The accuracy of prehospital triage decisions in English trauma networks - a case-cohort study.

BACKGROUND: Care for injured patients in England is provided by inclusive regional trauma networks. Ambulance services use triage tools to identify patients with major trauma who would benefit from expedited Major Trauma Centre (MTC) care. However, there has been no investigation of triage performance, despite its role in ensuring effective and efficient MTC care. This study aimed to investigate the accuracy of prehospital major trauma triage in representative English trauma networks. METHODS: A diagnostic case-cohort study was performed between November 2019 and February 2020 in 4 English regional trauma networks as part of the Major Trauma Triage Study (MATTS). Consecutive patients with acute injury presenting to participating ambulance services were included, together with all reference standard positive cases, and matched to data from the English national major trauma database. The index test was prehospital provider triage decision making, with a positive result defined as patient transport with a pre-alert call to the MTC. The primary reference standard was a consensus definition of serious injury that would benefit from expedited major trauma centre care. Secondary analyses explored different reference standards and compared theoretical triage tool accuracy to real-life triage decisions. RESULTS: The complete-case case-cohort sample consisted of 2,757 patients, including 959 primary reference standard positive patients. The prevalence of major trauma meeting the primary reference standard definition was 3.1% (n=54/1,722, 95% CI 2.3 - 4.0). Observed prehospital provider triage decisions demonstrated overall sensitivity of 46.7% (n=446/959, 95% CI 43.5-49.9) and specificity of 94.5% (n=1,703/1,798, 95% CI 93.4-95.6) for the primary reference standard. There was a clear trend of decreasing sensitivity and increasing specificity from younger to older age groups. Prehospital provider triage decisions commonly differed from the theoretical triage tool result, with ambulance service clinician judgement resulting in higher specificity. CONCLUSIONS: Prehospital decision making for injured patients in English trauma networks demonstrated high specificity and low sensitivity, consistent with the targets for cost-effective triage defined in previous economic evaluations. Actual triage decisions differed from theoretical triage tool results, with a decreasing sensitivity and increasing specificity from younger to older ages.

Randomised controlled trial of analgesia for the management of acute severe pain from traumatic injury: study protocol for the paramedic analgesia comparing ketamine and morphine in trauma (PACKMaN).

BACKGROUND: Prehospital analgesia is often required after traumatic injury, currently morphine is the strongest parenteral analgesia routinely available for use by paramedics in the United Kingdom (UK) when treating patients with severe pain. This protocol describes a multi-centre, randomised, double blinded trial comparing the clinical and cost-effectiveness of ketamine and morphine for severe pain following acute traumatic injury. METHODS: A two arm pragmatic, phase III trial working with two large NHS ambulance services, with an internal pilot. Participants will be randomised in equal numbers to either (1) morphine or (2) ketamine by IV/IO injection. We aim to recruit 446 participants over the age of 16 years old, with a self-reported pain score of 7 or above out of 10. Randomised participants will receive a maximum of 20 mg of morphine, or a maximum of 30 mg of ketamine, to manage their pain. The primary outcome will be the sum of pain intensity difference. Secondary outcomes measure the effectiveness of pain relief and overall patient experience from randomisation to arrival at hospital as well as monitoring the adverse events, resource use and cost-effectiveness outcomes. DISCUSSION: The PACKMAN study is the first UK clinical trial addressing the clinical and cost-effectiveness of ketamine and morphine in treating acute severe pain from traumatic injury treated by NHS paramedics. The findings will inform future clinical practice and provide insights into the effectiveness of ketamine as a prehospital analgesia. TRIAL REGISTRATION: ISRCTN, ISRCTN14124474. Registered 22 October 2020, https://www.isrctn.com/ISRCTN14124474.

Characteristics of Restart a Heart 2019 event locations in the UK.

