Analysis of clinical isolates of Propionibacterium acnes by optimised RAPD

Random amplification of polymorphic DNA (RAPD) was evaluated as a genotypic method for typing clinical strains of Propionibacterium acnes. RAPD can suffer from problems of reproducibility if parameters are not standardised. In this study the reaction conditions were optimised by adjusting template DNA concentration and buffer constituents. All isolates were typeable using the optimised RAPD protocol which was found to be highly discriminatory (Simpson's diversity index, 0.98) and reproducible. Typing of P. acnes by optimised RAPD is an invaluable tool for the epidemiological investigation of P. acnes for which no other widely accepted method currently exists. © 2003 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.

Optometry:science, techniques and clinical management

An introduction to the theory and practice of optometry in one succinct volume. From the fundamental science of vision to clinical techniques and the management of common ocular conditions, this book encompasses the essence of contemporary optometric practice. Now in full colour and featuring over 400 new illustrations, this popular text which will appeal to both students and practitioners wishing to keep up to date has been revised significantly. The new edition incorporates recent advances in technology and a complete overview of clinical procedures to improve and update everyday patient care. Contributions from well-known international experts deliver a broad perspective and understanding of current optometric practice. A useful aid for students and the newly qualified practitioner, while providing a rapid reference guide for the more experienced clinician.

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.

Clinical studies of spatial and temporal aspects of vision: an investigation using psychophysical and electrophysiological techniques

Separate physiological mechanisms which respond to spatial and temporal stimulation have been identified in the visual system. Some pathological conditions may selectively affect these mechanisms, offering a unique opportunity to investigate how psychophysical and electrophysiological tests reflect these visual processes, and thus enhance the use of the tests in clinical diagnosis. Amblyopia and optical blur were studied, representing spatial visual defects of neural and optical origin, respectively. Selective defects of the visual pathways were also studied - optic neuritis which affects the optic nerve, and dementia of the Alzheimer type in which the higher association areas are believed to be affected, but the primary projections spared. Seventy control subjects from 10 to 79 years of age were investigated. This provided material for an additional study of the effect of age on the psychophysical and electrophysiological responses. Spatial processing was measured by visual acuity, the contrast sensitivity function, or spatial modulation transfer function (MTF), and the pattern reversal and pattern onset-offset visual evoked potential (VEP). Temporal, or luminance, processing was measured by the de Lange curve, or temporal MTF, and the flash VEP. The pattern VEP was shown to reflect the integrity of the optic nerve, geniculo striate pathway and primary projections, and was related to high temporal frequency processing. The individual components of the flash VEP differed in their characteristics. The results suggested that the P2 component reflects the function of the higher association areas and is related to low temporal frequency processing, while the Pl component reflects the primary projection areas. The combination of a delayed flash P2 component and a normal latency pattern VEP appears to be specific to dementia of the Alzheimer type and represents an important diagnostic test for this condition.

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.

Effects of yellow filters on visual acuity, contrast sensitivity and reading under conditions of forward light scatter

Background Yellow filters are sometimes recommended to people with low vision. Our aim was investigate the effects of three commercial yellow filters on visual acuity and contrast sensitivity (with and without glare) and reading (without glare) under conditions of forward light scatter (FLS). Method Fifty-five healthy subjects were assessed with Corning Photochromic Filters (CPFs) 450, 511 and 527 and a filter producing FLS. The effects on log MAR visual acuity, Pelli–Robson contrast sensitivity with and without glare, and reading (measured with MNRead charts) without glare were determined. Results Statistically significant differences were found between the overall effect of glare and between CPFs for visual acuity and contrast sensitivity. A gradual decline in visual acuity, contrast sensitivity and reading with increasing CPF absorption was noted. Conclusion Effects of CPF450, 511, 527 on visual acuity, contrast sensitivity and reading under conditions of FLS were negative but not clinically significant.

