Australian consensus: Treatment goals for moderate to severe psoriasis in the era of targeted therapies - Considerations for paediatric patients.

BACKGROUND: Treatment goals have been established in Australia to facilitate the management of adults with moderate to severe psoriasis. The Australasian College of Dermatologists sought to determine if and how these adult treatment goals could be modified to accommodate the needs of paediatric and adolescent patients. METHODS: A modified Delphi approach was used. Comprehensive literature review and guideline evaluation resulted in the development of statements and other questions to establish current clinical practices. Two rounds of anonymous voting were undertaken, with a collaborative meeting held in between to discuss areas of discordance. Overall, consensus was defined as achievement of ≥75% agreement in the range 7-9 on a 9-point scale (1 strongly disagree; 9 strongly agree). RESULTS: Consensus was achieved on 23/29 statements in round 1 and 17/18 statements in round 2. There was a high level of concordance with treatment criteria in the adult setting. The limitations of applying assessment tools developed for use in adult patients to the paediatric setting were highlighted. Treatment targets in the paediatric setting should include objective metrics for disease severity and psychological impact on the patients and their family, and be based on validated, age-appropriate tools. CONCLUSION: While the assessment, classification and management of moderate to severe psoriasis in paediatric patients aligns with metrics established for adults, it is vital that nuances in the transition from childhood to adolescence be taken into account. Future research should focus on psoriasis severity assessment scales specific to the paediatric setting.

High-flow nasal oxygen for children's airway surgery to reduce hypoxaemic events: a randomised controlled trial.

BACKGROUND: Tubeless upper airway surgery in children is a complex procedure in which surgeons and anaesthetists share the same operating field. These procedures are often interrupted for rescue oxygen therapy. The efficacy of nasal high-flow oxygen to decrease the frequency of rescue interruptions in children undergoing upper airway surgery is unknown. METHODS: In this multicentre randomised trial conducted in five tertiary hospitals in Australia, children aged 0-16 years who required tubeless upper airway surgery were randomised (1:1) by a web-based randomisation tool to either nasal high-flow oxygen delivery or standard oxygen therapy (oxygen flows of up to 6 L/min). Randomisation was stratified by site and age (<1 year, 1-4 years, and 5-16 years). Subsequent tubeless upper airway surgery procedures in the same child could be included if there were more than 2 weeks between the procedures, and repeat surgical procedures meeting this condition were considered to be independent events. The oxygen therapy could not be masked, but the investigators remained blinded until outcome data were locked. The primary outcome was successful anaesthesia without interruption of the surgical procedure for rescue oxygenation. A rescue oxygenation event was defined as an interruption of the surgical procedure to deliver positive pressure ventilation using either bag mask technique, insertion of an endotracheal tube, or laryngeal mask to improve oxygenation. There were ten secondary outcomes, including the proportion of procedures with a hypoxaemic event (SpO2 <90%). Analyses were done on an intention-to-treat (ITT) basis. Safety was assessed in all enrolled participants. This trial is registered in the Australian New Zealand Clinical Trials Registry, ACTRN12618000949280, and is completed. FINDINGS: From Sept 4, 2018, to April 12, 2021, 581 procedures in 487 children were randomly assigned to high-flow oxygen (297 procedures) or standard care (284 procedures); after exclusions, 528 procedures (267 assigned to high-flow oxygen and 261 assigned to standard care) in 483 children (293 male and 190 female) were included in the ITT analysis. The primary outcome of successful anaesthesia without interruption for tubeless airway surgery was achieved in 236 (88%) of 267 procedures on high-flow oxygen and in 229 (88%) of 261 procedures on standard care (adjusted risk ratio [RR] 1·02, 95% CI 0·96-1·08, p=0·82). There were 51 (19%) procedures with a hypoxaemic event in the high-flow oxygen group and 57 (22%) in the standard care group (RR 0·86, 95% CI 0·58-1·24). Of the other prespecified secondary outcomes, none showed a significant difference between groups. Adverse events of epistaxis, laryngospasm, bronchospasm, hypoxaemia, bradycardia, cardiac arrest, hypotension, or death were similar in both study groups. INTERPRETATION: Nasal high-flow oxygen during tubeless upper airway surgery did not reduce the proportion of interruptions of the procedures for rescue oxygenation compared with standard care. There were no differences in adverse events between the intervention groups. These results suggest that both approaches, nasal high-flow or standard oxygen, are suitable alternatives to maintain oxygenation in children undergoing upper airway surgery. FUNDING: Thrasher Research Fund, the Australian and New Zealand College of Anaesthetists, the Society for Paediatric Anaesthesia in New Zealand and Australia.

