Search

Background: The aim of this feasibility study was to adapt and model a behavioural intervention for anxiety with autistic adults with moderate to severe intellectual disabilities. Method: Twenty-eight autistic adults with moderate or severe intellectual disabilities, 37 carers, and 40 therapists took part in this single-group non-randomised feasibility study designed to test intervention feasibility and acceptability, outcome measures, and research processes. Results: The intervention was judged as feasible and acceptable by autistic adults with intellectual disabilities, carers, and therapists. Minor intervention revisions were suggested. Carers completed 100% of outcome measures and the missing data rate was low. Complying with legislation governing the inclusion of participants who lack capacity to decide whether they wanted to take part in this study led to an average 5-week enrolment delay. Conclusion: The intervention and associated study processes were judged to be feasible and acceptable and should now be tested within a larger randomised trial.

Abstract Background Use of antibiotics is the main driver of antimicrobial resistance which is considered one of the biggest threats to human health. In Denmark, most antibiotics are prescribed in general practice. Acute lower respiratory tract infections, including community-acquired pneumonia (CAP), are among the most frequent indications for antibiotic prescribing. Phenoxymethylpenicillin is established as first-line treatment in general practice in Denmark. However, the treatment duration with phenoxymethylpenicillin is mostly based on traditions. Both 5 and 7 days of treatment is recommended in Danish guidelines, and when asking the general practitioners about what treatment duration, they prescribe the variation is even bigger. Several hospital-based studies have proven short course (≤ 6 days) antibiotic treatment non-inferior to long course (≥ 7 days) treatment of CAP. No evidence exists on the optimal treatment duration for CAP in non-hospitalised patients. This randomised controlled trial aim to investigate the optimal treatment duration with phenoxymethylpenicillin for CAP in adults diagnosed in general practice in Denmark. Methods This is an open-label, pragmatic, randomised controlled, five-arm DURATIONS trial. Participants will be recruited from at least 24 general practices in Denmark. Eligible participants are adults, with no pre-existing lung disease, presenting with symptoms of CAP, and in whom the general practitioner finds it relevant to treat with antibiotics. The study will compare treatment with phenoxymethylpenicillin 1.2 MIE q.i.d. in 3, 4, 5, 6, and 7 days. Discussion This study will provide evidence for the optimal antibiotic treatment duration of CAP in general practice and inform future guidelines on CAP in all countries using phenoxymethylpenicillin for the treatment of acute respiratory tract infections in adults. The results of this study might also be used to guide treatment recommendations in other countries using phenoxymethylpenicillin. Moreover, a (potential) reduction in antibiotic use might lower the development of antimicrobial resistance, increase patient treatment adherence, reduce risks of adverse events, and lower the economical exp Trial registration ClinicalTrials.gov: NCT06295120. Registered 28 February 2024. The Scientific Ethics Committee for the North Denmark Region: N-20230039.

Background: Almost no research has been published reporting on evaluations of the effectiveness of psychological interventions for people with severe to profound intellectual disabilities and depression. This paper describes the development and initial feasibility testing of an adapted Behavioural Activation therapy (BeatIt2) for this population. Method: Phase 1 of the study examined participant recruitment and willingness to be randomised in the context of a planned Randomised Controlled Trial (RCT). Phase 2 examined the feasibility of delivering the intervention. Results: Twenty adults with a severe or profound intellectual disability and clinically significant depression were recruited to Phase 1 of the study. In Phase 2, there was 100% participant retention for those recruited to the study at 6-month follow-up. The BeatIt2 therapy was reported to be acceptable for participants. Conclusion: COVID disruption meant that it was not possible to complete the planned feasibility RCT. The positive findings suggest that additional evaluation of BeatIt2 is warranted.

Background Interventions for anxiety need to be adapted to meet the needs of autistic people with moderate to severe learning disabilities and successfully modelled before evidence about efficacy can be generated from clinical trials. Objectives The objectives were to: (1) adapt a behavioural intervention for anxiety, develop an intervention fidelity checklist and logic model, and appraise candidate outcome measures, together with carers, autistic people, and clinicians, (2) characterise treatment-as-usual, (3) model the adapted intervention to determine the acceptability and feasibility for all stakeholders, judge the appropriateness of outcome measures, examine the feasibility and acceptability of consent and associated processes and (4) describe factors that facilitate or challenge intervention delivery. Design This study had two phases. Phase 1a: using consensus methods, an intervention adaptation group was formed who met to adapt the intervention, appraise candidate outcome measures, and contribute to the development of the intervention fidelity checklists and logic model. Phase 1b: a national online survey was conducted with professionals to characterise treatment-as-usual. Phase 2: this was a single-group non-randomised feasibility study designed to model the intervention to test intervention feasibility and acceptability, outcome measures, and aspects of the research process. Setting Participants were recruited from National Health Service community adult learning disabilities teams in England. Participants Participants aged 16 and over with a diagnosis of autism, moderate to severe learning disabilities, an anxiety disorder, and a carer who was available to take part in the intervention. For those who lacked capacity to make a decision about taking part, a consultee had to provide advice that the participant should be included in the study. Interventions The intervention comprised 12 sessions alongside treatment-as-usual. Main outcome measures The feasibility and acceptability of the intervention and research processes, outcome measure completion rates, and intervention adherence. Results The intervention was successfully adapted and modelled with 28 autistic participants with moderate to severe learning disabilities. The intervention was judged to be feasible and acceptable by autistic adults with learning disabilities, carers, and therapists. Carers and therapists suggested minor intervention revisions. Carers completed 100% of outcome measures and the missing data rate was low; however, they indicated that some of the questions were repetitive and said they had difficulty responding to some items. The use of the Mental Capacity Act, 2005, led to an average 5-week delay to participant enrolment. The accrual rate was affected by the COVID-19 pandemic and improved during the summer and early autumn of 2022. Limitations Randomisation was not modelled within this feasibility study, although carers and therapists indicated that this would be acceptable. Conclusions The BEAMS-ID intervention and associated study processes were judged to be feasible and acceptable. The intervention required minor revision. Future work The BEAMS-ID intervention should be tested further within a trial. Study registration This study is registered as ISRCTN12637590. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR129804) and is published in full in Health Technology Assessment; Vol. 28, No. 72. See the NIHR Funding and Awards website for further award information. Plain language summary This study was about autistic adults with moderate to severe learning disabilities who have anxiety. There are good interventions for anxiety, but these need to change to meet the needs of autistic adults with moderate to severe learning disabilities. An example of such an intervention is called exposure therapy. This study had two parts. In the first part, we worked with autistic adults, carers and family members, and professionals to adapt an existing anxiety intervention. We also completed a national survey to find out what interventions people are getting now. In the second part, the intervention was tested with 28 autistic adults with moderate to severe learning disabilities. We asked participants, carers and clinicians about their experiences of being part of the study and receiving the intervention. We successfully changed an existing intervention together with autistic adults, carers and family members, and professionals. The intervention included relaxation training and exposure therapy. From our national survey, we found out that autistic people with moderate to severe learning disabilities who have problems with anxiety are most often offered psychological interventions (e.g. relaxation) or medication (e.g. sertraline) for anxiety. Exposure therapy was not offered very frequently. We tried out our intervention and autistic people with moderate to severe learning disabilities told us that they liked coming to the intervention and liked that their carer attended. Carers liked taking part in the research and were positive about the intervention. Therapists told us that the intervention was suitable and were positive about the training they received in delivering the intervention. Both carers and therapists suggested some changes to the intervention to help improve it in the future. We recommended that a larger study should now be completed. Scientific summary Background A large number of people with autism and learning disabilities have problems with anxiety. There is evidence that talking psychological therapies are an effective intervention for anxiety, but many of these interventions have not been tested with people who have both autism and learning disabilities. These interventions need to be adapted before they can be used with this population because of their difficulties with verbal communication, restricted and repetitive behaviours, and behaviours that challenge. Objectives We aimed to (1) work with our patient and public involvement (PPI) partners to adapt an existing intervention manual for anxiety disorders for use with autistic adults with moderate to severe learning disabilities and (2) complete a feasibility study to try out our intervention and seek feedback from participants, families and therapists. In addition, we collected information about what interventions people are currently receiving to characterise treatment-as-usual (TAU) and test out some outcome measures. Phase 1a: adaptation Our objectives were: to establish an intervention adaptation group (IAG) and, during a series of meetings, adapt an existing intervention to treat anxiety symptoms in autistic adults who have moderate to severe learning disabilities to develop an intervention fidelity checklist that can be used alongside the intervention manual to appraise and consider several candidate outcome measures of anxiety-related symptoms and make a recommendation for use within Phase 2 to develop an intervention logic model. Phase 1b: description of treatment-as-usual Our objective was to complete a national survey of existing interventions for adults with anxiety disorders who have moderate to severe learning disabilities. The survey was constructed using items adapted from the Template for Intervention Description and Replication (TIDieR) checklist to ensure a clear description of TAU. This phase ran concurrently with Phase 1a and Phase 2. This allowed for the capture of data to allow for the characterisation of TAU, including any specific interventions offered. We invited participation from all community-based services for people with autism and/or learning disabilities across the United Kingdom. Phase 2: feasibility study Our objectives were: to model the manualised intervention to determine the acceptability and feasibility for all stakeholders, including autistic adults with moderate to severe learning disabilities, carers, and clinicians, and adjust as required to judge the appropriateness, including response rates, of our measures of anxiety-related symptomatology for use within a larger study to examine the feasibility and acceptability of consent and associated processes in the context of the Mental Capacity Act, 2005 and to describe factors that facilitate or challenge the implementation of our intervention. Methods Study design Phase 1a (intervention adaptation) An IAG was established, and during a series of five meetings an existing intervention used to treat anxiety symptoms in adults with autism was adapted for use with people who also have moderate to severe learning disabilities. Phase 1b (treatment-as-usual survey) A national survey of existing community-based interventions for adults with anxiety disorders who have moderate to severe learning disabilities was conducted. The TIDieR checklist was used to inform the development of our survey questions to ensure a clear description of TAU. Phase 2 (feasibility study) This study was a single-arm, non-randomised, feasibility study, with autistic people who have moderate to severe learning disabilities. Participants and their carers received the adapted intervention developed in Phase 1a, in conjunction with any other intervention they were receiving. Both qualitative and quantitative research methods were used to address key components of feasibility. Setting and participants Phase 1a (intervention adaptation) The IAG included eight key stakeholders who were representatives from our PPI partners, carers and family members, people with autism and/or learning disabilities, and clinicians, along with members of the research team. Phase 1b (treatment-as-usual survey) All services for adults with autism and learning disabilities (and learning disabilities services providing support to those who also have autism); this included NHS mental health and learning disabilities services, and the independent and charitable sector, including social enterprises within the UK. The total of number of survey responses was N = 76. Phase 2 (feasibility study) This single-arm non-randomised feasibility study took place within the NHS health services in England. We aimed to recruit up to 30 participants from the following NHS services across England: Coventry and Warwickshire Partnership NHS Trust, Herefordshire and Worcestershire Health and Care NHS Trust, Leicestershire Partnership NHS Trust, Solent NHS Trust, and Mersey Care NHS Foundation Trust. A total of 28 participants were enrolled, and 18% were from a non-white background, while 53.6% had severe learning disabilities. Intervention Participants within this study received up to 12 sessions of individual and manualised behaviour therapy, each lasting between 60 and 90 minutes with support from carers. The intervention was exposure therapy and was adapted for use with this population and manualised. Assessment of feasibility of delivery and acceptability of the intervention We examined the views of participants, parents/carers, and therapists to address (1) intervention accessibility and acceptability, (2) helpful/unhelpful aspects, including barriers to change, (3) the value of our adaptations, (4) relationships with therapists, (5) acceptability of consent processes, (6) acceptability of outcome measures and (7) acceptability of randomisation within a future trial. We completed semistructured interviews with seven parents/carers and eight therapists. Interviews using Talking Mats® were also completed with five autistic adults with moderate to severe learning disabilities who received the intervention to explore their experience of the intervention and their outcomes. Collection of outcome data Phase 1a (intervention adaptation) We held five meetings with the IAG and made use of consensus methods following discussion to make decisions about intervention adaptations, the content of our fidelity checklist, and our selection of candidate outcome measures. Phase 1b Questions for the TAU survey included the type of support/intervention, who, how and where it is delivered, along with dose and any modifications adapted from the TIDieR checklist. The online survey was delivered using Qualtrics (Qualtrics, Provo, UT, USA) or as a telephone interview. This phase lasted 14 months, running concurrently with Phase 1a and Phase 2. Phase 2 Participants were enrolled in the study for approximately 6 months. Participants were assessed at three times points: (1) screening for eligibility, (2) baseline assessment within 4 weeks before commencement of the intervention and (3) within 4 weeks following the completion of the intervention. Eligibility assessments included measures of adaptive behaviour, autistic symptoms, and symptoms of anxiety disorders. Our outcome assessments included measures of anxiety, emotional and behavioural problems, behaviours that challenge, and engagement within the community. Patient and public involvement and engagement Patient and public involvement and engagement was firmly and genuinely an integral part of our methodology. We partnered with the National Autistic Society (NAS), who worked collaboratively with us to adapt our intervention, along with carers, autistic people, and clinicians. They helped prepare study documentation, recruit participants, and collaboratively disseminate information about this study. Autistic people, carers and clinicians were members of the Study Steering Group and shared oversight of our project progress. Our IAG was formed of carers, autistic people and clinicians who are experienced with working with autistic people with moderate to severe learning disabilities. Results Phase 1a We successfully adapted the intervention, developed a logic model and intervention fidelity checklist, and chose outcome measures collaboratively with the IAG. Phase 1b Seventy-eight health and social care professionals responded to our survey and 76 provided data about TAU. The majority worked for the NHS. The most frequently offered anxiety intervention was described as psychological interventions, but exposure therapy was said to be infrequently provided. Respondents also described the adaptations they made to psychological interventions for use with adults with learning disability. These adaptations included: providing communication support, adjusting session content or activities, adjusting the timing, duration, frequency and number of sessions, involving carers within the intervention, or making changes to a person’s environment. The next most offered intervention was medication. Respondents also described less frequently offered interventions including speech and language therapy, occupational therapy, sensory strategies, communication training, increased staff support, touch therapy and music therapy. Four respondents indicated that physical health support was also offered as an intervention for anxiety. Phase 2 (1) Acceptability and feasibility of the intervention: the intervention was feasible to deliver and acceptable to autistic adults with moderate to severe learning disabilities, carers and therapists. Carers and therapists made some suggestions for revisions to the intervention which focused upon reinforcing the importance of consistent carer attendance during the intervention, and the inclusion of further guidance about ensuring that the intervention is person-centred by adapting the timing, frequency, and number of intervention sessions, making use of bespoke or personalised intervention materials, further guidance about delivering relaxation, and strengthening information about the nature and degree of adaptations that can be made by therapists. All suggestions were considered feasible to implement. (2) Appropriateness of outcome measures: percentage of missing data across the outcome measures was low and ranged from 0% to 2.38% and carers completed 100% of all outcome measures. However, carers commented that some of the items were repetitive, and some said they had difficulties answering some questions. However, others said they were acceptable and easy to complete. (3) Feasibility and acceptability of consent and associated processes: carers indicated that the study participant information sheets and associated processes were clear, helpful, and straightforward. Seventy-nine per cent of autistic participants with moderate to severe learning disabilities were judged to lack capacity to make a decision about taking part in this study. On average, it took nearly 5 weeks to seek consultee advice and enrol these participants. (4) Factors that facilitate or challenge the implementation of our intervention: autistic participants with moderate to severe learning disabilities indicated that they liked coming to the intervention sessions and the information booklets that were used during the intervention. They also indicated that they liked some core aspects of the intervention (e.g. fear ladders, relaxation, visual schedules). Carers indicated that the intervention facilitators were adaptations to meet individual needs, the experience of attending therapy and a positive therapeutic relationship with the therapist. Therapists reported that the intervention facilitators were the inclusion of a clear structure, therapist understanding of people with learning disabilities, carer understanding and engagement, effectively meeting carer need, using adapted materials, high-quality training in the intervention, access to supervision, specific aspects of the intervention (e.g. preference assessments, reinforcement, carer-only sessions, positive therapeutic relationship), and intervention flexibility. Carers reported that the key barriers were not directly attributable to the intervention (e.g. illness, holidays, or lack of staff), or were related to challenges accessing intervention material to be used during exposure, or difficulties with using the intervention with some individuals due to additional complexity, the quantity of information provided, and the time commitment required. Therapists suggested that the barriers were challenges adapting relaxation techniques, difficulties with participant engagement and motivation, different carers attending intervention sessions, difficulties with some intervention components with some individuals, quantity of information, and behaviours that challenge. Conclusions The BEAMS-ID intervention was judged to be feasible to deliver and acceptable to autistic adults with moderate to severe learning disabilities, carers and therapists. Carers and therapists made some helpful suggestions for revisions which can be easily incorporated into the existing manualised intervention with minor revision. This study took place during the COVID-19 pandemic and the recruitment of participants during Phase 2 was at a lower rate than anticipated, considering that the study was funded prior to the onset of the pandemic. Nevertheless, 93% of the planned sample size was successfully recruited, and it was noted that the accrual rate improved during the summer of 2022 and was higher within sites who joined towards the end of the study period. The participant attrition rate was low and not attributable to the intervention or study processes. This study benefited from genuine patient and public involvement and engagement during the adaptation of the intervention, development of fidelity checklist and logic model, choice of outcome measures and study management. Following minor revisions to the intervention, and further consideration of outcome measures based upon carer feedback, the BEAMS-ID intervention should be tested in a randomised trial. Protocol The study protocol is available from https://fundingawards.nihr.ac.uk/award/NIHR129804. Study registration This study is registered as ISRCTN12637590. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR129804) and is published in full in Health Technology Assessment; Vol. 28, No. 72. See the NIHR Funding and Awards website for further award information.

