Status quo of Extracellular Vesicle isolation and detection methods for clinical utility.

Extracellular vesicles (EVs) are nano-sized particles that hold tremendous potential in the clinical space, as their biomolecular profiles hold a key to non-invasive liquid biopsy for cancer diagnosis and prognosis. EVs are present in most bodily fluids, hence are easily obtainable from patients, advantageous to that of traditional, invasive tissue biopsies and imaging techniques. However, there are certain constraints that hinder clinical use of EVs. The translation of EV biomarkers from "bench-to-bedside" is encumbered by the methods of EV isolation and subsequent biomarker detection currently implemented in laboratories. Although current isolation and detection methods are effective, they lack practicality, with their requirement for high bodily fluid volumes, low equipment availability, slow turnaround times and high costs. The high demand for techniques that overcome these limitations has resulted in significant advancements in nanotechnological devices. These devices are designed to integrate EV isolation and biomarker detection into a one-step method of direct EV detection from bodily fluids. This provides promise for the acceleration of EVs into current clinical standards. This review highlights the importance of EVs as cancer biomarkers, the methodological obstacles currently faced in clinical studies and how novel nanodevices could advance clinical translation.

Increased family psychosocial focus during children's developmental assessments: a study of parents' views.

BACKGROUND: Family psychosocial challenges during the early years of a child's life are associated with later mental and physical health problems for the child. An increased psychosocial focus on parents in routine child developmental assessments may therefore be justified. METHODS: Participants in this qualitative study included 11 mothers and one parental couple (mother and father) with children aged 9-23 months. Participants were recruited to Project Family Wellbeing through their general practice in Denmark. Twelve interviews were conducted, transcribed and analysed with a deductive approach. The topic guide drew on the core components of the Health Belief Model, which also served as a framework for the coding that was conducted using thematic analysis. RESULTS: Results are presented in four themes and 11 subthemes in total. Parents welcome discussion of their psychosocial circumstances during their child's developmental assessments. Clinicians' initiatives to address psychosocial challenges and alignment of parents' and clinicians' expectations may be required to allow this discussion. A flowing conversation, an open communication style and a trustful relationship facilitate psychosocial discussion. Barriers included short consultation time, concerns about how information was used and when parents found specific psychosocial aspects stigmatising or irrelevant to discuss. CONCLUSION: Enquiry about the family's psychosocial circumstances in routine developmental assessments is acceptable among parents. Alignment of clinical and parental expectations of developmental assessments could facilitate the process. Future research should examine the predictive validity of the various components of developmental assessments. TRIAL REGISTRATION: This is a qualitative study. The study participants are part of the cohort from Project Family Wellbeing (FamilieTrivsel). The project's trial registry number: NCT04129359. Registered October 16th 2019.

Collaboration between general practitioners and health visitors about children of concern in Denmark: a qualitative study.

Primary health care services are responsible for preventive measures to optimize child development in the first years of life. In Denmark, these services are shared between general practitioners and municipality health visitors. National guidelines mandate collaboration between these professionals but in reality, they work in parallel. We aimed to explore how professionals experience collaboration and communication regarding children with professional concern about their wellbeing. Seventeen semi-structured interviews were conducted with general practitioners, and health visitors. Both professions considered closer collaboration to be important in meeting children's needs. Barriers to collaboration and communication included differing legal obligations, Information Technology-systems (IT), lack of financial incentives, lack of mutual professional acknowledgment and respect, and absence of routines for sharing knowledge. The traditional division of responsibilities between physicians and nurses in which all professionals involved in preventive child health care are acculturated seems to impede collaboration based on unequal professional status. IT infrastructure needs to support information sharing and structures to support informal meetings between professionals are warranted to support more collaborative practice.

Clinicians' experiences in signposting an online mental health resource to expectant mothers: a qualitative study.