INTRODUCTION: Restart a Heart (RSAH) is an annual CPR mass training initiative delivered predominantly by ambulance services in the UK. The aim of this study was to identify to what extent voluntary participation in the 2019 initiative delivered training to the population with the highest need. METHODS: A cross-sectional observational study of location characteristics for RSAH training events conducted by UK ambulance services. Descriptive statistics were used to analyse event and area characteristics. National cardiac arrest registry data were used to establish proportions of training coverage in "hot spot" areas with above national median incidence of cardiac arrest and below median bystander CPR rates. The significance of observed differences were tested using chi-square for proportions and t-test for means. RESULTS: Twelve of 14 UK ambulance services participated, training 236,318 people. Most of the events (82%) were held in schools, and schoolchildren comprised most participants (81%). RSAH events were held in areas that were less densely populated (p < 0.001), were more common in affluent areas (p < 0.001), and had a significantly lower proportion of black residents (p < 0.05) and higher proportion of white residents (p < 0.05). Events were held in 28% of known "hot spot" areas in England. CONCLUSION: With mandatory CPR training for school children in England, Scotland and Wales there is an opportunity to re-focus RSAH resources to deliver training for all age groups in OHCA "hot spots", communities with higher proportions of black residents, and areas of deprivation. In Northern Ireland, we recommend targeting schools in areas with similar characteristics.

Burden of disease associated with X-linked hypophosphataemia in adults: a systematic literature review.

This systematic review collated evidence on the burden of XLH in adults. Data captured highlight the substantial ongoing burden of XLH in adulthood and identified unmet needs. Greater awareness and understanding of the impact of XLH in adulthood are needed to improve care and outcomes in adults with XLH. INTRODUCTION: X-linked hypophosphataemia (XLH) is a rare metabolic bone disease characterized by renal phosphate wasting and musculoskeletal manifestations. Whilst the disease's impact in children is well documented, information on the effects of this progressive, debilitating condition on adults is lacking. This systematic review aimed to collate existing evidence on the burden of XLH in adulthood to identify unmet needs. METHODS: MEDLINE, Embase and Cochrane Library databases and recent congress reports were searched on 19 February 2019 for English-language publications describing the medical, humanistic and socio-economic impact of XLH in adults (≥ 18 years old). In addition, a structured Internet search was conducted. RESULTS: Of the 2351 articles identified, 91 met the selection criteria along with 44 congress abstracts. Data show that adults with XLH experience a range of clinical manifestations, particularly skeletal deformities and (pseudo)fractures, along with pain, dental abnormalities and impaired physical function and mobility. XLH in adulthood impacts on quality of life and places limitations on daily activities. The level of healthcare resource utilization among adults with XLH is indicative of substantial socio-economic burden; further research is needed to quantitate the economic impact on the healthcare system, society and patients. Adults with XLH may not receive appropriate care and treatment; a possible explanation for this is a lack of awareness among healthcare professionals. CONCLUSION: XLH in adults is associated with considerable disease burden and unmet needs. Forthcoming studies and increased awareness of the impact of XLH in adulthood should help to improve management of XLH in adulthood and patient outcomes.

Building-Integrated Photovoltaic/Thermal (BIPVT): LCA of a façade-integrated prototype and issues about human health, ecosystems, resources.

Building-Integrated Photovoltaic/Thermal (BIPVT) technology offers multiple advantages; however, these types of installations include materials such as Photovoltaic (PV) cells and metals which considerably influence BIPVT environmental impact. Therefore, there is a need to evaluate BIPVT environmental profile, for instance by means of Life Cycle Assessment (LCA). In light of the issues mentioned above, the present article is an LCA study that assesses the environmental performance of a BIPVT prototype that has been developed and patented at the Ulster University (Belfast, UK). The investigation places emphasis on material manufacturing, based on Cumulative Energy Demand (CED), Global Warming Potential (GWP), ReCiPe, Ecological footprint and USEtox. The results show that according to all the adopted methods/environmental indicators and based on primary materials, the PV cells and the two vessels (steel) are the components with the three highest impacts. Scenarios which include recycling of steel, plastics and brass (landfill for the other materials has been assumed), based on CED, GWP 100a and ReCiPe endpoint, have been examined. It was found that steel recycling offers a considerable impact reduction, ranging from 47% to 85%. Furthermore, the impact of the proposed BIPVT module per m2 of thermal absorber has been calculated. The results, based on primary materials, show 4.92 GJprim/m2 and 0.34 t CO2.eq/m2 (GWP 100a). In addition, according to USEtox/ecotoxicity, USEtox/human toxicity-non-cancer (scenario based on primary materials), the PV cells present the highest contributions to the total impact of the module: 55% in terms of ecotoxicity and 86% concerning human toxicity/non-cancer. A comparison with literature is provided. Moreover, a separate section of the article is about factors which influence BIPVT environmental profile, discussing parameters such as the storage materials and the end-of-life management.

