Writing clinical practice guidelines in controlled natural language

Clinicians could benefit from decision support systems incorporating the knowledge contained in clinical practice guidelines. However, the unstructured form of these guidelines makes them unsuitable for formal representation. To address this challenge we translated a complete set of pediatric guideline recommendations into Attempto Controlled English (ACE). One experienced pediatrician, one physician and a knowledge engineer assessed that a suitably extended version of ACE can accurately and naturally represent the clinical concepts and the proposed actions of the guidelines. Currently, we are developing a systematic and replicable approach to authoring guideline recommendations in ACE

OWL-based acquisition and editing of computer-interpretable guidelines with the CompGuide editor

Computer-Interpretable Guidelines (CIGs) are the dominant medium for the delivery of clinical decision support, given the evidence-based nature of their source material. Therefore, these machine-readable versions have the ability to improve practitioner performance and conformance to standards, with availability at the point and time of care. The formalisation of Clinical Practice Guideline knowledge in a machine-readable format is a crucial task to make it suitable for the integration in Clinical Decision Support Systems. However, the current tools for this purpose reveal shortcomings with respect to their ease of use and the support offered during CIG acquisition and editing. In this work, we characterise the current landscape of CIG acquisition tools based on the properties of guideline visualisation, organisation, simplicity, automation, manipulation of knowledge elements, and guideline storage and dissemination. Additionally, we describe the CompGuide Editor, a tool for the acquisition of CIGs in the CompGuide model for Clinical Practice Guidelines that also allows the editing of previously encoded guidelines. The Editor guides the users throughout the process of guideline encoding and does not require proficiency in any programming language. The features of the CIG encoding process are revealed through a comparison with already established tools for CIG acquisition.COMPETE, Grant/Award Number: POCI-01-0145-FEDER-007043; FCT - Fundacao para a Ciencia e Tecnologia, Grant/Award Number: UID/CEC/00319/201

Is a combination of varenicline and nicotine patch more effective in helping smokers quit than varenicline alone? A randomised controlled trial

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Rapid reduction versus abrupt quitting for smokers who want to stop soon: a randomised controlled non-inferiority trial

Background: The standard way to stop smoking is to stop abruptly on a quit day with no prior reduction in consumption of cigarettes. Many smokers feel that reduction is natural and if reduction programmes were offered, many more might take up treatment. Few trials of reduction versus abrupt cessation have been completed. Most are small, do not use pharmacotherapy, and do not meet the standards necessary to obtain a marketing authorisation for a pharmacotherapy.\ud Design/Methods: We will conduct a non-inferiority andomised trial of rapid reduction versus standard abrupt cessation among smokers who want to stop smoking. In the reduction arm,participants will be advised to reduce smoking consumption by half in the first week and to 25% of baseline in the second, leading up to a quit day at which participants will stop smoking completely.This will be assisted by nicotine patches and an acute form of nicotine replacement therapy. In the abrupt arm participants will use nicotine patches only, whilst smoking as normal, for two weeks prior to a quit day, at which they will also stop smoking completely. Smokers in either arm will have standard withdrawal orientated behavioural support programme with a combination of nicotine patches and acute nicotine replacement therapy post-cessation.\ud Outcomes/Follow-up: The primary outcome of interest will be prolonged abstinence from smoking, with secondary trial outcomes of point prevalence, urges to smoke and withdrawal\ud symptoms. Follow up will take place at 4 weeks, 8 weeks and 6 months post-quit day

Nicotine patch preloading for smoking cessation (the preloading trial): study protocol for a randomized controlled trial