ABSTRACT Background HIV Pre‐Exposure Prophylaxis (PrEP) has been available in Wales since 2017. The coronavirus disease (COVID‐19) pandemic impacted UK sexual health services, leading to a reduction in service provision. There is a lack of research on the experiences of PrEP users during this time. Objective We aimed to explore the experiences of PrEP users in Wales following the introduction of COVID‐19 pandemic measures. Methods We conducted a secondary data analysis of two prior interview studies (DO‐PrEP and UPrEP). Data collection was undertaken between May 2020 and February 2021 using remote interviewing. Semi‐structured interviews were conducted. Participants were ≥18 years of age, residents of Wales, current or previous PrEP users, and men who have sex with men (MSM). Reflexive thematic analysis was conducted. Results A total of 32 interviews were included in the analysis. Themes include the following: (1) PrEP use during COVID‐19, (2) sexual behaviour and relationship changes following COVID‐19 restrictions, (3) NHS service provision during the COVID‐19 pandemic, and (4) wider contextual effects of the pandemic. Participants reported a change in PrEP use (pausing or switching to event‐based PrEP). Participants reported reduced access to clinics and appointments. Support for changing to event‐based PrEP was varied. Social isolation resulted in varied responses to lockdown rules, especially in later lockdowns. Conclusion This study provides patient perspectives on the challenges the COVID‐19 pandemic posed to PrEP use and access. It offers insights into the broader support needs around PrEP use when an individual's circumstances change. Flexible models of PrEP provision, which can be adapted to the patient's needs, will be essential as PrEP delivery extends into the wider community. Patient and Public Contribution Both the DO‐PrEP and UPrEP studies received input from various stakeholders in the design of the topic guides for the study; these included public lay members, PrEP users, PrEP providers, and individuals involved with HIV advocacy and policy.

Abstract Background We evaluated the clinical and cost-effectiveness of manualised sensory integration therapy (SIT) for autistic children with sensory processing difficulties in a two-arm randomised controlled trial. Trial processes and contextual factors which may have affected intervention outcomes were explored within a nested process evaluation. This paper details the process evaluation methods and results. We also discuss implications for evaluation of individual level, tailored interventions in similar populations. Methods The process evaluation was conducted in line with Medical Research Council guidance. Recruitment, demographics, retention, adherence, and adverse effects are reported using descriptive statistics. Fidelity of intervention delivery is reported according to the intervention scoring manual. Qualitative interviews with therapists and carers were undertaken to explore the acceptability of the intervention and trial processes. Qualitative interviews with carers explored potential contamination. Results Recruitment, reach and retention within the trial met expected thresholds. One hundred thirty-eight children and carers were recruited (92% of those screened and 53.5% of those who expressed an interest) with 77.5% retained at 6 months and 69.9% at 12 months post-randomisation. The intervention was delivered with structural and process fidelity with the majority (78.3%) receiving a ‘sufficient dose’ of intervention. However, there was considerable individual variability in the receipt of sessions. Carers and therapists reported that trial processes were generally acceptable though logistical challenges such as appointment times, travel and COVID restrictions were frequent barriers to receiving the intervention. No adverse effects were reported. Conclusions The process evaluation was highly valuable in identifying contextual factors that could impact the effectiveness of this individualised intervention. Rigorous evaluations of interventions for autistic children are important, especially given the limitations such as limited sample sizes and short-term follow-up as faced by previous research. One of the challenges lies in the variability of outcomes considered important by caregivers, as each autistic child faces unique challenges. It is crucial to consider the role of parents or other caregivers in facilitating access to these interventions and how this may impact effectiveness. Trial registration This trial is registered as ISRCTN14716440. August 11, 2016.

Abstract Background One in five children with an intellectual disability in the UK display behaviours that challenge. Despite associated impacts on the children themselves, their families, and services, little research has been published about how best to design, organise, and deliver health and care services to these children. The purpose of this study was to describe how services are structured and organised (“service models”) in England for community-based health and care services for children with intellectual disability who display behaviours that challenge. Methods Survey data about services were collected from 161 eligible community-based services in England. Staff from 60 of these services were also interviewed. A combination of latent class and descriptive analysis, coupled with consultation with family carers and professionals was used to identify and describe groupings of similar services (i.e., “service models”). Results The latent class analysis, completed as a first step in the process, supported a distinction between specialist services and non-specialist services for children who display behaviours that challenge. Planned descriptive analyses incorporating additional study variables were undertaken to further refine the service models. Five service models were identified: Child and Adolescent Mental Health Services (CAMHS) (n = 69 services), Intellectual Disability CAMHS (n = 28 services), Children and Young People Disability services (n = 25 services), Specialist services for children who display behaviours that challenge (n = 27 services), and broader age range services for children and/or adolescents and adults (n= 12 services). Conclusions Our analysis led to a typology of five service models for community health and care services for children with intellectual disabilities and behaviours that challenge in England. Identification of a typology of service models is a first step in building evidence about the best provision of services for children with intellectual disabilities who display behaviours that challenge. The methods used in the current study may be useful in research developing service typologies in other specialist fields of health and care. Study registration Trial Registration: Current Controlled Trials ISRCTN88920546, Date assigned 05/07/2022.

Young people use slang for identifying themselves with a particular social group, gaining social recognition and respect from that group, and expressing their emotional state. One feature of Internet slang is its active use by youth in online communication, which, under certain conditions, may cause problematic Internet use (PIU). We conducted two studies in young Russian speakers (n[subscript 1] = 115, n[subscript 2] = 106). In study 1, participants were asked to rate a set of slang and common words using Self-Assessment Manikin. The study revealed that the most reliable predictor of higher emotional ratings was word familiarity. There were no significant effects of slang vs. common words or word frequency. In study 2, we used a dual lexical decision task to reveal the effects of word characteristics and propensity for PIU on reaction time (RT) for Internet slang words in pairs with semantically related vs. unrelated common words. Study 2 did not reveal any significant semantic priming effect. Word frequency was a significant predictor of lexical decision facilitation. Common, but not slang, word valence and dominance significantly affected RT in the opposite direction. Individuals with higher cognitive preoccupation with the Internet responded significantly faster, while those more likely to use online communication for mood regulation responded significantly slower to the stimuli. Apparently, on explicit and implicit levels, in-depth knowledge of Internet slang can be one the PIU markers. The results are discussed in line with Davis' approach to determining the general pathological Internet use.

