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Skin cancer is the most common malignancy in the UK, and up to a third of lesions are ulcerated at the time of excision. Ulceration has been shown to increase the risk of developing surgical site infection following excision, with some studies finding infection rates of 33%. However, no specific guidelines for the use of antibiotic prophylaxis in such cases exist. We surveyed 129 clinicians (covering Dermatology, Plastic Surgery, Ear, Nose and Throat Surgery, and Oral and Maxillofacial Surgery) who all excise skin lesions on a regular basis. There was significant variability in their practice with regard to antibiotic prophylaxis, with 9% always prescribing them and 19% never prescribing them. Variation exists both among and between specialities. This variation increases the risk of antimicrobial resistance and shows a paucity of good clinical evidence, indicating that a well-designed clinical trial is needed to guide future practice., (© 2021 British Association of Dermatologists.)

Background: Hidradenitis suppurativa (HS) is a chronic, painful, inflammatory skin disease with estimates of prevalence in the European population of 1%-2%. Despite being a relatively common condition, the evidence base for management of HS is limited. European and North American management guidelines rely on consensus for many aspects of treatment and within the UK variations in management of HS have been identified. The HS James Lind Alliance Priority Setting Partnership (PSP) published a top 10 list of future HS research priorities including both medical and surgical interventions. The aims of the THESEUS study are to inform the design of future HS randomised controlled trials (RCTs) and to understand how HS treatments are currently used. THESEUS incorporates several HS PSP research priorities, including investigation of oral and surgical treatments. Core outcome domains have been established by the HIdradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC) and THESEUS is designed to validate instruments to measure the domains., Methods and Analysis: The THESEUS study is a prospective observational cohort study. Participants, adults with active HS of any severity, will be asked to select one of five HS treatment options that is appropriate for their HS care. Participants will be allocated to their chosen treatment intervention and followed for a period of up to 12 months. Outcomes will be assessed at 3-monthly intervals using HISTORIC core outcome instruments. Video recordings of the surgical and laser operations will provide informational and training videos for future trials. Nested mixed-methods studies will characterise the interventions in clinical practice, understand facilitators and barriers to recruitment into future HS RCTs and examine patients' and clinicians' perspectives on HS treatment choices., Trial Registration Number: ISRCTN69985145., Competing Interests: Competing interests: JRI: Consultant for UCB Pharma, Novartis, Boehringer Ingelheim and ChemoCentryx; Advisory Boards for Kymera Therapeutics,Viela Bio and Insmed; Honoraria for BJD Editor-in-Chief, UpToDate HS chapter author; Copyright holder for HiSQOL, HS Patient Global Assessment, HS Investigator Global Assessment, and HS Guideline lead for British Association of Dermatologists. JR is funded by a National Institute of Health Research (NIHR) Postdoctoral Fellowship (PDF-2017-10-075). This represents independent research funded by the NIHR., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Blood biomarkers have the potential to help identify COVID-19 patients with bacterial coinfection in whom antibiotics are indicated. During the COVID-19 pandemic, procalcitonin testing was widely introduced at hospitals in the UK to guide antibiotic prescribing. We have determined the impact of this on hospital-level antibiotic consumption., Methods: We conducted a retrospective, controlled interrupted time series analysis of organization-level data describing antibiotic dispensing, hospital activity and procalcitonin testing for acute hospitals/hospital trusts in England and Wales during the first wave of COVID-19 (24 February to 5 July 2020)., Results: In the main analysis of 105 hospitals in England, introduction of procalcitonin testing in emergency departments/acute medical admission units was associated with a statistically significant decrease in total antibiotic use of -1.08 (95% CI: -1.81 to -0.36) DDDs of antibiotic per admission per week per trust. This effect was then lost at a rate of 0.05 (95% CI: 0.02-0.08) DDDs per admission per week. Similar results were found specifically for first-line antibiotics for community-acquired pneumonia and for COVID-19 admissions rather than all admissions. Introduction of procalcitonin in the ICU setting was not associated with any significant change in antibiotic use., Conclusions: At hospitals where procalcitonin testing was introduced in emergency departments/acute medical units this was associated with an initial, but unsustained, reduction in antibiotic use. Further research should establish the patient-level impact of procalcitonin testing in this population and understand its potential for clinical effectiveness., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: It has been demonstrated that antibiotic prescribing for Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) can be safely reduced in primary care when general practitioners have access to C-reactive protein (CRP) rapid testing., Aim: To investigate the factors associated with post-consultation COPD health status in patients presenting with AECOPD in this setting., Design and Setting: A cohort study of patients enrolled in a randomised controlled trial. Patients aged 40+ years with a clinical diagnosis of COPD who presented in primary care across England and Wales with an AECOPD were included., Methods: Participants were contacted for follow-up at one- and two-weeks by phone and attended the practice four weeks after the index consultation. The outcome of interest was the Clinical COPD Questionnaire (CCQ) score. Multivariable multilevel linear regression models fitted to examine the factors associated with COPD health status in the four-weeks following consultation for an AECOPD., Results: A total of 649 patients were included, with 1947 CCQ total scores analysed. Post-consultation CCQ total scores were significantly higher (worse) in participants with diabetes (adjusted mean difference [AMD]=0.26; 95% confidence interval (CI) 0.08-0.45), obese patients compared to those with normal body mass index (AMD = 0.25, 95% CI 0.07-0.43), and those who were prescribed oral antibiotics in the prior 12 months (AMD = 0.26; 95% CI 0.11-0.41), but only the two latter associations remained after adjusting for other sociodemographic variables., Conclusion: COPD health status was worse in the four weeks following primary care consultation for AECOPD in patients with obesity and those prescribed oral antibiotics in the preceding year., Competing Interests: Authors DG, NF, HA, KH, PW, ET-J, BS, GN, RL, NK, JB, and CCB report grants from the National Institute for Health Research during the conduct of this study. NF also reports payments from Abbott for chairing and presenting at scientific meeting. CL reports grants from Abbott Diagnostics outside of the submitted work. RP reports grants from Health and Care Research Wales Research for Public and Patient Benefit, grants from Welsh Government/Ser Cymru, grants from Kidney Research UK and British Renal Society, grants from National Institute for Health Research Health Technology Assessment outside the submitted work. All other authors (HS, HM, AC, and MFA) report no potential competing interests., (© 2022 Gillespie et al.)

Background: Living in deprived areas is associated with poorer outcomes after certain vascular procedures and surgical site infection in other specialties. Our primary objective was to determine whether living in more income-deprived areas was associated with groin wound surgical site infection after arterial intervention. Secondary objectives were to determine whether living in more income-deprived areas was associated with mortality and clinical consequences of surgical site infection. Methods: Postal code data for patients from the United Kingdom who were included in the Groin Wound Infection after Vascular Exposure (GIVE) multicenter cohort study was used to determine income deprivation, based on index of multiple deprivation (IMD) data. Patients were divided into three IMD groups for descriptive analysis. Income deprivation score was integrated into the final multivariable model for predicting surgical site infection. Results: Only patients from England had sufficient postal code data, analysis included 772 groin incisions (624 patients from 22 centers). Surgical site infection occurred in 9.7% incisions (10.3% of patients). Surgical site infection was equivalent between income deprivation tertiles (tertile 1 = 9.5%; tertile 2 = 10.3%; tertile 3 = 8.6%; p = 0.828) as were the clinical consequences of surgical site infection and mortality. Income deprivation was not associated with surgical site infection in multivariable regression analysis (odds ratio [OR], 0.574; 95% confidence interval [CI], 0.038-8.747; p = 0.689). Median age at time of procedure was lower for patients living in more income-deprived areas (tertile 1 = 68 years; tertile 2 = 72 years; tertile 3 = 74 years; p < 0.001). Conclusions: We found no association between living in an income-deprived area and groin wound surgical site infection, clinical consequences of surgical site infection and mortality after arterial intervention. Patients living in more income-deprived areas presented for operative intervention at a younger age, with similar rates of comorbidities to patients living in less income-deprived areas.

