral health, instill a positive attitude in children and their parents regarding oral health, instill confidence in children regarding their ability to undergo dental treatment successfully and complete treatment in a safe and expeditious manner with the least invasive technique possible. These goals can only be achieved by using methods of behavior management that encourage positive communication and reduce anxiety for the patient, parent, and staff while educating children and parents about the importance of oral health. All behavior management techniques must consider the risks and benefits to the child, his or her parents, as well as the dental staff.

A pragmatic randomised controlled trial to evaluate the cost-effectiveness of a physical activity intervention as a treatment for depression: the treating depression with physical activity (TREAD) trial.

OBJECTIVE: The TREAting Depression with physical activity (TREAD) study investigated the cost-effectiveness of a physical activity intervention, in addition to usual general practitioner care, as a treatment for people with depression. DESIGN: An individually randomised, pragmatic, multicentre randomised controlled trial with follow-up at 4, 8 and 12 months. A subset of participants took part in a qualitative study that investigated the acceptability and perceived benefits of the intervention. SETTING: General practices in the Bristol and Exeter areas. PARTICIPANTS: Aged 18-69 years with an International Statistical Classification of Diseases and Related Health Problems, 10th Edition (ICD-10) diagnosis of depression and scoring ≥ 14 on the Beck Depression Inventory (BDI). Those who were unable to complete self-administered questionnaires in English, with medical contraindications to physical activity or with psychosis, bipolar disorder or serious drug abuse were excluded. INTERVENTIONS: We devised an intervention designed to encourage choice and autonomy in the adoption of physical activity. It consisted of up to three face-to-face and ten telephone contacts delivered by a trained physical activity facilitator over an 8-month period. MAIN OUTCOME MEASURES: The primary outcome was the BDI score measured at 4 months. Secondary outcomes included depressive symptoms over the 12 months and quality of life, antidepressant use and level of physical activity. RESULTS: The study recruited 361 patients, with 182 randomised to the intervention arm and 179 to the usual care arm; there was 80% retention at the 4-month follow-up. The intervention group had a slightly lower BDI score at 4 months [-0.54, 95% confidence interval (CI) -3.06 to 1.99] but there was no evidence that the intervention improved outcome for depression. Neither was there any evidence to suggest a difference in the prescription of or self-reported use of antidepressants. However, the amount of physical activity undertaken by those who had received the intervention was increased (odds ratio 2.3, 95% CI 1.3 to 3.9) and was sustained beyond the end of the intervention. From a health-care perspective, the intervention group was more costly than the usual care group, with the cost of the intervention £220 per person on average. It is therefore extremely unlikely that the intervention is cost-effective as a treatment for depression using current willingness-to-pay thresholds. CONCLUSIONS: This physical activity intervention is very unlikely to lead to any clinical benefit in terms of depressive symptoms or to be a cost-effective treatment for depression. Previous research has reported some benefit and there are three possible reasons for this discrepancy: first, even though the intervention increased self-reported physical activity, the increase in activity was not sufficiently large to lead to a measurable influence; second, only more vigorous activity might be of benefit; and third, previous studies had recruited individuals with a pre-existing commitment to physical activity. Future research is needed to identify and explain the mechanisms by which depression might be effectively treated, including, in particular, specific guidance on the optimum type, intensity and duration of physical activity required to produce a therapeutic effect. TRIAL REGISTRATION: Current Controlled Trials ISRCTN16900744. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 10. See the HTA programme website for further project information.

Validation of a passive stereophotogrammetry system for imaging of the breast: a geometric analysis.

The overall aim of this study was to assess the accuracy, reproducibility and stability of a high resolution passive stereophotogrammetry system to image a female mannequin torso, to validate measurements made on the textured virtual surface compared with those obtained using manual techniques and to develop an approach to make objective measurements of the female breast. 3D surface imaging was carried out on a textured female torso and measurements made in accordance with the system of mammometrics. Linear errors in measurements were less than 0.5mm, system calibration produced errors of less than 1.0mm over 94% over the surface and intra-rater reliability measured by ICC=0.999. The mean difference between manual and digital curved surface distances was 1.36 mm with maximum and minimum differences of 3.15 mm and 0.02 mm, respectively. The stereophotogrammetry system has been demonstrated to perform accurately and reliably with specific reference to breast assessment.