Background Stigma contributes to the negative social conditions persons with intellectual disabilities are exposed to, and it needs tackling at multiple levels. Standing Up for Myself is a psychosocial group intervention designed to enable individuals with intellectual disabilities to discuss stigmatising encounters in a safe and supportive setting and to increase their self-efficacy in managing and resisting stigma. Objectives To adapt Standing Up for Myself to make it suitable as a digital intervention; to evaluate the feasibility and acceptability of Digital Standing Up for Myself and online administration of outcome measures in a pilot; to describe usual practice in the context of the coronavirus disease 2019 pandemic to inform future evaluation. Design Adaptation work followed by a single-arm pilot of intervention delivery. Setting and participants Four third and education sector organisations. Individuals with mild-to-moderate intellectual disabilities, aged 16+, members of existing groups, with access to digital platforms. Intervention Digital Standing Up for Myself intervention. Adapted from face-to-face Standing Up for Myself intervention, delivered over four weekly sessions, plus a 1-month follow-up session. Outcomes Acceptability and feasibility of delivering Digital Standing Up for Myself and of collecting outcome and health economic measures at baseline and 3 months post baseline. Outcomes are mental well-being, self-esteem, self-efficacy in rejecting prejudice, reactions to discrimination and sense of social power. Results Adaptation to the intervention required changes to session duration, group size and number of videos; otherwise, the content remained largely the same. Guidance was aligned with digital delivery methods and a new group member booklet was produced. Twenty-two participants provided baseline data. The intervention was started by 21 participants (four groups), all of whom were retained at 3 months. Group facilitators reported delivering the intervention as feasible and suggested some refinements. Fidelity of the intervention was good, with over 90% of key components observed as implemented by facilitators. Both facilitators and group members reported the intervention to be acceptable. Group members reported subjective benefits, including increased confidence, pride and knowing how to deal with difficult situations. Digital collection of all outcome measures was feasible and acceptable, with data completeness ≥ 95% for all measures at both time points. Finally, a picture of usual practice has been developed as an intervention comparator for a future trial. Limitations The pilot sample was small. It remains unclear whether participants would be willing to be randomised to a treatment as usual arm or whether they could be retained for 12 months follow-up. Conclusions The target number of groups and participants were recruited, and retention was good. It is feasible and acceptable for group facilitators with some training and supervision to deliver Digital Standing Up for Myself. Further optimisation of the intervention is warranted. Future work To maximise the acceptability and reach of the intervention, a future trial could offer the adapted Digital Standing Up for Myself, potentially alongside the original face-to-face version of the intervention. Study registration This study was registered as ISRCTN16056848. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: 17/149/03) and is published in full in Public Health Research; Vol. 12, No. 1. See the NIHR Funding and Awards website for further award information. Plain language summary People with intellectual disabilities (or ‘learning disabilities’ in United Kingdom language) are more likely to experience poor physical and mental health than the general population. Stigma (negative stereotypes, prejudice and discrimination) has been linked to lower self-esteem, quality of life, and mental and physical ill health. Efforts to empower people with intellectual disabilities themselves to challenge stigma with a view to improving well-being, health and self-esteem are lacking. In 2017, we developed Standing Up for Myself, a brief group-based programme for people with mild-to-moderate intellectual disabilities aged 16+ to address this gap. As this study got underway, face-to-face meetings were suspended due to the coronavirus disease 2019 pandemic. We used the opportunity to assess whether Standing Up for Myself could be delivered through web-based meetings. We adapted Standing Up for Myself for digital delivery, with close input from advisors with intellectual disabilities and experienced group facilitators. We then tested the digital version in charity and education settings to evaluate if Digital Standing Up for Myself could be delivered as planned and how acceptable it was to group facilitators and participants. Four groups, with a total of 22 members, signed up to try Digital Standing Up for Myself. One participant dropped out before starting Standing Up for Myself, and the other 21 continued until the end of the programme. Retention and attendance were good; participants on average attended four of the five sessions. Ninety per cent of the core programme requirements were fully delivered as detailed in the Digital Standing Up for Myself manual. Problems with technology were manageable, although facilitators found using the Standing Up for Myself Wiki platform (an online platform for storage and sharing of resources) difficult, particularly when sharing video content. Facilitators felt acceptable levels of privacy were achieved and there were no reports of undue distress. All facilitators and many group members said they would recommend Digital Standing Up for Myself to others. Group members shared how the programme benefitted them, noting increased awareness about disabilities, and for some increased confidence, pride and independence. Some had learnt how to stand up for themselves and manage difficult situations and took pride in this. Completing outcome and health cost measures via web-based meetings was acceptable and data were largely fully complete and useable. Scientific summary Background Approximately 1.4–2% of the UK population have an intellectual disability. Individuals with intellectual disabilities face substantial social and health inequalities and are at increased risk of experiencing mental health problems. One factor compounding these inequalities is the impact of stigma, whereby individuals experience negative stereotyping, prejudice and discrimination associated with intellectual disability. Interventions that seek to reduce stigma are needed at multiple levels. The Standing Up for Myself (STORM) programme targets the person with an intellectual disability themselves and seeks to empower them as agent of positive change. It seeks to empower individuals with intellectual disabilities to challenge stigma they face in everyday encounters, thus potentially improving well-being and reducing inequalities, alongside interventions at community and institutional/societal levels to reduce stigma. An earlier pilot of the STORM programme showed it to be a promising intervention which could be delivered in community, third sector (i.e. ‘charities’ that typically provide services to achieve social goals) and education settings to existing groups of individuals with intellectual disabilities, aged 16 years and above. Some issues were highlighted which were to be addressed as part of a feasibility study with the intention of progressing to a fully powered randomised controlled trial (RCT). The start of the feasibility study coincided with the outbreak of the coronavirus disease 2019 (COVID-19) pandemic and the first national lockdown during month 6 of the original project. Following a necessary pause, the study management team saw a unique opportunity to revise the study to examine the potential of STORM as a digital intervention. Adapting STORM to make it suitable for digital delivery would allow the programme to be available to a much wider audience and potentially future-proof it in the context of the ongoing pandemic. Extensive patient and public involvement (PPI) work generated evidence in line with the National Institute for Health and Care Excellence (Evidence Standards Framework for Digital Health Technologies, 2019, www.nice.org.uk/Media/Default/About/what-we-do/our-programmes/evidence-standards-framework/digital-evidence-standards-framework.pdf) framework for digital health technologies and indicated that the creation of a digital version of STORM was important to potential future users and professionals. We, therefore, proposed to adapt the STORM programme for digital delivery to groups of individuals with mild-to-moderate intellectual disabilities. Working closely with PPI partners we planned, following adaptation of the intervention, to deliver the digital programme to four groups as part of a small pilot study. We also engaged experts on digital inclusion and learning design to ensure that the adapted digital version of STORM was optimised for engagement of people with intellectual disabilities and delivery by group facilitators with varying experience and skills in digital delivery. Objectives to adapt the existing STORM intervention for online delivery (Digital STORM), ensuring the content, number of sessions and direct contact time were the same for both STORM and Digital STORM; to pilot the Digital STORM intervention in order to investigate the feasibility of recruitment to and retention of participants in Digital STORM; and adherence, fidelity and acceptability of Digital STORM, when delivered to groups of people with mild-to-moderate intellectual disabilities online; to test digital administration of the study outcome and health economics measures; to build on community assessments to describe what usual practice might look like for groups of people with mild-to-moderate intellectual disabilities in the wake of COVID-19, to inform a potential future trial. Methods Design and procedure Digital STORM was an adaptation of the original STORM intervention, designed for online delivery, piloted with four groups of young people and adults with mild-to-moderate intellectual disabilities. Adaptation and pilot work took place during months 14–21 of the overall 24-month project in distinct phases of work: Intervention adaptation (months 14–17) An Intervention Adaptation Group (IAG) was established to oversee the adaptation and report progress to oversight committees. The group included all members of the PPI advisory group (people with intellectual disabilities, the independent co-chair), experienced group facilitators from third and education sector organisations (from our stakeholder group), Mencap as our intervention delivery partner, digital inclusion experts and members of the research team. The focus of this group was to maximise access to and engagement with Digital STORM to ensure it would be inclusive and to address potential barriers to access to and/or engagement with the intervention. Pilot of Digital STORM (months 18–21) The adapted intervention was then piloted with four groups (N = 22). Priority was given to groups that had expressed interest in participating in STORM at the point of having to pause the original study in March 2020 due to the first national coronavirus disease 2019 (COVID-19) lockdown. Of the four pilot groups, at least one would need to do some additional work to allow all its group members to access Digital STORM. This would allow us to explore ‘live’ how issues relating to access to technology, support, and provisions to ensure privacy are managed. Following delivery of the adapted digital intervention, pilot group facilitators were interviewed about their experiences to assess barriers and facilitators to implementation. Participants took part in focus groups to access their views on the intervention, the delivery mechanisms, and the intervention’s subjective impact. The focus groups were co-led by a member of the PPI advisory group and a researcher in three cases and by a researcher alone in one case and recorded. Decision phase (month 22) Oversight committees met at regular intervals throughout the adaptation and pilot phases to monitor progress. They reviewed findings from the pilot against the progression criteria and made recommendations to the National Institute for Health and Care Research (NIHR) regarding the potential for a future funding application. Inclusion and exclusion criteria Groups from third and education sector organisations were included where they had a willing facilitator and organisational support in place, were meeting or restarting meetings as a group for at least 3 further months and were willing to replace five of their meetings with Digital STORM. Groups needed at least three and no more than eight members with intellectual disabilities to participate. Groups were excluded if they were run as part of the National Health Service, or if some of their regular members declined taking part in Digital STORM and if it was not possible to find alternative meeting times for those who wanted to participate. Individual participants were included if they were aged 16 years or older, had mild-to-moderate intellectual disabilities, capacity to provide informed consent, were able to complete the outcome measures and could engage with the intervention in English. They needed to be a member of an established (educational, activity, social or self-advocacy focused) group; to have access to the internet, a device to join web meetings, and support to access web-based meetings when needed. Participants were excluded from the research if they did not provide consent. Intervention Adaptation of the STORM intervention for delivery using web-based video meetings (Digital STORM), consisting of four weekly 90-minute sessions and a 90-minute follow-up session (delivered around 4 weeks after session four). An intervention manual and a Wiki (a web platform designed as both a repository of intervention resources and an aide to delivering session content) was provided to facilitators. Outcomes The primary outcome of the adaptation phase was the feasibility and acceptability of delivering STORM to groups in a web-delivered format (Digital STORM). Secondary outcomes of the adaptation phase were the feasibility of remotely collecting outcomes, health economics and process data and the description of ‘Usual practice’, that is, activities usually undertaken within the group setting, in a changed service delivery context. Analyses Pilot data (baseline demographics, responses to outcome measures, adherence and fidelity ratings) were described descriptively. The feasibility of economic evaluation was assessed using completion rates of included measures [Service Information Schedule (SIS), EuroQol-Youth version, and Client Service Receipt Inventory]. Intervention costs were calculated using SIS data. Qualitative interviews and focus groups were conducted to explore barriers and facilitators to participation in the intervention. Interview and focus group transcripts were analysed thematically using Framework analysis; a sample of transcripts was double coded. Progression criteria were included to determine suitability for moving to a future trial of Digital STORM. Results The STORM intervention was successfully adapted for online delivery (objective 1). The IAG addressed issues such as access to the digital intervention, engagement with it and potential risks to managing participant privacy. Minor adjustments were made to the STORM intervention to allow for digital delivery. Content was slightly streamlined to ensure each session could be covered within the 60-minute sessions. Resources were created to support participation in online group work (for participants) and for running sessions (for facilitators). A revised intervention logic model for Digital STORM was also created. Digital STORM was both feasible and acceptable when delivered to groups online (objective 2). Targets for recruitment into the pilot of Digital STORM were met with 4 groups taking part and 22 participants providing informed consent, 1 of whom dropped out before starting the intervention. There was good attendance across sessions (median attendance 5 out of 5 sessions, with 20 of 21 participants attending 3 or more sessions) and the majority of participants missed no more than 15 minutes of any one intervention session due to technical difficulties. Accordingly, there was a strong indicator of feasibility for progression to a future trial. There was also a strong indicator for the acceptability of Digital STORM. Facilitators found the recording of sessions acceptable and over 90% of the core intervention requirements were met in full. Feasibility and acceptability were also examined through interviews (with facilitators) and focus groups (with participants). Resources supported facilitators’ delivery of sessions though some reported challenges when playing and sharing videos in online meetings and with trying to co-ordinate moving between video sharing via the STORM Wiki platform, the manual and operating the meeting platform. Feasibility of administering study outcome measures was also demonstrated (objective 3). Participants completed outcome measures via web-based platforms at baseline and post intervention. This enabled the research team to recruit from a wider geographical area than would have been possible using face-to-face data collection methods. Data completeness was very high – only one response was missing across all measures. Similarly, data completeness for economic evaluation was very good with no barriers to future data collection identified. Group members’ experience of completing measures was positive and they felt positive about the digital approach as a method for data collection in future. Finally, it was determined that many organisations delivering group sessions had made the transition to online delivery and were running virtual groups. This supports the possibility of including a control arm that described ‘usual practice’ as part of a future trial (objective 4). Conclusions The STORM digital adaptation and pilot was a well-delivered package of work. Results evidence that all progression criteria were achieved in full. Oversight committees therefore recommend progression to a full trial. Strengths and limitations The key strength of this work was the ability of the team to work flexibly and creatively to adapt to the changing situation of the pandemic. Involvement of experts by experience meant the rationale for creating a digital version of STORM was supported by all stakeholders and the accessibility of the processes and resources was considered carefully from a user perspective. A number of limitations need noting. These include the small sample size for the pilot; long-term retention was not established; those taking part all did so with the knowledge they would receive the intervention, thus the ability to randomise was not confirmed; the video sharing platform was not optimal – other approaches might have worked better; qualitative work could not capture the views of all those who took part in the pilot. Study registration This study was registered as ISRCTN16056848. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: 17/149/03) and is published in full in Public Health Research; Vol. 12, No. 1. See the NIHR Funding and Awards website for further award information.

