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Clinical and cost-effectiveness of donepezil, rivastigmine and galantamine for Alzheimer's disease: a rapid and systematic review.

BACKGROUND: Alzheimer's disease is the most common cause of dementia and is characterised by an insidious onset and slow deterioration. The estimated prevalence of Alzheimer's disease for a standard health authority (500,000 people) is about 3330. Current service involves a wide range of agencies, and drug therapy for some patients. OBJECTIVES: To provide a rapid and systematic review of the clinical effectiveness and cost-effectiveness of donepezil, rivastigmine and galantamine in the symptomatic treatment of people suffering from Alzheimer's disease. METHODS: A systematic review of the literature was undertaken. METHODS - DATA SOURCES: Searches were made of electronic databases, including MEDLINE, EMBASE, The Cochrane Library, Database of Abstracts of Reviews of Effectiveness, NHS Economic Evaluation Database, National Research Register, Science Citation Index, BIOSIS, EconLit, MRC Trials database, Early Warning System, Current Controlled Trials, TOXLINE, Index of Scientific and Technical Proceedings, and Getting Easier Access to Reviews. All sources were searched over the period covered by the databases up to March/July 2000. Bibliographies of related papers were assessed for relevant studies and experts were contacted for advice and peer review, and to identify additional published and unpublished references. Manufacturer submissions to the National Institute for Clinical Excellence (NICE) were reviewed. METHODS - STUDY SELECTION: Studies were included if they fulfilled the following criteria: (1) INTERVENTION: donepezil, rivastigmine or galantamine used to treat Alzheimer's disease. (2) PARTICIPANTS: people diagnosed with Alzheimer's disease who meet the criteria for treatment with donepezil, rivastigmine and galantamine. (3) OUTCOMES: measures assessing changes in cognition, function, behaviour and mood, quality of life (including studies assessing carer well-being and carer-input), and time to institutionalisation. (4) DESIGN: systematic reviews of randomised controlled trials (RCTs) and RCTs comparing donepezil, rivastigmine or galantamine with placebo or each other or non-drug comparators were included in the review of effectiveness. Economic studies of donepezil, rivastigmine or galantamine used to treat Alzheimer's disease that included a comparator (or placebo) and both the costs and consequence (outcomes) of treatment were included in the review of cost-effectiveness. Studies in non-English language, and abstracts and conference poster presentations of systematic reviews, RCTs and economic evaluations were excluded. Two reviewers identified studies by independently screening study titles and abstracts, and then by examining the full text of selected studies to decide inclusion. METHODS - DATA EXTRACTION AND QUALITY ASSESSMENT: Data extraction and quality assessment were undertaken by one reviewer and checked by a second reviewer, with any disagreements resolved through discussion. The quality of RCTs was assessed using the Jadad scale and the quality of systematic reviews was assessed using criteria developed by the NHS Centre for Reviews and Dissemination. The quality of economic evaluation studies was assessed by their internal validity (i.e. the methods used) using a standard checklist, and external validity (i.e. the generalisability of the economic study to the population of interest) using a series of relevant questions. METHODS - DATA SYNTHESIS: The clinical effectiveness and cost-effectiveness of donepezil, rivastigmine and galantamine were synthesised through a narrative review with full tabulation of results of all included studies. In the economic evaluation, the reviewers assessed whether adjustments could be made to existing models to reflect the current situation in England and Wales. RESULTS - CLINICAL EFFECTIVENESS: (1) Donepezil--three systematic reviews and five RCTs (plus four studies from industry (unpublished data, submitted as commercial in confidence)) were found. Results suggest that donepezil is beneficial when assessed using global and cognitive outcome measures. (2) Rivastigmine--three systematic reviews and five RCTs (plus two studies from industry (unpublished data, submitted as commercial in confidence)) were found. Results suggest that rivastigmine is beneficial in terms of global outcome measures. (3) Galantamine--one systematic review and three RCTs (plus three studies from industry (unpublished data, submitted as commercial in confidence)) were found. Results suggest that galantamine is beneficial in terms of global, cognitive and functional scales. RESULTS - SUMMARY OF BENEFITS: It is difficult to quantify benefits from the evidence available in the literature. Statistically significant improvements in tests such as ADAS-cog (Alzheimer's Disease Assessment Scale cognitive subscale) may not be reflected in changes in daily life. (ABSTRACT TRUNCATED)

Alzheimer Disease↗

Intravascular ultrasound-guided interventions in coronary artery disease: a systematic literature review, with decision-analytic modelling, of outcomes and cost-effectiveness.