BACKGROUND: Poor maternal mental well-being and a lack of secure parent-infant attachment, have been identified as important factors associated with adverse mental health outcomes later in a child's life. Interventions designed to care for maternal mental well-being during pregnancy and early parenthood, are therefore likely to support healthy child development. Mentalization is a skill parents can practice, improving the emotional bond to the child, offering insights into their own and the child's mental states and potentially improving parental mental well-being. Most pregnant women in Denmark schedule antenatal consultations in general practice, potentially offering a solid platform to promote web-based interventions aiming to enhance mentalization skills. Signposting towards online resources has several advantages including high accessibility, ease of distribution and cost-effectiveness. We aimed to explore the attitudes and experiences of clinicians in general practice in signposting women towards a web-intervention to increase parental mentalization skills. METHODS: The intervention was offered to pregnant women at their primary preventive antenatal consultation in Danish general practice around week eight of pregnancy, and was designed to be incorporated into the following antenatal- and pediatric consultations until the child's second birthday. Semi-structured interviews about clinicians' experiences with signposting the intervention were conducted with 11 general practitioners (GP), three practice midwives (MW) and one practice nurse (NR). RESULTS: Clinicians wanted to enhance the focus on mental well-being in pregnancy and early childhood during preventive consultations. The main barriers to signposting the web-program were decreasing motivation over time, lack of financial viability and time limitations. Utilizing a psychoeducational web-intervention was generally accepted by clinicians, but ideally not carried out solely in general practice. CONCLUSION: Signposting web-programs to improve parental mentalization skills can be welcomed by clinicians in general practice but need to be more tailored to suit the everyday workflow of the clinics. Addressing parental mentalization remains largely unchartered territory for pregnant women and clinicians alike, therefore training clinicians on the subject and its presentation should be offered. TRIAL REGISTRATION: The study is part of a larger project that has been approved by the Research Ethics Committee at the University of Copenhagen, Nov. 2019 (reference number 504-0111/19-5000).

Factors in early pregnancy predicting pregnancy-related pain in the second and third trimester.

INTRODUCTION: Pain during pregnancy affects women's well-being, causes worry and is a risk factor for the child and the mother during labor. The aim was to investigate the relative importance of an extensive set of pregnancy-related physiological symptoms and psychosocial factors assessed in the first trimester compared with the occurrence of pregnancy-related pain symptoms later in the pregnancy. MATERIAL AND METHODS: Included were all women who booked an appointment for a first prenatal visit in one of 125 randomly selected general practitioner practices in Eastern Denmark from April 2015 to August 2016. These women answered an electronic questionnaire containing questions on the occurrence of five pregnancy-related pain symptoms: back pain, leg cramps, pelvic cavity pain, pelvic girdle pain and uterine contractions. The questionnaire also included sociodemographic questions and questions on chronic diseases, physical symptoms, mental health symptoms, lifestyle and reproductive background. The questionnaire was repeated in each trimester. The relative importance of this set of factors from the first trimester on the five pregnancy-related pain symptoms compared with the second and third trimesters was assessed in a dominance analysis. RESULTS: A total of 1491 women were included. The most important factor for pregnancy-related pain in the second trimester and third trimester is the presence of the corresponding pain in the first trimester. Parity was associated with pelvic cavity pain and uterine contractions in the following pregnancies. For back pain and pelvic cavity pain, the odds increased as the women's estimated low self-assessed fitness decreased and had low WHO-5 wellbeing scores. CONCLUSIONS: When including physical risk factors, sociodemographic factors, psychological factors and clinical risk factors, women's experiences of pregnancy-related pain in the first trimester are the most important predictors for pain later in pregnancy. Beyond the expected positive effects of pregnancy-related pain, notably self-assessed fitness, age and parity were predictive for pain later in pregnancy.

Increasing the psychosocial focus in child developmental assessments: a qualitative study.

