Stratification of Sepsis Patients on Admission into the Intensive Care Unit According to Differential Plasma Metabolic Phenotypes.

Delayed diagnosis of patients with sepsis or septic shock is associated with increased mortality and morbidity. UPLC-MS and NMR spectroscopy were used to measure panels of lipoproteins, lipids, biogenic amines, amino acids, and tryptophan pathway metabolites in blood plasma samples collected from 152 patients within 48 h of admission into the Intensive Care Unit (ICU) where 62 patients had no sepsis, 71 patients had sepsis, and 19 patients had septic shock. Patients with sepsis or septic shock had higher concentrations of neopterin and lower levels of HDL cholesterol and phospholipid particles in comparison to nonsepsis patients. Septic shock could be differentiated from sepsis patients based on different concentrations of 10 lipids, including significantly lower concentrations of five phosphatidylcholine species, three cholesterol esters, one dihydroceramide, and one phosphatidylethanolamine. The Supramolecular Phospholipid Composite (SPC) was reduced in all ICU patients, while the composite markers of acute phase glycoproteins were increased in the sepsis and septic shock patients within 48 h admission into ICU. We show that the plasma metabolic phenotype obtained within 48 h of ICU admission is diagnostic for the presence of sepsis and that septic shock can be differentiated from sepsis based on the lipid profile.

Behavior Change Techniques Involved in Physical Activity Interventions for Children With Chronic Conditions: A Systematic Review.

BACKGROUND: Behavior change techniques (BCTs) have been extensively used in physical activity interventions for children, however, no systematic reviews have synthesized their effects. PURPOSE: The present review aimed to identify the most promising BCTs used in physical activity interventions associated with (i) increased physical activity behavior and (ii) positive psychosocial outcomes in children with chronic conditions. METHODS: A systematic search of 6 databases identified 61 articles as eligible for inclusion. Data, including BCTs, were extracted from these studies and analyzed descriptively. Due to the heterogeneity of interventions, chronic conditions, and outcome measures, a meta-analysis was not conducted. RESULTS: Social support (unspecified), graded tasks, generalization of target behavior, and credible source were the most commonly reported and most promising (i.e., present in 2+ studies evidencing significant effects) BCTs across all studies. These BCTs were found to be especially relevant to improving psychosocial outcomes in the short- and long-term and improving physical activity behaviors in the long-term. Meanwhile, to improve short-term physical activity behaviors, in addition to social support (unspecified), action planning, goal setting (behavior), and problem solving were found to be promising BCTs. CONCLUSIONS: The BCTs identified in this review may be relevant to incorporate when planning future interventions to support physical activity and psychosocial outcomes for children with chronic conditions.

Children with chronic conditions experience several barriers to engaging in physical activity. In order to overcome these unique barriers, physical activity interventions would need to incorporate specific strategies (called behavior change techniques [BCTs]) to encourage physical activity participation. The present review sought to identify BCTs that were successfully applied to physical activity interventions to increase physical activity behavior and improve psychosocial outcomes for children with chronic conditions. Across the 61 studies included within this review, the most commonly applied BCTs were providing instruction, allowing opportunities to practice the behavior, and demonstration of the behavior. Social support was also found to be the a successful BCT to increase physical activity behavior and improve psychosocial outcomes in the short- and long-term. Future physical activity interventions aimed at supporting physical activity behavior and psychosocial outcomes of children with chronic conditions could benefit from incorporating these strategies within intervention planning and delivery.

Systemic antibiotics for symptomatic apical periodontitis and acute apical abscess in adults.