Abstract Background HIV pre-exposure prophylaxis (PrEP) is a medication that prevents the acquisition of HIV. It has been targeted towards men who have sex with men (MSM). Since its introduction there have been concerns raised around changes in sexual behaviour such as increased condomless anal intercourse (CAI), leading to an elevation in sexually transmitted infections (STIs). With antimicrobial resistant strains of STIs rising, there are concerns that PrEP may be contributing to this growth. This study aims to understand how MSM conceptualise the relationship between PrEP, STIs and antimicrobial resistance (AMR). Methods Twenty semi-structured interviews were conducted online using Zoom. Participants include a mix of PrEP related experiences (never used, currently use, previously used). Reflexive thematic analysis was undertaken by the lead author with 10% of transcripts double coded. Results MSM in Wales have positive views and a good knowledge of PrEP and awareness of bacterial STIs. PrEP is perceived by many to lead to a reduction in condom use and increase in STIs but reported condom use behaviours presented to be stable in terms of PrEP initiation. PrEP use is influenced by increased concern for HIV and minimal concern for bacterial STIs. Awareness of AMR STIs was lacking. Conclusions There is a belief that PrEP use will lead to an increase in STI rates through reduced condom use, despite reported behaviours often being stable in relation to PrEP initiation, PrEP stigma may be influencing this dichotomy. Concern and awareness for resistant STIs is low, with little association to PrEP.

Abstract Background Preterm birth, especially at less than 30 weeks’ gestation, is significantly associated with respiratory, neurodevelopmental and growth abnormalities. The AZTEC study has recruited 799 infants born at

Abstract Introduction HIV pre‐exposure prophylaxis (PrEP) involves the use of antiretroviral medication in HIV‐negative individuals considered to be at risk of acquiring HIV. It has been shown to prevent HIV and has been available in Wales since July 2017. Measuring and understanding adherence to PrEP is complex as it relies on the simultaneous understanding of both PrEP use and sexual activity. We aimed to understand the experiences of men who have sex with men (MSM) living in Wales initiating, implementing and persisting with HIV PrEP. Methods We conducted semistructured interviews with MSM PrEP users in Wales who participated in a cohort study of PrEP use and sexual behaviour. Following completion of the cohort study, participants were invited to take part in a semistructured interview about their experiences of taking PrEP. We aimed to include both individuals who had persisted with and discontinued PrEP during the study. The interview topic guide was informed by the ABC taxonomy for medication adherence and the theory of planned behaviour. We analysed our data using reflexive thematic analysis. Results Twenty‐one participants were interviewed, five having discontinued PrEP during the cohort study. The developed themes focused on triggers for initiating PrEP, habitual behaviour, drivers for discontinuation and engagement with sexual health services. Stigma surrounding both PrEP and HIV permeated most topics, acting as a driver for initiating PrEP, an opportunity to reduce discrimination against people living with HIV, but also a concern around the perception of PrEP users. Conclusion This is the first study to investigate PrEP‐taking experiences incorporating established medication adherence taxonomy. We highlight key experiences regarding the initiation, implementation and persistence with PrEP and describe how taking PrEP may promote positive engagement with sexual health services. These findings may be useful for informing PrEP rollout programmes and need to be explored in other key populations. Patient and Public Contribution PrEP users, in addition to PrEP providers and representatives of HIV advocacy and policy, were involved in developing the topic guide for this study.

Abstract Background The AZTEC trial is a multi-centre, randomised, placebo-controlled trial of azithromycin to improve survival without development of chronic lung disease of prematurity (CLD) in preterm infants. The statistical analysis plan for the clinical outcomes of the AZTEC trial is described. Methods and design A double-blind, randomised, placebo-controlled trial of a 10-day course of intravenous azithromycin (20 mg/kg for 3 days; 10 mg/kg for 7 days) administered to preterm infants born at

Abstract Background Support, such as information, advice and therapies, can play a vital role in the lives of families of autistic children. However, little is known about the support experiences of UK parents and carers. Aim To explore experiences of and access to support for families of children with autism and sensory processing difficulties, from the perspective of parents and carers. Methods Semi‐structured, timeline‐assisted interviews were conducted with parents/carers of 30 children aged 5–11, exploring experiences of support. Framework analysis was used to identify themes in the interview data. Results Support varied widely and was not accessed equitably. Specialist autism support, together with support from other parents and voluntary organizations, was perceived as more useful than statutory and nonspecialist provision. Unmet support needs included an ongoing point of contact for information and advice for parents, and access to direct therapy and specialist mental health provision for children. Conclusions Findings emphasize the need for a clear pathway of support following autism diagnosis, autism‐specific training for professional service providers and specialist provision tailored to the needs of autistic children. Patient or Public Contribution An advisory group of four parents of children with autism provided feedback on study procedures and materials, including participant information sheets and timeline completion instructions.

Abstract Background Antibiotics are frequently prescribed for acute exacerbations of COPD (AECOPD) even though most do not have a bacterial aetiology. Biomarkers may help clinicians target antibiotic use by identifying AECOPD caused by bacterial pathogens. We aimed to summarise current evidence on the diagnostic accuracy of biomarkers for detecting bacterial versus non-bacterial AECOPD. Methods We searched Embase and Medline using a search strategy including terms for COPD, biomarkers and bacterial infection. Data regarding diagnostic accuracy for each biomarker in predicting bacterial cause of exacerbation were extracted and summarised. We used to QUADAS-2 tool to assess risk of bias. Results Of 509 papers identified, 39 papers evaluating 61 biomarkers were eligible for inclusion. Moderate quality evidence was found for associations between serum C-reactive protein (CRP), serum procalcitonin (PCT), sputum interleukin (IL)-8 and sputum tumour necrosis factor alpha (TNF-α), and the presence of bacterial pathogens in the sputum of patients with AECOPD. Having bacterial pathogens was associated with a mean difference (higher) CRP and PCT of 29.44 mg/L and 0.76 ng/mL respectively. There was inconsistent or weak evidence for associations between bacterial AECOPD and higher levels of sputum IL-1β, IL-6, myeloperoxidase (MPO) and neutrophil elastase (NE). We did not find any consistent evidence of diagnostic value for other biomarkers. Conclusions There is moderate evidence from heterogeneous studies that serum CRP and PCT are of value in differentiating bacterial from non-bacterial AECOPD, and little evidence for other biomarkers. Further high-quality research on the role of biomarkers in identifying bacterial exacerbations is needed.

Abstract Background The COVID-19 pandemic and its associated restrictions stopped people freely engaging in sexual behaviour. We explored sexual behaviour amongst men who have sex with men (MSM) using mixed methods during the multiple lockdowns in Wales. Methods An online survey was advertised on social media platforms (focusing on Welsh LGBT groups), from June 2020 to July 2020. MSM over 16 years were invited to take part if they were resident in Wales. Qualitative interviews were undertaken as part of a study examining knowledge and awareness of sexual health. Interviews were conducted between September 2020 and February 2021 via Zoom©. Interview data was analysed thematically and integrated with survey data. Results The survey received 70 responses, 60% (n = 42) reported not having sexual activity during lockdown. Restrictions altered the number of new sexual partners per week with over 80% (n = 56) not having any new sexual partners for the 12 weeks of the first lockdown. However, as the weeks progressed following the first lockdown there was an increase in the number of new sexual partners. Interview data indicated that the COVID-19 pandemic had a large impact on reducing sexual behaviour with other MSM in Wales. ‘Lockdown fatigue’ was viewed to result in different levels of adherence to the lockdown rules depending on the lockdown being discussed. Of those engaging in sex outside the rules, ‘shame’ was commonly reported. The restrictions were believed to have a positive impact on reducing the spread of sexually transmitted infections. Conclusions The COVID-19 pandemic and associated restrictions had a significant impact on sexual behaviours among MSM in Wales, with the majority fully adhering to the lockdown rules. Although the population were largely compliant with the lockdown restrictions, lockdown fatigue may suggest that any future lockdowns might not have the same effect.

Abstract Background Many individuals with intellectual disability (ID) have not learnt basic reading skills by the time that they reach adulthood, potentially limiting their access to critical information. READ-IT is an online reading programme developed from the Headsprout® Early Reading (HER®) intervention and supplemented by support strategies tailored for adults with ID. HER® has been successfully used to teach adults with ID to read in a forensic setting by trained staff. The aim of this study is to assess the feasibility of delivering READ-IT to adults with ID by family carers/support workers and will assess whether it would be feasible to conduct a later definitive randomised controlled trial (RCT) of the effectiveness of the programme. The study will aim to contribute to the evidence base on improving outcomes for adults with ID and their caregivers. Methods This study is a feasibility RCT, with embedded process evaluation. Forty-eight adults with ID will be recruited and allocated to intervention: control on a 1:1 basis. Intervention families will be offered the READ-IT programme immediately, continuing to receive usual practice and control participants will be offered the opportunity to receive READ-IT at the end of the trial follow-up period and will continue to receive usual practice. Data will be collected at baseline and 6 months post-randomisation. Discussion The results of this study will inform a potential future definitive trial, to evaluate the effectiveness of READ-IT to improve reading skills. Such a trial would have significant scientific impact internationally in the intellectual disability field. Trial registration ISRCTN11409097

BackgroundResistance to antibiotics is rising and threatens future antibiotic effectiveness. 'Antibiotic targeting' ensures patients who may benefit from antibiotics receive them, while being safely withheld from those who may not. Point-of-care tests may assist with antibiotic targeting by allowing primary care clinicians to establish if symptomatic patients have a viral, bacterial, combined, or no infection. However, because organisms can be harmlessly carried, it is important to know if the presence of the virus/bacteria is related to the illness for which the patient is being assessed. One way to do this is to look for associations with more severe/prolonged symptoms and test results. Previous research to answer this question for acute respiratory tract infections has given conflicting results with studies has not having enough participants to provide statistical confidence.AimTo undertake a synthesis of IPD from both randomised controlled trials (RCTs) and observational cohort studies of respiratory tract infections (RTI) in order to investigate the prognostic value of microbiological data in addition to, or instead of, clinical symptoms and signs.MethodsA systematic search of Cochrane Central Register of Controlled Trials, Ovid Medline and Ovid Embase will be carried out for studies of acute respiratory infection in primary care settings. The outcomes of interest are duration of disease, severity of disease, repeated consultation with new/worsening illness and complications requiring hospitalisation. Authors of eligible studies will be contacted to provide anonymised individual participant data. The data will be harmonised and aggregated. Multilevel regression analysis will be conducted to determine key outcome measures for different potential pathogens and whether these offer any additional information on prognosis beyond clinical symptoms and signs.Trial registrationPROSPERO Registration number: CRD42023376769.

