The clinical assessment of systemic hypertension in optometric practice

This thesis sets out to examine in detail the condition of systemic hypertension (high Blood Pressure) in relation to optometric practice in the United Kingdom. Systemic hypertension, which is asymptomatic in the early stages, is diagnosed from the Blood Pressure (BP) measurement recorded by a sphygmomanometer and/or from the complications that have developed in target organs. Optometric practice based surveys revealed that diagnosed systemic hypertension was the most prevalent cardiovascular medical condition (20.5%). Measurement of BP of patients in this sample revealed that if an optometrist included sphygmomanometry into the sight examination then at least one patient each day would be referred for suspect systemic hypertension. Optometric opinion felt that the measurement of BP in optometric practice would advance the profession, being appreciated by both patients and General Practitioners (GPs), but was felt to be an unnecessary routine procedure. The present sight examination for the systemic hypertensive is similar to that of the normotensive patient, but may involve an altered fundus examination and a visual field test. The GPs were in favour of optometric BP measurement and a future role in the share care management of the systemic hypertensive. The application of a new pictorial grading scale for the grading of vascular changes associated with pre-malignant systemic hypertension was found to be both accurate and reliable. Clinical trial of the grading scale in optometric practice found positive correlations between BP and increasing severity of the retinal vascular features. The subtle pre-malignant vascular changes require reliable accurate detection and analysis to assist in the management of the systemic hypertensive patient. Vessel width was shown to decrease with increasing age. Image analysis of the A/V ratio, arteriolar tortuosity and focal calibre changes revealed a positive correlation to the patient's BP (p<0.001). The retinal vasculature is relatively stable longitudinally with only minor changes in response to early disease states. Age and elevated BP increased a patient's risk of developing systemic medical conditions over a two-year period. The application of the pictorial grading scale to optometric practice and training the optometrist in the use of sphygmomanometry would improve the management of the systemic hypertensive patient in optometric practice. Future advances in image analysis hold substantial benefits for the detection and monitoring of subtle vascular changes associated with systemic hypertension.

The clinical utility of the middle latency and 40Hz auditory evoked potentials in audiological electrodiagnosis

The two elcctrophysiological tests currently favoured in the clinical measurement of hearing threshold arc the brainstorm evoked potential (BAEP) and the slow vertex response (SVR). However, both tests possess disadvantages. The BAEP is the test of choice in younger patients as it is stable at all levels of arousal, but little information has been obtained to date at a range of frequencies. The SVR is frequency specific but is unreliable in certain adult subjects and is unstable during sleep or in young children. These deficiencies have prompted research into a third group of potentials, the middle latency response (MLR) and the 40HZ responses. This research has compared the SVR and 40HZ response in waking adults and reports that the 40HZ test can provide a viable alternative to the SVR provided that a high degree of subject relaxation is ensured. A second study examined the morphology of the MLR and 40HZ during sleep. This work suggested that these potentials arc markedly different during sleep and that methodological factors have been responsible for masking these changes in previous studies. The clinical possibilities of tone pip BAEPs were then examined as these components were proved to be the only stable responses present in sleep. It was found that threshold estimates to 5OOHz, lOOOHz and 4000Hz stimuli could be made to within 15dBSL in most cases. A final study looked more closely at methods of obtaining frequency specific information in sleeping subjects. Threshold estimates were made using established BAEP parameters and this was compared to a 40HZ procedure which recorded a series of BAEPs over a 100msec. time sweep. Results indicated that the 40mHz procedure was superior to existing techniques in estimating threshold to low frequency stimuli. This research has confirmed a role for the MLR and 40Hz response as alternative measures of hearing capability in waking subjects and proposes that the 40Hz technique is useful in measuring frequency specific thresholds although the responses recorded derive primarily from the brainstem.