Introduction: Procalcitonin (PCT) is a biomarker more specific for bacterial infection and responds quicker than other commonly used biomarkers such as C reactive protein, but is not routinely used in the National Health Service (NHS). Studies mainly in adults show that using PCT to guide clinicians may reduce antibiotic use, reduce hospital stay, with no associated adverse effects such as increased rates of hospital re-admission, incomplete treatment of infections, relapse or death. A review conducted for National Institute for Health and Care Excellence recommends further research on PCT testing to guide antibiotic use in children., Methods and Analysis: Biomarker-guided duration of Antibiotic Treatment in Children Hospitalised with confirmed or suspected bacterial infection is a multi-centre, prospective, two-arm, individually Randomised Controlled Trial (RCT) with a 28-day follow-up and internal pilot. The intervention is a PCT-guided algorithm used in conjunction with best practice. The control arm is best practice alone. We plan to recruit 1942 children, aged between 72 hours and up to 18 years old, who are admitted to the hospital and being treated with intravenous antibiotics for suspected or confirmed bacterial infection. Coprimary outcomes are duration of antibiotic use and a composite safety measure. Secondary outcomes include time to switch from broad to narrow spectrum antibiotics, time to discharge, adverse drug reactions, health utility and cost-effectiveness. We will also perform a qualitative process evaluation. Recruitment commenced in June 2018 and paused briefly between March and May 2020 due to the COVID-19 pandemic., Ethics and Dissemination: The trial protocol was approved by the HRA and NHS REC (North West Liverpool East REC reference 18/NW/0100). We will publish the results in international peer-reviewed journals and present at scientific meetings., Trial Registration Number: ISRCTN11369832., Competing Interests: Competing interests: EDC is a member of NIHR Invention for Innovation panel, member of NICE Diagnostic advisory committee April 2014–September 2020, Member of MRC DPFS panel and MRC COVID-19 Agile panel. SNF is an NIHR Senior Investigator. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Deciding whether to proceed with a major lower limb amputation is life-changing and complex, and it is crucial that the right decision is made at the right time. However, medical specialists are known to poorly predict risk when assessing patients for major surgery, and there is little guidance and research regarding decisions about amputation. The process of shared decision-making between doctors and patients during surgical consultations is also little understood. Therefore, the aim of this study is to analyse in depth the communication, consent, risk prediction and decision-making process in relation to major lower limb amputation., Methods and Analysis: Consultations between patients and surgeons at which major lower limb amputation is discussed will be audio-recorded for 10-15 patients. Semi-structured follow-up interviews with patients (and relatives/carers) will then be conducted at two time points: as soon as possible/appropriate after a decision has been reached regarding surgery, and approximately 6 months later. Semi-structured interviews will also be conducted with 10-15 healthcare professionals working in the UK National Health Service (NHS) involved in amputation decision-making. This will include surgeons, anaesthetists and specialist physiotherapists at 2-4 NHS Health Boards/Trusts in Wales and England. Discourse analysis will be used to analyse the recorded consultations; interviews will be analysed thematically. Finally, workshops will be held with patients and healthcare professionals to help synthesise and interpret findings., Ethics and Dissemination: The study has been approved by Wales REC 7 (20/WA/0351). Study findings will be published in international peer-reviewed journal(s) and presented at national and international scientific meetings. Findings will also be disseminated to a wide NHS and lay audience via presentations at meetings and written summaries for key stakeholder groups., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Paediatric mortality rates in the United Kingdom are amongst the highest in Europe. Clinically missed deterioration is a contributory factor. Evidence to support any single intervention to address this problem is limited, but a cumulative body of research highlights the need for a systems approach., Methods: An evidence-based, theoretically informed, paediatric early warning system improvement programme (PUMA Programme) was developed and implemented in two general hospitals (no onsite Paediatric Intensive Care Unit) and two tertiary hospitals (with onsite Paediatric Intensive Care Unit) in the United Kingdom. Designed to harness local expertise to implement contextually appropriate improvement initiatives, the PUMA Programme includes a propositional model of a paediatric early warning system, system assessment tools, guidance to support improvement initiatives and structured facilitation and support. Each hospital was evaluated using interrupted time series and qualitative case studies. The primary quantitative outcome was a composite metric (adverse events), representing the number of children monthly that experienced one of the following: mortality, cardiac arrest, respiratory arrest, unplanned admission to Paediatric Intensive Care Unit, or unplanned admission to Higher Dependency Unit. System changes were assessed qualitatively through observations of clinical practice and interviews with staff and parents. A qualitative evaluation of implementation processes was undertaken., Results: All sites assessed their paediatric early warning systems and identified areas for improvement. All made contextually appropriate system changes, despite implementation challenges. There was a decline in the adverse event rate trend in three sites; in one site where system wide changes were organisationally supported, the decline was significant (ß = -0.09 (95% CI: - 0.15, - 0.05); p = < 0.001). Changes in trends coincided with implementation of site-specific changes., Conclusions: System level change to improve paediatric early warning systems can bring about positive impacts on clinical outcomes, but in paediatric practice, where the patient population is smaller and clinical outcomes event rates are low, alternative outcome measures are required to support research and quality improvement beyond large specialist centres, and methodological work on rare events is indicated. With investment in the development of alternative outcome measures and methodologies, programmes like PUMA could improve mortality and morbidity in paediatrics and other patient populations., (© 2021. The Author(s).)

Polypharmacy and smoking are associated with higher symptom severity in men with lower urinary tract symptoms presenting to primary care. These are potentially modifiable risk factors that can be targeted when managing these patients., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: To explore patient experiences, understanding and perceptions of analgesia following major lower limb amputation., Design: Qualitative interview study, conducted as part of a randomised controlled feasibility trial., Setting: Participants were recruited from two general hospitals in South Wales., Participants: Interview participants were patients enrolled in PLACEMENT (Perineural Local Anaesthetic Catheter aftEr Major lowEr limb amputatioN Trial): a randomised controlled feasibility trial comparing the use of perineural catheter (PNC) versus standard care for postoperative pain relief following major lower limb amputation. PLACEMENT participants who completed 5-day postoperative follow-up, were able and willing to participate in a face-to-face interview, and had consented to be contacted, were eligible to take part in the qualitative study. A total of 20 interviews were conducted with 14 participants: 10 male and 4 female., Methods: Semi-structured, face-to-face interviews were conducted with participants over two time points: (1) up to 1 month and (2) at least 6 months following amputation. Interviews were audio-recorded, transcribed verbatim and analysed using a framework approach., Results: Interviews revealed unanticipated benefits of PNC usage for postoperative pain relief. Participants valued the localised and continuous nature of this mode of analgesia in comparison to opioids. Concerns about opioid dependence and side effects of pain relief medication were raised by participants in both treatment groups, with some reporting trying to limit their intake of analgesics., Conclusions: Findings suggest routine placement of a PNC following major lower limb amputation could reduce postoperative pain, particularly for patient groups at risk of postoperative delirium. This method of analgesic delivery also has the potential to reduce preoperative anxiety, alleviate the burden of pain management and minimise opioid use. Future research could further examine the comparison between patient-controlled analgesia and continuous analgesia in relation to patient anxiety and satisfaction with pain management., Trial Registration Number: ISRCTN: 85710690; EudraCT: 2016-003544-37., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Secondary bacterial infection in COVID-19 patients is associated with increased mortality and disproportionately affects critically ill patients. This single-centre retrospective observational study investigates the comparative efficacy of change in procalcitonin (PCT) and other commonly available biomarkers in revealing or predicting microbiologically proven secondary infection in critical COVID-19 patients. Adult patients admitted to an intensive care unit (ICU) with confirmed SARS-CoV-2 infection between 9 March 2020 and 5 June 2020 were recruited to the study. For daily biomarker and secondary infection, laboratory-confirmed bloodstream infection (LCBI) and ventilator-associated pneumonia/tracheobronchitis (VAP/VAT) data were collected. We observed a PCT rise in 53 (81.5%) of the patients, a C-reactive protein (CRP) rise in 55 (84.6%) and a white blood cell count (WBC) rise in 61 (93.8%). Secondary infection was confirmed in 33 (50.8%) of the patients. A PCT rise was present in 97.0% of patients with at least one confirmed VAP/VAT and/or LCBI event. CRP and WBC rises occurred in 93.9% and 97.0% of patients with confirmed VAP/VAT and/or LCBI, respectively. Logistic regression analysis found that, when including all biomarkers in the same model, there was a significant association between PCT rise and the occurrence of LCBI and/or VAP/VAT (OR = 14.86 95%CI: 2.20, 342.53; p = 0.021). Conversely, no statistically significant relationship was found between either a CRP rise ( p = 0.167) or a WBC rise ( p = 0.855) and the occurrence of VAP/VAT and/or LCBI. These findings provide a promising insight into the usefulness of PCT measurement in predicting the emergence of secondary bacterial infection in ICU.