Short-stay urgent hospital admissions of children with convulsions: A mixed methods exploratory study to inform out of hospital care pathways.

OBJECTIVE: To inform interventions focused on safely reducing urgent paediatric short stay admissions (SSAs) for convulsions. METHODS: Routinely acquired administrative data from hospital admissions in Scotland between 2015-2017 investigated characteristics of unscheduled SSAs (an urgent admission where admission and discharge occur on the same day) for a diagnosis of febrile and/or afebrile convulsions. Semi-structured interviews to explore perspectives of health professionals (n = 19) making referral or admission decisions about convulsions were undertaken. Interpretation of mixed methods findings was complemented by interviews with four parents with experience of unscheduled SSAs of children with convulsion. RESULTS: Most SSAs for convulsions present initially at hospital emergency departments (ED). In a subset of 10,588 (11%) of all cause SSAs with linked general practice data available, 72 (37%) children with a convulsion contacted both the GP and ED pre-admission. Within 30 days of discharge, 10% (n = 141) of children admitted with afebrile convulsions had been readmitted to hospital with a further convulsion. Interview data suggest that panic and anxiety, through fear that the situation is life threatening, was a primary factor driving hospital attendance and admission. Lengthy waits to speak to appropriate professionals exacerbate parental anxiety and can trigger direct attendance at ED, whereas some children with complex needs had direct access to convulsion professionals. CONCLUSIONS: SSAs for convulsions are different to SSAs for other conditions and our findings could inform new efficient convulsion-specific pre and post hospital pathways designed to improve family experiences and reduce admissions and readmissions.

The Neo-Open Reading Frame Peptides That Comprise the Tumor Framome Are a Rich Source of Neoantigens for Cancer Immunotherapy.

Identification of immunogenic cancer neoantigens as targets for therapy is challenging. Here, we integrate the whole-genome and long-read transcript sequencing of cancers to identify the collection of neo-open reading frame peptides (NOP) expressed in tumors. We termed this collection of NOPs the tumor framome. NOPs represent tumor-specific peptides that are different from wild-type proteins and may be strongly immunogenic. We describe a class of hidden NOPs that derive from structural genomic variants involving an upstream protein coding gene driving expression and translation of noncoding regions of the genome downstream of a rearrangement breakpoint, i.e., where no gene annotation or evidence for transcription exists. The entire collection of NOPs represents a vast number of possible neoantigens particularly in tumors with many structural genomic variants and a low number of missense mutations. We show that NOPs are immunogenic and epitopes derived from NOPs can bind to MHC class I molecules. Finally, we provide evidence for the presence of memory T cells specific for hidden NOPs in peripheral blood from a patient with lung cancer. This work highlights NOPs as a major source of possible neoantigens for personalized cancer immunotherapy and provides a rationale for analyzing the complete cancer genome and transcriptome as a basis for the detection of NOPs.

Differentiation signals induce APOBEC3A expression via GRHL3 in squamous epithelia and squamous cell carcinoma.