Clinical decision support system for point of care use: ontology driven design and software implementation

OBJECTIVES: The objective of this research was to design a clinical decision support system (CDSS) that supports heterogeneous clinical decision problems and runs on multiple computing platforms. Meeting this objective required a novel design to create an extendable and easy to maintain clinical CDSS for point of care support. The proposed solution was evaluated in a proof of concept implementation. METHODS: Based on our earlier research with the design of a mobile CDSS for emergency triage we used ontology-driven design to represent essential components of a CDSS. Models of clinical decision problems were derived from the ontology and they were processed into executable applications during runtime. This allowed scaling applications' functionality to the capabilities of computing platforms. A prototype of the system was implemented using the extended client-server architecture and Web services to distribute the functions of the system and to make it operational in limited connectivity conditions. RESULTS: The proposed design provided a common framework that facilitated development of diversified clinical applications running seamlessly on a variety of computing platforms. It was prototyped for two clinical decision problems and settings (triage of acute pain in the emergency department and postoperative management of radical prostatectomy on the hospital ward) and implemented on two computing platforms-desktop and handheld computers. CONCLUSIONS: The requirement of the CDSS heterogeneity was satisfied with ontology-driven design. Processing of application models described with the help of ontological models allowed having a complex system running on multiple computing platforms with different capabilities. Finally, separation of models and runtime components contributed to improved extensibility and maintainability of the system.

Clinical evaluation of a multifocal aspheric diffractive intraocular lens

Aim: To evaluate the performance of an aspheric diffractive multifocal acrylic intraocular lens (IOL), ZMB00 1-Piece Tecnis. Setting: Five sites across Europe. Methods: Fifty-two patients with cataracts (average age 68.5±10.5 years, 35 female) were bilaterally implanted with the aspheric diffractive multifocal IOL after completing a questionnaire regarding their optical visual symptoms, use of visual correction and their visual satisfaction. The questionnaire was completed again 4-6 months after surgery along with measures of uncorrected and best-corrected distance and near visual acuity, under photopic and mesopic lighting, reading ability, defocus curve testing and ocular examination for adverse events. Results: The residual refractive error was 0.01±0.47D with 56% of eyes within ±0.25D and 97% within ±1.0D. Uncorrected visual acuity was 0.02±0.10logMAR at distance and 0.15±0.30 logMAR at near, only reducing to 0.07±0.10logMAR at distance and 0.21±0.25logMAR at near in mesopic conditions.The defocus curve showed a near addition between 2.5-3.0 D allowing a reading acuity of 0.08±0.13 logMAR, with a range of clear vision <0.3 logMAR of ∼4.0 D. The average reading speed was 121.4±30.8 words per minute. Spectacle independence was 100% for distance and 88% for near, with high levels of satisfaction reported. Overall rating of vision without glasses could be explained (r=0.760) by preoperative best-corrected distance acuity, postoperative reading acuity and postoperative uncorrected distance acuity in photopic conditions (p<0.001). Only two minor adverse events occurred. Conclusions: The ZMB00 1-Piece Tecnis multifocal IOL provides a good visual outcome at distance and near with minimal adverse effects.

Effects of lipoic acid and dihydrolipoic acid on total erythrocytic thiols under conditions of restricted glucose in vitro

The effects of lipoic acid and dihydrolipoic acid were explored on total thiol maintenance in diabetic and non-diabetic human erythrocytes in vitro over 22 hr in a 37°C incubation system with no added glucose. Over 18-22.5 hr after treatment in both non-diabetic and diabetic cells, lipoic acid (1 mM) was associated with greater loss of cellular thiols than dihydrolipoic acid (1 mM), compared to respective control values. At 0.1 mM, in non-diabetic cells, although lipoic acid-treated cells' thiol levels were significantly lower than control, there was no significant difference between dihydrolipoic acid-treated cells and control cells regarding thiol levels. In addition, at 0.1 mM, dihydrolipoic acid-treated diabetic cells showed a reduction in thiol levels compared to control. At 0.01 mM, lipoic acid-treated cells had significantly lower measured thiol levels compared with diabetic cells exposed to dihydrolipoic acid, whereas in non-diabetic cells, dihydrolipoic acid-treated erythrocytic thiol levels were significantly greater than those treated with lipoic acid, although there were no other significant differences between the groups. At 22.5 hr, control values of methaemoglobin rose to 6.4 ± 1.1% in diabetic cells and 3.6 ± 2.1% in non-diabetic cells. Lipoic acid (1 mM) showed greater methaemoglobin formation in diabetic rather than non-diabetic cells (13.6 ± 1.5% versus 11.6 ± 1.5%), whereas dihydrolipoic acid-treated diabetic and non-diabetic cells were less potent in methaemoglobin generation (8.5 ± 2.4% and 8.4 ± 1.4%, respectively). These studies suggest that in certain circumstances such as hypoglycaemia, lipoic acid administration may actually be detrimental to cellular oxidant protection status. © 2006 The Authors.

