Preclinical models of myocardial infarction: from mechanism to translation

Approximately 7 million people are affected by acute myocardial infarction (MI) each year, and despite significant therapeutic and diagnostic advancements, MI remains a leading cause of mortality worldwide. Pre-clinical animal models have significantly advanced our understanding of MI and enable the development of therapeutic strategies to combat this debilitating disease. Notably, some drugs currently used to treat MI and heart failure (HF) in patients had initially been studied in pre-clinical animal models. Despite this, pre-clinical models are limited in their ability to fully recapitulate the complexity of MI in humans. The pre-clinical model must be carefully selected to maximise the translational potential of experimental findings. This review describes current experimental models of MI and considers how they have been used to understand drug mechanisms of action (MOA) and support translational medicine development

Diurnal variation on tear stability and correlation with tear cytokine concentration

Producción CientíficaPurpose: To investigate the effect of time of day on tear evaporation rate (TER) and tear break-up time, and its possible relationship with the concentration of inflammatory tear molecules (cytokines) in healthy subjects. Methods: Participants with healthy ocular surfaces attended 3 visits, including the screening visit (V0), the 2nd visit (V1) and the 3rd visit (V2). There were 7-day intervals between visits. Participants with Dry Eye Disease (DED) were excluded by using appropriate clinical tests during V0. Clinical evaluation (TER and Non-Invasive Tear Break-Up Time (NITBUT)) and tear collection were performed during V1 and V2, between 9 and 10AM and 3-4PM. The relative humidity and temperature of the examination room were also measured. The tear fluid concentrations of 15 cytokines were measured by multiplex bead analysis. Results: Seven men and 10 women (mean age ± S.D; 25.1 ± 6.63 years old) participated in the study. There were no differences in neither the TER and NITBUT outcomes, nor humidity and temperature among times or visits. Eleven out of the 15 cytokines measured were detectable in tear fluids in > 50% of the participants. In the tear levels, no significant (p > 0.05) inter- and/or intra-day differences were detected for EGF, fractalkine, IL-1RA, IL-1β and IP-10. However, significant inter-day differences were found in the tear levels of IL-10 (p = 0.027), IFN-γ (p = 0.035) and TNF-α(p = 0.04) and intra-day differences in the tear levels of IL-8/CXCL8 (p = 0.034) and MCP-1 (p = 0.002). A significant correlation between TER and IL1-β, IL-2, and Fractalkine (p = 0.03, p = 0.03 and p = 0.046, respectively) was found at V1. Conclusions: NITBUT and TER values had no significant variability over the course of a day (AM versus PM), or on different days in healthy participants when humidity and temperature were constant. However, some tear molecule levels did show inter- and intra-day variability, having an inconsistent and moderate correlation with TER diurnal variation

Selective decontamination of the digestive tract in critically ill patients treated in intensive care units: a mixed-methods feasibility study (the SuDDICU study)

Background: Hospital-acquired infections (HAIs) are a major cause of morbidity and mortality. Critically ill patients in intensive care units (ICUs) are particularly susceptible to these infections. One intervention that has gained much attention in reducing HAIs is selective decontamination of the digestive tract (SDD). SDD involves the application of topical non-absorbable antibiotics to the oropharynx and stomach and a short course of intravenous (i.v.) antibiotics. SDD may reduce infections and improve mortality, but has not been widely adopted in the UK or internationally. Hence, there is a need to identify the reasons for low uptake and whether or not further clinical research is needed before wider implementation would be considered appropriate. Objectives: The project objectives were to (1) identify and describe the SDD intervention, (2) identify views about the evidence base, (3) identify acceptability of further research and (4) identify feasibility of further randomised controlled trials (RCTs). Design : A four-stage approach involving (1) case studies of two ICUs in which SDD is delivered including observations, interviews and documentary analysis, (2) a three-round Delphi study for in-depth investigation of clinicians' views, including semi-structured interviews and two iterations of questionnaires with structured feedback, (3) a nationwide online survey of consultants in intensive care medicine and clinical microbiology and (4) semistructured interviews with international clinical triallists to identify the feasibility of further research. Setting : Case studies were set in two UK ICUs. Other stages of this research were conducted by telephone and online with NHS staff working in ICUs. Participants : (1) Staff involved in SDD adoption or delivery in two UK ICUs, (2) ICU experts (intensive care consultants, clinical microbiologists, hospital pharmacists and ICU clinical leads), (3) all intensive care consultants and clinical microbiologists in the UK with responsibility for patients in ICUs were invited and (4) international triallists, selected from their research profiles in intensive care, clinical trials and/or implementation trials. Interventions : SDD involves the application of topical non-absorbable antibiotics to the oropharynx and stomach and a short course of i.v. antibiotics. Main outcome measures: Levels of support for, or opposition to, SDD in UK ICUs; views about the SDD evidence base and about barriers to implementation; and feasibility of further SDD research (e.g. likely participation rates). Results : (1) The two case studies identified complexity in the interplay of clinical and behavioural components of SDD, involving multiple staff. However, from the perspective of individual staff, delivery of SDD was regarded as simple and straightforward. (2) The Delphi study (n = 42) identified (a) specific barriers to SDD implementation, (b) uncertainty about the evidence base and (c) bimodal distributions for key variables, e.g. support for, or opposition to, SDD. (3) The national survey (n = 468) identified uncertainty about the effect of SDD on antimicrobial resistance, infection rates, mortality and cost-effectiveness. Most participants would participate in further SDD research. (4) The triallist interviews (n = 10) focused largely on the substantial challenges of conducting a large, multinational clinical effectiveness trial. Conclusions : There was considerable uncertainty about possible benefits and harms of SDD. Further large-scale clinical effectiveness trials of SDD in ICUs may be required to address these uncertainties, especially relating to antimicrobial resistance. There was a general willingness to participate in a future effectiveness RCT of SDD. However, support was not unanimous. Future research should address the barriers to acceptance and participation in any trial. There was some, but a low level of, interest in adoption of SDD, or studies to encourage implementation of SDD into practice

Current approaches to soft contact lens handling training - Global perspectives

Purpose All neophyte contact lens wearers require training on how to handle contact lenses. Currently, almost no published information exists describing the most common approaches used by those involved in such training in soft contact lens wearers. This study aimed to gather information on the approaches taken by those conducting this training worldwide. Methods An online survey was created in English and translated to Spanish and distributed internationally via social media, conference attendees, and professional contacts. The anonymous survey included information on workplace setting of respondents, information about the typical approaches used for application and removal of soft contact lenses, length of the appointment, and success rate with their approach. Survey responses were received between May 2021 and April 2022. Results A total of 511 individuals completed the survey and responses were received from 31 countries with 48.7% from the UK. The most common approach taught for application was to have the patient hold the upper eyelashes (84.7%) and to hold the lower eyelid with the same hand as the lens (89.4%). Lenses were applied directly to the cornea by 57.7% of the respondents. The most common approach taught for lens removal was to drag the lens inferiorly from the cornea prior to removal (49.3%). Most respondents did not use videos to aid the teaching appointment (62.0%); however, they felt that their approach was successful in most cases (90). Application and removal training sessions lasted a median of 30 min and contact lenses were typically dispensed after the instructor witnessing successful application and removal three times. Conclusion Various methods are adopted globally for training of application and removal of soft contact lenses, with many advising a patient-specific approach is required for success. The results of this survey provide novel insights into soft contact lens handling training in clinical practice

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