Two APOBEC (apolipoprotein-B mRNA editing enzyme catalytic polypeptide-like) DNA cytosine deaminase enzymes (APOBEC3A and APOBEC3B) generate somatic mutations in cancer, driving tumour development and drug resistance. Here we used single cell RNA sequencing to study APOBEC3A and APOBEC3B expression in healthy and malignant mucosal epithelia, validating key observations with immunohistochemistry, spatial transcriptomics and functional experiments. Whereas APOBEC3B is expressed in keratinocytes entering mitosis, we show that APOBEC3A expression is confined largely to terminally differentiating cells and requires Grainyhead-like transcription factor 3 (GRHL3). Thus, in normal tissue, neither deaminase appears to be expressed at high levels during DNA replication, the cell cycle stage associated with APOBEC-mediated mutagenesis. In contrast, we show that in squamous cell carcinoma tissues, there is expansion of GRHL3 expression and activity to a subset of cells undergoing DNA replication and concomitant extension of APOBEC3A expression to proliferating cells. These findings indicate a mechanism for acquisition of APOBEC3A mutagenic activity in tumours.

Evaluation of a mobile COVID-19 vaccination van outreach service in an outer South London borough.

BACKGROUND: This study aimed to explore differences in users of a COVID-19 mobile vaccine van service and users of a COVID-19 static vaccination hub, and the impact of changes in national COVID-19 vaccine policy on vaccine uptake. METHODS: The age distribution of male and female service users in each service was compared. The average number of vaccines administered per hour per week was analysed. RESULTS: Females aged 80-89 represented 51.9% (95% CI 49.5-54.3%) of female vaccine van users compared with 2.8% (95% CI 2.5-3.1%) of female static hub users. The static hub had significantly greater proportions of female service users in all other age brackets.For males, the greatest difference was in those aged 70-79 who represented 29.8% (95% CI 27-32.6%) of vaccine van users and 16.6% (95% CI 16-17.2%) static hub users.Fewer vaccines were administered 2-3 weeks before the COVID-19 autumn booster policy change compared with 2-3 weeks after; 1.92 versus 6.25 vaccines per hour, respectively (Mann-Whitney U = 7, n1 = 11, n2 = 8, P < 0.01 two-tailed). CONCLUSIONS: These findings suggest that a mobile vaccine van service is an effective model for increasing COVID-19 vaccination uptake in elderly residents, particularly after a national policy change.

Improving the mental health of farmers: what types of remote support are acceptable, feasible, and improve outcomes? A feasibility RCT.

BACKGROUND: The farming community have high rates of poor mental health, and are relatively 'hard to reach' with mental health services. The aim of this study was therefore to undertake a feasibility RCT, based on two mental health interventions. These were (1) CBT based 'Living Life to the Full for Farming Communities' (LLTTF-F; www.llttf.com ), and (2) a holistic social and emotional support service delivered by the Royal Scottish Agricultural Benevolent Institution (RSABI). The feasibility was supplemented by process evaluation. METHODS: This feasibility study aimed to recruit 40 individuals from the farming community who were experiencing a common health problem defined as a score of > = 8 on PHQ-9. A snowball approach was used to recruit interested individuals who had an association with farming. An initial telephone call screened for eligibility and obtained consent to randomisation to the two specified interventions, or to a thirdly group receiving a combination of both LLTTF-F and 'Social and emotional support'. Participants were permitted to override the randomised option if they expressed a strong preference before the interventions began. RESULTS: Thirty-two participants provided baseline and three-month data. All three interventions showed positive improvements on PHQ-9 scores as follows: the 'combined intervention' mean baseline score was 18.1 compared to 12.0 at 3-month follow-up (mean change 6.1). 'Social and emotional support' mean baseline score was 11.3 compared to 6.7 at 3-month follow-up (mean change 4.6). 'LLTTF-F CBT-based intervention only' mean baseline score was 11.8 compared to 4.5 at 3-month follow-up (mean change 7.3). The retention rate was 81% at three months. In a sub-group of the LLTTF-F CBT-based intervention online materials were supplemented by telephone guided support. This approach received very positive feedback. CONCLUSIONS: Recruitment from the farming community required intense effort, and good engagement can then be retained for at least three months. There is evidence that the interventions used were feasible, and tentative evidence that they had a demonstrable effect on mental wellbeing, with the LLTTFF providing the largest effect on PHQ-9 scores. Trial Registration Number ISRCTN27173711, submitted 25/08/2023, confirmed 22/092023.