Summary: Determining the protection an individual has to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VoCs) is crucial for future immune surveillance, vaccine development, and understanding of the changing immune response. We devised an informative assay to current ELISA-based serology using multiplexed, baited, targeted proteomics for direct detection of multiple proteins in the SARS-CoV-2 anti-spike antibody immunocomplex. Serum from individuals collected after infection or first- and second-dose vaccination demonstrates this approach and shows concordance with existing serology and neutralization. Our assays show altered responses of both immunoglobulins and complement to the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.1) VoCs and a reduced response to Omicron (B1.1.1529). We were able to identify individuals who had prior infection, and observed that C1q is closely associated with IgG1 (r > 0.82) and may better reflect neutralization to VoCs. Analyzing additional immunoproteins beyond immunoglobulin (Ig) G, provides important information about our understanding of the response to infection and vaccination. Motivation: Assays for measuring serum antibody responses are typically limited to measurement of a total or single immunoglobulin isotype. The antibody response is far more complex, with multiple immunoglobulin classes, isotypes, and complement factors involved. This is a potential wealth of information that is typically understudied and missed by existing tests. The global COVID-19 pandemic has highlighted the need to understand better the immune response in respect to vaccine development and emerging new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants. Using the ability of tandem mass spectrometry to multiplex and directly and accurately measure the antibody complex, we devised an alternative assay to capture this valuable information.

Introduction There is increasing interest in the relationship between acute infections and acute cardiovascular events. Most previous research has focused on understanding whether the risk of acute cardiovascular events increases following a respiratory tract infection. The relationship between urinary tract infections (UTIs) and acute cardiovascular events is less well studied. Therefore, the aim of this study is to determine whether there is a causal relationship between UTI and acute myocardial infarction (MI) or stroke.Methods and analysis We will undertake a self-controlled case series study using linked anonymised general practice, hospital admission and microbiology data held within the Secure Anonymised Information Linkage (SAIL) Databank. Self-controlled case series is a relatively novel study design where individuals act as their own controls, thereby inherently controlling for time-invariant confounders. Only individuals who experience an exposure and outcome of interest are included.We will identify individuals in the SAIL Databank who have a hospital admission record for acute MI or stroke during the study period of 2010–2020. Individuals will need to be aged 30–100 during the study period and be Welsh residents for inclusion. UTI will be identified using general practice, microbiology and hospital admissions data. We will calculate the incidence of MI and stroke in predefined risk periods following an UTI and in ‘baseline’ periods (without UTI exposure) and use conditional Poisson regression models to derive incidence rate ratios.Ethics and dissemination Data access, research permissions and approvals have been obtained from the SAIL independent Information Governance Review Panel, project number 0972. Findings will be disseminated through conferences, blogs, social media threads and peer-reviewed journals. Results will be of interest internationally to primary and secondary care clinicians who manage UTIs and may inform future clinical trials of preventative therapy.

Background: Carers report unmet need for occupational therapy services addressing sensory difficulties in autism, yet insufficient evidence exists to recommend a therapeutic approach. Objectives: Our aim was to determine the clinical effectiveness and cost-effectiveness of sensory integration therapy for children with autism and sensory difficulties across behavioural, functional and quality-of-life outcomes. Design: We carried out a parallel-group randomised controlled trial, incorporating an internal pilot and a process evaluation. Randomisation utilised random permuted blocks. Setting and participants: Children were recruited via services and self-referral in Wales and England. Inclusion criteria were having an autism diagnosis, being in mainstream primary education and having definite/probable sensory processing difficulties. Exclusion criteria were having current/previous sensory integration therapy and current applied behaviour analysis therapy. Intervention: The intervention was manualised sensory integration therapy delivered over 26 weeks and the comparator was usual care. Outcomes: The primary outcome was problem behaviours (determined using the Aberrant Behavior Checklist), including irritability/agitation, at 6 months. Secondary outcomes were adaptive behaviour, functioning and socialisation (using the Vineland Adaptive Behavior Scales); carer stress (measured using the Autism Parenting Stress Index); quality of life (measured using the EuroQol-5 Dimensions and Carer Quality of Life); functional change (according to the Canadian Occupational Performance Measure); sensory processing (determined using the Sensory Processing Measure™ at screening and at 6 months to examine mediation effects); and cost-effectiveness (assessed using the Client Service Receipt Inventory). Every effort was made to ensure that outcome assessors were blind to allocation. Results: A total of 138 participants were randomised (n = 69 per group). Usual care was significantly different from the intervention, which was delivered with good fidelity and adherence and minimal contamination, and was associated with no adverse effects. Trial procedures and outcome measures were acceptable. Carers and therapists reported improvement in daily functioning. The primary analysis included 106 participants. There were no significant main effects of the intervention at 6 or 12 months. The adjusted mean difference between groups on the Aberrant Behavior Checklist – irritability at 6 months post randomisation was 0.40 (95% confidence interval –2.33 to 3.14; p = 0.77). Subgroup differences in irritability/agitation at 6 months were observed for sex of child (intervention × female = 6.42, 95% confidence interval 0.00 to 12.85; p = 0.050) and attention deficit hyperactivity disorder (intervention × attention deficit hyperactivity disorder = –6.77, 95% confidence interval –13.55 to –0.01; p = 0.050). There was an effect on carer stress at 6 months by region (intervention × South England = 7.01, 95% confidence interval 0.45 to 13.56; p = 0.04) and other neurodevelopmental/genetic conditions (intervention × neurodevelopmental/genetic condition = –9.53, 95% confidence interval –18.08 to –0.98; p = 0.030). Carer-rated goal performance and satisfaction increased across sessions (p

Microbiological data are used as indicators of infection, for diagnosis, and the identification of antimicrobial resistance in trials of antimicrobial stewardship interventions. However, several problems have been identified in a recently conducted systematic review (e.g., inconsistency in reporting and oversimplified outcomes), which motivates the need to understand and improve the use of these data including analysis and reporting. We engaged key stakeholders including statisticians, clinicians from both primary and secondary care, and microbiologists. Discussions included issues identified in the systematic review and questions about the value of using microbiological data in clinical trials, perspectives on current microbiological outcomes reported in trials, and alternative statistical approaches to analyse these data. Various factors (such as unclear sample collection process, dichotomising or categorising complex microbiological data, and unclear methods of handling missing data) were identified that contributed to the low quality of the microbiological outcomes and the analysis of these outcomes in trials. Whilst not all of these factors would be easy to overcome, there is room for improvement and a need to encourage researchers to understand the impact of misusing these data. This paper discusses the experience and challenges of using microbiological outcomes in clinical trials.

Abstract Background Up to 50% of medicines are not used as intended, resulting in poor health and economic outcomes. Medicines optimisation is ‘a person-centred approach to safe and effective medicines use, to ensure people obtain the best possible outcomes from their medicines’. The purpose of this exercise was to co-produce a prioritised research agenda for medicines optimisation using a multi-stakeholder (patient, researcher, public and health professionals) approach. Methods A three-stage, multiple method process was used including: generation of preliminary research questions (Stage 1) using a modified Nominal Group Technique; electronic consultation and ranking with a wider multi-stakeholder group (Stage 2); a face-to-face, one-day consensus meeting involving representatives from all stakeholder groups (Stage 3). Results In total, 92 research questions were identified during Stages 1 and 2 and ranked in order of priority during stage 3. Questions were categorised into four areas: ‘Patient Concerns’ [e.g. is there a shared decision (with patients) about using each medicine?], ‘Polypharmacy’ [e.g. how to design health services to cope with the challenge of multiple medicines use?], ‘Non-Medical Prescribing’ [e.g. how can the contribution of non-medical prescribers be optimised in primary care?], and ‘Deprescribing’ [e.g. what support is needed by prescribers to deprescribe?]. A significant number of the 92 questions were generated by Patient and Public Involvement representatives, which demonstrates the importance of including this stakeholder group when identifying research priorities. Conclusions A wide range of research questions was generated reflecting concerns which affect patients, practitioners, the health service, as well the ethical and philosophical aspects of the prescribing and deprescribing of medicines. These questions should be used to set future research agendas and funding commissions.

Background Stillbirths are reported as one of the most neglected tragedies in global health, with around 2m stillbirths occurring annually and the majority occurring in low- and middle income countries (LMICs). Many antenatal stillbirths are due to preventable conditions such as maternal infections and non-communicable diseases. Almost half of all stillbirths occur during the intrapartum period, with many linked to obstetric complications. Known risk factors for stillbirths overall include young or advancing maternal age, fetal infection, maternal hypertensive conditions, perinatal asphyxia, history of previous stillbirth, obstetric complications, intrauterine growth restriction and abruptio placenta/placenta praevia. Common non-clinical risk factors include lack of education, socioeconomic deprivation and substandard antenatal care. Methods A single site prospective observational study conducted over three-months was conducted in a tertiary referral hospital in Kano, Nigeria. Eligible participants were mothers presenting at the site in labour and their babies. Demographic and clinical data were collected by paper-based questionnaires. Data were collected on living environment, health and medical history, pregnancy history and pregnancy/birth factors. Each mother answered pre-delivery questions, with potential follow-on questions dependent on birth outcome. Further data points were collected from clinical observations. Photographs were taken of stillborn babies to support data collected and to aid the UK team on classifying degrees of maceration in an attempt to identify antenatal and intrapartum fetal death. Findings Higher odds of stillbirth were associated with low levels of education, a further distance to travel from home to the hospital, living in a shack, maternal hypertension and having had a previous stillbirth after adjusting for all sociodemographic and health features. Higher odds of intrapartum stillbirth included; shoulder presentation, compound presentation and breech presentation compared to cephalic presentation. Other birth related factors associated with higher odds of stillbirth included reported birthing complications, duration of labour being >=18 hours), antepartum haemorrhage, prolonged/obstructed labour, vaginal breech delivery, emergency Caesarean-section delivery, and signs of trauma to the neonate. Conclusions Identified risk factors associated with stillbirths are relatively amenable to intervention and a lot of work has been conducted globally, so the development of intervention with sufficient funding should be a relatively rapid process. For collaborations please contact: Email: miltonrl1@cardiff.ac.uk

