Using the COM-B framework to elucidate facilitators and barriers to COVID-19 vaccine uptake in pregnant women: a qualitative study.

Since April 2021, COVID-19 vaccines have been recommended for pregnant women. Despite this, COVID-19 vaccine uptake in this group is low compared to the non-pregnant population of childbearing age. Our aim was to understand barriers and facilitators to COVID-19 vaccine uptake among pregnant women in Northern Ireland using the COM-B framework, and so to make recommendations for public health interventions. The COM-B proposes that human behaviour is influenced by the extent to which a person has the capability, opportunity, and motivation to enact that behaviour. Understanding the factors underpinning behaviour through this lens helps discern what needs to change to change behaviour, therefore supporting the development of targeted interventions.This study consisted of eight semi-structured interviews with new/expectant mothers who did not receive a COVID-19 vaccine dose while pregnant since April 2021, and a focus group with five participants who received at least one COVID-19 vaccine dose while pregnant. Interview and focus group data were analysed using semi-deductive reflexive thematic analysis framed by a subtle realist approach. The COM-B was used to categorise codes and subthemes were developed within each COM-B construct.Within Psychological Capability, subthemes captured the need for consistent and reliable COVID-19 vaccine information and access to balanced and jargon-free, risk-benefit information that is tailored to the pregnant individual. The behaviour/opinions of family, friends, and local healthcare providers had a powerful influence on COVID-19 vaccine decisions (Social Opportunity). Integrating the COVID-19 vaccine as part of routine antenatal pathways was believed to support access and sense of familiarity (Physical Opportunity). Participants valued health autonomy, however experienced internal conflict driven by concerns about long-term side effects for their baby (Reflective Motivation). Feelings of fear, lack of empathy from healthcare providers, and anticipated guilt commonly underpinned indecision as to whether to get the vaccine (Automatic Motivation).Our study highlighted that the choice to accept a vaccine during pregnancy generates internal conflict and worry. Several participants cited their concern was primarily around the safety for their baby. Healthcare professionals (HCPs) play a significant part when it comes to decision making about COVID-19 vaccines among pregnant women. HCPs and pregnant women should be involved in the development of interventions to improve the delivery and communication of information.

Adverse events following first and second dose COVID-19 vaccination in England, October 2020 to September 2021: a national vaccine surveillance platform self-controlled case series study.

BackgroundPost-authorisation vaccine safety surveillance is well established for reporting common adverse events of interest (AEIs) following influenza vaccines, but not for COVID-19 vaccines.AimTo estimate the incidence of AEIs presenting to primary care following COVID-19 vaccination in England, and report safety profile differences between vaccine brands.MethodsWe used a self-controlled case series design to estimate relative incidence (RI) of AEIs reported to the national sentinel network, the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub. We compared AEIs (overall and by clinical category) 7 days pre- and post-vaccination to background levels between 1 October 2020 and 12 September 2021.ResultsWithin 7,952,861 records, 781,200 individuals (9.82%) presented to general practice with 1,482,273 AEIs, 4.85% within 7 days post-vaccination. Overall, medically attended AEIs decreased post-vaccination against background levels. There was a 3-7% decrease in incidence within 7 days after both doses of Comirnaty (RI: 0.93; 95% CI: 0.91-0.94 and RI: 0.96; 95% CI: 0.94-0.98, respectively) and Vaxzevria (RI: 0.97; 95% CI: 0.95-0.98). A 20% increase was observed after one dose of Spikevax (RI: 1.20; 95% CI: 1.00-1.44). Fewer AEIs were reported as age increased. Types of AEIs, e.g. increased neurological and psychiatric conditions, varied between brands following two doses of Comirnaty (RI: 1.41; 95% CI: 1.28-1.56) and Vaxzevria (RI: 1.07; 95% CI: 0.97-1.78).ConclusionCOVID-19 vaccines are associated with a small decrease in medically attended AEI incidence. Sentinel networks could routinely report common AEI rates, contributing to reporting vaccine safety.

First dose ChAdOx1 and BNT162b2 COVID-19 vaccinations and cerebral venous sinus thrombosis: A pooled self-controlled case series study of 11.6 million individuals in England, Scotland, and Wales.