Real-World Evaluation of the Feasibility, Acceptability and Safety of a Remote, Self-Management Parkinson's Disease Care Pathway: A Healthcare Improvement Initiative.

BACKGROUND: There is significant unmet need for effective and efficiently delivered care for people with Parkinson's disease (PwP). We undertook a service improvement initiative to co-develop and implement a new care pathway, Home Based Care (HBC), based on supported self-management, remote monitoring and the ability to trigger a healthcare contact when needed. OBJECTIVE: To evaluate feasibility, acceptability and safety of Home Based Care. METHODS: We evaluated data from the first 100 patients on HBC for 6 months. Patient monitoring, performed at baseline and 6-monthly, comprised motor (MDS-UPDRS II and accelerometer), non-motor (NMSQ, PDSS-2, HADS) and quality of life (PDQ) measures. Care quality was audited against Parkinson's UK national audit standards. Process measures captured feasibility. Acceptability was assessed using a mixed-methods approach comprising questionnaires and semi-structured interviews. RESULTS: Between October 2019 and January 2021, 108 PwP were enrolled onto HBC, with data from 100 being available at 6 months. Over 90% of all questionnaires were returned, 97% were complete or had < 3 missing items. Reporting and communications occurred within agreed timeframes. Compared with baseline, after 6m on HBC, PD symptoms were stable; more PwP felt listened to (90% vs. 79%) and able to seek help (79% vs. 68%). HBC met 93% of national audit criteria. Key themes from the interviews included autonomy and empowerment. CONCLUSIONS: We have demonstrated acceptability, feasibility and safety of our novel remotely delivered Parkinson's care pathway. Ensuring scalability will widen its reach and realize its benefits for underserved communities, enabling formal comparisons with standard care and cost-effectiveness evaluation.

Resveratrol activation of SIRT1/MFN2 can improve mitochondria function, alleviating doxorubicin-induced myocardial injury.

Background: Doxorubicin is a widely used cytotoxic chemotherapy agent for treating different malignancies. However, its use is associated with dose-dependent cardiotoxicity, causing irreversible myocardial damage and significantly reducing the patient's quality of life and survival. In this study, an animal model of doxorubicin-induced cardiomyopathy was used to investigate the pathogenesis of doxorubicin-induced myocardial injury. This study also investigated a possible treatment strategy for alleviating myocardial injury through resveratrol therapy in vitro. Methods: Adult male C57BL/6J mice were randomly divided into a control group and a doxorubicin group. Body weight, echocardiography, surface electrocardiogram, and myocardial histomorphology were measured. The mechanisms of doxorubicin cardiotoxicity in H9c2 cell lines were explored by comparing three groups (phosphate-buffered saline, doxorubicin, and doxorubicin with resveratrol). Results: Compared to the control group, the doxorubicin group showed a lower body weight and higher systolic arterial pressure, associated with reduced left ventricular ejection fraction and left ventricular fractional shortening, prolonged PR interval, and QT interval. These abnormalities were associated with vacuolation and increased disorder in the mitochondria of cardiomyocytes, increased protein expression levels of α-smooth muscle actin and caspase 3, and reduced protein expression levels of Mitofusin2 (MFN2) and Sirtuin1 (SIRT1). Compared to the doxorubicin group, doxorubicin + resveratrol treatment reduced caspase 3 and manganese superoxide dismutase, and increased MFN2 and SIRT1 expression levels. Conclusion: Doxorubicin toxicity leads to abnormal mitochondrial morphology and dysfunction in cardiomyocytes and induces apoptosis by interfering with mitochondrial fusion. Resveratrol ameliorates doxorubicin-induced cardiotoxicity by activating SIRT1/MFN2 to improve mitochondria function.

Investigating trial design variability in trials of disease-modifying therapies in Parkinson's disease: a scoping review protocol.

