Co-design workshops to develop evidence synthesis summary formats for use by clinical guideline development groups.

BACKGROUND: Evidence synthesis is used by decision-makers in various ways, such as developing evidence-based recommendations for clinical guidelines. Clinical guideline development groups (GDGs) typically discuss evidence synthesis findings in a multidisciplinary group, including patients, healthcare providers, policymakers, etc. A recent mixed methods systematic review (MMSR) identified no gold standard format for optimally presenting evidence synthesis findings to these groups. However, it provided 94 recommendations to help produce more effective summary formats for general evidence syntheses (e.g., systematic reviews). To refine the MMSR recommendations to create more actionable guidance for summary producers, we aimed to explore these 94 recommendations with participants involved in evidence synthesis and guideline development. METHODS: We conducted a descriptive qualitative study using online focus group workshops in February and March 2023. These groups used a participatory co-design approach with interactive voting activities to identify preferences for a summary format's essential content and style. We created a topic guide focused on recommendations from the MMSR with mixed methods support, ≥ 3 supporting studies, and those prioritized by an expert advisory group via a pragmatic prioritization exercise using the MoSCoW method (Must, Should, Could, and Will not haves). Eligible participants must be/have been involved in GDGs and/or evidence synthesis. Groups were recorded and transcribed. Two independent researchers analyzed transcripts using directed content analysis with 94 pre-defined codes from the MMSR. RESULTS: Thirty individuals participated in six focus groups. We coded 79 of the 94 pre-defined codes. Participants suggested a "less is more" structured approach that minimizes methodological steps and statistical data, promoting accessibility to all audiences by judicious use of links to further information in the full report. They emphasized concise, consistently presented formats that highlight key messages, flag readers to indicators of trust in the producers (i.e., logos, websites, and conflict of interest statements), and highlight the certainty of evidence (without extenuating details). CONCLUSIONS: This study identified guidance based on the preferences of guideline developers and evidence synthesis producers about the format of evidence synthesis summaries to support decision-making. The next steps involve developing and user-testing prototype formats through one-on-one semi-structured interviews to optimize evidence synthesis summaries and support decision-making.

An international modified Delphi process supported updating the web-based "right review" tool.

OBJECTIVES: The proliferation of evidence synthesis methods makes it challenging for reviewers to select the ''right'' method. This study aimed to update the Right Review tool (a web-based decision support tool that guides users through a series of questions for recommending evidence synthesis methods) and establish a common set of questions for the synthesis of both quantitative and qualitative studies (https://rightreview.knowledgetranslation.net/). STUDY DESIGN AND SETTING: A 2-round modified international electronic modified Delphi was conducted (2022) with researchers, health-care providers, patients, and policy makers. Panel members rated the importance/clarity of the Right Review tool's guiding questions, evidence synthesis type definitions and tool output. High agreement was defined as at least 70% agreement. Any items not reaching high agreement after round 2 were discussed by the international Project Steering Group. RESULTS: Twenty-four experts from 9 countries completed round 1, with 12 completing round 2. Of the 46 items presented in round 1, 21 reached high agreement. Twenty-seven items were presented in round 2, with 8 reaching high agreement. The Project Steering Group discussed items not reaching high agreement, including 8 guiding questions, 9 review definitions (predominantly related to qualitative synthesis), and 2 output items. Three items were removed entirely and the remaining 16 revised and edited and/or combined with existing items. The final tool comprises 42 items; 9 guiding questions, 25 evidence synthesis definitions and approaches, and 8 tool outputs. CONCLUSION: The freely accessible Right Review tool supports choosing an appropriate review method. The design and clarity of this tool was enhanced by harnessing the Delphi technique to shape ongoing development. The updated tool is expected to be available in Quarter 1, 2025.

Identification of eating, drinking and swallowing difficulties for people living with early-stage dementia: A systematic review.

