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Fingerprints are created by elevations and depressions on the fingertip pads. Each person has their own unique fingerprints which can be used in the identification of that individual when alive, during the immediate postmortem period, or even after the digits have become mummified. Mummification can occur naturally; it can be partial (such as localized to only the hands and feet, extensive, or complete. Obtaining fingerprints after the skin has become mummified can be attempted while the digits remaining intact with the hand; however, the digits may need to be removed from the hand and the finger pads may also need to be separated from the underlying bone to secure an adequate fingerprint. Frequently, the mummified tissue needs to be rehydrated; numerous solutions have been used that increase the turgor of the digits, provide softening and pliability of the tissue, and enhance the details of the finger pad ridges. An aqueous solution of sodium carbonate (either combined with acetic acid or combined with 95 percent ethanol and distilled water) was found to be most effective for rehydration. Thereafter, various techniques can be attempted to obtain the fingerprint. These include the traditional method of inking and rolling of the finger or photographing the finger. Powders (such as aluminum powder, black fingerprint powder, white cornstarch-based powder, or fluorescent powder) can be used to enhance the ridge features; adhesive tape can be pressed against the powdered digit and the print pattern preserved by applying the adhesive tape to a clear transparency sheet. In addition, molds (using modeling clay or silicone rubber) and casts (using plaster of Paris, dental casting materials, or putty) can be made of the digits; either the molds or the casts or both can be photographed with or without prior application of fingerprint powder. Transillumination, using a fiber optic light source to illuminate the epidermis and underlying remaining dermis of a scraped and defleshed finger pad can be used to demonstrate the finger ridge pattern when the photographing the tip of the digit. In summary, forensic dermatology can have an integral role in obtaining fingerprints from mummified digits, which can be successfully used for the identification of the decedent., Competing Interests: Declaration of competing interest None, (Copyright © 2024. Published by Elsevier Inc.)

Background and Objectives: Older adults experiencing neurocognitive disease (NCD) contend with complex care often characterized by high emotional strain. Mitigating complex care with decision support tools can clarify options. When used in conjunction with the practice of shared decision making (SDM), these tools can improve satisfaction and confidence in treatment. The use of these tools for cognitive health has increased, but more is needed to understand how these tools incorporate social needs into treatment plans., Research Design and Methods: We conducted an environmental scan using a MEDLINE-informed search strategy and feedback from an expert steering committee to characterize current tools and approaches for engaging older adults experiencing NCD. We assessed their application and development, incorporation of social determinants, goals or preferences, and inclusion of caregivers in their design., Results: We identified 11 articles, 7 of which show that SDM helps guide tool development and that most center on clinical decision making. Types of tools varied by clinical site and those differences reflected patient need. A collective value across tools was their use to forge meaningful conversations. Most tools appeared designed without the explicit goal to elicit patient social needs or incorporate nonclinical strategies into treatment plans., Discussion and Implications: Several challenges and opportunities exist that center on strategies to engage patients in the design and testing of tools that support conversations with clinicians about cognitive health. Future work should focus on building and testing adaptable tools that support patient and family social care needs beyond clinical care settings., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: Low health literacy is associated with worse health outcomes, including for cardiovascular disease (CVD). However, general practitioners (GPs) have limited support to identify and address patient health literacy needs in CVD prevention consultations. This study explored GPs' experiences of patient health literacy needs during CVD risk assessment and management consultations., Methods: Semi-structured interviews with 18 GPs in Tasmania, Australia in 2021. A Framework Analysis approach was used to code transcripts to a thematic framework., Results: GPs perceptions on patient health literacy informed three themes: 1. Methods of estimating health literacy; 2. GPs' perceptions about the impact of health literacy on CVD prevention including risk factor knowledge and behaviours; and 3. Strategies for communicating with patients experiencing health literacy challenges. The findings show that while no formal tools were used to assess health literacy in this sample, perceived health literacy can change GPs' communication and prevention strategies., Conclusion: The findings raise concerns about the equity of choices made available to patients, based on subjective perceptions of their health literacy level., Practice Implication: GPs could be better supported to assess and address patient health literacy needs in CVD prevention consultations., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Carissa Bonner reports financial support was provided by National Health and Medical Research Council. Carissa Bonner reports financial support was provided by Heart Foundation. Mark R. Nelson reports a relationship with Novartis Lipid Advisory Board that includes: board membership. CB and MRN are involved in the current CVD prevention guideline revision released in July 2023., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: The Therapy Outcome Measure (TOM) comprises many profession and client group-specific adapted scales based on the International Classification of Functioning Model, used by different Health Care Professionals (HCPs). A new Multidisciplinary stroke TOM scale (MDT Stroke TOMs) was developed by amalgamating the relevant scales. This study aimed to develop a scale to describe patients' abilities and improve communication and collaboration within the stroke Multidisciplinary Team (MDT). The present study investigated the inter-rater and intra-rater reliability of this adaptation., Materials and Methods: The MDT Stroke TOM Scale was developed by combining and rewording four profession-specific adapted TOM scales following iterative trials and discussions leading to an agreed version. 150 stroke Allied Health Professional (AHPs) and nurses were trained virtually in TOM and the MDT Stroke TOM Scale. Ten AHP and nursing raters from five professions evaluated ten composite stroke case studies for inter-rater reliability. Six participated in the intra-rater reliability review of the same three case studies at different time points. Reliability was quantified using intraclass correlation coefficients and measurement error using the smallest detectable change., Results: There was good to excellent concordance between the raters in terms of scoring. Raters' scores were also consistent. The MDT Stroke TOMs is being used consistently across the South West London Stroke Network., Conclusion: The Stroke MDT TOMs is psychometrically robust and should assist with improving team work in the rehabilitation of stroke patients and their carers. Future research may use MDT Stroke TOM to promote interprofessional team working and facilitate communication in Stroke Rehabilitation.

Background: People with multiple and persistent physical symptoms have impaired quality of life and poor experiences of health care. We aimed to evaluate the effectiveness of a community-based symptom-clinic intervention in people with multiple and persistent physical symptoms, hypothesising that this symptoms clinic plus usual care would be superior to usual care only., Methods: The Multiple Symptoms Study 3 was a pragmatic, multicentre, parallel-group, individually randomised controlled trial conducted in 108 general practices in the UK National Health Service in four regions of England between Dec 6, 2018, and June 30, 2023. Participants were individually randomised (1:1) to the symptom-clinic intervention plus usual care or to usual care only via a computer-generated, pseudo-random list stratified by trial centre. Allocation was done by the trial statistician and concealed with a centralised, web-based randomisation system; masking participants was not possible due to the nature of the intervention. The symptom-clinic intervention was a sequence of up to four medical consultations that aimed to elicit a detailed clinical history, fully hear and validate the participant, offer rational explanations for symptoms, and assist the participant to develop ways of managing their symptoms; it was delivered by general practitioners with an extended role. The primary outcome was Patient Health Questionnaire-15 (PHQ-15) score 52 weeks after randomisation, analysed by intention to treat. The trial is registered on the ISRCTN registry (ISRCTN57050216)., Findings: 354 participants were randomly assigned; 178 (50%) were assigned to receive the community-based symptoms clinic plus usual care and 176 (50%) were assigned to receive usual care only. At the primary-outcome point of 52 weeks, PHQ-15 scores were 14·1 (SD 3·7) in the group receiving usual care and 12·2 (4·5) in the group receiving the intervention. The adjusted between-group difference of -1·82 (95% CI -2·67 to -0·97) was statistically significantly in favour of the intervention group (p<0·0001). There were 39 adverse events in the group receiving usual care and 36 adverse events in the group receiving the intervention. There were no statistically significant between-group differences in the proportion of participants who had non-serious adverse events (-0·03, 95% CI -0·11 to 0·05) or serious adverse events (0·02, -0·02 to 0·07). No serious adverse event was deemed to be related to the trial intervention., Interpretation: Our symptom-clinic intervention, which focused on explaining persistent symptoms to participants in order to support self-management, led to sustained improvement in multiple and persistent physical symptoms., Funding: UK National Institute for Health and Care Research., Competing Interests: Declaration of interests CB has received publisher royalties from Wiley. JD was a member of the Health and Social Care Delivery Research Board for the UK National Institute for Health and Care Research. 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: Pathology services represent an ideal setting to integrate absolute cardiovascular disease (CVD) risk estimation when patients attend for routine cholesterol testing. This study aimed to explore the process of implementing CVD risk estimation into point-of-care service delivery by pathology staff to inform future implementation and sustainability., Methods: A new service for CVD risk estimation via a self-directed screening station was implemented into 14 pathology service sites across Tasmania, Australia. Before implementation, observations at pathology services (n = 26) and semi-structured interviews were undertaken with 26 pathology staff (88% female, 77% aged 41-60 years) to identify factors that could impact implementation of the service. The process of implementation was then evaluated using participant observations and clinical trial recruitment data. Transcripts and field notes were analysed thematically according to the Medical Research Council Framework and used to develop a programme logic model to understand how the service could be adapted to be successfully integrated into routine workflow at pathology services., Results: Eight key themes were identified during the pre-implementation phase as important factors that could impact upon integration of CVD risk estimation into pathology services. Themes related to factors within the organisation, including available resources, logistics and workflow, as well as having sufficient time to complete the intervention. Additional factors related to the individual motivations of staff, collaborative leadership and patient characteristics. Success of implementation varied among sites, requiring the trialling of different strategies to support uptake of the service and patient recruitment., Conclusions: Implementing CVD risk estimation into point-of-care pathology services required an understanding of the core implementation components specific to each context, and for implementation strategies to be targeted to the individual and organisational contexts. The generated programme logic model may be useful in guiding future implementation endeavours within these services and aiding the selection of apt implementation strategies., Trial Registration: ClinicalTrials.gov Identifier: NCT04896021, registered 19/05/2021, https://clinicaltrials.gov/study/NCT04896021., (© 2024 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons Ltd.)