INTRODUCTION: Parkinson's disease (PD) is a debilitating neurological disorder for which the identification of disease-modifying interventions represents a major unmet need. Diverse trial designs have attempted to mitigate challenges of population heterogeneity, efficacious symptomatic therapy and lack of outcome measures that are objective and sensitive to change in a disease modification setting. It is not clear whether consensus is emerging regarding trial design choices. Here, we report the protocol of a scoping review that will provide a contemporary update on trial design variability for disease-modifying interventions in PD. METHODS AND ANALYSIS: The Population, Intervention, Comparator, Outcome and Study design (PICOS) framework will be used to structure the review, inform study selection and analysis. The databases MEDLINE, Web of Science, Cochrane and the trial registry ClinicalTrials.gov will be systematically searched to identify published studies and registry entries in English. Two independent reviewers will screen study titles, abstracts and full text for eligibility, with disagreements being resolved through discussion or by a third reviewer where necessary. Data on general study information, eligibility criteria, outcome measures, trial design, retention and statistically significant findings will be extracted into a standardised form. Extracted data will be presented in a descriptive analysis. We will report our findings using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Scoping Review extension. ETHICS AND DISSEMINATION: This work will provide an overview of variation and emerging trends in trial design choices for disease-modifying trials of PD. Due to the nature of this study, there are no ethical or safety considerations. We plan to publish our findings in a peer-reviewed journal.

Identifying and prioritising future interventions with stakeholders to improve paediatric urgent care pathways in Scotland, UK: a mixed-methods study.

OBJECTIVES: To identify and prioritise interventions, from the perspectives of parents and health professionals, which may be alternatives to current unscheduled paediatric urgent care pathways. DESIGN: FLAMINGO (FLow of AdMissions in chIldren and youNG peOple) is a sequential mixed-methods study, with public and patient involvement (PPI) throughout. Data linkage for urgent admissions and three referral sources: emergency department, out of hours service and general practice, was followed by qualitative interviews with parents and professionals. Findings were presented and discussed at a stakeholder intervention prioritisation event. SETTING: National Health Service in Scotland, UK. PARTICIPANTS: Quantitative data: children with urgent medical admission to hospital from 2015 to 2017. Qualitative interviews: parents and health professionals with experiences of urgent short stay hospital admissions of children. PPI engagement was conducted with nine parent-toddler groups and a university-based PPI advisory group. Stakeholder event: parents, health professionals and representatives from Scottish Government, academia, charities and PPI attended. RESULTS: Data for 171 039 admissions which included 92 229 short stay admissions were analysed and 48 health professionals and 21 parents were interviewed. The stakeholder event included 7 parents, 12 health professionals and 28 other stakeholders. Analysis and synthesis of all data identified seven interventions which were prioritised at the stakeholder event: (1) addressing gaps in acute paediatric skills of health professionals working in community settings; (2) assessment and observation of acutely unwell children in community settings; (3) creation of holistic children's 'hubs'; (4) adoption of 'hospital at home' models; and three specialised care pathways for subgroups of children; (5) convulsions; (6) being aged <2 years old; and (7) wheeze/bronchiolitis. Stakeholders prioritised interventions 1, 2 and 3; these could be combined into a whole population intervention. Barriers to progressing these include resources, staffing and rurality. CONCLUSIONS: Health professionals and families want future interventions that are patient-centred, community-based and aligned to outcomes that matter to them.

Regional variations in short stay urgent paediatric hospital admissions: a sequential mixed-methods approach exploring differences through data linkage and qualitative interviews.

