Cross-Sector Review of Drivers and Available 3Rs Approaches for Acute Systemic Toxicity Testing

Acute systemic toxicity studies are carried out in many sectors in which synthetic chemicals are manufactured or used and are among the most criticized of all toxicology tests on both scientific and ethical grounds. A review of the drivers for acute toxicity testing within the pharmaceutical industry led to a paradigm shift whereby in vivo acute toxicity data are no longer routinely required in advance of human clinical trials. Based on this experience, the following review was undertaken to identify (1) regulatory and scientific drivers for acute toxicity testing in other industrial sectors, (2) activities aimed at replacing, reducing, or refining the use of animals, and (3) recommendations for future work in this area

PRImary care Streptococcal Management (PRISM) study:In vitro study, diagnostic cohorts and a pragmatic adaptive randomised controlled trial with nested qualitative study and cost-effectiveness study

Background: Antibiotics are still prescribed to most patients attending primary care with acute sore throat, despite evidence that there is modest benefit overall from antibiotics. Targeting antibiotics using either clinical scoring methods or rapid antigen detection tests (RADTs) could help. However, there is debate about which groups of streptococci are important (particularly Lancefield groups C and G), and uncertainty about the variables that most clearly predict the presence of streptococci. Objective: This study aimed to compare clinical scores or RADTs with delayed antibiotic prescribing. Design: The study comprised a RADT in vitro study; two diagnostic cohorts to develop streptococcal scores (score 1; score 2); and, finally, an open pragmatic randomised controlled trial with nested qualitative and cost-effectiveness studies. Setting: The setting was UK primary care general practices. Participants: Participants were patients aged ≥ 3 years with acute sore throat. Interventions: An internet program randomised patients to targeted antibiotic use according to (1) delayed antibiotics (control group), (2) clinical score or (3) RADT used according to clinical score. Main outcome measures: The main outcome measures were self-reported antibiotic use and symptom duration and severity on seven-point Likert scales (primary outcome: mean sore throat/difficulty swallowing score in the first 2-4 days). Results: The IMI TestPack Plus Strep A (Inverness Medical, Bedford, UK) was sensitive, specific and easy to use. Lancefield group A/C/G streptococci were found in 40% of cohort 2 and 34% of cohort 1. A five-point score predicting the presence of A/C/G streptococci [FeverPAIN: Fever; Purulence; Attend rapidly (≤ 3 days); severe Inflammation; and No cough or coryza] had moderate predictive value (bootstrapped estimates of area under receiver operating characteristic curve: 0.73 cohort 1, 0.71 cohort 2) and identified a substantial number of participants at low risk of streptococcal infection. In total, 38% of cohort 1 and 36% of cohort 2 scored ≤ 1 for FeverPAIN, associated with streptococcal percentages of 13% and 18%, respectively. In an adaptive trial design, the preliminary score (score 1; n = 1129) was replaced by FeverPAIN (n = 631). For score 1, there were no significant differences between groups. For FeverPAIN, symptom severity was documented in 80% of patients, and was lower in the clinical score group than in the delayed prescribing group (-0.33; 95% confidence interval -0.64 to -0.02; p = 0.039; equivalent to one in three rating sore throat a slight rather than moderately bad problem), and a similar reduction was observed for the RADT group (-0.30; -0.61 to 0.00; p = 0.053). Moderately bad or worse symptoms resolved significantly faster (30%) in the clinical score group (hazard ratio 1.30; 1.03 to 1.63) but not the RADT group (1.11; 0.88 to 1.40). In the delayed group, 75/164 (46%) used antibiotics, and 29% fewer used antibiotics in the clinical score group (risk ratio 0.71; 0.50 to 0.95; p = 0.018) and 27% fewer in the RADT group (0.73; 0.52 to 0.98; p = 0.033). No significant differences in complications or reconsultations were found. The clinical score group dominated both other groups for both the cost/quality-adjusted life-years and cost/change in symptom severity analyses, being both less costly and more effective, and cost-effectiveness acceptability curves indicated the clinical score to be the most likely to be cost-effective from an NHS perspective. Patients were positive about RADTs. Health professionals' concerns about test validity, the time the test took and medicalising self-limiting illness lessened after using the tests. For both RADTs and clinical scores, there were tensions with established clinical experience. Conclusions: Targeting antibiotics using a clinical score (FeverPAIN) efficiently improves symptoms and reduces antibiotic use. RADTs used in combination with FeverPAIN provide no clear advantages over FeverPAIN alone, and RADTs are unlikely to be incorporated into practice until health professionals' concerns are met and they have experience of using them. Clinical scores also face barriers related to clinicians' perceptions of their utility in the face of experience. This study has demonstrated the limitation of using one data set to develop a clinical score. FeverPAIN, derived from two data sets, appears to be valid and its use improves outcomes, but diagnostic studies to confirm the validity of FeverPAIN in other data sets and settings are needed. Experienced clinicians need to identify barriers to the use of clinical scoring methods. Implementation studies that address perceived barriers in the use of FeverPAIN are needed

How to evaluate sexual health in cancer patients:Development of the EORTC sexual health questionnaire for cancer patients