Abstract Background Children with intellectual disability have an IQ < 70, associated deficits in adaptive skills and are at increased risk of having clinically concerning levels of behaviour problems. In addition, parents of children with intellectual disability are likely to report high levels of mental health and other psychological problems. The Early Positive Approaches to Support (E-PAtS) programme for family caregivers of young children (5 years and under) with intellectual and developmental disabilities is a group-based intervention which aims to enhance parental psychosocial wellbeing and service access and support positive development for children. The aim of this study is to assess the feasibility of delivering E-PAtS to family caregivers of children with intellectual disability by community parenting support service provider organisations. The study will inform a potential, definitive RCT of the effectiveness and cost-effectiveness of E-PAtS. Methods This study is a feasibility cluster randomised controlled trial, with embedded process evaluation. Up to 2 family caregivers will be recruited from 64 families with a child (18 months to 5 years) with intellectual disability at research sites in the UK. Participating families will be allocated to intervention: control on a 1:1 basis; intervention families will be offered the E-PAtS programme immediately, continuing to receive usual practice, and control participants will be offered the opportunity to attend the E-PAtS programme at the end of the follow-up period and will continue to receive usual practice. Data will be collected at baseline, 3 months post-randomisation and 12 months post-randomisation. The primary aim is to assess feasibility via the assessment of: recruitment of service provider organisations; participant recruitment; randomisation; retention; intervention adherence; intervention fidelity and the views of participants, intervention facilitators and service provider organisations regarding intervention delivery and study processes. The secondary aim is preliminary evaluation of a range of established outcome measures for individual family members, subsystem relationships and overall family functioning, plus additional health economic outcomes for inclusion in a future definitive trial. Discussion The results of this study will inform a potential future definitive trial, to evaluate the effectiveness and cost-effectiveness of the E-PAtS intervention to improve parental psychosocial wellbeing. Such a trial would have significant scientific impact internationally in the intellectual disability field. Trial registration ISRCTN70419473

Background:Stillbirths are a poignant representation of global inequality. Nigeria is documented to have the second highest rate; yet, the reporting system is inadequate in most Nigerian healthcare facilities. The aim was to identify the determinants of stillbirth among deliveries in the Murtala Muhammad Specialist Hospital (MMSH), Kano, Nigeria.Methods:Two study designs were used: a case-control study (S1) and a prospective cohort study (S2). Both studies were carried out at the MMSH. For S1, stillbirths were retrospectively matched to a livebirth by time (target of 24 hours' time variation) to establish a case-control study with a 1:1 ratio. Eligibility into S2 included all mothers who were presented at the MMSH in labour regardless of birth outcome. Both were based on recruitment durations, not sample sizes (3 months and 2 months, respectively, 2017–2018). The demographic and clinical data were collected through paper-based questionnaires. Univariable logistic regression was used. Multivariable logistic regression was used to explore relationships between area type and other specific factors.Findings:Stillbirth incidence in S2 was 180/1,000 births. Stillbirth was associated with the following factors; no maternal education, previous stillbirth(s), prematurity, living in both semi-rural and rural settings, and having extended time periods between rupture of membranes and delivery. Findings of the multivariable analysis (S1 and S2) indicated that the odds of stillbirth, for those living in a rural area, were further exacerbated in those mothers who had no education, lived in a shack, or had any maternal disease.Interpretation:This research identifies the gravity of this situation in this area and highlights the need for action. Further understanding of some of the findings and exploration into associations are required to inform intervention development.Funding:This collaboration was partially supported by funding from Health and Care Research Wales.

Background: Parents of children with intellectual disability are 1.5–2 times more likely than other parents to report mental health difficulties. There is a lack of clinically effective and cost-effective group well-being interventions designed for family carers of young children with intellectual disability. Aim: To examine the feasibility of a randomised controlled trial of the clinical effectiveness and cost-effectiveness of the Early Positive Approaches to Support (E-PAtS) intervention. Design: A feasibility study (including randomisation of families into a two-arm trial), questionnaires to assess the feasibility of proposed outcome measures (including resource use and health-related quality of life) and practitioner/family carer interviews. An additional question was included in an online UK survey of families, conducted by the research team to assess usual practice, and a survey of provider organisations. Setting: Families recruited from community contexts (i.e. third sector, local authority services, special schools) and self-referral. The E-PAtS intervention was delivered by trained community-based providers. Participants: Families with at least one child aged 1.5–5 years with an intellectual disability. At least one parent had to have English-language ability (spoken) for E-PAtS programme participation and participants had to provide informed consent. Interventions: E-PAtS intervention – two caregivers from each family invited to eight 2.5-hour group sessions with usual practice. Usual practice – other support provided to the family, including other parenting support. Objectives: To assess randomisation willingness/feasibility, recruitment of providers/parents, retention, usual practice, adherence, fidelity and feasibility of proposed outcome measures (including the Warwick–Edinburgh Mental Well-Being Scale as the proposed primary outcome measure, and parent anxiety/depression, parenting, family functioning/relationships, child behavioural/emotional problems and adaptive skills, child and parent quality of life, and family services receipt as the proposed secondary outcome measures). Results: Seventy-four families (95 carers) were recruited from three sites (with 37 families allocated to the intervention). From referrals, the recruitment rate was 65% (95% confidence interval 56% to 74%). Seventy-two per cent of families were retained at the 12-month follow-up (95% confidence interval 60% to 81%). Exploratory regression analysis showed that the mean Warwick–Edinburgh Mental Well-Being Scale well-being score was 3.96 points higher in the intervention group (95% confidence interval –1.39 to 9.32 points) at 12 months post randomisation. High levels of data completeness were achieved on returned questionnaires. Interviews (n = 25) confirmed that (1) recruitment, randomisation processes and the intervention were acceptable to family carers, E-PAtS facilitators and community staff; (2) E-PAtS delivery were consistent with the logic model; and (3) researchers requesting consent in future for routine data would be acceptable. Recorded E-PAtS sessions demonstrated good fidelity (96% of components present). Adherence (i.e. at least one carer from the family attending five out of eight E-PAtS sessions) was 76%. Health-related quality-of-life and services receipt data were gathered successfully. An online UK survey to assess usual practice (n = 673) showed that 10% of families of young children with intellectual disability received any intervention over 12 months. A provider survey (n = 15) indicated willingness to take part in future research. Limitations: Obtaining session recordings for fidelity was difficult. Recruitment processes need to be reviewed to improve diversity and strategies are needed to improve primary outcome completion. Conclusions: Study processes were feasible. The E-PAtS intervention was well received and outcomes for families were positive. A barrier to future organisation participation is funding for intervention costs. A definitive trial to test the clinical effectiveness and cost-effectiveness of E-PAtS would be feasible. Trial registration: Current Controlled Trials ISRCTN70419473. Funding: This project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 10, No. 2. See the NIHR Journals Library website for further project information.

Background: Parents of children with intellectual disabilities are likely to experience poorer mental well-being and face challenges accessing support. Early Positive Approaches to Support (E-PAtS) is a group-based programme, co-produced with parents and professionals, based on existing research evidence and a developmental systems approach to support parental mental well-being. The aim of this study was to assess the feasibility of community service provider organisations delivering E-PAtS to parents/family caregivers of young children with intellectual disability, to inform a potential definitive randomised controlled trial of the effectiveness and cost-effectiveness of E-PAtS.Methods: This study was a feasibility cluster randomised controlled trial, with embedded process evaluation. Up to two parents/family caregivers of a child (18 months to

Abstract Background Autism spectrum disorder (ASD) is a common lifelong condition affecting 1 in 100 people. ASD affects how a person relates to others and the world around them. Difficulty responding to sensory information (noise, touch, movement, taste, sight) is common, and might include feeling overwhelmed or distressed by loud or constant low-level noise (e.g. in the classroom). Affected children may also show little or no response to these sensory cues. These ‘sensory processing difficulties’ are associated with behaviour and socialisation problems, and affect education, relationships, and participation in daily life. Sensory integration therapy (SIT) is a face-to-face therapy or treatment provided by trained occupational therapists who use play-based sensory-motor activities and the just-right challenge to influence the way the child responds to sensation, reducing distress, and improving motor skills, adaptive responses, concentration, and interaction with others. With limited research into SIT, this protocol describes in detail how the intervention will be defined and evaluated. Methods This is a two-arm pragmatic individually 1:1 randomised controlled trial with an internal pilot of SIT versus usual care for primary school aged children (aged 4 to 11 years) with ASD and sensory processing difficulties; 216 children will be recruited from multiple sources. Therapy will be delivered in clinics meeting full fidelity criteria for manualised SIT over 26 weeks (face-to-face sessions: two per week for 10 weeks, two per month for 2 months; telephone call: one per month for 2 months). Follow-up assessments will be completed at 6 and 12 months post-randomisation. Prior to recruitment, therapists will be invited to participate in focus groups/interviews to explore what is delivered as usual care in trial regions; carers will be invited to complete an online survey to map out their experience of services. Following recruitment, carers will be given diaries to record their contact with services. Following intervention, carer and therapist interviews will be completed. Discussion Results of this trial will provide high-quality evidence on the clinical and cost effectiveness of SIT aimed at improving behavioural, functional, social, educational, and well-being outcomes for children and well-being outcomes for carers and families. Trial registration ISRCTN14716440. Registered on 8 November 2016.

Background: Care homes are an increasingly important sector of care. Care home residents are particularly vulnerable to infections and are often prescribed antibiotics, driving antibiotic resistance. Probiotics may be a cheap and safe way to reduce antibiotic use. Efficacy and possible mechanisms of action are yet to be rigorously evaluated in this group. Objective: The objective was to evaluate efficacy and explore mechanisms of action of a daily oral probiotic combination in reducing antibiotic use and infections in care home residents. Design: This was a multicentre, parallel, individually randomised, placebo-controlled, double-blind trial, with qualitative evaluation and mechanistic studies. Setting: A total of 310 care home residents were randomised from 23 UK care homes (from December 2016 to May 2018). Participants: The participants were care home residents aged ≥ 65 years who were willing and able to give informed consent or, if they lacked capacity to consent, had a consultee to advise about participation on their behalf. Intervention: A daily capsule containing an oral probiotic combination of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12 (n = 155) or matched placebo (n = 155) for up to 1 year. Main outcome measures: The primary outcome was cumulative systemic antibiotic administration days for all-cause infections. Secondary outcomes included incidence and duration of infections, antibiotic-associated diarrhoea, quality of life, hospitalisations and the detection of resistant Enterobacterales cultured from stool samples (not exclusively). Methods: Participants were randomised (1 : 1) to receive capsules containing probiotic or matched placebo. Minimisation was implemented for recruiting care home and care home resident sex. Care home residents were followed up for 12 months with a review by a research nurse at 3 months and at 6–12 months post randomisation. Care home residents, consultees, care home staff and all members of the trial team, including assessors and statisticians, were blinded to group allocation. Results: Care home residents who were randomised to probiotic had a mean 12.9 cumulative systemic antibiotic administration days (standard error 1.49 days) (n = 152) and care home residents randomised to placebo had a mean 12.0 cumulative systemic antibiotic administration days (standard error 1.50 days) (n = 153) (adjusted incidence rate ratio = 1.13, 95% confidence interval 0.79 to 1.63; p = 0.495). There was no evidence of any beneficial effects on incidence and duration of infections, antibiotic-associated diarrhoea, quality of life, hospitalisations, the detection of resistant Enterobacterales cultured from stool samples or other secondary outcomes. There was no evidence that this probiotic combination improved blood immune cell numbers, subtypes or responses to seasonal influenza vaccination. Conclusions: Care home residents did not benefit from daily consumption of a combination of the probiotics Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12 to reduce antibiotic consumption. Limitations: Limitations included the following: truncated follow-up of some participants; higher than expected probiotics in stool samples at baseline; fewer events than expected meant that study power may have been lower than anticipated; standard infection-related definitions were not used; and findings are not necessarily generalisable because effects may be strain specific and could vary according to patient population. Future work: Future work could involve further rigorous efficacy, mechanisms and effectiveness trials of other probiotics in other population groups and settings regarding antibiotic use and susceptibility to and recovery from infections, in which potential harms should be carefully studied. Trial registration: Current Controlled Trials ISRCTN16392920. Funding: This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and NIHR partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 7. See the NIHR Journals Library website for further project information.

