An audit and feedback intervention for reducing antibiotic prescribing in general dental practice:the RAPiD Cluster Randomised Controlled Trial

Acknowledgments: We thank the TRiaDS Research Methodology Group, including Irene Black, Debbie Bonetti, Heather Cassie, Martin Eccles, Sandra Eldridge, Jill J. Francis, Jeremy M. Grimshaw, Lorna Macpherson, Lorna McKee, Susan Michie, Nigel Pitts, Derek Richards, Douglas Stirling, Colin Tilley, Carole Torgerson, Shaun Treweek, Luke Vale, and Alan Walker for their guidance and contribution to the design and development of the study. We also thank Maria Prior for overseeing the running of the study, drafting of the published protocol, and her contribution to the design and analysis of the process evaluation. Thanks are also extended to Jill Farnham, Jenny Eades, Sarah Blackburn, and Lorna Barnsley for providing invaluable administrative support for this study. The views expressed in this article are those of the authors and may not reflect those of the funder. Funding: This study was conducted as part of the TRiaDS programme of implementation research which is funded by NHS Education for Scotland (NES). The Health Services Research Unit which is funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates supported the study. The funder had no influence over the design, conduct, analysis and write up of the study. Data Availability: Researchers can request to access the data from the Information Services Division of NHS National Services Scotland http://www.isdscotland.org/. Some restrictions may apply for the protection of privacy and appropriate usage of the data.Peer reviewedPublisher PD

CD4-Independent Human Immunodeficiency Virus Infection Involves Participation of Endocytosis and Cathepsin B

During a comparison of the infectivity of mNDK, a CD4-independent human immunodeficiency virus type 1 (HIV-1) strain, to various cell lines, we found that HeLa cells were much less susceptible than 293T and TE671 cells. Hybridoma cells between HeLa and 293T cells were as susceptible as 293T cells, suggesting that cellular factors enhance the mNDK infection in 293T cells. By screening a cDNA expression library in HeLa cells, cystatin C was isolated as an enhancer of the mNDK infection. Because cathepsin B protease, a natural ligand of cystatin C, was upregulated in HeLa cells, we speculated that the high levels of cathepsin B activities were inhibitory to the CD4-independent infection and that cystatin C enhanced the infection by impairing the excessive cathepsin B activity. Consistent with this idea, pretreatment of HeLa cells with 125 µM of CA-074Me, a cathepsin B inhibitor, resulted in an 8-fold enhancement of the mNDK infectivity. Because cathepsin B is activated by low pH in acidic endosomes, we further examined the potential roles of endosomes in the CD4-independent infection. Suppression of endosome acidification or endocytosis by inhibitors or by an Eps15 dominant negative mutant reduced the infectivity of mNDK in which CD4-dependent infections were not significantly impaired. Taken together, these results suggest that endocytosis, endosomal acidification, and cathepsin B activity are involved in the CD4-independent entry of HIV-1

Evaluating an audit and feedback intervention for reducing antibiotic prescribing behaviour in general dental practice (the RAPiD trial): a partial factorial cluster randomised trial protocol

BACKGROUND: Antibiotic prescribing in dentistry accounts for 9% of total antibiotic prescriptions in Scottish primary care. The Scottish Dental Clinical Effectiveness Programme (SDCEP) published guidance in April 2008 (2nd edition, August 2011) for Drug Prescribing in Dentistry, which aims to assist dentists to make evidence-based antibiotic prescribing decisions. However, wide variation in prescribing persists and the overall use of antibiotics is increasing. METHODS: RAPiD is a 12-month partial factorial cluster randomised trial conducted in NHS General Dental Practices across Scotland. Its aim is to compare the effectiveness of individualised audit and feedback (A&F) strategies for the translation into practice of SDCEP recommendations on antibiotic prescribing. The trial uses routinely collected electronic healthcare data in five aspects of its design in order to: identify the study population; apply eligibility criteria; carry out stratified randomisation; generate the trial intervention; analyse trial outcomes. Eligibility was determined on contract status and a minimum level of recent NHS treatment provision. All eligible dental practices in Scotland were simultaneously randomised at baseline either to current audit practice or to an intervention group. Randomisation was stratified by single-handed/multi-handed practices. General dental practitioners (GDPs) working at intervention practices will receive individualised graphical representations of their antibiotic prescribing rate from the previous 14 months at baseline and an update at six months. GDPs could not be blinded to their practice allocation. Intervention practices were further randomised using a factorial design to receive feedback with or without: a health board comparator; a supplementary text-based intervention; additional feedback at nine months. The primary outcome is the total antibiotic prescribing rate per 100 courses of treatment over the year following delivery of the baseline intervention. A concurrent qualitative process evaluation will apply theory-based approaches using the Consolidated Framework for Implementation Research to explore the acceptability of the interventions and the Theoretical Domains Framework to identify barriers and enablers to evidence-based antibiotic prescribing behaviour by GDPs. DISCUSSION: RAPiD will provide a robust evaluation of A&F in dentistry in Scotland. It also demonstrates that linked administrative datasets have the potential to be used efficiently and effectively across all stages of an randomised controlled trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN49204710