On the West Indian weevil genus Lachnopus Schönherr, 1840 (Coleoptera: Curculionidae: Entiminae): descriptions of six new species, a proposal for species-groups, and an annotated checklist.

We here describe and illustrate six new species of the genus Lachnopus, the most taxonomically chaotic group of entimines in the Caribbean region. These species are Lachnopus cozumelus Girón O'Brien, sp. nov. from Cozumel Island, Mexico, Lachnopus karphos Girón O'Brien, sp. nov. from Mayaguana Island in the Bahamas, Lachnopus lucayanus Girón O'Brien, sp. nov. from Eleuthera in the Bahamas and Providenciales in the Turks and Caicos Islands, Lachnopus petilusquamus Girón O'Brien, sp. nov. from Eleuthera in the Bahamas, Lachnopus rhabdotus Girón O'Brien, sp. nov. from Providenciales in the Turks and Caicos Islands and Lachnopus vanessablockae Girón O'Brien, sp. nov. from the Cayman Islands. These constitute the first species of the genus described for each island group, and expand the geographical range of the genus, by including the Lucayan Archipelago, the Cayman Islands and Cozumel Island. Individuals of L. vanessablockae have been collected on the Cayman endemic banana orchid (Myrmecophila thomsoniana (Orchidaceae)), which represents the first reported occurrence of Lachnopus weevils as pollinators. In addition, we present an annotated checklist of the species of Lachnopus, including collecting localities, host plants, and biological notes obtained from the literature or collection data from labels of collections' specimens. Lachnopus coffeae Marshall, 1922 is recorded for the first time for Grand Bahama, which appears to be an introduction associated with citrus from Puerto Rico. We also list the fossil species attributed to the genus. Comments on some morphological characters and their variation across the genus are included. Species-groups within the genus are proposed, including diagnostic features to recognize them. Some taxonomic conflicts found in collections are pointed out. This paper compiles fundamental information, and assembles a framework for future revisionary work on Lachnopus.

Predictors of responses to immune checkpoint blockade in advanced melanoma.

Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs. Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB. Based on this assay, we retrospectively observed, in eight cohorts enrolling 190 MMel patients treated with ipilimumab, that PD-L1 expression on peripheral T cells was prognostic on overall and progression-free survival. Moreover, detectable CD137 on circulating CD8+ T cells was associated with the disease-free status of resected stage III MMel patients after adjuvant ipilimumab + nivolumab (but not nivolumab alone). These biomarkers should be validated in prospective trials in MMel.The clinical management of metastatic melanoma requires predictors of the response to checkpoint blockade. Here, the authors use immunological assays to identify potential prognostic/predictive biomarkers in circulating blood cells and in tumor-infiltrating lymphocytes from patients with resected stage III melanoma.

Caring for Obese Children- A change in Paradigm.

Childhood Obesity is a problem of epidemic proportions. The causes are complex and treatment results are variable with much research ongoing. We analysed the initial assessment forms of a group of patients attending the W82GO! Healthy Lifestyle service at The Children's University Hospital, Temple Street to look at the population and their specific needs. Our analysis revealed a high proportion of emotional and behavioural problems along with bullying. This group of patients are complex and a multi-disciplinary team approach is essential in their treatment.

Post-admission outcomes of participants in the PARAMEDIC trial: A cluster randomised trial of mechanical or manual chest compressions.