BACKGROUND: The prevalence of dementia is increasing, bringing a range of challenges, such as eating, drinking and swallowing (EDS) difficulties, that are associated with aspiration, which can be fatal. Early identification of EDS difficulty in early-stage dementia could prevent complications, but reliable indicators are needed to help develop pathways to support the diagnosis. Previous reviews of this area require updating. AIMS: To identify reliable and clinically measurable indicators of EDS difficulty used in early-stage dementia. METHODS & PROCEDURES: A systematic search was conducted using common databases (MEDLINE, EMBASE and PsychInfo). Articles reporting indicators of EDS difficulty in early-stage dementia or mild cognitive impairment were included. The reliability of included studies was critically appraised using the risk of bias tools. Study outcomes were narratively reviewed by considering the reliability, clinical measurability and applicability of EDS indicators to early-stage dementia. OUTCOMES & RESULTS: Initial searches returned 2443 articles. After removing duplicates, limiting to English language and human studies, 1589 articles remained. After reviewing titles, 60 abstracts were reviewed, yielding 18 full-text articles. A total of 12 articles were excluded that did not report at least one indicator of EDS difficulty in early-stage dementia, or where the reported association was not strong. Six included studies that reported eight indicators of EDS difficulty in early-stage dementia (four studies including people with Alzheimer's disease). On the balance of measurability, reliability and applicability, the most promising indicators of EDS difficulty were: delayed oral transit, rinsing ability, sarcopenia and polypharmacy. Additional, less reliable and applicable indicators included: always opened lips and non-amnestic mild cognitive impairment, especially in men. The delayed pharyngeal response is subjectively measured when instrumental assessment is not available and the 'candy sucking test' cannot be recommended because there is an inherent choking risk. CONCLUSIONS & IMPLICATIONS: EDS difficulty in early-stage dementia can be highlighted by indicators that could be combined to create enhanced pathways to support the early identification of EDS difficulties for people living with early-stage dementia with a view to preventing complications and facilitating informed discussions regarding wishes in the event of further deterioration. Exploring the experiences of people living with dementia and their families' perspectives on potential indicators of EDS difficulty may add to the existing evidence base. WHAT THIS PAPER ADDS: What is already known on the subject Early identification of EDS difficulty in early-stage dementia may prevent complications, but more reliable and clinically measurable indicators of EDS difficulty are needed to help develop pathways to support diagnosis. What this paper adds to existing knowledge A comprehensive range of studies related to EDS identification in early-stage dementia have been selected and reviewed. Across six included studies, the most promising indicators of EDS difficulty in early-stage dementia included delayed oral transit, poor rinsing ability, presence of sarcopenia and polypharmacy. What are the potential or actual clinical implications of this work? This study could help to develop pathways to support the early identification of EDS difficulties for people living with early-stage dementia with a view to preventing complications and facilitating informed discussions regarding wishes in the event of further deterioration.

Exploring the connection between dementia and eating, drinking and swallowing difficulty: Findings from home-based semi-structured interviews.

BACKGROUND: Eating, drinking and swallowing (EDS) difficulties are important to identify early. Awareness of EDS changes starts with those living with dementia or their family carers. However, little is known about early identification from the perspective of people with dementia. AIM: The aim of this study was to understand the experience of EDS by people living with dementia in their own home. METHODS: Published evidence pertaining to EDS difficulties in dementia was used to inform an online semi-structured interview guide. Four people living with dementia and a third-sector Empowerment Lead were invited to become co-researchers. People living with dementia and their carers were invited to be interviewed. We enquired about their past and present experiences, and future expected changes in EDS, information needs, opinions on early problem identification, and lifestyle modifications following onset of EDS difficulty. Narrative concepts of heroes and villains in their 'stories' were identified. Responses were subjected to framework analysis informed by narrative enquiry. RESULTS: Seven people living with dementia and five family carers were interviewed. The overarching theme was a 'missed connection' between EDS difficulty and dementia. Where EDS difficulties were identified, 'compensatory changes' and a need for 'access to information' were noted. CONCLUSIONS: The connection between potential EDS difficulties and a dementia diagnosis may not be made, even though EDS changes were recognised by people living with dementia and their family carers. This may be explained by behaviours that mask problems or allow individuals to cope or compensate. Reduced awareness may also be due to inadequate access to information and lack of specialist services. If the connection between dementia and EDS difficulty is missed it could further delay access to support services. WHAT THIS PAPER ADDS: What is already known on the subject The prevalence of dementia is increasing and is expected to affect 9% of the population by 2040. EDS difficulties are common in people living with dementia and predispose to poorer outcomes. Better awareness of EDS changes early in the disease process of dementia or at preclinical stages can identify individuals at risk and allow for intervention prior to advanced EDS difficulties developing. What this paper adds to existing knowledge This paper reports the perspective of people living with dementia and family carers and provides insights into experiences of EDS and the challenges faced and identifies commonalities. The connection between potential EDS difficulties and dementia is missed despite various changes reported by both people living with dementia and their family carers, who tend to make compensatory lifestyle changes without support. What are the potential or actual clinical implications of this work? Lack of awareness of the connection between potential EDS difficulties and dementia may arise due to inadequate access to information to support people living with dementia and their family carers. Access to such information is needed and the quality assurance of information from reputable sources is important to people living with dementia. There is a need for greater service user awareness of signs of EDS difficulty and how to access specialist services.