BACKGROUND: Dental pain can have a detrimental effect on quality of life. Symptomatic apical periodontitis and acute apical abscess are common causes of dental pain and arise from an inflamed or necrotic dental pulp, or infection of the pulpless root canal system. Clinical guidelines recommend that the first-line treatment for these conditions should be removal of the source of inflammation or infection by local operative measures, and that systemic antibiotics are currently only recommended for situations where there is evidence of spreading infection (cellulitis, lymph node involvement, diffuse swelling) or systemic involvement (fever, malaise). Despite this, there is evidence that dentists frequently prescribe antibiotics in the absence of these signs. There is concern that this could contribute to the development of antibiotic-resistant bacteria. This review is the second update of the original version first published in 2014. OBJECTIVES: To evaluate the effects of systemic antibiotics provided with or without surgical intervention (such as extraction, incision and drainage of a swelling, or endodontic treatment), with or without analgesics, for symptomatic apical periodontitis and acute apical abscess in adults. SEARCH METHODS: We searched Cochrane Oral Health's Trials Register (26 February 2018 (discontinued)), CENTRAL (2022, Issue 10), MEDLINE Ovid (23 November 2022), Embase Ovid (23 November 2022), CINAHL EBSCO (25 November 2022) and two trials registries, and performed a grey literature search. There were no restrictions on language or date of publication. SELECTION CRITERIA: Randomised controlled trials of systemic antibiotics in adults with a clinical diagnosis of symptomatic apical periodontitis or acute apical abscess, with or without surgical intervention (considered in this situation to be extraction, incision and drainage, or endodontic treatment) and with or without analgesics. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the results of the searches against inclusion criteria, extracted data and assessed risk of bias. We used a fixed-effect model in the meta-analysis as there were fewer than four studies. We contacted study authors to request missing information. We used GRADE criteria to assess the certainty of the evidence. MAIN RESULTS: There was one new completed trial on this topic since the last update in 2018. In total, we included three trials with 134 participants. Systemic antibiotics versus placebo with surgical intervention and analgesics for symptomatic apical periodontitis or acute apical abscess One trial (72 participants) compared the effects of a single preoperative dose of clindamycin versus a matched placebo when provided with a surgical intervention (endodontic chemo-mechanical debridement and filling) and analgesics to adults with symptomatic apical periodontitis. We assessed this study at low risk of bias. There were no differences in participant-reported pain or swelling across trial arms at any time point assessed. The median values for pain (numerical rating scale 0 to 10) were 3.0 in both groups at 24 hours (P = 0.219); 1.0 in the antibiotic group versus 2.0 in the control group at 48 hours (P = 0.242); and 0 in both groups at 72 hours and seven days (P = 0.116 and 0.673, respectively). The risk ratio of swelling when comparing preoperative antibiotic to placebo was 0.50 (95% confidence interval (CI) 0.10 to 2.56; P = 0.41). The certainty of evidence for all outcomes in this comparison was low. Two trials (62 participants) compared the effects of a seven-day course of oral phenoxymethylpenicillin (penicillin VK) versus a matched placebo when provided with a surgical intervention (total or partial endodontic chemo-mechanical debridement) and analgesics to adults with acute apical abscess or symptomatic necrotic tooth. Participants in both trials also received oral analgesics. We assessed one study at high risk of bias and the other at unclear risk of bias. There were no differences in participant-reported pain or swelling at any time point assessed. The mean difference for pain (short ordinal numerical scale 0 to 3, where 0 was no pain) was -0.03 (95% CI -0.53 to 0.47) at 24 hours; 0.32 (95% CI -0.22 to 0.86) at 48 hours; and 0.08 (95% CI -0.38 to 0.54) at 72 hours. The standardised mean difference for swelling was 0.27 (95% CI -0.23 to 0.78) at 24 hours; 0.04 (95% CI -0.47 to 0.55) at 48 hours; and 0.02 (95% CI -0.49 to 0.52) at 72 hours. The certainty of evidence for all the outcomes in this comparison was very low. Adverse effects, as reported in two studies, were diarrhoea (one participant in the placebo group), fatigue and reduced energy postoperatively (one participant in the antibiotic group) and dizziness preoperatively (one participant in the antibiotic group). Systemic antibiotics without surgical intervention for adults with symptomatic apical periodontitis or acute apical abscess We found no studies that compared the effects of systemic antibiotics with a matched placebo delivered without a surgical intervention for symptomatic apical periodontitis or acute apical abscess in adults. AUTHORS' CONCLUSIONS: The evidence suggests that preoperative clindamycin for adults with symptomatic apical periodontitis results in little to no difference in participant-reported pain or swelling at any of the time points included in this review when provided with chemo-mechanical endodontic debridement and filling under local anaesthesia. The evidence is very uncertain about the effect of postoperative phenoxymethylpenicillin for adults with localised apical abscess or a symptomatic necrotic tooth when provided with chemo-mechanical debridement and oral analgesics. We found no studies which compared the effects of systemic antibiotics with a matched placebo delivered without a surgical intervention for symptomatic apical periodontitis or acute apical abscess in adults.