Aging is associated with a decline in many components of the immune system (immunosenescence). Probiotics may improve the immune response in older people. The objective was to determine the effect of the combination of two probiotic organisms [Lacticaseibacillus (previously known as Lactobacillus) rhamnosus GG (LGG) and Bifidobacterium animalis subsp. lactis, BB-12 (BB-12)] on a range of immune biomarkers measured in the blood of older people resident in care homes in the UK. In a randomized controlled trial, older people [aged 67–97 (mean 86) years] resident in care homes received the combination of LGG+BB-12 (1.3–1.6 × 109 CFU per day) or placebo for up to 12 months. Full blood count, blood immune cell phenotypes, plasma immune mediator concentrations, phagocytosis, and blood culture responses to immune stimulation were all measured. Response to seasonal influenza vaccination was measured in a subset of participants. Paired samples (i.e., before and after intervention) were available for 30 participants per group. LGG and BB-12 were more likely to be present in feces in the probiotic group and were present at higher numbers. There was no significant effect of the probiotics on components of the full blood count, blood immune cell phenotypes, plasma immune mediator concentrations, phagocytosis by neutrophils and monocytes, and blood culture responses to immune stimulation. There was an indication that the probiotics improved the response to seasonal influenza vaccination with significantly (p = 0.04) higher seroconversion to the A/Michigan/2015 vaccine strain in the probiotic group than in the placebo group (47 vs. 15%).

Background Normalisation process theory reports the importance of contextual integration in successfully embedding novel interventions, with recent propositions detailing the role that ‘plasticity’ of intervention components and ‘elasticity’ of an intended setting contribute. We report on the introduction of a clinical pathway assessing patient non-responsiveness to treatment for glaucoma and ocular hypertension. The aim of this study was to assess the feasibility of implementing the Cardiff Model of Glaucoma Care into hospital eye services, identifying any issues of acceptability for staff through the filter of normalisation process theory. Methods A prospective observational study was undertaken in four hospital eye services. This incorporated detailed qualitative semi-structured interviews with staff (n = 8) to gather their perceptions on the intervention’s usefulness and practicality. In addition, observational field notes of patient and staff consultations (n = 88) were collected, as well as broader organisational observations from within the research sites (n = 52). Data collection and analysis was informed by the normalisation process theory framework. Results Staff reported the pathway led to beneficial knowledge on managing patient treatment, but the model was sometimes perceived as overly prescriptive. This perception varied significantly based on the composition of clinics in relation to staff experience, staff availability and pre-existing clinical structures. The most commonly recounted barrier came in contextually integrating into sites where wider administrative systems were inflexible to intervention components. Conclusions Flexibility will be the key determinant of whether the clinical pathway can progress to wider implementation. Addressing the complexity and variation associated with practice between clinics required a remodelling of the pathway to maintain its central benefits but enhance its plasticity. Our study therefore helps to confirm propositions developed in relation to normalisation process theory, contextual integration, intervention plasticity, and setting elasticity. This enables the transferability of findings to healthcare settings other than ophthalmology, where any novel intervention is implemented.

Idiopathic drop attacks are falls to the floor, without warning, and without loss of consciousness, for which the cause is uncertain. They are poorly studied but recent research suggests that many idiopathic drop attacks may be usefully considered within the spectrum of functional neurological disorder (FND).The aim of this study was to test a cognitive behavioural model of idiopathic drop attacks, in order to inform formulation and treatment. Interviews and diaries were completed by seven individuals experiencing drop attacks, and were analysed using a grounded theory qualitative data approach.Through the coding and synthesis of data into themes, a proposed cognitive behavioural model was identified, with a main precipitating event in all cases being a fall related to another cause, such as a mechanical fall or a fall due to medical reasons. Additional precipitating factors identified included situational triggers, high levels of stress, and dissociation. A maintaining cycle of thoughts, emotion and behaviour is outlined.Our proposed theory is consistent with current cognitive behavioural models of FND. A cognitive behavioural understanding of drop attacks when considered part of FND aids formulation in clinical practice, and suggests that cognitive behavioural therapy interventions for FND may also be applicable in this population.

Public perceptions of pandemic viral threats and government policies can influence adherence to containment, delay, and mitigation policies such as physical distancing, hygienic practices, use of physical barriers, uptake of testing, contact tracing, and vaccination programs. The UK COVID-19 Public Experiences (COPE) study aims to identify determinants of health behaviour using the Capability, Opportunity, Motivation (COM-B) model using a longitudinal mixed-methods approach. Here, we provide a detailed description of the demographic and self-reported health characteristics of the COPE cohort at baseline assessment, an overview of data collected, and plans for follow-up of the cohort. The COPE baseline survey was completed by 11,113 UK adult residents (18+ years of age). Baseline data collection started on the 13th of March 2020 (10-days before the introduction of the first national COVID-19 lockdown in the UK) and finished on the 13th of April 2020. Participants were recruited via the HealthWise Wales (HWW) research registry and through social media snowballing and advertising (Facebook®, Twitter®, Instagram®). Participants were predominantly female (69%), over 50 years of age (68%), identified as white (98%), and were living with their partner (68%). A large proportion (67%) had a college/university level education, and half reported a pre-existing health condition (50%). Initial follow-up plans for the cohort included in-depth surveys at 3-months and 12-months after the first UK national lockdown to assess short and medium-term effects of the pandemic on health behaviour and subjective health and well-being. Additional consent will be sought from participants at follow-up for data linkage and surveys at 18 and 24-months after the initial UK national lockdown. A large non-random sample was recruited to the COPE cohort during the early stages of the COVID-19 pandemic, which will enable longitudinal analysis of the determinants of health behaviour and changes in subjective health and well-being over the course of the pandemic.

Antibiotic treatment failure is used as an outcome in randomised trials and observational studies of antibiotic treatment strategies and may comprise different events that indicate failure to achieve a desired clinical response. However, the lack of a universally recognised definition has led to considerable variation in the types of events included. We undertook a systematic review of published studies investigating antibiotic treatment strategies for common uncomplicated infections, aiming to describe variation in terminology and components of the antibiotic treatment failure outcomes. We searched Medline, Embase, and the Cochrane Central Register of Clinical trials for English language studies published between January 2010 and January 2021. The population of interest was ambulatory patients seen in primary care or outpatient settings with respiratory tract (RTI), urinary tract (UTI), or skin and soft tissue infection (SSTI), where different antibiotic prescribing strategies were compared, and the outcome was antibiotic treatment failure. We narratively summarised key features from eligible studies and used frequencies and proportions to describe terminology, components, and time periods used to ascertain antibiotic treatment failure outcomes. Database searches identified 2967 unique records, from which 36 studies met our inclusion criteria. This included 10 randomised controlled trials and 26 observational studies, with 20 studies of RTI, 12 of UTI, 4 of SSTI, and 2 of both RTI and SSTI. We identified three key components of treatment failure definitions: prescription changes, escalation of care, and change in clinical condition. Prescription changes were most popular in studies of UTI, while changes in clinical condition were most common in RTI and SSTI studies. We found substantial variation in the definition of antibiotic treatment failure in included studies, even amongst studies of the same infection subtype and study design. Considerable further work is needed to develop a standardised definition of antibiotic treatment failure in partnership with patients, clinicians, and relevant stakeholders.

Introduction Chronic lung disease of prematurity (CLD), also known as bronchopulmonary dysplasia (BPD), is a cause of significant respiratory morbidity in childhood and beyond. Coupled with lung immaturity, infections (especially by Ureaplasma spp) are implicated in the pathogenesis of CLD through promotion of pulmonary inflammation. Azithromycin, which is a highly effective against Ureaplasma spp also has potent anti-inflammatory properties. Thus, azithromycin therapy may improve respiratory outcomes by targeting infective and inflammatory pathways. Previous trials using macrolides have not been sufficiently powered to definitively assess CLD rates. To address this, the azithromycin therapy for chronic lung disease of prematurity (AZTEC) trial aims to determine if a 10-day early course of intravenous azithromycin improves rates of survival without CLD when compared with placebo with an appropriately powered study.Methods and analysis 796 infants born at less than 30 weeks’ gestational age who require at least 2 hours of continuous respiratory support within the first 72 hours following birth are being enrolled by neonatal units in the UK. They are being randomised to receive a double-blind, once daily dose of intravenous azithromycin (20 mg/kg for 3 days, followed by 10 mg/kg for a further 7 days), or placebo. CLD is being assessed at 36 weeks’ PMA. Whether colonisation with Ureaplasma spp prior to randomisation modifies the treatment effect of azithromycin compared with placebo will also be investigated. Secondary outcomes include necrotising enterocolitis, intraventricular/cerebral haemorrhage, retinopathy of prematurity and nosocomial infections, development of antibiotic resistance and adverse reactions will be monitored.Ethics and dissemination Ethics permission has been granted by Wales Research Ethics Committee 2 (Ref 18/WA/0199), and regulatory permission by the Medicines and Healthcare Products Regulatory Agency (Clinical Trials Authorisation reference 21323/0050/001–0001). The study is registered on ISRCTN (ISRCTN11650227). The study is overseen by an independent Data Monitoring Committee and an independent Trial Steering Committee. We shall disseminate our findings via national and international peer-reviewed journals, and conferences. A summary of the findings will also be posted on the trial website.

Introduction As of 2015, as part of the implementation of the Welsh Government primary care plan and primary care clusters, the Welsh Government has encouraged non-medical healthcare professionals working in primary care to train as independent prescribers (IPs).Objectives This research aimed to identify the number of NMIPs in primary care in Wales and describe their prescribing trend of items between 2011 and 2018, in order to compare their prescribing pattern before and after the implementation of primary care clusters for Wales.Design Retrospective secondary data analysis and interrupted time series analysis in order to compare prescribing by non-medical independent prescribers (NMIPs) preimplementation and postimplementation of primary care clusters across Wales.Results Over the study period, 600 NMIPs (nurses n=474 and pharmacists n=104) had prescribed at least one item. The number of nurse IPs increased by 108% and pharmacists by 325% (pharmacists had the largest increase between July 2015 and March 2018). The number of items prescribed by NMIPs increased over time by an average of 1380 per month (95% CI 904 to 1855, p

Objectives To assess the acceptability and feasibility of using a theory-based electronic learning intervention designed to support appropriate antibiotic prescribing by nurse and pharmacist independent prescribers for patients presenting with common, acute, uncomplicated self-limiting respiratory tract infections (RTIs).Design Experimental with mixed methods; preintervention and postintervention online surveys and semistructured interviews.Setting Primary care settings across the UK.Participants 11 nurse and 4 pharmacist prescribers.Intervention A theory-based brief interactive animation electronic learning activity comprised a consultation scenario by a prescriber with an adult presenting with a common, acute, uncomplicated self-limiting RTI to support a ‘no antibiotic prescribing strategy’.Outcome measures Recruitment, response and attrition rates were assessed. The overall usefulness of the intervention was assessed by analysing prescribers’ self-reported confidence and knowledge in treating patients with RTIs before and after undertaking the intervention, and views on the relevance of the intervention to their work. Acceptability of the intervention was assessed in semistructured interviews. The feasibility of data collection methods was assessed by recording the number of study components completed by prescribers.Results 15 prescribers (maximum sample size) consented and completed all four stages of the study. Prescribers reported high to very high levels of confidence and knowledge preintervention and postintervention, with slight postintervention increases in communicating with patients and a slight reduction in building rapport. Qualitative findings supported quantitative findings; prescribers were reassured of their own practice which in turn increased their confidence and knowledge in consultations. The information in the intervention was not new to prescribers but was applicable and useful to consolidate learning and enable self-reflection. Completing the e-learning intervention was acceptable to prescribers.Conclusions It was feasible to conduct the study. The intervention was acceptable and useful to prescribers. Future work will add complex clinical content in the intervention before conducting a full trial.