OBJECTIVES: The aim of this sequential mixed-methods study was to describe and understand how paediatric short stay admission (SSA) rates vary across Health Board regions of Scotland. DESIGN: Exploratory sequential mixed-methods study. Routinely acquired data for the annual (per capita) SSA to hospital were compared across the 11 regions. Five diverse regions with different SSA per capita formed cases for qualitative interviews with health professionals and parents to explore how care pathways, service features and geography may influence decisions to admit. SETTING: Scotland. PARTICIPANTS: All children admitted to hospital 2015-2017. Healthcare staff (n=48) and parents (n=15) were interviewed. RESULTS: Of 171 039 urgent hospital admissions, 92 229 were SSAs, with a fivefold variation between 14 and 69/1000 children/year across regions. SSAs were higher for children in the most deprived compared with the least deprived communities. When expressed as a ratio of highest to lowest SSA/1000 children/year for diagnosed conditions between regions, the ratio was highest (10.1) for upper respiratory tract infection and lowest (2.8) for convulsions. Readmissions varied between 0.80 and 2.52/1000/year, with regions reporting higher SSA rates more likely to report higher readmission rates (r=0.70, p=0.016, n=11). Proximity and ease of access to services, local differences in service structure and configuration, national policy directives and disparities in how an SSA is defined were recognised by interviewees as explaining the observed regional variations in SSAs. Socioeconomic deprivation was seldom spontaneously raised by professionals when reflecting on reasons to refer or admit a child. Instead, greater emphasis was placed on the wider social circumstances and parents' capacity to cope with and manage their child's illness at home. CONCLUSION: SSA rates for children vary quantitatively by region, condition and area deprivation and our interviews identify reasons for this. These findings can usefully inform future care pathway interventions.

NEAL: an open-source tool for audio annotation.

Passive acoustic monitoring is used widely in ecology, biodiversity, and conservation studies. Data sets collected via acoustic monitoring are often extremely large and built to be processed automatically using artificial intelligence and machine learning models, which aim to replicate the work of domain experts. These models, being supervised learning algorithms, need to be trained on high quality annotations produced by experts. Since the experts are often resource-limited, a cost-effective process for annotating audio is needed to get maximal use out of the data. We present an open-source interactive audio data annotation tool, NEAL (Nature+Energy Audio Labeller). Built using R and the associated Shiny framework, the tool provides a reactive environment where users can quickly annotate audio files and adjust settings that automatically change the corresponding elements of the user interface. The app has been designed with the goal of having both expert birders and citizen scientists contribute to acoustic annotation projects. The popularity and flexibility of R programming in bioacoustics means that the Shiny app can be modified for other bird labelling data sets, or even to generic audio labelling tasks. We demonstrate the app by labelling data collected from wind farm sites across Ireland.

Metabolomics of head and neck cancer in biofluids: an integrative systematic review.

INTRODUCTION: Head and neck cancer (HNC) is the fifth most common cancer globally. Diagnosis at early stages are critical to reduce mortality and improve functional and esthetic outcomes associated with HNC. Metabolomics is a promising approach for discovery of biomarkers and metabolic pathways for risk assessment and early detection of HNC. OBJECTIVES: To summarize and consolidate the available evidence on metabolomics and HNC in plasma/serum, saliva, and urine. METHODS: A systematic search of experimental research was executed using PubMed and Web of Science. Available data on areas under the curve was extracted. Metabolic pathway enrichment analysis were performed to identify metabolic pathways altered in HNC. Fifty-four studies were eligible for data extraction (33 performed in plasma/serum, 15 in saliva and 6 in urine). RESULTS: Metabolites with high discriminatory performance for detection of HNC included single metabolites and combination panels of several lysoPCs, pyroglutamate, glutamic acid, glucose, tartronic acid, arachidonic acid, norvaline, linoleic acid, propionate, acetone, acetate, choline, glutamate and others. The glucose-alanine cycle and the urea cycle were the most altered pathways in HNC, among other pathways (i.e. gluconeogenesis, glycine and serine metabolism, alanine metabolism, etc.). Specific metabolites that can potentially serve as complementary less- or non-invasive biomarkers, as well as metabolic pathways integrating the data from the available studies, are presented. CONCLUSION: The present work highlights utility of metabolite-based biomarkers for risk assessment, early detection, and prognostication of HNC, as well as facilitates incorporation of available metabolomics studies into multi-omics data integration and big data analytics for personalized health.

Engaging the agricultural community in the development of mental health interventions: a qualitative research study.