Objective: To assess accuracy of telephone triage in identifying need for emergency care among those with suspected COVID-19 infection and identify factors which affect triage accuracy., Design: Observational cohort study., Setting: Community telephone triage provided in the UK by Yorkshire Ambulance Service NHS Trust (YAS)., Participants: 40 261 adults who contacted National Health Service (NHS) 111 telephone triage services provided by YAS between 18 March 2020 and 29 June 2020 with symptoms indicating COVID-19 infection were linked to Office for National Statistics death registrations and healthcare data collected by NHS Digital., Outcome: Accuracy of triage disposition was assessed in terms of death or need for organ support up to 30 days from first contact., Results: Callers had a 3% (1200/40 261) risk of serious adverse outcomes (death or organ support). Telephone triage recommended self-care or non-urgent assessment for 60% (24 335/40 261), with a 1.3% (310/24 335) risk of adverse outcomes. Telephone triage had 74.2% sensitivity (95% CI: 71.6 to 76.6%) and 61.5% specificity (95% CI: 61% to 62%) for the primary outcome. Multivariable analysis suggested respiratory comorbidities may be overappreciated, and diabetes underappreciated as predictors of deterioration. Repeat contact with triage service appears to be an important under-recognised predictor of deterioration with 2 contacts (OR 1.77, 95% CI: 1.14 to 2.75) and 3 or more contacts (OR 4.02, 95% CI: 1.68 to 9.65) associated with false negative triage., Conclusion: Patients advised to self-care or receive non-urgent clinical assessment had a small but non-negligible risk of serious clinical deterioration. Repeat contact with telephone services needs recognition as an important predictor of subsequent adverse outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: In recent years, hand drying has been highlighted as a key step in appropriate hand hygiene, as moisture on hands can increase the transfer of micro-organisms from hands to surfaces and vice versa., Aim: To understand bacterial and viral aerosolization following hand drying, and study the transfer of micro-organisms from hands to surfaces after drying using different methods., Methods: Groups of five volunteers had their hands pre-washed with soap, rinsed and dried, then inoculated with a concentrated mixture of Pseudomonas fluorescens and MS2 bacteriophage. Volunteers entered an empty washroom, one at a time, and rinsed their hands with water or washed their hands with soap prior to drying with a jet dryer or paper towels. Each volunteer applied one hand successively to various surfaces, while their other hand was sampled using the glove juice method. Both residual bacteria and viruses were quantified from the washroom air, surface swabs and hand samples., Findings: P. fluorescens and MS2 bacteriophages were rarely aerosolized while drying hands for any of the drying methods studied. Results also showed limited, and similar, transfer of both micro-organisms studied on to surfaces for all drying methods., Conclusion: The use of jet dryers or paper towels produces low levels of aerosolization when drying hands in a washroom. Similarly, all drying methods result in low transfer to surfaces. While the coronavirus disease 2019 pandemic raised concerns regarding public washrooms, this study shows that all methods tested are hygienic solutions for dry washed hands., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The hallmark of epidermolysis bullosa (EB) is fragile attachment of epithelia due to genetic variants in cell adhesion genes. We describe 16 EB patients treated in the ear, nose, and throat department of a tertiary pediatric hospital linked to the United Kingdom's national EB unit between 1992 and 2023. Patients suffered a high degree of morbidity and mortality from laryngotracheal stenosis. Variants in laminin subunit alpha-3 (LAMA3) were found in 10/15 patients where genotype was available. LAMA3 encodes a subunit of the laminin-332 heterotrimeric extracellular matrix protein complex and is expressed by airway epithelial basal stem cells. We investigated the benefit of restoring wild-type LAMA3 expression in primary EB patient-derived basal cell cultures. EB basal cells demonstrated weak adhesion to cell culture substrates, but could otherwise be expanded similarly to non-EB basal cells. In vitro lentiviral overexpression of LAMA3A in EB basal cells enabled them to differentiate in air-liquid interface cultures, producing cilia with normal ciliary beat frequency. Moreover, transduction restored cell adhesion to levels comparable to a non-EB donor culture. These data provide proof of concept for a combined cell and gene therapy approach to treat airway disease in LAMA3-affected EB., Competing Interests: Declaration of interests The authors declare no competing interests. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. For the purpose of open access, the corresponding author has applied a CC BY public copyright license to any author accepted manuscript version arising from this submission., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Patients with cancer have the unique ability of being able to offer valuable insights into how cancer therapeutics may impact the overall patient experience and improve clinical outcomes. Patient engagement could therefore contribute to tailoring treatment strategies and research design according to patient needs. This study evaluated patient engagement in prostate cancer research by identifying patient input in the prostate cancer literature. We performed a keyword cluster analysis of articles from multiple databases and congresses in which patients provided input on disease management or were involved in study design, manuscript authorship or presentation of results (patient voice). In total, 112 studies were included. Patients were involved in the design of 11 studies and were credited as authors in four studies. This review suggests a lack of meaningful patient involvement in prostate cancer research and publications.