Optimising the clinical analysis of retinal image quality in the human eye

Visual perception is dependent on both light transmission through the eye and neuronal conduction through the visual pathway. Advances in clinical diagnostics and treatment modalities over recent years have increased the opportunities to improve the optical path and retinal image quality. Higher order aberrations and retinal straylight are two major factors that influence light transmission through the eye and ultimately, visual outcome. Recent technological advancements have brought these important factors into the clinical domain, however the potential applications of these tools and considerations regarding interpretation of data are much underestimated. The purpose of this thesis was to validate and optimise wavefront analysers and a new clinical tool for the objective evaluation of intraocular scatter. The application of these methods in a clinical setting involving a range of conditions was also explored. The work was divided into two principal sections: 1. Wavefront Aberrometry: optimisation, validation and clinical application The main findings of this work were: • Observer manipulation of the aberrometer increases variability by a factor of 3. • Ocular misalignment can profoundly affect reliability, notably for off-axis aberrations. • Aberrations measured with wavefront analysers using different principles are not interchangeable, with poor relationships and significant differences between values. • Instrument myopia of around 0.30D is induced when performing wavefront analysis in non-cyclopleged eyes; values can be as high as 3D, being higher as the baseline level of myopia decreases. Associated accommodation changes may result in relevant changes to the aberration profile, particularly with respect to spherical aberration. • Young adult healthy Caucasian eyes have significantly more spherical aberration than Asian eyes when matched for age, gender, axial length and refractive error. Axial length is significantly correlated with most components of the aberration profile. 2. Intraocular light scatter: Evaluation of subjective measures and validation and application of a new objective method utilising clinically derived wavefront patterns. The main findings of this work were: • Subjective measures of clinical straylight are highly repeatable. Three measurements are suggested as the optimum number for increased reliability. • Significant differences in straylight values were found for contact lenses designed for contrast enhancement compared to clear lenses of the same design and material specifications. Specifically, grey/green tints induced significantly higher values of retinal straylight. • Wavefront patterns from a commercial Hartmann-Shack device can be used to obtain objective measures of scatter and are well correlated with subjective straylight values. • Perceived retinal stray light was similar in groups of patients implanted with monofocal and multi focal intraocular lenses. Correlation between objective and subjective measurements of scatter is poor, possibly due to different illumination conditions between the testing procedures, or a neural component which may alter with age. Careful acquisition results in highly reproducible in vivo measures of higher order aberrations; however, data from different devices are not interchangeable which brings the accuracy of measurement into question. Objective measures of intraocular straylight can be derived from clinical aberrometry and may be of great diagnostic and management importance in the future.

The antimicrobial efficacy of copper alloy furnishing in the clinical environment:a crossover study

Objective. To determine whether copper incorporated into hospital ward furnishings and equipment can reduce their surface microbial load. Design. A crossover study. Setting. Acute care medical ward with 19 beds at a large university hospital. Methods. Fourteen types of frequent-touch items made of copper alloy were installed in various locations on an acute care medical ward. These included door handles and push plates, toilet seats and flush handles, grab rails, light switches and pull cord toggles, sockets, overbed tables, dressing trolleys, commodes, taps, and sink fittings. Their surfaces and those of equivalent standard items on the same ward were sampled once weekly for 24 weeks. The copper and standard items were switched over after 12 weeks of sampling to reduce bias in usage patterns. The total aerobic microbial counts and the presence of indicator microorganisms were determined. Results. Eight of the 14 copper item types had microbial counts on their surfaces that were significantly lower than counts on standard materials. The other 6 copper item types had reduced microbial numbers on their surfaces, compared with microbial counts on standard items, but the reduction did not reach statistical significance. Indicator microorganisms were recovered from both types of surfaces; however, significantly fewer copper surfaces were contaminated with vancomycin-resistant enterococci, methicillin-susceptible Staphylococcus aureus, and coliforms, compared with standard surfaces. Conclusions. Copper alloys (greater than or equal to 58% copper), when incorporated into various hospital furnishings and fittings, reduce the surface microorganisms. The use of copper in combination with optimal infection-prevention strategies may therefore further reduce the risk that patients will acquire infection in healthcare environments.

Imaging of the human fundus in the clinical setting:past present and future

The human fundus is a complex structure that can be easily visualized and the world of ophthalmology is going through a golden era of new and exciting fundus imaging techniques; recent advances in technology have allowed a significant improvement in the imaging modalities clinicians have available to formulate a diagnostic and treatment plan for the patient, but there is constant on-going work to improve current technology and create new ideas in order to gather as much information as possible from the human fundus. In this article we shall summarize the imaging techniques available in the standard medical retina clinic (i.e. not limited to the research lab) and delineate the technologies that we believe will have a significant impact on the way clinicians will assess retinal and choroidal pathology in the not too distant future.

A randomised controlled trial of the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia:the ECLIPSE trial

