Reconsideration of blood donation testing strategy for human T-cell lymphotropic virus in Australia.

BACKGROUND AND OBJECTIVES: Universal testing of blood donations for human T-cell lymphotropic virus (HTLV) in Australia may no longer be appropriate given the low prevalence of HTLV infection and the mitigating effect of universal leucodepletion for cellular components. This study aimed to determine the most appropriate HTLV testing strategy using the Risk-Based Decision-Making Framework for Blood Safety. MATERIALS AND METHODS: The risk of HTLV transfusion-transmission using three testing strategies (universal, new-donor and no testing) and cost-effectiveness of the first two strategies were assessed using adaptations of published mathematical models. RESULTS: The overall prevalence for 2004-2014 was three HTLV-positives per million donations. It was estimated that annually, universal testing incurred a cost of approximately AUD $3 million and prevented 83 HTLV-positive cellular components from being issued, and new-donor testing cost approximately $225 000 and prevented 81 components. The number of cases of transfusion-transmitted HTLV and HTLV-associated disease prevented per year by universal and new-donor testing was essentially equivalent. According to preset risk thresholds, the risk of transfusion-transmission was negligible for universal and new-donor testing, and minimal without testing. CONCLUSION: Transfusion-transmission of HTLV is a minimal risk in Australia even without testing. However, any revision of testing strategy must consider not only risk and cost-effectiveness, but also stakeholder, ethical and regulatory perspectives. Considering all relevant criteria, new-donor testing is judged the optimal strategy because it is able to achieve almost the same outcomes as universal testing, at a fraction of the cost.

Anti-HCV immunoblot indeterminate results in blood donors: non-specific reactivity or past exposure to HCV?

BACKGROUND AND OBJECTIVE: The significance of anti-HCV immunoblot (IB) indeterminate results can be difficult to determine. We analysed results for blood donors tested on the MP Diagnostics HCV Blot 3.0 IB assay to determine whether indeterminate results representing past exposure to HCV could be distinguished from those due to non-specific reactivity. MATERIALS AND METHODS: Results for all donors tested by IB during the study period (July 2010 to December 2013) were included in this study. RESULTS: Of 131 donors tested by IB, 34 (26.0%) were negative, 38 (29.0%) were indeterminate, and 59 (45.0%) were positive. There was no significant difference in IB band reactivity strength between indeterminate and positive donors. The PRISM HCV chemiluminescent immunoassay (ChLIA) sample to cut-off (s/co) ratio distribution for the indeterminate donors was significantly higher than for those with biological false reactivity (P = 0·037), but significantly lower than for donors who were IB positive/HCV RNA negative (P < 0·001) or IB not tested/HCV RNA positive (P < 0·001). Of donors available for follow-up, 53.1% of the indeterminate group disclosed a putative risk factor for HCV infection compared to 39.4% (P < 0·001) for the IB-negative group, 76.6% (P = 0·065) for the IB-positive group and 83.4% (P < 0·001) for the HCV RNA-positive group. CONCLUSION: The results of this study indicate that PRISM ChLIA s/co ratios >2·00 with IB indeterminate results predict exposure to HCV, particularly in the presence of putative risk factors for HCV infection. These findings may be applied to optimizing counselling of donors with indeterminate HCV results.

Improving the economic value of photographic screening for optical coherence tomography-detectable macular oedema: a prospective, multicentre, UK study.

OBJECTIVES: To determine the best photographic surrogate markers for detecting sight-threatening macular oedema (MO) in people with diabetes attending UK national screening programmes. DESIGN: A multicentre, prospective, observational cohort study of 3170 patients with photographic signs of diabetic retinopathy visible within the macular region [exudates within two disc diameters, microaneurysms/dot haemorrhages (M/DHs) and blot haemorrhages (BHs)] who were recruited from seven study centres. SETTING: All patients were recruited and imaged at one of seven study centres in Aberdeen, Birmingham, Dundee, Dunfermline, Edinburgh, Liverpool and Oxford. PARTICIPANTS: Subjects with features of diabetic retinopathy visible within the macular region attending one of seven diabetic retinal screening programmes. INTERVENTIONS: Alternative referral criteria for suspected MO based on photographic surrogate markers; an optical coherence tomographic examination in addition to the standard digital retinal photograph. MAIN OUTCOME MEASURES: (1) To determine the best method to detect sight-threatening MO in people with diabetes using photographic surrogate markers. (2) Sensitivity and specificity estimates to assess the costs and consequences of using alternative strategies. (3) Modelled long-term costs and quality-adjusted life-years (QALYs). RESULTS: Prevalence of MO was strongly related to the presence of lesions and was roughly five times higher in subjects with exudates or BHs or more than two M/DHs within one disc diameter. Having worse visual acuity was associated with about a fivefold higher prevalence of MO. Current manual screening grading schemes that ignore visual acuity or the presence of M/DHs could be improved by taking these into account. Health service costs increase substantially with more sensitive/less specific strategies. A fully automated strategy, using the automated detection of patterns of photographic surrogate markers, is superior to all current manual grading schemes for detecting MO in people with diabetes. The addition of optical coherence tomography (OCT) to each strategy, prior to referral, results in a reduction in costs to the health service with no decrement in the number of MO cases detected. CONCLUSIONS: Compared with all current manual grading schemes, for the same sensitivity, a fully automated strategy, using the automated detection of patterns of photographic surrogate markers, achieves a higher specificity for detecting MO in people with diabetes, especially if visual acuity is included in the automated strategy. Overall, costs to the health service are likely to increase if more sensitive referral strategies are adopted over more specific screening strategies for MO, for only very small gains in QALYs. The addition of OCT to each screening strategy, prior to referral, results in a reduction in costs to the health service with no decrement in the number of MO cases detected. STUDY REGISTRATION: This study has been registered as REC/IRAS 07/S0801/107, UKCRN ID 9063 and NIHR HTA 06/402/49. SOURCE OF FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 51. See the HTA programme website for further project information.