Barriers and co-designed strategies for the implementation of negative pressure wound therapy in acute pediatric burn care in Australia: A mixed method study.

PURPOSE: Pediatric burn injuries are a global clinical issue causing significant morbidity. Early adjunctive negative pressure wound therapy improves re-epithelialization rates in children with burns, yet adoption in acute burn care is inconsistent. This investigation aimed to determine barriers to the implementation of adjunctive negative pressure wound therapy for the acute management of pediatric burns and co-design targeted implementation strategies. METHODS: A sequential mixed methods design was used explore barriers to adjunctive negative pressure wound therapy implementation in acute pediatric burn care. An online questionnaire was disseminated to healthcare professionals within four major Australian pediatric hospitals, each with a dedicated burns service. Barriers were coded according to the Consolidated Framework for Implementation Research (CFIR). Semi-structured interviews with senior clinicians tailored implementation strategies to local contexts. A stakeholder consensus meeting consolidated implementation strategies and local processes. RESULTS: Sixty-three healthcare professionals participated in the questionnaire, and semi-structured interviews involved nine senior burn clinicians. We identified eight implementation barriers across all five CFIR domains then co-designed targeted strategies to address identified barriers. Barriers included lack of available resources, limited access to knowledge and information, individual stage of change, patient needs and resources, limited knowledge and beliefs about the intervention, lack of external policies, intervention complexity, and poor implementation planning. CONCLUSION: Multiple contextual factors affect negative pressure wound therapy uptake in acute pediatric burn settings. Results will inform a multi-state stepped-wedge cluster randomized controlled trial. Additional resources, education, training, updated policies, and guidelines are required for successful implementation. It is anticipated that adjunctive negative pressure wound therapy, in conjunction with tailored implementation strategies, will enhance adoption and sustainability. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry: ACTRN12622000166774. Registered 1 February 2022.

Comprehensive Lipidomic Workflow for Multicohort Population Phenotyping Using Stable Isotope Dilution Targeted Liquid Chromatography-Mass Spectrometry.

Dysregulated lipid metabolism underpins many chronic diseases including cardiometabolic diseases. Mass spectrometry-based lipidomics is an important tool for understanding mechanisms of lipid dysfunction and is widely applied in epidemiology and clinical studies. With ever-increasing sample numbers, single batch acquisition is often unfeasible, requiring advanced methods that are accurate and robust to batch-to-batch and interday analytical variation. Herein, an optimized comprehensive targeted workflow for plasma and serum lipid quantification is presented, combining stable isotope internal standard dilution, automated sample preparation, and ultrahigh performance liquid chromatography-tandem mass spectrometry with rapid polarity switching to target 1163 lipid species spanning 20 subclasses. The resultant method is robust to common sources of analytical variation including blood collection tubes, hemolysis, freeze-thaw cycles, storage stability, analyte extraction technique, interinstrument variation, and batch-to-batch variation with 820 lipids reporting a relative standard deviation of <30% in 1048 replicate quality control plasma samples acquired across 16 independent batches (total injection count = 6142). However, sample hemolysis of ≥0.4% impacted lipid concentrations, specifically for phosphatidylethanolamines (PEs). Low interinstrument variability across two identical LC-MS systems indicated feasibility for intra/inter-lab parallelization of the assay. In summary, we have optimized a comprehensive lipidomic protocol to support rigorous analysis for large-scale, multibatch applications in precision medicine. The mass spectrometry lipidomics data have been deposited to massIVE: data set identifiers MSV000090952 and 10.25345/C5NP1WQ4S.