BACKGROUND: Intravascular ultrasound (IVUS) is the generic name for any ultrasound technology used in vivo within the blood vessels. More specifically, intracoronary ultrasound enables imaging of the coronary arteries from within the lumen. This review concentrates on the role of intracoronary ultrasound as an adjunct to interventional cardiology. OBJECTIVES: (1) To identify the literature on IVUS for guiding coronary interventions, and to synthesise evidence about outcomes compared with outcomes when IVUS guidance has not been used. (2) To use this evidence, together with other information about costs and outcomes, to model the cost effectiveness of IVUS guidance. (3) To synthesise the evidence on the reproducibility of measurements of cross-sectional area made using IVUS. METHODS DATA SOURCES: (1) Electronic searches of MEDLINE, EMBASE, Science Citation Index, Index to Scientific and Technical Proceedings, Engineering Compendex, Engineering Page One, Cochrane Library, Inside (British Library), 1990-98. (2) Contacting experts and centres of expertise, 1990-99. (3) Internet search, 1990-99. METHODS STUDY SELECTION: Studies of IVUS-guided coronary interventions performed on humans were included in the review. Non-English language studies were also included when they covered IVUS-guided stenting or angioplasty. Control evidence regarding outcomes without IVUS guidance was sought only from randomised controlled trials (RCTs). Studies investigating the reproducibility of measurements of cross-sectional area were included only if the results were expressed in terms of the mean and standard deviation of paired differences. METHODS DATA EXTRACTION: Checklists that covered study details, patient characteristics and results were completed independently by three reviewers. Consensus was reached on any disagreements. Local data were gathered on the costs of IVUS-guided stenting. METHODS DATA SYNTHESIS: Overall event rates were calculated by pooling patient results from the included studies. A decision-analytic model was used to combine information from the literature with cost estimates, in order to predict cost-effectiveness in terms of cost per restenosis event avoided by the use of IVUS guidance. The analysis was performed from the perspective of the healthcare provider. Sensitivity analysis was undertaken. A simple extrapolation was made to long-term outcome so that cost-utility (using quality-adjusted life years (QALYs)) could be estimated. The minimum detectable change in cross-sectional area was estimated from the reproducibility results. RESULTS: Only one study on IVUS-guided angioplasty satisfied the inclusion criteria, and there were no studies on IVUS-guided atherectomy or other IVUS-guided interventions that satisfied the inclusion criteria. Of the 15 articles on IVUS-guided stenting that satisfied the inclusion criteria, seven presented data on outcomes at 6 months post-intervention. The angiographic restenosis rate was 16 +/- 1%. This compared with 24 +/- 2% derived from five articles on stenting without IVUS guidance. Data for follow-up periods longer than 6 months were presented in only two studies. Data from a total of five studies were included in the decision-analytic model. The cost per restenosis event avoided was 1545 pound sterling. After extrapolation to long-term outcome, the calculated cost per QALY was 6438 pound sterling. The baseline QALY gain was only 0.03 years. Sensitivity analysis resulted in large differences between the best- and worst-case scenarios, for example, from a saving of 5000 pound sterling to a cost of 24,000 pound sterling restenosis event avoided. The smallest changes in cross-sectional area that could be measured were 1.6 mm2 by a single observer and 1.9 mm2 by different observers. CONCLUSIONS: Implications for healthcare: The evidence available is too weak for there to be any reliable implications for clinical practice. (ABSTRACT TRUNCATED)

Algorithms↗

[Paul Dorveau (July 21, 1851 - January 7 1938), a librarian of the Ecole supérieure de pharmacie de Paris and cofounder of the Société d'histoire de la pharmacie].

Paul Dorveaux was appointed librarian of the Ecole supérieure de pharmacie de Paris in 1884. He was associated to the foundation of the Société d' histoire de la pharmacie in 1913 because of his numerous national and international relations. This physician scholar devoted his life to the study of the medical and pharmaceutical history. Born in Lorraine he published studies on Metz pharmacy history. We owe him publications on the statutes of apothecary communities, pharmacy shops and libraries inventories, apothecaries biographies, new editions of ancient pharmacy books and a host of medical sciences studies. Paul Dorveauz published about 300 books and articles.

Education, Pharmacy↗

Identification of human gene structure using linear discriminant functions and dynamic programming.