Epidemiology of blindness attributable to diabetes in Scotland: change over 20 years in a defined population.

AIMS: To establish the incidence and prevalence of blindness attributable to diabetes in a defined population in Scotland during the period 2000-2009, and to compare these figures with published data from the previous decade in the same population. METHODS: All blind registrations during 2000-2009 in Fife, Scotland, UK were examined and included if diabetic retinopathy/maculopathy was the main cause of blindness. The annual incidence and point prevalence on 31 December 2009 of registered blindness attributable to diabetes were calculated in both the total population and the population with diabetes. These data were compared with figures for the period 1990-1999, using a two-tailed t-test, and subjected to Poisson regression analysis. RESULTS: In the population with diabetes, the mean incidence of blindness attributable to diabetes was 42.7 (sd 24.2, 95% CI 25- 60) per 100 000 per year for 2000-2009, compared with 64.3 for 1990-1999 (P = 0.062). The relative risk of developing blindness per year was 0.894 (95% CI 0.811- 0.988, P = 0.028) for 2000- 2009. The point prevalence on 31 December 2009 was 167 per 100 000 in the population with diabetes, vs 210 on 31 December 1999. CONCLUSION: Compared with the previous decade, the prevalence of blindness attributable to diabetes has decreased in the population with diabetes, with a trend towards a decrease in its incidence. This may be a consequence of an increased denominator population, resulting from better recording of diabetes and changes to the diagnostic criteria. Over the decade 2000-2009, the incidence of blindness attributable to diabetes fell by a mean of 10.6% per year in the population with diabetes.

Using electronic referral with digital imaging between primary and secondary ophthalmic services: a long term prospective analysis of regional service redesign.

PURPOSE: Demands on publicly funded ophthalmic services worldwide continue to increase with new treatments, waiting time targets, working time limits, and restricted budgets. These highlight the necessity to develop innovative ways of utilising existing capacity more effectively. METHOD: A new regional, fully electronic ophthalmic-referral service with digital imaging was trialled using existing information-technology (IT) infrastructure. Following successful pilot study, the service was rolled out regionally. Service delivery data was prospectively collated for all the attendances in the year prior to (2006) and the year following (2008) introduction. RESULTS: Comparing 2006 against 2008, median waiting times reduced (14 vs 4 weeks), and fewer new patients were observed (8714 vs 7462 P<0.0001), with 1359 referrals receiving electronic diagnosis (e-diagnosis). New patient did not arrive (635 vs 503 P<0.0001) and emergencies also reduced (2671 v 1984 P<0.0001). DISCUSSION: Novel use of existing IT infrastructure improves communication between primary and secondary care. This promotes more effective use of limited outpatient capacity by retaining patients with non-progressive, asymptomatic pathology in the community, whilst fast-tracking patients with sight-threatening disease. Resultant significant, sustained improvements in regional service delivery point to a simple model that could easily be adopted by other providers of universal healthcare globally.

Patient-reported complications from fiducial marker implantation for prostate image-guided radiotherapy.