Strong recommendations from low certainty evidence: a cross-sectional analysis of a suite of national guidelines.

BACKGROUND: Clinical guidelines should be based on a thorough evaluation of the evidence and generally include a rating of the quality of evidence and assign a strength to recommendations. Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance warns against making strong recommendations when the certainty of the evidence is low or very low, but has identified five paradigmatic situations (e.g. life-threatening situations) where this may be justified. AIMS AND OBJECTIVES: We aimed to characterize the strength of recommendations and certainty of the evidence in Irish National Clinical Guidelines using the GRADE approach. METHODS: All National Clinical Guidelines from the National Clinical Effectiveness Committee (NCEC) website using the GRADE approach (fully or partially) were included. All recommendations and their corresponding certainty of the evidence, strength of recommendations and justifications were extracted. Authors classified instances of strong recommendations with low certainty evidence (referred to as discordant recommendations) into one of the five paradigmatic situations. Descriptive statistics were calculated. RESULTS: From the 29 NCEC Clinical Guidelines available at the time of analysis, we identified 8 guidelines using GRADE with a total of 240 recommendations; 38 recommendations did not use the GRADE approach and were excluded. Half of the included guidelines focused on emergency situations. In the final dataset of 202 recommendations, 151 (74.7%) were classified as strong and 51 (25.3%) as conditional. Of the 151 strong recommendations, 55 (36.4%) were supported by high or moderate certainty evidence and 96 (63.6%) by low or very low certainty evidence and were considered discordant. Of these 96 discordant recommendations, 55 (73.7%) were consistent with one of the five paradigmatic situations. However, none were specifically described as such within the guidelines. CONCLUSIONS: The proportion of discordant recommendations identified in this analysis was higher than some previous international studies (range of all strong recommendations being discordant 30-50%), but similar to other guidelines focused on emergency situations. The majority of discordant recommendations could be mapped to one of the five situations, but no National Clinical Guideline explicitly referenced this. Guideline developers require further guidance to enable greater transparency in the reporting of the reasons for discordant recommendations.

Perspectives on the production, and use, of rapid evidence in decision making during the COVID-19 pandemic: a qualitative study.

OBJECTIVES: To describe perceptions of providing, and using rapid evidence, to support decision making by two national bodies (one public health policy and one front-line clinical practice) during the COVID-19 pandemic. DESIGN: Descriptive qualitative study (March-August 2020): 25 semistructured interviews were conducted, transcribed verbatim and thematically analysed. SETTING: Data were obtained as part of an evaluation of two Irish national projects; the Irish COVID-19 Evidence for General Practitioners project (General Practice (GP) project) which provided relevant evidence to address clinical questions posed by GPs; and the COVID-19 Evidence Synthesis Team (Health Policy project) which produced rapid evidence products at the request of the National Public Health Emergency Team. PARTICIPANTS: Purposive sample of 14 evidence providers (EPs: generated and disseminated rapid evidence) and 11 service ssers (SUs: GPs and policy-makers, who used the evidence). MAIN OUTCOME MEASURES: Participant perceptions. RESULTS: The Policy Project comprised 27 EPs, producing 30 reports across 1432 person-work-days. The GP project comprised 10 members from 3 organisations, meeting 49 times and posting evidence-based answers to 126 questions. Four unique themes were generated. 'The Work' highlighted that a structured but flexible organisational approach to producing evidence was essential. Ensuring quality of evidence products was challenging, particularly in the context of absent or poor-quality evidence. 'The Use' highlighted that rapid evidence products were considered invaluable to decision making. Trust and credibility of EPs were key, however, communication difficulties were highlighted by SUs (eg, website functionality). 'The Team' emphasised that a highly skilled team, working collaboratively, is essential to meeting the substantial workload demands and tight turnaround time. 'The Future' highlighted that investing in resources, planning and embedding evidence synthesis support, is crucial to national emergency preparedness. CONCLUSIONS: Rapid evidence products were considered invaluable to decision making. The credibility of EPs, a close relationship with SUs and having a highly skilled and adaptable team to meet the workload demands were identified as key strengths that optimised the utilisation of rapid evidence. ETHICS APPROVAL: Ethical approval was obtained from the National Research Ethics Committee for COVID-19-related Research, Ireland.

