Search

Objectives Our recent systematic review determined that remote patient monitoring (RPM) interventions can reduce acute care use. However, effectiveness varied within and between populations. Clinicians, researchers, and policymakers require more than evidence of effect; they need guidance on how best to design and implement RPM interventions. Therefore, this study aimed to explore these results further to (1) identify factors of RPM interventions that relate to increased and decreased acute care use and (2) develop recommendations for future RPM interventions.Design Realist review—a qualitative systematic review method which aims to identify and explain why intervention results vary in different situations. We analysed secondarily 91 studies included in our previous systematic review that reported on RPM interventions and the impact on acute care use. Online databases PubMed, EMBASE and CINAHL were searched in October 2020. Included studies were published in English during 2015–2020 and used RPM to monitor an individual’s biometric data (eg, heart rate, blood pressure) from a distance.Primary and secondary outcome measures Contextual factors and potential mechanisms that led to variation in acute care use (hospitalisations, length of stay or emergency department presentations).Results Across a range of RPM interventions 31 factors emerged that impact the effectiveness of RPM innovations on acute care use. These were synthesised into six theories of intervention success: (1) targeting populations at high risk; (2) accurately detecting a decline in health; (3) providing responsive and timely care; (4) personalising care; (5) enhancing self-management, and (6) ensuring collaborative and coordinated care.Conclusion While RPM interventions are complex, if they are designed with patients, providers and the implementation setting in mind and incorporate the key variables identified within this review, it is more likely that they will be effective at reducing acute hospital events.PROSPERO registration number CRD42020142523.

Objective Chronic diseases are associated with increased unplanned acute hospital use. Remote patient monitoring (RPM) can detect disease exacerbations and facilitate proactive management, possibly reducing expensive acute hospital usage. Current evidence examining RPM and acute care use mainly involves heart failure and omits automated invasive monitoring. This study aimed to determine if RPM reduces acute hospital use.Methods A systematic literature review of PubMed, Embase and CINAHL electronic databases was undertaken in July 2019 and updated in October 2020 for studies published from January 2015 to October 2020 reporting RPM and effect on hospitalisations, length of stay or emergency department presentations. All populations and disease conditions were included. Two independent reviewers screened articles. Quality analysis was performed using the Joanna Briggs Institute checklist. Findings were stratified by outcome variable. Subgroup analysis was undertaken on disease condition and RPM technology.Results From 2050 identified records, 91 studies were included. Studies were medium-to-high quality. RPM for all disease conditions was reported to reduce admissions, length of stay and emergency department presentations in 49% (n=44/90), 49% (n=23/47) and 41% (n=13/32) of studies reporting each measure, respectively. Remaining studies largely reported no change. Four studies reported RPM increased acute care use. RPM of chronic obstructive pulmonary disease (COPD) was more effective at reducing emergency presentation than RPM of other disease conditions. Similarly, invasive monitoring of cardiovascular disease was more effective at reducing hospital admissions versus other disease conditions and non-invasive monitoring.Conclusion RPM can reduce acute care use for patients with cardiovascular disease and COPD. However, effectiveness varies within and between populations. RPM’s effect on other conditions is inconclusive due to limited studies. Further analysis is required to understand underlying mechanisms causing variation in RPM interventions. These findings should be considered alongside other benefits of RPM, including increased quality of life for patients.PROSPERO registration number CRD42020142523.

Differential diagnosis in adult cohorts with social difficulty is confounded by comorbid mental health conditions, common etiologies, and shared phenotypes. Identifying shared and discriminating profiles can facilitate intervention and remediation strategies. The objective of the study was to identify salient features of a composite test battery of cognitive and mood measures using a machine learning paradigm in clinical cohorts with social interaction difficulties. We recruited clinical participants who met standardized diagnostic criteria for autism spectrum disorder (ASD: n = 62), early psychosis (EP: n = 48), or social anxiety disorder (SAD: N = 83) and compared them with a neurotypical comparison group (TYP: N = 43). Using five machine-learning algorithms and repeated cross-validation, we trained and tested classification models using measures of cognitive and executive function, lower- and higher-order social cognition and mood severity. Performance metrics were the area under the curve (AUC) and Brier Scores. Sixteen features successfully differentiated between the groups. The control versus social impairment cohorts (ASD, EP, SAD) were differentiated by social cognition, visuospatial memory and mood measures. Importantly, a distinct profile cluster drawn from social cognition, visual learning, executive function and mood, distinguished the neurodevelopmental cohort (EP and ASD) from the SAD group. The mean AUC range was between 0.891 and 0.916 for social impairment versus control cohorts and, 0.729 to 0.781 for SAD vs neurodevelopmental cohorts. This is the first study that compares an extensive battery of neuropsychological and self-report measures using a machine learning protocol in clinical and neurodevelopmental cohorts characterized by social impairment. Findings are relevant for diagnostic, intervention and remediation strategies for these groups.

Abstract Background There is a strong research imperative to investigate effective treatment options for adolescents and adults with autism spectrum disorder (ASD). Elevated social anxiety, difficulties with social functioning and poor mental health have all been identified as core treatment targets for this group. While theoretical models posit a strong bidirectionality between social anxiety and ASD social functioning deficits, few interventions have targeted both domains concurrently. Of the two group interventions previously conducted with adolescents and adults with ASD, significant results have only been observed in either social anxiety or social functioning, and have not generalised to changes in overall mood. The aim of this study was to evaluate the potential benefit, tolerability and acceptability of a group cognitive-behaviour therapy (CBT) intervention in young adults with ASD. Primary treatment outcomes were social anxiety symptoms and social functioning difficulties; secondary outcomes were self-reported mood and overall distress. Method Ten groups of participants completed an eight-week, modified group CBT intervention targeting both social anxiety and social functioning, that included social skills training, exposure tasks and behavioural experiment components. Seventy-eight adolescents and young adults with ASD, without intellectual impairment, aged between 16 and 38 (M = 22.77; SD = 5.31), were recruited from the community, Headspace centres and the Autism Clinic for Translational Research at the Brain and Mind Centre, University of Sydney. Outcomes (social anxiety, social functioning and mood) were measured pre- and post-intervention via self-report questionnaires (administered either online or through the return of hard-copy booklets), and participants were invited to provide anonymous feedback on the intervention (at the mid-point and end of the intervention). Results Participants demonstrated statistically significant improvements on all outcome measures in response to the intervention. Specifically, social anxiety symptoms decreased (p