BACKGROUND: Previous studies have indicated a need for increased psychosocial focus on children and their families to improve children's wellbeing and mental health. Child developmental assessments could be a place to implement changes to achieve this. A standardised record might be helpful to clinicians trying to increase psychosocial focus. The aim of this study is to investigate clinical barriers and facilitators when introducing standardised child records with increased focus on psychosocial wellbeing and mental health into child developmental assessments. METHODS: This is a qualitative study based on 12 semi-structured interviews with four midwives and nine doctors who carry out child developmental assessments in general practice. Data is analysed in the framework of Normalisation Process Theory. RESULTS: General practice-based clinicians were positive towards increasing the psychosocial focus in child developmental assessments. The main barriers when clinicians used the standardised child records were: feeling forced to ask certain questions, in turn making the conversation rigid; leaving less room for parents to bring up other issues; making clinicians feel awkward when addressing problems that they cannot solve; the need for extended consultation time; and medico-legal concerns when registering findings. The experience of positive aspects when using the standardised child records facilitated continuous use of the records. Positive aspects included having a standardised approach to recording important findings, thereby uncovering psychosocial problems that could potentially be overlooked. Additionally, structured observation of parent-child interaction and gaining a new vocabulary to describe the findings were valued by clinicians. Balancing a standardised approach with clinicians' ability to steer the consultation and explore topics in depth while preserving the potential for patients to bring up other issues became an important theme. CONCLUSION: Clinicians need to be well-equipped to handle psychosocial problems through coping strategies, referral options and communication techniques in the psychosocial domain. The parent-child-interaction assessment might expose potentially dysfunctional parenting behaviours and could improve communication between health professionals. Implementing standardised child development records with an increased psychosocial focus is feasible but improvements could optimise the use of the records. Parental views on an increased psychosocial focus during child developmental assessments should be investigated prior to further implementation. TRIAL REGISTRATION: Trial registry number for the FamilieTrivsel (Family Wellbeing) trial: NCT04129359.

Oncogenic allelic interaction in Xiphophorus highlights hybrid incompatibility.

Mixing genomes of different species by hybridization can disrupt species-specific genetic interactions that were adapted and fixed within each species population. Such disruption can predispose the hybrids to abnormalities and disease that decrease the overall fitness of the hybrids and is therefore named as hybrid incompatibility. Interspecies hybridization between southern platyfish and green swordtails leads to lethal melanocyte tumorigenesis. This occurs in hybrids with tumor incidence following progeny ratio that is consistent with two-locus interaction, suggesting melanoma development is a result of negative epistasis. Such observations make Xiphophorus one of the only two vertebrate hybrid incompatibility examples in which interacting genes have been identified. One of the two interacting loci has been characterized as a mutant epidermal growth factor receptor. However, the other locus has not been identified despite over five decades of active research. Here we report the localization of the melanoma regulatory locus to a single gene, rab3d, which shows all expected features of the long-sought oncogene interacting locus. Our findings provide insights into the role of egfr regulation in regard to cancer etiology. Finally, they provide a molecular explainable example of hybrid incompatibility.

Cross-cultural adaptation and its impact on research in emergency care.

The perspective of patients is increasingly recognised as important to care improvement and innovation. Patient questionnaires such as patient-reported outcome measures may often require cross-cultural adaptation (CCA) to gather their intended information most effectively when used in cultures and languages different to those in which they were developed. The use of CCA could be seen as a practical step in addressing the known problems of inclusion, diversity and access in medical research.An example of the recent adaptation of a patient-reported outcome measure for use with ED patients is used to explore some key features of CCA, introduce the importance of CCA to emergency care practitioners and highlight the limitations of CCA.

Barriers and facilitators to the administration of prehospital tranexamic acid: a paramedic interview study using the theoretical domains framework.

BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic drug used to prevent bleeding. It was introduced as an intervention for post-traumatic haemorrhage across emergency medical services (EMS) in the UK during 2012. However, despite strong evidence of effectiveness, prehospital TXA administration rates are low. This study used the theoretical domains framework (TDF) to identify barriers and facilitators to the administration of TXA to trauma patients by EMS providers (paramedics) in the UK. METHODS: Interviews were completed with 18 UK paramedics from a single EMS provider organisation. A convenience sampling approach was used, and interviews continued until thematic saturation was reached. Semistructured telephone interviews explored paramedics' experiences of administering TXA to trauma patients, including identifying whether or not patients were at risk of bleeding. Data were analysed inductively using thematic analysis (stage 1). Themes were mapped to the theoretical domains of the TDF to identify behavioural theory-derived barriers and facilitators to the administration of TXA to trauma patients (stage 2). Belief statements were identified and assessed for importance according to prevalence, discordance and evidence base (stage 3). RESULTS: Barriers and facilitators to paramedics' administration of TXA to trauma patients were represented by 11 of the 14 domains of the TDF. Important barriers included a lack of knowledge and experience with TXA (Domain: Knowledge and Skills), confusion and restrictions relating to the guidelines for TXA administration (Domain: Social/professional role and identity), a lack of resources (Domain: Environmental context and resources) and difficulty in identifying patients at risk of bleeding (Domain: Memory, attention and decision processes). CONCLUSIONS: This study presents a behavioural theory-based approach to identifying barriers and facilitators to the prehospital administration of TXA to trauma patients in the UK. It identifies multiple influencing factors that may serve as a basis for developing an intervention to increase prehospital administration of TXA.

Temperature measurement of babies born in the pre-hospital setting: analysis of ambulance service data and qualitative interviews with paramedics.

BACKGROUND: Birth before arrival at hospital (BBA) is associated with unfavourable perinatal outcomes and increased mortality. An important risk factor for mortality following BBA is hypothermia, and emergency medical services (EMS) providers are well placed to provide warming strategies. However, research from the UK suggests that EMS providers (paramedics) do not routinely record neonatal temperature following BBA. This study aimed to determine the proportion of cases in which neonatal temperature is documented by paramedics attending BBAs in the South West of England and to explore the barriers to temperature measurement by paramedics. METHODS: A two-phase multi-method study. Phase I involved an analysis of anonymised data from electronic patient care records between 1 February 2017 and 31 January 2020 in a single UK ambulance service, to determine 1) the frequency of BBAs attended and 2) the percentage of these births where a neonatal temperature was recorded, and what proportion of these were hypothermic. Phase II involved interviews with 20 operational paramedics from the same ambulance service, to explore their experiences of, and barriers and facilitators to, neonatal temperature measurement and management following BBA. RESULTS: There were 1582 'normal deliveries' attended by paramedics within the date range. Neonatal temperatures were recorded in 43/1582 (2.7%) instances, of which 72% were below 36.5°C. Data from interviews suggested several barriers and potential facilitators to paramedic measurement of neonatal temperature. Barriers included unavailable or unsuitable equipment, prioritisation of other care activities, lack of exposure to births, and uncertainty regarding responsibilities and roles. Possible facilitators included better equipment, physical prompts, and training and awareness-raising around the importance of temperature measurement. CONCLUSIONS: This study demonstrates a lack of neonatal temperature measurement by paramedics in the South West following BBA, and highlights barriers and facilitators that could serve as a basis for developing an intervention to improve neonatal temperature measurement.

Factors influencing conveyance of older adults with minor head injury by paramedics to the emergency department: a multiple methods study.