Systematic review of the efficacy, effectiveness and safety of recombinant haemagglutinin seasonal influenza vaccines for the prevention of laboratory-confirmed influenza in individuals ≥18 years of age.

The most effective means of preventing seasonal influenza is through vaccination. In this systematic review, we investigated the efficacy, effectiveness and safety of recombinant haemagglutinin (HA) seasonal influenza vaccines to prevent laboratory-confirmed influenza. A systematic literature search was conducted in electronic databases and grey literature sources up to 7 February 2020. Randomised controlled trials and non-randomised studies of interventions were eligible for inclusion. The search returned 28,846 records, of which 10 studies on recombinant HA influenza vaccine met our inclusion criteria. One study found that the quadrivalent recombinant HA influenza vaccine had higher relative vaccine efficacy (rVE) in preventing laboratory-confirmed influenza during the 2014-15 season compared with traditional quadrivalent vaccination in adults aged ≥50 years (rVE = 30%, 95% CI 10%-47%, moderate-certainty evidence). In a subgroup analysis, higher rVE was reported for influenza A (rVE = 36%, 95% CI 14% to 53%), but not for B (non-significant). Another study reported higher efficacy for the trivalent recombinant HA vaccine compared with placebo (VE = 45%, 95% CI 19-63, 1 RCT, low-certainty evidence) in adults aged 18-55 years. With the exception of a higher rate of chills (RR = 1.33, 95% CI 1.03-1.72), the safety profile of recombinant HA vaccines was comparable to that of traditional influenza vaccines. The evidence base for the efficacy and effectiveness of recombinant HA influenza vaccines is limited at present, although one study found that the quadrivalent recombinant HA influenza vaccine had higher rVE compared with traditional quadrivalent vaccination in adults aged ≥50 years.

Systematic review of the efficacy, effectiveness and safety of high-dose seasonal influenza vaccines for the prevention of laboratory-confirmed influenza in individuals ≥18 years of age.

This review sought to assess the efficacy, effectiveness and safety of high-dose inactivated influenza vaccines (HD-IIV) for the prevention of laboratory-confirmed influenza in individuals aged 18 years or older. A systematic literature search was conducted in electronic databases and grey literature sources up to 7 February 2020. Randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) were included. The search returned 28,846 records, of which 36 studies were included. HD-IIV was shown to have higher relative vaccine efficacy in preventing influenza compared with standard-dose influenza vaccines (SD-IIV3) in older adults (Vaccine effectiveness (VE) = 24%, 95% CI 10-37, one RCT). One NRSI demonstrated significant effect for HD-IIV3 against influenza B (VE = 89%, 95% CI 47-100), but not for influenza A(H3N2) (VE = 22%, 95% CI -82 to 66) when compared with no vaccination in older adults. HD-IIV3 showed significant relative effect compared with SD-IIV3 for influenza-related hospitalisation (VE = 11.8%, 95% CI 6.4-17.0, two NRSIs), influenza- or pneumonia-related hospitalisation (VE = 13.7%, 95% CI 9.5-17.7, three NRSIs), influenza-related hospital encounters (VE = 13.1%, 95% CI 8.4-17.7, five NRSIs), and influenza-related office visits (VE = 3.5%, 95% CI 1.5-5.5, two NRSIs). For safety, HD-IIV were associated with significantly higher rates of local and systemic adverse events compared with SD-IIV (combined local reactions, pain at injection site, swelling, induration, headache, chills and malaise). From limited data, compared with SD-IIV, HD-IIV were found to be more effective in the prevention of laboratory-confirmed influenza, for a range of proxy outcome measures, and associated with more adverse events.

Systematic review of the efficacy, effectiveness and safety of cell-based seasonal influenza vaccines for the prevention of laboratory-confirmed influenza in individuals ≥18 years of age.

