The cost-effectiveness of procalcitonin for guiding antibiotic prescribing in individuals hospitalized with COVID-19: part of the PEACH study.

BACKGROUND: Many hospitals introduced procalcitonin (PCT) testing to help diagnose bacterial coinfection in individuals with COVID-19, and guide antibiotic decision-making during the COVID-19 pandemic in the UK. OBJECTIVES: Evaluating cost-effectiveness of using PCT to guide antibiotic decisions in individuals hospitalized with COVID-19, as part of a wider research programme. METHODS: Retrospective individual-level data on patients hospitalized with COVID-19 were collected from 11 NHS acute hospital Trusts and Health Boards from England and Wales, which varied in their use of baseline PCT testing during the first COVID-19 pandemic wave. A matched analysis (part of a wider analysis reported elsewhere) created groups of patients whose PCT was/was not tested at baseline. A model was created with combined decision tree/Markov phases, parameterized with quality-of-life/unit cost estimates from the literature, and used to estimate costs and quality-adjusted life years (QALYs). Cost-effectiveness was judged at a £20 000/QALY threshold. Uncertainty was characterized using bootstrapping. RESULTS: People who had baseline PCT testing had shorter general ward/ICU stays and spent less time on antibiotics, though with overlap between the groups' 95% CIs. Those with baseline PCT testing accrued more QALYs (8.76 versus 8.62) and lower costs (£9830 versus £10 700). The point estimate was baseline PCT testing being dominant over no baseline testing, though with uncertainty: the probability of cost-effectiveness was 0.579 with a 1 year horizon and 0.872 with a lifetime horizon. CONCLUSIONS: Using PCT to guide antibiotic therapy in individuals hospitalized with COVID-19 is more likely to be cost-effective than not, albeit with uncertainty.

Short-term risk prediction after major lower limb amputation: PERCEIVE study.

BACKGROUND: The accuracy with which healthcare professionals (HCPs) and risk prediction tools predict outcomes after major lower limb amputation (MLLA) is uncertain. The aim of this study was to evaluate the accuracy of predicting short-term (30 days after MLLA) mortality, morbidity, and revisional surgery. METHODS: The PERCEIVE (PrEdiction of Risk and Communication of outcomE following major lower limb amputation: a collaboratIVE) study was launched on 1 October 2020. It was an international multicentre study, including adults undergoing MLLA for complications of peripheral arterial disease and/or diabetes. Preoperative predictions of 30-day mortality, morbidity, and MLLA revision by surgeons and anaesthetists were recorded. Probabilities from relevant risk prediction tools were calculated. Evaluation of accuracy included measures of discrimination, calibration, and overall performance. RESULTS: Some 537 patients were included. HCPs had acceptable discrimination in predicting mortality (931 predictions; C-statistic 0.758) and MLLA revision (565 predictions; C-statistic 0.756), but were poor at predicting morbidity (980 predictions; C-statistic 0.616). They overpredicted the risk of all outcomes. All except three risk prediction tools had worse discrimination than HCPs for predicting mortality (C-statistics 0.789, 0.774, and 0.773); two of these significantly overestimated the risk compared with HCPs. SORT version 2 (the only tool incorporating HCP predictions) demonstrated better calibration and overall performance (Brier score 0.082) than HCPs. Tools predicting morbidity and MLLA revision had poor discrimination (C-statistics 0.520 and 0.679). CONCLUSION: Clinicians predicted mortality and MLLA revision well, but predicted morbidity poorly. They overestimated the risk of mortality, morbidity, and MLLA revision. Most short-term risk prediction tools had poorer discrimination or calibration than HCPs. The best method of predicting mortality was a statistical tool that incorporated HCP estimation.

Understanding the support experiences of families of children with autism and sensory processing difficulties: A qualitative study.

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.

Development of Core Outcome Sets for People Undergoing Major Lower Limb Amputation for Complications of Peripheral Vascular Disease.

OBJECTIVE: Every year, thousands of patients with peripheral vascular disease undergo major lower limb amputation. Despite this, evidence for optimal management is weak. Core outcome sets capture consensus on the most important outcomes for a patient group to improve the consistency and quality of research. The aim was to define short and medium term core outcome sets for studies involving patients undergoing major lower limb amputation. METHODS: A systematic review of the literature and focus groups involving patients, carers, and healthcare professionals were used to derive a list of potential outcomes. Findings informed a three round online Delphi consensus process, where outcomes were rated for both short and medium term studies. The results of the Delphi process were discussed at a face to face consensus meeting, and recommendations were made for each core outcome set. RESULTS: A systematic review revealed 45 themes to carry forward to the consensus survey. These were supplemented by a further five from focus groups. The consensus survey received responses from 123 participants in round one, and 91 individuals completed all three rounds. In the final round, nine outcomes were rated as "core" for short term studies and a further nine for medium term studies. Wound infection and healing were rated as "core" for both short and medium term studies. Outcomes related to mortality, quality of life, communication, and additional healthcare needs were also rated as "core" for short term studies. In medium term studies, outcomes related to quality of life, mobility, and social integration/independence were rated as "core". The face to face stakeholder meeting ratified inclusion of all outcomes from the Delphi and suggested that deterioration of the other leg and psychological morbidity should also be reported for both short and medium term studies. CONCLUSION: Consensus was established on 11 core outcomes for short and medium term studies. It is recommended that all future studies involving patients undergoing major lower limb amputation should report these outcomes.