BACKGROUND: Head injury (HI) in older adults due to low-energy falls result in a substantial number of emergency department (ED) attendances. However, mortality associated with minor HI is very low. Reducing conveyance to hospital is important for older adults and is a priority for the National Health Service (NHS). Therefore, paramedics are required to make accurate decisions regarding conveyance to the ED. This study used routine data and semi-structured interviews to explore the factors that influence paramedic decision-making when considering whether to convey an adult aged 65 years and over with a minor HI to the ED. METHODS: Semi-structured telephone interviews were completed with ten UK paramedics from a single EMS (ambulance) provider organisation. Interviews explored the factors influencing the paramedics' conveyance decision-making in adults aged 65 years and over with a minor HI. Data were initially analysed inductively to develop a thematic framework. A retrospective analysis of ambulance service data was also completed to determine the scope and scale of the issue in Southwest England. An in-depth audit of 100 conveyed patient records was used to determine the proportion of patients conveyed to the ED who met National Institute for Health and Care Excellence (NICE) and Joint Royal Colleges Ambulance Liaison Committee (JRCALC) guidelines. RESULTS: In 2019 South Western Ambulance Service NHS Foundation Trust (SWASFT) attended 15,650 emergency calls to patients aged 65 and over with minor HI, with 70.5% conveyed to ED. 81% of conveyed patients met NICE and JRCALC guideline criteria for conveyance, with the remainder conveyed due to wound care or other medical concerns. The framework developed from the interviews comprised four themes: resources; patient factors; consequences; paramedic factors. Important factors included: the patient's social situation; guidelines; clinical support availability; the history and presentation of the patient; risk. CONCLUSION: This study examined paramedic conveyance decisions for older people with minor HI. It identified multiple influencing factors, highlighting the complex nature of these decisions, and may serve as a basis for developing an intervention to safely decrease ED conveyance in this patient group.

Identification of Novel Genes Involved in Hyperglycemia in Mice.

Current attempts to prevent and manage type 2 diabetes have been moderately effective, and a better understanding of the molecular roots of this complex disease is important to develop more successful and precise treatment options. Recently, we initiated the collective diabetes cross, where four mouse inbred strains differing in their diabetes susceptibility were crossed with the obese and diabetes-prone NZO strain and identified the quantitative trait loci (QTL) Nidd13/NZO, a genomic region on chromosome 13 that correlates with hyperglycemia in NZO allele carriers compared to B6 controls. Subsequent analysis of the critical region, harboring 644 genes, included expression studies in pancreatic islets of congenic Nidd13/NZO mice, integration of single-cell data from parental NZO and B6 islets as well as haplotype analysis. Finally, of the five genes (Acot12, S100z, Ankrd55, Rnf180, and Iqgap2) within the polymorphic haplotype block that are differently expressed in islets of B6 compared to NZO mice, we identified the calcium-binding protein S100z gene to affect islet cell proliferation as well as apoptosis when overexpressed in MIN6 cells. In summary, we define S100z as the most striking gene to be causal for the diabetes QTL Nidd13/NZO by affecting ß-cell proliferation and apoptosis. Thus, S100z is an entirely novel diabetes gene regulating islet cell function.

Current provision of general practitioner services in or alongside emergency departments in England.

BACKGROUND: In 2017, general practitioners in or alongside the emergency department (GPED), an approach that employs GPs in or alongside the ED to address increasing ED demand, was advocated by the National Health Service in England and supported by capital funding. However, little is known about the models of GPED that have been implemented. METHODS: Data were collected at two time points: September 2017 and December 2019, on the GPED model in use (if any) at 163/177 (92%) type 1 EDs in England. Models were categorised according to a taxonomy as 'inside/integrated', 'inside/parallel', 'outside/onsite' or 'outside/offsite'. Multiple data sources used included: on-line surveys, interviews, case study data and publicly available information. RESULTS: An increase of EDs using GPED was observed from 81% to 95% over the study period. 'Inside/parallel' was the most frequently used model: 30% (44/149) in 2017, rising to 49% (78/159) in 2019. The adoption of 'inside/integrated' models fell from 26% (38/149) to 9% (15/159). Capital funding was received by 87% (142/163) of the EDs sampled. We identified no significant difference between the GPED model adopted and observable characteristics of EDs of annual attendance, 4-hour wait, rurality and deprivation within the population served. CONCLUSION: The majority of EDs in England have now adopted GPED. The availability of capital funding to finance structural changes so that separate GP services can be provided may explain the rise in parallel models and the decrease in integrated models. Further research is required to understand the relative effectiveness of the various models of GPED identified.

A qualitative study on conveyance decision-making during emergency call outs to people with dementia: the HOMEWARD project.