The most effective means of preventing seasonal influenza is through strain-specific vaccination. In this study, we investigated the efficacy, effectiveness and safety of cell-based trivalent and quadrivalent influenza vaccines. A systematic literature search was conducted in electronic databases and grey literature sources up to 7 February 2020. Randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) were eligible for inclusion. Two reviewers independently screened, extracted data and assessed the risk of bias of included studies. Certainty of evidence for key outcomes was assessed using the GRADE methodology. The search returned 28,846 records, of which 868 full-text articles were assessed for relevance. Of these, 19 studies met the inclusion criteria. No relative efficacy data were identified for the direct comparison of cell-based vaccines compared with traditional vaccines (egg-based). Efficacy data were available comparing cell-based trivalent influenza vaccines with placebo in adults (aged 18-49 years). Overall vaccine efficacy was 70% against any influenza subtype (95% CI 61%-77%, two RCTS), 82% against influenza A(H1N1) (95% CI 71%-89%, 2 RCTs), 72% against influenza A(H3N2) (95% CI 39%-87%, 2 RCTs) and 52% against influenza B (95% CI 30%-68%, 2 RCTs). Limited and heterogeneous data were presented for effectiveness when compared with no vaccination. One NRSI compared cell-based trivalent and quadrivalent vaccination with traditional trivalent and quadrivalent vaccination, finding a small but significant difference in favour of cell-based vaccines for influenza-related hospitalisation, hospital encounters and physician office visits. The safety profile of cell-based trivalent vaccines was comparable to traditional trivalent influenza vaccines. Compared with placebo, cell-based trivalent influenza vaccines have demonstrated greater efficacy in adults aged 18-49 years. Overall cell-based vaccines are well-tolerated in adults, however, evidence regarding the effectiveness of these vaccines compared with traditional seasonal influenza vaccines is limited.

Systematic review of the efficacy, effectiveness and safety of MF59® adjuvanted seasonal influenza vaccines for the prevention of laboratory-confirmed influenza in individuals ≥18 years of age.

The most effective means of preventing seasonal influenza is through vaccination. In this systematic review, we investigated the efficacy, effectiveness and safety of MF59® adjuvanted trivalent and quadrivalent influenza vaccines to prevent laboratory-confirmed influenza. A systematic literature search was conducted in electronic databases and grey literature sources up to 7 February 2020. Randomised controlled trials and non-randomised studies of interventions (NRSIs) were eligible for inclusion. The search returned 28,846 records, of which 48 studies on MF59® adjuvanted vaccines met our inclusion criteria. No efficacy trials were identified. In terms of vaccine effectiveness (VE), MF59® adjuvanted trivalent influenza vaccines were effective in preventing laboratory-confirmed influenza in older adults (aged ≥65 years) compared with no vaccination (VE = 45%, 95% confidence interval (CI) 23%-61%, 5 NRSIs across 3 influenza seasons). By subtype, significant effect was found for influenza A(H1N1) (VE = 61%, 95% CI 44%-73%) and B (VE = 29%, 95% CI 5%-46%), but not for A(H3N2). In terms of relative VE, there was no significant difference comparing MF59® adjuvanted trivalent vaccines with either non-adjuvanted trivalent or quadrivalent vaccines. Compared with traditional trivalent influenza vaccines, MF59® adjuvanted trivalent influenza vaccines were associated with a greater number of local adverse events (RR = 1.90, 95% CI 1.50-2.39) and systemic reactions (RR = 1.18, 95% CI 1.02-1.38). In conclusion, MF59® adjuvanted trivalent influenza vaccines were found to be more effective than 'no vaccination'. Based on limited data, there was no significant difference comparing the effectiveness of MF59® adjuvanted vaccines with their non-adjuvanted counterparts.

Investigating how the GRADE Evidence to Decision (EtD) framework is used in Clinical Guidelines: a scoping review protocol.

Introduction: The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) evidence to decision (EtD) framework provides a structured and transparent approach for clinical guideline developers to use when formulating recommendations. Understanding how stakeholders use the EtD framework will inform how best to provide future training and support. This scoping review objective is to identify the key characteristics of how the GRADE EtD framework is used and identify studies on perception of use by those involved in developing clinical guidelines. Methods: JBI methodology for scoping reviews will be followed. This scoping review will consider both peer review published literature and grey literature. This will include empirical studies on the use of EtDs (including both quantitative, qualitative, and mixed methods primary research articles) and discussion papers/ commentaries on the experience of using the EtD. It will also include a random sample of publicly available populated EtDs identified from databases and repositories of GRADE guidelines. The search strategy will aim to locate both published and unpublished documents. First, we will conduct an exploratory search of MEDLINE and Embase (Elsevier), supplemented with citation analysis of included articles. Populated EtDs will be identified through searches of databases and repositories of GRADE guidelines. Two researchers will independently screen, select, and extract identified documents. Data will be presented in tables and summarized descriptively. Conclusion: This scoping review will identify the key characteristics of how the GRADE EtD framework is currently being used in clinical guidelines. Review findings can be used to inform future guidance and requirements for using GRADE EtD, as well as training on how to consider the criteria in developing recommendations. Results will be disseminated through publications in peer - reviewed journals and conference presentations. We will present our findings to relevant stakeholders via the networks of the co-author team at a one-day workshop.