Background: Accurate prediction of outcomes following surgery with high morbidity and mortality rates is essential for informed shared decision-making between patients and clinicians. It is unknown how accurately healthcare professionals predict outcomes following major lower-limb amputation (MLLA). Several MLLA outcome-prediction tools have been developed. These could be valuable in clinical practice, but most require validation in independent cohorts before routine clinical use can be recommended. The primary aim of this study is to evaluate the accuracy of healthcare professionals' predictions of outcomes in adult patients undergoing MLLA for complications of chronic limb-threatening ischaemia (CLTI) or diabetes. Secondary aims include the validation of existing outcome-prediction tools., Method: This study is an international, multicentre prospective observational study including adult patients undergoing a primary MLLA for CLTI or diabetes. Healthcare professionals' accuracy in predicting outcomes at 30-days (death, morbidity and MLLA revision) and 1-year (death, MLLA revision and ambulation) will be evaluated. Sixteen existing outcome-prediction tools specific to MLLA will be examined for validity. Data collection began on 1 October 2020; the end of follow-up will be 1 May 2022. The C-statistic, Hosmer-Lemeshow test, reclassification tables and Brier score will be used to evaluate the predictive performance of healthcare professionals and prediction tools, respectively., Study Registration and Dissemination: This study will be registered locally at each centre in accordance with local policies before commencing data collection, overseen by local clinician leads. Results will be disseminated to all centres, and any subsequent presentation(s) and/or publication(s) will follow a collaborative co-authorship model., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.)

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., Competing Interests: The authors have declared that no competing interests exist.

Background: Lower urinary tract symptoms (LUTS) are common in males aged ≥40 years and have a considerable impact on quality of life. Management can be complex, and although most LUTS could be treated effectively in primary care, referrals to urology outpatients are increasing., Aim: To explore GPs' experiences of managing LUTS together with patients' experiences of and preferences for treatment in primary care., Design and Setting: Telephone interviews were conducted with GPs and male patients presenting to primary care with bothersome LUTS., Method: Eleven GPs and 25 male patients were purposively sampled from 20 GP practices in three UK regions: Newcastle upon Tyne, Bristol, and South Wales. Interviews were conducted between May 2018 and January 2019, and were analysed using a framework approach., Results: Difficulty establishing causes and differentiating between prostate and bladder symptoms were key challenges to the diagnosis of LUTS in primary care, often making treatment a process of trial and error. Pharmacological treatments were commonly ineffective and often caused side effects. Despite this, patients were generally satisfied with GP consultations and expressed a preference for treatment in primary care., Conclusion: Managing LUTS in primary care is a more accessible option for patients. Given the challenges of LUTS diagnosis, an effective diagnostic tool for use by GPs would be beneficial. Ensuring bothersome LUTS are not dismissed as a normal part of ageing is essential in improving patients' quality of life. Greater exploration of the role of non-pharmacological treatments is needed., (© The Authors.)

Objective: The decision to undertake a major lower limb amputation can be complex. This review evaluates the performance of risk prediction tools in estimating mortality, morbidity, and other outcomes following amputation., Methods: A systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The MEDLINE, Embase, and Cochrane databases were searched to identify studies reporting on risk prediction tools that predict outcomes following amputation. Outcome measures included the accuracy of the risk tool in predicting a range of post-operative complications, including mortality (both short and long term), peri-operative morbidity, need for re-amputation, and ambulation success. A narrative synthesis was performed in accordance with the Guidance on the Conduct of Narrative Synthesis In Systematic Reviews., Results: The search identified 518 database records. Twelve observational studies, evaluating 13 risk prediction tools in a total cohort of 61 099 amputations, were included. One study performed external validation of an existing risk prediction tool, while all other studies developed novel tools or modified pre-existing generic calculators. Two studies conducted external validation of the novel/modified tools. Nine tools provided risk estimations for mortality, two tools provided predictions for post-operative morbidity, two for likelihood of ambulation, and one for re-amputation to the same or higher level. Most mortality prediction tools demonstrated acceptable discrimination performance with C statistic values ranging from 0.65 to 0.81. Tools estimating the risk of post-operative complications (0.65 - 0.74) and necessity for re-amputation (0.72) also performed acceptably. The Blatchford Allman Russell tool demonstrated outstanding discrimination for predicting functional mobility outcomes post-amputation (0.94). Overall, most studies were at high risk of bias with poor external validity., Conclusion: This review identified several risk prediction tools that demonstrate acceptable to outstanding discrimination for objectively predicting an array of important post-operative outcomes. However, the methodological quality of some studies was poor, external validation studies are generally lacking, and there are no tools predicting other important outcomes, especially quality of life., Competing Interests: Conflicts of interest Daniel Norvell and Joseph Czerniecki were involved in the development of the AMPREDICT tools,(18)(,)(22)(,)(26) and Christopher Twine and Emma Thomas-Jones developed UKAmpRisk.(23) Ryan A. Preece, Nafi Dilaver, Cherry-Ann Waldron, Philip Pallmann, Emma Thomas-Jones, Brenig L. Gwilym, Christopher P. Twine, and David C. Bosanquet are currently part of the team running PERCEIVE.(33), (Copyright © 2021 European Society for Vascular Surgery. All rights reserved.)

Background: Invasive urodynamics is used to investigate the causes of lower urinary tract symptoms; a procedure usually conducted in secondary care by specialist practitioners. No study has yet investigated the feasibility of carrying out this procedure in a non-specialist setting. Therefore, the aim of this study was to explore, using qualitative methodology, the feasibility and acceptability of conducting invasive urodynamic testing in primary care., Methods: Semi-structured interviews were conducted during the pilot phase of the PriMUS study, in which men experiencing bothersome lower urinary tract symptoms underwent invasive urodynamic testing along with a series of simple index tests in a primary care setting. Interviewees were 25 patients invited to take part in the PriMUS study and 18 healthcare professionals involved in study delivery. Interviews were audio-recorded, transcribed verbatim and analysed using a framework approach., Results: Patients generally found the urodynamic procedure acceptable and valued the primary care setting due to its increased accessibility and familiarity. Despite some logistical issues, facilitating invasive urodynamic testing in primary care was also a positive experience for urodynamic nurses. Initial issues with general practitioners receiving and utilising the results of urodynamic testing may have limited the potential benefit to some patients. Effective approaches to study recruitment included emphasising the benefits of the urodynamic test and maintaining contact with potential participants by telephone. Patients' relationship with their general practitioner was an important influence on study participation., Conclusions: Conducting invasive urodynamics in primary care is feasible and acceptable and has the potential to benefit patients. Facilitating study procedures in a familiar primary care setting can impact positively on research recruitment. However, it is vital that there is a support network for urodynamic nurses and expertise available to help interpret urodynamic results.

A minority of patients presenting to hospital with COVID-19 have bacterial co-infection. Procalcitonin testing may help identify patients for whom antibiotics should be prescribed or withheld. This study describes the use of procalcitonin in English and Welsh hospitals during the first wave of the COVID-19 pandemic. A web-based survey of antimicrobial leads gathered data about the use of procalcitonin testing. Responses were received from 148/151 (98%) eligible hospitals. During the first wave of the COVID-19 pandemic, there was widespread introduction and expansion of PCT use in NHS hospitals. The number of hospitals using PCT in emergency/acute admissions rose from 17 (11%) to 74/146 (50.7%) and use in Intensive Care Units (ICU) increased from 70 (47.6%) to 124/147 (84.4%). This increase happened predominantly in March and April 2020, preceding NICE guidance. Approximately half of hospitals used PCT as a single test to guide decisions to discontinue antibiotics and half used repeated measurements. There was marked variation in the thresholds used for empiric antibiotic cessation and guidance about interpretation of values. Procalcitonin testing has been widely adopted in the NHS during the COVID-19 pandemic in an unevidenced, heterogeneous way and in conflict with relevant NICE guidance. Further research is needed urgently that assesses the impact of this change on antibiotic prescribing and patient safety.

