OBJECTIVES:To report long-term clinical efficacy, safety, pharmacokinetics, immunogenicity and seroneutralization results of AZD7442 (monoclonal antibodies tixagevimab-cilgavimab) in patients hospitalized with COVID-19. METHODS:In this phase 3, double-blind, randomized, multicentre trial, hospitalized adults with PCR-confirmed SARS-CoV-2 infection were randomly assigned 1:1 to receive AZD7442 or placebo, and followed-up until day 456, with repeated blood sample collections until day 365. Clinical endpoints included clinical status, mortality, rehospitalization, SARS-CoV-2 reinfection, and adverse events. Antidrug antibodies and serum drug concentrations were measured. Analyses were performed on the modified intention-to-treat (mITT) populations, defined as participants who actually received the intervention. RESULTS:Between April 28, 2021, and June 23, 2022, 237 participants were randomly assigned to AZD7442 (n = 127) or placebo (n = 110), and 123 participants actually received AZD7442. Participants were infected with pre-Omicron variants in 58.8% (133/226) of cases, versus 33.2% (75/226) of Omicron BA1, BA2, or BA5, and 8% (18/226) missing data. There was no significant difference in the distribution of the 7-point ordinal scale between the AZD7442 and placebo groups, either on day 15 (primary endpoint) (OR = 0.93 [0.54-1.61], p 0.81), or any other time point. Significantly more rehospitalizations occurred between discharge and day 456 among participants who received AZD7442 in the global mITT population (OR = 2.04 [1.03-4.05], p 0.04), but not in the antigen-positive mITT population (OR = 1.78 [0.80-3.94], p 0.15). No significant differences were observed in mortality, SARS-CoV-2 reinfection, or adverse events. In the AZD7442 group, 12 of 87 participants (13.8%) had treatment-emergent antidrug antibodies versus 5 of 69 (7.2%) in the placebo group (OR = 2.02 [0.66-6.14], p 0.21). Serum drug concentrations were detectable up to day 365 for all sampled participants (35/35). Neutralizing antibody titres were significantly higher in the AZD7442 group up to day 180. CONCLUSIONS:AZD7442 did not demonstrate any clinical benefit and was safe up to 15 months. This study also provides valuable data on the pharmacokinetics, immunogenicity, and neutralizing activity of AZD7442 in patients hospitalized with COVID-19.

Abstract Background Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants. Methods Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures. Results Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modified intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49–69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute difference and 95% CI − 0.1% [− 8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (− 3.2% [− 9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a significant interaction between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated participants were on average 11 years older, with more comorbidities. Conclusion This clinical trial was prematurely stopped for external evidence and therefore underpowered to conclude on a potential survival benefit of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these findings warrant further investigation in other trials and real-world studies. Trial registration Bari-SolidAct is registered at NCT04891133 (registered May 18, 2021) and EUClinicalTrials.eu ( 2022-500385-99-00 ).

BackgroundThe Solidarity trial among COVID-19 inpatients has previously reported interim mortality analyses for four repurposed antiviral drugs. Lopinavir, hydroxychloroquine, and interferon (IFN)-β1a were discontinued for futility but randomisation to remdesivir continued. Here, we report the final results of Solidarity and meta-analyses of mortality in all relevant trials to date.MethodsSolidarity enrolled consenting adults (aged ≥18 years) recently hospitalised with, in the view of their doctor, definite COVID-19 and no contraindication to any of the study drugs, regardless of any other patient characteristics. Participants were randomly allocated, in equal proportions between the locally available options, to receive whichever of the four study drugs (lopinavir, hydroxychloroquine, IFN-β1a, or remdesivir) were locally available at that time or no study drug (controls). All patients also received the local standard of care. No placebos were given. The protocol-specified primary endpoint was in-hospital mortality, subdivided by disease severity. Secondary endpoints were progression to ventilation if not already ventilated, and time-to-discharge from hospital. Final log-rank and Kaplan-Meier analyses are presented for remdesivir, and are appended for all four study drugs. Meta-analyses give weighted averages of the mortality findings in this and all other randomised trials of these