Development of advanced technique to identify gene structure is one of the main challenges of the Human Genome Project. Discriminant analysis was applied to the construction of recognition functions for various components of gene structure. Linear discriminant functions for splice sites, 5'-coding, internal exon, and 3'-coding region recognition have been developed. A gene structure prediction system FGENE has been developed based on the exon recognition functions. We compute a graph of mutual compatibility of different exons and present a gene structure models as paths of this directed acyclic graph. For an optimal model selection we apply a variant of dynamic programming algorithm to search for the path in the graph with the maximal value of the corresponding discriminant functions. Prediction by FGENE for 185 complete human gene sequences has 81% exact exon recognition accuracy and 91% accuracy at the level of individual exon nucleotides with the correlation coefficient (C) equals 0.90. Testing FGENE on 35 genes not used in the development of discriminant functions shows 71% accuracy of exact exon prediction and 89% at the nucleotide level (C = 0.86). FGENE compares very favorably with the other programs currently used to predict protein-coding regions. Analysis of uncharacterized human sequences based on our methods for splice site (HSPL, RNASPL), internal exons (HEXON), all type of exons (FEXH) and human (FGENEH) and bacterial (CDSB) gene structure prediction and recognition of human and bacterial sequences (HBR) (to test a library for E. coli contamination) is available through the University of Houston, Weizmann Institute of Science network server and a WWW page of the Human Genome Center at Baylor College of Medicine.

Algorithms↗

Shortcomings in the evaluation of students' clinical skills and behaviors in medical school.

The authors review the methods by which U.S. medical schools have evaluated student achievement during the twentieth century, especially for the assessment of noncognitive abilities, including clinical skills and behaviors. With particular reference to the current decade, information collected by the Liaison Committee on Medical Education (LCME) is used to examine the congruence of assessment methods with the rising tide of understanding--and accreditation requirements--that knowledge, competence, and behavioral objectives require different methods of assessment to measure the extent of students' learning in each domain. Amongst 97 medical schools having accreditation surveys between July 1993 and June 1998, only 186 of 751 basic science courses tested students' noncognitive achievements in things such as the preparation for and participation in small-group conferences, the quality of case-based discussion, library research and literature reviews, and research projects, despite staking out scholarship, habits of life-long learning, and reasoned thinking as educational objectives. In the clerkships of these schools, structured and observed assessments of clinical skills--with standardized patients and/or OSCEs--contributed 7.4-23.1% to a student's grade (depending on the clerkship discipline), while the predominant contribution (50-70% across the clerkships) was made by resident and faculty ratings that were based largely on recollections of case presentations and discussions having little relationship to interpersonal skills, rapport with patients, and logical and sequenced history taking and physical examination. On a more optimistic note, the results show that the number of schools using standardized patients in one or more clerkships increased between 1993 and 1998 from 34.1% to 50.4% of the 125 schools in the United States, and the number of schools using standardized patients in comprehensive fourth-year examinations increased from 19.1% to 48% of the total. Despite such progress, this study shows that too many medical schools still fail to employ evaluation methods that specifically assess students' achievement of the skills and behaviors they need to learn to practice medicine. The findings of this article explain why accreditors are paying closer attention to how well schools provide measured assurances that students learn what the faculties set out to teach.

Accreditation↗

A comparison of the currency of secondary information sources in the biochemical literature. II. MEDLINE online and on CD-ROM.

The currency of selected versions of the MEDLINE database on CD-ROM and in online format was studied. The arrival of issues from 72 monthly journals and nine weekly titles during a 3-month period was monitored and their appearance in the various MEDLINE formats were recorded. Availability data for MEDLINE published by the National Library of Medicine were used as a baseline and subsequent distribution delays for the different MEDLINE formats were calculated. The study suggests a delay of approximately 2 weeks for indexing and mounting the MEDLINE file on to host computers for online access. A delay of 6-8 weeks was calculated for the MEDLINE data to be encoded on to compact disk, shipped and posted to the library customer. The currency of the MEDLINE database formats was compared with a weekly current-awareness service, CURRENT CONTENTS ON DISKETTE LIFE SCIENCES (CCOD). The majority of papers were indexed and distributed in CCOD within 10 weeks of publication date. Most papers appeared within 15 weeks in the online MEDLINE format and within 20 weeks in CD-ROM MEDLINE. The primary journal arrived at the library site within 5 weeks in most cases.

CD-ROM↗

[Le Quercinois, Guillaume Jacob, physician and surgeon at the Montpellier School, artisan of the reform of medical sciences in Spain the the 18th century].