The consumption frequency and portion size of discretionary snacks are thought to contribute to a greater food intake and risk of overweight or obesity in the developed world but evidence from epidemiological studies is inconclusive. To investigate this, we systematically evaluated evidence on the effects of discretionary snack consumption on weight status, energy intake, and diet quality. Articles involving discretionary snacks reported against the outcome measures of any primary, peer-reviewed study using human participants from free-living conditions for all age groups were included. A total of 14,780 titles were identified and 40 eligible publications were identified. Three key outcomes were reported: weight status (n = 35), energy intake (n = 11), and diet quality (n = 3). Increased discretionary snack consumption may contribute modestly to energy intake, however, there is a lack of consistent associations with increased weight/BMI. Although cross-sectional analyses offered conflicting findings, longitudinal studies in adults showed a consistent positive relationship between discretionary snack intake and increasing weight or body mass index. Given that experimental findings suggest reducing the size of discretionary snacks could lead to decreased consumption and subsequent energy intake, food policy makers and manufacturers may find it valuable to consider altering the portion and/or packaging size of discretionary snacks., (© 2024 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Introduction: Impairments after critical illness, termed the post-intensive care syndrome, are an increasing focus of research in Australasia. However, this research is yet to be cohesively synthesised and/or summarised., Objective: The aim of this scoping review was to explore patient outcomes of survivorship research, identify measures, methodologies, and designs, and explore the reported findings in Australasia., Inclusion Criteria: Studies reporting outcomes for adult survivors of critical illness from Australia and New Zealand in the following domains: physical, functional, psychosocial, cognitive, health-related quality of life (HRQoL), discharge destination, health care use, return to work, and ongoing symptoms/complications of critical illness., Methods: The Joanna Briggs Institute scoping review methodology framework was used. A protocol was published on the open science framework, and the search used Ovid MEDLINE, Scopus, ProQuest, and Google databases. Eligible studies were based on reports from Australia and New Zealand published in English between January 2000 and March 2022., Results: There were 68 studies identified with a wide array of study aims, methodology, and designs. The most common study type was nonexperimental cohort studies (n = 17), followed by studies using secondary analyses of other study types (n = 13). HRQoL was the most common domain of recovery reported. Overall, the identified studies reported that impairments and activity restrictions were associated with reduced HRQoL and reduced functional status was prevalent in survivors of critical illness. About 25% of 6-month survivors reported some form of disability. Usually, by 6 to12 months after critical illness, impairments had improved., Conclusions: Reports of long-term outcomes for survivors of critical illness in Australia highlight that impairments and activity limitations are common and are associated with poor HRQoL. There was little New Zealand-specific research related to prevalence, impact, unmet needs, ongoing symptoms, complications from critical illness, and barriers to recovery., (Copyright © 2023 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Guidelines for sepsis recommend treating those at highest risk within 1 hour. The emergency care system can only achieve this if sepsis is recognised and prioritised. Ambulance services can use prehospital early warning scores alongside paramedic diagnostic impression to prioritise patients for treatment or early assessment in the emergency department., Objectives: To determine the accuracy, impact and cost-effectiveness of using early warning scores alongside paramedic diagnostic impression to identify sepsis requiring urgent treatment., Design: Retrospective diagnostic cohort study and decision-analytic modelling of operational consequences and cost-effectiveness., Setting: Two ambulance services and four acute hospitals in England., Participants: Adults transported to hospital by emergency ambulance, excluding episodes with injury, mental health problems, cardiac arrest, direct transfer to specialist services, or no vital signs recorded., Interventions: Twenty-one early warning scores used alongside paramedic diagnostic impression, categorised as sepsis, infection, non-specific presentation, or other specific presentation., Main Outcome Measures: Proportion of cases prioritised at the four hospitals; diagnostic accuracy for the sepsis-3 definition of sepsis and receiving urgent treatment (primary reference standard); daily number of cases with and without sepsis prioritised at a large and a small hospital; the minimum treatment effect associated with prioritisation at which each strategy would be cost-effective, compared to no prioritisation, assuming willingness to pay £20,000 per quality-adjusted life-year gained., Results: Data from 95,022 episodes involving 71,204 patients across four hospitals showed that most early warning scores operating at their pre-specified thresholds would prioritise more than 10% of cases when applied to non-specific attendances or all attendances. Data from 12,870 episodes at one hospital identified 348 (2.7%) with the primary reference standard. The National Early Warning Score, version 2 (NEWS2), had the highest area under the receiver operating characteristic curve when applied only to patients with a paramedic diagnostic impression of sepsis or infection (0.756, 95% confidence interval 0.729 to 0.783) or sepsis alone (0.655, 95% confidence interval 0.63 to 0.68). None of the strategies provided high sensitivity (> 0.8) with acceptable positive predictive value (> 0.15). NEWS2 provided combinations of sensitivity and specificity that were similar or superior to all other early warning scores. Applying NEWS2 to paramedic diagnostic impression of sepsis or infection with thresholds of > 4, > 6 and > 8 respectively provided sensitivities and positive predictive values (95% confidence interval) of 0.522 (0.469 to 0.574) and 0.216 (0.189 to 0.245), 0.447 (0.395 to 0.499) and 0.274 (0.239 to 0.313), and 0.314 (0.268 to 0.365) and 0.333 (confidence interval 0.284 to 0.386). The mortality relative risk reduction from prioritisation at which each strategy would be cost-effective exceeded 0.975 for all strategies analysed., Limitations: We estimated accuracy using a sample of older patients at one hospital. Reliable evidence was not available to estimate the effectiveness of prioritisation in the decision-analytic modelling., Conclusions: No strategy is ideal but using NEWS2, in patients with a paramedic diagnostic impression of infection or sepsis could identify one-third to half of sepsis cases without prioritising unmanageable numbers. No other score provided clearly superior accuracy to NEWS2. Research is needed to develop better definition, diagnosis and treatments for sepsis., Study Registration: This study is registered as Research Registry (reference: researchregistry5268)., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/136/10) and is published in full in Health Technology Assessment ; Vol. 28, No. 16. See the NIHR Funding and Awards website for further award information.

Objectives: The objective was to report and analyse the characteristics and results of open aortopexy and thoracoscopic aortopexy for the treatment of airway malacia in a paediatric population., Methods: We report a retrospective consecutive case series of paediatric patients undergoing aortopexy for the treatment of airway malacia at a quaternary referral centre between December 2006 and January 2021. Outcome measures included days to extubation, continued need for non-invasive ventilation, further intervention in the form of tracheostomy and death., Results: 169 patients underwent aortopexy: 147 had open procedures (135 via median/limited median sternotomy and 12 thoracotomy) and 22 thoracoscopic. Mean follow up was 8.46 yrs (range 1-20 yrs). Most common site of airway malacia was the trachea (n = 106, 62.7 %), and 48 (28.4 %) had additional involvement at the bronchi with tracheobronchomalacia (TBM). 15 (8.9 %) had bronchomalacia (BM) only. Incidence of bronchial disease was lower in the thoracoscopic than open group (13.6 % vs 40.82 %; p < 0.0001). Mean time to extubation was 1.45 days, 2.59 days, 5.23 days in tracheomalacia, TBM and BM groups, respectively (p = 0.0047). Mean time to extubation was 1.35 days, 2 days, 3.67 days, and 5 days in patients with external vascular compression, TOF/OA, primary airway malacia, and laryngeal reconstruction, respectively (p = 0.0002). There were 21 deaths across the cohort, and all were in the open group. 71.4 % (n = 15) had bronchial involvement of their airway malacia., Conclusions: Open and thoracoscopic aortopexy are effective treatments for airway malacia in children. We have identified that involvement of the bronchi is a risk factor for adverse outcomes, and the optimum treatment for this patient cohort is still debatable., Level of Evidence: IV., Type of Study: Retrospective Study., (Copyright © 2023. Published by Elsevier Inc.)

Background: Ambulance services need to identify and prioritise patients with sepsis for early hospital assessment. We aimed to determine the accuracy of early warning scores alongside paramedic diagnostic impression to identify sepsis that required urgent treatment., Methods: We undertook a retrospective diagnostic cohort study involving adult emergency medical cases transported to Sheffield Teaching Hospitals ED by Yorkshire Ambulance Service in 2019. We used routine ambulance service data to calculate 21 early warning scores and categorise paramedic diagnostic impressions as sepsis, infection, non-specific presentation or other presentation. We linked cases to hospital records and identified those meeting the sepsis-3 definition who received urgent hospital treatment for sepsis (reference standard). Analysis determined the accuracy of strategies that combined early warning scores at varying thresholds for positivity with paramedic diagnostic impression., Results: We linked 12 870/24 955 (51.6%) cases and identified 348/12 870 (2.7%) with a positive reference standard. None of the strategies provided sensitivity greater than 0.80 with positive predictive value greater than 0.15. The area under the receiver operating characteristic curve for the National Early Warning Score, version 2 (NEWS2) applied to patients with a diagnostic impression of sepsis or infection was 0.756 (95% CI 0.729, 0.783). No other early warning score provided clearly superior accuracy to NEWS2. Paramedic impression of sepsis or infection had sensitivity of 0.572 (0.519, 0.623) and positive predictive value of 0.156 (0.137, 0.176). NEWS2 thresholds of >4, >6 and >8 applied to patients with a diagnostic impression of sepsis or infection, respectively, provided sensitivities and positive predictive values of 0.522 (0.469, 0.574) and 0.216 (0.189, 0.245), 0.447 (0.395, 0.499) and 0.274 (0.239, 0.313), and 0.314 (0.268, 0.365) and 0.333 (0.284, 0.386)., Conclusion: No strategy is ideal but using NEWS2 alongside paramedic diagnostic impression of infection or sepsis could identify one-third to half of sepsis cases without prioritising unmanageable numbers. No other score provided clearly superior accuracy to NEWS2., Trial Registration Number: researchregistry5268, https://www.researchregistry.com/browse-the-registry%23home/registrationdetails/5de7bbd97ca5b50015041c33/., Competing Interests: Competing interests: All authors declare grant funding to their employing institutions from the National Institute for Health Research., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Purpose: Anti-PD-1 therapy provides clinical benefit in 40-50% of patients with relapsed and/or metastatic head and neck squamous cell carcinoma (RM-HNSCC). Selection of anti- PD-1 therapy is typically based on patient PD-L1 immunohistochemistry (IHC) which has low specificity for predicting disease control. Therefore, there is a critical need for a clinical biomarker that will predict clinical benefit to anti-PD-1 treatment with high specificity., Methods: Clinical treatment and outcomes data for 103 RM-HNSCC patients were paired with RNA-sequencing data from formalin-fixed patient samples. Using logistic regression methods, we developed a novel biomarker classifier based on expression patterns in the tumor immune microenvironment to predict disease control with monotherapy PD-1 inhibitors (pembrolizumab and nivolumab). The performance of the biomarker was internally validated using out-of-bag methods., Results: The biomarker significantly predicted disease control (65% in predicted non-progressors vs. 17% in predicted progressors, p < 0.001) and was significantly correlated with overall survival (OS; p = 0.004). In addition, the biomarker outperformed PD-L1 IHC across numerous metrics including sensitivity (0.79 vs 0.64, respectively; p = 0.005) and specificity (0.70 vs 0.61, respectively; p = 0.009)., Conclusion: This novel assay uses tumor immune microenvironment expression data to predict disease control and OS with high sensitivity and specificity in patients with RM-HNSCC treated with anti-PD-1 monotherapy., (© 2023. The Author(s).)