drugs among hospital inpatients. Solidarity is registered with ISRCTN, ISRCTN83971151, and ClinicalTrials.gov, NCT04315948.FindingsBetween March 22, 2020, and Jan 29, 2021, 14 304 potentially eligible patients were recruited from 454 hospitals in 35 countries in all six WHO regions. After the exclusion of 83 (0·6%) patients with a refuted COVID-19 diagnosis or encrypted consent not entered into the database, Solidarity enrolled 14 221 patients, including 8275 randomly allocated (1:1) either to remdesivir (ten daily infusions, unless discharged earlier) or to its control (allocated no study drug although remdesivir was locally available). Compliance was high in both groups. Overall, 602 (14·5%) of 4146 patients assigned to remdesivir died versus 643 (15·6%) of 4129 assigned to control (mortality rate ratio [RR] 0·91 [95% CI 0·82–1·02], p=0·12). Of those already ventilated, 151 (42·1%) of 359 assigned to remdesivir died versus 134 (38·6%) of 347 assigned to control (RR 1·13 [0·89–1·42], p=0·32). Of those not ventilated but on oxygen, 14·6% assigned to remdesivir died versus 16·3% assigned to control (RR 0·87 [0·76–0·99], p=0·03). Of 1730 not on oxygen initially, 2·9% assigned to remdesivir died versus 3·8% assigned to control (RR 0·76 [0·46–1·28], p=0·30). Combining all those not ventilated initially, 11·9% assigned to remdesivir died versus 13·5% assigned to control (RR 0·86 [0·76–0·98], p=0·02) and 14·1% versus 15·7% progressed to ventilation (RR 0·88 [0·77–1·00], p=0·04). The non-prespecified composite outcome of death or progression to ventilation occurred in 19·6% assigned to remdesivir versus 22·5% assigned to control (RR 0·84 [0·75–0·93], p=0·001). Allocation to daily remdesivir infusions (vs open-label control) delayed discharge by about 1 day during the 10-day treatment period. A meta-analysis of mortality in all randomised trials of remdesivir versus no remdesivir yielded similar findings.InterpretationRemdesivir has no significant effect on patients with COVID-19 who are already being ventilated. Among other hospitalised patients, it has a small effect against death or progression to ventilation (or both).FundingWHO.

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered new approaches in clinical research. These include the conduct of adaptive platform trials, such as RECOVERY [[1]Mullard A. COVID-19 platform trial delivers.Nat Rev Drug Discov. 2020; 19: 501Google Scholar], REMAP-CAP and DisCoVeRy [[2]Ader F. Discovery French Trial Management TeamProtocol for the DisCoVeRy trial: multicentre, adaptive, randomised trial of the safety and efficacy of treatments for COVID-19 in hospitalised adults.BMJ Open. 2020; 10e041437Crossref PubMed Scopus (32) Google Scholar]. Platform trials allow the study of several target treatments in the same disease context on a perpetual basis, with therapies being allowed to enter or leave the platform based on a decision algorithm [[3]Woodcock J. LaVange L.M. Master protocols to study multiple therapies, multiple diseases, or both.N Engl J Med. 2017; 377: 62-70Crossref PubMed Scopus (607) Google Scholar]. DisCoVeRy is part of a European project, EU-RESPONSE, originally set up in France as a WHO Solidarity trial add-on study [[4]WHO COVID-19 solidarity therapeutics trial. World Health Organization, 2021https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-clinical-trial-for-covid-19-treatmentsGoogle Scholar]. EU-RESPONSE is funded by the Horizon 2020 programme to allow the expansion of DisCoVeRy to other European/associated countries, and the launch of 'EU-SolidAct', a second-generation pan-European platform trial for coronavirus disease 2019 (COVID-19)/emerging infectious diseases, implemented to extend what was initiated by DisCoVeRy. These trials have faced multiple hurdles. Under the 2001/20/EC Directive, approval of multinational clinical trials in Europe requires parallel and independent submissions to the national competent authority (NCA) and ethics committee (EC) of each participating country. Since 2009, the European Medicines Agency has developed a Voluntary Harmonization Procedure (VHP) whereby a single application is sent to one reference NCA coordinating the response of all NCAs, before a national phase takes place in each country. Some Member States offer the involvement of ECs (VHP plus process). Whereas DisCoVeRy used multiple national applications (VHP not possible because the trial received initial approval in France), EU-SolidAct opted for the VHP. In DisCoVeRy, five countries were involved at the onset of the pandemic, in 2020. The median review times were 13 days (interquartile range (IQR) 7–17 days) and 17 days (IQR 15–21 days) for NCAs and ECs, respectively. In 2021, the new treatment arm required the submission of an amendment that applied not only to the