BACKGROUND: Several countries restricted the administration of ChAdOx1 to older age groups in 2021 over safety concerns following case reports and observed versus expected analyses suggesting a possible association with cerebral venous sinus thrombosis (CVST). Large datasets are required to precisely estimate the association between Coronavirus Disease 2019 (COVID-19) vaccination and CVST due to the extreme rarity of this event. We aimed to accomplish this by combining national data from England, Scotland, and Wales. METHODS AND FINDINGS: We created data platforms consisting of linked primary care, secondary care, mortality, and virological testing data in each of England, Scotland, and Wales, with a combined cohort of 11,637,157 people and 6,808,293 person years of follow-up. The cohort start date was December 8, 2020, and the end date was June 30, 2021. The outcome measure we examined was incident CVST events recorded in either primary or secondary care records. We carried out a self-controlled case series (SCCS) analysis of this outcome following first dose vaccination with ChAdOx1 and BNT162b2. The observation period consisted of an initial 90-day reference period, followed by a 2-week prerisk period directly prior to vaccination, and a 4-week risk period following vaccination. Counts of CVST cases from each country were tallied, then expanded into a full dataset with 1 row for each individual and observation time period. There was a combined total of 201 incident CVST events in the cohorts (29.5 per million person years). There were 81 CVST events in the observation period among those who a received first dose of ChAdOx1 (approximately 16.34 per million doses) and 40 for those who received a first dose of BNT162b2 (approximately 12.60 per million doses). We fitted conditional Poisson models to estimate incidence rate ratios (IRRs). Vaccination with ChAdOx1 was associated with an elevated risk of incident CVST events in the 28 days following vaccination, IRR = 1.93 (95% confidence interval (CI) 1.20 to 3.11). We did not find an association between BNT162b2 and CVST in the 28 days following vaccination, IRR = 0.78 (95% CI 0.34 to 1.77). Our study had some limitations. The SCCS study design implicitly controls for variables that are constant over the observation period, but also assumes that outcome events are independent of exposure. This assumption may not be satisfied in the case of CVST, firstly because it is a serious adverse event, and secondly because the vaccination programme in the United Kingdom prioritised the clinically extremely vulnerable and those with underlying health conditions, which may have caused a selection effect for individuals more prone to CVST. Although we pooled data from several large datasets, there was still a low number of events, which may have caused imprecision in our estimates. CONCLUSIONS: In this study, we observed a small elevated risk of CVST events following vaccination with ChAdOx1, but not BNT162b2. Our analysis pooled information from large datasets from England, Scotland, and Wales. This evidence may be useful in risk-benefit analyses of vaccine policies and in providing quantification of risks associated with vaccination to the general public.

Interim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study.

BACKGROUND: The BNT162b2 mRNA (Pfizer-BioNTech) and ChAdOx1 nCoV-19 (Oxford-AstraZeneca) COVID-19 vaccines have shown high efficacy against disease in phase 3 clinical trials and are now being used in national vaccination programmes in the UK and several other countries. Studying the real-world effects of these vaccines is an urgent requirement. The aim of our study was to investigate the association between the mass roll-out of the first doses of these COVID-19 vaccines and hospital admissions for COVID-19. METHODS: We did a prospective cohort study using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19-EAVE II-database comprising linked vaccination, primary care, real-time reverse transcription-PCR testing, and hospital admission patient records for 5·4 million people in Scotland (about 99% of the population) registered at 940 general practices. Individuals who had previously tested positive were excluded from the analysis. A time-dependent Cox model and Poisson regression models with inverse propensity weights were fitted to estimate effectiveness against COVID-19 hospital admission (defined as 1-adjusted rate ratio) following the first dose of vaccine. FINDINGS: Between Dec 8, 2020, and Feb 22, 2021, a total of 1 331 993 people were vaccinated over the study period. The mean age of those vaccinated was 65·0 years (SD 16·2). The first dose of the BNT162b2 mRNA vaccine was associated with a vaccine effect of 91% (95% CI 85-94) for reduced COVID-19 hospital admission at 28-34 days post-vaccination. Vaccine effect at the same time interval for the ChAdOx1 vaccine was 88% (95% CI 75-94). Results of combined vaccine effects against hospital admission due to COVID-19 were similar when restricting the analysis to those aged 80 years and older (83%, 95% CI 72-89 at 28-34 days post-vaccination). INTERPRETATION: Mass roll-out of the first doses of the BNT162b2 mRNA and ChAdOx1 vaccines was associated with substantial reductions in the risk of hospital admission due to COVID-19 in Scotland. There remains the possibility that some of the observed effects might have been due to residual confounding. FUNDING: UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK.

Variations in COVID-19 vaccination uptake among people in receipt of psychotropic drugs: cross-sectional analysis of a national population-based prospective cohort.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has disproportionately affected people with mental health conditions. AIMS: We investigated the association between receiving psychotropic drugs, as an indicator of mental health conditions, and COVID-19 vaccine uptake. METHOD: We conducted a cross-sectional analysis of a prospective cohort of the Northern Ireland adult population using national linked primary care registration, vaccination, secondary care and pharmacy dispensing data. Univariable and multivariable logistic regression analyses investigated the association between anxiolytic, antidepressant, antipsychotic, and hypnotic use and COVID-19 vaccination status, accounting for age, gender, deprivation and comorbidities. Receiving any COVID-19 vaccine was the primary outcome. RESULTS: There were 1 433 814 individuals, of whom 1 166 917 received a COVID-19 vaccination. Psychotropic medications were dispensed to 267 049 people. In univariable analysis, people who received any psychotropic medication had greater odds of receiving COVID-19 vaccination: odds ratio (OR) = 1.42 (95% CI 1.41-1.44). However, after adjustment, psychotropic medication use was associated with reduced odds of vaccination (ORadj = 0.90, 95% CI 0.89-0.91). People who received anxiolytics (ORadj = 0.63, 95% CI 0.61-0.65), antipsychotics (ORadj = 0.75, 95% CI 0.73-0.78) and hypnotics (ORadj = 0.90, 95% CI 0.87-0.93) had reduced odds of being vaccinated. Antidepressant use was not associated with vaccination (ORadj = 1.02, 95% CI 1.00-1.03). CONCLUSIONS: We found significantly lower odds of vaccination in people who were receiving treatment with anxiolytic and antipsychotic medications. There is an urgent need for evidence-based, tailored vaccine support for people with mental health conditions.