Nonsevere Burn Induces a Prolonged Systemic Metabolic Phenotype Indicative of a Persistent Inflammatory Response Postinjury.

Globally, burns are a significant cause of injury that can cause substantial acute trauma as well as lead to increased incidence of chronic comorbidity and disease. To date, research has primarily focused on the systemic response to severe injury, with little in the literature reported on the impact of nonsevere injuries (<15% total burn surface area; TBSA). To elucidate the metabolic consequences of a nonsevere burn injury, longitudinal plasma was collected from adults (n = 35) who presented at hospital with a nonsevere burn injury at admission, and at 6 week follow up. A cross-sectional baseline sample was also collected from nonburn control participants (n = 14). Samples underwent multiplatform metabolic phenotyping using 1H nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry to quantify 112 lipoprotein and glycoprotein signatures and 852 lipid species from across 20 subclasses. Multivariate data modeling (orthogonal projections to latent structures-discriminate analysis; OPLS-DA) revealed alterations in lipoprotein and lipid metabolism when comparing the baseline control to hospital admission samples, with the phenotypic signature found to be sustained at follow up. Univariate (Mann-Whitney U) testing and OPLS-DA indicated specific increases in GlycB (p-value < 1.0e-4), low density lipoprotein-2 subfractions (variable importance in projection score; VIP > 6.83e-1) and monoacyglyceride (20:4) (p-value < 1.0e-4) and decreases in circulating anti-inflammatory high-density lipoprotein-4 subfractions (VIP > 7.75e-1), phosphatidylcholines, phosphatidylglycerols, phosphatidylinositols, and phosphatidylserines. The results indicate a persistent systemic metabolic phenotype that occurs even in cases of a nonsevere burn injury. The phenotype is indicative of an acute inflammatory profile that continues to be sustained postinjury, suggesting an impact on systems health beyond the site of injury. The phenotypes contained metabolic signatures consistent with chronic inflammatory states reported to have an elevated incidence postburn injury. Such phenotypic signatures may provide patient stratification opportunities, to identify individual responses to injury, personalize intervention strategies, and improve acute care, reducing the risk of chronic comorbidity.

The seductive allure of spatial biology: accelerating new discoveries in the life sciences.

Spatial biology is a rapidly developing field which enables the visualization of protein and transcriptomic data while preserving tissue context and architecture. Initially used in discovery, there is growing promise for translational and diagnostic assay developments. Immediate applications are in precision medicine, such as being able to match patients to optimal therapies through better understanding the tumor microenvironment. However, it also has ramifications for many other disciplines (e.g. immunology, cancer, infectious disease and digital pathology). With increasingly massive data sets being generated, data storage, curation, analysis and sharing require more computational approaches and artificial intelligence-powered tools to fully utilize spatial tools. Here, we discuss spatial biology as an important convergent science approach to tackling complex global challenges in areas such as health.

Psychometric Properties of an Adapted Stigma Scale and Experiences of Stigma Associated with HIV Pre-exposure Prophylaxis Use Among Men Who have Sex with Men: A Mixed Methods Study.

Stigma may influence the use of HIV pre-exposure prophylaxis (PrEP). However, there is an absence of robust measures for PrEP-related stigma. We describe an adaptation of a HIV stigma scale for use in PrEP users and experiences of PrEP users in Wales (UK) with regards to PrEP-related stigma. A mixed methods study was conducted where PrEP users completed questionnaire items about PrEP-related stigma and a subset were interviewed about their experiences of taking PrEP. We adapted items from the HIV stigma scale and assessed construct validity and internal consistency. We analysed interview data using a framework approach, with themes focussing on enacted and anticipated stigma in order to identify areas for scale refinement. Our measure had good psychometric properties but additional items may be useful (e.g. specific instances of enacted stigma, concerns around homonegativity). Further work is needed to develop this scale and validate it in a larger sample.