Background: C-reactive protein (CRP) point-of-care testing can reduce antibiotic use in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in primary care, without compromising patient care. Further safe reductions may be possible., Aim: To investigate the associations between presenting features and antibiotic prescribing in patients with AECOPD in primary care., Design and Setting: Secondary analysis of a randomised controlled trial of participants presenting with AECOPD in primary care (the PACE trial)., Method: Clinicians collected participants' demographic features, comorbid illnesses, clinical signs, and symptoms. Antibiotic prescribing decisions were made after participants were randomised to receive a point-of-care CRP measurement or usual care. Multivariable regression models were fitted to explore the association between patient and clinical features and antibiotic prescribing, and extended to further explore any interactions with CRP measurement category (CRP not measured, CRP <20 mg/l, or CRP ≥20 mg/l)., Results: A total of 649 participants from 86 general practices across England and Wales were included. Odds of antibiotic prescribing were higher in the presence of clinician-recorded crackles (adjusted odds ratio [AOR] = 5.22, 95% confidence interval [CI] = 3.24 to 8.41), wheeze (AOR = 1.64, 95% CI = 1.07 to 2.52), diminished vesicular breathing (AOR = 2.95, 95% CI = 1.70 to 5.10), or clinician-reported evidence of consolidation (AOR = 34.40, 95% CI = 2.84 to 417.27). Increased age was associated with lower odds of antibiotic prescribing (AOR per additional year increase = 0.98, 95% CI = 0.95 to 1.00), as was the presence of heart failure (AOR = 0.32, 95% CI = 0.12 to 0.85)., Conclusion: Several demographic features and clinical signs and symptoms are associated with antibiotic prescribing in AECOPD. Diagnostic and prognostic value of these features may help identify further safe reductions., (© The Authors.)

Decreased heart rate variability (HRV) is considered a common marker of autonomic dysfunction that contributes to poor health outcomes. While some studies have suggested that children with autism spectrum disorder (ASD) show reduced HRV, research is yet to consider whether this may be associated with medication use and symptom severity. This study examined the relationship between resting state HRV, medication use and symptom severity in children diagnosed with ASD. Children with ASD (N = 86), aged between 3 and 12 years (M = 8.09), were compared to 44 neurotypical children of similar age (M = 7.15). Laboratory assessment of HRV involved 5 min of non-invasive baseline electrocardiogram assessments while participants viewed an age-appropriate non-verbal animated video. Time-domain and frequency-domain HRV measures were analyzed. ASD symptom severity was assessed using the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) and Social Responsiveness Scale (SRS-2). Results indicated that children with ASD exhibited reduced resting HRV relative to neurotypical children. Subsequent analyses within the ASD group suggested that this group difference was greater in children who were taking psychotropic medication (N = 36). Our data also provides tentative evidence of a relationship between HRV and social impairment symptoms in children with ASD, with more severe repetitive behaviors (as measured by the ADOS-2) associated with decreased resting HRV. Overall, these findings suggest that HRV may be atypical in children with ASD and suggest the importance of exploring HRV as a risk factor for cardiovascular health in this group. LAY SUMMARY: Cardiac activity, such as heart rate variability (HRV), can provide insight into the autonomic nervous system. This study reports on the association between resting-state HRV and autonomic nervous system activity in young children with autism spectrum disorder (ASD) compared to neurotypical children. These results may help us understand what underlies autonomic nervous system dysfunction and the potential pathophysiological mechanisms leading to increased cardiovascular risk in ASD., (© 2020 International Society for Autism Research and Wiley Periodicals LLC.)

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., (Copyright © 2020 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background: Cardiovascular disease is the leading cause of death in Australia. Investment in research solutions has been demonstrated to yield health and a 9.8-fold return economic benefit. The sector, however, is severely challenged with success rates of traditional peer-reviewed funding in decline. Here, we aimed to understand the perceived challenges faced by the cardiovascular workforce in Australia prior to the COVID-19 pandemic., Methods: We used an online survey distributed across Australian cardiovascular societies/councils, universities and research institutes over a period of 6 months during 2019, with 548 completed responses. Inclusion criteria included being an Australian resident or an Australian citizen who lived overseas, and a current or past student or employee in the field of cardiovascular research., Results: The mean age of respondents was 42±13 years, 47% were male, 85% had a full-time position, and 40% were a group leader or laboratory head. Twenty-three per cent (23%) had permanent employment, and 82% of full-time workers regularly worked >40 hours/week. Sixty-eight per cent (68%) said they had previously considered leaving the cardiovascular research sector. If their position could not be funded in the next few years, a staggering 91% of respondents would leave the sector. Compared to PhD- and age-matched men, women were less likely to be a laboratory head and to feel they had a long-term career path as a cardiovascular researcher, while more women were unsure about future employment and had considered leaving the sector (all p<0.05). Greater job security (76%) and government and philanthropic investment in cardiovascular research (72%) were highlighted by responders as the main changes to current practices that would encourage them to stay., Conclusion: Strategic solutions, such as diversification of career pathways and funding sources, and moving from a competitive to a collaborative culture, need to be a priority to decrease reliance on government funding and allow cardiovascular researchers to thrive., (Copyright © 2020 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Background: To determine whether differential all-cause hospital readmission exists for men and women 2 years after percutaneous coronary intervention (PCI) treatment for acute coronary syndrome (ACS), and to identify potential autonomic and psychological pathways contributing to this association., Methods: Four hundred and sixteen (416) patients admitted with ACS were recruited from coronary care wards. Participants attended the study centre at one (T0) and 12 (T1) months following discharge. Heart rate variability (HRV) was used to assess autonomic functioning measured via a three-lead electrocardiogram. Psychological variables of interest (pathological worry, depression and phobic anxiety) were measured using validated self-report questionnaires. Percutaneous coronary intervention treatment data were collected from hospital records. The primary outcome was 2-year all-cause hospital readmission (yes/no). Logistic regression modelling using both complete case analysis and multiple imputation analysis was applied., Results: Men who received PCI had a significant reduction in the odds of being rehospitalised over the following 2 years, relative to women who did not (OR=0.45, 95% CI=0.20, 0.98). No other group benefited to this extent. Adjustment for age, ACS severity and Very Low Frequency (VLF) Power appeared to strengthen the association in both the complete case analysis and multiple imputation analysis models. The inclusion of depression and worry also marginally explained these associations in the multiple imputation analysis model., Conclusions: Men who receive PCI after ACS were less likely to be readmitted to hospital over the following 2 years than their female counterparts. The small sample size of women and observational study design limit interpretation of the findings. However, heart rate variability, specifically VLF power, requires further investigation as a driver of such sex-specific outcomes., (Copyright © 2020 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