BACKGROUND: The PARAMEDIC cluster randomised trial evaluated the LUCAS mechanical chest compression device, and did not find evidence that use of mechanical chest compression led to an improvement in survival at 30 days. This paper reports patient outcomes from admission to hospital to 12 months after randomisation. METHODS: Information about hospital length of stay and intensive care management was obtained through linkage with Hospital Episode Statistics and the Intensive Care National Audit and Research Centre. Patients surviving to hospital discharge were approached to complete questionnaires (SF-12v2, EQ-5D, MMSE, HADS and PTSD-CL) at 90days and 12 months. The study is registered with Current Controlled Trials, number ISRCTN08233942. RESULTS: 377 patients in the LUCAS arm and 658 patients in the manual chest compression were admitted to hospital. Hospital and intensive care length of stay were similar. Long term follow-up assessments were limited by poor response rates (53.7% at 3 months and 55.6% at 12 months). Follow-up rates were lower in those with worse neurological function. Among respondents, long term health related quality of life outcomes and emotional well-being was similar between groups. Cognitive function, measured by MMSE, was marginally lower in the LUCAS arm mean 26.9 (SD 3.7) compared to control mean 28.0 (SD 2.3), adjusted mean difference -1.5 (95% CI -2.6 to -0.4). CONCLUSION: There were no clinically important differences identified in outcomes at long term follow-up between those allocated to the mechanical chest compression compared to those receiving manual chest compression.

Characteristics of patients who are not resuscitated in out of hospital cardiac arrests and opportunities to improve community response to cardiac arrest.

AIM: This study explores why resuscitation is withheld when emergency medical staff arrive at the scene of a cardiac arrest and identifies modifiable factors associated with this decision. METHODS: This is a secondary analysis of unselected patients who sustained an out of hospital cardiac arrest attended by ambulance vehicles participating in a randomized controlled trial of a mechanical chest compression device (PARAMEDIC trial). Patients were categorized as 'non-resuscitation' patients if there was a do-not-attempt-cardiopulmonary-resuscitation (DNACPR) order, signs unequivocally associated with death or resuscitation was deemed futile (15min had elapsed since collapse with no bystander-CPR and asystole recorded on EMS arrival). RESULTS: Emergency Medical Services attended 11,451 cardiac arrests. Resuscitation was attempted or continued by Emergency Medical Service staff in 4805 (42%) of cases. Resuscitation was withheld in 6646 cases (58%). 711 (6.2%) had a do not attempt resuscitation decision, 4439 (38.8%) had signs unequivocally associated with death and in 1496 cases (13.1%) CPR was considered futile. Those where resuscitation was withheld due to futility were characterised by low bystander CPR rates (7.2%) and by being female. CONCLUSIONS: Resuscitation was withheld by ambulance staff in over one in ten (13.1%) victims of out of hospital cardiac arrest on the basis of futility. These cases were associated with a very low rate of bystander CPR. Future studies should explore strengthening the 'Chain of Survival' to increase the community bystander CPR response and evaluate the effect on the numbers of survivors from out of hospital cardiac arrest.

Granzyme M has a critical role in providing innate immune protection in ulcerative colitis.

Inflammatory bowel disease (IBD) is an immunoregulatory disorder, associated with a chronic and inappropriate mucosal immune response to commensal bacteria, underlying disease states such as ulcerative colitis (UC) and Crohn's disease (CD) in humans. Granzyme M (GrzM) is a serine protease expressed by cytotoxic lymphocytes, in particular natural killer (NK) cells. Granzymes are thought to be involved in triggering cell death in eukaryotic target cells; however, some evidence supports their role in inflammation. The role of GrzM in the innate immune response to mucosal inflammation has never been examined. Here, we discover that patients with UC, unlike patients with CD, display high levels of GrzM mRNA expression in the inflamed colon. By taking advantage of well-established models of experimental UC, we revealed that GrzM-deficient mice have greater levels of inflammatory indicators during dextran sulfate sodium (DSS)-induced IBD, including increased weight loss, greater colon length reduction and more severe intestinal histopathology. The absence of GrzM expression also had effects on gut permeability, tissue cytokine/chemokine dynamics, and neutrophil infiltration during disease. These findings demonstrate, for the first time, that GrzM has a critical role during early stages of inflammation in UC, and that in its absence colonic inflammation is enhanced.

The Manual Work Instability Scale: development and validation.