Background: Procalcitonin (PCT) is a blood marker used to help diagnose bacterial infections and guide antibiotic treatment. PCT testing was widely used/adopted during the COVID-19 pandemic in the UK., Objectives: Primary: to measure the difference in length of early (during first 7 days) antibiotic prescribing between patients with COVID-19 who did/did not have baseline PCT testing during the first wave of the pandemic. Secondary: to measure differences in length of hospital/ICU stay, mortality, total days of antibiotic prescribing and resistant bacterial infections between these groups., Methods: Multi-centre, retrospective, observational, cohort study using patient-level clinical data from acute hospital Trusts/Health Boards in England/Wales. Inclusion: patients ≥16 years, admitted to participating Trusts/Health Boards and with a confirmed positive COVID-19 test between 1 February 2020 and 30 June 2020., Results: Data from 5960 patients were analysed: 1548 (26.0%) had a baseline PCT test and 4412 (74.0%) did not. Using propensity-score matching, baseline PCT testing was associated with an average reduction in early antibiotic prescribing of 0.43 days [95% confidence interval (CI): 0.22-0.64 days, P < 0.001) and of 0.72 days (95% CI: 0.06-1.38 days, P = 0.03] in total antibiotic prescribing. Baseline PCT testing was not associated with increased mortality or hospital/ICU length of stay or with the rate of antimicrobial-resistant secondary bacterial infections., Conclusions: Baseline PCT testing appears to have been an effective antimicrobial stewardship tool early in the pandemic: it reduced antibiotic prescribing without evidence of harm. Our study highlights the need for embedded, rapid evaluations of infection diagnostics in the National Health Service so that even in challenging circumstances, introduction into clinical practice is supported by evidence for clinical utility., Study Registration Number: ISRCTN66682918., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: Clinical tools are needed in general practice to help identify children who are seriously ill. The Liverpool quick Sequential Organ Failure Assessment (LqSOFA) was validated in an emergency department and performed well. The National Paediatric Early Warning System (PEWS) has been introduced in hospitals throughout England with hopes for implementation in general practice., Aim: To validate the LqSOFA and National PEWS in general practice., Design and Setting: Secondary analysis of 6703 children aged <5 years presenting to 225 general practices in England and Wales with acute illnesses, linked to hospital data., Method: Variables from the LqSOFA and National PEWS were mapped onto study data to calculate score totals. A primary outcome of admission within 2 days of GP consultation was used to calculate sensitivity, specificity, negative predictive values (NPVs), positive predictive values (PPVs), and area under the receiver operating characteristic curve (AUC)., Results: A total of 104/6703 children were admitted to hospital within 2 days (pre-test probability 1.6%) of GP consultation. The sensitivity of the LqSOFA was 30.6% (95% confidence interval [CI] = 21.8% to 41.0%), with a specificity of 84.7% (95% CI = 83.7% to 85.6%), PPV of 3.0% (95% CI = 2.1% to 4.4%), NPV of 98.7% (95% CI = 98.4% to 99.0%), and AUC of 0.58 (95% CI = 0.53 to 0.63). The sensitivity of the National PEWS was 81.0% (95% CI = 71.0% to 88.1%), with a specificity of 32.5% (95% CI = 31.2% to 33.8%), PPV of 1.9% (95% CI = 1.5% to 2.5%), NPV of 99.1% (95% CI = 98.4% to 99.4%), and AUC of 0.66 (95% CI = 0.59 to 0.72)., Conclusion: Although the NPVs appear useful, owing to low pre-test probabilities rather than discriminative ability, neither tool accurately identified admissions to hospital. Unconsidered use by GPs could result in unsustainable referrals., (© The Authors.)

Background: Systematic reviews have reported conflicting evidence on whether macrolide antibiotics reduce rates of chronic lung disease of prematurity (CLD) in at-risk preterm infants born at less than 30 weeks' gestation, including in those colonised with pulmonary Ureaplasma spp. Since an adequately powered trial has been lacking, we aimed to assess if the macrolide azithromycin improved survival without the development of physiologically defined moderate or severe CLD in preterm infants., Methods: AZTEC was a multicentre, double-blind, randomised, placebo-controlled trial conducted in 28 tertiary neonatal intensive care units in the UK. Infants were eligible if they were born at less than 30 weeks' gestation and had received at least 2 h of either non-invasive (continuous positive airway pressure or humidified high flow nasal cannula therapy) or invasive respiratory support (via endotracheal tube) within 72 h of birth. Eligible infants were randomly allocated in a 1:1 ratio using random permuted blocks of four to receive either intravenous azithromycin at 20 mg/kg per day for 3 days followed by 10 mg/kg for 7 days, or to placebo. Allocation was stratified by centre and gestational age at birth (<28 weeks vs ≥28 weeks). Azithromycin and placebo vials were encased in tamper-evident custom cardboard cartons to ensure masking for clinicians, parents, and the research team. The primary outcome was survival without development of physiologically defined moderate or severe CLD at 36 weeks' postmenstrual age. Outcomes and safety were analysed on an intention-to-treat basis (all randomly allocated infants, regardless of any post-randomisation events). The study was registered with ISRCRN (11650227) and is closed., Findings: Infants were recruited between Oct 9, 2019, and March 22, 2022. 799 (53·1%) of 1505 eligible infants underwent random allocation; three infants were withdrawn, including consent to use their data, leaving 796 infants for analysis. Survival without moderate or severe CLD occurred in 166 (42%) of 394 infants in the intervention group and 179 (45%) of 402 in the placebo group (three-level adjusted OR [aOR] 0·84, 95% CI 0·55-1·29, p=0·43). Pulmonary Ureaplasma spp colonisation did not influence treatment effect. Overall, seven serious adverse events were reported for the azithromycin group (five graded as severe, two as moderate), and six serious adverse events were reported in the placebo group (two severe, two moderate, and two mild), as assessed by the local principal investigators., Interpretation: Since prophylactic use of azithromycin did not improve survival without development of physiologically-defined CLD, regardless of Ureaplasma spp colonisation, it cannot be recommended in clinical practice., Funding: UK National Institute for Health and Care Research., Competing Interests: Declaration of interests SK, JL, DG, KH, NK, ET-J, MT, JM, and JB received funding from NIHR HTA as coapplicants for this project. JM reports payments or honoraria for lectures from Institut Biochimique SA, support for attending meetings from Fred Hutchinson Cancer Centre, and patents issued and pending. SK reports receiving grant funding outside of this work from the Medical Research Council, Aspire Pharma, and Moulton Foundation; and consultancy fees from Aspire Pharma during the past 36 months. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Many hospitals introduced procalcitonin (PCT) testing to help diagnose bacterial coinfection in individuals with COVID-19, and guide antibiotic decision-making during the COVID-19 pandemic in the UK., Objectives: Evaluating cost-effectiveness of using PCT to guide antibiotic decisions in individuals hospitalized with COVID-19, as part of a wider research programme., Methods: Retrospective individual-level data on patients hospitalized with COVID-19 were collected from 11 NHS acute hospital Trusts and Health Boards from England and Wales, which varied in their use of baseline PCT testing during the first COVID-19 pandemic wave. A matched analysis (part of a wider analysis reported elsewhere) created groups of patients whose PCT was/was not tested at baseline. A model was created with combined decision tree/Markov phases, parameterized with quality-of-life/unit cost estimates from the literature, and used to estimate costs and quality-adjusted life years (QALYs). Cost-effectiveness was judged at a £20 000/QALY threshold. Uncertainty was characterized using bootstrapping., Results: People who had baseline PCT testing had shorter general ward/ICU stays and spent less time on antibiotics, though with overlap between the groups' 95% CIs. Those with baseline PCT testing accrued more QALYs (8.76 versus 8.62) and lower costs (£9830 versus £10 700). The point estimate was baseline PCT testing being dominant over no baseline testing, though with uncertainty: the probability of cost-effectiveness was 0.579 with a 1 year horizon and 0.872 with a lifetime horizon., Conclusions: Using PCT to guide antibiotic therapy in individuals hospitalized with COVID-19 is more likely to be cost-effective than not, albeit with uncertainty., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: Information on the quality of life of people hospitalised with COVID-19 is important, both in assessing the burden of disease and the cost-effectiveness of treatments. However, there were potential barriers to collecting such evidence., Objective: To review the existing evidence on quality of life for people hospitalised with COVID-19, with a focus on the amount of evidence available and methods used., Design: A scoping review with systematic searches., Results: A total of 35 papers were selected for data extraction. The most common study type was economic evaluation ( N  = 13), followed by cross-sectional ( N  = 10). All economic evaluations used published utility values for other conditions to represent COVID-19 inpatients' quality of life. The most popular quality-of-life survey measure was the Pittsburgh Sleep Quality Index ( N  = 8). There were 12 studies that used a mental health-related survey and 12 that used a sleep-related survey. Five studies used EQ-5D, but only one collected responses from people in the acute phase of COVID-19. Studies reported a negative impact on quality of life for people hospitalised with COVID-19, although many studies did not include a formal comparison group., Limitations: Although it used systematic searches, this was not a full systematic review., Conclusion: Quality-of-life data were collected from people hospitalised with COVID-19 from relatively early in the pandemic. However, there was a lack of consensus as to what survey measures to use, and few studies used generic health measures. Economic evaluations for COVID-19 treatments did not use utilities collected from people with COVID-19. In future health crises, researchers should be vigilant for opportunities to collect quality-of-life data from hospitalised patients but should try to co-ordinate as well as ensuring generic health measures are used more., Funding: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR132254.