Pragmatic RAndomised controlled trial of a trauma-focused guided self-help Programme versus InDividual trauma-focused cognitive Behavioural therapy for post-traumatic stress disorder (RAPID): trial protocol.

BACKGROUND: There is good evidence that trauma-focused therapies for Post-Traumatic Stress Disorder are effective. However, they are not always feasible to deliver due a shortage of trained therapists and demands on the patient. An online trauma-focused Guided Self-Help (GSH) programme which could overcome these barriers has shown promise in a pilot study. This study will be the first to evaluate GSH against standard face-to-face therapy to assess its suitability for use in the NHS. METHODS: The study is a large-scale multi-centre pragmatic randomised controlled non-inferiority trial, with assessors masked to treatment allocation. One hundred and ninety-two participants will be randomly allocated to receive either face-to-face trauma-focused cognitive behaviour therapy (TFCBT) or trauma-focused online guided self-help (GSH). The primary outcome will be the severity of symptoms of PTSD over the previous week as measured by the Clinician Administered PTSD Scale for DSM5 (CAPS-5) at 16 weeks post-randomisation. Secondary outcome measures include PTSD symptoms over the previous month as measured by the CAPS-5 at 52 weeks plus the Impact of Event Scale - revised (IES-R), Work and Social Adjustment Scale (WSAS), Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder-7 (GAD-7), Alcohol Use Disorders Test (AUDIT-O), Multidimensional Scale for Perceived Social Support (MSPSS), short Post-Traumatic Cognitions Inventory (PTCI), Insomnia Severity Index (ISI) and General Self Efficacy Scale (GSES) measured at 16 and 52 weeks post-randomisation. Changes in health-related quality of life will be measured by the EQ-5D and the level of healthcare resource utilisation for health economic analysis will be determined by an amended version of the Client Socio-Demographic and Service Receipt Inventory European Version. The Client Satisfaction Questionnaire (CSQ) will be collected at 16 weeks post-randomisation to evaluate treatment satisfaction. DISCUSSION: This study will be the first to compare online GSH with usual face-to-face therapy for PTSD. The strengths are that it will test a rigorously developed intervention in a real world setting to inform NHS commissioning. The potential challenges of delivering such a pragmatic study may include participant recruitment, retention and adherence, therapist retention, and fidelity of intervention delivery. TRIAL REGISTRATION: ISRCTN13697710 registered on 20/12/2016.

Clinicians' views and experiences of interventions to enhance the quality of antibiotic prescribing for acute respiratory tract infections.

BACKGROUND: Evidence shows a high rate of unnecessary antibiotic prescriptions in primary care in Europe and the United States. Given the costs of widespread use and associated antibiotic resistance, reducing inappropriate use is a public health priority. OBJECTIVE: We aimed to explore clinicians' experiences of training in communication skills and use of a patient booklet and/or a C-reactive protein (CRP) point-of-care test to reduce antibiotic prescribing for acute respiratory tract infections (RTIs). DESIGN: We used a qualitative research approach, interviewing clinicians who participated in a randomised controlled trial (RCT) testing two contrasting interventions. PARTICIPANTS: General practice clinicians in Belgium, England, The Netherlands, Poland, Spain and Wales participated in the study. APPROACH: Sixty-six semi-structured interviews were transcribed verbatim, translated into English where necessary, and analysed using thematic and framework analysis. KEY RESULTS: Clinicians from all countries attributed benefits for themselves and their patients to using both interventions. Clinicians reported that the communication skills training and use of the patient booklet gave them greater confidence in addressing patient expectations for an antibiotic by providing answers to common questions and supporting the clinician's own explanations. Clinicians felt the booklet could be used for a variety of patients and for different types of infections. The CRP test was viewed as a tool to decrease diagnostic uncertainty, to support non-prescription decisions, and to reassure patients, but was only necessary when clinicians were uncertain about the need for antibiotics. CONCLUSION: Providing clinicians with training and support tools for use in practice was received positively and was valued by clinicians across countries. Interventions seemed to have influenced behaviour by increasing clinician knowledge about illness severity and prescribing, increasing confidence in making non-prescribing decisions when antibiotics were unnecessary, and enabling clinicians to anticipate positive outcomes when making such decisions. Addressing such determinants of behaviour change enabled interventions to be relevant for clinicians working across different contexts.