Between- and Within-Individual Sociodemographic and Psychological Determinants of PrEP Adherence Among Men Who have Sex with Men Prescribed a Daily PrEP Regimen in Wales.

We investigated the determinants of daily PrEP use and coverage of condomless anal sex (CAS) by PrEP among men who have sex with men in Wales, UK. We measured PrEP use by electronic monitors and CAS by secure online surveys. We defined PrEP use based on daily medication cap openings and coverage as CAS episodes preceded by ≥ 3 days of PrEP use and followed by ≥ 2 days of PrEP use. We included 57 participants (5463 observations). An STI diagnosis was associated with lower PrEP use but also lower PrEP coverage. Older adults had higher PrEP use. A belief that other PrEP users took PrEP as prescribed was associated with lower PrEP coverage. An STI diagnosis is an important cue for an intervention, reflecting episodes of high-risk sexual behaviour and low PrEP coverage. Other results provide a basis for the development of an evidence-informed intervention for promoting coverage of PrEP.

An international RAND/UCLA expert panel to determine the optimal diagnosis and management of burn inhalation injury.

BACKGROUND: Burn inhalation injury (BII) is a major cause of burn-related mortality and morbidity. Despite published practice guidelines, no consensus exists for the best strategies regarding diagnosis and management of BII. A modified DELPHI study using the RAND/UCLA (University of California, Los Angeles) Appropriateness Method (RAM) systematically analysed the opinions of an expert panel. Expert opinion was combined with available evidence to determine what constitutes appropriate and inappropriate judgement in the diagnosis and management of BII. METHODS: A 15-person multidisciplinary panel comprised anaesthetists, intensivists and plastic surgeons involved in the clinical management of major burn patients adopted a modified Delphi approach using the RAM method. They rated the appropriateness of statements describing diagnostic and management options for BII on a Likert scale. A modified final survey comprising 140 statements was completed, subdivided into history and physical examination (20), investigations (39), airway management (5), systemic toxicity (23), invasive mechanical ventilation (29) and pharmacotherapy (24). Median appropriateness ratings and the disagreement index (DI) were calculated to classify statements as appropriate, uncertain, or inappropriate. RESULTS: Of 140 statements, 74 were rated as appropriate, 40 as uncertain and 26 as inappropriate. Initial intubation with ≥ 8.0 mm endotracheal tubes, lung protective ventilatory strategies, initial bronchoscopic lavage, serial bronchoscopic lavage for severe BII, nebulised heparin and salbutamol administration for moderate-severe BII and N-acetylcysteine for moderate BII were rated appropriate. Non-protective ventilatory strategies, high-frequency oscillatory ventilation, high-frequency percussive ventilation, prophylactic systemic antibiotics and corticosteroids were rated inappropriate. Experts disagreed (DI ≥ 1) on six statements, classified uncertain: the use of flexible fiberoptic bronchoscopy to guide fluid requirements (DI = 1.52), intubation with endotracheal tubes of internal diameter < 8.0 mm (DI = 1.19), use of airway pressure release ventilation modality (DI = 1.19) and nebulised 5000IU heparin, N-acetylcysteine and salbutamol for mild BII (DI = 1.52, 1.70, 1.36, respectively). CONCLUSIONS: Burns experts mostly agreed on appropriate and inappropriate diagnostic and management criteria of BII as in published guidance. Uncertainty exists as to the optimal diagnosis and management of differing grades of severity of BII. Future research should investigate the accuracy of bronchoscopic grading of BII, the value of bronchial lavage in differing severity groups and the effectiveness of nebulised therapies in different severities of BII.

Identifying barriers and facilitators to the inclusion of older adults living in UK care homes in research: a scoping review.