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16176. In addition to this overview, in which are identified 'Other protein targets' which fall outside of the subsequent categorisation, there are six areas of focus: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate., (© 2023 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.)

Introduction: The objective of this study was to describe and analyze residents' perceptions of characteristics on the expansive/restrictive continuum of their clinical learning environment., Methods: We conducted a quantitative, descriptive and cross-sectional study. A self-administered questionnaire was designed, programmed and applied to residents at the Faculty of Medicine of the National Autonomous University of Mexico. The instrument was structured in eight sections, and for this article, Section 3, which referred to clinical environments and violence was considered. The questionnaire had an 85% response rate, with 12,612 residents from 113 medical units and 78 specialties participating. The reliability and internal consistency measured with alpha omega obtained a value of ω 0.835 (CI; 0.828-0.843)., Results: Unpleasant, competitive, tense and conflictive contexts were related to restrictive environments. Sexual orientation influenced the perception of intolerance in the clinical setting with respect to discriminatory comments, such that for gender minorities, the environment was experienced as exclusionary. First-year residents perceived environments as more aggressive, a perception that tended to decrease in later years of residency., Discussion: Abuses in power relations, rigid hierarchical positions and offensive clinical interactions may foster restrictive environments. In such settings, the reproduction of socio-culturally learned violence is feasible; however, asymmetrical relationships may be deconstructed and transformed.

Objective: Betahistine has not been proven to be superior to placebo in the BEMED study, a multicenter, double-blind, randomized, placebo controlled trial. Our study aimed to establish the prescribing practices of clinicians in England in relation to betahistine and to assess if there has been any change in prescribing practices since the publication of the BEMED trial., Study Design: Retrospective study and clinician survey., Patients: All patients who were prescribed betahistine from primary care., Main Outcome Measure: Total quantity of betahistine prescribed and total actual cost., Results: The average total monthly quantity prescribed was 11,143,253 tablets (range, 10,056,516-12,276,423). Prescribing did not decrease from the period before (January 2014-February 2016) to after (February 2016-February 2021) the publication of the BEMED trial, with the average monthly prescribing before publication being 11,294,848 tablets (range, 10,280,942- 12,276,423) and the average monthly prescribing after publication being 11,081,123 tablets (range, 10,056,516-11,915,707). The average actual monthly cost increased from the period before publication to after publication from a sum of £279,264.82 to a sum of £428,846.22. Most (90.5%) of the survey respondents prescribed betahistine for Menière's disease. Less than half (38.09%) prescribed betahistine for indications other than Menière's disease. Only 45.24% of the clinicians were aware of the results of the BEMED trial., Conclusions: Knowledge of the BEMED trial among otology and neurotology subspecialists is lacking. The results of the BEMED have made no difference to prescribing practice, and in fact, the cost of the medication to the health bill has increased., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2023, Otology & Neurotology, Inc.)

This narrative review examines the mechanisms underlying the development of cardiovascular disease (CVD) and metabolic diseases (MDs), along with their association with sarcopenia. Furthermore, non-pharmacological interventions to address sarcopenia in patients with these conditions are suggested. The significance of combined training in managing metabolic disease and secondary sarcopenia in type II diabetes mellitus is emphasized. Additionally, the potential benefits of resistance and aerobic training are explored. This review emphasises the role of nutrition in addressing sarcopenia in patients with CVD or MDs, focusing on strategies such as optimising protein intake, promoting plant-based protein sources, incorporating antioxidant-rich foods and omega-3 fatty acids and ensuring sufficient vitamin D levels. Moreover, the potential benefits of targeting gut microbiota through probiotics and prebiotic fibres in sarcopenic individuals are considered. Multidisciplinary approaches that integrate behavioural science are explored to enhance the uptake and sustainability of behaviour-based sarcopenia interventions. Future research should prioritise high-quality randomized controlled trials to refine exercise and nutritional interventions and investigate the incorporation of behavioural science into routine practices. Ultimately, a comprehensive and multifaceted approach is essential to improve health outcomes, well-being and quality of life in older adults with sarcopenia and coexisting cardiovascular and metabolic diseases.

Objective: Using a qualitative design this study aimed to (1) explore the experience of people living with osteoarthritis (OA), (2) gain an understanding of their navigation of the health system and, (3) explore their opinions on the role of exercise and joint replacement surgery for the management of OA., Methods: Purposive sampling was used to recruit 26 participants with knee OA, aged 45 years and over, from Tasmania, Australia. Semi-structured interviews were audio-recorded, transcribed, coded, and thematically analysed to document participant understanding and experience of OA and their opinions on the role of exercise and surgery in managing OA., Results: Of the 26 participants, 80% (n = 21) were female with a mean age of 66 years. The main theme identified was that individuals with knee OA were navigating a maze of OA treatments. Three related subthemes were that participants: (i) perceived their general practitioner did not have an ongoing role in their OA care, (ii) self-directed their management and, (iii) sampled from a 'smorgasbord' of treatment options, including low-value care options. Two other major themes were: the role of exercise for OA management, and surgery as a last resort., Conclusion: Our findings suggest that OA patients may not be choosing consistent, high-value care for their OA. This highlights the importance of an evidence-based multi-disciplinary approach to guide patients to self-manage their OA and support their navigation of the health system. Reducing emphasis on the pathway to surgery and streamlining access to conservative management strategies may assist people to receive high-value care., (© 2022 The Authors. Musculoskeletal Care published by John Wiley & Sons Ltd.)

Background: Adherence to preventative inhaled therapies in people with cystic fibrosis (CF) is low, resulting in potentially avoidable health losses and the need for costly rescue therapies., Objectives: To estimate the cost-effectiveness of the CFHealthHub (CFHH) intervention to support adherence to inhaled medications., Methods: A state transition model was developed to assess the cost-effectiveness of the CFHH intervention versus usual care from the perspective of the UK National Health Service and Personal Social Services over a lifetime horizon. Costs and health outcomes were discounted at a rate of 3.5 percent per annum. Costs were valued at 2021/22 prices. The model structure includes health states defined by survival status, level of lung function, and transplant history. Treatment effects were modeled by changing the probabilities of transitioning between lung function states and reducing exacerbation rates. Model parameters were informed by the CFHH trial, CF Registry data, routine cost databases, literature, and expert opinion. Deterministic and probabilistic sensitivity analyses were undertaken to assess uncertainty., Results: The CFHH intervention is expected to generate additional health gains and cost savings compared with usual care. Assuming that it is delivered for 10 years, the CFHH intervention is expected to generate 0.17 additional quality-adjusted life years and cost savings of GBP 1,600 (EUR 1,662) per patient., Conclusions: The CFHH intervention is expected to dominate usual care, irrespective of the duration over which the intervention is delivered. The modeled benefits and cost savings are smaller than initially expected and are sensitive to relative treatment effects on lung function.