Background: The use of nicotine replacement therapy before quitting smoking is called nicotine preloading. Standard smoking cessation protocols suggest commencing nicotine replacement therapy only on the first day of quitting smoking (quit day) aiming to reduce withdrawal symptoms and craving. However, other, more successful smoking cessation pharmacotherapies are used prior to the quit day as well as after. Nicotine preloading could improve quit rates by reducing satisfaction from smoking prior to quitting and breaking the association between smoking and reward. A systematic literature review suggests that evidence for the effectiveness of preloading is inconclusive and further trials are needed. Methods/Design: This is a study protocol for a multicenter, non-blinded, randomized controlled trial based in the United Kingdom, enrolling 1786 smokers who want to quit, funded by the National Institute for Health Research, Health Technology Assessment program, and sponsored by the University of Oxford. Participants will primarily be recruited through general practices and smoking cessation clinics, and randomized (1:1) either to use 21 mg nicotine patches, or not, for four weeks before quitting, whilst smoking as normal. All participants will be referred to receive standard smoking cessation service support. Follow-ups will take place at one week, four weeks, six months and 12 months after quit day. The primary outcome will be prolonged, biochemically verified six-month abstinence. Additional outcomes will include point prevalence abstinence and abstinence of four-week and 12-month duration, side effects, costs of treatment, and markers of potential mediators and moderators of the preloading effect. Discussion: This large trial will add substantially to evidence on the effectiveness of nicotine preloading, but also on its cost effectiveness and potential mediators, which have not been investigated in detail previously. A range of recruitment strategies have been considered to try and compensate for any challenges encountered in recruiting the large sample, and the multicentre design means that knowledge can be shared between recruitment teams. The pragmatic study design means that results will give a realistic estimate of the success of the intervention if it were to be rolled out as part of standard smoking cessation service practice. Trial registration: Current Controlled Trials ISRCTN33031001. Registered 27 April 2012

Equidistribution of zeros of holomorphic sections in the non compact setting

We consider N-tensor powers of a positive Hermitian line bundle L over a non-compact complex manifold X. In the compact case, B. Shiffman and S. Zelditch proved that the zeros of random sections become asymptotically uniformly distributed with respect to the natural measure coming from the curvature of L, as N tends to infinity. Under certain boundedness assumptions on the curvature of the canonical line bundle of X and on the Chern form of L we prove a non-compact version of this result. We give various applications, including the limiting distribution of zeros of cusp forms with respect to the principal congruence subgroups of SL2(Z) and to the hyperbolic measure, the higher dimensional case of arithmetic quotients and the case of orthogonal polynomials with weights at infinity. We also give estimates for the speed of convergence of the currents of integration on the zero-divisors.Comment: 25 pages; v.2 is a final update to agree with the published pape

The GuideLine Implementability Appraisal (GLIA): development of an instrument to identify obstacles to guideline implementation

BACKGROUND: Clinical practice guidelines are not uniformly successful in influencing clinicians' behaviour toward best practices. Implementability refers to a set of characteristics that predict ease of (and obstacles to) guideline implementation. Our objective is to develop and validate a tool for appraisal of implementability of clinical guidelines. METHODS: Indicators of implementability were identified from the literature and used to create items and dimensions of the GuideLine Implementability Appraisal (GLIA). GLIA consists of 31 items, arranged into 10 dimensions. Questions from 9 of the 10 dimensions are applied individually to each recommendation of the guideline. Decidability and Executability are critical dimensions. Other dimensions are Global, Presentation and Formatting, Measurable Outcomes, Apparent Validity, Flexibility, Effect on Process of Care, Novelty/Innovation, and Computability. We conducted a series of validation activities, including validation of the construct of implementability, expert review of content for clarity, relevance, and comprehensiveness, and assessment of construct validity of the instrument. Finally, GLIA was applied to a draft guideline under development by national professional societies. RESULTS: Evidence of content validity and preliminary support for construct validity were obtained. The GLIA proved to be useful in identifying barriers to implementation in the draft guideline and the guideline was revised accordingly. CONCLUSION: GLIA may be useful to guideline developers who can apply the results to remedy defects in their guidelines. Likewise, guideline implementers may use GLIA to select implementable recommendations and to devise implementation strategies that address identified barriers. By aiding the design and operationalization of highly implementable guidelines, our goal is that application of GLIA may help to improve health outcomes, but further evaluation will be required to support this potential benefit

Critical points and supersymmetric vacua, III: String/M models

A fundamental problem in contemporary string/M theory is to count the number of inequivalent vacua satisfying constraints in a string theory model. This article contains the first rigorous results on the number and distribution of supersymmetric vacua of type IIb string theories compactified on a Calabi-Yau 3-fold $X$ with flux. In particular, complete proofs of the counting formulas in Ashok-Douglas and Denef-Douglas are given, together with van der Corput style remainder estimates. We also give evidence that the number of vacua satisfying the tadpole constraint in regions of bounded curvature in moduli space is of exponential growth in $b_3(X)$.Comment: Final revision for publication in Commun. Math. Phys. Minor corrections and editorial change