BACKGROUND: With an ageing population, older adults will have more complex health and social care needs and many of these older adults will be living in care homes. Despite the growth in care home populations, care home residents are often excluded from research that could potentially benefit their care. The purpose of this scoping review is to explore resident-related barriers and facilitators to including older people living in UK care homes in research and to identify potential approaches to modify such barriers. METHOD: The 6-stage scoping review methodology framework proposed by Arksey and O'Malley guided this review. Five electronic databases (MedLine, PsychINFO, Scopus, Web of Science, CINAHL) and grey literature were searched. Identified articles went through two levels of screening, and those deemed relevant were collated, summarised and reported using a thematic analysis approach. RESULTS: 90 reports were eligible for inclusion and were synthesised into 7 themes and related subthemes: (1) research design; (2) understanding and beliefs about research (resident and care home staff); (3) communication; (4) relationships; (5) eligibility criteria (resident and care home); (6) preference-based decisions; and (7) care home staff and environment. Given the complex interplay of the factors identified, both direct and indirect factors were included. CONCLUSIONS: A number of recurring barriers and facilitators to the inclusion of care home residents in research are reported. However, isolating resident-related barriers was complex as both direct and indirect factors must be considered as influential. Understanding the barriers and facilitators to inclusion will enable these factors to be addressed and increase the evidence-base for care provided to older people living in care homes.

"I just get scared it's going to happen again": a qualitative study of the psychosocial impact of pediatric burns from the child's perspective.

BACKGROUND: Advances in medicine have improved the chances of survival following burn injuries, however, psychosocial outcomes have not seen the same improvement, and burn injuries can be distressing for both the child or young person, negatively affecting their wellbeing. Pediatric burn patients are at a higher risk of developing psychopathology compared to the general population. In order to promote resilience and prevent psychopathology post-burn injury for pediatric burn patients, it is crucial to understand the experience of children and young people after a burn. This study aimed to understand the psychosocial impact that a pediatric burn has as perceived by the pediatric burn patient. METHODS: Seven pediatric burn patients were interviewed from the Perth Metropolitan area on average 3.1 years after their injury. All participants had been admitted to hospital for their acute injury and stayed for a median length of 2 days in hospital. Interviews with pediatric patients took place online, and the patients were asked about their mental health, coping strategies, changes to lifestyle and supports following their burn injury. The interviews were transcribed and then thematically analysed using an inductive approach. RESULTS: Three overarching themes were developed from the interviews: burn-specific impact on the child or young person (including appearance concerns, family factors, and lifestyle factors), the psychological impact (including positive and negative impact on mental health), and factors supporting the recovery journey (including coping strategies and support services). The participants in our study highlighted issues they faced during recovery, the positive and negative impacts of the injury and recovery process and provided suggestions for future opportunities to bolster resilience and promote growth for pediatric burn patients who may face similar challenges in the future. CONCLUSION: Factors that improve the mental health and wellbeing of pediatric burn patients should be promoted, such as mental health and social supports, the promotion of adaptive coping mechanisms, and meeting the needs of the family unit as a whole. Ultimately, the implementation of trauma-focused, family centred interventions is crucial for the psychosocial recovery of pediatric burn survivors.

Planning ahead for research participation: survey of public and professional stakeholders' views about the acceptability and feasibility of advance research planning.

BACKGROUND: Anticipatory planning in the UK focuses on supporting people who anticipate periods of impaired capacity to express their wishes about future care through processes such as advance care planning. Other countries have extended anticipatory planning to include processes for people to prospectively express their preferences about research participation. Advance research planning (ARP) is thought to extend autonomy and ensure that 'proxy' decisions about research are based on their wishes and preferences. METHODS: A cross-sectional survey was conducted with two stakeholder groups (members of the public including people living with capacity-affecting conditions and family members; researchers and other professionals) who were recruited via research registries and other routes. Online questionnaires were used to capture the perspectives of the two groups. Responses were analysed using descriptive statistics and content analysis. RESULTS: A total of 327 participants (members of the public n = 277, professionals n = 50) completed the survey (November 2022 - March 2023). ARP was supported by 97% of public contributors and 94% of professionals. Participants thought that ARP should include the person's general wishes about research, specific types of studies, and who should make decisions on their behalf. They identified a number of challenges, including how ARP could take account of changes in individuals' preferences or circumstances whilst protecting their rights and interests. Implementation barriers included the potential time, complexity, and cost involved. These could be addressed by embedding ARP in existing anticipatory planning pathways and aligning it with other research enrolment activities. Relationships and trust played a key role, including underpinning who should support the delivery of ARP, how they are trained, and when it is undertaken. CONCLUSIONS: There were high levels of support for introducing ARP in the UK. Further research should explore practical barriers and stakeholder concerns and identify any unintended consequences. Future activities should include developing ARP interventions alongside training and other resources, and also focus on public awareness campaigns, and engaging policymakers and other stakeholders.