BACKGROUND: Paramedics are increasingly required to make complex decisions as to whether they should convey a patient to hospital or manage their condition at the scene. Dementia can be a significant barrier to the assessment process. However, to our knowledge no research has specifically examined the process of decision-making by paramedics in relation to people with dementia. This qualitative study was designed to investigate the factors influencing the decision-making process during Emergency Medical Services (EMS) calls to older people with dementia who did not require immediate clinical treatment. METHODS: This qualitative study used a combination of observation, interview and document analysis to investigate the factors influencing the decision-making process during EMS calls to older people with dementia. A researcher worked alongside paramedics in the capacity of observer and recruited eligible patients to participate in case studies. Data were collected from observation notes of decision-making during the incident, patient care records and post incident interviews with participants, and analysed thematically. FINDINGS: Four main themes emerged from the data concerning the way that paramedics make conveyance decisions when called to people with dementia: 1) Physical condition; the key factor influencing paramedics' decision-making was the physical condition of the patient. 2) Cognitive capacity; most of the participants preferred not to remove patients with a diagnosis of dementia from surroundings familiar to them, unless they deemed it absolutely essential. 3) Patient circumstances; this included the patient's medical history and the support available to them. 4) Professional influences; participants also drew on other perspectives, such as advice from colleagues or information from the patient's General Practitioner, to inform their decision-making. CONCLUSION: The preference for avoiding unnecessary conveyance for patients with dementia, combined with difficulties in obtaining an accurate patient medical history and assessment, mean that decision-making can be particularly problematic for paramedics. Further research is needed to find reliable ways of assessing patients and accessing information to support conveyance decisions for EMS calls to people with dementia.

Taxonomy of the form and function of primary care services in or alongside emergency departments: concepts paper.

Primary care services in or alongside emergency departments look and function differently and are described using inconsistent terminology. Research to determine effectiveness of these models is hampered by outdated classification systems, limiting the opportunity for data synthesis to draw conclusions and inform decision-making and policy. We used findings from a literature review, a national survey of Type 1 emergency departments in England and Wales, staff interviews, other routine data sources and discussions from two stakeholder events to inform the taxonomy. We categorised the forms inside or outside the emergency department: inside primary care services may be integrated with emergency department patient flow or may run parallel to that activity; outside services may be offered on site or off site. We then describe a conceptual spectrum of integration: identifying constructs that influence how the services function-from being closer to an emergency medicine service or to usual primary care. This taxonomy provides a basis for future evaluation of service models that will comprise the evidence base to inform policy-making in this domain. Commissioners and service providers can consider these constructs in characterising and designing services depending on local circumstances and context.

Cluster randomised comparison of the effectiveness of 100% oxygen versus titrated oxygen in patients with a sustained return of spontaneous circulation following out of hospital cardiac arrest: a feasibility study. PROXY: post ROSC OXYgenation study.

BACKGROUND: Hyperoxia following out of hospital cardiac arrest (OHCA) is associated with a poor outcome. Animal data suggest the first hour post resuscitation may be the most important. In the UK the first hour usually occurs in the prehospital environment. METHODS: A prospective controlled trial, cluster randomised by paramedic, comparing titrated oxygen with 100% oxygen for the first hour after return of spontaneous circulation (ROSC) following OHCA. The trial was done in a single emergency medical services (EMS) system in the United Kingdom (UK) admitting patients to three emergency departments. This was a feasibility trial to determine whether EMS staff (UK paramedics) can be successfully recruited and deliver the intervention. RESULTS: One hundred and fifty seven paramedics were approached and 46 (29%) were consented, randomised and trained. During the study period 624 patients received a resuscitation attempt. A study paramedic was in attendance at 73 (12%) of these active resuscitations. Thirty-five patients were recruited to the trial, 32 (91%) were transported to hospital and 13 (37%) survived to 90 days. The intervention was initiated in 27/35 (77%) of enrolled patients. A reliable oxygen saturation trace was obtained in 22/35 (69%) of patients. Data collection was complete in 33/35 (94%) of patients. CONCLUSIONS: It may be feasible to complete a randomised trial of titrated versus unrestricted oxygen in the first hour after ROSC following OHCA in the UK. However, the relatively few eligible patients and incomplete initiation of the allocated intervention are challenges to future research. TRIAL REGISTRATION: ISRCTN 49548506 retrospectively registered on 24.11.2016.