Trust, openness and continuity of care influence acceptance of antibiotics for children with respiratory tract infections: a four country qualitative study.

BACKGROUND: Clinician-parent interaction and health system influences on parental acceptance of prescribing decisions for children with respiratory tract infections (RTIs) may be important determinants of antibiotic use. OBJECTIVE: To achieve a deeper understanding of parents' acceptance, or otherwise, of clinicians' antibiotic prescribing decisions for children with RTIs. METHODS: Qualitative interviews with parents of child patients who had recently consulted in primary care with a RTI in four European countries, with a five-stage analytic framework approach (familiarization, developing a thematic framework from interview questions and emerging themes, indexing, charting and interpretation). RESULTS: Fifty of 63 parents accepted clinicians' management decisions, irrespective of antibiotic prescription. There were no notable differences between networks. Parents ascribed their acceptance to a trusting and open clinician-patient relationship, enhanced through continuity of care, in which parents felt able to express their views. There was a lack of congruence about antibiotics between parents and clinicians in 13 instances, mostly when parents disagreed about clinicians' decision to prescribe (10 accounts) rather than objecting to withholding antibiotics (three accounts). All but one parent adhered to the prescribing decision, although some modified how the antibiotic was administered. CONCLUSIONS: Parents from contrasting countries indicated that continuity of care, open communication in consultations and clinician-patient trust was important in acceptance of management of RTI in their children and in motivating adherence. Interventions to promote appropriate antibiotic use in children should consider a focus on eliciting parents' perspectives and promoting and building on continuity of care within a trusting clinician-patient relationship.

Rehabilitation experiences following major lower limb amputation due to complications of vascular disease: a UK qualitative study.

PURPOSE: Rehabilitation experiences of lower limb amputees with poorer physical health have not been fully explored. This study aimed to qualitatively explore experiences of rehabilitation amongst patients who had recently undergone amputation due to complications of vascular disease. METHODS: Semi-structured, face-to-face interviews were conducted with 14 patients participating in the PLACEMENT randomised controlled feasibility trial (ISRCTN: 85710690; EudraCT: 2016-003544-37), which investigated the effectiveness of using a perineural catheter for postoperative pain relief following major lower limb amputation. Framework analysis was used to identify key themes and compare participant data. FINDINGS: Three main themes and corresponding sub-themes were identified: (i) other patients as inspiration; (ii) other patients as competition; and (iii) imagined futures. Perceptions relating to other patients played a key role in rehabilitation, providing a source of motivation, support, and competition. Participants' imagined futures were uncertain, and this was compounded by a lack of information and delays in equipment and/or adaptations. CONCLUSIONS: Findings highlight the importance of fellow patients in supporting rehabilitation following lower limb amputation. Enabling contact with other patients should thus be a key consideration when planning rehabilitation. There is a clear unmet need for realistic information relating to post-amputation recovery, tailored to the needs of individual patients.

There is a clear unmet need for patient information on rehabilitation following major lower limb amputation.Information about future mobility - particularly prosthesis use - should be realistic and individually tailored.The key role of fellow patients should be fully considered when planning post-amputation rehabilitation.

Exploring critical intervention features and trial processes in the evaluation of sensory integration therapy for autistic children.

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.

Integrating qualitative research within a clinical trials unit: developing strategies and understanding their implementation in contexts.

BACKGROUND/AIMS: The value of using qualitative methods within clinical trials is widely recognised. How qualitative research is integrated within trials units to achieve this is less clear. This paper describes the process through which qualitative research has been integrated within Cardiff University's Centre for Trials Research (CTR) in Wales, UK. We highlight facilitators of, and challenges to, integration. METHODS: We held group discussions on the work of the Qualitative Research Group (QRG) within CTR. The content of these discussions, materials for a presentation in CTR, and documents relating to the development of the QRG were interpreted at a workshop attended by group members. Normalisation Process Theory (NPT) was used to structure analysis. A writing group prepared a document for input from members of CTR, forming the basis of this paper. RESULTS: Actions to integrate qualitative research comprised: its inclusion in Centre strategies; formation of a QRG with dedicated funding/roles; embedding of qualitative research within operating systems; capacity building/training; monitoring opportunities to include qualitative methods in studies; maximising the quality of qualitative research and developing methodological innovation. Facilitators of these actions included: the influence of the broader methodological landscape within trial/study design and its promotion of the value of qualitative research; and close physical proximity of CTR qualitative staff/students allowing sharing of methodological approaches. Introduction of innovative qualitative methods generated interest among other staff groups. Challenges included: pressure to under-resource qualitative components of research, preference for a statistical stance historically in some research areas and funding structures, and difficulties faced by qualitative researchers carving out individual academic profiles when working across trials/studies. CONCLUSIONS: Given that CTUs are pivotal to the design and conduct of RCTs and related study types across multiple disciplines, integrating qualitative research into trials units is crucial if its contribution is to be fully realised. We have made explicit one trials unit's experience of embedding qualitative research and present this to open dialogue on ways to operationalise and optimise qualitative research in trials. NPT provides a valuable framework with which to theorise these processes, including the importance of sense-making and legitimisation when introducing new practices within organisations.