We aimed to examine whether a lifestyle intervention was effective in reducing cardiovascular disease (CVD) risk in individuals at high-risk of developing diabetes in a low- and middle-income setting. The Kerala Diabetes Prevention Program was evaluated by a cluster-randomized controlled trial (2013-2016) of 1007 individuals (aged 30-60 years) at high-risk for diabetes (Indian Diabetes Risk Score ≥ 60 and without diabetes) in Kerala state, India. Sixty polling areas in Kerala were randomized to intervention or control groups by an independent statistician using a computer-generated randomization sequence. Participants from 30 intervention communities received a 12-month structured peer-support lifestyle intervention program involving 15 group sessions and linked community activities, aimed at supporting and maintaining lifestyle change. The primary outcome for this analysis was the predicted 10-year CVD risk at two years, assessed using the Framingham Risk Score. The mean age at baseline was 46.0 (SD: 7.5) years, and 47.2% were women. Baseline 10-year CVD risk was similar between study groups. The follow-up rate at two years was 95.7%. The absolute risk reduction in predicted 10-year CVD risk between study groups was 0.69% (95% CI: 0.09% to 1.29%, p=0.024) at one year and 0.69% (95% CI: 0.10% to 1.29%, p=0.023) at two years. The favorable change in CVD risk with the intervention condition was mainly due to the reduction in tobacco use (change index: -0.25, 95% CI: -0.42 to -0.09). Our findings suggest that a community-based peer-support lifestyle intervention could reduce CVD risk in individuals at high-risk of developing diabetes in India. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry ACTRN12611000262909., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Lower urinary tract symptoms (LUTS) is a bothersome condition affecting older men which can lead to poor quality of life. General practitioners (GPs) currently have no easily available assessment tools to help effectively diagnose causes of LUTS and aid discussion of treatment with patients. Men are frequently referred to urology specialists who often recommend treatments that could have been initiated in primary care. GP access to simple, accurate tests and clinician decision tools are needed to facilitate accurate and effective patient management of LUTS in primary care., Methods and Analysis: PRImary care Management of lower Urinary tract Symptoms (PriMUS) is a prospective diagnostic accuracy study based in primary care. The study will determine which of a number of index tests used in combination best predict three urodynamic observations in men who present to their GP with LUTS. These are detrusor overactivity, bladder outlet obstruction and/or detrusor underactivity. Two cohorts of participants, one for development of the prototype diagnostic tool and other for validation, will undergo a series of simple index tests and the invasive reference standard (invasive urodynamics). We will develop and validate three diagnostic prediction models based on each condition and then combine them with management recommendations to form a clinical decision support tool., Ethics and Dissemination: Ethics approval is from the Wales Research Ethics Committee 6. Findings will be disseminated through peer-reviewed journals and conferences, and results will be of interest to professional and patient stakeholders., Trial Registration Number: ISRCTN10327305., Competing Interests: Competing interests: One of the index tests, Flowtaker, was developed by a team from Newcastle upon Tyne Hospitals (NuTH) and Newcastle University, including two individuals who are grant co-applicants, members of the study management team and co-authors (AB and MiD). In 2014, the device was licensed to MMS (Enschede, the Netherlands) and royalties from the sale of the device were paid to NuTH (not to the individuals). MMS was subsequently acquired by Laborie who removed Flowtaker from the market in January 2018., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Background: Antibiotics are prescribed to >70% of patients presenting in primary care with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The PACE randomised controlled trial found that a C-reactive protein point-of-care test (CRP-POCT) management strategy for AECOPD in primary care resulted in a 20% reduction in patient-reported antibiotic consumption over 4 weeks., Aim: To understand perceptions of the value of CRP-POCT for guiding antibiotic prescribing for AECOPD; explore possible mechanisms, mediators, and pathways to effects; and identify potential barriers and facilitators to implementation from the perspectives of patients and clinicians., Design and Setting: Qualitative process evaluation in UK general practices., Method: Semi-structured telephone interviews with 20 patients presenting with an AECOPD and 20 primary care staff, purposively sampled from the PACE study. Interviews were audio-recorded, transcribed, and analysed using framework analysis., Results: Patients and clinicians felt that CRP-POCT was useful in guiding clinicians' antibiotic prescribing decisions for AECOPD, and were positive about introduction of the test in routine care. The CRP-POCT enhanced clinician confidence in antibiotic prescribing decisions, reduced decisional ambiguity, and facilitated communication with patients. Some clinicians thought the CRP-POCT should be routinely used in consultations for AECOPD; others favoured use only when there was decisional uncertainty. CRP-POCT cartridge preparation time and cost were potential barriers to implementation., Conclusion: CRP-POCT-guided antibiotic prescribing for AECOPD had high acceptability, but commissioning arrangements and further simplification of the CRP-POCT need attention to facilitate implementation in routine practice., (©The Authors.)

The current coronavirus (COVID-19) pandemic is again reminding us of the importance of using telehealth to deliver care, especially as means of reducing the risk of cross-contamination caused by close contact. For telehealth to be effective as part of an emergency response it first needs to become a routinely used part of our health system. Hence, it is time to step back and ask why telehealth is not mainstreamed. In this article, we highlight key requirements for this to occur. Strategies to ensure that telehealth is used regularly in acute, post-acute and emergency situations, alongside conventional service delivery methods, include flexible funding arrangements, training and accrediting our health workforce. Telehealth uptake also requires a significant change in management effort and the redesign of existing models of care. Implementing telehealth proactively rather than reactively is more likely to generate greater benefits in the long-term, and help with the everyday (and emergency) challenges in healthcare.

Objective: Major lower limb amputation is the highest risk lower limb procedure in vascular surgery. Despite this, few high quality studies have examined factors contributing to mortality. The aim was to identify independent risk factors for peri-operative morbidity and mortality and develop reliable models for estimating risk., Methods: All patients undergoing lower limb amputation above the ankle entered into the UK National Vascular Registry (January 2014-December 2016) were included. Missing data were handled using multiple imputation. Models were developed to evaluate independent risk factors for mortality (the primary outcome) and morbidity using logistic regression, minimising the Bayesian information criterion to balance complexity and model fit. Ethical approval for the study was granted (Wales REC 3 ref:16/WA/0353)., Results: All 9549 above ankle joint amputations in the registry were included. Overall, 865 patients (9.1%) died before leaving hospital. Independent factors associated with mortality were emergency admission, bilateral operation, age, American Society of Anesthesiologists' grade, abnormal electrocardiogram, and increased white cell count or creatinine (p < .01 for all). Independent factors reducing mortality were transtibial operation, increased albumin or patient weight, and previous ipsilateral revascularisation procedures (p < .01 for all). A risk model incorporating these factors had good discrimination (C-statistic 0.79, 95% confidence interval 0.77-0.80) and excellent calibration. Morbidity rates were high, with 6.6%, 9.7%, and 4.3% of patients suffering cardiac, respiratory, and renal complications, respectively. The risk model was also predictive of morbidity outcomes (C-statistics 0.74, 0.69, and 0.74, respectively)., Conclusion: Morbidity and mortality after lower limb amputation are high in the UK. Some potentially modifiable factors for quality improvement initiatives have been identified and accurate predictive models that could assist patient counselling and decision making have been developed., (Copyright © 2019 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: Christopher C Butler reports that Afinion C-reactive protein devices and associated training given to participating general practices were provided by Alere Inc. (now Abbott Diagnostics, IL, USA) at no cost to the study. He has received fees for participating in a Roche Molecular Systems Advisory Board meeting on 4 and 5 February 2016 about point-of-care testing; held an investigator-initiated grant from Roche Molecular Diagnostics (Roche Molecular Systems Inc., CA, USA) to evaluate the analytic performance of the cobas® Liat® point-of-care device for detecting influenza using samples from a separately funded study; and is part of a publicly funded research consortia that includes industrial partners. He was a member of the Medical Research Council–National Institute for Health Research (MRC–NIHR) Efficacy and Mechanism Evaluation Board (2012–16). He has been a NIHR Senior Investigator since 2016. Kerenza Hood was a member of the Health Technology Assessment (HTA) programme Funding Boards Policy Group (formerly Clinical Studies Group) (2016 to present), the HTA General Board (2016 to present) and the NIHR Clinical Trials Unit Standing Advisory Committee (2014 to 2019). Gurudutt Naik reports non-financial support from Alere Inc. Carl Llor reports grants from the European Commission (Seventh Framework Programme and Horizon 2020), the Catalan Society of Family Medicine, Abbott Diagnostics and Instituto de Salud Carlos III (Spanish Ministry of Health) outside the submitted work. Rhiannon Phillips reports that her current post is a fellowship funded by Health and Care Research Wales as part of the Primary and Emergency Care Research Centre Wales research centre grant.

