A 6-month open-label study of the effectiveness and tolerability of galantamine in patients with Alzheimer's disease

The objective of this study was to assess the effectiveness and tolerability of galantamine in patients with mild-to-moderate Alzheimer's disease (AD) in everyday clinical practice. Patient selection was made on 36 sequential patients attending Belfast City Hospital Memory Clinic between December 2000 and June 2001. Patients were treated with galantamine for 6 months, starting from 4 mg twice daily increasing to 8 mg twice daily and then to 12 mg twice daily at 4-weekly intervals. Patients (25 females, 11 males), mean age 78 years (59-90), were diagnosed with probable AD and had a mini-mental state examination (MMSE) score of 10-26. Efficacy was assessed using the MMSE, neuropsychiatric inventory (NPI), neuropsychiatric inventory caregiver distress (NPI-D) scale and the Bristol activities of daily living (B-ADL) scale at baseline and after 3 and 6 months of treatment. Mean improvements were noted on all four measures of efficacy at 3 and 6 months; improvements were significant on the MMSE, NPI and NPI-D at 3 months and on the NPI-D at 6 months. Galantamine was overall well tolerated. The most common adverse events were gastrointestinal, particularly nausea. Four patients stopped treatment due to adverse events, and seven were stabilised on 8 mg twice daily as they were unable to tolerate the target dose. This naturalistic study confirms clinical trial data, which shows galantamine improves cognition and behavioural symptoms and is overall well tolerated. © 2004 Blackwell Publishing Ltd.

A Survey of Search Methodologies and Automated System Development for Examination Timetabling

Exam timetabling is one of the most important administrative activities that takes place in academic institutions. In this paper we present a critical discussion of the research on exam timetabling in the last decade or so. This last ten years has seen an increased level of attention on this important topic. There has been a range of significant contributions to the scientific literature both in terms of theoretical andpractical aspects. The main aim of this survey is to highlight the new trends and key research achievements that have been carried out in the last decade.We also aim to outline a range of relevant important research issues and challenges that have been generated by this body of work.

We first define the problem and review previous survey papers. Algorithmic approaches are then classified and discussed. These include early techniques (e.g. graph heuristics) and state-of-the-art approaches including meta-heuristics, constraint based methods, multi-criteria techniques, hybridisations, and recent new trends concerning neighbourhood structures, which are motivated by raising the generality of the approaches. Summarising tables are presented to provide an overall view of these techniques. We discuss some issues on decomposition techniques, system tools and languages, models and complexity. We also present and discuss some important issues which have come to light concerning the public benchmark exam timetabling data. Different versions of problem datasetswith the same name have been circulating in the scientific community in the last ten years which has generated a significant amount of confusion. We clarify the situation and present a re-naming of the widely studied datasets to avoid future confusion. We also highlight which research papershave dealt with which dataset. Finally, we draw upon our discussion of the literature to present a (non-exhaustive) range of potential future research directions and open issues in exam timetabling research.

The clinical effectiveness and cost-effectiveness of screening for open angle glaucoma:A systematic review and economic evaluation