Long-term risk prediction after major lower limb amputation: 1-year results of the PERCEIVE study.

BACKGROUND: Decision-making when considering major lower limb amputation is complex and requires individualized outcome estimation. It is unknown how accurate healthcare professionals or relevant outcome prediction tools are at predicting outcomes at 1-year after major lower limb amputation. METHODS: An international, multicentre prospective observational study evaluating healthcare professional accuracy in predicting outcomes 1 year after major lower limb amputation and evaluation of relevant outcome prediction tools identified in a systematic search of the literature was undertaken. Observed outcomes at 1 year were compared with: healthcare professionals' preoperative predictions of death (surgeons and anaesthetists), major lower limb amputation revision (surgeons) and ambulation (surgeons, specialist physiotherapists and vascular nurse practitioners); and probabilities calculated from relevant outcome prediction tools. RESULTS: A total of 537 patients and 2244 healthcare professional predictions of outcomes were included. Surgeons and anaesthetists had acceptable discrimination (C-statistic = 0.715), calibration and overall performance (Brier score = 0.200) when predicting 1-year death, but performed worse when predicting major lower limb amputation revision and ambulation (C-statistics = 0.627 and 0.662 respectively). Healthcare professionals overestimated the death and major lower limb amputation revision risks. Consultants outperformed trainees, especially when predicting ambulation. Allied healthcare professionals marginally outperformed surgeons in predicting ambulation. Two outcome prediction tools (C-statistics = 0.755 and 0.717, Brier scores = 0.158 and 0.178) outperformed healthcare professionals' discrimination, calibration and overall performance in predicting death. Two outcome prediction tools for ambulation (C-statistics = 0.688 and 0.667) marginally outperformed healthcare professionals. CONCLUSION: There is uncertainty in predicting 1-year outcomes following major lower limb amputation. Different professional groups performed comparably in this study. Two outcome prediction tools for death and two for ambulation outperformed healthcare professionals and may support shared decision-making.

Primary care clinicians' perceptions of antibiotic resistance: a multi-country qualitative interview study.

OBJECTIVES: To explore and compare primary care clinicians' perceptions of antibiotic resistance in relation to the management of community-acquired lower respiratory tract infection (LRTI) in contrasting European settings. METHODS: Qualitative interview study with 80 primary care clinicians in nine European countries. Data were subjected to a five-stage analytical framework approach (familiarization; developing a thematic framework from the interview questions and the themes emerging from the data; indexing; charting; and mapping to search for interpretations in the data). Preliminary analysis reports were sent to all network facilitators for validation. RESULTS: Most clinicians stated that antibiotic resistance was not a problem in their practice. Some recommended enhanced feedback about local resistance rates. Northern European respondents generally favoured using the narrowest-spectrum agent, motivated by containing resistance, whereas southern/eastern European respondents were more motivated by maximizing the potential of a rapid treatment effect and so justified empirical use of broad-spectrum antibiotics. Antibiotic treatment failure was ascribed largely to viral aetiology rather than resistant bacteria. Clinicians generally agreed that resistance will become more serious without enhanced antibiotic stewardship or new drug discovery. CONCLUSIONS: If current rates of antibiotic resistance are likely to result in important treatment failures, then provision of local resistance data is likely to enhance clinicians' sense of importance of the issue. Interventions to enhance the quality of antibiotic prescribing in primary care should address perceptions, particularly in the south and east of Europe, that possible advantages to patients from antibiotic treatment in general, and from newer broad-spectrum compared with narrow-spectrum agents, outweigh disadvantages to patients and society from associated effects on antibiotic resistance.

The acceptability of a guided internet-based trauma-focused self-help programme (Spring) for post-traumatic stress disorder (PTSD).