Background: Clinical registries are effective for monitoring clinical practice, yet manual data collection can limit their implementation and sustainability. The objective of this study was to assess the feasibility of using a data capture tool to collect cardiac rehabilitation (CR) minimum variables from electronic hospital administration databases to populate a new CR registry in Australia., Methods: Two CR facilities located in Melbourne, Australia participated, providing data on 42 variables including: patient socio-demographics, risk factors and co-morbidities, CR program information (e.g. number of CR sessions), process indicators (e.g. wait time) and patient outcomes (e.g. change in exercise capacity). A pre-programmed, automated data capture tool (GeneRic Health Network Information for the Enterprise [20]: https://www.grhanite.com/) (GRHANITE™) was installed at the sites to extract data available in an electronic format from hospital sites. Additionally, clinicians entered data on CR patients into a purpose-built web-based tool (Research Electronic Data Capture: https://www.project-redcap.org/) (REDCap). Formative evaluation including staff feedback was collected., Results: The GRHANITE™ tool was successfully installed at the two CR sites and data from 176 patients (median age = 67 years, 76% male) were securely extracted between September-December 2017. Data pulled electronically from hospital databases was limited to seven of the 42 requested variables. This is due to CR sites only capturing basic patient information (e.g. socio-demographics, CR appointment bookings) in hospital administrative databases. The remaining clinical information required for the CR registry was collected in formats (e.g. paper-based, scanned or Excel spreadsheet) deemed unusable for electronic data capture. Manually entered data into the web-tool enabled data collection on all remaining variables. Compared to historical methods of data collection, CR staff reported that the REDCap tool reduced data entry time., Conclusions: The key benefits of a scalable, automated data capture tool like GRHANITE™ cannot be fully realised in settings with under-developed electronic health infrastructure. While this approach remains promising for creating and maintaining a registry that monitors the quality of CR provided to patients, further investment is required in the digital platforms underpinning this approach., (Copyright © 2019 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Objective: To develop standardised programme content for Australian phase II cardiac rehabilitation (CR) programme., Design: Using the RAND/UCLA appropriateness method (RAM), a two-phase process including a comprehensive literature review and a two round modified Delphi process was undertaken to develop and validate content of a standardised CR programmes., Participants: An invited multidisciplinary expert advisory group (EAG; n=16), including CR health professionals (nurses, allied health professionals, cardiologist), academics, policy makers, representation from the Australian Cardiovascular Health and Rehabilitation Association and consumers, provided oversight of the literature review and assisted with development of best practice statements. Twelve members of the EAG went onto participate in the modified Delphi process rating the necessity of statements in two rounds on a scale of 1 (not necessary) to 9 (essential)., Main Outcome Measure: Best practice statements that achieved a median score of ≥8 on a nine-point scale were categorised as 'essential'; statements that achieved a median score of ≥6 were categorised as 'desirable' and statements with a median score of <6 were omitted., Results: 49 best practice statements were developed from the literature across ten areas of care within four module domains (CR foundations, developing heart health knowledge, psychosocial health and life beyond CR). At the end of a two-round validation process a total of 47 best practice statements were finalised; 29 statements were rated as essential, 18 as desirable and 2 statements were omitted., Conclusions: For the first time in Australia, an evidence-based and consensus-led standardised programme content for phase II CR has been developed that can be provided to CR coordinators., Competing Interests: Competing interests: SC received financial support from a Deakin University Dean’s Postdoctoral Research Fellowship. SC has also undertaken short-term consultancy for Medibank Private, not directly related to this work. ET received financial support from a National Health and Medical Research Council postgraduate scholarship (1113920)., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To determine the feasibility of undertaking a randomised controlled effectiveness trial evaluating the use of a perineural catheter (PNC) after major lower limb amputation with postoperative pain as the primary outcome., Design: Randomised controlled feasibility trial., Setting: Two vascular Centres in South Wales, UK., Participants: 50 patients scheduled for major lower limb amputation (below or above knee) for complications of peripheral vascular disease., Interventions: The treatment arm received a PNC placed adjacent to the sciatic or tibial nerve at the time of surgery, with continuous infusion of levobupivacaine hydrochloride 0.125% for up to 5 days. The control arm received neither local anaesthetic nor PNC. Both arms received usual perioperative anaesthesia and postoperative analgesia., Primary and Secondary Outcome Measures: The primary outcomes were the proportion of eligible patients who were randomised and the proportion of recruited patients who provided primary effectiveness outcome data. Secondary outcomes were: the proportion of recruited patients reaching 2 and 6 month follow-up and supplying pain data; identification of key cost drivers; development of an economic analysis framework for a future effectiveness trial; identification of barriers to recruitment and site set-up; and identification of the best way to measure postoperative pain., Results: Seventy-six of 103 screened patients were deemed eligible over a 10 month period. Fifty (64.5%) of these patients were randomised, with one excluded in the perioperative period. Forty-five (91.3%) of 49 recruited patients provided enough pain scores on a 4-point verbal rating scale to allow primary effectiveness outcome evaluation. Attrition rates were high; 18 patients supplied data at 6 month follow-up. Costs were dominated by length of hospital stay. Patients and healthcare professionals reported that trial processes were acceptable., Conclusions: Recruitment of patients into a trial comparing PNC use to usual care after major lower limb amputation with postoperative pain measured on a 4-point verbal rating scale is feasible. Evaluation of longer-term symptoms is difficult., Trial Registration Number: ISRCTN: 85 710 690. EudraCT: 2016-003544-37., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Little is known about clinicians' experiences of using a point-of-care test (POCT) to inform management of urinary tract infection (UTI) in general practice., Aim: To explore experiences of using the Flexicult test to inform management of UTI and views on requirements for an optimal POCT to inform successful implementation., Design & Setting: Telephone interviews with 35 primary care clinicians and healthcare professionals in Wales, England, Spain, and the Netherlands, who had participated in a trial of the Flexicult POCT for UTI based on urine culture., Method: Thematic analysis of semi-structured interviews., Results: Most primary care clinicians interviewed agreed on the need for a POCT in UTI management, and that the Flexicult POCT delivered quicker results than laboratory results used in usual care, reassured patients, boosted their confidence in decision-making, and reminded them about antibiotic stewardship. However, clinicians also reported difficulties in interpreting results, limitations on when the Flexicult could be used, and concerns that testing all patients would strain care delivery and prolong patient discomfort when delaying decisions until a non-rapid POCT result was available. An optimal POCT would produce more rapid results, and be reliable and easy to use. Uptake into routine care would be enhanced by: clear guidance on which patients should be tested; training for interpreting 'grey area' results; reiterating that even 'straightforward' cases might be better managed with a test; clear messages about stopping unnecessary antibiotics versus completing a course; and better self-management strategies to accompany implementation of delayed, or non-prescription of, antibiotics., Conclusion: Primary care clinicians believe that POCT tests could play a useful role in the management of UTI and gave clear recommendations for successful implementation., (Copyright © 2019, The Authors.)

Background: Point-of-care testing of C-reactive protein (CRP) may be a way to reduce unnecessary use of antibiotics without harming patients who have acute exacerbations of chronic obstructive pulmonary disease (COPD)., Methods: We performed a multicenter, open-label, randomized, controlled trial involving patients with a diagnosis of COPD in their primary care clinical record who consulted a clinician at 1 of 86 general medical practices in England and Wales for an acute exacerbation of COPD. The patients were assigned to receive usual care guided by CRP point-of-care testing (CRP-guided group) or usual care alone (usual-care group). The primary outcomes were patient-reported use of antibiotics for acute exacerbations of COPD within 4 weeks after randomization (to show superiority) and COPD-related health status at 2 weeks after randomization, as measured by the Clinical COPD Questionnaire, a 10-item scale with scores ranging from 0 (very good COPD health status) to 6 (extremely poor COPD health status) (to show noninferiority)., Results: A total of 653 patients underwent randomization. Fewer patients in the CRP-guided group reported antibiotic use than in the usual-care group (57.0% vs. 77.4%; adjusted odds ratio, 0.31; 95% confidence interval [CI], 0.20 to 0.47). The adjusted mean difference in the total score on the Clinical COPD Questionnaire at 2 weeks was -0.19 points (two-sided 90% CI, -0.33 to -0.05) in favor of the CRP-guided group. The antibiotic prescribing decisions made by clinicians at the initial consultation were ascertained for all but 1 patient, and antibiotic prescriptions issued over the first 4 weeks of follow-up were ascertained for 96.9% of the patients. A lower percentage of patients in the CRP-guided group than in the usual-care group received an antibiotic prescription at the initial consultation (47.7% vs. 69.7%, for a difference of 22.0 percentage points; adjusted odds ratio, 0.31; 95% CI, 0.21 to 0.45) and during the first 4 weeks of follow-up (59.1% vs. 79.7%, for a difference of 20.6 percentage points; adjusted odds ratio, 0.30; 95% CI, 0.20 to 0.46). Two patients in the usual-care group died within 4 weeks after randomization from causes considered by the investigators to be unrelated to trial participation., Conclusions: CRP-guided prescribing of antibiotics for exacerbations of COPD in primary care clinics resulted in a lower percentage of patients who reported antibiotic use and who received antibiotic prescriptions from clinicians, with no evidence of harm. (Funded by the National Institute for Health Research Health Technology Assessment Program; PACE Current Controlled Trials number, ISRCTN24346473.)., (Copyright © 2019 Massachusetts Medical Society.)