A Hybrid Architecture (CO-CONNECT) to Facilitate Rapid Discovery and Access to Data Across the United Kingdom in Response to the COVID-19 Pandemic: Development Study.

BACKGROUND: COVID-19 data have been generated across the United Kingdom as a by-product of clinical care and public health provision, as well as numerous bespoke and repurposed research endeavors. Analysis of these data has underpinned the United Kingdom's response to the pandemic, and informed public health policies and clinical guidelines. However, these data are held by different organizations, and this fragmented landscape has presented challenges for public health agencies and researchers as they struggle to find relevant data to access and interrogate the data they need to inform the pandemic response at pace. OBJECTIVE: We aimed to transform UK COVID-19 diagnostic data sets to be findable, accessible, interoperable, and reusable (FAIR). METHODS: A federated infrastructure model (COVID - Curated and Open Analysis and Research Platform [CO-CONNECT]) was rapidly built to enable the automated and reproducible mapping of health data partners' pseudonymized data to the Observational Medical Outcomes Partnership Common Data Model without the need for any data to leave the data controllers' secure environments, and to support federated cohort discovery queries and meta-analysis. RESULTS: A total of 56 data sets from 19 organizations are being connected to the federated network. The data include research cohorts and COVID-19 data collected through routine health care provision linked to longitudinal health care records and demographics. The infrastructure is live, supporting aggregate-level querying of data across the United Kingdom. CONCLUSIONS: CO-CONNECT was developed by a multidisciplinary team. It enables rapid COVID-19 data discovery and instantaneous meta-analysis across data sources, and it is researching streamlined data extraction for use in a Trusted Research Environment for research and public health analysis. CO-CONNECT has the potential to make UK health data more interconnected and better able to answer national-level research questions while maintaining patient confidentiality and local governance procedures.

Estimating the impact on patient safety of enabling the digital transfer of patients' prescription information in the English NHS.

OBJECTIVES: To estimate the number and burden of medication errors associated with prescription information transfer within the National Health Service (NHS) in England and the impact of implementing an interoperable prescription information system (a single digital prescribing record shared across NHS settings) in reducing these errors. METHODS: We constructed a probabilistic mathematical model. We estimated the number of transition medication errors that would be undetected by standard medicines reconciliation, based on published literature, and scaled this up based on the annual number of hospital admissions. We used published literature to estimate the proportion of errors that lead to harm and applied this to the number of errors to estimate the associated burden (healthcare resource use and deaths). Finally, we used reported effect sizes for electronic prescription information sharing interventions to estimate the impact of implementing an interoperable prescription information system on number of errors and resulting harm. RESULTS: Annually, around 1.8 million (95% credibility interval (CrI) 1.3 to 2.6 million) medication errors were estimated to occur at hospital transitions in England, affecting approximately 380 000 (95% CrI 260 397 to 539 876) patient episodes. Harm from these errors affects around 31 500 (95% CrI 22 407 to 42 906) patients, with 36 500 (95% CrI 25 093 to 52 019) additional bed days of inpatient care (costing around £17.8 million (95% CrI £12.4 to £24.9 million)) and >40 (95% CrI 9 to 146) deaths. Assuming the implementation of an interoperable prescription information system could reduce errors by 10% and 50%, there could be 180 000-913 000 fewer errors, 3000-15 800 fewer people who experience harm and 4-22 lives saved annually. CONCLUSIONS: An interoperable prescription information system could provide major benefits for patient safety. Likely additional benefits include healthcare professional time saved, improved patient experience and care quality, quicker discharge and enhanced cross-organisational medicines optimisation. Our findings provide vital safety and economic evidence for the case to adopt interoperable prescription information systems.

A SARS-CoV-2 minimum data standard to support national serology reporting.

BACKGROUND: Healthcare laboratory systems produce and capture a vast array of information, yet do not always report all of this to the national infrastructure within the United Kingdom. The global COVID-19 pandemic brought about a much greater need for detailed healthcare data, one such instance being laboratory testing data. The reporting of qualitative laboratory test results (e.g. positive, negative or indeterminate) provides a basic understanding of levels of seropositivity. However, to better understand and interpret seropositivity, how it is determined and other factors that affect its calculation (i.e. levels of antibodies), quantitative laboratory test data are needed. METHOD: 36 data attributes were collected from 3 NHS laboratories and 29 CO-CONNECT project partner organisations. These were assessed against the need for a minimum dataset to determine data attribute importance. An NHS laboratory feasibility study was undertaken to assess the minimum data standard, together with a literature review of national and international data standards and healthcare reports. RESULTS: A COVID serology minimum data standard (CSMDS) comprising 12 data attributes was created and verified by 3 NHS laboratories to allow national granular reporting of COVID serology results. To support this, a standardised set of vocabulary terms was developed to represent laboratory analyser systems and laboratory information management systems. CONCLUSIONS: This paper puts forward a minimum viable standard for COVID-19 serology data attributes to enhance its granularity and augment the national reporting of COVID-19 serology laboratory results, with implications for future pandemics.