Temperature elevation during simulated polymethylmethacrylate (PMMA) cranioplasty in a cadaver model.

The aims of this study were to: (i) obtain temperature measurements during in vitro polymerisation of polymethylmethacrylate (PMMA) disks of a range of thicknesses; and (ii) obtain tissue temperature measurements at various locations within a skull defect during a simulated PMMA cranioplasty procedure using a cadaver. In vitro, higher temperatures were recorded with increasing PMMA thickness. During the simulated cranioplasty, the maximum temperature was observed inside the PMMA sample, with nearby tissues being exposed to temperatures of greater than 50 degrees C over prolonged periods. There is conflicting information in the literature concerning the sensitivity of brain tissue and bone to elevated temperatures. Preoperatively fabricated PMMA cranioplasty prostheses are recommended.

Algorithms for digital image processing in diabetic retinopathy.

This work examined recent literature on digital image processing in the field of diabetic retinopathy. Algorithms were categorized into 5 steps (preprocessing; localization and segmentation of the optic disk; segmentation of the retinal vasculature; localization of the macula and fovea; localization and segmentation of retinopathy). The variety of outcome measures, use of a gold standard or ground truth, data sample sizes and the use of image databases is discussed. It is intended that our classification of algorithms into a small number of categories, definition of terms and discussion of evolving techniques will provide guidance to algorithm designers for diabetic retinopathy.

Technical validation of the Di3D stereophotogrammetry surface imaging system.

The purpose of this work was to assess the technical performance of a three-dimensional surface imaging system for geometric accuracy and maximum field of view. The system was designed for stereophotogrammetry capture of digital images from three-dimensional surfaces of the head, face, and neck. A mannequin head was prepared for imaging by adding texture in the form of red paint, and facial landmarks as black ink dots. The mannequin was imaged at the manufacturer's recommended settings for human studies. Colour-coded surface difference images among repeated exposures were computed. We compared measurements of physical linear distance with digital measurements. The three-dimensional stereophotogrammetry system had a mean error in the three-dimensional surfaces of 0.057mm, a repeatability error (variance) of 0.0016mm, a mean error of 0.6mm in linear measurements compared with manual measurements, and a field of view of 170 degrees horizontally and 102 degrees vertically.

Effect of suprarenal fixation of aortic stent-grafts on the renal artery ostia: assessment of morphological changes by virtual intravascular endoscopy.

PURPOSE: To investigate the morphological effects of suprarenal fixation of aortic stent-grafts on the renal artery ostia (RaO) by analysis of suprarenal stent wire distribution and vascular calcification across the RaO using virtual intravascular endoscopy (VIE). METHODS: Fourteen consecutive patients (11 men; mean age 75 years) from a single institution were studied following endovascular aortic aneurysm repair (EVAR) using the Zenith endograft system from September 1999 to March 2002. Imaging assessment included computed tomographic (CT) measurement of renal artery intraluminal ostial diameter and quantification and analysis of uncovered stent struts across the RaO and radiological determination of RaO calcification. Morphological changes following EVAR at 3 time points (before and within 1 week after stent-grafting, and at the most recent follow-up) were compared for each patient to determine whether suprarenal stent struts or RaO calcification affected intraluminal ostial diameter. Renal function was assessed by temporal measurements of serum creatinine concentration and creatinine clearance. RESULTS: The renal ostium was distorted to variable degrees in all cases at a mean follow-up of 41+/-6.6 months. An increase in ostial diameter was identified in most patients if the right RaO was calcified when comparing the 1-week postoperative and most recent follow-up CT images (p<0.05). There was no direct relationship between the number of stent struts crossing the RaO and the morphological/dimensional changes (p>0.05). Renal function was not significantly affected. CONCLUSION: Patients undergoing suprarenal fixation of aortic stent-grafts experienced morphological changes of the RaO to a variable extent at midterm follow-up. Although the presence of stent struts did not significantly affect dimensional changes, we observed that calcification at the renal artery ostium may influence the development of atherosclerotic effects as a direct relationship between the calcification and ostial diameter. Future studies utilizing VIE to determine the long-term safety of this technique in these particular patients requires investigation.