BACKGROUND: Increasing awareness of the burden of absenteeism and reduced performance at work highlights the importance of early identification of individuals experiencing work instability (WI), a mismatch between functional and cognitive abilities and job demands. AIMS: To develop and validate a screening questionnaire to measure WI in manual workers. METHODS: Questionnaire items were generated via qualitative interviews with manual workers and a draft survey instrument was completed by workers in a variety of fields. Rasch analysis was used interactively to assess the psychometric aspects of the emerging scale, including unidimensionality and absence of item bias (differential item functioning). RESULTS: A total of 17 qualitative interviews generated 110 potential items for the questionnaire. The item set resolved to a 25-item scale, which satisfied model expectations (item residual mean = -0.13, SD = 1.04; person residual mean = -0.29, SD = 0.75), had good reliability (alpha = 0.86) and strict unidimensionality (t-test 7.5% confidence interval 3.8-11.2). CONCLUSIONS: The Manual Work Instability Scale is a short psychometrically robust questionnaire based on the concept of WI, which incorporates both musculoskeletal symptoms and relevant psychosocial factors. It may prove effective in screening and identifying WI in workers in predominantly physical occupations.

Comparison of spinal deformity in children with Chiari I malformation with and without syringomyelia: matched cohort study.

PURPOSE: To describe curve patterns in patients with Chiari malformation I (CIM) without syringomyelia, and compare to patients with Chiari malformation with syringomyelia (CIM + SM). METHODS: Review of medical records from 2000 to 2013 at a single institution was performed to identify CIM patients with scoliosis. Patients with CIM were matched (1:1) by age and gender to CIM + SM. Radiographic curve patterns, MRI-based craniovertebral junction parameters, and associated neurological signs were compared between the two cohorts. RESULTS: Eighteen patients with CIM-associated scoliosis in the absence of syringomyelia were identified; 14 (78 %) were female, with mean age of 11.5 ± 4.5 years. Mean tonsillar descent was 9.9 ± 4.1 mm in the CIM group and 9.1 ± 3.0 mm in the CIM + SM group (p = 0.57). Average syrinx diameter in the CIM + SM group was 9.0 ± 2.7 mm. CIM patients demonstrated less severe scoliotic curves (32.1° vs. 46.1°, p = 0.04), despite comparable thoracic kyphosis (43.7° vs. 49.6°, p = 0.85). Two (11 %) patients with CIM demonstrated thoracic apex left deformities compared to 9/18 (50 %) in the CIM + SM cohort (p = 0.01). Neurological abnormalities were only observed in the group with syringomyelia (6/18, or 33 %; p = 0.007). CONCLUSION: In the largest series specifically evaluating CIM and scoliosis, we found that these patients appear to present with fewer atypical curve features, with less severe scoliotic curves, fewer apex left curves, and fewer related neurological abnormalities than CIM + SM. Notably, equivalent thoracic kyphosis was observed in both groups. Future studies are needed to better understand pathogenesis of spinal deformity in CIM with and without SM.

CD3bright signals on γδ T cells identify IL-17A-producing Vγ6Vδ1+ T cells.

Interleukin-17A (IL-17A) is a pro-inflammatory cytokine that has an important role at mucosal sites in a wide range of immune responses including infection, allergy and auto-immunity. γδ T cells are recognized as IL-17 producers, but based on the level of CD3 expression, we now define the remarkable ability of a CD3(bright) γδ T-cell subset with an effector memory phenotype to rapidly produce IL-17A, but not interferon-γ. CD3(bright) γδ T cells uniformly express the canonical germline encoded Vγ6/Vδ1(+) T-cell receptor. They are widely distributed with a preferential representation in the lungs and skin are negatively impacted in the absence of retinoic acid receptor-related orphan receptor gammat expression or endogenous flora. This population responded rapidly to various stimuli in a mechanism involving IL-23 and NOD-like receptor family, pyrin domain containing 3 (NLRP3)-inflammasome-dependent IL-1ß. Finally, we demonstrated that IL-17-producing CD3(bright) γδ T cells responded promptly and strongly to pneumococcal infection and during skin inflammation. Here, we propose a new way to specifically analyze IL-17-producing Vγ6/Vδ1(+) T cells based on the level of CD3 signals. Using this gating strategy, our data reinforce the crucial role of this γδ T-cell subset in respiratory and skin disorders.