The effectiveness and acceptability of evidence synthesis summary formats for clinical guideline development groups: a mixed-methods systematic review.

INTRODUCTION: Clinical guideline development often involves a rigorous synthesis of evidence involving multidisciplinary stakeholders with different priorities and knowledge of evidence synthesis; this makes communicating findings complex. Summary formats are typically used to communicate the results of evidence syntheses; however, there is little consensus on which formats are most effective and acceptable for different stakeholders. METHODS: This mixed-methods systematic review (MMSR) aimed to evaluate the effectiveness and acceptability (e.g. preferences and attitudes and preferences towards) of evidence synthesis summary formats for GDG members. We followed the PRISMA 2020 guideline and Joanna Briggs Institute Manual for Evidence Synthesis for MMSRs. We searched six databases (inception to April 20, 2021) for randomised controlled trials (RCTs), RCTs with a qualitative component, and qualitative studies. Screening, data extraction, and quality appraisal were performed in duplicate. Qualitative findings were synthesised using meta-aggregation, and quantitative findings are described narratively. RESULTS: We identified 17,240 citations and screened 54 full-text articles, resulting in 22 eligible articles (20 unique studies): 4 articles reported the results of 5 RCTs, one of which also had a qualitative component. The other 18 articles discussed the results of 16 qualitative studies. Therefore, we had 5 trials and 17 qualitative studies to extract data from. Studies were geographically heterogeneous and included a variety of stakeholders and summary formats. All 5 RCTs assessed knowledge or understanding with 3 reporting improvement with newer formats. The qualitative analysis identified 6 categories of recommendations: 'presenting information', 'tailoring information' for end users, 'trust in producers and summary', 'knowledge required' to understand findings, 'quality of evidence', and properly 'contextualising information'. Across these categories, the synthesis resulted in 126 recommendations for practice. Nine recommendations were supported by both quantitative and qualitative evidence and 116 by only qualitative. A majority focused on how to present information (n = 64) and tailor content for different end users (n = 24). CONCLUSIONS: This MMSR provides guidance on how to improve evidence summary structure and layout. This can be used by synthesis producers to better communicate to GDGs. Study findings will inform the co-creation of evidence summary format prototypes based on GDG member's needs. Trial registration The protocol for this project was previously published, and the project was preregistered on Open Science Framework (Clyne and Sharp, Evidence synthesis and translation of findings for national clinical guideline development: addressing the needs and preferences of guideline development groups, 2021; Sharp and Clyne, Evidence synthesis summary formats for decision-makers and Clinical Guideline Development Groups: A mixed-methods systematic review protocol, 2021).

Another Step Toward Hepatitis C Elimination: An Economic Evaluation of an Irish National Birth Cohort Testing Program.

OBJECTIVES: We aimed to evaluate the cost-effectiveness of offering once-off birth cohort testing for hepatitis C virus (HCV) to people in Ireland born between 1965 and 1985, the cohort with the highest reported prevalence of undiagnosed chronic HCV infection. METHODS: Systematic and opportunistic HCV birth cohort testing programs, implemented over a 4-year timeframe, were compared with the current practice of population risk-based testing only in a closed-cohort decision tree and Markov model hybrid over a lifetime time horizon. Outcomes were expressed in quality-adjusted life-years (QALYs). Costs were presented from the health system's perspective in 2020 euro (€). Uncertainty was assessed via deterministic, probabilistic, scenario, and threshold analyses. RESULTS: In the base case, systematic testing yielded the largest cost and health benefits, followed by opportunistic testing and risk-based testing. Compared with risk-based testing, the incremental cost-effectiveness ratio for opportunistic testing was €14 586 (95% confidence interval €4185-€33 527) per QALY gained. Compared with opportunistic testing, the incremental cost-effectiveness ratio for systematic testing was €16 827 (95% confidence interval €5106-€38 843) per QALY gained. These findings were robust across a range of sensitivity analyses. CONCLUSIONS: Both systematic and opportunistic birth cohort testing would be considered an efficient use of resources, but systematic testing was the optimal strategy at willingness-to-pay threshold values typically used in Ireland. Although cost-effective, any decision to introduce birth cohort testing for HCV (in Ireland or elsewhere) must be balanced with considerations regarding the feasibility and budget impact of implementing a national testing program given high initial costs and resource use.

Effectiveness of rapid antigen testing for screening of asymptomatic individuals to limit the transmission of SARS-CoV-2: A rapid review.