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.

Clinical characteristics of patients with epilepsy in a specialist neuropsychiatry service

Neuropsychiatry services provide specialist input into the assessment and management of behavioral symptoms associated with a range of neurological conditions, including epilepsy. Despite the centrality of epilepsy to neuropsychiatry and the recent expansion of neuropsychiatry service provision, little is known about the clinical characteristics of patients with epilepsy who are routinely seen by a specialist neuropsychiatry service. This retrospective study filled this gap by retrospectively evaluating a naturalistic series of 60 consecutive patients with epilepsy referred to and assessed within a neuropsychiatry setting. Fifty-two patients (86.7%) had active epilepsy and were under the ongoing care of the referring neurologist for seizure management. The majority of patients (N = 42; 70.0%) had a diagnosis of localization-related epilepsy, with temporal lobe epilepsy as the most common epilepsy type (N = 37; 61.7%). Following clinical assessment, 39 patients (65.0%) fulfilled formal diagnostic criteria for at least one psychiatric disorder; nonepileptic attack disorder (N = 37; 61.7%), major depression (N = 23; 38.3%), and generalized anxiety disorder (N = 16; 26.7%) were the most commonly diagnosed comorbidities. The clinical characteristics of patients seen in specialist neuropsychiatry settings are in line with the results from previous studies in neurology clinics in terms of both epilepsy and psychiatric comorbidity. Our findings confirm the need for the development and implementation of structured care pathways for the neuropsychiatric aspects of epilepsy, with focus on comorbid nonepileptic attacks and affective and anxiety symptoms. This is of particular importance in consideration of the impact of behavioral symptoms on patients' health-related quality of life.

Investigating the utility of clinical assessments to predict success with presbyopic contact lens correction

PURPOSE: To determine the utility of a range of clinical and non-clinical indicators to aid the initial selection of the optimum presbyopic contact lens. In addition, to assess whether lens preference was influenced by the visual performance compared to the other designs trialled (intra-subject) or compared to participants who preferred other designs (inter-subject). METHODS: A double-masked randomised crossover trial of Air Optix Aqua multifocal, PureVision 2 for Presbyopia, Acuvue OASYS for Presbyopia, Biofinity multifocal and monovision was conducted on 35 presbyopes (54.3±6.2years). Participant lifestyle, personality, pupil characteristics and aberrometry were assessed prior to lens fitting. After 4 weeks of wear, high and low contrast visual acuity (VA) under photopic and mesopic conditions, reading speed, Near Activity Visual Questionnaire (NAVQ) rating, subjective quality-of-vision scoring, defocus curves, stereopsis, halometry, aberrometry and ocular physiology were quantified. RESULTS: After trialling all the lenses, preference was mixed (n=12 Biofinity, n=10 monovision, n=7 Purevision, n=4 Air Optix Aqua, n=2 Oasys). Lens preference was not dependent on personality (F=1.182, p=0.323) or the hours spent working at near (p=0.535) or intermediate (p=0.759) distances. No intersubject or strong intrasubject relationships emerged between lens preference and reading speed, NAVQ rating, halo size, aberrometry or ocular physiology (p>0.05). CONCLUSIONS: Participant lifestyle and personality, ocular optics, contact lens visual performance and ocular physiology provided poor indicators of the preferred lens type after 4 weeks of wear. This is confounded by the wide range of task visual demands of presbyopes and the limited optical differences between current multifocal contact lens designs.