Background: The central aim was to examine the accuracy of the full range of daily activities recorded in self-report time-use diaries against data from two objective passive data collection devices (wearable camera and accelerometer) serving as criterion reference instruments. This enabled systematic checks and comparisons on the timing, sequence and duration of activities recorded from the three data sources., Methods: Participants (n = 148) were asked to complete a single-day self-report paper time-use diary designed for use in the Harmonised European Time Use Study (HETUS), while simultaneously wearing a camera that continuously recorded images of their activities, and an accelerometer tracking physical movement. In a reconstruction interview shortly after the data collection period, participants viewed the camera images to help researchers interpret the image sequences. Of the initial 148 recruits (multi-seed snowball sample, 59% women, aged 18-91, 43% > 40) 131 returned usable diary and camera records (of whom 124 also provided a usable whole-day accelerometer record. We compare time allocation estimates from the diary and camera records, and also match the diary and camera records to the simultaneously recorded accelerometer vector magnitudes., Results: The data were examined at three analytic levels: aggregate, individual diarist and timeslot. The most important finding is that the estimates of mean daily time devoted to 8 of the 10 main activities differ by < 10% in the camera and diary records. The single case of major divergence (eating) can be explained by a systematic difference between the procedures followed by the self-reporting diarist and the observer coding the camera records. There are more substantial differences at the respondent level, paired t-tests showing significant differences in time spent in the 4/10 categories. 45% of all variation in the accelerometer vector magnitudes in the timeslots is explained by camera and diary records. Detailed activity classifications perform much better than METs as predictors of actigraphy., Conclusions: The comparison of the diary with the camera and accelerometer records strongly supports using diary methodology for studying the full range of daily activity, particularly at aggregate levels. Accelerometer data could be combined with diary measures to improve estimation of METs equivalents for various types of active and sedentary behaviour.

Objective: To assess (1) how well validated existing paediatric track and trigger tools (PTTT) are for predicting adverse outcomes in hospitalised children, and (2) how effective broader paediatric early warning systems are at reducing adverse outcomes in hospitalised children., Design: Systematic review., Data Sources: British Nursing Index, Cumulative Index of Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effectiveness, EMBASE, Health Management Information Centre, Medline, Medline in Process, Scopus and Web of Knowledge searched through May 2018., Eligibility Criteria: We included (1) papers reporting on the development or validation of a PTTT or (2) the implementation of a broader early warning system in paediatric units (age 0-18 years), where adverse outcome metrics were reported. Several study designs were considered., Data Extraction and Synthesis: Data extraction was conducted by two independent reviewers using template forms. Studies were quality assessed using a modified Downs and Black rating scale., Results: 36 validation studies and 30 effectiveness studies were included, with 27 unique PTTT identified. Validation studies were largely retrospective case-control studies or chart reviews, while effectiveness studies were predominantly uncontrolled before-after studies. Metrics of adverse outcomes varied considerably. Some PTTT demonstrated good diagnostic accuracy in retrospective case-control studies (primarily for predicting paediatric intensive care unit transfers), but positive predictive value was consistently low, suggesting potential for alarm fatigue. A small number of effectiveness studies reported significant decreases in mortality, arrests or code calls, but were limited by methodological concerns. Overall, there was limited evidence of paediatric early warning system interventions leading to reductions in deterioration., Conclusion: There are several fundamental methodological limitations in the PTTT literature, and the predominance of single-site studies carried out in specialist centres greatly limits generalisability. With limited evidence of effectiveness, calls to make PTTT mandatory across all paediatric units are not supported by the evidence base., Prospero Registration Number: CRD42015015326., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

The relationship between altered default mode network (DMN) connectivity and abnormal serotonin function in major depressive disorder (MDD) has not been investigated. Using intravenous citalopram and resting-state fMRI, we investigated DMN intra-network connectivity and serotonin function in 77 healthy controls and patients with MDD. There were no significant main effects of MDD or citalopram on DMN intra-network connectivity; however, significant interactions indicated that group differences under saline were modified by citalopram. In MDD patients during saline infusion, in contrast with controls, the DMN (i) did not include the precuneus that was instead part of an anti-correlated network but (ii) did include amygdala that was part of the anti-correlated network in controls. Citalopram infusion in MDD patients restored the pattern seen in controls under saline. In healthy controls, citalopram infusion disengaged the precuneus from the DMN and engaged the amygdala, partially reproducing the abnormalities seen under saline in MDD. In exploratory analyses within the MDD group, greater rumination self-ratings were associated with greater intra-network connectivity of the anterior cingulate cortex with the DMN. We hypothesise that, in MDD, disengagement of the precuneus from the DMN relates to overgeneral memory bias in rumination. The opposite effect, with greater engagement of the amygdala in the DMN, reflects the negative valence of rumination. Reversal of these abnormalities by citalopram suggests that they may be related to impaired serotonin function. That citalopram engaged the amygdala in the DMN in controls may relate to the paradoxical effects on aversive processing seen with acute SSRIs in healthy subjects.

Objective: Phobic anxiety is a risk factor for poor prognosis following Acute Coronary Syndrome (ACS). A psychophysiological marker of vagal function, autonomic dysfunction may play a critical role in this relationship. The aim of the study was two-fold: to assess whether phobic anxiety was characterised by autonomic dysfunction (heart rate variability) in the short (1-month) and longer term (12-months) following ACS, and (ii) to quantify the extent to which HRV parameters modified the effect of phobic anxiety on all-cause hospital readmission over 2 years., Methods: The ADVENT study followed 416 ACS patients. At 1-month following discharge (T0), phobic anxiety and autonomic functioning were assessed using the Crown Crisp Index (CCI) and 11 indices of heart rate variability (HRV), respectively. HRV was measured again at 12-months (T1) (n = 359). Hospital readmission (all cause) was derived from an audit of hospital records by two medically trained research fellows. Generalised linear modelling (GLM) was used to first determine the association between CCI score at T0 and HRV parameters at T0 and T1. Binary logistic regression was used to measure the relationship between CCI scores and readmission (yes/no) and the extent to which HRV parameters modified this effect., Results: CCI scores were associated with 7 of the 11 indices of HRV: Average RR (ms), SDRR (ms), RMSSD (ms), SDSD (ms), pRR50 (%), LF Powers (ms2) and HF Powers (ms2) at T0 but not T1. CCI scores at T0 significantly predicted likelihood of readmission to hospital in the subsequent 2 year period. No parameter of HRV at T0 modified this effect., Limitations: We were unable to provide adjudicated major adverse coronary events outcome data, or account for changes in medication adherence, diet or physical activity., Conclusions: While phobic anxiety is associated with both reduced vagal function in the short term after an ACS event and 2 year all cause readmission, HRV does not appear to be the pathway by which phobic anxiety drives this outcome., (Copyright © 2018. Published by Elsevier B.V.)

Background: Ageing populations and increasing survival following acute coronary syndrome has resulted in large numbers of people living with cardiovascular disease and at high risk of hospitalizations. Rising hospital admissions have a significant financial cost to the healthcare system., Aim: The purpose of this study was to determine whether cardiac rehabilitation is protective against long-term hospital readmission (frequency and length) following acute coronary syndrome., Methods: Data from 416 Australian patients with acute coronary syndrome enrolled in the Anxiety Depression and heart rate Variability in cardiac patients: Evaluating the impact of Negative emotions on functioning after Twenty four months (ADVENT) prospective cohort study between January 2013-June 2014 was analyzed secondarily. Participants self-reported cardiac rehabilitation attendance over the 12 months post-discharge. All-cause readmission data were extracted from hospital records 24 months post-index event. The association between cardiac rehabilitation and all-cause readmission, frequency of readmissions, and length of stay was assessed using three methods (a) regression analysis, (b) propensity score matching, and (c) inverse probability treatment weighting., Results: Overall, 416 patients consented (53% of eligible patients), of which 414 (99.5%) survived the first 30 days post-discharge and were included in the analysis. Medical records were located for 409 participants after 24 months (98% follow-up rate). In total, 267 (65%) reported attending cardiac rehabilitation; there were 392 readmissions by 239 patients. Cardiac rehabilitation attendance was not associated with all-cause hospital readmission; however, it was associated with lower frequency of hospital admissions (odds ratio 0.53, 95% confidence interval: 0.31-0.91 p-value:0.022) and length of stay (coefficient -1.21 days, 95% confidence interval: -2.46-0.26; marginally significant p-value: 0.055) in adjusted models., Conclusion: This study substantiates the long-term benefits of cardiac rehabilitation on readmissions, including length of stay, which would result in lower costs to the healthcare system.