Using sociotechnical theory to understand medication safety work in primary care and prescribers' use of clinical decision support: a qualitative study.

OBJECTIVES: The concept of safety work draws attention to the intentional work of ensuring safety within care systems. Clinical decision support (CDS) has been designed to enhance medication safety in primary care by providing decision-making support to prescribers. Sociotechnical theory understands that healthcare settings are complex and dynamically connected systems of fluid networks, human agents, changing relationships and social processes. This study aimed to understand the relationship between safety work and the use of CDS. DESIGN AND SETTING: This qualitative study took place across nine different general practices in England. Stakeholders included general practitioners (GPs) and general practice-based pharmacists and nurse prescribers. Semi-structured interviews were conducted to illicit how the system was used by the participants in the context of medication safety work. Data analysis conducted alongside data collection was thematic and drew on socio-technical theory. PARTICIPANTS: Twenty-three interviews were conducted with 14 GPs, three nurse prescribers and three practice pharmacists between February 2018 and June 2020. RESULTS: Safety work was contextually situated in a complex network of relationships. Three interconnected themes were interpreted from the data: (1) the use of CDS within organisational and social practices and workflows; (2) safety work and the use of CDS within the interplay between prescribers, patients and populations; and (3) the affordances embedded in CDS systems. CONCLUSION: The use of sociotechnical theory here extends current thinking in patient safety particularly in the ways that safety work was co-constituted with the use of CDS alerts. This has implications for implementation and use to ensure that the contexts into which such CDS systems are implemented are taken into account. Understanding how alerts can adapt safety culture will help improve the efficacy of CDS systems, enhance prescribing safety and help to further understand how safety work is achieved in primary care.

Understanding the lived experience of chronic pain: A systematic review and synthesis of qualitative evidence syntheses.

Background: Although multiple measures of the causes and consequences of chronic non-cancer pain (CNCP) are available and can inform pain management, no quantitative summary of these measures can describe the meaning of pain for a patient. The lived experience of pain tends to be a blind spot in pain management. This study aimed to: (1) integrate qualitative research investigating the lived experience of a range of CNCP conditions; (2) establish common qualitative themes in CNCP experience; and (3) evaluate the relevance of our results through a survey questionnaire based on these themes, administered across the United Kingdom. Methods: Four bibliographic databases were searched from inception to February 2021 to identify Qualitative Evidence Syntheses (QES) that investigated the lived experience of CNCP and its impact on everyday life and activities. Themes and trends were derived by thematic qualitative analysis in collaboration with two patient and public involvement representatives who co-created twenty survey statements. The survey was developed for testing the QES themes for validity in people living with pain. Results: The research team identified and screened 1323 titles, and considered 86 abstracts, including 20 in the final review. Eight themes were developed from the study findings: (1) my pain gives rise to negative emotions; (2) changes to my life and to myself; (3) adapting to my new normal; (4) effects of my pain management strategies; (5) hiding and showing my pain; (6) medically explaining my pain; (7) relationships to those around me; and (8) working while in pain. Each theme gave rise to one or two survey questions. The survey was shared with members of the UK pain community over a 2-week period in November 2021, and was completed by 1219 people, largely confirming the above themes. Conclusion/Implications: This study provides a validated summary of the lived experience of CNCP. It highlights the adverse nature, complications, and consequences of living with CNCP in the UK and the multiple shortcomings in the ways in which pain is addressed by others in the UK. Our findings are consistent with published meta-ethnographies on chronic non-malignant musculoskeletal pain and chronic low-back pain. Despite the underrepresentation of qualitative research in the pain literature compared to quantitative approaches, for understanding the complexity of the lived experience of pain, qualitative research is an essential tool.

Effectiveness of the perioperative encounter in promoting regular exercise and physical activity: a systematic review and meta-analysis.

Background: Low levels of physical activity (PA) are associated with poorer health outcomes. The perioperative encounter (extending from initial contact in primary care to beyond discharge from hospital) is potentially a good time to intervene, but data regarding the effectiveness of interventions are scarce. To address this, we systematically reviewed existing literature to evaluate the effectiveness of interventions applied perioperatively to facilitate PA in the medium to long-term (at least six months after the intervention). Methods: In this systematic review and meta-analysis, we searched Central Register of Controlled Trials (CENTRAL, Cochrane Library), MEDLINE, CINAHL, Embase, PsycInfo, and SPORTDiscus from database inception to October 22nd 2020, with an updated search done on August 4th 2022. We searched clinical trials registers, and conducted forward- and backward-citation searches. We included randomised controlled trials and quasi-randomised trials comparing PA interventions with usual care, or another PA intervention, in adults who were scheduled for, or had recently undergone, surgery. We included trials which reported our primary outcomes: amount of PA or whether participants were engaged in PA at least six months after the intervention. A random effects meta-analysis was used to pool data across studies as risk ratios (RR), or standardised mean differences (SMDs), which we interpreted using Cohen. We used the Cochrane risk of bias tool and used GRADE to assess the certainty of the evidence. This study is registered with PROSPERO, CRD42019139008. Findings: We found 57 trials including 8548 adults and compared 71 interventions facilitating PA. Most interventions were started postoperatively and included multiple components. Compared with usual care, interventions may slightly increase the number of minutes of PA per day or week (SMD 0.17, 95% CI 0.09-0.26; 14 studies, 2172 participants; I2 = 0%), and people's engagement in PA at the study's end (RR 1.19, 95% CI 0.96-1.47; 9 studies, 882 participants; I2 = 25%); this was moderate-certainty evidence. Some studies compared two different types of interventions but it was often not feasible to combine data in analysis. The effect estimates generally indicated little difference between intervention designs and we judged all the evidence for these comparisons to be very low certainty. Thirty-six studies (63%) had low risk of selection bias for sequence generation, 27 studies (47%) had low risk of bias for allocation concealment, and 56 studies (98%) had a high risk of performance bias. For detection bias for PA outcomes, we judged 30 studies (53%) that used subjective measurement tools to have a high risk of detection bias. Interpretation: Interventions delivered in the perioperative setting, aimed at enhancing PA in the medium to long-term, may have overall benefit. However, because of imprecision in some of the findings, we could not rule out the possibility of no change in PA. Funding: National Institute for Health Research Health Services and Delivery Research programme (NIHR127879).