Background: Guided internet-based, cognitive behavioural therapy with a trauma-focus (i-CBT-TF) is recommended in guidelines for post-traumatic stress disorder (PTSD). There is limited evidence regarding its acceptability, with significant dropout from individual face-to-face CBT-TF, suggesting non-acceptability at least in some cases.Objective: To determine the acceptability of a guided internet-based CBT-TF intervention, 'Spring', in comparison with face-to-face CBT-TF for mild to moderate PTSD.Method: Treatment adherence, satisfaction, and therapeutic alliance were measured quantitatively for participants receiving 'Spring' or face-to-face CBT-TF as part of a Randomised Controlled Trial. Qualitative interviews were conducted with a purposive sample of therapists and participants.Results: 'Spring' guided internet-based CBT-TF was found to be acceptable, with over 89% participants fully or partially completing the programme. Therapy adherence and alliance for 'Spring' and face-to-face CBT-TF did not differ significantly, apart from post-treatment participant-reported alliance, which was in favour of face-to-face CBT-TF. Treatment satisfaction was high for both treatments, in favour of face-to-face CBT-TF. Interviews with participants receiving, and therapists delivering 'Spring' corroborated its acceptability.Conclusions: Guided internet-based CBT-TF is acceptable for many people with mild to moderate PTSD. Findings provide insights into future implementation, highlighting the importance of personalising guided self-help, depending on an individual's presentation, and preferences.

Guided internet-based trauma-focused CBT is an acceptable treatment for PTSD.A model of acceptability explained 45% of variance in treatment outcome.Importance of adapting guided self-help to suit presentation and preferences.

Impact of the COVID-19 pandemic on domiciliary care workers in Wales, UK: a data linkage cohort study using the SAIL Databank.

OBJECTIVES: To quantify population health risks for domiciliary care workers (DCWs) in Wales, UK, working during the COVID-19 pandemic. DESIGN: A population-level retrospective study linking occupational registration data to anonymised electronic health records maintained by the Secure Anonymised Information Linkage Databank in a privacy-protecting trusted research environment. SETTING: Registered DCW population in Wales. PARTICIPANTS: Records for all linked DCWs from 1 March 2020 to 30 November 2021. PRIMARY AND SECONDARY OUTCOME MEASURES: Our primary outcome was confirmed COVID-19 infection; secondary outcomes included contacts for suspected COVID-19, mental health including self-harm, fit notes, respiratory infections not necessarily recorded as COVID-19, deaths involving COVID-19 and all-cause mortality. RESULTS: Confirmed and suspected COVID-19 infection rates increased over the study period to 24% by 30 November 2021. Confirmed COVID-19 varied by sex (males: 19% vs females: 24%) and age (>55 years: 19% vs <35 years: 26%) and were higher for care workers employed by local authority social services departments compared with the private sector (27% and 23%, respectively). 34% of DCWs required support for a mental health condition, with mental health-related prescribing increasing in frequency when compared with the prepandemic period. Events for self-harm increased from 0.2% to 0.4% over the study period as did the issuing of fit notes. There was no evidence to suggest a miscoding of COVID-19 infection with non-COVID-19 respiratory conditions. COVID-19-related and all-cause mortality were no greater than for the general population aged 15-64 years in Wales (0.1% and 0.034%, respectively). A comparable DCW workforce in Scotland and England would result in a comparable rate of COVID-19 infection, while the younger workforce in Northern Ireland may result in a greater infection rate. CONCLUSIONS: While initial concerns about excess mortality are alleviated, the substantial pre-existing and increased mental health burden for DCWs will require investment to provide long-term support to the sector's workforce.

Developing a model for decision-making around antibiotic prescribing for patients with COVID-19 pneumonia in acute NHS hospitals during the first wave of the COVID-19 pandemic: qualitative results from the Procalcitonin Evaluation of Antibiotic use in COVID-19 Hospitalised patients (PEACH Study).

OBJECTIVE: To explore and model factors affecting antibiotic prescribing decision-making early in the pandemic. DESIGN: Semistructured qualitative interview study. SETTING: National Health Service (NHS) trusts/health boards in England and Wales. PARTICIPANTS: Clinicians from NHS trusts/health boards in England and Wales. METHOD: Individual semistructured interviews were conducted with clinicians in six NHS trusts/health boards in England and Wales as part of the Procalcitonin Evaluation of Antibiotic use in COVID-19 Hospitalised patients study, a wider study that included statistical analysis of procalcitonin (PCT) use in hospitals during the first wave of the pandemic. Thematic analysis was used to identify key factors influencing antibiotic prescribing decisions for patients with COVID-19 pneumonia during the first wave of the pandemic (March to May 2020), including how much influence PCT test results had on these decisions. RESULTS: During the first wave of the pandemic, recommendations to prescribe antibiotics for patients with COVID-19 pneumonia were based on concerns about secondary bacterial infections. However, as clinicians gained more experience with COVID-19, they reported increasing confidence in their ability to distinguish between symptoms and signs caused by SARS-CoV-2 viral infection alone, and secondary bacterial infections. Antibiotic prescribing decisions were influenced by factors such as clinician experience, confidence, senior support, situational factors and organisational influences. A decision-making model was developed. CONCLUSION: This study provides insight into the decision-making process around antibiotic prescribing for patients with COVID-19 pneumonia during the first wave of the pandemic. The importance of clinician experience and of senior review of decisions as factors in optimising antibiotic stewardship is highlighted. In addition, situational and organisational factors were identified that could be optimised. The model presented in the study can be used as a tool to aid understanding of the complexity of the decision-making process around antibiotic prescribing and planning antimicrobial stewardship support in the context of a pandemic. TRIAL REGISTRATION NUMBER: ISRCTN66682918.