countries already involved, but also to the eight countries that had started recruiting since the first approval. The median amendments review time was 47.5 days (IQR 34.25–63.5 days) for 10 of the 13 countries and 35.5 days (IQR 27.75–58.5 days) for 8 of the 13 countries, for NCAs and ECs, respectively. The shorter time frame observed in 2020 is related to the fast-track procedure implemented for all of these countries at the beginning of the pandemic. The fast-track procedure was withdrawn in 2021. Duplicate reviews of the protocol with similar questions/queries were requested from various countries (See Table 1).Table 1Assessment time (days) for (inter)national approval for DisCoVeRyCountryFirst submission (2020)Amendments (2021)ECNCAECNCAAustria2117pendingpendingBelgium15132816Czech Republicpending aSome local regulations require approval by the national competent authority before submission to the ethics committee.98France031733GreecependingpendingHungary2732Ireland10856Luxembourg17192842Norway4938Polandpending aSome local regulations require approval by the national competent authority before submission to the ethics committee.66Portugal41743§67Slovakiapending aSome local regulations require approval by the national competent authority before submission to the ethics committee.53Spain87pendingMedian (IQR)17 (15-21)13 (7-17)35.5 (27.75-58.5)47.5 (34.25-63.5)Abbreviations:EC, ethics committee; IQR, interquartile range; NCA, national competent authoritya Some local regulations require approval by the national competent authority before submission to the ethics committee. Open table in a new tab Abbreviations:EC, ethics committee; IQR, interquartile range; NCA, national competent authority For EU-SolidAct, the VHP and VHP + assessment took 56 days. However, the duration of the subsequent national phase varied from a few days to several months. The median review time was 20.5 days (IQR 12.5–43.5 days) for 14 of the 16 countries and 35 days (IQR 29–42 days) for 9 of the 16 countries, for NCAs and ECs, respectively. The time frame for substantial amendments, including adding a new arm, is expected to be 50 days (See Table 2).Table 2Assessment time (days) for (inter)national approval for SolidActCountryInternationalNationalVHPVHP+NCAECAustriax21PendingBelgiumx2PendingCzech Republic4427Francex196Germanyx134PendingGreece14Hungaryx4242IrelandX383ItalyX12LuxembourgX9136Norwayx529Portugalx3384SlovakiaX2030Spainx4835SwitzerlandXTurkeyMedian (IQR)20.5 (12.5–43.5)35 (29–42)Abbreviations:EC, ethics committee; IQR, interquartile range; NCA, national competent authority; VHP, voluntary harmonization procedure Open table in a new tab Abbreviations:EC, ethics committee; IQR, interquartile range; NCA, national competent authority; VHP, voluntary harmonization procedure The aim of these clinical trials is to urgently obtain clinically relevant results and propose therapeutic and preventive solutions. Prolonged evaluation times are therefore obstacles to finding these solutions and to the subsequent rapid development of best clinical care for patients. In comparison, in the UK, where the conduct of clinical trials seems to have been more successful, with the support of the competent authorities, COVID-19 studies were swiftly revised to accelerate the approval process during the health crisis. The National Institute for Health Research established a single UK-wide process to prioritize COVID-19 research as Urgent Public Health Research early in the pandemic [5National Institute for Health Research (NIHR)– Written evidence (COV0041).https://committees.parliament.uk/writtenevidence/8275/pdf/Date accessed: October 4, 2021Google Scholar, 6Fast track review guidance for COVID-19 studies.https://www.hra.nhs.uk/covid-19-research/fast-track-review-guidance-covid-19-studies/Date accessed: October 4, 2021Google Scholar, 7Guidance clinical trials applications for coronavirus (COVID-19).https://www.gov.uk/guidance/clinical-trials-applications-for-coronavirus-covid-19Date accessed: October 4, 2021Google Scholar]. This enabled the implementation of a fast-track review or process by offering reviews by the Research Ethics Committee and NCA with the submission of one application reviewed and the issue of approval within days. There were challenges in drafting the information leaflet as well. The adaptation of each leaflet to local regulations, including the size of the document and the number of consents to be drafted per party required by ECs, led to numerous exchanges and submission extensions. Some hurdles are expected to be reduced by the new Regulation 536/2014 on clinical trials, which is to come into force in January 2022 (see Appendix 1). This regulation will ensure that rules for conducting clinical trials are identical throughout the European Union (EU) and