Competing Interests: Conflicts of interest R.C.-J. was a NIHR HTA Associate Board Member (May 2018 to March 2020). F.C. is a consultant for UCB Pharma and received a fee from Daylong for participating in a hidradenitis suppurativa consensus meeting. L.H. has received consultancy fees from the University of Oxford for an educational grant funded by Pfizer, unrelated to the submitted work. K.H. is a member of the NIHR Research Professors Panel (2019–­present), and was a member of the NIHR HTA General Committee (2016–22) and the NIHR HTA Funding Committee Policy Group (2017–22). J.R.I. receives a stipend as Editor-in-Chief of the British Journal of Dermatology and an authorship honorarium from UpToDate. He is a consultant for Abbvie, Boehringer Ingelheim, ChemoCentryx, Citryll, MoonLake, Novartis, UCB Pharma and UNION Therapeutics, and has served on advisory boards for Insmed, Kymera Therapeutics and Viela Bio. He is co-copyright holder of HiSQOL, Investigator Global Assessment and Patient Global Assessment instruments for HS. His department receives income from the copyright of the Dermatology Life Quality Instrument (DLQI) and related instruments.

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

Although sex differences in amyotrophic lateral sclerosis (ALS) have not been studied systematically, numerous clinical and preclinical studies have shown sex to be influential in disease prognosis. Moreover, with the development of advanced imaging tools, the difference between male and female brain in structure and function and their response to neurodegeneration are more definitive. As discussed in this review, ALS patients exhibit a sex bias pertaining to the features of the disease, and their clinical, pathological, (and pathophysiological) phenotypes. Several epidemiological studies have indicated that this sex disparity stems from various aetiologies, including sex-specific brain structure and neural functioning, genetic predisposition, age, gonadal hormones, susceptibility to traumatic brain injury (TBI)/head trauma and lifestyle factors., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Hidradenitis suppurativa (HS) is a chronic, painful disease affecting flexures and other skin regions, producing nodules, abscesses and skin tunnels. Laser treatment targeting hair follicles and deroofing of skin tunnels are standard HS interventions in some countries but are rarely offered in the UK., Objectives: To describe current UK HS management pathways and influencing factors to inform the design of future randomized controlled trials (RCTs)., Methods: THESEUS was a nonrandomized 12-month prospective cohort study set in 10 UK hospitals offering five interventions: oral doxycycline 200 mg daily; oral clindamycin and rifampicin both 300 mg twice daily for 10 weeks, extended for longer in some cases; laser treatment targeting hair follicles; deroofing; and conventional surgery. The primary outcome was the combination of clinician-assessed eligibility and participant hypothetical willingness to receive each intervention. The secondary outcomes were the proportion of participants selecting each intervention as their final treatment option; the proportion who switch treatments; treatment fidelity; and attrition rates. THESEUS was prospectively registered on the ISRCTN registry: ISRCTN69985145., Results: The recruitment target of 150 participants was met after 18 months, in July 2021, with two pauses due to the COVID-19 pandemic. Baseline demographics reflected the HS secondary care population: average age 36 years, 81% female, 20% non-White, 64% current or ex-smokers, 86% body mass index ≥ 25, 68% with moderate disease, 19% with severe disease and 13% with mild disease. Laser was the intervention with the highest proportion (69%) of participants eligible and willing to receive treatment, then deroofing (58%), conventional surgery (54%), clindamycin and rifampicin (44%), and doxycycline (37%). Laser was ranked first choice by the greatest proportion of participants (41%). Attrition rates were 11% and 17% after 3 and 6 months, respectively. Concordance with doxycycline was 52% after 3 months due to lack of efficacy, participant choice and adverse effects. Delays with procedural interventions were common, with only 43% and 26% of participants starting laser and deroofing, respectively, after 3 months. Uptake of conventional surgery was too small to characterize the intervention. Switching treatment was uncommon and there were no serious adverse events., Conclusions: THESEUS has established laser treatment and deroofing for HS in the UK and demonstrated their popularity with patients and clinicians for future RCTs., Competing Interests: Conflicts of interest J.R.I. receives a stipend as Editor-in-Chief of the British Journal of Dermatology and an authorship honorarium from UpToDate. He is a consultant for AbbVie, Boehringer Ingelheim, ChemoCentryx, Citryll, MoonLake, Novartis and UCB Pharma and has served on advisory boards for Insmed, Kymera Therapeutics and Viela Bio. He is co-copyright holder of HiSQOL, Investigator Global Assessment and Patient Global Assessment instruments for hidradenitis suppurativa (HS). His department receives income from the copyright of the Dermatology Life Quality Instrument (DLQI) and related instruments. R.C.-J. was a UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Associate Board Member (May 2018 to March 2020). F.C. is a consultant for UCB Pharma and received a fee from Daylong for participating in a HS consensus meeting. L.H. has received consultancy fees from the University of Oxford for an educational grant funded by Pfizer, unrelated to the submitted work. K.H. is a member of the NIHR HTA General Committee (2016–2022), the NIHR HTA Funding Committee Policy Group (2017–2022) and the NIHR Research Professors Panel (2019–present)., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Importance: Measures of the proportion of individuals living in households with a firearm (HFR), over time, across states, and by demographic groups are needed to evaluate disparities in firearm violence and the effects of firearm policies., Objective: To estimate HFR across states, years, and demographic groups in the US., Design, Setting, and Participants: In this survey study, substate HFR totals from 1990 to 2018 were estimated using bayesian multilevel regression with poststratification to analyze survey data on HFR from the Behavioral Risk Factor Surveillance System and the General Social Survey. HFR was estimated for 16 substate demographic groups defined by gender, race, marital status, and urbanicity in each state and year., Exposures: Survey responses indicating household firearm ownership were analyzed and compared with a common proxy for firearm ownership, the fraction of suicides completed with a firearm (FSS)., Main Outcome and Measure: HFR, FSS, and their correlations and differences., Results: Among US adults in 2018, HFR was significantly higher among married, nonurban, non-Hispanic White and American Indian male individuals (65.0%; 95% credible interval [CI], 61.5%-68.7%) compared with their unmarried, urban, female counterparts from other racial and ethnic groups (7.3%; 95% CIs, 6.0%-9.2%). Marginal HFR rates for larger demographic groups also revealed important differences, with racial minority groups and urban dwellers having less than half the HFR of either White and American Indian (39.5%; 95% CI, 37.4%-42.9% vs 17.2%; 95% CI, 15.5%-19.9%) or nonurban populations (46.0%; 95% CI, 43.8%-49.5% vs 23.1%; 95% CI, 21.3%-26.2%). Population growth among groups less likely to own firearms, rather than changes in ownership within demographic groups, explains 30% of the 7 percentage point decline in HFR nationally from 1990 to 2018. Comparing HFR estimates with FSS revealed the expected high overall correlation across states (r = 0.84), but scaled FSS differed from HFR by as many as 20 percentage points for some states and demographic groups., Conclusions and Relevance: This survey study of HFR providing detailed, publicly available HFR estimates highlights key disparities among individuals in households with firearms across states and demographic groups; it also identifies potential biases in the use of FSS as a proxy for firearm ownership rates. These findings are essential for researchers, policymakers, and public health experts looking to address geographic and demographic disparities in firearm violence.