Real world treatment of juvenile-onset systemic lupus erythematosus: Data from the UK JSLE cohort study.

BACKGROUND: In the absence of clinical trials evidence, Juvenile-onset Systemic Lupus Erythematosus (JSLE) treatment plans vary. AIM: To explore 'real world' treatment utilising longitudinal UK JSLE Cohort Study data. METHODS: Data collected between 07/2009-05/2020 was used to explore the choice/sequence of immunomodulating drugs from diagnosis. Multivariate logistic regression determined how organ-domain involvement (pBILAG-2004) impacted treatment choice. RESULT: 349 patients met inclusion criteria, median follow-up 4-years (IQR:2,6). Mycophenolate mofetil (MMF) was most commonly used for the majority of organ-domains, and significantly associated with renal involvement (OR:1.99, 95% CI:1.65-2.41, pc < 0.01). Analyses assessing the sequence of immunomodulators focused on 197/349 patients (meeting relevant inclusion/exclusion criteria). 10/197 (5%) solely recieved hydroxychloroquine/prednisolone, 62/197 (31%) received a single-immunomodulator, 69/197 (36%) received two, and 36/197 patients (28%) received ≥three immunomodulators. The most common first and second line immunomodulator was MMF. Rituximab was the most common third-line immunomodulator. CONCLUSIONS: Most UK JSLE patients required ≥two immunomodulators, with MMF used most commonly.

Sampling the skin surface chemistry for diagnosis and prognosis.

Skin and wound blotting are non-invasive techniques used to sample the skin and wound surface chemistry, whereby a nitrocellulose membrane is applied to an intact or broken cutaneous surface to detect biomarkers. However, there has been no comprehensive review of the evidence for the techniques used and data obtained to date. The primary aim of this study was to review the utilities of surface blotting for the diagnosis and prognosis of physiological, pre-disease, and pathological states. The secondary aim was to summarise the procedural steps. A systematic literature search was conducted on 9 July 2021 using Medline, Embase, and Google Scholar databases. Investigators used McMaster's Critical Review Form for Quantitative Studies to assess quality, then performed a narrative synthesis reporting according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Twenty-five studies were reviewed. Eighteen studies were of good quality, and seven were of moderate quality. These studies conducted skin and wound blotting on 176 animals and 1546 humans. Studies reported physiological and pathological states for diagnosis and prediction of conditions, including skin tears, wound healing, biofilm detection, and skin barrier function. The four steps for blotting are surface preparation, blot preparation, application and removal of blot, and analysis. This review demonstrates that blotting can determine the skin and wound surface chemistry using a versatile and reproducible technique. However, future research is needed to validate the technique and skin biomarkers identified.

Local burn wound environment versus systemic response: Comparison of proteins and metabolites.

In this study, paired blood plasma (BP) and blister fluid (BF) samples from five paediatric burn patients were analysed using mass spectrometry to compare their protein and metabolite composition. The relative quantification of proteins was achieved through a label-free data independent acquisition mode. The relative quantification of metabolites was achieved using a Shimadzu Smart Metabolite Database gas chromatography mass spectrometry (GCMS) targeted assay. In total, 562 proteins and 141 individual metabolites were identified in the samples. There was 81% similarity in the proteins present in the BP and BF, with 50 and 54 unique proteins found in each sample type respectively. BF contained keratinocyte proliferation-related proteins and blood plasma contained abundant blood clotting proteins and apolipoproteins. BF contained more carbohydrates and less alpha-hydroxy acid metabolites than the BP. In this study, there were unique proteins and metabolites in BF and BP which were reflective of the local wound environment and systemic environments respectively. The results from this study demonstrate that the biomolecule content of BF is mostly the same as blood, but it also contains information specific to the local wound environment.