will also allow a coordinated assessment of clinical trial applications and especially the protocol and the product between Member States [[8]European Commissionhttps://ec.europa.eu/health/human-use/clinical-trials/regulation_enDate: 2021Date accessed: October 4, 2021Google Scholar,[9]Regulation (EU) No 536/2014 Questions & Answers – draft July 2021.https://ec.europa.eu/health/sites/default/files/files/eudralex/vol-10/regulation5362014_qa_en.pdfDate accessed: October 4, 2021Google Scholar]. Nevertheless, it seems that the coordinated process under this regulation will not apply to all the steps of approval. For example, it will not apply to patient information and consent, which will continue to be dealt with at site level. We therefore suggest the following considerations when implementing this legislation (See Table S1).-For EU-funded platform trials during the pandemic, to reach a single decision the assessment involving NCAs and ECs must be mandatory for all Member States.-A protocol pre-submission review involving all relevant NCAs/ECs is needed, to discuss potential grounds for non-approval early on.-During the health crisis, enabling the implementation of a fast-track process by offering review by a research EC and an NCA, with submission of one application reviewed within 1 week.-Amendments must be subject to fast-track review.-Repurposing trials to test drugs with known safety profiles should be seen as low-risk trials, with shorter timelines. The definition of 'low intervention trials' under Regulation 536/2014 must include such trials. Here, we have focused on inpatient studies. One should acknowledge that outpatient trials in which the logistics are challenging (e.g. test turnaround time, contacting people with a positive test, quarantine limiting study visits) will be even more difficult to implement if national rules continue to be defined without any EU harmonization and without taking the need for trials into account. Negotiations of agreements between the trial sponsor and sites, and translations into local languages, represent a major bottleneck. Some sites insist on using their own templates, which requires valuable time and resources in order to understand regional legislation and its legal language. The flowchart shown in Fig. 1 illustrates these hurdles. Following this, we suggest the development of a pan-European site agreement template by the EC, which allows an electronic signature for all parties, and its translation into all European languages. Acceptance of this template by implementing sites/institutions could be an eligibility criterion for publicly funded multinational trials in the EU. Mention should be made on the information sheet of the sharing of individual participants' data by EU Member States participating in the trial for public health benefits. Immediate availability of sufficient funding is critical for the success of multinational trials in a pandemic. This pandemic has demonstrated that implementing an EU seed grant programme is critical when sponsored funding is not yet available but the problem demands immediate investigation [[10]Messersmith J. Stoddart-Osumah C. Lennon M. Wirtz D. Emergency seed funding for COVID-19 research: lessons from Johns Hopkins University.J Clin Invest. 2021; 131e14561Crossref Scopus (5) Google Scholar]. The substantial and ambitious seed grant will allow the research to start quickly. Bottom-up funding mechanisms based on competitive calls are too slow, and have resulted in duplication and fragmentation of trials. We propose:-A top-down decision mechanism established at EU level that promptly releases appropriate budgets, using funding mechanisms from the Horizon Europe budget and/or ERA4Health in coordination with the European Health Emergency Preparedness and Response Authority (HERA)-Subsequent funding of intervention arms from the same public sources, with levels of funding adapted to the nature of the trial-Safeguards to ensure public health relevance, independence and scientific excellence. Europe, despite its diversity, must be capable of responding unanimously and rapidly to any health crisis; establishing effective medical collaboration is key to responding to epidemics/pandemics. Regulatory, legal and financial hurdles have significantly slowed down the efficient conduct of clinical trials, which is unacceptable during an active pandemic. Adaptive, large clinical trials during pandemics should be considered a critical countermeasure, and the pace of regulatory approval should be consistent with the urgency of this situation. This is also applicable to non-emergencies and to multicentre clinical trials in general. There is a definite need to overcome these hurdles to prepare Europe for the next pandemic and to make United Europe of Research a reality.