Australia has recently legalised mitochondrial donation. However, key ethical and legal issues still need to be addressed. This paper maps the relevant issues and offers some suggestions for how they ought to be resolved., (© 2022 Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: COVID-19 infected millions of people and increased mortality worldwide. Patients with suspected COVID-19 utilised emergency medical services (EMS) and attended emergency departments, resulting in increased pressures and waiting times. Rapid and accurate decision-making is required to identify patients at high-risk of clinical deterioration following COVID-19 infection, whilst also avoiding unnecessary hospital admissions. Our study aimed to develop artificial intelligence models to predict adverse outcomes in suspected COVID-19 patients attended by EMS clinicians., Method: Linked ambulance service data were obtained for 7,549 adult patients with suspected COVID-19 infection attended by EMS clinicians in the Yorkshire and Humber region (England) from 18-03-2020 to 29-06-2020. We used support vector machines (SVM), extreme gradient boosting, artificial neural network (ANN) models, ensemble learning methods and logistic regression to predict the primary outcome (death or need for organ support within 30 days). Models were compared with two baselines: the decision made by EMS clinicians to convey patients to hospital, and the PRIEST clinical severity score., Results: Of the 7,549 patients attended by EMS clinicians, 1,330 (17.6%) experienced the primary outcome. Machine Learning methods showed slight improvements in sensitivity over baseline results. Further improvements were obtained using stacking ensemble methods, the best geometric mean (GM) results were obtained using SVM and ANN as base learners when maximising sensitivity and specificity., Conclusions: These methods could potentially reduce the numbers of patients conveyed to hospital without a concomitant increase in adverse outcomes. Further work is required to test the models externally and develop an automated system for use in clinical settings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The role of the inflammatory milieu in prostate cancer progression is not well understood. Differences in inflammatory signaling between localized and metastatic disease may point to opportunities for early intervention., Methods: We modeled PCa disease progression by analyzing RNA-seq of localized vs. metastatic patient samples, followed by CIBERSORTx to assess their immune cell populations. The VHA CDW registry of PCa patients was analyzed for anti-TNF clinical outcomes., Results: We observed statistically significant opposing patterns of IL-6 and TNFα expression between localized and metastatic disease. IL-6 was robustly expressed in localized disease and downregulated in metastatic disease. The reverse was observed with TNFα expression. Metastatic disease was also characterized by downregulation of adhesion molecule E-selectin, matrix metalloproteinase ADAMTS-4 and a shift to M2 macrophages whereas localized disease demonstrated a preponderance of M1 macrophages. Treatment with anti-TNF agents was associated with earlier stage disease at diagnosis., Conclusions: Our data points to clearly different inflammatory contexts between localized and metastatic prostate cancer. Primary localized disease demonstrates local inflammation and adaptive immunity, whereas metastases are characterized by immune cold microenvironments and a shift towards resolution of inflammation and tissue repair. Therapies that interfere with these inflammatory networks may offer opportunities for early intervention in monotherapy or in combination with immunotherapies and anti-angiogenic approaches., (© 2022. The Author(s).)

>276,000 Americans will be diagnosed with invasive breast cancer, lobular carcinoma in situ, or ductal carcinoma in situ this year and most will undergo breast surgery as part of their care. Although prognosis is excellent, many patients experience persistent post-surgical pain (PSP), which has no satisfactory pharmacological treatment. The causal contributions of pain-associated psychological factors (e.g., catastrophic thoughts about pain, psychological flexibility, self-efficacy) to the continuing burden of PSP have not yet been determined and may be opportune intervention targets. The randomized trial described here will compare the benefits of three manualized behavioral interventions for individuals with PSP. Participants will receive either: 1) self-guided health education (SGHE); 2) interventionist-guided health education (IGHE); or 3) interventionist-guided pain coping skills training with elements of acceptance and commitment therapy that specially target catastrophic thoughts about pain, self-efficacy, and psychological flexibility (CST-PSP). Participants will prospectively complete validated assessments of primary outcomes (PSP severity and interference) at baseline (pre-intervention) and 3-, 6-, and 12-months later. Validated measures of emotional distress and cancer-specific distress will be assessed as secondary outcomes. To test their roles as drivers of PSP, catastrophic thoughts about pain, self-efficacy, and psychological flexibility, will be assessed and statistically analyzed as mediators of hypothesized beneficial effects. The interventions' impacts on pain sensitivity and central sensitization will be investigated to test these physiological pathways as proximal drivers of PSP. To better characterize the patient experience, additional validated measures will be explored for associations with PSP, along with demographic and clinical factors. Trial registration: https://clinicaltrials.gov/ct2/show/NCT04225585, registered January 13, 2020., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: The absence of submucosal ganglion cells does not reliably distinguish Hirschsprung disease from non Hirschsprung disease in anorectal line biopsies. Calretinin staining might be helpful in these biopsies. To determine its value, we analyzed calretinin positive mucosal neurites in anorectal line biopsies., Methods: Two pediatric pathologists, without access to patient data, evaluated calretinin positive mucosal neurites in anorectal line junctional mucosa in archival rectal biopsies contributed by 17 institutions. A separate investigator compiled patient information and sent data for statistical analysis., Results: Biopsies with anorectal junctional mucosa from 115 patients were evaluated for calretinin positive mucosal neurites. 20/20 Hirschsprung disease biopsies were negative. 87/88 non Hirschsprung disease biopsies and 7/7 post pullthrough Hirschsprung disease neorectal biopsies were positive. Statistical analysis of the 108 non pullthrough biopsies yielded an accuracy of 99.1% (sensitivity 100%, specificity 98.9%). Age range was preterm to 16 years. Biopsy size was less than 1 mm to over 1 cm., Conclusions: Absence of calretinin positive mucosal neurites at the anorectal line was highly accurate in distinguishing Hirschsprung disease from non Hirschsprung disease cases in this blinded retrospective study. Calretinin staining is useful for interpreting biopsies from the physiologic hypoganglionic zone up to the anorectal line.

Objective: Granular myringitis is a chronic and difficult-to-treat condition of the tympanic membrane. This paper presents a minimally invasive treatment technique using the potassium titanyl phosphate laser., Design: A retrospective case review of patients who underwent potassium titanyl phosphate laser treatment between 2015 and 2020 was performed. All patients underwent final telephone follow up in 2020 to ascertain whether they had any ongoing myringitis symptoms, and all were offered further face-to-face follow up., Results: Fourteen patients with myringitis were identified, with one patient having both ears affected. Of the 15 affected ears, 2 required a second treatment, resulting in a total of 17 laser treatment cases. At the first post-operative review, the appearance of the drum had improved in 10 out of 17 treatments (59 per cent)., Conclusion: Potassium titanyl phosphate laser surface tympanoplasty may provide safe, quick and effective resolution of myringitis.

Introduction: A sample size justification is required for all studies and should give the minimum number of subjects to be recruited for the study to achieve its primary objective. The aim of this review is to describe sample sizes from agreement studies with continuous or categorical endpoints and different methods of assessing agreement, and to determine whether sample size justification was provided., Methods: Data were gathered from the PubMed repository with a time interval of 28 th September 2018 to 28 th September 2020. The search returned 5257 studies of which 82 studies were eligible for final assessment after duplicates and ineligible studies were excluded., Results: We observed a wide range of sample sizes. Forty-six studies (56%) used a continuous outcome measure, 28 (34%) used categorical and eight (10%) used both. Median sample sizes were 50 (IQR 25 to 100) for continuous endpoints and 119 (IQR 50 to 271) for categorical endpoints. Bland-Altman limits of agreement (median sample size 65; IQR 35 to 124) were the most common method of statistical analysis for continuous variables and Kappa coefficients for categorical variables (median sample size 71; IQR 50 to 233). Of the 82 studies assessed, only 27 (33%) gave justification for their sample size., Conclusions: Despite the importance of a sample size justification, we found that two-thirds of agreement studies did not provide one. We recommend that all agreement studies provide rationale for their sample size even if they do not include a formal sample size calculation., (© 2022. The Author(s).)

