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.

Impact of senescence and disease on the structural and functional performance of the visual pathway

The diagnosis and monitoring of ocular disease presents considerable clinical difficulties for two main reasons i) the substantial physiological variation of anatomical structure of the visual pathway and ii) constraints due to technical limitations of diagnostic hardware. These are further confounded by difficulties in detecting early loss or change in visual function due to the masking of disease effects, for example, due to a high degree of redundancy in terms of nerve fibre number along the visual pathway. This thesis addresses these issues across three areas of study: 1. Factors influencing retinal thickness measures and their clinical interpretation As the retina is the principal anatomical site for damage associated with visual loss, objective measures of retinal thickness and retinal nerve fibre layer thickness are key to the detection of pathology. In this thesis the ability of optical coherence tomography (OCT) to provide repeatable and reproducible measures of retinal structure at the macula and optic nerve head is investigated. In addition, the normal physiological variations in retinal thickness and retinal nerve fibre layer thickness are explored. Principal findings were: • Macular retinal thickness and optic nerve head measurements are repeatable and reproducible for normal subjects and diseased eyes • Macular and retinal nerve fibre layer thickness around the optic nerve correlate negatively with axial length, suggesting that larger eyes have thinner retinae, potentially making them more susceptible to damage or disease • Foveola retinal thickness increases with age while retinal nerve fibre layer thickness around the optic nerve head decreases with age. Such findings should be considered during examination of the eye with suspect pathology or in long-term disease monitoring 2. Impact of glucose control on retinal anatomy and function in diabetes Diabetes is a major health concern in the UK and worldwide and diabetic retinopathy is a major cause of blindness in the working population. Objective, quantitative measurements of retinal thickness. particularly at the macula provide essential information regarding disease progression and the efficacy of treatment. Functional vision loss in diabetic patients is commonly observed in clinical and experimental studies and is thought to be affected by blood glucose levels. In the first study of its kind, the short term impact of fluctuations in blood glucose levels on retinal structure and function over a 12 hour period in patients with diabetes are investigated. Principal findings were: • Acute fluctuations in blood glucose levels are greater in diabetic patients than normal subjects • The fluctuations in blood glucose levels impact contrast sensitivity scores. SWAP visual fields, intraocular pressure and diastolic pressure. This effect is similar for type 1 and type 2 diabetic patients despite the differences in their physiological status. • Long-term metabolic control in the diabetic patient is a useful predictor in the fluctuation of contrast sensitivity scores. • Large fluctuations in blood glucose levels and/or visual function and structure may be indicative of an increased risk of development or progression of retinopathy 3. Structural and functional damage of the visual pathway in glaucomatous optic neuropathy The glaucomatous eye undergoes a number of well documented pathological changes including retinal nerve fibre loss and optic nerve head damage which is correlated with loss of functional vision. In experimental glaucoma there is evidence that glaucomatous damage extends from retinal ganglion cells in the eye, along the visual pathway, to vision centres in the brain. This thesis explores the effects of glaucoma on retinal nerve fibre layer thickness, ocular anterior anatomy and cortical structure, and its correlates with visual function in humans. Principal findings were: • In the retina, glaucomatous retinal nerve fibre layer loss is less marked with increasing distance from the optic nerve head, suggesting that RNFL examination at a greater distance than traditionally employed may provide invaluable early indicators of glaucomatous damage • Neuroretinal rim area and retrobulbar optic nerve diameter are strong indicators of visual field loss • Grey matter density decreases at a rate of 3.85% per decade. There was no clear evidence of a disease effect • Cortical activation as measured by fMRI was a strong indicator of functional damage in patients with significant neuroretinal rim loss despite relatively modest visual field defects These investigations have shown that the effects of senescence are evident in both the anterior and posterior visual pathway. A variety of anatomical and functional diagnostic protocols for the investigation of damage to the visual pathway in ocular disease are required to maximise understanding of the disease processes and thereby optimising patient care.