Abstract Background Previous self-harm is one of the strongest predictors of future self-harm and suicide. Increased risk of repeated self-harm and suicide exists amongst patients presenting to hospital with high-risk self-harm and major self-harm repeaters. However, so far evidence-based training in the management of self-harm for mental health professionals is limited. Within this context, we aim to develop, implement and evaluate a training programme, SAMAGH, Self-harm Assessment and Management Programme for General Hospitals in Ireland. SAMAGH aims to (a) reduce hospital-based self-harm repetition rates and (b) increase rates of mental health assessments being conducted with self-harm patients. We also aim to evaluate the training on self-harm knowledge, attitudes, and skills related outcomes of healthcare professionals involved in the training. Methods/design The study will be conducted in three phases. First, the SAMAGH Training Programme has been developed, which comprises two parts: 1) E-learning Programme and 2) Simulation Training. Second, SAMAGH will be delivered to healthcare professionals from general hospitals in Ireland. Third, an outcome and process evaluation will be conducted using a pre-post design. The outcome evaluation will be conducted using aggregated data from the National Self-Harm Registry Ireland (NSHRI) on self-harm repetition rates from all 27 public hospitals in Ireland. Aggregated data based on the 3-year average (2016, 2017, 2018) self-harm repetition rates prior to the implementation of the SAMAGH will be used as baseline data, and NSHRI data from 6 and 12 months after the implementation of SAMAGH will be used as follow-up. For the process evaluation, questionnaires and focus groups will be administered and conducted with healthcare professionals who completed the training. Discussion This study will contribute to the evidence base regarding the effectiveness of an evidence informed training programme that aims to reduce repeated hospital self-harm presentations and to improve compliance with self-harm assessment and management. This study is also expected to contribute to self-harm and suicide training with the possibility of being translated to other settings. Its feasibility will be evaluated through a process evaluation.

Background Previous self-harm is one of the strongest predictors of future self-harm and suicide. Increased risk of repeated self-harm and suicide exists amongst patients presenting to hospital with high-risk self-harm and major self-harm repeaters. However, so far evidence-based training in the management of self-harm for mental health professionals is limited. Within this context, we aim to develop, implement and evaluate a training programme, SAMAGH, S elf-harm A ssessment and M anagement Programme for G eneral H ospitals in Ireland. SAMAGH aims to (a) reduce hospital-based self-harm repetition rates and (b) increase rates of mental health assessments being conducted with self-harm patients. We also aim to evaluate the training on self-harm knowledge, attitudes, and skills related outcomes of healthcare professionals involved in the training. Methods/design The study will be conducted in three phases. First, the SAMAGH Training Programme has been developed, which comprises two parts: 1) E-learning Programme and 2) Simulation Training. Second, SAMAGH will be delivered to healthcare professionals from general hospitals in Ireland. Third, an outcome and process evaluation will be conducted using a pre-post design. The outcome evaluation will be conducted using aggregated data from the National Self-Harm Registry Ireland (NSHRI) on self-harm repetition rates from all 27 public hospitals in Ireland. Aggregated data based on the 3-year average (2016, 2017, 2018) self-harm repetition rates prior to the implementation of the SAMAGH will be used as baseline data, and NSHRI data from 6 and 12 months after the implementation of SAMAGH will be used as follow-up. For the process evaluation, questionnaires and focus groups will be administered and conducted with healthcare professionals who completed the training. Discussion This study will contribute to the evidence base regarding the effectiveness of an evidence informed training programme that aims to reduce repeated hospital self-harm presentations and to improve compliance with self-harm assessment and management. This study is also expected to contribute to self-harm and suicide training with the possibility of being translated to other settings. Its feasibility will be evaluated through a process evaluation.