ePrescribing-Based Antimicrobial Stewardship Practices in an English National Health Service Hospital: Qualitative Interview Study Among Medical Prescribers and Pharmacists.

BACKGROUND: Antimicrobial resistance, the ability of microorganisms to survive antimicrobial drugs, is a public health emergency. Although electronic prescribing (ePrescribing)-based interventions designed to reduce unnecessary antimicrobial usage exist, these often do not integrate effectively with existing workflows. As a result, ePrescribing-based interventions may have limited impact in addressing antimicrobial resistance. OBJECTIVE: We sought to understand the existing ePrescribing-based antimicrobial stewardship (AMS) practices in an English hospital preceding the implementation of functionality designed to improve AMS. METHODS: We conducted 18 semistructured interviews with medical prescribers and pharmacists with varying levels of seniority exploring current AMS practices and investigating potential areas for improvement. Participants were recruited with the help of local gatekeepers. Topic guides sought to explore both formal and informal practices surrounding AMS, and challenges and opportunities for ePrescribing-based intervention. We coded audio-recorded and transcribed data with the help of the Technology, People, Organizations, and Macroenvironmental factors framework, allowing emerging themes to be added inductively. We used NVivo 12 (QSR International) to facilitate coding. RESULTS: Antimicrobial prescribing and review processes were characterized by competing priorities and uncertainty of prescribers and reviewers around prescribing decisions. For example, medical prescribers often had to face trade-offs between individual patient benefit and more diffuse population health benefits, and the rationale for prescribing decisions was not always clear. Prescribing involved a complex set of activities carried out by various health care practitioners who each only had a partial and temporary view of the whole process, and whose relationships were characterized by deeply engrained hierarchies that shaped interactions and varied across specialties. For example, newly qualified doctors and pharmacists were hesitant to change a consultant's prescribing decision when reviewing prescriptions. Multidisciplinary communication, collaboration, and coordination promoted good AMS practices by reducing uncertainty. CONCLUSIONS: Design of ePrescribing-based interventions to improve AMS needs to take into account the multitude of actors and organizational complexities involved in the prescribing and review processes. Interventions that help reduce prescriber or reviewer uncertainty and improve multidisciplinary collaboration surrounding initial antimicrobial prescribing and subsequent prescription review are most likely to be effective. Without such attention, interventions are unlikely to fulfill their goal of improving patient outcomes and combatting antimicrobial resistance.

A complex ePrescribing-based Anti-Microbial Stewardship (ePAMS+) intervention for hospitals combining technological and behavioural components: protocol for a feasibility trial.

BACKGROUND: Antimicrobial resistance is a leading global public health threat, with inappropriate use of antimicrobials in healthcare contributing to its development. Given this urgent need, we developed a complex ePrescribing-based Anti-Microbial Stewardship intervention (ePAMS+). METHODS: ePAMS+ includes educational and organisational behavioural elements, plus guideline-based clinical decision support to aid optimal antimicrobial use in hospital inpatients. ePAMS+ particularly focuses on prompt initiation of antimicrobials, followed by early review once test results are available to facilitate informed decision-making on stopping or switching where appropriate. A mixed-methods feasibility trial of ePAMS+ will take place in two NHS acute hospital care organisations. Qualitative staff interviews and observation of practice will respectively gather staff views on the technical component of ePAMS+ and information on their use of ePAMS+ in routine work. Focus groups will elicit staff and patient views on ePAMS+; one-to-one interviews will discuss antimicrobial stewardship with staff and will record patient experiences of receiving antibiotics and their thoughts on inappropriate prescribing. Qualitative data will be analysed thematically. Fidelity Index development will enable enactment of ePAMS+ to be measured objectively in a subsequent trial assessing the effectiveness of ePAMS+. Quantitative data collection will determine the feasibility of extracting data and deriving key summaries of antimicrobial prescribing; we will quantify variability in the primary outcome, number of antibiotic defined daily doses, to inform the future larger-scale trial design. DISCUSSION: This trial is essential to determine the feasibility of implementing the ePAMS+ intervention and measuring relevant outcomes, prior to evaluating its clinical and cost-effectiveness in a full scale hybrid cluster-randomised stepped-wedge clinical trial. Findings will be shared with study sites and with qualitative research participants and will be published in peer-reviewed journals and presented at academic conferences. TRIAL REGISTRATION: The qualitative and Fidelity Index research were approved by the Health and Research Authority and the North of Scotland Research Ethics Service (ref: 19/NS/0174). The feasibility trial and quantitative analysis (protocol v1.0, 15 December 2021) were approved by the London South East Research Ethics Committee (ref: 22/LO/0204) and registered with ISRCTN ( ISRCTN 13429325 ) on 24 March 2022.