Effect of a Strategy of a Supraglottic Airway Device vs Tracheal Intubation During Out-of-Hospital Cardiac Arrest on Functional Outcome: The AIRWAYS-2 Randomized Clinical Trial.

Importance: The optimal approach to airway management during out-of-hospital cardiac arrest is unknown. Objective: To determine whether a supraglottic airway device (SGA) is superior to tracheal intubation (TI) as the initial advanced airway management strategy in adults with nontraumatic out-of-hospital cardiac arrest. Design, Setting, and Participants: Multicenter, cluster randomized clinical trial of paramedics from 4 ambulance services in England responding to emergencies for approximately 21 million people. Patients aged 18 years or older who had a nontraumatic out-of-hospital cardiac arrest and were treated by a participating paramedic were enrolled automatically under a waiver of consent between June 2015 and August 2017; follow-up ended in February 2018. Interventions: Paramedics were randomized 1:1 to use TI (764 paramedics) or SGA (759 paramedics) as their initial advanced airway management strategy. Main Outcomes and Measures: The primary outcome was modified Rankin Scale score at hospital discharge or 30 days after out-of-hospital cardiac arrest, whichever occurred sooner. Modified Rankin Scale score was divided into 2 ranges: 0-3 (good outcome) or 4-6 (poor outcome; 6 = death). Secondary outcomes included ventilation success, regurgitation, and aspiration. Results: A total of 9296 patients (4886 in the SGA group and 4410 in the TI group) were enrolled (median age, 73 years; 3373 were women [36.3%]), and the modified Rankin Scale score was known for 9289 patients. In the SGA group, 311 of 4882 patients (6.4%) had a good outcome (modified Rankin Scale score range, 0-3) vs 300 of 4407 patients (6.8%) in the TI group (adjusted risk difference [RD], -0.6% [95% CI, -1.6% to 0.4%]). Initial ventilation was successful in 4255 of 4868 patients (87.4%) in the SGA group compared with 3473 of 4397 patients (79.0%) in the TI group (adjusted RD, 8.3% [95% CI, 6.3% to 10.2%]). However, patients randomized to receive TI were less likely to receive advanced airway management (3419 of 4404 patients [77.6%] vs 4161 of 4883 patients [85.2%] in the SGA group). Two of the secondary outcomes (regurgitation and aspiration) were not significantly different between groups (regurgitation: 1268 of 4865 patients [26.1%] in the SGA group vs 1072 of 4372 patients [24.5%] in the TI group; adjusted RD, 1.4% [95% CI, -0.6% to 3.4%]; aspiration: 729 of 4824 patients [15.1%] vs 647 of 4337 patients [14.9%], respectively; adjusted RD, 0.1% [95% CI, -1.5% to 1.8%]). Conclusions and Relevance: Among patients with out-of-hospital cardiac arrest, randomization to a strategy of advanced airway management with a supraglottic airway device compared with tracheal intubation did not result in a favorable functional outcome at 30 days. Trial Registration: ISRCTN Identifier: 08256118.

Standing thyroidectomy in 10 horses.