PURPOSE:The purpose of this study was to explore the knowledge, attitudes and practices of health professionals working in clinical trials, to pharmacovigilance and adverse drug reaction (ADR) reporting.METHODS:A mixed methods study comprising an online questionnaire disseminated from September to November 2018, three semi-structured interviews and four focus groups. The qualitative components were conducted with a random sample of questionnaire participants who had provided their contact details (n = 24). The qualitative interviews were conducted at a location convenient to the participant's place of work between October and December 2018.RESULTS:One hundred forty-eight participants completed the questionnaire. Study coordinators/project managers represented the largest group of participants ( 28.6%, n = 38). Poor knowledge or understanding of ADR reporting was the most frequently cited barrier to ADR reporting (75%, n = 93). The most common enabler to reporting was having a clear understanding of an ADR definition (85.7%, n = 108). Focus group and interview participants described having limited staff as a barrier to reporting an ADR. They welcomed the prospect of pharmacovigilance training and indicated that face-to-face training would be preferred to provision of online training.CONCLUSION:This study highlights key factors that influence the reporting of ADRs in clinical trials. Although the findings are specifically related to the clinical trial environment in Ireland, they may provide a useful platform for optimising the future conduct of trials. This research suggests that ADR reporting may be improved through provision of enhanced pharmacovigilance training to clinical trial staff.

Background Previous self-harm is one of the strongest predictors of future self-harm and suicide. Increased risk of repeated self-harm and suicide exists amongst patients presenting to hospital with high-risk self-harm and major self-harm repeaters. However, so far evidence-based training in the management of self-harm for mental health professionals is limited. Within this context, we aim to develop, implement and evaluate a training programme,SAMAGH, Self-harmAssessment andManagement Programme forGeneralHospitals in Ireland. SAMAGH aims to (a) reduce hospital-based self-harm repetition rates and (b) increase rates of mental health assessments being conducted with self-harm patients. We also aim to evaluate the training on self-harm knowledge, attitudes, and skills related outcomes of healthcare professionals involved in the training. Methods/design The study will be conducted in three phases. First, the SAMAGH Training Programme has been developed, which comprises two parts: 1) E-learning Programme and 2) Simulation Training. Second, SAMAGH will be delivered to healthcare professionals from general hospitals in Ireland. Third, an outcome and process evaluation will be conducted using a pre-post design. The outcome evaluation will be conducted using aggregated data from the National Self-Harm Registry Ireland (NSHRI) on self-harm repetition rates from all 27 public hospitals in Ireland. Aggregated data based on the 3-year average (2016, 2017, 2018) self-harm repetition rates prior to the implementation of the SAMAGH will be used as baseline data, and NSHRI data from 6 and 12 months after the implementation of SAMAGH will be used as follow-up. For the process evaluation, questionnaires and focus groups will be administered and conducted with healthcare professionals who completed the training. Discussion This study will contribute to the evidence base regarding the effectiveness of an evidence informed training programme that aims to reduce repeated hospital self-harm presentations and to improve compliance with self-harm assessment and management. This study is also expected to contribute to self-harm and suicide training with the possibility of being translated to other settings. Its feasibility will be evaluated through a process evaluation.

Cystic Fibrosis is the most common life limiting genetic disease affecting Caucasians. The life expectancy of this cohort has increased and is predicted to reach retirement age. As most CF patients are diagnosed from birth, they undergo educational and management programs throughout their lives. However numerous studies have identified various knowledge gaps. This paper presents a scoping literature review of the available educational interventions for adult CF patients. This review follows the framework as outlined by Arksey et al. [9]. A search string is entered into four databases and the resulting literature is downloaded into the academic reference manager software, Mendeley version 1.16.1. The manuscripts are then subjected to title, abstract, and introduction refinement. The remaining manuscripts are then reviewed under the following headings: 1) Aims/Objective, 2) Patient Demographic, 3) Educational Focus, 4) Research Type Conducted, 5) Methodologies, 6) Results, and 7) Author Noted Limitations. Of the 3649 manuscripts, only eight remained after the refinement stages. A significant amount of the papers that were excluded focused on CF pediatric patients only. Of the remaining papers, four manuscripts focused solely on CF adults. Seven of the papers identified a range of issues with CF education, including anxiety, knowledge gaps, and a lack of educational teams. Five papers introduced an educational intervention, only one was for CF adults only. Two of the interventions were ICT based. Of the manuscripts, one intervention that targeted both children and adults was reported as being implemented into the hospital services long term. From the final papers reviewed, it is apparent that there appears to be an issue with adult CF education and knowledge gaps. With CF survival rates rising and a new aging CF population emerging, there is a need for educational programs and interventions to meet the changing needs of the CF adult population.