Adverse events after first and second doses of COVID-19 vaccination in England: a national vaccine surveillance platform self-controlled case series study.

OBJECTIVES: To estimate the incidence of adverse events of interest (AEIs) after receiving their first and second doses of coronavirus disease 2019 (COVID-19) vaccinations, and to report the safety profile differences between the different COVID-19 vaccines. DESIGN: We used a self-controlled case series design to estimate the relative incidence (RI) of AEIs reported to the Oxford-Royal College of General Practitioners national sentinel network. We compared the AEIs that occurred seven days before and after receiving the COVID-19 vaccinations to background levels between 1 October 2020 and 12 September 2021. SETTING: England, UK. PARTICIPANTS: Individuals experiencing AEIs after receiving first and second doses of COVID-19 vaccines. MAIN OUTCOME MEASURES: AEIs determined based on events reported in clinical trials and in primary care during post-license surveillance. RESULTS: A total of 7,952,861 individuals were vaccinated with COVID-19 vaccines within the study period. Among them, 781,200 individuals (9.82%) presented to general practice with 1,482,273 AEIs. Within the first seven days post-vaccination, 4.85% of all the AEIs were reported. There was a 3-7% decrease in the overall RI of AEIs in the seven days after receiving both doses of Pfizer-BioNTech BNT162b2 (RI = 0.93; 95% CI: 0.91-0.94) and 0.96; 95% CI: 0.94-0.98), respectively) and Oxford-AstraZeneca ChAdOx1 (RI = 0.97; 95% CI: 0.95-0.98) for both doses), but a 20% increase after receiving the first dose of Moderna mRNA-1273 (RI = 1.20; 95% CI: 1.00-1.44)). CONCLUSIONS: COVID-19 vaccines are associated with a small decrease in the incidence of medically attended AEIs. Sentinel networks could routinely report common AEI rates, which could contribute to reporting vaccine safety.

Understanding factors that could influence patient acceptability of the use of the PINCER intervention in primary care: A qualitative exploration using the Theoretical Framework of Acceptability.

INTRODUCTION: Medication errors are an important cause of morbidity and mortality. The pharmacist-led IT-based intervention to reduce clinically important medication errors (PINCER) intervention was shown to reduce medication errors when tested in a cluster randomised controlled trial and when implemented across one region of England. Now that it has been rolled out nationally, and to enhance findings from evaluations with staff and stakeholders, this paper is the first to report patients' perceived acceptability on the use of PINCER in primary care and proposes suggestions on how delivery of PINCER related care could be delivered in a way that is acceptable and not unnecessarily burdensome. METHODS: A total of 46 participants living with long-term health conditions who had experience of medication reviews and/or monitoring were recruited through patient participant groups and social media. Semi-structured, qualitative interviews and focus groups were conducted face-to-face or via telephone. A thematic analysis was conducted and findings mapped to the constructs of the Theoretical Framework of Acceptability (TFA). RESULTS: Two themes were identified and interpreted within the most relevant TFA construct: Perceptions on the purpose and components of PINCER (Affective Attitude and Intervention Coherence) and Perceived patient implications (Burden and Self-efficacy). Overall perceptions on PINCER were positive with participants showing good understanding of the components. Access to medication reviews, which PINCER related care can involve, was reported to be limited and a lack of consistency in practitioners delivering reviews was considered challenging, as was lack of communication between primary care and other health-care providers. Patients thought it would be helpful if medication reviews and prescription renewal times were synchronised. Remote medication review consultations were more convenient for some but viewed as a barrier to communication by others. It was acknowledged that some patients may be more resistant to change and more willing to accept changes initiated by general practitioners. CONCLUSIONS: Participants found the concept of PINCER acceptable; however, acceptability could be improved if awareness on the role of primary care pharmacists is raised and patient-pharmacist relationships enhanced. Being transparent with communication and delivering streamlined and consistent but flexible PINCER related care is recommended.

Understanding factors influencing uptake and sustainable use of the PINCER intervention at scale: A qualitative evaluation using Normalisation Process Theory.