Pragmatic randomised controlled trial of guided self-help versus individual cognitive behavioural therapy with a trauma focus for post-traumatic stress disorder (RAPID).

Background: Guided self-help has been shown to be effective for other mental conditions and, if effective for post-traumatic stress disorder, would offer a time-efficient and accessible treatment option, with the potential to reduce waiting times and costs. Objective: To determine if trauma-focused guided self-help is non-inferior to individual, face-to-face cognitive-behavioural therapy with a trauma focus for mild to moderate post-traumatic stress disorder to a single traumatic event. Design: Multicentre pragmatic randomised controlled non-inferiority trial with economic evaluation to determine cost-effectiveness and nested process evaluation to assess fidelity and adherence, dose and factors that influence outcome (including context, acceptability, facilitators and barriers, measured qualitatively). Participants were randomised in a 1 : 1 ratio. The primary analysis was intention to treat using multilevel analysis of covariance. Setting: Primary and secondary mental health settings across the United Kingdom's National Health Service. Participants: One hundred and ninety-six adults with a primary diagnosis of mild to moderate post-traumatic stress disorder were randomised with 82% retention at 16 weeks and 71% at 52 weeks. Nineteen participants and ten therapists were interviewed for the process evaluation. Interventions: Up to 12 face-to-face, manualised, individual cognitive-behavioural therapy with a trauma focus sessions, each lasting 60-90 minutes, or to guided self-help using Spring, an eight-step online guided self-help programme based on cognitive-behavioural therapy with a trauma focus, with up to five face-to-face meetings of up to 3 hours in total and four brief telephone calls or e-mail contacts between sessions. Main outcome measures: Primary outcome: the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, at 16 weeks post-randomisation. Secondary outcomes: included severity of post-traumatic stress disorder symptoms at 52 weeks, and functioning, symptoms of depression, symptoms of anxiety, alcohol use and perceived social support at both 16 and 52 weeks post-randomisation. Those assessing outcomes were blinded to group assignment. Results: Non-inferiority was demonstrated at the primary end point of 16 weeks on the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [mean difference 1.01 (one-sided 95% CI -∞ to 3.90, non-inferiority p = 0.012)]. Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, score improvements of over 60% in both groups were maintained at 52 weeks but the non-inferiority results were inconclusive in favour of cognitive-behavioural therapy with a trauma focus at this timepoint [mean difference 3.20 (one-sided 95% confidence interval -∞ to 6.00, non-inferiority p = 0.15)]. Guided self-help using Spring was not shown to be more cost-effective than face-to-face cognitive-behavioural therapy with a trauma focus although there was no significant difference in accruing quality-adjusted life-years, incremental quality-adjusted life-years -0.04 (95% confidence interval -0.10 to 0.01) and guided self-help using Spring was significantly cheaper to deliver [£277 (95% confidence interval £253 to £301) vs. £729 (95% CI £671 to £788)]. Guided self-help using Spring appeared to be acceptable and well tolerated by participants. No important adverse events or side effects were identified. Limitations: The results are not generalisable to people with post-traumatic stress disorder to more than one traumatic event. Conclusions: Guided self-help using Spring for mild to moderate post-traumatic stress disorder to a single traumatic event appears to be non-inferior to individual face-to-face cognitive-behavioural therapy with a trauma focus and the results suggest it should be considered a first-line treatment for people with this condition. Future work: Work is now needed to determine how best to effectively disseminate and implement guided self-help using Spring at scale. Trial registration: This trial is registered as ISRCTN13697710. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/192/97) and is published in full in Health Technology Assessment; Vol. 27, No. 26. See the NIHR Funding and Awards website for further award information.