The bronchial tree structure is a complex form within the human lung. It consists of many intertwining pipes which decrease in size and increase in number as you travel deeper into the structure. To amplify the difficulty this poses, visual learning aids accessible to students both in a lab environment and self-learning environment are generally two dimensional. Gamification techniques for education and eLearning have been proven beneficial in advancing many area of medical pedagogy. This paper presents a system intended to disseminate lung anatomy knowledge to medical students, as well as novice bronchoscopists. To achieve this, a 3D bronchial structure was modelled to match that of schematic drawings provided to medical students. This model was then imported into a 3D learning system that had been created using a game engine and designed for deployment on a web-based platform. This framework provides a learning environment in which the user can navigate through the bronchial pipes and interact with interest points to learn about the anatomical structure. The framework also includes a quiz environment, adapting the interest points as quiz questions. The quiz includes dynamically generated feedback, providing a means of self-assessment for the user. This environment also incorporates game metaphors such as points of interest, levels, objectives, and a heads up display (HUD). Similarly, the environment uses player pawn flying navigation with keyboard and mouse input, reflecting the navigation found in many first-person games. Future developments for this system involve the inclusion of pathologies to compliment anatomical knowledge. It is also anticipated that the system will be further extended to include other pedagogical content regarding the thoracic cavity.

Despite the growth of e-learning, its methods have yet to be incorporated into all educational modules within the discipline of medicine. As such, its integration into some educational methods for the study of complex diseases may benefit both students and trainees. In particular, the strategies demonstrated in blended, multimedia and web-based interactive platforms may enhance its overall communication. Cystic Fibrosis is a complex genetic disease which affects various parts of the body. These effects prove difficult to communicate through the written form alone and visual media elements are often incorporated to encourage a better understanding. However this foundational understanding of the disease has the potential to be enhanced further through the utilisation of e-learning techniques. In this paper, current content and resources in the field of e-learning for the disease Cystic Fibrosis and other complex lung diseases are compared and interrogated for possible areas of improvement and expansion. It was found that there was a lack of e-learning visualisers and simulators that demonstrated the mucus effects caused by Cystic Fibrosis within the lungs. As such, a Cystic Fibrosis visualiser and simulator was created using both 3D and web technologies and presented to medical students for evaluation. It was found that the visualiser aided in initial primary understanding of the mucus effects on the lungs, however, it was also found that it could not be used for further advanced teaching without improvements. In this way, it was established that the visualiser, in its simplicity, could be used to educate patients and families about Cystic Fibrosis mucus effects on the lungs.

