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    Nerve agents: emergency preparedness.

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    Nerve agents (NAs) are a highly toxic group of chemical warfare agents. NAs are organophosphorus esters with varying physical and chemical properties depending on the individual agent. The most recently developed class of NA is , the existence of which was first revealed in the early 1990s, just before Russia signed the Chemical Weapons Convention. In 1984, Iraq became the first nation to deploy NA on the battlefield when they used tabun against Iranian military forces in Majnoon Island near Basra. The first terrorist use of an NA is believed to be the attack in Matsumoto, Japan, on 27 June 1994 by the Aum Shinrikyo doomsday cult. Symptoms and ultimate toxicity from NA poisoning are related to the agent involved, the form and degree of exposure, and rapidity of medical treatment. The classic toxidrome of significant exposure to NA comprises bronchorrhoea, bronchospasm, bradycardia and convulsions, with an onset period of as early as a few seconds depending on the mode and extent of exposure. If medical management is not instituted rapidly, death may occur in minutes by asphyxiation and cardiac arrest. In the UK, emergency preparedness for NA poisoning includes an initial operational response programme across all blue light emergency services and key first responders. This paper describes the development, pathophysiology, clinical effects and current guidance for management of suspected NA poisoning. It also summarises the known events in which NA poisoning has been confirmed

    Myocardial fibrosis in asymptomatic and symptomatic chronic severe primary mitral regurgitation and relationship to tissue characterisation and left ventricular function on cardiovascular magnetic resonance.

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    BACKGROUND Myocardial fibrosis occurs in end-stage heart failure secondary to mitral regurgitation (MR), but it is not known whether this is present before onset of symptoms or myocardial dysfunction. This study aimed to characterise myocardial fibrosis in chronic severe primary MR on histology, compare this to tissue characterisation on cardiovascular magnetic resonance (CMR) imaging, and investigate associations with symptoms, left ventricular (LV) function, and exercise capacity. METHODS Patients with class I or IIa indications for surgery underwent CMR and cardiopulmonary exercise testing. LV biopsies were taken at surgery and the extent of fibrosis was quantified on histology using collagen volume fraction (CVF) compared to autopsy controls without cardiac pathology. RESULTS 120 consecutive patients (64 ± 13 years; 71% male) were recruited; 105 patients underwent MV repair while 15 chose conservative management. LV biopsies were obtained in 86 patients (234 biopsy samples in total). MR patients had more fibrosis compared to 8 autopsy controls (median: 14.6% [interquartile range 7.4-20.3] vs. 3.3% [2.6-6.1], P < 0.001); this difference persisted in the asymptomatic patients (CVF 13.6% [6.3-18.8], P < 0.001), but severity of fibrosis was not significantly higher in NYHA II-III symptomatic MR (CVF 15.7% [9.9-23.1] (P = 0.083). Fibrosis was patchy across biopsy sites (intraclass correlation 0.23, 95% CI 0.08-0.39, P = 0.001). No significant relationships were identified between CVF and CMR tissue characterisation [native T1, extracellular volume (ECV) or late gadolinium enhancement] or measures of LV function [LV ejection fraction (LVEF), global longitudinal strain (GLS)]. Although the range of ECV was small (27.3 ± 3.2%), ECV correlated with multiple measures of LV function (LVEF: Rho = - 0.22, P = 0.029, GLS: Rho = 0.29, P = 0.003), as well as NTproBNP (Rho = 0.54, P < 0.001) and exercise capacity (%PredVOmax: R = - 0.22, P = 0.030). CONCLUSIONS Patients with chronic primary MR have increased fibrosis before the onset of symptoms. Due to the patchy nature of fibrosis, CMR derived ECV may be a better marker of global myocardial status. Clinical trial registration Mitral FINDER study; Clinical Trials NCT02355418, Registered 4 February 2015, https://clinicaltrials.gov/ct2/show/NCT02355418

    Defining the medical coverage of ballistic protection to the pelvis and thigh.

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    INTRODUCTION Pelvis, lower limb and associated genital injury caused by explosive devices was responsible for mortality and considerable long-term morbidity for the UK Armed Forces during combat operations in Afghanistan, resulting in the issue of a pelvic protection system in 2010. The aim of this current research was to determine the medical coverage of the pelvis and thigh and to define the vertical dimensions of ballistic protective material for future pelvic protection (PP). METHOD CT scans from 120 male UK Armed Forces personnel were analysed to identify the anthropometric landmarks and vertical boundaries of coverage for the pelvis and thigh. Pelvic height was the vertical distance between the upper border of the iliac crest in the midaxillary plane to the most inferior point of the ischial tuberosity of the pelvis. Upper thigh height was proposed as a 100 mm fixed distance below the ischial tuberosities, enabling a tourniquet to be reproducibly applied. These distances were compared with the ballistic component of the five sizes of tier 1 PP using a paired t-test. RESULTS The vertical components of coverage measured using CT scans were all significantly less (p<0.01) compared with all five sizes of tier 1 PP; for example, the ballistic component of the smallest size of tier 1 PP measured 410 mm, which was larger than the 99th percentile male, which measured 346 mm on CT scans. CONCLUSIONS While all sizes of tier 1 PP provide coverage to the pelvis and upper thigh structures, there is an opportunity to optimise future PP. For example, comparing the large size of tier 1 PP to the 50th percentile male demonstrated an opportunity to reduce the ballistic protective component by 31%. Reducing the quantity of material used will improve heat dissipation and user comfort and reduce material mass and acquisition costs

    Burns objective scar scale (BOSS): Validation of an objective measurement devices based burn scar scale panel.