Barriers and facilitators to the use of personal information documents in health and social care settings for people living with dementia: A thematic synthesis and mapping to the COM-B framework.

INTRODUCTION: People living with dementia experience communication difficulties. Personal information documents, or healthcare passports, enable communication of information essential for the care of a person with dementia. Despite the potential for providing person-centred care, personal information documents are not ubiquitously used. The Capability Opportunity Motivation-Behaviour (COM-B) model can be used to understand factors determining individuals' behaviours. OBJECTIVES: This study aimed to identify the barriers to and facilitators of the use of healthcare passports for people living with dementia through a systematic review methodology. METHODS: A systematic search of six electronic databases was undertaken. Grey literature was searched using three databases. All study types reporting barriers to or facilitators of the use of personal information documents in the care of adults living with dementia in high-income countries were included. Study quality was assessed using the NICE Quality Appraisal Checklist. Thematic synthesis was used to develop descriptive themes, which were subsequently mapped to the COM-B framework. RESULTS: Nineteen papers were included. Themes included training, awareness, embedding the process in norms and appreciating the value of the personal information documents. A broad range of barriers and facilitators was identified within each COM-B domain. CONCLUSION: This framework provides a starting point for evidence-informed initiatives to improve the use of personal information documents in the care of people with dementia. PATIENT AND PUBLIC CONTRIBUTION: This is a review of studies and did not involve patients or the public. Review results will guide evaluation of a local personal information document, which will be designed with input from the Dementia Champions Network (includes carers and other stakeholders).

Experiences of men who have sex with men when initiating, implementing and persisting with HIV pre-exposure prophylaxis.

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

Development of a core outcome set for the evaluation of interventions to prevent COVID-19 in care homes (COS-COVID-PCARE Study).

BACKGROUND: People living in care homes have experienced devastating impact from COVID-19. As interventions to prevent the transmission of COVID-19 are developed and evaluated, there is an urgent need for researchers to agree on the outcomes used when evaluating their effectiveness. Having an agreed set of outcomes that are used in all relevant trials can ensure that study results can be compared. OBJECTIVE: The aim of the study was to develop a core outcome set (COS) for trials assessing the effectiveness of pharmacological and non-pharmacological interventions for preventing COVID-19 infection and transmission in care homes. METHODS: The study used established COS methodology. A list of candidate outcomes was identified by reviewing registered trials to evaluate interventions to prevent COVID-19 in care homes. Seventy key stakeholders participated in a Delphi survey, rating the candidate outcomes on a nine-point scale over two rounds, with the opportunity to propose additional outcomes. Stakeholders included care home representatives (n = 19), healthcare professionals (n = 20), people with personal experience of care homes (n = 7), researchers (n = 15) and others (n = 9). Outcomes were eligible for inclusion if they met an a priori threshold. A consensus meeting with stakeholders resulted in agreement of the final outcome set. RESULTS: Following the Delphi and consensus meeting, twenty-four outcomes were recommended for inclusion. These are grouped across four domains of infection, severity of illness, mortality, and 'other' (intervention specific or life impact). Due to the considerable heterogeneity between care homes, residents, and interventions, the relevance and importance of outcomes may differ between trial contexts. Intervention-specific outcomes would be included only where relevant to a given trial, thus reducing the measurement burden. CONCLUSION: Using a rapid response approach, a COS for COVID-19 prevention interventions in care homes has been developed. Future work should focus on identifying instruments for measuring these outcomes, and the interpretation and application of the COS across different trial contexts. Beyond COVID-19, the outcomes identified in this COS may have relevance to other infectious diseases in care homes, and the rapid response approach may be useful as preparation for future pandemics.

Changing sexual behaviours amongst MSM during the COVID-19 restrictions in Wales: a mixed methods study.

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