Background: Decision-making when considering major lower limb amputation is complex and requires individualized outcome estimation. It is unknown how accurate healthcare professionals or relevant outcome prediction tools are at predicting outcomes at 1-year after major lower limb amputation., Methods: An international, multicentre prospective observational study evaluating healthcare professional accuracy in predicting outcomes 1 year after major lower limb amputation and evaluation of relevant outcome prediction tools identified in a systematic search of the literature was undertaken. Observed outcomes at 1 year were compared with: healthcare professionals' preoperative predictions of death (surgeons and anaesthetists), major lower limb amputation revision (surgeons) and ambulation (surgeons, specialist physiotherapists and vascular nurse practitioners); and probabilities calculated from relevant outcome prediction tools., Results: A total of 537 patients and 2244 healthcare professional predictions of outcomes were included. Surgeons and anaesthetists had acceptable discrimination (C-statistic = 0.715), calibration and overall performance (Brier score = 0.200) when predicting 1-year death, but performed worse when predicting major lower limb amputation revision and ambulation (C-statistics = 0.627 and 0.662 respectively). Healthcare professionals overestimated the death and major lower limb amputation revision risks. Consultants outperformed trainees, especially when predicting ambulation. Allied healthcare professionals marginally outperformed surgeons in predicting ambulation. Two outcome prediction tools (C-statistics = 0.755 and 0.717, Brier scores = 0.158 and 0.178) outperformed healthcare professionals' discrimination, calibration and overall performance in predicting death. Two outcome prediction tools for ambulation (C-statistics = 0.688 and 0.667) marginally outperformed healthcare professionals., Conclusion: There is uncertainty in predicting 1-year outcomes following major lower limb amputation. Different professional groups performed comparably in this study. Two outcome prediction tools for death and two for ambulation outperformed healthcare professionals and may support shared decision-making., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Objective: To explore and model factors affecting antibiotic prescribing decision-making early in the pandemic., Design: Semistructured qualitative interview study., Setting: National Health Service (NHS) trusts/health boards in England and Wales., Participants: Clinicians from NHS trusts/health boards in England and Wales., Method: Individual semistructured interviews were conducted with clinicians in six NHS trusts/health boards in England and Wales as part of the Procalcitonin Evaluation of Antibiotic use in COVID-19 Hospitalised patients study, a wider study that included statistical analysis of procalcitonin (PCT) use in hospitals during the first wave of the pandemic. Thematic analysis was used to identify key factors influencing antibiotic prescribing decisions for patients with COVID-19 pneumonia during the first wave of the pandemic (March to May 2020), including how much influence PCT test results had on these decisions., Results: During the first wave of the pandemic, recommendations to prescribe antibiotics for patients with COVID-19 pneumonia were based on concerns about secondary bacterial infections. However, as clinicians gained more experience with COVID-19, they reported increasing confidence in their ability to distinguish between symptoms and signs caused by SARS-CoV-2 viral infection alone, and secondary bacterial infections. Antibiotic prescribing decisions were influenced by factors such as clinician experience, confidence, senior support, situational factors and organisational influences. A decision-making model was developed., Conclusion: This study provides insight into the decision-making process around antibiotic prescribing for patients with COVID-19 pneumonia during the first wave of the pandemic. The importance of clinician experience and of senior review of decisions as factors in optimising antibiotic stewardship is highlighted. In addition, situational and organisational factors were identified that could be optimised. The model presented in the study can be used as a tool to aid understanding of the complexity of the decision-making process around antibiotic prescribing and planning antimicrobial stewardship support in the context of a pandemic., Trial Registration Number: ISRCTN66682918., Competing Interests: Competing interests: All authors (with the exception of RH) and members of the PEACH consortium received funding from NIHR COVID Learning and Recovery Call programme (NIHR132254) for the PEACH Study and for the delivery of this manuscript. ET-J, JE, LB-H, PP and WM (main authors) and ST (consortium) all received funding from NIHR-HTA programme for delivery of the PRONTO trial (NIHR17/136/13). EC, ET-J, PP and LB-H received funding from NIHR for the BATCH trial (15/188/42). EC, ET-J and PP received funding from MRC-NIHR EME for contribution to the PRECISE study (NIHR129960). PH received funding from Abbot Laboratories for attending the European Network for Antimicrobial Stewardship in Point of Care. PH has also previously held post as Vice Chancellor for British Society for Antimicrobial Chemotherapy (BSAC) and is currently a committee member., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hidradenitis suppurativa is a chronic inflammatory skin disease characterised by recurrent inflammatory lesions and skin tunnels in flexural sites such as the axilla. Deroofing of skin tunnels and laser treatment are standard hidradenitis suppurativa interventions in some countries but not yet introduced in the United Kingdom., Objective: To understand current hidradenitis suppurativa management pathways and what influences treatment choices to inform the design of future randomised controlled trials., Design: Prospective 12-month observational cohort study, including five treatment options, with nested qualitative interviews and an end-of-study consensus workshop., Setting: Ten United Kingdom hospitals with recruitment led by dermatology and plastic surgery departments., Participants: Adults with active hidradenitis suppurativa of any severity not adequately controlled by current treatment., Interventions: Oral doxycycline 200 mg once daily; oral clindamycin and rifampicin, both 300 mg twice daily for 10 weeks initially; laser treatment targeting the hair follicle (neodymium-doped yttrium aluminium garnet or alexandrite); deroofing; and conventional surgery., Main Outcome Measures: Primary outcome was the proportion of participants who are eligible, and hypothetically willing, to use the different treatment options. Secondary outcomes included proportion of participants choosing each of the study interventions, with reasons for their choices; proportion of participants who switched treatments; treatment fidelity; loss to follow-up rates over 12 months; and efficacy outcome estimates to inform outcome measure instrument responsiveness., Results: Between February 2020 and July 2021, 151 participants were recruited, with two pauses due to the COVID-19 pandemic. Follow-up rates were 89% and 83% after 3 and 6 months, decreasing to 70% and 44% at 9 and 12 months, respectively, because pandemic recruitment delays prevented all participants reaching their final review. Baseline demographics included an average age of 36 years, 81% female, 20% black, Asian or Caribbean, 64% current or ex-smokers and 86% with a raised body mass index. Some 69% had moderate disease, 19% severe disease and 13% mild disease. Regarding the study's primary outcome, laser treatment was the intervention with the highest proportion (69%) of participants who were eligible and hypothetically willing to receive treatment, followed by deroofing (58%), conventional surgery (54%), the combination of oral clindamycin and rifampicin (44%) and doxycycline (37%). Considering participant willingness in isolation, laser was ranked first choice by the greatest proportion (41%) of participants. The cohort study and qualitative study demonstrated that participant willingness to receive treatment was strongly influenced by their clinician. Fidelity to oral doxycycline was only 52% after 3 months due to lack of effectiveness, participant preference and adverse effects. Delays receiving procedural interventions were common, with only 43% and 26% of participants commencing laser therapy and deroofing, respectively, after 3 months. Treatment switching was uncommon and there were no serious adverse events. Daily pain score text messages were initiated in 110 participants. Daily responses reduced over time with greatest concordance during the first 14 days., Limitations: It was not possible to characterise conventional surgery due to a low number of participants., Conclusion: The Treatment of Hidradenitis Suppurativa Evaluation Study established deroofing and laser treatment for hidradenitis suppurativa in the United Kingdom and developed a network of 10 sites for subsequent hidradenitis suppurativa randomised controlled trials., Future Work: The consensus workshop prioritised laser treatment and deroofing as interventions for future randomised controlled trials, in some cases combined with drug treatment., Trial Registration: This trial is registered as ISRCTN69985145., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/35/64) and is published in full in Health Technology Assessment ; Vol. 27, No. 30. See the NIHR Funding and Awards website for further award information.