Background: The aim of the study is to describe the development of a comprehensive European Organisation for Research and Treatment of Cancer (EORTC) questionnaire to assess sexual health of female and male cancer patients and for cancer survivors. Methods: According to the EORTC guidelines, the development of an EORTC sexual health questionnaire is typically organised in four phases. The first phases comprise a literature search following interviews with patient and health care professionals (HCPs) (phase 1) and the operationalization into items (phase 2). The translation process is formally conducted according to the EORTC QLG Translation guidelines with a rigorous forward-backward procedure supported by native speakers. Results: Studies on sexuality in oncology patients which were identified by a literature search predominantly focused on issues of activity, experiences of sexual dysfunction, and satisfaction with sexual functioning. The literature review identified themes beyond these aspects. In total 53 potentially relevant issues were presented to 107 patients and 83 HCPs, different evaluations were found. Conclusions: A questionnaire that includes physical, psychological, and social aspects of sexuality of cancer survivors will be needed. Pre-testing and validation of the questionnaire will be done in future (phases 3 and 4). Divergent ratings of patients and professionals should be further investigated. Keywords: Cancer; sexual health; European Organisation for Research and Treatment of Cancer (EORTC) sexual health questionnair

Knowledge translation strategies to improve the use of evidence in public health decision making in local government: intervention design and implementation plan

Background:&nbsp;Knowledge translation strategies are an approach to increase the use of evidence within policy and practice decision-making contexts. In clinical and health service contexts, knowledge translation strategies have focused on individual behavior change, however the multi-system context of public health requires a multi-level, multi-strategy approach. This paper describes the design of and implementation plan for a knowledge translation intervention for public health decision making in local government. Methods: Four preliminary research studies contributed findings to the design of the intervention: a systematic review of knowledge translation intervention effectiveness research, a scoping study of knowledge translation perspectives and relevant theory literature, a survey of the local government public health workforce, and a study of the use of evidence-informed decision-making for public health in local government. A logic model was then developed to represent the putative pathways between intervention inputs, processes, and outcomes operating between individual-, organizational-, and system-level strategies. This formed the basis of the intervention plan. Results: The systematic and scoping reviews identified that effective and promising strategies to increase access to research evidence require an integrated intervention of skill development, access to a knowledge broker, resources and tools for evidence-informed decision making, and networking for information sharing. Interviews and survey analysis suggested that the intervention needs to operate at individual and organizational levels, comprising workforce development, access to evidence, and regular contact with a knowledge broker to increase access to intervention evidence; develop skills in appraisal and integration of evidence; strengthen networks; and explore organizational factors to build organizational cultures receptive to embedding evidence in practice. The logic model incorporated these inputs and strategies with a set of outcomes to measure the intervention\u27s effectiveness based on the theoretical frameworks, evaluation studies, and decision-maker experiences. Conclusion: Documenting the design of and implementation plan for this knowledge translation intervention provides a transparent, theoretical, and practical approach to a complex intervention. It provides significant insights into how practitioners might engage with evidence in public health decision making. While this intervention model was designed for the local government context, it is likely to be applicable and generalizable across sectors and settings.</div

Games and simulations in teaching and learning

Available from British Library Lending Division - LD:85/26864(Games) / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

International Refinement Workshop and Formal Methods Pacific ’98

The International Refinement Workshop and Formal Methods Pacific 1998 (IRW/FMP'98), as the title suggests, is a combined event. FMP'98 itself incorporates the 7th Australasian Refinement Workshop and the 4th New Zealand Formal Program Development Colloquium, and follows the inaugural FMP'97 in Wellington. The Australasian Refinement Workshop (ARW) series began in 1990, to provide a forum for researchers in program refinement. The New Zealand Formal Program Development Colloquium (NZFPDC) series began in 1994 with similar aims. In 1997 the ARW and NZFPDC joined forces in Wellington under the umbrella name Formal Methods Pacific (FMP). The more general name, and regional focus better reflects the broader range of interests of participants and presented papers, while satisfying the need for a regional conference covering formal methods. The event became the International Refinement Workshop with the postponement of the 7th British Refinement Workshop, and the welcome support of IRW/FMP'98 by the British Computer Society FACS. IRW/FMP'98 is being held concurrently with The 11th International Conference on Theorem Proving in Higher Order Logics (TPHOLs'98) at The Australian National University. Papers for IRW/FMP'98 were sought in two streams: Completed Work and Work in Progress. The Work in Progress stream provides a forum for discussion of work that has not yet reached maturity. Submissions were vetted for relevance, but not refereed. This volume presents the Work in Progress papers.Conference Papers: Reasoning about Grover's Quantum Search Algorithm using Probabilistic wp / By Michael Butler and Pieter Hartel -- Care2 and its Type System / By Keith Harwood -- A Proof Framework with IO Regular Expressions for Dataow Networks / By Yuji Hayashi, Tadashi Yamaguchi and Eiichi Miyamo -- Can Component Object Model (COM) be Formalized: The Formal Semantics of the COMEL Language / By Rosziati Ibrahim and Clemens Szyperski -- Modelling Specification-based Testing of Interactive Systems / By Ian MacColl and David Carrington -- A Superposition Refinement of Component-based Systems / By Winnie Weiqun Qiu and John Zic -- I Went Down To The Crossroads: Conjoining Catamorphisms / By Martin Schwenke -- Using the Object Calculus to build an Object-Oriented Refinement Calculus / By Jamie Shield and David Carrington -- Equivalences and Refinement / By Igor V. Tarasyuk -- Local Stores in C++ / By Mark Utting and James Dunwoody -- Teaching Formal Methods Lite / By Mark Utting and Steve Reeves -- Issues for a Temporal Refinement Calculus / By Ron van der Meyden and Yoram Mose