Background: Most patients presenting with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in primary care are prescribed antibiotics, but these may not be beneficial, and they can cause side effects and increase the risk of subsequent resistant infections. Point-of-care tests (POCTs) could safely reduce inappropriate antibiotic prescribing and antimicrobial resistance. Objective: To determine whether or not the use of a C-reactive protein (CRP) POCT to guide prescribing decisions for AECOPD reduces antibiotic consumption without having a negative impact on chronic obstructive pulmonary disease (COPD) health status and is cost-effective. Design: A multicentre, parallel-arm, randomised controlled open trial with an embedded process, and a health economic evaluation. Setting: General practices in Wales and England. A UK NHS perspective was used for the economic analysis. Participants: Adults (aged ≥ 40 years) with a primary care diagnosis of COPD, presenting with an AECOPD (with at least one of increased dyspnoea, increased sputum volume and increased sputum purulence) of between 24 hours’ and 21 days’ duration. Intervention: CRP POCTs to guide antibiotic prescribing decisions for AECOPD, compared with usual care (no CRP POCT), using remote online randomisation. Main outcome measures: Patient-reported antibiotic consumption for AECOPD within 4 weeks post randomisation and COPD health status as measured with the Clinical COPD Questionnaire (CCQ) at 2 weeks. For the economic evaluation, patient-reported resource use and the EuroQol-5 Dimensions were included. Results: In total, 653 participants were randomised from 86 general practices. Three withdrew consent and one was randomised in error, leaving 324 participants in the usual-care arm and 325 participants in the CRP POCT arm. Antibiotics were consumed for AECOPD by 212 out of 274 participants (77.4%) and 150 out of 263 participants (57.0%) in the usual-care and CRP POCT arm, respectively [adjusted odds ratio 0.31, 95% confidence interval (CI) 0.20 to 0.47]. The CCQ analysis comprised 282 and 281 participants in the usual-care and CRP POCT arms, respectively, and the adjusted mean CCQ score difference at 2 weeks was 0.19 points (two-sided 90% CI –0.33 to –0.05 points). The upper limit of the CI did not contain the prespecified non-inferiority margin of 0.3. The total cost from a NHS perspective at 4 weeks was £17.59 per patient higher in the CRP POCT arm (95% CI –£34.80 to £69.98; p = 0.408). The mean incremental cost-effectiveness ratios were £222 per 1% reduction in antibiotic consumption compared with usual care at 4 weeks and £15,251 per quality-adjusted life-year gained at 6 months with no significant changes in sensitivity analyses. Patients and clinicians were generally supportive of including CRP POCT in the assessment of AECOPD. Conclusions: A CRP POCT diagnostic strategy achieved meaningful reductions in patient-reported antibiotic consumption without impairing COPD health status or increasing costs. There were no associated harms and both patients and clinicians valued the diagnostic strategy. Future work: Implementation studies that also build on our qualitative findings could help determine the effect of this intervention over the longer term. Trial registration: Current Controlled Trials ISRCTN24346473. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 15. See the NIHR Journals Library website for further project information.

Background: Most people with sore throat do not benefit from antibiotic treatment, but nearly three-quarters of those presenting in primary care are prescribed antibiotics. A test that is predictive of bacterial infection could help guide antibiotic prescribing. Calprotectin is a biomarker of neutrophilic inflammation, and may be a useful marker of bacterial throat infections. Aim: To assess the feasibility of measuring calprotectin from throat swabs, and assess whether individuals with sore throats likely to be caused by streptococcal infections have apparently higher throat calprotectin levels than other individuals with sore throat and healthy volunteers. Design & setting: A proof of concept case–control study was undertaken, which compared primary care patients with sore throats and healthy volunteers. Method: Baseline characteristics and throat swabs were collected from 30 primary care patients with suspected streptococcal sore throat, and throat swabs were taken from 10 volunteers without sore throat. Calprotectin level determination and rapid antigen streptococcal testing were conducted on the throat swab eluents. Calprotectin levels in the following groups were compared: volunteers without a sore throat; all patients with a sore throat; patients with a sore throat testing either negative or positive for streptococcal antigen; and those with lower and higher scores on clinical prediction rules for streptococcal sore throat. Results: Calprotectin was detected in all throat swab samples. Mean calprotectin levels were numerically higher in patients with sore throat compared with healthy volunteers, and sore throat patients who had group A streptococci antigen detected compared with those who did not. Conclusion: Calprotectin can be measured from throat swab samples and levels are consistent with the hypothesis that streptococcal infection leads to higher throat calprotectin levels. This hypothesis will be tested in a larger study.

The author argues reading, hearing, and then composing musical lyrics involving grammatical concerns can help college writing students to edit more effectively for a song's grammar topic. Explaining that the songs need to offer specific advice, such as how to both spot and correct the grammatical problem, the writer offers lyrical examples and provides scholarly evidence for this approach. The essay explains what Grammar Jam is, why music can work, and how to use the tactic in the classroom.

Purpose: Process evaluations generate important data on the extent to which interventions are delivered as intended. However, the tendency to focus only on assessment of pre-specified structural aspects of fidelity has been criticised for paying insufficient attention to implementation processes and how intervention-context interactions influence programme delivery. This paper reports findings from a process evaluation nested within a randomised controlled trial of the Strengthening Families Programme 10–14 (SFP 10–14) in Wales, UK. It uses Extended Normalisation Process Theory to theorise how interaction between SFP 10–14 and local delivery systems - particularly practitioner commitment/capability and organisational capacity - influenced delivery of intended programme activities: fidelity (adherence to SFP 10–14 content and implementation requirements); dose delivered; dose received (participant engagement); participant recruitment and reach (intervention attendance). Methods: A mixed methods design was utilised. Fidelity assessment sheets (completed by practitioners), structured observation by researchers, and routine data were used to assess: adherence to programme content; staffing numbers and consistency; recruitment/retention; and group size and composition. Interviews with practitioners explored implementation processes and context. Results: Adherence to programme content was high - with some variation, linked to practitioner commitment to, and understanding of, the intervention’s content and mechanisms. Variation in adherence rates was associated with the extent to which multi-agency delivery team planning meetings were held. Recruitment challenges meant that targets for group size/composition were not always met, but did not affect adherence levels or family engagement. Targets for staffing numbers and consistency were achieved, though capacity within multi-agency networks reduced over time. Conclusions: Extended Normalisation Process Theory provided a useful framework for assessing implementation and explaining variation by examining intervention-context interactions. Findings highlight the need for process evaluations to consider both the structural and process components of implementation to explain whether programme activities are delivered as intended and why.

Abstract Background Findings suggest approximately one in six people with intellectual disability engage in ‘challenging behaviours’, which include aggression towards others/property and self-injurious actions. In residential settings, actions of staff members can make challenging behaviours more likely to occur, or make these behaviours worse. In particular, negative attitudes from members of staff and lack of understanding about the reasons for challenging behaviour are contributory factors. ‘Who’s Challenging Who?’ (WCW) training is designed to emphasise the role of staff in residential settings as a challenge also to people with intellectual disability. The course is delivered jointly by a trainer with intellectual disability who has been labelled as having challenging behaviour, along with a trainer without intellectual disability. Methods This is a cluster randomised two-arm trial of WCW training versus a waiting list control. Overall, 118 residential settings will be recruited and randomised on a 1:1 ratio. Within each setting, two members of staff will be invited to take part in the trial. Participants will complete assessments at baseline and at 6 and 20 weeks. WCW is a half day initial training course with some follow-on coaching to ensure implementation. The primary outcome is changes in staff empathy towards people with challenging behaviour. Secondary outcomes at the staff level include confidence, attitudes and work-related well-being. Secondary outcomes at the residential setting level include recorded incidents of aggressive challenging behaviour, and use of any restrictive practices. Discussion If the results of the cluster randomised trial are positive, we will disseminate the findings widely and make all training manuals and materials freely available for anyone in intellectual disability services (and beyond) to use. Our training approach may have wider implications in other areas of social care. It may also provide a generally applicable model for how to train people with intellectual disability to act as co-trainers in intellectual disability social care settings. People with intellectual disability and challenging behaviour have already been involved centrally with the design, development and pilot evaluation of WCW and will also be fully involved throughout this trial. Trial registration Registered on the International Standard Randomised Controlled Trial Number registry on 8th December 2015: ISRCTN53763600 .

Abstract Background Most patients presenting with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in primary care are prescribed an antibiotic, which may not always be appropriate and may cause harm. C-reactive protein (CRP) is an acute-phase biomarker that can be rapidly measured at the point of care and may predict benefit from antibiotic treatment in AECOPD. It is not clear whether the addition of a CRP point-of-care test (POCT) to clinical assessment leads to a reduction in antibiotic consumption without having a negative impact on COPD health status. Methods/design This is a multicentre, individually randomised controlled trial (RCT) aiming to include 650 participants with a diagnosis of AECOPD in primary care. Participants will be randomised to be managed according to usual care (control) or with the addition of a CRP POCT to guide antibiotic prescribing. Antibiotic consumption for AECOPD within 4 weeks post randomisation and COPD health status (total score) measured by the Clinical COPD Questionnaire (CCQ) at 2 weeks post randomisation will be co-primary outcomes. Primary analysis (by intention-to-treat) will determine differences in antibiotic consumption for superiority and COPD health status for non-inferiority. Secondary outcomes include: COPD health status, CCQ domain scores, use of other COPD treatments (weeks 1, 2 and 4), EQ-5D utility scores (weeks 1, 2 and 4 and month 6), disease-specific, health-related quality of life (HRQoL) at 6 months, all-cause antibiotic consumption (antibiotic use for any condition) during first 4 weeks post randomisation, total antibiotic consumption (number of days during first 4 weeks of antibiotic consumed for AECOPD/any reason), antibiotic prescribing at the index consultation and during following 4 weeks, adverse effects over the first 4 weeks, incidence of pneumonia (weeks 4 and 6 months), health care resource use and cost comparison over the 6 months following randomisation. Prevalence and resistance profiles of bacteria will be assessed using throat and sputum samples collected at baseline and 4-week follow-up. A health economic evaluation and qualitative process evaluation will be carried out. Discussion If shown to be effective (i.e. leads to a reduction in antibiotic use with no worse COPD health status), the use of the CRP POCT could lead to better outcomes for patients with AECOPD and help reduce selective pressures driving the development of antimicrobial resistance. PACE will be one of the first studies to evaluate the cost-effectiveness of a POCT biomarker to guide clinical decision-making in primary care on patient-reported outcomes, antibiotic prescribing and antibiotic resistance for AECOPD. Trial registration ISRCTN registry, ID: ISRCTN24346473 . Registered on 20 August 2014.

Abstract The introduction of an exotic species may alter food webs within the ecosystem and significantly affect the biodiversity of indigenous species at different trophic levels. It has been postulated that recent introduction of the brown marmorated stinkbug (Halyomorpha halys (Stål)) represents an evolutionary trap for native parasitoids, as they accept H. halys egg masses as a host but produce no viable progeny. Interspecific interactions between European egg parasitoid, Trissolcus cultratus (Mayr), and an Asian parasitoid, Trissolcus japonicus (Ashmead), were assessed by providing egg masses to T. cultratus at various time intervals following the initial parasitization by T. japonicus. The suitability of the host for the parasitoid development was re‐assessed by providing T. cultratus with fresh and frozen egg masses of various ages. The likelihood of T. cultratus being able to attack previously parasitized egg masses was determined by assessing the duration of egg mass guarding behavior by T. japonicus following parasitization. The results of experiments examining the interspecific interactions between a native European egg parasitoid, T. cultratus, and an Asian parasitoid, T. japonicus (a candidate for the biological control of H. halys), showed that the native species can act as facultative hyperparasitoid of the exotic one. Although this is only possible during certain stages of T. japonicus development, the presence of the introduced parasitoid may reduce the impact of the evolutionary trap for indigenous parasitoid species. There is a possibility that the occurrence of facultative hyperparasitism between scelionid parasitoids associated with stinkbugs is common. This resulting intraguild predation could promote conservation and stabilization of natural communities by impacting the diversity and population dynamics of native stinkbugs and their parasitoids (e.g., by allowing native parasitoids to avoid wasting reproductive effort on unsuitable hosts), or reduce success of biological control programs (e.g., by reducing the population size of the exotic parasitoids).