OBJECTIVE: To describe a surgical technique for thyroidectomy in horses with thyroid neoplasia under standing sedation and local anesthesia. STUDY DESIGN: Retrospective study. ANIMALS: Client-owned horses (n = 10). METHODS: Medical records of horses with a history of thyroid enlargement were included in the study if thyroid gland enlargement was treated surgically via hemi- or bilateral thyroidectomy, with the horse standing and sedated. Data derived from follow-up clinical examination, performance level, recurrence, and cosmetic outcome were evaluated. RESULTS: Thyroid enlargement was unilateral in 8 and bilateral in 2 horses. Histopathological findings included adenomas (5/10), adenocarcinomas (2/10), cystic hyperplasia (2/10), and C-cell adenoma (1/10). No major complications were encountered during or after surgery. All horses resumed their previous level of exercise within 6 weeks. Recurrence was diagnosed in 1 horse, 7 months after excision, and a second surgery was required. Recurrent laryngeal nerve neuropathy and seroma formation subsequent to surgery were not recorded in any of the cases. CONCLUSION: Thyroidectomy can safely be performed with the horse standing and sedated with local anesthesia. CLINICAL RELEVANCE: Performing standing thyroidectomy does not increase intraoperative or postoperative complications and could be considered for horses with thyroid enlargement amenable to surgery.

The 'Necksafe' head articulation control system: a novel cervical immobilisation device.

INTRODUCTION: The early application of a semirigid disposable cervical collar following trauma is considered a routine practice. The aim of these devices is to immobilise the cervical spine and minimise the risk of additional neurological damage. However, these collars provide only partial immobilisation, are uncomfortable and are associated with a number of complications. Our team designed and tested a novel cervical immobilisation device that aims to improve immobilisation with reduced complications: the 'Necksafe'. METHODS: Human volunteers were recruited and consented to test the novel Necksafe device in comparison with a conventional collar (the AMBU Perfit ACE) in a range of evaluations. These included assessments of the cervical range of movement (CROM) that occurred during scripted movements of the head and neck, and the effect of the new and conventional devices on jugular vein dimensions, assessed using ultrasound scanning. RESULTS: CROM analysis showed that, under standardised testing conditions, the Necksafe device offers cervical immobilisation that is at least equivalent to a conventional collar, and is superior in the planes of extension, lateral flexion and rotation. Ultrasound examination of the jugular veins was inconclusive and did not reveal any differences in jugular venous diameter or flow. Qualitative feedback from ambulance paramedics was highly supportive of the new design, suggesting that it is more comfortable, easier to fit, less confining and better tolerated than a conventional collar, with improved immobilisation effectiveness. CONCLUSIONS: The results of quantitative and qualitative testing are highly supportive of the new Necksafe design, with improved cervical immobilisation, comfort and access to the airway.

Challenges and enablers to implementation of the Additional Roles Reimbursement Scheme in primary care: a qualitative study.

BACKGROUND: The Additional Roles Reimbursement Scheme (ARRS) was set up to recruit 26 000 additional staff into general practice by 2024, with the aim of increasing patient access to appointments. Despite the potential benefits of integrating ARRS practitioners into primary care, their implementation has not always been straightforward. AIM: To explore the challenges and enablers to implementation of the ARRS including its impact on primary and secondary care systems. DESIGN AND SETTING: Qualitative interview study with ARRS healthcare professionals and key professional stakeholders involved in staff education or scheme implementation across three integrated care systems in England. METHOD: Participants (n = 37) were interviewed using semi-structured individual or paired interviews. Interviews were audio-recorded and transcribed. Data were analysed using framework analysis until data saturation occurred. RESULTS: Using framework analysis, 10 categories were identified. Three were categorised as successes: staff valued but their impact unclear; multiple and certain roles maximise impact; and training hub support. Seven were categorised as challenges: scheme inflexibility; creating a sustainable workforce with career progression; managing scope and expectations; navigating supervision and roadmap progression; infrastructure and integration challenges; ARRS roles impact on wider systems; and tensions and perspectives of existing staff. CONCLUSION: Most ARRS staff felt valued, but the scheme broadened expertise available in primary care rather than reducing GP burden, which was originally anticipated. Some PCNs, especially those in areas of high deprivation, found it difficult to meet the population's needs as a result of the scheme's inflexibility, potentially leading to greater health inequalities in primary care. Recommendations are proposed to optimise the effective implementation of the primary care workforce model. Further research is required to explore administrative role solutions, further understand the impact of health inequalities, and investigate the wellbeing of ARRS staff.