Background: Cardiac rehabilitation (CR) is a proven model of secondary prevention, but new sites, providing quality care, are needed in low-resource settings. This study (1) described the development of International Council of Cardiovascular Prevention and Rehabilitation's (ICCPR) Program Certification and (2a) tested its implementation, considering (b) appropriateness of quality standards for these settings., Methods: The Steering Committee finalized 13 standards, requiring 70% be met. They are assessed initially through International CR Registry (ICRR) program survey and patient data; if Certification appears possible, a two-hour virtual site assessment is arranged to corroborate. Standard operating procedures for Assessor training were developed. A multi-method pilot study was then undertaken with a quantitative (description of quality indicators) and qualitative (focus groups on MS Teams) component. ICRR sites with post-program data by April 2022 were invited to participate. Two team members independently analyzed focus group transcripts, using a deductive-thematic approach with NVIVO., Results: Five CR programs from the Eastern Mediterranean, South-East Asian and American regions participated. Upon application, with some data cleaning, initially four programs were eligible to proceed to virtual site assessment. Ultimately, all five programs were certified, each meeting a minimum of 12/13 standards (peak MET increase and program completion rate were not met by some centres). Four themes resulted from the two focus groups of 13 site data stewards: motivation and benefits (eg, international recognition, additional program resources), logistics (eg, communication, cost, site visit process), the standards and their assessment (eg, balance of rigor and feasibility), and suggestions for improvement (eg, website)., Conclusion: ICCPR's Program Certification has been demonstrated to be feasible, rigorous, and acceptable. Standards are attainable in low-resource settings. Certified programs reap benefits including additional resources. This first international Certification is suitable for low-resource settings, to complement that from the American and European CR Societies., Competing Interests: AC serves on the Program Certification Steering Committee and also put his program forward for certification consideration. To mitigate any conflict, assessment of his site’s data and the virtual site assessment were handled by other members of the committee without communication with AC until the decision had been reached. Two other authors were involved in this paper and their site was assessed, however they did not play a role in assessing their own site or have access to their certification data. Otherwise, the authors declare that they have no conflicts of interest., (© 2023 Turk-Adawi et al.)