Background: Children with hearing loss associated with otitis media with effusion (OME) are commonly managed through surgical intervention, hearing aids or watchful waiting. A safe, inexpensive, effective medical treatment would enhance treatment options. Small, poorly conducted trials have found a short-term benefit from oral steroids., Objective: To determine the clinical effectiveness and cost-effectiveness of a 7-day course of oral steroids in improving hearing at 5 weeks in children with persistent OME symptoms and current bilateral OME and hearing loss demonstrated by audiometry., Design: Double-blind, individually randomised, placebo-controlled trial., Setting: Ear, nose and throat outpatient or paediatric audiology and audiovestibular medicine clinics in Wales and England., Participants: Children aged 2-8 years, with symptoms of hearing loss attributable to OME for at least 3 months, a diagnosis of bilateral OME made on the day of recruitment and audiometry-confirmed hearing loss., Interventions: A 7-day course of oral soluble prednisolone, as a single daily dose of 20 mg for children aged 2-5 years or 30 mg for 6- to 8-year-olds, or matched placebo., Main Outcome Measures: Acceptable hearing at 5 weeks from randomisation. Secondary outcomes comprised acceptable hearing at 6 and 12 months, tympanometry, otoscopic findings, health-care consultations related to OME and other resource use, proportion of children who had ventilation tube (grommet) surgery at 6 and 12 months, adverse effects, symptoms, functional health status, health-related quality of life, short- and longer-term cost-effectiveness., Results: A total of 389 children were randomised. Satisfactory hearing at 5 weeks was achieved by 39.9% and 32.8% in the oral steroid and placebo groups, respectively (absolute difference of 7.1%, 95% confidence interval -2.8% to 16.8%; number needed to treat = 14). This difference was not statistically significant. The secondary outcomes were consistent with the picture of a small or no benefit, and we found no subgroups that achieved a meaningful benefit from oral steroids. The economic analysis showed that treatment with oral steroids was more expensive and accrued fewer quality-adjusted life-years than treatment as usual. However, the differences were small and not statistically significant, and the sensitivity analyses demonstrated large variation in the results., Conclusions: OME in children with documented hearing loss and attributable symptoms for at least 3 months has a high rate of spontaneous resolution. Discussions about watchful waiting and other interventions will be enhanced by this evidence. The findings of this study suggest that any benefit from a short course of oral steroids for OME is likely to be small and of questionable clinical significance, and that the treatment is unlikely to be cost-effective and, therefore, their use cannot be recommended., Future Work: Studies exploring optimal approaches to sharing natural history data and enhancing shared decision-making are needed for this condition., Trial Registration: Current Controlled Trials ISRCTN49798431 and EudraCT 2012-005123-32., 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. 22, No. 61. See the NIHR Journals Library website for further project information., Competing Interests: Christopher C Butler is a National Institute for Health Research (NIHR) senior investigator. Kerenza Hood and Amanda Roberts are members of the NIHR Health Technology Assessment General Board. Kerenza Hood is a member of the NIHR Clinical Trials Unit Standing Committee.

Competing Interests: Conflict of interest: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Background: Patient-reported outcomes measures in clinical trials ensure that evaluations of effectiveness focus on outcomes that are important to patients. In relapsing-remitting conditions, such as eczema, repeated measurements may allow a more accurate reflection of disease burden and treatment effect than less frequent measurements. We asked parents/carers of children with eczema taking part in a trial of bath emollients to complete weekly questionnaires for 16 weeks., Methods: The objective of this study was to determine the acceptability and practicality of collecting weekly measures of eczema severity online for 16 weeks in children aged 1 to 11 years as part of the BATHE study. BATHE randomised patients to bath emollients plus standard eczema care or standard eczema care only. The primary outcome was eczema severity, measured by the seven-item Patient-Oriented Eczema Measure (POEM) repeated weekly for 16 weeks. Acceptability was explored through qualitative interviews with 10 participants. Interviews were audio-recorded, transcribed and analysed thematically. Practicality was assessed by exploring the completeness of the data and keeping a log of any problems., Results: Four hundred and eighty-two participants were recruited to the trial and 429 opted to complete measures online (89.0%). Data were collected online for 83% of time points over the 16-week period and there was no association between socio-demographic characteristics and data completeness. Two hundred and six (48%) completed their weekly data every week for 16 weeks and 341 (79%) completed it at least 80% of the time. The mean number of weeks completed was 13.3 out of 16 (SD 4.2). Interviewees said that they understood the rationale behind weekly collection and some welcomed this as it helped them realise how their child's eczema changed weekly. Whilst some interviewees spoke of weekly questionnaires as onerous, others said that they found them quick and easy. Reminders were welcomed. Parents/carers seemed happy to receive telephone reminders and it was sometimes useful for eliciting problems relating to obtaining trial medication or password problems for online data collection., Conclusions: Amongst this population, high levels of data completeness suggests that weekly completion of the online questionnaire appears to be acceptable and feasible over a 16-week period., Trial Registration: ISRCTN84102309 . Registered on 9 December 2013.

Background: Childhood eczema is very common. Treatment often includes emollient bath additives, despite there being little evidence of their effectiveness., Objectives: To determine the clinical effectiveness and cost-effectiveness of emollient bath additives in the management of childhood eczema., Design: Pragmatic, randomised, open-label, multicentre superiority trial with two parallel groups., Setting: Ninety-six general practices in Wales, the west of England and southern England. Invitation by personal letter or opportunistically., Participants: Children aged between 12 months and 12 years fulfilling the UK Diagnostic Criteria for Atopic Eczema. Children with inactive or very mild eczema (a score of ≤ 5 on the Nottingham Eczema Severity Scale) were excluded, as were children who bathed less than once per week or whose parents/carers were not prepared to accept randomisation., Interventions: The intervention group were prescribed bath additives by their usual clinical team and were asked to use them regularly for 12 months. The control group were asked to use no bath additives for 12 months. Both groups continued standard eczema management, including regular leave-on emollients and topical corticosteroids (TCSs) when required., Main Outcome Measures: The primary outcome was eczema control measured by Patient Oriented Eczema Measure [POEM, 0 (clear) to 28 (severe)] weekly for 16 weeks. The secondary outcomes were eczema severity over 1 year (4-weekly POEM), number of eczema exacerbations, disease-specific quality of life (QoL) (Dermatitis Family Impact Questionnaire), generic QoL (Child Health Utility-9 Dimensions) and type and quantity of topical steroid/calcineurin inhibitors prescribed. Children were randomised (1 : 1) using online software to either bath additives plus standard eczema care or standard eczema care alone, stratified by recruiting centre, and there was open-label blinding., Results: From December 2014 to May 2016, 482 children were randomised: 51% were female, 84% were white and the mean age was 5 years ( n  = 264 in the intervention group, n  = 218 in the control group). Reported adherence to randomised treatment allocation was > 92% in both groups, with 76.7% of participants completing at least 12 (80%) of the first 16 weekly questionnaires for the primary outcome. Baseline POEM score was 9.5 [standard deviation (SD) 5.7] in the bath additives group and 10.1 (SD 5.8) in the no bath additives group. Average POEM score over the first 16 weeks was 7.5 (SD 6.0) in the bath additives group and 8.4 (SD 6.0) in the no bath additives group, with no statistically significant difference between the groups. After controlling for baseline severity and confounders (ethnicity, TCS use, soap substitute use) and allowing for clustering of participants within centres and responses within participants over time, POEM scores in the no bath additive group were 0.41 points higher than in the bath additive group (95% confidence interval -0.27 to 1.10), which is well below the published minimal clinically important difference of 3 points. There was no difference between groups in secondary outcomes or in adverse effects such as redness, stinging or slipping., Limitations: Simple randomisation resulted in an imbalance in baseline group size, although baseline characteristics were well balanced between groups., Conclusion: This trial found no evidence of clinical benefit of including emollient bath additives in the standard management of childhood eczema., Future Work: Further research is required on optimal regimens of leave-on emollients and the use of emollients as soap substitutes., Trial Registration: Current Controlled Trials ISRCTN84102309., Funding: This project was funded by the NIHR Health Technology Assessment Programme and will be published in full in Health Technology Assessment ; Vol. 22, No. 57. See the NIHR Journals Library website for further project information., Competing Interests: Matthew J Ridd is a member of the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) General Board. Nick A Francis was a member of the HTA Antimicrobial Resistance Themed Call Board during the study. Amanda Roberts is a member of the HTA General Board. As patient and public involvement co-applicant, Amanda Roberts also received an attendance allowance and travel expenses from the University of Southampton in order to attend meetings. Emma Thomas-Jones reports grants from the NIHR HTA programme during the conduct of the study. Hywel C Williams is Director of the NIHR HTA programme. Paul Little is a member of the NIHR Journals Library Board.