OBJECTIVES: To report on complications from transrectal ultrasound-guided insertion of fiducial markers for prostate image-guided radiotherapy. METHODS: 234 patients who underwent transrectal fiducial marker insertion for prostate cancer image-guided radiotherapy were assessed retrospectively by questionnaire with regard to the duration and severity of eight symptoms experienced following the procedure. Pain during the implantation procedure was assessed according to the Wong-Baker faces pain scale. RESULTS: Of 234 patients, 32% had at least one new symptom after the procedure. The commonest new symptom following the procedure was urinary frequency affecting 16% of patients who had not been troubled by frequency beforehand. Haematuria, rectal bleeding, dysuria and haematospermia affected 9-13% of patients, mostly at Grade 1 or 2. Pain, obstruction, and fever and shivers affected 3-4% of patients. Grade 3 rectal bleeding, haematuria, fever and shivers, and urinary frequency affected 0.5-1.5% of patients. Only one patient had a Grade 4 complication (i.e. fever and shivers). Overall, 9% of patients had symptoms lasting more than 2 weeks. The commonest symptoms that lasted more than 2 weeks were frequency, dysuria, obstructive symptoms and rectal bleeding. Mean pain score during the procedure was 1.1 (range 0-5). CONCLUSION: Transrectal ultrasound-guided fiducial marker insertion for image-guided radiotherapy is well tolerated in the majority of prostate cancer patients. Most symptoms were Grade 1 or 2 in severity. Symptoms in the majority of patients last under 2 weeks. The most serious complication was sepsis in our study.

External quality assurance for image grading in the Scottish Diabetic Retinopathy Screening Programme.

AIMS: To develop and evaluate an image grading external quality assurance system for the Scottish Diabetic Retinopathy Screening Programme. METHOD: A web-based image grading system was developed which closely matches the current Scottish national screening software. Two rounds of external quality assurance were run in autumn 2008 and spring 2010, each time using the same 100 images. Graders were compared with a consensus standard derived from the top-level graders' results. After the first round, the centre lead clinicians and top-level graders reviewed the results and drew up guidance notes for the second round. RESULTS: Grader sensitivities ranged from 60.0 to 100% (median 92.5%) in 2008, and from 62.5 to 100% (median 92.5%) in 2010. Specificities ranged from 34.0 to 98.0% (median 86%) in 2008, and 54.0 to 100% (median 88%) in 2010. There was no difference in sensitivity between grader levels, but first-level graders had a significantly lower specificity than level-two and level-three graders. In 2008, one centre had a lower sensitivity but higher specificity than the majority of centres. Following the feedback from the first round, overall agreement improved in 2010 and there were no longer any significant differences between centres. CONCLUSIONS: A useful educational tool has been developed for image grading external quality assurance.

Towards the clinical application of X-ray phase contrast imaging.

Synchrotron-based propagation-based imaging, a type of phase contrast imaging, produces better soft tissue image contrast than conventional radiography. To determine whether the technique is directly transferable to the clinical environment for routine diagnostic or screening imaging, a micro-focus (100 microm spot-size) Molybdenum X-ray source with 0.03 mm molybdenum filtration was installed at a local hospital. Breast tissue samples, excised masses and mastectomies, were obtained directly from surgery and imaged at three geometries. The first geometry was optimised for visualizing phase contrast effects using a ray-line argument, the second was the same as that employed by Konica-Minolta in their commercial phase contrast system, and the third was the conventional contact arrangement. The three images taken of each tissue sample were comparatively scored in a pair-wise fashion. Scoring was performed by radiologist expert in mammography, general radiologists, associated clinicians and radiographers on high-resolution mammography rated monitors at two separate locations. Scoring indicated that the optimised and Konica geometries both outperformed the conventional mammographic geometry. An unexpected complication within the trial was the effect that the scoring platform and the associated display tools had on some of the scorer's responses. Additionally, the trial revealed that none of the conventional descriptors for image quality were adequate in the presence of phase contrast enhancements.

Planning and implementing an implanted fiducial programme for prostate cancer radiation therapy.

Using implanted gold seeds as fiducial markers to verify the position of the prostate in radiation therapy is well accepted and is becoming the standard of practice and requirement for international multicentre trials. In 2006 the decision was made at the Peter MacCallum Caner Centre (Peter Mac) to plan for and implement this process as standard clinical practice for radical dose prostate treatments (74-78 Gy). Before this, programme verification of field placement for prostate cancer radiation treatment was routinely carried out using regular off-line electronic portal imaging with matching of bony anatomy. A small multidisciplinary team investigated and assisted in the implementation of this new practice across the Peter Mac sites at East Melbourne and our three satellite centres. Issues considered included seed size, number and position in the prostate, implant equipment, imaging equipment and procedure and consent and information forms. The use of a custom made fiducial pack, comprehensive patient information and a daily on-line imaging process was implemented. The experience of the first 28 patients at Peter Mac from January 2007 to May 2007 inclusive is reported on.

Floppy iris behaviour during cataract surgery: associations and variations.