Background: Inhaler technique errors are common in chronic obstructive pulmonary disease (COPD) treatment, potentially leading to poor disease management. Our pooled analysis approach assessed correct use and ease-of-use of a placebo ELLIPTA dry-powder inhaler (DPI) in patients with COPD., Methods: Adults with COPD from open-label/non-blinded studies evaluating a placebo ELLIPTA DPI and reporting outcomes of correct use (based on the ELLIPTA DPI patient information leaflet [PIL]) and/or ease-of-use were included. Correct use and ease-of use at study end were primary and secondary endpoints, respectively. Data from patients in the placebo ELLIPTA DPI arm of each study were pooled, and the intent-to-treat (ITT) population was used for all analyses., Results: Four placebo ELLIPTA DPI studies, reporting correct use (n = 4) and ease-of-use (n = 2), were included in the analysis. The ITT population comprised 1232 patients (mean age 66.2 years). For the primary endpoint, 80.1% (n = 975/1217) of patients demonstrated correct use at study end (95% confidence interval [CI]: 77.8%-82.3%). For the secondary endpoint, 95.7% (n = 797/833) of patients rated placebo ELLIPTA DPI use "easy"/"very easy" at study end (95% CI: 94.1%-97.0%). Correct use and "easy"/"very easy" user ratings remained high across younger (40-64 years) and older (≥65 years) age groups., Conclusions: Across age groups, most patients used the placebo ELLIPTA DPI correctly and rated it "easy"/"very easy" to use. Consistent with the Global Initiative for Chronic Obstructive Lung Disease 2021 report, our findings emphasize that proper training and clear instructions on PILs are important for optimal inhaler use., Competing Interests: RJ, KC, RS, LS, and JR report employment with, and stock/share ownership in, GSK during study conduct. KC is currently employed by AstraZeneca and LS is no longer employed by GSK. TMS received research support from West-Ward Pharmaceuticals, Theravance Biopharma US, Inc., GSK, Pearl Therapeutics, Chiesi, AstraZeneca, Novartis, Boehringer Ingelheim, Forest, Compleware, Evidera, Oncocyte, Teva, Vapotherm, Sunovion, Proterix BioPharma, Seer, and Sanofi. TMS has also received speaker fees from GSK, Mylan Inc./Theravance Biopharma US, Inc., and Sunovion, and consulting fees from Vapotherm. DIB received grant/research/clinical trial support from GSK, Teva, AstraZeneca, Pearl Therapeutics, Novartis, Genentech, Inc., Merck, Boehringer Ingelheim, Amgen, Aimmune, Shire, and Biocryst and consulted/participated in advisory boards for GSK, ALK America, Gerson-Lehman, and Guidepoint Global. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The registered dose for imatinib is 400 mg/d, despite high inter-patient variability in imatinib plasmatic exposure. Therapeutic drug monitoring (TDM) is routinely used to maximize a drug’s efficacy or tolerance. We decided to conduct a prospective randomized trial (OPTIM-imatinib trial) to assess the value of TDM in patients with chronic phase chronic myelogenous treated with imatinib as first-line therapy (NCT02896842). Eligible patients started imatinib at 400 mg daily, followed by imatinib [C]min assessment. Patients considered underdosed ([C]min < 1000 ng/mL) were randomized in a dose-increase strategy aiming to reach the threshold of 1000 ng/mL (TDM arm) versus standard imatinib management (control arm). Patients with [C]min levels ≥ 1000 ng/mL were treated following current European Leukemia Net recommendations (observational arm). The primary endpoint was the rate of major molecular response (MMR, BCR::ABL1IS ≤ 0.1%) at 12 months. Out of 133 evaluable patients on imatinib 400 mg daily, 86 patients had a [C]min < 1000 ng/mL and were randomized. The TDM strategy resulted in a significant increase in [C]min values with a mean imatinib daily dose of 603 mg daily. Patients included in the TDM arm had a 12-month MMR rate of 67% (95% CI, 51−81) compared to 39% (95% CI, 24−55) for the control arm (p = 0.017). This early advantage persisted over the 3-year study period, in which we considered imatinib cessation as a censoring event. Imatinib TDM was feasible and significantly improved the 12-month MMR rate. This early advantage may be beneficial for patients without easy access to second-line TKIs.

Background: Precision medicine incorporating genetic profiling is becoming a standard of care in medical oncology. However, in the field of radiation oncology there is limited use of genetic profiling and the impact of germline genetic biomarkers on radiosensitivity, radioresistance, or patient outcomes after radiation therapy is poorly understood. In HNSCC, the toxicity associated with treatment can cause delays or early cessation which has been associated with worse outcomes. Identifying potential biomarkers which can help predict toxicity, as well as response to treatment, is of significant interest., Methods: Patients with HNSCC who received RT and underwent next generation sequencing of somatic tumor samples, transcriptome RNA-seq with matched normal tissue samples were included. Patients were then grouped by propensity towards increased late vs. early toxicity (Group A) and those without (Group B), assessed by CTCAE v5.0. The groups were then analyzed for association of specific germline variants with toxicity and clinical outcomes., Results: In this study we analyzed 37 patients for correlation between germline variants and toxicity. We observed that TSC2, HLA-A, TET2, GEN1, NCOR2 and other germline variants were significantly associated with long term toxicities. 34 HNSCC patients treated with curative intent were evaluated for clinical outcomes. Group A had significantly improved overall survival as well as improved rates of locoregional recurrence and metastatic disease. Specific variants associated with improved clinical outcomes included TSC2, FANCD2, and PPP1R15A, while the HLA-A and GEN1 variants were not correlated with survival or recurrence. A group of five HLA-DMA/HLA-DMB variants was only found in Group B and was associated with a higher risk of locoregional recurrence., Conclusions: This study indicates that germline genetic biomarkers may have utility in predicting toxicity and outcomes after radiation therapy and deserve further investigation in precision radiation medicine approaches., (© 2022. The Author(s).)

Composite outcomes are widely used in clinical research. Existing literature has considered the pros and cons of composite outcomes in clinical trials, but their extensive use in clinical prediction has received much less attention. Clinical prediction assists decision-making by directing patients with higher risks of adverse outcomes toward interventions that provide the greatest benefits to those at the greatest risk. In this article, we summarize our existing understanding of the advantages and disadvantages of composite outcomes, consider how these relate to clinical prediction, and highlight the problem of key predictors having markedly different associations with individual components of the composite outcome. We suggest that a "composite outcome fallacy" may occur when a clinical prediction model is based on strong associations between key predictors and one component of a composite outcome (such as mortality) and used to direct patients toward intervention when these predictors actually have an inverse association with a more relevant component of the composite outcome (such as the use of a lifesaving intervention). We propose that clinical prediction scores using composite outcomes should report their accuracy for key components of the composite outcome and examine for inconsistencies among predictor variables., (Copyright © 2022 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Objective: To assess accuracy of emergency medical service (EMS) telephone triage in identifying patients who need an EMS response and identify factors which affect triage accuracy., Design: Observational cohort study., Setting: Emergency telephone triage provided by Yorkshire Ambulance Service (YAS) National Health Service (NHS) Trust., Participants: 12 653 adults who contacted EMS telephone triage services provided by YAS between 2 April 2020 and 29 June 2020 assessed by COVID-19 telephone triage pathways were included., Outcome: Accuracy of call handler decision to dispatch an ambulance was assessed in terms of death or need for organ support at 30 days from first contact with the telephone triage service., Results: Callers contacting EMS dispatch services had an 11.1% (1405/12 653) risk of death or needing organ support. In total, 2000/12 653 (16%) of callers did not receive an emergency response and they had a 70/2000 (3.5%) risk of death or organ support. Ambulances were dispatched to 4230 callers (33.4%) who were not conveyed to hospital and did not deteriorate. Multivariable modelling found variables of older age (1 year increase, OR: 1.05, 95% CI: 1.04 to 1.05) and presence of pre-existing respiratory disease (OR: 1.35, 95% CI: 1.13 to 1.60) to be predictors of false positive triage., Conclusion: Telephone triage can reduce ambulance responses but, with low specificity. A small but significant proportion of patients who do not receive an initial emergency response deteriorated. Research to improve accuracy of EMS telephone triage is needed and, due to limitations of routinely collected data, this is likely to require prospective data collection., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Objective: To investigate the feasibility of 'parkrun' for people with knee osteoarthritis (OA) and examine its potential to improve symptoms and increase physical activity., Design: This uncontrolled mixed methods pilot study enrolled people with knee OA not meeting physical activity guidelines. Participants were asked to walk in four consecutive parkrun events supervised by an exercise physiologist/physiotherapist. Feasibility was assessed by recruitment data (numbers screened and time to enrol 15 participants), adherence to the protocol, acceptability (measured by confidence, enjoyment, difficulty ratings and qualitative interviews), and safety (adverse events). Secondary measures were changes in knee pain, function, stiffness, and physical activity levels., Results: Participants (n ​= ​17) were enrolled over 11 months and recruitment was slower than anticipated. Fourteen participants attended all four parkruns and three of these participants shortened the 5 ​km course to ∼3 ​km. Across all four parkruns, 75% of participants reported high confidence that they could complete the upcoming parkrun and the majority (87%) enjoyed participating. Most participants rated parkrun either "slightly difficult" (38.5%) or "moderately difficult" (35%) and two mild adverse events were reported. Participants showed improvements in knee pain, function, stiffness, and physical activity levels., Conclusions: This pilot study demonstrates parkrun's feasibility, acceptability, safety and, its potential to improve knee OA symptoms and physical activity levels. Participating in parkrun was acceptable and enjoyable for some, but not all participants. The scalability, accessibility and wide appeal of parkrun supports the development of larger programs of research to evaluate the use of parkrun for people with knee OA., Competing Interests: Authors L. Sutton, M.N Moore, A. Grunseit, D. Aitken are registered parkrunners. This study was funded by the Medibank Better Health Foundation. Authors Kim Jose and Saliu Balogun have no disclosures. L. Sutton is the recipient of the Farrell Foundation Research Scholarship, Myles Moore is the recipient of a Broadreach Elite PhD Scholarship. Tania Winzenberg is the recipient of less than $10,000 in funding from AMGEN Australia for the preparation of educational materials. Dawn Aitken is the recipient of a 10.13039/501100000925National Health and Medical Research Council (NHMRC)/Medical Research Future Fund (MRFF) Fellowship to support her salary. Anne Grunseit received salary support from the Prevention Research Support Program by the 10.13039/501100008810New South Wales Ministry of Health and is a member of the parkrun Global Research Board (as of August 2021). Verity Cleland is supported by a Heart Foundation of Australia Future Leader Fellowship (ID 104892). The views, thoughts, and opinions expressed in the manuscript belong solely to the author/s, and do not necessarily reflect the position of parkrun or the parkrun Research Board. SD, standard deviation; BMI, body mass index; MET, metabolic equivalent; VAS, visual analogue scale; WOMAC, Western Ontario and McMaster Universities Arthritis Index; NSAID, non-steroidal anti-inflammatory drugs; OARSI, Osteoarthritis Research Society International., (© 2022 The Authors.)