Objectives: To assess whether open angle glaucoma (OAG) screening meets the UK National Screening Committee criteria, to compare screening strategies with case finding, to estimate test parameters, to model estimates of cost and cost-effectiveness, and to identify areas for future research. Data sources: Major electronic databases were searched up to December 2005. Review methods: Screening strategies were developed by wide consultation. Markov submodels were developed to represent screening strategies. Parameter estimates were determined by systematic reviews of epidemiology, economic evaluations of screening, and effectiveness (test accuracy, screening and treatment). Tailored highly sensitive electronic searches were undertaken. Results: Most potential screening tests reviewed had an estimated specificity of 85% or higher. No test was clearly most accurate, with only a few, heterogeneous studies for each test. No randomised controlled trials (RCTs) of screening were identified. Based on two treatment RCTs, early treatment reduces the risk of progression. Extrapolating from this, and assuming accelerated progression with advancing disease severity, without treatment the mean time to blindness in at least one eye was approximately 23 years, compared to 35 years with treatment. Prevalence would have to be about 3-4% in 40 year olds with a screening interval of 10 years to approach cost-effectiveness. It is predicted that screening might be cost-effective in a 50-year-old cohort at a prevalence of 4% with a 10-year screening interval. General population screening at any age, thus, appears not to be cost-effective. Selective screening of groups with higher prevalence (family history, black ethnicity) might be worthwhile, although this would only cover 6% of the population. Extension to include other at-risk cohorts (e.g. myopia and diabetes) would include 37% of the general population, but the prevalence is then too low for screening to be considered cost-effective. Screening using a test with initial automated classification followed by assessment by a specialised optometrist, for test positives, was more cost-effective than initial specialised optometric assessment. The cost-effectiveness of the screening programme was highly sensitive to the perspective on costs (NHS or societal). In the base-case model, the NHS costs of visual impairment were estimated as £669. If annual societal costs were £8800, then screening might be considered cost-effective for a 40-year-old cohort with 1% OAG prevalence assuming a willingness to pay of £30,000 per quality-adjusted life-year. Of lesser importance were changes to estimates of attendance for sight tests, incidence of OAG, rate of progression and utility values for each stage of OAG severity. Cost-effectiveness was not particularly sensitive to the accuracy of screening tests within the ranges observed. However, a highly specific test is required to reduce large numbers of false-positive referrals. The findings that population screening is unlikely to be cost-effective are based on an economic model whose parameter estimates have considerable uncertainty, in particular, if rate of progression and/or costs of visual impairment are higher than estimated then screening could be cost-effective. Conclusions: While population screening is not cost-effective, the targeted screening of high-risk groups may be. Procedures for identifying those at risk, for quality assuring the programme, as well as adequate service provision for those screened positive would all be needed. Glaucoma detection can be improved by increasing attendance for eye examination, and improving the performance of current testing by either refining practice or adding in a technology-based first assessment, the latter being the more cost-effective option. This has implications for any future organisational changes in community eye-care services. Further research should aim to develop and provide quality data to populate the economic model, by conducting a feasibility study of interventions to improve detection, by obtaining further data on costs of blindness, risk of progression and health outcomes, and by conducting an RCT of interventions to improve the uptake of glaucoma testing. © Queen's Printer and Controller of HMSO 2007. All rights reserved.

Targeting relatives of patients with primary open angle glaucoma: the help the family glaucoma project.

PURPOSE:

To assess the knowledge of patients with open angle glaucoma (OAG) and their family members about OAG risk factors and to study the referral of family members for eye examinations.

DESIGN:

Cross-sectional survey and prospective cohort study.

METHODS:

We interviewed OAG patients (probands) at the Wilmer Eye Institute and their biologically related parents, siblings, and children about their knowledge of OAG risk factors. Qualified family members were offered an eye examination through the EyeCare America program. Three months after initial contact, a follow-up telephone questionnaire determined the outcome of the referral.

RESULTS:

Among 102 probands and 100 (of 230 eligible) family members who were interviewed, there was high awareness that OAG is related to older age (85% both groups). More probands knew of the association with higher intraocular pressure (95%) compared with family (78%). Yet, 21% of both groups were not aware that OAG is hereditary, and only 53% of probands and 30% of family members knew that OAG is more common in certain ethnic groups. Only two-thirds of probands had suggested that family members have an eye examination. Eighty percent of family members had had an eye examination within the last year; of 21 with no recent examination, 66% (13/21) accepted referral.

CONCLUSIONS:

The Help the Family Glaucoma project developed a novel approach to identify those at high-risk for OAG. Screening of relatives of OAG patients deserves further study in a more representative selection of the general population.

Directed Selection using Reinforcement Learning for the Examination Timetabling Problem

Traditional heuristic approaches to the Examination Timetabling Problem normally utilize a stochastic method during Optimization for the selection of the next examination to be considered for timetabling within the neighbourhood search process. This paper presents a technique whereby the stochastic method has been augmented with information from a weighted list gathered during the initial adaptive construction phase, with the purpose of intelligently directing examination selection. In addition, a Reinforcement Learning technique has been adapted to identify the most effective portions of the weighted list in terms of facilitating the greatest potential for overall solution improvement. The technique is tested against the 2007 International Timetabling Competition datasets with solutions generated within a time frame specified by the competition organizers. The results generated are better than those of the competition winner in seven of the twelve examinations, while being competitive for the remaining five examinations. This paper also shows experimentally how using reinforcement learning has improved upon our previous technique.