Abstract Background Evidence based consensus guidelines for venous thromboembolism (VTE) prevention are broadly accepted to be effective and safe for more than three decades (Clagett GP et al, 1992). However VTE continues to be associated with a major global burden of disease with 3.9 million cases of HAT during one year among 1.1 billion citizens of high income countries (Jha AK et al, 2013). Therefore prevention is the key to reduce death and disability resulting from VTE (Kahn S et al, Gould MK et al & Falck-Yitter Y et al, 2012). Ireland like many other countries has yet to implement a mandatory risk assessment tool and thromboprophylaxis (TP) policy nationally. Aims The aim of this study was to calculate the proportion of inpatients who had a VTE risk assessment performed and received appropriate TP in a large tertiary referral hospital. This information will be vital for baseline data for implementation of a new national policy for prevention of HAT. Methods This audit was performed at Cork University Hospital on 4 pre specified days between November 2014 to February 2015. All adult inpatients (Medical and Surgical) excluding maternity and psychiatric were included. Patients on therapeutic anticoagulation were also excluded. The patients' medical chart and drug prescription chart were reviewed to determine whether or not a VTE risk assessment was documented for each patient and if they had received appropriate TP. If no risk assessment had been performed, trained researchers applied the National Institute for health and Care Excellence (NICE) guidelines 92 (Jan 2010) for VTE risk assessment and prevention. Following the risk assessment patients were divided into three categories, high risk of VTE with low risk of bleeding; high risk of VTE with significant risk of bleeding and low risk of VTE. From this the proportion of patients in each group that received appropriate TP were calculated. Results A total of 1019 patients were enrolled the majority were medical patients 63.5% (n=648). The mean age of patients was 69 years. Females accounted for 52% of patients. Average length of hospitalisation for each patient at the time of the audit was 6 days (range 1-664 days). Overall, a formal TP risk assessment was documented in only 24% (n=244) of all charts reviewed however TP was prescribed in 43.2% (n=441) of patients. See table.Table 1.High Risk of VTE low risk of bleedingHigh risk of VTE significant risk of bleedingLow risk of VTENo. of pts80.3% (n=819)16.6% (n=170)2.9% (n=30)VTE risk assessment documented21.9% (n=180)28.2% (n=55)30% (n=9)Received TP46.3% (n=380)28.8% (n=49)40% (n=12) Within the high risk category patients, 64.3% (n=526) medical. TP was only administered to 46.3% (n=380) of patients in the high risk category. This was almost evenly distributed between surgical 50.1% (n=147) and medical 43.4% (n=233) patients. Conclusion This audit was done as the initial step to develop a national policy to prevent HAT. As suspected, this audit highlights that a large proportion of hospitalised patients, both surgical and medical, continue to be at high risk for VTE despite the availability of preventative measures. There is clear illustration of under prescription of safe, effective and recommended means of VTE prevention. The current overall figure of less than 50% prescription of VTE thromboprophylaxis in high risk patients is a major patient safety concern. There are numerous recognised international guidelines for prevention of VTE, and an efficient method to implement these guidelines needs to be developed. Beyond developing national guidelines for TP, we need a co-ordinated approach to implement and monitor compliance with guidelines. Once the preliminary results of this audit were available to us in March 2015, urgent measures were taken to reduce the identified risk such as the establishment of a Hospital Thrombosis Group which developed a user friendly VTE risk assessment tool and TP policy. The VTE risk assessment tool was incorporated into the patients drug prescription chart and included a pre printed prescription for TP. It is now mandatory for the all patients to have a VTE risk assessment tool and TP prescribed if appropriate within 24hrs of admission. This was successfully piloted for four weeks in the acute medical assessment unit and is now incorporated into each patients drug chart throughout the hospital. This audit will be replicated in 6 months from introduction of this initiative, with an aim of >90% compliance. Disclosures No relevant conflicts of interest to declare.

Biobank Ireland Trust (BIT) was established in 2004 to promote and develop an Irish biobank network to benefit patients, researchers, industry, and the economy. The network commenced in 2008 with two hospital biobanks and currently consists of biobanks in the four main cancer hospitals in Ireland. The St. James's Hospital (SJH) Biobank coordinates the network. Procedures, based on ISBER and NCI guidelines, are standardized across the network. Policies and documents-Patient Consent Policy, Patient Information Sheet, Biobank Consent Form, Sample and Data Access Policy (SAP), and Sample Application Form have been agreed upon (after robust discussion) for use in each hospital. An optimum sequence for document preparation and submission for review is outlined. Once consensus is reached among the participating biobanks, the SJH biobank liaises with the Research and Ethics Committees, the Office of the Data Protection Commissioner, The National Cancer Registry (NCR), patient advocate groups, researchers, and other stakeholders. The NCR provides de-identified data from its database for researchers via unique biobank codes. ELSI issues discussed include the introduction of prospective consent across the network and the return of significant research results to patients. Only 4 of 363 patients opted to be re-contacted and re-consented on each occasion that their samples are included in a new project. It was decided, after multidisciplinary discussion, that results will not be returned to patients. The SAP is modeled on those of several international networks. Biobank Ireland is affiliated with international biobanking groups-Marble Arch International Working Group, ISBER, and ESBB. The Irish government continues to deliberate on how to fund and implement biobanking nationally. Meanwhile BIT uses every opportunity to promote awareness of the benefits of biobanking in events and in the media.