Introduction: Clinical presentation of both insomnia and obstructive sleep apnea (COMISA) is common. Approximately 30% of clinical cohorts with OSA have insomnia symptoms and vice versa. The underlying pathophysiology of COMISA is multifactorial. This poses a complex clinical challenge. Currently, there are no clinical guidelines or recommendations outside of continuous positive airway pressure (CPAP) therapy and cognitive behavioral therapy for insomnia (CBTi). Clinically translatable precision medicine approaches to characterize individual causes or endotypes may help optimize future pharmacological management of COMISA., Areas Covered: This review article provides an up-to-date account of COMISA and its consequences, the underlying pathophysiology of sleep apnea, insomnia and COMISA, current treatment approaches and limitations, pharmacotherapy targets and future priorities., Expert Opinion: There are multiple promising emerging therapies, but clinical trial data specifically in COMISA populations are lacking. This is a priority for future investigation to inform development of evidence-based guidelines. Pharmacotherapies, particularly for insomnia, do not target the underlying causes of the disorder thus, are indicated for short-term use only and should remain second line. Future multidisciplinary research should be directed toward the multifactorial nature of COMISA and the challenges of adapting COMISA treatment in clinical practice and overcoming the practical barriers that health-care providers and consumers encounter.

Competing Interests: Conflicts of interest J.R.I. is the Editor in Chief of the British Journal of Dermatology. PL is an Associate Editor of the British Journal of Dermatology.

Background: Delayed methotrexate elimination can occur in patients undergoing high-dose methotrexate cancer treatment. Effectiveness of glucarpidase for rapidly reducing methotrexate concentrations was shown in compassionate-use trials in patients aged 0-84 years., Methods: We performed post hoc analyses of infants (≥28 days to <2 years), children (≥2 to <12 years), adolescents (≥12 to <15 years), and young adults (≥15 to <25 years) from four multicenter, open-label, single-arm, glucarpidase compassionate-use trials. Patients had toxic methotrexate levels due to delayed methotrexate elimination and/or renal dysfunction, and received glucarpidase (50 U/kg). The primary endpoint was clinically important reduction (CIR) in plasma methotrexate (methotrexate ≤1 μmol/L at all post-glucarpidase measurements) based on high-performance liquid chromatography., Results: Among 86 patients included in efficacy analyses, CIR was achieved by zero of one infant (0.0%), five of 16 children (31.3%), seven of 24 adolescents (29.2%), and 26/45 young adults (57.8%). Median methotrexate reduction was 98.7% or higher in each group 15 minutes post-glucarpidase. Patients with pre-glucarpidase methotrexate less than 50 μmol/L (35/42, 83.3%) were more likely to achieve CIR than those with methotrexate 50 μmol/L or higher (1/37, 2.7%). The most common treatment-related adverse event was paresthesia, occurring in three adolescents (4.5%) and six young adults (5.2%). No other treatment-related adverse event occurred in 5% or higher of any age group., Conclusion: After accounting for pre-glucarpidase methotrexate levels, glucarpidase efficacy at inducing CIR in pediatric/young adult patients was consistent, with efficacy observed in the overall study population (i.e., patients aged 0-84), and no unexpected safety findings were observed. These findings demonstrate glucarpidase (50 U/kg) is an effective and well-tolerated dose for pediatric, adolescent, and young adult patients., (© 2023 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Introduction: The BATCH trial is a multi-centre randomised controlled trial to compare procalcitonin-guided management of severe bacterial infection in children with current management. PRECISE is a mechanistic sub-study embedded into the BATCH trial. This paper describes the statistical analysis plan for the BATCH trial and PRECISE sub-study., Methods: The BATCH trial will assess the effectiveness of an additional procalcitonin test in children (aged 72 h to 18 years) hospitalised with suspected or confirmed bacterial infection to guide antimicrobial prescribing decisions. Participants will be enrolled in the trial from randomisation until day 28 follow-up. The co-primary outcomes are duration of intravenous antibiotic use and a composite safety outcome. Target sample size is 1942 patients, based on detecting a 1-day reduction in intravenous antibiotic use (90% power, two-sided) and on a non-inferiority margin of 5% risk difference in the composite safety outcome (90% power, one-sided), while allowing for up to 10% loss to follow-up., Results: Baseline characteristics will be summarised overall, by trial arm, and by whether patients were recruited before or after the pause in recruitment due to the COVID-19 pandemic. In the primary analysis, duration of intravenous antibiotic use will be tested for superiority using Cox regression, and the composite safety outcome will be tested for non-inferiority using logistic regression. The intervention will be judged successful if it reduces the duration of intravenous antibiotic use without compromising safety. Secondary analyses will include sensitivity analyses, pre-specified subgroup analyses, and analysis of secondary outcomes. Two sub-studies, including PRECISE, involve additional pre-specified subgroup analyses. All analyses will be adjusted for the balancing factors used in the randomisation, namely centre and patient age., Conclusion: We describe the statistical analysis plan for the BATCH trial and PRECISE sub-study, including definitions of clinical outcomes, reporting guidelines, statistical principles, and analysis methods. The trial uses a design with co-primary superiority and non-inferiority endpoints. The analysis plan has been written prior to the completion of follow-up., Trial Registration: BATCH: ISRCTN11369832, registered 20 September 2017, doi.org/10.1186/ISRCTN11369832., Precise: ISRCTN14945050, registered 17 December 2020, doi.org/10.1186/ISRCTN14945050., (© 2023. The Author(s).)