Introduction: As a recently established division, we sought to reflect on the development of our paediatric airway surgery service, and prospectively examine the diagnoses that underwent microlaryngobronchoscopy (MLB) to help quantify the evolving population demographics of paediatric airway disorders., Material and Methods: This was a prospective longitudinal study conducted of all paediatric MLBs performed by a single surgeon in a tertiary paediatric ENT centre between 2012 and 2019., Results: A total of 1040 MLBs were performed in 498 patients at the paediatric ENT centre of the Royal London Hospital. Median age at first procedure was 19 months. Median follow-up was 48 months. Primary diagnoses were laryngomalacia (21%), subglottic stenosis (SGS - 18%), laryngeal cleft (13%), and normal anatomy (28.3%). Repeat procedures were needed in 39.1% patients, who underwent a median of 2 repeat procedures. SGS (57.7%) constituted majority of the repeat category, followed by laryngeal cleft (12.36%), laryngomalacia (10.15%), unilateral/bilateral vocal cord palsy(4.24%) and laryngeal papilloma(4.24%). Laryngeal papilloma constituted largest number of procedures per patient (Median = 4, IQR = 5.75), followed by subglottic web and SGS. Mean length of stay(LOS) was 0.67 ± 0.96 days(d), with laryngeal cleft cases recording longest mean LOS. There was a steady increase in proportion of day-surgeries across study period [6.9% (2012) vs 59%(2019)]., Conclusion: SGS constitutes the major bulk of paediatric airway surgery, reflective of increasing number of premature births and prolonged intubation among neonates. Day-case MLB is a safe and feasible option in selected patients. This long-term data provides useful information to accurately prognosticate patients regarding potential number of repeat procedures for each diagnosis., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Tools proposed to triage patient acuity in COVID-19 infection have only been validated in hospital populations. We estimated the accuracy of five risk-stratification tools recommended to predict severe illness and compared accuracy to existing clinical decision making in a prehospital setting., Methods: An observational cohort study using linked ambulance service data for patients attended by Emergency Medical Service (EMS) crews in the Yorkshire and Humber region of England between 26 March 2020 and 25 June 2020 was conducted to assess performance of the Pandemic Respiratory Infection Emergency System Triage (PRIEST) tool, National Early Warning Score (NEWS2), WHO algorithm, CRB-65 and Pandemic Medical Early Warning Score (PMEWS) in patients with suspected COVID-19 infection. The primary outcome was death or need for organ support., Results: Of the 7549 patients in our cohort, 17.6% (95% CI 16.8% to 18.5%) experienced the primary outcome. The NEWS2 (National Early Warning Score, version 2), PMEWS, PRIEST tool and WHO algorithm identified patients at risk of adverse outcomes with a high sensitivity (>0.95) and specificity ranging from 0.3 (NEWS2) to 0.41 (PRIEST tool). The high sensitivity of NEWS2 and PMEWS was achieved by using lower thresholds than previously recommended. On index assessment, 65% of patients were transported to hospital and EMS decision to transfer patients achieved a sensitivity of 0.84 (95% CI 0.83 to 0.85) and specificity of 0.39 (95% CI 0.39 to 0.40)., Conclusion: Use of NEWS2, PMEWS, PRIEST tool and WHO algorithm could improve sensitivity of EMS triage of patients with suspected COVID-19 infection. Use of the PRIEST tool would improve sensitivity of triage without increasing the number of patients conveyed to hospital., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Post Intensive Care Syndrome (PICS) was defined by the Society of Critical Care Medicine in 2012 with subsequent international research highlighting poor long-term outcomes; reduced quality of life; and impairments, for survivors of critical illness. To date, there has been no published research on the long-term outcomes of survivors of critical illness in New Zealand., Objective: The aim of this study is to explore long-term outcomes after critical illness in New Zealand. The primary objectives are to describe and quantify symptoms and disability, explore possible risk factors, and to identify unmet needs in survivors of critical illness., Methods: This will be a mixed methods study with 2 components. First, a prospective cohort study of approximately 100 participants with critical illness will be followed up at 1, 6, and 12 months after hospital discharge. The primary outcome will be disability assessed using the World Health Organization Disability Assessment Scale 2.0. Secondary outcomes will focus on mental health using the Hospital Anxiety and Depression Scale and the Impact of Events Scale-revised, cognitive function using the Montreal Cognitive Assessment (Montreal Cognitive Assessment-BLIND), and health-related quality of life using the European Quality of Life-Five Dimension-Five Level. The second element of the study will use qualitative grounded theory methods to explore participants experiences of recovery and highlight unmet needs., Results: This study was approved by the New Zealand Northern A Health and Disability Ethics Committee on August 16, 2021 (21/NTA/107), and has been registered with the Australian New Zealand Clinical Trials Registry on October 5, 2021. SPLIT ENZ is due to start recruitment in early 2022, aiming to enroll 125 patients over 2 years. Data collection is estimated to be completed by 2024-2025 and will be published once all data are available for reporting., Conclusions: Although international research has identified the prevalence of PICS and the extent of disability in survivors of critical illness, there is no published research in New Zealand. Research in this field is particularly pressing in the context of COVID-19, an illness that may include PICS in its sequelae., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN1262100133588; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382566&showOriginal=true&isReview=true., International Registered Report Identifier (irrid): PRR1-10.2196/35936., (©Lynsey Sutton, Elliot Bell, Susanna Every-Palmer, Mark Weatherall, Paul Skirrow. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 17.03.2022.)