AIM: To assess the association of floppy iris behaviour during cataract surgery with use of alpha-1-antagonists and diabetes mellitus. METHODS: 1842 eyes of 1786 patients undergoing phacohoemulsification surgery were prospectively enrolled. The use of commonly prescribed alpha-1-antagonists and the presence or absence of diabetes mellitus were noted. The occurrence of any of the features of the intraoperative floppy iris syndrome (IFIS) was noted by surgeons blinded to the patient's history. RESULTS: 57% of patients receiving tamsulosin showed features of IFIS compared with 1% of the non-tamsulosin group (p<0.001). Of these, more than half the patients manifested the syndrome in an incomplete form. Only 1 of the 51 patients receiving other alpha-1-antagonists had IFIS. Diabetes was also not associated with IFIS (p = 1). CONCLUSIONS: Tamsulosin is significantly associated with floppy iris behaviour during cataract surgery. But not all of these patients will necessarily show all or any features of IFIS. The floppy iris syndrome is likely to represent a continuum of severity. Various undefined factors, diabetes not being one of them, may have a contributory role. Non-selective alpha-1-antagonists are unlikely to be associated with IFIS.

MRI in the assessment of internal derangement and pain within the temporomandibular joint: a pictorial essay.

In this pictorial essay we aim to illustrate the normal temporomandibular joint (TMJ) and the common abnormalities of the osseous, cartilaginous and soft tissue components. These include disc (meniscus) displacement, deformities and perforations, abnormalities of disc and condylar movement, joint effusions, synovial proliferation, condylar deformity and erosions, degenerative change and abnormal retrodiscal enhancement.

Calcification on the chest X-ray: a pictorial review.

There are numerous causes of calcification on the chest radiograph. Their striking appearance can lead to anxiety among junior medical staff. This article aims to categorize these appearances, and to give examples of the most common causes seen.

A Saccharomyces gene family involved in invasive growth, cell-cell adhesion, and mating.

The cell wall of bakers' yeast contains a family of glycosyl-phosphatidylinositol (GPI)-linked glycoproteins of domain structure similar to the adhesins of pathogenic fungi. In wild-type cells each of these proteins has a unique function in different developmental processes (mating, invasive growth, cell-cell adhesion, or filamentation). What unifies these developmental events is adhesion, either to an inert substrate or to a cell. Although they differ in their specificities, many of these proteins can substitute for each other when overexpressed. For example, Flo11p is required during vegetative growth for haploid invasion and diploid filamentation, whereas Fig2p is required for mating. When overexpressed, Flo11p and Fig2p can function in mating, invasion, filamentation, and flocculation. The ability of Flo11p to supply Fig2p function in mating depends on its intracellular localization to the mating projection, where Fig2p normally functions in the adhesion of mating cells. Our data show that even distant family members retain the ability to carry out disparate functions if localized and expressed appropriately.

Appendiceal rupture during pelvic ultrasound examination.

A case of rupture of the appendix during pelvic ultrasound is presented.

Gastrostomy: an improved technique.

Gastrostomy is a commonly performed procedure. The forceps described in this article help make this procedure easier and safer to carry out, reducing the need for complex and costly equipment. The forceps used have been adapted from standard surgical steel instruments by soldering a guidance device to one jaw. This device enables guided placement of a needle alongside the forceps tip. Any hospital technical service department could adapt standard forceps for this procedure.

Percutaneous transhepatic changing of an endoscopically placed stent.

Biliary stents are commonly positioned for the relief of obstructive jaundice secondary to malignancy. It is occasionally necessary to percutaneously replace a biliary stent placed by the endoscopist. This is usually because there has been progression of the tumour, which has prevented further endoscopic access. The technique described has real merit since it can further extend palliation.

Development of proliferative retinopathy in patients with long-standing insulin-dependent diabetes mellitus.

PURPOSE AND METHOD: Some patients with long-standing insulin-dependent diabetes mellitus (IDDM) develop little or no retinopathy. Using a clinic-based questionnaire and examination, we investigated a group of patients with over 40 years or more of IDDM who had been followed up at the King's Diabetes Centre for an average of 40 years. We compared those who had developed proliferative diabetic retinopathy during their disease with those with minimal or no retinopathy. RESULTS: The study did not find any statistically significant differences between the two groups to suggest why some long-term insulin-dependent diabetics develop little retinopathy. Those who developed sight-threatening retinal complications did so at an average of 35 years after diagnosis and it resulted in little visual disablement. Very few patients in either group had developed other significant complications. CONCLUSIONS: This study details an interesting group of patients with long-term IDDM mellitus with a mean follow-up period of 40 years. Some patients with long-standing IDDM develop little or no retinopathy. With the advent of community ophthalmic screening, these patients are now rarely seen in the eye clinic. Those who did develop retinal complications and required treatment have remarkably little visual disablement. However, these complications developed late in the history of their disease, emphasising the need for continued screening.