Rapid antigen detection tests (RADTs) offer advantages over gold-standard reverse transcription polymerase chain reaction (RT-PCR) tests in that they are cheaper and provide faster results, thus enabling prompt isolation of positive SARS-CoV-2 cases and quarantine of close contacts. The aim of this study was to collate and synthesise empirical evidence on the effectiveness of rapid antigen testing for the screening (including serial testing) and surveillance of asymptomatic individuals to limit the transmission of SARS-CoV-2. A rapid review was undertaken in MEDLINE (EBSCO), EMBASE (OVID), Cochrane Library, Europe PMC and Google Scholar up until 19 July 2021, supplemented by a grey literature search. Of the identified 1222 records, 19 reports referring to 16 studies were included. Eight included studies examined the effectiveness of RADTs for population-level screening, four for pre-event screening and four for serial testing (schools, a prison, a university sports programme and in care homes). Overall, there is uncertainty regarding the effectiveness of rapid antigen testing for the screening of asymptomatic individuals to limit the transmission of SARS-CoV-2. This uncertainty is due to the inconsistent results, the relatively low number of studies identified, the predominantly observational and/or uncontrolled nature of the study designs used, and concerns regarding methodological quality. Given this uncertainty, more real-world research evidence in relevant settings, which is of good quality and timely, as well as economic evaluation, is required to inform public policy on the widespread use of RADTs in asymptomatic individuals.

ADAPTE with modified Delphi supported developing a National Clinical Guideline: stratification of clinical risk in pregnancy.

OBJECTIVES: Adaptation has been proposed as an alternative to de novo development to take advantage of existing clinical guidelines (guidelines) and reduce duplication. We describe the process of incorporating a modified Delphi method to reach formal consensus and inform locally relevant clinical recommendations during the development, through the ADAPTE process, of the Irish National Clinical Guideline No. 23 Stratification of Clinical Risk in Pregnancy. METHODS: A systematic search of guideline repositories, websites, and bibliographic databases was conducted. Quality appraisal was undertaken using AGREE II. Risk factors indicating the need for additional care were identified and extracted from high-quality guidelines. A three-round modified Delphi panel comprising healthcare stakeholders, was convened to agree and tailor risk factors. RESULTS: Of seven relevant international guidelines identified, three were considered high quality and contained a combined 59 risk factors potentially suitable for adaptation. Following the three-round Delphi process, 49 risk factors were included in the final guideline. Excluded risk factors were generally considered to be too broad to be useful for the Irish context. CONCLUSION: We believe that a formal consensus technique included within the ADAPTE process increased the rigor and transparency of this process and ensured the inclusion of more locally relevant risk factors.

Challenges encountered during the systematic review of newer and enhanced influenza vaccines and recommendations for the future.

There are a variety of challenges in the conduct of systematic reviews of influenza vaccines. We describe our experience of completing four systematic reviews of newer and enhanced inactivated seasonal influenza vaccines. The reporting of the included studies created significant challenges for study identification, data extraction and analysis. Those challenges have implications for the resources required to conduct reviews and, more significantly, for the accuracy of the estimated treatment effect. There is a substantial burden of morbidity and mortality associated with seasonal influenza, and the evidence used to support vaccination strategies requires regular review. An improved review process will facilitate robust decision-making both nationally and internationally. We recommend the development of reporting guidelines, increased engagement between researchers and decision makers, a database of identified trials, and research into search optimisation.

Transmission of SARS-CoV-2 by children: a rapid review, 30 December 2019 to 10 August 2020.

BackgroundThe role of children in the transmission of SARS-CoV-2 during the early pandemic was unclear.AimWe aimed to review studies on the transmission of SARS-CoV-2 by children during the early pandemic.MethodsWe searched MEDLINE, Embase, the Cochrane Library, Europe PubMed Central and the preprint servers medRxiv and bioRxiv from 30 December 2019 to 10 August 2020. We assessed the quality of included studies using a series of questions adapted from related tools. We provide a narrative synthesis of the results.ResultsWe identified 28 studies from 17 countries. Ten of 19 studies on household and close contact transmission reported low rates of child-to-adult or child-to-child transmission. Six studies investigated transmission of SARS-CoV-2 in educational settings, with three studies reporting 183 cases from 14,003 close contacts who may have contracted COVID-19 from children index cases at their schools. Three mathematical modelling studies estimated that children were less likely to infect others than adults. All studies were of low to moderate quality.ConclusionsDuring the early pandemic, it appeared that children were not substantially contributing to household transmission of SARS-CoV-2. School-based studies indicated that transmission rates in this setting were low. Large-scale studies of transmission chains using data collected from contact tracing and serological studies detecting past evidence of infection would be needed to verify our findings.