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    AIMS Hypertrophic scars in burn survivors are a major cause of morbidity but the development of evidence based treatments is hampered by the lack of objective measurements of these scars. The objective of our study is to investigate the most accurate parameters for objective scar assessment and to create a combination score to facilitate the use of a panel of objective scar measurement tools. METHODS Three independent assessors evaluated fifty five scar sites on fifty five burn patients with both the subjective modified Vancouver Scar Scale (mVSS) and a panel of objective measurement tools including the DSM II Colormeter, Cutometer, Dermascan high frequency ultrasound. The sensitivity and specificity of the objective scar parameters in predicting a mVSS score of 6 or more using the Receiving Operator Characteristic Area under the curve (ROC AUC) was then calculated and the most accurate parameters were combined to create an objective global scar score. RESULTS The ROC AUC values were found to be highest for the Dermascan scar thickness (0.897), dermal intensity and intensity ratio (0.914 and 0.919), Cutometer R0 value (0.942), and R0 ratio (0.944). For colour measurements, ratios of scar to normal skin performed better than the single parameters for both erythema and pigmentation measurements: DSM II Erythema ratio vs Erythema (0.885 vs 0.818), DSM II a* ratio vs a* (0.848 vs 0.741); DSM II Melanin ratio vs Melanin (0.854 vs 0.761), DSM II L* ratio vs L* (0.862 vs 0.767). Analysis of the ROC AUC with chi-square test values showed that the highest AUC (0.786) was obtained with the combination of the Cutometer R0, Dermascan scar thickness, intensity and their respective scar to normal skin ratios. A total score of 5 and above (out of 6 parameters) had the highest combined sensitivity (69.0%) and specificity (83.3%). CONCLUSION The objective parameters for the DSM II Colormeter, Cutometer and Dermascan high frequency ultrasound were all found to have moderate to strong ROC AUC values and combination of the Cutometer R0 and Dermascan scar thickness and intensity values can be used to create an objective global scar scale that can accurately differentiate patients with hypertrophic burn scarring from non-hypertrophic scars or normal skin

    Management of venous thromboembolism in patients experiencing direct oral anticoagulant treatment failure: a single-center review of practice and outcomes.

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    Direct oral anticoagulants (DOACs) have gained in popularity over vitamin K antagonists for the treatment of venous thromboembolism, however their efficacy is not routinely monitored. It is therefore a clinical challenge to know how to respond when treatment with DOACs fails, and there is little formal guidance on how to manage these patients. We sought to characterize VTE patients who experienced DOAC failure at our institution, and rationalize subsequent treatment strategies. We collated the details of 54 consecutive patients with suboptimal response or breakthrough thrombosis on a DOAC, from our large specialist-led thrombosis clinic. Initial treatment changes were recorded, as well as long-term anticoagulation therapy and treatment outcomes. On first recognition of DOAC failure, 69% of patients were temporarily switched to therapeutic-dose low molecular weight heparin; most of the remaining patients were treated with an alternative DOAC regimen. After a limited period of parenteral treatment, 84% of patients returned to oral anticoagulation, the majority of whom experienced no further treatment failures. By the end of follow-up, 72% of patients were either on long-term DOAC therapy or had completed treatment altogether. In the absence of evidence or guidelines, brief rescue of anticoagulation with parenteral therapy can be an effective strategy when treatment with a DOAC fails

    The outcomes of biliary drainage by percutaneous transhepatic cholangiography for the palliation of malignant biliary obstruction in England between 2001 and 2014: a retrospective cohort study.

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    INTRODUCTION Relieving obstructive jaundice in inoperable pancreato-biliary cancers improves quality of life and permits chemotherapy. Percutaneous transhepatic cholangiography with drainage and/or stenting relieves jaundice but can be associated with significant morbidity and mortality. Percutaneous transhepatic biliary drainage (PTBD) in malignant biliary obstruction was therefore examined in a national cohort to establish risk factors for poor outcomes. METHODS Retrospective study of adult patients undergoing PTBD for palliation of pancreato-biliary cancer in England between 2001 and 2014 identified from Hospital Episode Statistics. Multivariate logistic regression analysis was used to examine associations with mortality and the need for a repeat PTBD within 2 months. RESULTS 16 822 patients analysed (median age 72 (range 19-104) years, 50.3% men). 58% pancreatic and 30% biliary tract cancer. In-hospital and 30-day mortality were 15.3% (95% CI 14.7% to 15.9%) and 23.1% (22.4%-23.8%), respectively. 20.2% suffered a coded complication within 3 months. Factors associated with 30-day mortality: age (≥81 years OR 2.68 (95% CI 2.37 to 3.03), p<0.001), increasing comorbidity (Charlson score 20+, 3.10 (2.64-3.65), p<0.001), pre-existing renal dysfunction (2.37 (2.12-2.65), p<0.001) and non-pancreatic cancer (unspecified biliary tract 1.28 (1.08-1.52), p=0.004). Women had lower mortality (0.91 (0.84-0.98), p=0.011), as did patients undergoing PTBD in a 'higher volume' provider (84-180 PTBDs per year 0.68 (0.58-0.79), p<0.001). CONCLUSIONS In patients undergoing PTBD for the palliation of malignant biliary obstruction, 30-day mortality was high at 23.1%. Mortality was higher in older patients, men, those with increasing comorbidity, a cancer site other than pancreas and at 'lower-volume' PTBD providers

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