BACKGROUND: Heavy menstrual bleeding (HMB) is a common problem, yet evidence to inform decisions about initial medical treatment is limited. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) (Mirena(®), Bayer) compared with usual medical treatment, with exploration of women's perspectives on treatment. DESIGN: A pragmatic, multicentre randomised trial with an economic evaluation and a longitudinal qualitative study. SETTING: Women who presented in primary care. PARTICIPANTS: A total of 571 women with HMB. A purposeful sample of 27 women who were randomised or ineligible owing to treatment preference participated in semistructured face-to-face interviews around 2 and 12 months after commencing treatment. INTERVENTIONS: LNG-IUS or usual medical treatment (tranexamic acid, mefenamic acid, combined oestrogen-progestogen or progesterone alone). Women could subsequently swap or cease their allocated treatment. OUTCOME MEASURES: The primary outcome was the patient-reported score on the Menorrhagia Multi-Attribute Scale (MMAS) assessed over a 2-year period and then again at 5 years. Secondary outcomes included general quality of life (QoL), sexual activity, surgical intervention and safety. Data were analysed using iterative constant comparison. A state transition model-based cost-utility analysis was undertaken alongside the randomised trial. Quality-adjusted life-years (QALYs) were derived from the European Quality of Life-5 Dimensions (EQ-5D) and the Short Form questionnaire-6 Dimensions (SF-6D). The intention-to-treat analyses were reported as cost per QALY gained. Uncertainty was explored by conducting both deterministic and probabilistic sensitivity analyses. RESULTS: The MMAS total scores improved significantly in both groups at all time points, but were significantly greater for the LNG-IUS than for usual treatment [mean difference over 2 years was 13.4 points, 95% confidence interval (CI) 9.9 to 16.9 points; p < 0.001]. However, this difference between groups was reduced and no longer significant by 5 years (mean difference in scores 3.9 points, 95% CI -0.6 to 8.3 points; p = 0.09). By 5 years, only 47% of women had a LNG-IUS in place and 15% were still taking usual medical treatment. Five-year surgery rates were low, at 20%, and were similar, irrespective of initial treatments. There were no significant differences in serious adverse events between groups. Using the EQ-5D, at 2 years, the relative cost-effectiveness of the LNG-IUS compared with usual medical treatment was £1600 per QALY, which by 5 years was reduced to £114 per QALY. Using the SF-6D, usual medical treatment dominates the LNG-IUS. The qualitative findings show that women's experiences and expectations of medical treatments for HMB vary considerably and change over time. Women had high expectations of a prompt effect from medical treatments. CONCLUSIONS: The LNG-IUS, compared with usual medical therapies, resulted in greater improvement over 2 years in women's assessments of the effect of HMB on their daily routine, including work, social and family life, and psychological and physical well-being. At 5 years, the differences were no longer significant. A similar low proportion of women required surgical intervention in both groups. The LNG-IUS is cost-effective in both the short and medium term, using the method generally recommended by the National Institute for Health and Care Excellence. Using the alternative measures to value QoL will have a considerable impact on cost-effectiveness decisions. It will be important to explore the clinical and health-care trajectories of the ECLIPSE (clinical effectiveness and cost-effectiveness of levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia) trial participants to 10 years, by which time half of the cohort will have reached menopause. TRIAL REGISTRATION: Current Controlled Trials ISRCTN86566246. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 88. See the NIHR Journals Library website for further project information.

The clinical significance of medicines reconciliation in children admitted to hospital

Aims and Objectives: The NICE/NPSA guidance on Medicines Reconciliation in adults upon hospital admission excludes children under the age of 16.1 Hence the primary aim and objective of this study was to use medicines reconciliation to primarily identify if discrepancies occur upon hospital admission. Secondary objectives were to clinically assess for harm discrepancies that were identified in paediatric patients on long term medications at four hospitals across the UK. Method: Medicines reconciliation is a procedure where the current medication history of a patient prior to hospital admission would be taken and verifying the medication orders made at hospital admission against this history, addressing any discrepancies identified. Medicines reconciliation was carried out prospectively for 244 paediatric patients on chronic medication across four UK hospitals (Birmingham, London, Leeds and North Staffordshire) between January – May 2011. Medicines reconciliation was conducted by a clinical pharmacist using the following sources of information: 1) the patient's Pre-Admission Medication (PAM) from the patient's general practitioner 2) examination of the Patient's Own Medications brought into hospital, 3) a semi-structured interview with the parent-carers and 4) identification of admission medication orders written on the drug chart prior to clinical pharmacy input (Drug Chart). Discrepancies between the PAM and Drug Chart were documented and classified as intentional or unintentional. Intentional discrepancies were defined as changes that were made knowingly by the prescriber and confirmed. Unintentional discrepancies were assessed for clinical significance by an expert panel and assigned a significance score based on the likelihood of causing potential discomfort or clinical deterioration: class 1 unlikely, class 2 moderate and class 3 severe.2 Results: 1004 medication regimens were included from the 244 patients across the four sites. 588 of the 1004 (59%) medicines, had discrepancies between the PAM and Drug Chart; of these 36% (n = 209) were unintentional and included for clinically assessment. 189 drug discrepancies 30% were classified as class 1, 47% were class 2 and 23% were class 3 discrepancies. The remaining 20 discrepancies were cases where deviating from the PAM would have been the right thing to do, which might suggest that an intentional but undocumented discrepancy by the prescriber writing up the admission order may have occurred. Conclusion: The results suggest that medication discrepancies in paediatric patients do occur upon hospital admission, which do have a potential to cause harm and that medicines reconciliation is a potential solution to preventing such discrepancies. References: 1. National Institute for Health and Clinical Excellence. National Patient Safety Agency. PSG001. Technical patient safety solutions for medicines reconciliation on admission of adults to hospital. London: NICE; 2007. 2. Cornish, P. L., Knowles, S. R., Marchesano, et al. Unintended Medication Discrepancies at the Time of Hospital Admission. Archives of Internal Medicine 2005; 165:424–429