Purpose of Review: To describe the most recent findings related to lifestyle behaviors and migraine., Recent Findings: An individualized conceptualization of how lifestyle factors impact migraine activity has increased our understanding of the role of behavioral interventions for episodic migraine. Healthy diets of several types have been associated with migraine attack reduction, whereas disruptions in diet like skipping meals are associated with migraine attack onset. Both aerobic activity and lower intensity yoga interventions show promise for migraine prevention. Sleep disruption has been associated with migraine day and may have a bi-directional relationship. Both increases and decreases in stress have been associated with migraine activity. Evidence is converging around the principle that highly unusual disruptions in daily routine are particularly associated with migraine attack onset and that a consistent healthy lifestyle is a key feature of effective behavioral migraine prevention strategies., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The negative impact of trauma work has been well documented in mental health professionals. There are three main phenomena used to describe these effects: Secondary Traumatic Stress (STS), Vicarious Trauma (VT) and Compassion Fatigue (CF). To date, the majority of research has focused on the contribution of individual level factors. However, it is imperative to also understand the role of organizational factors., Objectives: This review examines the role of organizational factors in ameliorating or preventing STS, VT, and CF in mental health professionals. We further aimed to identify specific elements of these factors which are perceived to be beneficial and/or detrimental in mitigating against the effects of STS, VT, and CF., Method: Studies were identified by searching the electronic databases Medline, PsycINFO, Embase, Web of Science and SCOPUS with final searches taking place on 10 March 2021., Results: Twenty-three quantitative studies, eight qualitative studies, and five mixed methods studies were included in the final review. A narrative synthesis was conducted to analyse the findings. The results of the review highlight the importance of regular supervision within supportive supervisory relationships, strong peer support networks, and balanced and diverse caseloads. The value of having an organizational culture which acknowledges and validates the existence of STS was also imperative., Conclusions: Organizations have an ethical responsibility to support the mental health professionals they employ and provide a supportive environment which protects them against STS. This review provides preliminary evidence for the types of support that should be offered and highlights the gaps in the literature and where future research should be directed. Further research is needed to evaluate which strategies - and under what conditions - best ameliorate and prevent STS., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Introduction: The oncogenic human papillomaviruses (HPV) types 16 and 18 contribute to more than 73% cases of all HPV-related cancers and commonly affect the anogenital and head and neck region, with rapidly rising incidence rates of HPV-related oropharyngeal squamous cell carcinomas (OPSCC). HPV vaccination has the potential to decrease the burden of HPV-related disease, but vaccination rates remain low in many countries. We investigated the level of awareness of HPV, and HPV-OPSCC in particular, in a representative sample of the German population., Materials and Methods: As part of an online, population-based survey, an electronic questionnaire was administered to a representative sample of 1,095 adult individuals with a specific emphasis on awareness of HPV, transmission, and indicator symptoms of oropharyngeal cancer. Statistical analysis of levels of awareness and relation of these to age, gender, and socioeconomic background were conducted using the IBM SPSS Statistics Version 25.0., Results: 699/1,095 (63.8%) subjects had never heard of HPV. Of the subjects with awareness for HPV, 210 knew that HPV could be transmitted during sex (58.3%) and 138 recognized HPV as a risk factor for OPSCC (14.2%), unrelated to gender (p = 0.357), educational status (p = 0.581), or family status (p = 0.719). 416 subjects knew that a preventive vaccine against HPV existed (44.9%). Women were significantly more aware of HPV (34.2% vs. 22.8%, p < 0.001) and the vaccination (56.4% vs. 32.7%, p < 0.001) as were men. Younger individuals (age group 25-34) were significantly more aware of HPV (p < 0.001), likely as they were offered and/or had received the HPV vaccination. There was no regional variation of HPV awareness within the German state (p = 0.051)., Conclusion: Here we demonstrate a significant lack of awareness of HPV and HPV vaccination in a representative sample of the German population. Levels of awareness of the link of HPV and oropharyngeal cancer are particularly low, bearing in mind that this cancer is commonly affecting men and incidence rates are rapidly rising in many European countries and the USA. Awareness programs and further education are required to tackle the low awareness rates and increase the uptake of the vaccination program not only in Germany, but also worldwide., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Purpose: Cancer survivors are often sedentary. Self-monitoring may promote physical activity through self-activation. We conducted a pilot trial to evaluate whether wearable activity tracker with personalized text message feedback would increase physical activity., Methods: We enrolled 30 patients with solid tumor cancers into a non-randomized prospective intervention trial (NCT02627079): 15 had completed treatment in the past year and 15 under active treatment. Each participant received an activity tracker and daily text messages personalized to their activity level. We assessed patient-reported outcomes and 6-min walk (6 MW) at baseline and 3 months., Results: Twenty-six participants completed the study. There was substantial variation in baseline activity. Overall, 39% of participants increased their steps taken by at least 20%, and 23% increased their 6 MW distance by 20% or more. More participants who had completed treatment strongly agreed (73%) that the intervention increased their exercise levels than those receiving active treatment (47%). At 3 months, there was a significant improvement in median Beck Depression Inventory-II and Godin Leisure Index composite scores. At 6 months, 72% still wore their activity tracker at least 4 days per week., Conclusion: We found that the intervention was well-accepted with a high completion rate at 3 months and continued self-use at 6 months. In this pilot study of combined activity tracker and motivational messaging, we found a signal for increased physical activity over a 3-month period. Future research is needed to study this technique for its impact on activity and other physical and psychological measures of well-being., Implication for Cancer Survivors: Activity tracker with personalized motivational messaging may be useful in promoting physical activity in cancer survivors., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Obstructive sleep apnoea (OSA) describes an irregular night-time breathing pattern that is present in approximately 1.8% of children and can have a negative impact on quality of life. The use of antibiotics postoperatively is controversial. They are commonly prescribed; however, they can also be associated with side effects and resistance. This study explores the role of antibiotics in the post-operative management of children with OSA in a cohort of children., Methods: We conducted a retrospective cohort study of children undergoing surgery for OSA or sleep disordered breathing (SDB) at a tertiary paediatric ENT referral centre from November 2018 to November 2019., Results: This study identified 382 children who had undergone surgical treatment for OSA or sleep disordered breathing (SDB); 319 underwent adenotonsillectomy, 53 adenoidectomy and 10 tonsillectomies. Antibiotics were given post-operatively to 158 (41%) patients and 18 (11%) of these patients presented to hospital with post-operative complications. A higher number of patients re-presented to hospital from the group who did not receive antibiotics (p = 0.982). Bleeding (p = 0.886) and infection (p = 0.823) were also more common in those children who did not receive antibiotics., Conclusion: Antibiotics led to fewer complications and re-presentations to hospital in children undergoing operative management of OSA; however, this trend was not found to be statistically significant., (© 2021. Crown.)

Gastric cancer is a leading cause of cancer-related deaths worldwide. Recently, clinical studies have demonstrated that many of those with advanced gastric cancer are responsive to immune checkpoint antibody therapy, although the median survival even with these new agents is less than 12 months for advanced disease. The gastrointestinal peptide gastrin has been shown to stimulate growth of gastric cancer in a paracrine and autocrine fashion through the cholecystokinin-B receptor (CCK-BR), a receptor that is expressed in at least 56.6% of human gastric cancers. In the current investigation, we studied the role of the gastrin-CCK-BR pathway in vitro and in vivo as well as the expression of the CCK-BR in a human gastric cancer tissue array. CCK-BR and PD-L1 receptor expression and gastrin peptide was found in two murine gastric cancer cells (NCC-S1 and YTN-16) by qRT-PCR and immunocytochemistry. Treatment of NCC-S1 cells with gastrin resulted in increased growth. In vivo , the effects of a cancer vaccine that targets gastrin peptide (polyclonal antibody stimulator-PAS) alone or in combination with a Programed Death-1 antibody (PD-1 Ab) was evaluated in immune competent mice (N = 40) bearing YTN-16 gastric tumors. Mice were treated with PBS, PD-1 Ab (50 µg), PAS (250 µg), or the combination of PD-1 Ab with PAS. Tumor growth was significantly slower than controls in PAS-treated mice, and tumor growth was decreased even more in combination-treated mice. There were no metastases in any of the mice treated with PAS either alone or in combination with PD-1 Ab. Tumor proliferation by the Ki67 staining was significantly decreased in mice treated with PAS monotherapy or the combination therapy. PAS monotherapy or combined with PD-1 Ab increased tumor CD8+ T-lymphocytes and decreased the number of immunosuppressive M2-polarized tumor-associated macrophages. CCK-BR expression was identified in samples from a human tissue array by immunohistochemistry confirming the clinical relevance of this study. These results confirm the significance of the gastrin-CCK-BR signaling pathway in gastric cancer and suggest that the addition of a gastrin vaccine, PAS, to therapy with an immune checkpoint antibody may decrease growth and metastases of gastric cancer by altering the tumor microenvironment., Competing Interests: Authors TP, AC and LS are employees of Cancer Advances, Inc. and the company owns the patent rights to PAS. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Cancer Advances, Inc. through a sponsored research agreement with Georgetown University. The funder had the following involvement with the study: Conception and design, Acquisition of data, Analysis and interpretation of data, and Writing, review and/ or revision of manuscript., (Copyright © 2021 Smith, Cao, Chen, Mahmood, Phillips, Sutton and Cato.)