Post-traumatic stress disorder is a common, disabling condition that can occur following major traumatic events. Typical symptoms include distressing reliving, avoidance of reminders and feeling a current sense of threat. First-choice treatments for post-traumatic stress disorder are individual, face-to-face talking treatments, of 12­16 hours duration, including cognitive behavioural therapy with a trauma focus. If equally effective treatments could be developed that take less time and can be largely undertaken in a flexible manner at home, this would improve accessibility, reduce waiting times and hence the burden of disease. RAPID was a randomised controlled trial using a web-based programme called Spring. The aim was to determine if trauma-focused guided self-help provided a faster and cheaper treatment for post-traumatic stress disorder than first-choice face-to-face therapy, while being equally effective. Guided self-help using Spring is delivered through eight steps. A therapist provides a 1-hour introductory meeting followed by four further, fortnightly sessions of 30 minutes each and four brief (around 5 minutes) telephone calls or e-mail contacts between sessions. At each session, the therapist reviews progress and guides the client through the programme, offering continued support, monitoring, motivation and problem-solving. One hundred and ninety-six people with post-traumatic stress disorder to a single traumatic event took part in the study. Guided self-help using Spring was found to be equally effective to first-choice face-to-face therapy at reducing post-traumatic stress disorder symptoms at 16 weeks. Very noticeable improvements were maintained at 52 weeks post-randomisation in both groups, when most results were inconclusive but in favour of face-to-face therapy. Guided self-help using Spring was significantly cheaper to deliver and appeared to be well-tolerated. It is noteworthy that not everyone benefitted from guided self-help using Spring, highlighting the importance of considering it on a person-by-person basis, and personalising interventions. But, the RAPID trial has demonstrated that guided self-help using Spring provides a low-intensity treatment option for people with post-traumatic stress disorder that is ready to be implemented in the National Health Service.

'The body gets used to them': patients' interpretations of antibiotic resistance and the implications for containment strategies.

BACKGROUND: Interventions promoting evidence based antibiotic prescribing and use frequently build on the concept of antibiotic resistance but patients and clinicians may not share the same assumptions about its meaning. OBJECTIVE: To explore patients' interpretations of 'antibiotic resistance' and to consider the implications for strategies to contain antibiotic resistance. DESIGN: Multi country qualitative interview study. PARTICIPANTS: One hundred and twenty-one adult patients from primary care research networks based in nine European countries who had recently consulted a primary care clinician with symptoms of Lower Respiratory Tract Infection (LRTI). APPROACH: Semi-structured interviews with patients following their consultation and subjected to a five-stage analytic framework approach (familiarization, developing a thematic framework from the interview questions and the themes emerging from the data, indexing, charting, and mapping to search for interpretations in the data), with local network facilitators commenting on preliminary reports. RESULTS: The dominant theme was antibiotic resistance as a property of a 'resistant human body', where the barrier to antibiotic effectiveness was individual loss of responsiveness. Less commonly, patients correctly conceptualized antibiotic resistance as a property of bacteria. Nevertheless, the over-use of antibiotics was a strong central concept in almost all patients' explanations, whether they viewed resistance as located in either the body or in bacteria. CONCLUSIONS: Most patients were aware of the link between antibiotic use and antibiotic resistance. The identification of the misinterpretation of antibiotic resistance as a property of the human body rather than bacterial cells could inform clearer clinician-patient discussions and public health interventions through emphasising the transferability of resistance, and the societal contribution individuals can make through more appropriate antibiotic prescribing and use.

"I don't mean to be rude, but could you put a mask on while I'm here?" A qualitative study of risks experienced by domiciliary care workers in Wales during the COVID-19 pandemic.

Domiciliary care workers (DCWs) continued to provide care to adults in their own homes throughout the COVID-19 pandemic. The evidence of the impact of COVID-19 on health outcomes of DCWs is currently mixed. The OSCAR study will quantify the impact of COVID-19 upon health outcomes of DCWs in Wales, explore causes of variation and extrapolate to the rest of the UK DCW population. An embedded qualitative study aimed to explore DCW experiences during the pandemic, including factors that may have varied risk of exposure to COVID-19 and adverse health and wellbeing outcomes. Registered DCWs working throughout Wales were invited to participate in a semi-structured telephone interview. 24 DCWs were interviewed between February and July 2021. Themes were identified through inductive analysis using thematic coding. Several themes emerged relating to risk of exposure to COVID-19. First, general changes to the role of the DCW during the pandemic were identified. Second, practical challenges for DCWs in the workplace were reported, including staff shortages, clients and families not following safety procedures, initial shortages of personal protective equipment (PPE), DCW criticism of standard use PPE, client difficulty with PPE and management of rapid antigen testing. Third, lack of government/employer preparation for a pandemic was described, including the reorganisation of staff clients and services, inadequate or confusing information for many DCWs, COVID-19 training and the need for improved practical instruction and limited official standard risk assessments for DCWs. Pressure to attend work and perceptions of COVID-19 risk and vaccination was also reported. In summary, this paper describes the risk factors associated with working during the pandemic. We have mapped recommendations for each problem using these qualitative findings including tailored training and better support for isolated team members and identified the required changes at several socio-ecological levels.

PROcalcitonin and NEWS2 evaluation for Timely identification of sepsis and Optimal use of antibiotics in the emergency department (PRONTO): protocol for a multicentre, open-label, randomised controlled trial.