Irish Media Coverage of COVID-19 Evidence-Based Research Reports From One National Agency.

BACKGROUND: How research findings are presented through domestic news can influence behaviour and risk perceptions, particularly during emergencies such as the coronavirus disease 2019 (COVID-19) pandemic. Monitoring media communications to track misinformation and find information gaps is an important component of emergency risk communication. Therefore, this study investigated the traditional media coverage of nine selected COVID-19 evidence-based research reports and associated press releases (PRs) published during the initial phases of the pandemic (April to July 2020) by one national agency. METHODS: NVivo was used for summative content analysis. 'Key messages' from each research report were proposed and 488 broadcast, print, and online media sources were coded at the phrase level. Manifest content was coded and counted to locate patterns in the data (what and how many) while latent content was analysed to further investigate these patterns (why and how). This included the coding of the presence of political and public health actors in coverage. RESULTS: Coverage largely did not misrepresent the results of the reports, however, selective reporting and the variability in the use of quotes from governmental and public health stakeholders changed and contextualised results in different manners than perhaps originally intended in the PR. Reports received varying levels of media attention. Coverage focused on more 'human-interest' stories (eg, spread of COVID-19 by children and excess mortality) as opposed to more technical reports (eg, focusing on viral load, antibodies, testing, etc). CONCLUSION: Our findings provide a case-study of European media coverage of evidence reports produced by a national agency. Results highlighted several strengths and weaknesses of current communication efforts.

Patients' spirituality perspectives at the end of life: a qualitative evidence synthesis.

BACKGROUND: Understanding patient perceptions of their spiritual needs when approaching the end of life is essential to support the delivery of patient-centred care. AIM: To conduct a qualitative evidence synthesis on spirituality and spiritual care needs at the end of life in all healthcare settings from the patients' perspective. DESIGN: Studies were included where they were primary qualitative studies exploring spirituality in patients with a life expectancy of 12 months or less in any setting. Two reviewers independently screened titles, extracted data and conducted methodological quality appraisal. A thematic synthesis was conducted. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) - Confidence in the Evidence from Reviews of Qualitative research (CERQual) was used to summarise the certainty of the evidence. DATA SOURCES: Six databases (Medline, Embase, Cochrane, CINAHL, PsycINFO, Applied Social Science Index and Abstracts) were searched from inception up to January 2019. RESULTS: Fifty papers (42 unique datasets), incorporating data from 710 patients were included. Studies recruited from a mix of inpatient, outpatient, hospice and community settings across 12 different countries. Three overarching themes were generated: the concept of spirituality, spiritual needs and distress, and spiritual care resources. Relationships were an intrinsic component of spirituality. CONCLUSION: Meeting patients' spiritual needs is an integral part of end-of-life care. This work emphasises that supporting relationships should be a central focus of spiritual care for patients at the end of life. PROSPERO REGISTRATION NUMBER: CRD42019122062.

Pharmacological interventions to prevent Covid-19 disease: A rapid review.

The aim of this rapid review was to determine the effectiveness of pharmacological interventions (excluding vaccines) to prevent coronavirus disease 2019 (Covid-19) or reduce the severity of disease. A systematic search of published peer-reviewed articles and non-peer-reviewed pre-prints was undertaken from 1 January 2020 to 17 August 2021. Four randomised controlled trials (RCTs) and one non-RCT were included; three trials (two RCTs and one non-RCT) tested ivermectin with or without carrageenan. While all reported some potential protective effect of ivermectin, these trials had a high risk of bias and the certainty of evidence was deemed to be 'very low'. One RCT tested bamlanivimab compared to placebo and reported a significantly reduced incidence of Covid-19 in the intervention group; this trial had a low risk of bias however the certainty of evidence was deemed 'very low'. The fifth RCT tested casirivimab plus imdevimab versus placebo and reported that the combination of monoclonal antibodies significantly reduced the incidence of symptomatic and asymptomatic SARS-CoV-2 infection, viral load, duration of symptomatic disease and the duration of a high viral load; this trial was deemed to have a low risk of bias, and the certainty of evidence was 'low'. The designations 'low' and 'very low' regarding the certainty of evidence indicate that the estimate of effect is uncertain and therefore is unsuitable for informing decision-making. At the time of writing, there is insufficient high quality evidence to support the use of pharmacological interventions to prevent Covid-19.