Systematic review and analysis of evidences on clinical efficacy and cost-effectiveness of biological drugs for the treatment of Ankylosing Spondylitis

Technology: Infliximab and comparator biological such as adalimumab, etanercept, golimumab. Conditions: Ankylosing spondylitis (AS) Issue: Infliximab is registered to be used in patients with AS. The aim of the Report is to evaluate the clinical efficacy and safety of infliximab and comparator biologicals for the treatment of adult AS. Methods: Systematic literature review and analysis as well as meta-analysis (direct and indirect comparison) of published randomised controlled clinical trials (RCT) were performed, all relevant health economics literature were identified ad analysed. Results: Clinical efficacy of biological therapies is based on good clinical evidences regarding to all clinical efficacy endpoints (ASAS20, ASAS40, ASAS 5/6, and BASDAI 50% response). Altogether, 22 trials are included in our meta-analysis, 12 infliximab, 3 adalimumab studies, 6 etanercept and 1 golimumab. Efficacy of biological treatments for the treatment of AS has been established by clinical scientific evidences, significant improvement at all outcomes considered was confirmed. According to the results of indirect comparison, there were no significant difference between biological treatments and placebo in terms of safety and tolerability endpoints. We found no significant difference between the clinical efficacy and safety of infliximab, adalimumab, etanercept and golimumab therapies. Cost-utility analysis of adalimumab and/or infliximab, etanercept and golimumab treatment for AS were performed in the UK, Canada, The Netherlands, Germany, Spain and France. There are no cost-utility studies from Eastern Central Europe. Implications for decision making: Efficacy of infliximab and comparator biologicals for the treatment of Ankylosing Spondylitis (AS) was proved by clinical evidence, significant improvement at all outcomes considered was confirmed. We found no significant differences in efficacy and safety of different biological treatments. Health economics results suggest that biological therapies are cost-effective alternatives for the treatment of AS in group of developed high income countries. There is a lack of health economics results in Central-Eastern European countries however these data are more and more required by governments and funders as part of the company economic dossiers.

Understanding the dynamics of information technology implementation: The case of clinical information systems

The ultimate intent of this dissertation was to broaden and strengthen our understanding of IT implementation by emphasizing research efforts on the dynamic nature of the implementation process. More specifically, efforts were directed toward opening the "black box" and providing the story that explains how and why contextual conditions and implementation tactics interact to produce project outcomes. In pursuit of this objective, the dissertation was aimed at theory building and adopted a case study methodology combining qualitative and quantitative evidence. Precisely, it examined the implementation process, use and consequences of three clinical information systems at Jackson Memorial Hospital, a large tertiary care teaching hospital.^ As a preliminary step toward the development of a more realistic model of system implementation, the study proposes a new set of research propositions reflecting the dynamic nature of the implementation process.^ Findings clearly reveal that successful implementation projects are likely to be those where key actors envision end goals, anticipate challenges ahead, and recognize the presence of and seize opportunities. It was also found that IT implementation is characterized by the systems theory of equifinality, that is, there are likely several equally effective ways to achieve a given end goal. The selection of a particular implementation strategy appears to be a rational process where actions and decisions are largely influenced by the degree to which key actors recognize the mediating role of each tactic and are motivated to action. The nature of the implementation process is also characterized by the concept of "duality of structure," that is, context and actions mutually influence each other. Another key finding suggests that there is no underlying program that regulates the process of change and moves it form one given point toward a subsequent and already prefigured end. For this reason, the implementation process cannot be thought of as a series of activities performed in a sequential manner such as conceived in stage models. Finally, it was found that IT implementation is punctuated by a certain indeterminacy. Results suggest that only when substantial efforts are focused on what to look for and think about, it is less likely that unfavorable and undesirable consequences will occur. ^