Paediatric early warning systems (PEWS) to reduce in-hospital mortality have been a laudable endeavour. Evaluation of their impact has rarely examined the internal validity of the components of PEWS in achieving desired outcomes. We highlight the assumptions made regarding the mode of action of PEWS and, as PEWS become more commonplace, this paper asks whether we really understand their function, process and outcome., Competing Interests: Competing interests: DR and GS are involved in the NHS England National Inpatient PEWS programme., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objectives: Current sepsis guidelines do not provide good risk stratification of subgroups in whom prompt IV antibiotics and fluid resuscitation might of benefit. We evaluated the utility of mid-regional pro-adrenomedullin (MR-proADM) in identification of patient subgroups at risk of requiring PICU or high-dependency unit (HDU) admission or fluid resuscitation., Design: Secondary, nonprespecified analysis of prospectively collected dataset., Setting: Pediatric Emergency Department in a United Kingdom tertiary center., Patients: Children less than 16 years old presenting with fever and clinical indication for venous blood sampling ( n = 1,183)., Interventions: None., Measurements and Main Results: Primary outcome measures were PICU/HDU admission or administration of fluid resuscitation, with a secondary outcome of definite or probable bacterial infection. Biomarkers were measured on stored plasma samples and children phenotyped into bacterial and viral groups using a previously published algorithm. Of the 1,183 cases, 146 children (12.3%) required fluids, 48 (4.1%) were admitted to the PICU/HDU, and 244 (20.6%) had definite or probable bacterial infection. Area under the receiver operating characteristic (AUC) was used to assess performance. MR-proADM better predicted fluid resuscitation (AUC, 0.73; 95% CI, 0.67-0.78), than both procalcitonin (AUC, 0.65; 95% CI, 0.59-0.71) and Pediatric Early Warning Score (PEWS: AUC, 0.62; 95% CI, 0.56-0.67). PEWS alone showed good accuracy for PICU/HDU admission 0.83 (0.78-0.89). Patient subgroups with high MR-proADM (≥ 0.7 nmol/L) and high procalcitonin (≥ 0.5 ng/mL) had increased association with PICU/HDU admission, fluid resuscitation, and bacterial infection compared with subgroups with low MR-proADM (< 0.7 nmol/L). For children with procalcitonin less than 0.5 ng/mL, high MR-proADM improved stratification for fluid resuscitation only., Conclusions: High MR-proADM and high procalcitonin were associated with increased likelihood of subsequent disease progression. Incorporating MR-proADM into clinical risk stratification may be useful in clinician decision-making regarding initiation of IV antibiotics, fluid resuscitation, and escalation to PICU/HDU admission., Competing Interests: Dr. Carrol is a National Institute for Health Research (NIHR) Senior Investigator; she received funding from the NIHR’s Research for Innovation, Speculation, and Creativity Programme grant (RC-PG-0309-10053). Dr. Pallmann’s institution received funding from the Health and Care Research Wales and National Institute for Health and Care Research. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus responsible for the coronavirus disease 2019 (COVID-19) pandemic. Although COVID-19 is a viral illness, many patients admitted to hospital are prescribed antibiotics, based on concerns that COVID-19 patients may experience secondary bacterial infections, and the assumption that they may respond well to antibiotic therapy. This has led to an increase in antibiotic use for some hospitalised patients at a time when accumulating antibiotic resistance is a major global threat to health. Procalcitonin (PCT) is an inflammatory marker measured in blood samples and widely recommended to help diagnose bacterial infections and guide antibiotic treatment. The PEACH study will compare patient outcomes from English and Welsh hospitals that used PCT testing during the first wave of the COVID-19 pandemic with those from hospitals not using PCT. It will help to determine whether, and how, PCT testing should be used in the NHS in future waves of COVID-19 to protect patients from antibiotic overuse. PEACH is a retrospective observational cohort study using patient-level clinical data from acute hospital Trusts and Health Boards in England and Wales. The primary objective is to measure the difference in antibiotic use between COVID-19 patients who did or did not have PCT testing at the time of diagnosis. Secondary objectives include measuring differences in length of stay, mortality, intensive care unit admission, and resistant bacterial infections between these groups.

Background: The accuracy with which healthcare professionals (HCPs) and risk prediction tools predict outcomes after major lower limb amputation (MLLA) is uncertain. The aim of this study was to evaluate the accuracy of predicting short-term (30 days after MLLA) mortality, morbidity, and revisional surgery., Methods: The PERCEIVE (PrEdiction of Risk and Communication of outcomE following major lower limb amputation: a collaboratIVE) study was launched on 1 October 2020. It was an international multicentre study, including adults undergoing MLLA for complications of peripheral arterial disease and/or diabetes. Preoperative predictions of 30-day mortality, morbidity, and MLLA revision by surgeons and anaesthetists were recorded. Probabilities from relevant risk prediction tools were calculated. Evaluation of accuracy included measures of discrimination, calibration, and overall performance., Results: Some 537 patients were included. HCPs had acceptable discrimination in predicting mortality (931 predictions; C-statistic 0.758) and MLLA revision (565 predictions; C-statistic 0.756), but were poor at predicting morbidity (980 predictions; C-statistic 0.616). They overpredicted the risk of all outcomes. All except three risk prediction tools had worse discrimination than HCPs for predicting mortality (C-statistics 0.789, 0.774, and 0.773); two of these significantly overestimated the risk compared with HCPs. SORT version 2 (the only tool incorporating HCP predictions) demonstrated better calibration and overall performance (Brier score 0.082) than HCPs. Tools predicting morbidity and MLLA revision had poor discrimination (C-statistics 0.520 and 0.679)., Conclusion: Clinicians predicted mortality and MLLA revision well, but predicted morbidity poorly. They overestimated the risk of mortality, morbidity, and MLLA revision. Most short-term risk prediction tools had poorer discrimination or calibration than HCPs. The best method of predicting mortality was a statistical tool that incorporated HCP estimation., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Using the Health Belief Model as a conceptual framework, we investigated the association between attitudes towards COVID-19, COVID-19 vaccinations, and vaccine hesitancy and change in these variables over a 9-month period in a UK cohort., Methods: The COPE study cohort (n = 11,113) was recruited via an online survey at enrolment in March/April 2020. The study was advertised via the HealthWise Wales research registry and social media. Follow-up data were available for 6942 people at 3 months (June/July 2020) and 5037 at 12 months (March/April 2021) post-enrolment. Measures included demographics, perceived threat of COVID-19, perceived control, intention to accept or decline a COVID-19 vaccination, and attitudes towards vaccination. Logistic regression models were fitted cross-sectionally at 3 and 12 months to assess the association between motivational factors and vaccine hesitancy. Longitudinal changes in motivational variables for vaccine-hesitant and non-hesitant groups were examined using mixed-effect analysis of variance models., Results: Fear of COVID-19, perceived susceptibility to COVID-19, and perceived personal control over COVID-19 infection transmission decreased between the 3- and 12-month surveys. Vaccine hesitancy at 12 months was independently associated with low fear of the disease and more negative attitudes towards COVID-19 vaccination. Specific barriers to COVID-19 vaccine uptake included concerns about safety and efficacy in light of its rapid development, mistrust of government and pharmaceutical companies, dislike of coercive policies, and perceived lack of relaxation in COVID-19-related restrictions as the vaccination programme progressed., Conclusions: Decreasing fear of COVID-19, perceived susceptibility to the disease, and perceptions of personal control over reducing infection-transmission may impact future COVID-19 vaccination uptake., (© 2022 The Authors. British Journal of Health Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Competing Interests: Conflict of interest: F.Z.M. is supported by a Senior Medical Research Fellowship from the Sylvia and Charles Viertel Charitable Foundation Fellowship. F.Z.M. (105663) and E.E.T. (105215) are supported by fellowships from the National Heart Foundation.

Introduction: The pharmacist's role in vaccination efforts continues to increase; therefore, it is essential to ensure that pharmacy students receive effective training to be confident and competent administering immunizations. The purpose of this research was to assess the impact of immunization training timing on students' hands-on experience and perception during pharmacy school., Methods: One hundred forty-five pharmacy schools were surveyed to determine details of their immunization training programs. A follow-up survey was sent to select schools to determine student comfort immunizing during introductory pharmacy practice experiences (IPPEs) and paid employment in pharmacy settings. Quantitative data regarding the number of immunizations delivered during IPPEs and work was collected. Questions also assessed attitudes regarding timing of immunization training and missed opportunities to immunize., Results: Results indicated students trained during their third professional year (PY3) were less comfortable giving immunizations during their IPPEs or work than those trained during the first professional year (PY1) or second professional year (PY2) (IPPE P < .01; work P < .01 PY1; P = .01 PY2). PY3s were more likely to prefer training earlier in the curriculum. PY2s and PY3s were more likely to believe the timing of their immunization training caused missed opportunities to deliver immunizations. The earlier the immunization training occurred in the curriculum, the more vaccinations the student administered., Conclusions: Providing immunization training programs to pharmacy students earlier in their curriculum provides students with superior experience and instills confidence., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier Inc.)