INTRODUCTION: Medication errors are an important cause of morbidity and mortality. The pharmacist-led IT-based intervention to reduce clinically important medication errors (PINCER) has demonstrated improvements in primary care medication safety, and whilst now the subject of national roll-out its optimal and sustainable use across health contexts has not been fully explored. As part of a qualitative evaluation we aimed to identify factors influencing successful adoption, embedding and sustainable use of PINCER across primary care settings in England, UK. METHODS: Semi-structured face-to-face or telephone interviews, including follow-up interviews and an online survey were conducted with professionals knowledgeable of PINCER. Interview recruitment targeted four early adopter regions; the survey was distributed nationally. Initial data analysis was inductive, followed by analysis using a coding framework. A deductive matrix approach was taken to map the framework to the Normalisation Process Theory (NPT). Themes were then identified. RESULTS: Fifty participants were interviewed, 18 participated in a follow-up interview. Eighty-one general practices and three Clinical Commissioning Groups completed the survey. Four themes were identified and interpreted within the relevant NPT construct: Awareness & Perceptions (Coherence), Receptivity to PINCER (Cognitive Participation), Engagement [Collective Action] and Reflections & Adaptations (Reflexive Monitoring). Variability was identified in how PINCER awareness was raised and how staff worked to operationalise the intervention. Facilitators for use included stakeholder investment, favourable evidence, inclusion in policy, incentives, fit with individual and organisational goals and positive experiences. Barriers included lack of understanding, capacity concerns, operational difficulties and the impact of COVID-19. System changes such as adding alerts on clinical systems were indicative of embedding and continued use. CONCLUSIONS: The NPT helped understand motives behind engagement and the barriers and facilitators towards sustainable use. Optimising troubleshooting support and encouraging establishments to adopt an inclusive approach to intervention adoption and utilisation could help accelerate uptake and help establish ongoing sustainable use.

Mindfulness-based intervention in patients with persistent pain in chest (MIPIC) of non-cardiac cause: a feasibility randomised control study.

OBJECTIVE: The study evaluated the feasibility of mindfulness-based cognitive therapy (MBCT) in patients with non-cardiac chest pain by assessing their willingness to participate and adhere to the programme, and for these data to help further refine the content of MBCT for chest pain. PATIENTS AND METHODS: This prospective 2:1 randomised controlled trial compared the intervention of adapted MBCT as an addition to usual care with just usual care in controls. Among 573 patients who attended the rapid access chest pain clinic over the previous 12 months and were not diagnosed with a cardiac cause but had persistent chest pain were invited. The intervention was a 2-hour, weekly, online guided 8-week MBCT course. Compliance with attendance and the home practice was recorded. Enrolled patients completed the Seattle angina questionnaire (SAQ), Hospital Anxiety and Depression Scale, Cardiac Anxiety Questionnaire, Five-Facet Mindfulness Questionnaire, and Euro Quality of Life-5 Dimensions-5 Level at baseline assessment and after 8-week period. RESULTS: Persistent chest pain was reported by 114 patients. Of these, 33 (29%) patients with a mean age of 54.2 (±12.2) years and 68% women, consented to the study. Baseline questionnaires revealed mild physical limitation (mean SAQ, 76.8±25), high levels of anxiety (76%) and depression (53%), modest cardiac anxiety (CAQ,1.78±0.61) and mindfulness score (FFMQ, 45.5±7.3). Six patients subsequently withdrew due to bereavement, caring responsibilities and ill health. Of the remaining 27 participants, 18 in the intervention arm attended an average of 5 sessions with 61% attending ≥6 sessions. Although not statistically powered, the study revealed a significant reduction in general anxiety, improved mindfulness and a trend towards improvement in SAQ scores in the intervention arm. CONCLUSION: One-third of patients with persistent non-cardiac chest pain were willing to participate in mindfulness-based therapy. An improvement in anxiety and mindfulness was detected in this feasibility study. A larger trial is required to demonstrate improvement in chest pain symptoms.

Methodological Issues in Using a Common Data Model of COVID-19 Vaccine Uptake and Important Adverse Events of Interest: Feasibility Study of Data and Connectivity COVID-19 Vaccines Pharmacovigilance in the United Kingdom.

BACKGROUND: The Data and Connectivity COVID-19 Vaccines Pharmacovigilance (DaC-VaP) UK-wide collaboration was created to monitor vaccine uptake and effectiveness and provide pharmacovigilance using routine clinical and administrative data. To monitor these, pooled analyses may be needed. However, variation in terminologies present a barrier as England uses the Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT), while the rest of the United Kingdom uses the Read v2 terminology in primary care. The availability of data sources is not uniform across the United Kingdom. OBJECTIVE: This study aims to use the concept mappings in the Observational Medical Outcomes Partnership (OMOP) common data model (CDM) to identify common concepts recorded and to report these in a repeated cross-sectional study. We planned to do this for vaccine coverage and 2 adverse events of interest (AEIs), cerebral venous sinus thrombosis (CVST) and anaphylaxis. We identified concept mappings to SNOMED CT, Read v2, the World Health Organization's International Classification of Disease Tenth Revision (ICD-10) terminology, and the UK Dictionary of Medicines and Devices (dm+d). METHODS: Exposures and outcomes of interest to DaC-VaP for pharmacovigilance studies were selected. Mappings of these variables to different terminologies used across the United Kingdom's devolved nations' health services were identified from the Observational Health Data Sciences and Informatics (OHDSI) Automated Terminology Harmonization, Extraction, and Normalization for Analytics (ATHENA) online browser. Lead analysts from each nation then confirmed or added to the mappings identified. These mappings were then used to report AEIs in a common format. We reported rates for windows of 0-2 and 3-28 days postvaccine every 28 days. RESULTS: We listed the mappings between Read v2, SNOMED CT, ICD-10, and dm+d. For vaccine exposure, we found clear mapping from OMOP to our clinical terminologies, though dm+d had codes not listed by OMOP at the time of searching. We found a list of CVST and anaphylaxis codes. For CVST, we had to use a broader cerebral venous thrombosis conceptual approach to include Read v2. We identified 56 SNOMED CT codes, of which we selected 47 (84%), and 15 Read v2 codes. For anaphylaxis, our refined search identified 60 SNOMED CT codes and 9 Read v2 codes, of which we selected 10 (17%) and 4 (44%), respectively, to include in our repeated cross-sectional studies. CONCLUSIONS: This approach enables the use of mappings to different terminologies within the OMOP CDM without the need to catalogue an entire database. However, Read v2 has less granular concepts than some terminologies, such as SNOMED CT. Additionally, the OMOP CDM cannot compensate for limitations in the clinical coding system. Neither Read v2 nor ICD-10 is sufficiently granular to enable CVST to be specifically flagged. Hence, any pooled analysis will have to be at the less specific level of cerebrovascular venous thrombosis. Overall, the mappings within this CDM are useful, and our method could be used for rapid collaborations where there are only a limited number of concepts to pool.