Shining in the center:central gaze cascade effect on product choice

Consumers' tendency to choose the option in the center of an array and the process underlying this effect is explored. Findings from two eye-tracking studies suggest that brands in the horizontal center receive more visual attention. They are more likely to be chosen. Investigation of the attention process revealed an initial central fixation bias, a tendency to look first at the central option, and a central gaze cascade effect, progressively increasing attention focused on the central option right prior to decision. Only the central gaze cascade effect was related to choice. An offline study with tangible products demonstrated that the centrally located item within a product category is chosen more often, even when it is not placed in the center of the visual field. Despite widespread use, memory-based attention measures were not correlated with eye-tracking measures. They did not capture visual attention and were not related to choice. © 2012 by JOURNAL OF CONSUMER RESEARCH, Inc.

The role of macular pigment assessment in clinical practice:a review

This review compares the results of studies that have investigated the impact of lutein and zeaxanthin supplementation on macular pigment optical density (MPOD) with those that have investigated the reliability of techniques used to measure macular pigment optical density. The review will focus on studies that have used heterochromatic flicker photometry for measurement of macular pigment optical density, as this is the only technique that is currently available commercially to clinicians. We identified articles that reported on supplementation with lutein and/or zeaxanthin and/or meso-zeaxanthin on macular pigment optical density measurement techniques published in peer-reviewed journals, through a multi-staged, systematic approach. Twenty-four studies have investigated the repeatability of MPOD measurements using heterochromatic flicker photometry. Of these, 10 studies provided a coefficient of repeatability or data from which the coefficient could be calculated, with a range in values of 0.06 to 0.58. The lowest coefficient of repeatability assessed on naïve subjects alone was 0.08. These values tell us that, at best, changes greater than 0.08 can be considered clinically significant and at worst, only changes greater than 0.58 can be considered clinically significant. Six studies assessed the effect of supplementation with up to 20 mg/day lutein on macular pigment optical density measured using heterochromatic flicker photometry and the mean increase in macular pigment optical density ranged from 0.025 to 0.09. It seems reasonable to conclude that the chance of eliciting an increase in macular pigment optical density during six months of daily supplementation with between 10 and 20 mg lutein that is of sufficient magnitude to be detected by using heterochromatic flicker photometry on an individual basis is small. Commercially available heterochromatic flicker photometers for macular pigment optical density assessment in the clinical environment appear to demonstrate particularly poor coefficient of repeatability values. Clinicians should exercise caution when considering the purchase of these instruments for potential monitoring of macular pigment optical density in response to supplementation in individual patients.

The vision strategy of golf putting

Golfers, coaches and researchers alike, have all keyed in on golf putting as an important aspect of overall golf performance. Of the three principle putting tasks (green reading, alignment and the putting action phase), the putting action phase has attracted the most attention from coaches, players and researchers alike. This phase includes the alignment of the club with the ball, the swing, and ball contact. A significant amount of research in this area has focused on measuring golfer’s vision strategies with eye tracking equipment. Unfortunately this research suffers from a number of shortcomings, which limit its usefulness. The purpose of this thesis was to address some of these shortcomings. The primary objective of this thesis was to re-evaluate golfer’s putting vision strategies using binocular eye tracking equipment and to define a new, optimal putting vision strategy which was associated with both higher skill and success. In order to facilitate this research, bespoke computer software was developed and validated, and new gaze behaviour criteria were defined. Additionally, the effects of training (habitual) and competition conditions on the putting vision strategy were examined, as was the effect of ocular dominance. Finally, methods for improving golfer’s binocular vision strategies are discussed, and a clinical plan for the optometric management of the golfer’s vision is presented. The clinical management plan includes the correction of fundamental aspects of golfers’ vision, including monocular refractive errors and binocular vision defects, as well as enhancement of their putting vision strategy, with the overall aim of improving performance on the golf course. This research has been undertaken in order to gain a better understanding of the human visual system and how it relates to the sport performance of golfers specifically. Ultimately, the analysis techniques and methods developed are applicable to the assessment of visual performance in all sports.

Discovering biomarkers for antidepressant response:protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort

Background: Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers ("biomarkers") of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. Methods: CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10-20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2-10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. Discussion: From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research. Trial registration: ClinicalTrials.gov identifier NCT01655706. Registered July 27, 2012.