BACKGROUND: Farmers and those involved in the wider agricultural industry have a high suicide rate. They are also a 'hard to reach' group who make less than average use of mental health services. There is therefore a need to understand how best to develop interventions that meet their needs. The aims of this study were to develop a deeper understanding of the farming context and target population and to engage farmers in the shaping of two potential mental health interventions that could be incorporated in a pilot RCT. METHODS: The study was informed throughout by a reference group, who assisted in co-production of the research materials. A snowball approach was used to recruit interested individuals who had an association with farming. Twenty one telephone interviews were undertaken and analysed using the six phases of thematic analysis proposed by Braun and Clarke. RESULTS: Key themes (and sub-themes shown in brackets) related to the study aims were: everyday life (work-life balance; isolation and loneliness); farm management (technology and social media; production, people management, learning and teaching; external pressures; livestock and farm production; financial aspects); demographics (effects of aging); engagement (appropriate wording when talking about mental health; recognising need for help; religion; normalising mental health issues; approaching the conversation); training (mental health training for supporters of the farming community; health & safety and the inclusion of mental health training); and personal stories and experiences, which was an emerging theme. CONCLUSIONS: Recruiting farmers into research studies is best done by meeting farmers where they are found, for example, farmers marts. Accessibility of content, tailoring to the farming community, and guided support are key to effective recruitment and retention.

Virtual medical research mentoring.

BACKGROUND: Medical research is important for professional advancement, and mentoring is a key means by which students and early-career doctors can engage in research. Contrasting international research collaborations, research mentoring programmes are often geographically limited. As the COVID-19 pandemic has led to increased use of online technology for classes and conferences, a virtual, international approach to medical research mentoring may be valuable. APPROACH: We hereby describe our experience at the Cardiovascular Analytics Group, a virtual international medical research mentoring group established in 2015. We make use of virtual platforms in multi-level mentoring with peer mentoring and emphasise active participation, early leadership, an open culture, accessible research support and a distributed research workflow. EVALUATION: With 63 active members from 14 different countries, the Group has been successful in training medical students and early-career medical graduates in academic medicine. Our members have led over 100 peer-reviewed publications of original research and reviews since 2015, winning 13 research prizes during this time. IMPLICATIONS: Our accessible-distributed model of virtual international medical research collaboration and multi-level mentoring is viable and efficient and caters to the needs of contemporary healthcare. Others should consider building similar models to improve medical research mentoring globally.

The Role of Robotic Surgery in Laryngeal Cancer.

Transoral robotic surgery (TORS) is a growing field in the treatment of head and neck cancers. Its benefits have been proven in the treatment of oropharynx HPV-positive squamous cell carcinoma, replacing chemoradiation as primary treatment of early-stage cancers or reducing the required radiation dosage, leading to improved functional outcomes without compromising oncological outcomes. There is also interest in the application of TORS for larynx cancer with the hope of achieving similar outcomes to replace open surgery or radiation treatments. Specifically, in the larynx, TORS can be used to resect supraglottic or glottic tumors.

Health visiting in the UK in light of the COVID-19 pandemic experience (RReHOPE): a realist review protocol.

INTRODUCTION: Health visiting services, providing support to under 5s and their families, are organised and delivered in very different ways in different parts of the UK. While there has been attention to the key components of health visiting practice and what works well and how, there is little research on how health visiting services are organised and delivered and how that affects their ability to meet their objectives. The COVID-19 pandemic rapidly disrupted service delivery from March 2020. This realist review aims to synthesise the evidence on changes during the pandemic to identify the potential for improving health visiting services and their delivery. METHODS AND ANALYSIS: This review will follow the RAMESES (Realist And Meta-narrative Evidence Syntheses: Evolving Standards) quality standards and Pawson's five iterative stages to locate existing theories, search for evidence, select literature, extract data, synthesise evidence and draw conclusions. It will be guided by stakeholder engagement with practitioners, commissioners, policymakers, policy advocates and people with lived experience. This approach will consider the emerging strategies and evolving contexts in which the services are delivered, and the varied outcomes for different groups. A realist logic of analysis will be used to make sense of what was happening to health visiting services during and following the pandemic response through the identification and testing of programme theories. Our refined programme theory will then be used to develop recommendations for improving the organisation, delivery and ongoing postpandemic recovery of health visiting services. ETHICS AND DISSEMINATION: General University Ethics Panel approval has been obtained from University of Stirling (reference 7662). Dissemination will build on links to policymakers, commissioners, providers, policy advocates and the public. A range of audiences will be targeted using outputs tailored to each. A final stakeholder event focused on knowledge mobilisation will aid development of recommendations. PROSPERO REGISTRATION NUMBER: CRD42022343117.