COVID-19 vaccine uptake, effectiveness, and waning in 82,959 health care workers: A national prospective cohort study in Wales.

BACKGROUND: While population estimates suggest high vaccine effectiveness against SARS-CoV-2 infection, the protection for health care workers, who are at higher risk of SARS-CoV-2 exposure, is less understood. METHODS: We conducted a national cohort study of health care workers in Wales (UK) from 7 December 2020 to 30 September 2021. We examined uptake of any COVID-19 vaccine, and the effectiveness of BNT162b2 mRNA (Pfizer-BioNTech) against polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection. We used linked and routinely collected national-scale data within the SAIL Databank. Data were available on 82,959 health care workers in Wales, with exposure extending to 26 weeks after second doses. RESULTS: Overall vaccine uptake was high (90%), with most health care workers receiving theBNT162b2 vaccine (79%). Vaccine uptake differed by age, staff role, socioeconomic status; those aged 50-59 and 60+ years old were 1.6 times more likely to get vaccinated than those aged 16-29. Medical and dental staff, and Allied Health Practitioners were 1.5 and 1.1 times more likely to get vaccinated, compared to nursing and midwifery staff. The effectiveness of the BNT162b2 vaccine was found to be strong and consistent across the characteristics considered; 52% three to six weeks after first dose, 86% from two weeks after second dose, though this declined to 53% from 22 weeks after the second dose. CONCLUSIONS: With some variation in rate of uptake, those who were vaccinated had a reduced risk of PCR-confirmed SARS-CoV-2 infection, compared to those unvaccinated. Second dose has provided stronger protection for longer than first dose but our study is consistent with waning from seven weeks onwards.

Investigating the uptake, effectiveness and safety of COVID-19 vaccines: protocol for an observational study using linked UK national data.

INTRODUCTION: The novel coronavirus SARS-CoV-2, which emerged in December 2019, has caused millions of deaths and severe illness worldwide. Numerous vaccines are currently under development of which a few have now been authorised for population-level administration by several countries. As of 20 September 2021, over 48 million people have received their first vaccine dose and over 44 million people have received their second vaccine dose across the UK. We aim to assess the uptake rates, effectiveness, and safety of all currently approved COVID-19 vaccines in the UK. METHODS AND ANALYSIS: We will use prospective cohort study designs to assess vaccine uptake, effectiveness and safety against clinical outcomes and deaths. Test-negative case-control study design will be used to assess vaccine effectiveness (VE) against laboratory confirmed SARS-CoV-2 infection. Self-controlled case series and retrospective cohort study designs will be carried out to assess vaccine safety against mild-to-moderate and severe adverse events, respectively. Individual-level pseudonymised data from primary care, secondary care, laboratory test and death records will be linked and analysed in secure research environments in each UK nation. Univariate and multivariate logistic regression models will be carried out to estimate vaccine uptake levels in relation to various population characteristics. VE estimates against laboratory confirmed SARS-CoV-2 infection will be generated using a generalised additive logistic model. Time-dependent Cox models will be used to estimate the VE against clinical outcomes and deaths. The safety of the vaccines will be assessed using logistic regression models with an offset for the length of the risk period. Where possible, data will be meta-analysed across the UK nations. ETHICS AND DISSEMINATION: We obtained approvals from the National Research Ethics Service Committee, Southeast Scotland 02 (12/SS/0201), the Secure Anonymised Information Linkage independent Information Governance Review Panel project number 0911. Concerning English data, University of Oxford is compliant with the General Data Protection Regulation and the National Health Service (NHS) Digital Data Security and Protection Policy. This is an approved study (Integrated Research Application ID 301740, Health Research Authority (HRA) Research Ethics Committee 21/HRA/2786). The Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub meets NHS Digital's Data Security and Protection Toolkit requirements. In Northern Ireland, the project was approved by the Honest Broker Governance Board, project number 0064. Findings will be made available to national policy-makers, presented at conferences and published in peer-reviewed journals.