Guillaume Jacob born in Castelnau-Montratier at the dawn of the XVIIIth century, physician of the School of Medicine of Montpellier was attracted by Spain during the reign of Philip V grand-son of Louis XIV. Nominated Professor of Anatomy at the Royal Society of Medicine of Sevilla, later Royal Academy, he worked during seventeen years to improve Spanish medical science: he informed himself in Paris of the discoveries of French scientists, obtained modern surgical instruments, books to enrich the library, laid the foundations of a botanical garden for medical plants and established links between the Royal Society of Sevilla and various European Royal Academies in order to allow exchanges.

France↗

Special programs in medical library education, 1957-1971. II. Analysis of the programs.

In this report, responses to a questionnaire to the directors of the sixteen past and present medical library education programs are presented. The questionnaires indicate a rather wide variety of training programs with emphases that vary from preparation of management personnel to preparation of subject specialists and those skilled in the techniques of information storage and retrieval. The content of the degree programs is fairly evenly divided among general retrieval and outside courses. The internship programs place more emphasis on the work experience than do the degree programs, supplementing this experience with appropriate courses in science, health sciences, management, and information storage and retrieval. Program directors indicated that new or expanded programs are needed in medical library education, although caution is reflected in comments concerning the limited job market. Most of the internship directors stated that they could not accommodate more individuals in their programs without expansion of staff and facilities.

Curriculum↗

On the design of the Health Sciences Library/Information Services building at the University of Maryland at Baltimore.

The architect provides his perspective on issues in designing a new library building, including: civic and urbanistic purposes of the building; the process of analysis and synthesis; and the place and meaning of 'library' today. Special attention is given to adjacencies, reader services, space devoted to the study of change, administration, and presentation and itinerary. A verbal floor-by-floor tour of the building is provided.

Architecture↗

An interactive histology image-barcode manual for a videodisc image library.

UNLABELLED: Cell Biology and HISTOLOGY (alias Microanatomy, alias Microscopic Anatomy) is a required course for first-year medical and dental students in most health science centers. The traditional approach used in teaching this discipline is to present photomicrographic images of structures to students in lecture using 35 mm slides of fields seen through the microscope. The students then spend many hours viewing and studying specimens of tissues using a light microscope in a laboratory setting. Students in traditional courses of histology spend an inordinate amount of time learning the component structures by attempting to find and identify them in tissue sections using a microscope, where the structure being sought is surrounded by a multitude of other structures with which they are also not familiar. With the recent availability of videodisc stored image libraries of histological samples, it is now possible to study histological principles without the use of the microscope as the primary learning tool. A videodisc entitled " HISTOLOGY: A Photographic Atlas" by S. Downing (published by Image Premastering Services Limited, Minneapolis, MN, 1991) has been incorporated into our histology course. Fifteen videodisc player stations are provided for 150 students. Images are retrieved by students using a bar code scanner attached to a videodisc player (Pioneer CLD-2400). Using this kind of image library, students can now learn basic histological structure, such as cell and tissue types, without the use of a microscope or as a tool for facilitating microscopy. The use of a videodisc library of randomly accessible images simplifies learning the basic components which all organs are composed of by presenting the learner with clear-cut examples to avoid confusion with other structures. However, videodisc players and TV monitors are still not appropriately priced for every student to own. This presents a problem in that the same images studied in class are not available to study and review outside of class. There is a need for resources for additional study outside of the institutional setting, for students to have and interact with to reinforce the learning experience in the teaching laboratory. A hard copy manual was created and is being used in our course; it incorporates photos captured from the videodisc. The images displayed in the manual are chosen to give the student one example of each histological component. Additional labeling is added to the images, and each image is accompanied by a bar code that may be used at a videodisc player with a bar code reader to retrieve the same color image from the disc displayed in larger format on a TV monitor. Each topic in the manual is accompanied by learning objectives and a statement of clinical relevance. Following the presentation of the images in each section of the manual, the students are encouraged to practice by viewing multiple examples of each structural component presented in the lesson. They can do this by using the bar-coded catalog supplied with each disc. The presentation of each topic concludes with a quiz composed of questions about images that the student can retrieve from the videodisc using barcodes in the text of the manual. Some of the images on the quiz are printed in miniature in the manual to provide the student with an opportunity for personal review at home when hardware to obtain and display images from a video disc is not available. This manual provides an answer to the dilemma faced by the learner when access to hardware is not available; reinforcement is therefore facilitated outside the teaching laboratory. This allows learning to continue outside of the classroom, using the same materials. (abstract truncated)

Computer-Assisted Instruction↗