Pathway to clozapine use:a comparison between a patient cohort from New Zealand and a cohort from the United Kingdom

Background and Objective: Clozapine has been available since the early 1990s. Studies continue to demonstrate its superior efficacy in treatment-resistant schizophrenia. Despite this, numerous studies show under-utilisation, delayed access and reluctance by psychiatrists to prescribe clozapine. This retrospective cross-sectional study compared the prescribing of clozapine in two adult cohorts under the care of large public mental health services in Auckland (New Zealand) and Birmingham (United Kingdom) on 31 March 2007. Method: Time from first presentation to clozapine initiation, prior antipsychotics trialled and antipsychotic co-prescribing were compared. Data included demographics, psychiatric diagnosis, co-morbid conditions, year of first presentation, admissions and pharmacological treatment (clozapine dose, start date, prior antipsychotics, co-prescribed antipsychotic). Results: Overall, 664 people were prescribed clozapine (402 Auckland; 262 Birmingham); mean daily dose of 384 mg (Auckland) and 429 mg (Birmingham). 53 % presented after 1990 and the average duration of time before starting clozapine was significantly longer in the Birmingham cohort (6.5 vs. 5.3 years) but this reduced in both cohorts to a 1-year mean in those presenting within the last 3 years. The average number of antipsychotics trialled pre-clozapine for those presenting since 1990 was significantly higher in the Birmingham cohort (4.3 vs. 3.1) but in both cohorts this similarly reduced in those presenting within the last 3 years. Antipsychotic co-prescribing was significantly higher in the Birmingham cohort (22.9 vs. 10.7 %). Conclusions: There is evidence that access to clozapine has improved over time in both cohorts, with a reduction in the duration between presentation and initiation of clozapine and number of different antipsychotics trialled pre-clozapine. These are very positive findings in terms of optimising outcomes with clozapine and are possibly due to the impact of guideline recommendations, increasing clinician, consumer and carer knowledge, and experience with clozapine and funding changes. © 2014 Springer International Publishing.

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.

Clinical characteristics and benefit of cataract intervention amongst UK domiciliary eye care recipients

Purpose: Given the ageing UK population and the high prevalence of activity-limiting illness and disability in the over 65s, the demand for domiciliary eye care services is set to grow significantly. Over 400,000 NHS domiciliary eye examinations are conducted each year, yet minimal research attention has been directed to this mode of practice or patient needs amongst this group. The study aimed to compare clinical characteristics and benefits of cataract surgery between conventional in-practice patients and domiciliary service users. Methods: Clinical characteristics were compared between patients in North-West England receiving NHS domiciliary eye care services (n = 197; median age 76.5 years), and an age-matched group of conventional in-practice patients (n = 107; median age 74.6 years). Data including reason for visit; logMAR uncorrected and best corrected distance (UDVA and CDVA) and near acuities (UNVA and CNVA); presence of ocular pathology and examination outcome were documented retrospectively. To compare the benefit of cataract surgery in terms of functional capacity between the patient groups, individuals undergoing routine referral for first-eye surgery completed the VF-14 questionnaire pre-operatively, and at 6 weeks post-operatively. Results: UDVA was similar between the two groups (median 0.48 and 0.50 logMAR in the domiciliary and practice groups, P = 0.916); CDVA was significantly worse in the domiciliary group (median 0.18 vs 0.08 logMAR, P<0.001), who were more likely to have clinically-significant cataract. Both groups showed similar improvements in VF-14 scores following cataract surgery (mean gains 24.4 ± 11.7, and 31.5 ± 14.7 points in the in-practice and domiciliary groups, respectively. P = 0.312). Conclusions: Patients receiving domiciliary eye care services are more likely to have poorer corrected vision than in-practice patients of a similar age, partly due to a higher prevalence of significant cataract. Despite limitations in their activities due to illness and disability, domiciliary patients experience similar gains in self-reported functional capacity following cataract surgery