Background: Following percutaneous coronary intervention (PCI), outpatient cardiac rehabilitation (CR) is essential for secondary prevention. However uptake of CR is suboptimal, despite strong evidence demonstrating benefits. The aim of this study was to identify contemporary trends and predictors of CR referral of PCI patients in Victoria., Methods: A prospective, observational study using data extracted from the Victorian Cardiac Outcomes Registry was undertaken. A total of 41,739 patients were discharged following PCI over the study period (2017-2020) and included for analysis., Results: Cardiac rehabilitation referral was 85%, with an increasing trend over time (p<0.001). Multivariable modelling identifying the independent predictors of CR referral included hospitals with high volumes of ST-elevation myocardial infarction patients (STEMI) (OR 4.89, 95% CI 4.41-5.20), STEMI diagnosis (OR 1.90, 95% CI 1.69-2.14), or treatment in a private hospital (OR 1.45, 95% CI 1.33-1.57). Predictors of non-referral included cardiogenic shock (OR 0.54, 95% CI 0.41-0.71), aged over 75 years (OR 0.62, 95% CI 0.57-0.68) and previous PCI (OR 0.66, 95% CI 0.62-0.70). Percutaneous coronary intervention patients with an acute coronary syndrome who were referred to CR were also more likely to be prescribed four or more major preventive pharmacotherapies, compared to those who were not referred (90% vs 82.1%, p<0.001)., Conclusion: Our contemporary multicentre analysis showed generally high CR referral rates which have increased over time. However, more effort is needed to target patients treated in the public sector, low volume STEMI hospitals or with short lengths of stay., (Copyright © 2022 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: Sepsis is a common, potentially life-threatening complication of infection. The optimal treatment for sepsis includes prompt antibiotics and intravenous fluids, facilitated by its early and accurate recognition. Currently, clinicians identify and assess severity of suspected sepsis using validated clinical scoring systems. In England, the National Early Warning Score 2 (NEWS2) has been mandated across all National Health Service (NHS) trusts and ambulance organisations. Like many clinical scoring systems, NEWS2 should not be used without clinical judgement to determine either the level of acuity or a diagnosis. Despite this, there is a tendency to overemphasise the score in isolation in patients with suspected infection, leading to the overprescription of antibiotics and potentially treatment-related complications and rising antimicrobial resistance. The biomarker procalcitonin (PCT) has been shown to be useful in specific circumstances to support appropriate antibiotics prescribing by identifying bacterial infection. PCT is not routinely used in the care of undifferentiated patients presenting to emergency departments (EDs), and the evidence base of its optimal usage is poor. The PROcalcitonin and NEWS2 evaluation for Timely identification of sepsis and Optimal (PRONTO) study is a randomised controlled trial (RCT) in adults with suspected sepsis presenting to the ED to compare standard clinical management based on NEWS2 scoring plus PCT-guided risk assessment with standard clinical management based on NEWS2 scoring alone and compare if this approach reduces prescriptions of antibiotics without increasing mortality., Methods and Analysis: PRONTO is a parallel two-arm open-label individually RCT set in up to 20 NHS EDs in the UK with a target sample size of 7676 participants. Participants will be randomised in a ratio of 1:1 to standard clinical management based on NEWS2 scoring or standard clinical management based on NEWS2 scoring plus PCT-guided risk assessment. We will compare whether the addition of PCT measurement to NEWS2 scoring can lead to a reduction in intravenous antibiotic initiation in ED patients managed as suspected sepsis, with at least no increase in 28-day mortality compared with NEWS2 scoring alone (in conjunction with local standard care pathways). PRONTO has two coprimary endpoints: initiation of intravenous antibiotics at 3 hours (superiority comparison) and 28-day mortality (non-inferiority comparison). The study has an internal pilot phase and group-sequential stopping rules for effectiveness and futility/safety, as well as a qualitative substudy and a health economic evaluation., Ethics and Dissemination: The trial protocol was approved by the Health Research Authority (HRA) and NHS Research Ethics Committee (Wales REC 2, reference 20/WA/0058). In England and Wales, the law allows the use of deferred consent in approved research situations (including ED studies) where the time dependent nature of intervention would not allow true informed consent to be obtained. PRONTO has approval for a deferred consent process to be used. Findings will be disseminated through peer-reviewed journals and presented at scientific conferences., Trial Registration Number: ISRCTN54006056., Competing Interests: Competing interests: EC is co-CI for the BATCH Trial (HTA 15/188/42) and the PEACH study (HTA Project: NIHR132254) on PCT use, and member of NICE Diagnostic advisory committee (2014–2020), and NICE Sepsis guideline development committee (2014-6). All other authors declare no competing interests., (© 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.)

Atypical sensory processing occurs in up to 97% of children on the autism spectrum. Children who are on the autism spectrum also commonly demonstrate challenging behaviors, and their caregivers report increased levels of strain in daily life. The aim of this study was to explore four sensory processing features; seeking, avoiding, sensitivity, and registration, and their relationships with maladaptive behaviors in children with autism, as well as with caregiver strain. Participants comprised 75 children with autism aged 7-12 years (M = 7.81). Caregivers completed three questionnaire measures examining child sensory processing, maladaptive behaviors, and perceptions of caregiver strain. We found avoiding significantly associated with irritability. Avoiding also displayed the strongest relationship with global caregiver strain. Avoiding and seeking were strongly related to hyperactivity/noncompliance (components of maladaptive behavior). A multiple regression was performed to explore how atypical sensory processing features and maladaptive behaviors together predicted caregiver strain. Together, maladaptive behaviors and sensory features accounted for 58% of the variance in total caregiver strain. The only significant individual predictor of total caregiver strain was sensory avoiding, which uniquely accounted for 5.76% of the variation. The findings suggest that atypical sensory processing is associated with overall caregiver strain, above that explained by maladaptive behaviors. Implications for targeted support for the benefit of the child, parents and family unit are discussed. LAY SUMMARY: Children who are on the autism spectrum often have differences in sensory processing. These children also tend to show challenging behaviors, and their caregivers can experience increased stress. This study looked at how sensory processing difficulties relate to such behaviors and caregiver stress. We found that both sensory processing and challenging behaviors were related to the amount of stress caregivers felt. This suggests that interventions may benefit from looking at sensory processing features when considering how to help reduce challenging behaviors and caregiver stress., (© 2022 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

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.