INTRODUCTION: Sepsis is a common, potentially life-threatening complication of infection. The optimal treatment for sepsis includes prompt antibiotics and intravenous fluids, facilitated by its early and accurate recognition. Currently, clinicians identify and assess severity of suspected sepsis using validated clinical scoring systems. In England, the National Early Warning Score 2 (NEWS2) has been mandated across all National Health Service (NHS) trusts and ambulance organisations. Like many clinical scoring systems, NEWS2 should not be used without clinical judgement to determine either the level of acuity or a diagnosis. Despite this, there is a tendency to overemphasise the score in isolation in patients with suspected infection, leading to the overprescription of antibiotics and potentially treatment-related complications and rising antimicrobial resistance. The biomarker procalcitonin (PCT) has been shown to be useful in specific circumstances to support appropriate antibiotics prescribing by identifying bacterial infection. PCT is not routinely used in the care of undifferentiated patients presenting to emergency departments (EDs), and the evidence base of its optimal usage is poor. The PROcalcitonin and NEWS2 evaluation for Timely identification of sepsis and Optimal (PRONTO) study is a randomised controlled trial (RCT) in adults with suspected sepsis presenting to the ED to compare standard clinical management based on NEWS2 scoring plus PCT-guided risk assessment with standard clinical management based on NEWS2 scoring alone and compare if this approach reduces prescriptions of antibiotics without increasing mortality. METHODS AND ANALYSIS: PRONTO is a parallel two-arm open-label individually RCT set in up to 20 NHS EDs in the UK with a target sample size of 7676 participants. Participants will be randomised in a ratio of 1:1 to standard clinical management based on NEWS2 scoring or standard clinical management based on NEWS2 scoring plus PCT-guided risk assessment. We will compare whether the addition of PCT measurement to NEWS2 scoring can lead to a reduction in intravenous antibiotic initiation in ED patients managed as suspected sepsis, with at least no increase in 28-day mortality compared with NEWS2 scoring alone (in conjunction with local standard care pathways). PRONTO has two coprimary endpoints: initiation of intravenous antibiotics at 3 hours (superiority comparison) and 28-day mortality (non-inferiority comparison). The study has an internal pilot phase and group-sequential stopping rules for effectiveness and futility/safety, as well as a qualitative substudy and a health economic evaluation. ETHICS AND DISSEMINATION: The trial protocol was approved by the Health Research Authority (HRA) and NHS Research Ethics Committee (Wales REC 2, reference 20/WA/0058). In England and Wales, the law allows the use of deferred consent in approved research situations (including ED studies) where the time dependent nature of intervention would not allow true informed consent to be obtained. PRONTO has approval for a deferred consent process to be used. Findings will be disseminated through peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION NUMBER: ISRCTN54006056.

Sensory integration therapy for children with autism and sensory processing difficulties: the SenITA RCT.

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 < 0.001), with a mean change of 2.75 (95% confidence interval 2.14 to 3.37) for performance and a mean change of 3.34 (95% confidence interval 2.63 to 4.40) for satisfaction. Health economic evaluation suggests that sensory integration therapy is not cost-effective compared with usual care alone. LIMITATIONS: Limitations included variability of the intervention setting (i.e. NHS vs. private), delay for some receiving therapy, an error in administration of Vineland Adaptive Behavior Scales and no measurement of comparator arm goal performance. CONCLUSIONS: The intervention did not demonstrate clinical benefit above standard care. Subgroup effects are hypothesis-generating only. The intervention is likely to be effective for individualised performance goals, although it is unclear whether effects were in addition to standard care or were maintained. FUTURE WORK: Further investigation of subgroup effects is needed. TRIAL REGISTRATION: This trial is registered as ISRCTN14716440. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 29. See the NIHR Journals Library website for further project information.

Children with autism often experience problems with processing sensory information (e.g. noise, touch, movement, taste and sight), and this can lead to problems in daily life. This study was designed to see if sensory integration therapy can help children with these difficulties. Sensory integration therapy is a type of face-to-face play-based treatment that is delivered by occupational therapists. We compared sensory integration therapy with the type of treatment normally offered to children with autism (i.e. 'usual care'). We recruited children and their carers from Wales and England. Children could take part in the study if they had an autism diagnosis, had sensory processing difficulties and were in mainstream primary education. The children taking part in the study were randomly split into two groups. Sixty-nine children were given sensory integration therapy and 69 children carried on with their usual care. The sensory integration therapy involved 24 face-to-face sessions in an occupational therapy clinic, followed by two telephone calls with the carer. The sensory integration therapy lasted for 26 weeks. We collected information on the type of care being given to children in the usual-care group. Carers of each child were asked questions about their child's behaviour 6 and 12 months after starting the study. Some carers also completed an interview to talk about what it was like taking part in the study. Therapists delivered the sensory integration therapy well. Carers and therapists said that they saw some improvements. However, sensory integration therapy was not significantly better than the usual care and is a more expensive option. We cannot say that sensory integration therapy is helpful for all children with autism and different sensory processing difficulties; however, it might be helpful for some children to focus on specific problems. Future work could focus on which children and problems it would help the most.