Universal Cooling Dynamics toward a Quantum Critical Point.

We investigate the loss of adiabaticity when cooling a many-body quantum system from an initial thermal state toward a quantum critical point. The excitation density, which quantifies the degree of adiabaticity of the dynamics, is found to obey scaling laws in the cooling velocity as well as in the initial and final temperatures of the cooling protocol. The scaling laws are universal, governed by the critical exponents of the quantum phase transition. The validity of these statements is shown analytically for a Kitaev quantum wire coupled to Markovian baths and argued to be valid under rather general conditions. Our results establish that quantum critical properties can be probed dynamically at finite temperature, without even varying the control parameter of the quantum phase transition.

Comparison of Sodium-Glucose Cotransporter-2 Inhibitor and Dipeptidyl Peptidase-4 Inhibitor on the Risks of New-Onset Atrial Fibrillation, Stroke and Mortality in Diabetic Patients: A Propensity Score-Matched Study in Hong Kong.

OBJECTIVE: To compare the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2Is) and dipeptidyl peptidase-4 inhibitors (DPP4Is) on adverse outcomes in diabetic patients in Hong Kong. METHODS: This was a retrospective population-based cohort study of type 2 diabetes mellitus patients (n = 72,746) treated with SGLT2I or DPP4I between January 1, 2015, and December 31, 2020, in Hong Kong. Patients with exposure to both DPP4I and SGLT2I therapy, without complete demographics or mortality data, or who had prior atrial fibrillation (AF) were excluded. The study outcomes were new-onset AF, stroke/transient ischemic attack, cardiovascular mortality and all-cause mortality. Propensity score matching (1:1 ratio) between SGLT2I and DPP4I users was performed. RESULTS: The unmatched study cohort included 21,713 SGLT2I users and 39,510 DPP4I users (total: n = 61,233 patients; 55.37% males, median age: 62.7 years [interquartile range (IQR): 54.6-71.9 years]). Over a median follow-up of 2030 (IQR: 1912-2117) days, 2496 patients (incidence rate [IR]: 4.07%) developed new-onset AF, 2179 patients (IR: 3.55%) developed stroke/transient ischemic attack, 1963 (IR: 3.20%) died from cardiovascular causes and 6607 patients (IR: 10.79%) suffered from all-cause mortality. After propensity score matching (SGLT2I: n = 21,713; DPP4I: n = 21,713), SGLT2I users showed lower incidence of new-onset AF (1.96% vs. 2.78%, standardized mean difference [SMD] = 0.05), stroke (1.80% vs. 3.52%, SMD = 0.11), cardiovascular mortality (0.47% vs. 1.56%, SMD = 0.11) and all-cause mortality (2.59% vs. 7.47%, SMD = 0.22) compared to DPP4I users. Cox regression found that SGLT2I users showed lower risk of new-onset AF (hazard ratio [HR]: 0.68, 95% confidence interval [CI]: [0.56, 0.83], P = 0.0001), stroke (HR: 0.64, 95% CI: [0.53, 0.79], P < 0.0001), cardiovascular mortality (HR: 0.39, 95% CI: [0.27, 0.56], P < 0.0001) and all-cause mortality (HR: 0.44, 95% CI: [0.37, 0.51], P < 0.0001) after adjusting for significant demographics, past comorbidities, medications and laboratory tests. CONCLUSIONS: Based on real-world data of type 2 diabetic patients in Hong Kong, SGLT2I use was associated with lower risk of incident AF, stroke/transient ischemic attack, and cardiovascular and all-cause mortality outcomes compared to DPP4I use.